INDIKASI TERAPI OHB
1. PENYAKIT DEKOMPRESI
2. EMBOLI GAS / UDARA
3. KERACUNAN CO
4. GAS GANGREN
5. OSTEOMYELISIS
6. BEDAH PLASTIK & REKONSTRUKSI
7. TRAUMATOLOGI
8. KASUS ORTOPEDI
9. PENYAKIT PEMBULUH DARAH TEPI
10. NEUROLOGI
( STROKE, MIGRAIN, DEMENSIA )
11. ENDOKRIN ( DM )
12. PASCA RADIASI
13. HEMATOLOGI
di tayangkan ulang oleh : dr.Erick Supondha (hyperbaric& diving medicine consultant) hiperbarik oksigen terapi >RS bethsaida , jakarta indonesia, (dokter hiperbarik/ahli hiperbarik/dokter kesehatan penyelaman)
021 99070050
Rabu, 26 Desember 2012
Selasa, 18 Desember 2012
MONOPLACE CHAMBER
monoplace chamber
sumber : Brosur Perry Baromedical ( File flash disk from Mr.Peter Manz)
di tayangkan ulang oleh : dr.Erick Supondha (hyperbaric& diving medicine consultant) hiperbarik oksigen terapi RS bethsaida , jakarta indonesia, (dokter hiperbarik/ahli hiperbarik/dokter kesehatan penyelaman)
021 99070050
Rabu, 12 Desember 2012
Hyperbaric Chamber
Salah satu fasilitas hiperbarik yang dimiliki oleh rumah sakit di wilayah asia tenggara.
sumber: file Hyperbaric Health Australia (Flash disk from Mr.Peter Manz)
di tayangkan ulang oleh : dr.Erick Supondha (hyperbaric& diving medicine consultant) hiperbarik oksigen terapi RS bethsaida , jakarta indonesia, (dokter hiperbarik/ahli hiperbarik/dokter kesehatan penyelaman)
021 99070050
Selasa, 04 Desember 2012
Ciguatera Fish Poisoning — New York City, 2010–2011
Ciguatera Fish Poisoning — New York City, 2010–2011
Weekly
February 1, 2013 / 62(04);61-65During August 2010–July 2011, the New York City Department of Health and Mental Hygiene (DOHMH) received reports of six outbreaks and one single case of ciguatera fish poisoning (CFP), involving a total of 28 persons. CFP results from consumption of certain large, predatory, tropical reef fish that have bioaccumulated ciguatoxins (CTX). CFP is characterized by various gastrointestinal, cardiovascular, and neurologic symptoms. A prolonged period of acute illness can result, and the neurologic symptoms can last months, with variable asymptomatic and symptomatic periods. The first two outbreaks and the single case, involving 13 persons, were reported during August 6–September 13, 2010. DOHMH distributed a health alert in November 2010 requesting health-care providers be alert for CFP signs and symptoms. The health alert resulted in identification of 11 more cases that month and an additional two outbreaks involving four persons in July 2011. In comparison, only four CFP outbreaks, involving 21 persons total, had been reported in New York City (NYC) during the preceding 10 years (2000–2009). DOHMH's investigation revealed that 13 persons became ill after eating barracuda, and 15 became ill after eating grouper. Although specific and highly sensitive laboratory analyses can detect and confirm CTX in fish, no practical field tests are available for fish monitoring programs. CFP prevention depends on educating the public, seafood suppliers, and distributors about known CFP endemic areas and high-risk fish species. Traceback investigations of fish associated with outbreaks provide valuable information regarding fishing areas associated with CFP. Not all fish from CFP endemic areas are ciguatoxic, but persons who eat fish from endemic regions are at higher risk for CFP. If an illness is suspected to be CFP, public health authorities should be notified and informed of the case history for possible investigation and intervention measures.
On August 6, 2010, an adolescent female aged 16 years, and her mother aged 47 years went to a hospital emergency department (ED) with diarrhea, light-headedness, and perioral tingling after eating barracuda purchased at a fish market in Queens, New York. Hours later, an additional four family members (three males and one female) who had eaten the same fish, reported tingling in their extremities. Two of the four also visited the ED. Later, the four who had gone to the ED experienced abdominal cramps, dizziness, headache, faintness, nausea, and vomiting. Hypotension and bradycardia persisted, despite volume resuscitation with normal saline. The treating physician suspected a link between the barracuda consumption and neurologic and gastrointestinal symptoms (Table 1), subsequently diagnosed CFP,* and contacted the NYC Poison Control Center (PCC). The PCC reported the incident to DOHMH, and a DOHMH inspector collected samples of barracuda from the fish market and the patients' home. The inspector also embargoed barracuda sale at the fish market.
Samples were analyzed for CTX at the Gulf Coast Seafood Laboratory of the Food and Drug Administration (FDA) using methods developed by FDA to confirm CFP cases. These methods included an in vitro mouse neuroblastoma cell assay for sodium channel toxins to provide a semiquantitative measure of composite ciguatoxicity in fish (1). Extracts that were positive by this method were subsequently analyzed by liquid chromatography–tandem mass spectrometry for unequivocal confirmation of ciguatoxins (1). One meal remnant was confirmed to contain Caribbean CTX-1 and -2 at a toxicity level of 1.1 µg/kg total C-CTX-1 equivalents, more than 10 times the FDA guidance level of 0.1 µg/kg total C-CTX-1 equivalents. The patients reported that some of their neurologic symptoms persisted for 2–5 months (Table 1).
During August–September 2010, an additional seven CFP cases were reported to DOHMH. These consisted of two outbreaks (outbreaks 2 and 3; Table 1) and a single case. All patients experienced symptoms consistent with CFP after eating barracuda purchased from fish markets in three different NYC boroughs and one restaurant (Table 2). On the evening of November 19, 2010, after reading the health alert about CFP, a physician reported a suspected CFP outbreak in Queens (outbreak 4). This new outbreak involved 11 persons from three families who had eaten fish labeled as grouper that was purchased from a Queens supermarket. Five hours after eating the fish, one family member visited the ED with vomiting, nausea, hypotension, and leg cramping. Shortly thereafter, other members of the family reported experiencing numbness and tingling, and two had bradycardia diagnosed several days after fish consumption. In contrast with previously reported cases, four patients experienced tooth pain or paradoxical dysesthesias (Table 1). New York State Department of Agriculture and Markets completed their traceback investigation and identified the same distributor involved in the barracuda-related CFP outbreak reported earlier that year.
On July 12, 2011, two separate outbreaks and an additional four cases that were associated with eating grouper at Manhattan restaurants were reported to DOHMH. One of the patients was a physically active man who swam >2 miles per day before his illness. After the onset of acute CFP symptoms, he had difficulty walking that persisted for several months. A sample of leftover fish was confirmed by FDA to contain 1.9 µg/kg total C-CTX-1 equivalents, exceeding the FDA guidance level by almost 20 times. Before this most recent outbreak, the implicated vendor was inspected by FDA and issued a warning letter detailing violations.
Reported by
Nathan Graber, MD, Faina Stavinsky, MS, Robert Hoffman, MD, Jessica Button, Nancy Clark, MA, New York City Dept of Health and Mental Hygiene; Scott Martin, MD, Stony Brook Univ Medical School, Stony Brook, New York. Alison Robertson, PhD, Food and Drug Administration. John Hustedt, MPH, Public Health Prevention Svc, CDC. Corresponding contributor: John Hustedt, johnhustedt@gmail.com, 212-788-4290.Editorial Note
CTX are naturally occurring toxins that can accumulate in commonly consumed coral reef fish (e.g., barracuda, grouper, snapper, amberjack, and surgeonfish). Precursors of CTX are derived from marine dinoflagellates (microalgae) that live on the surfaces of seaweeds and denuded corals. These microalgae are consumed by herbivorous fish and undergo bioconversion to the more potent CTX as they move through the food chain. CTX can accumulate in reef fish that eat other fish, reaching levels that can cause CFP among humans when consumed. The toxins are colorless, odorless, tasteless, and temperature-stable, making them difficult to detect or destroy. Consequently, CFP occurrence is not attributable to incorrect food handling, storage, preparation, or procurement methods. The attack rate can be 80%–90% among persons who have eaten a toxic fish, depending on the concentration of CTX in the fish, the total amount of fish consumed, and the consumer's body weight and health status (2). As in the outbreaks described in this report, symptomatology is variable.Initial treatment options for CFP are limited and supportive only. The majority of patients experience symptoms within 6–48 hours after eating contaminated fish. In an acutely symptomatic patient, any vital sign instability or electrolyte imbalance should be treated in accordance with the normal standard of care (3). Administration of intravenous mannitol was thought to reduce neuronal edema; however, a randomized double-blind, clinical trial found no evidence of mannitol being superior to normal saline, and mannitol can cause additional side effects, including hypotension, requiring caution during administration (4–6). Treatment of CFP symptoms (e.g., neuropathy, fatigue, and headache) with amitriptyline, sodium channel blockers, and pain medications all have been tried with variable success (4). Consultation with the local PCC is recommended and in NYC fulfills the reporting requirement.
This report reflects the importance of surveillance and outreach networks in responding to patients' histories, including food consumption, that are indicative of CFP, and highlights prevention challenges. Reports made to the NYC PCC allowed expeditious and effective action when the first cases of CFP were reported. Investigators notified other jurisdictions, consulted local health departments with expertise in CFP prevention and case management, and conducted outreach to NYC health-care providers. In southern Florida, where CFP is endemic, 68% of physicians who were presented with a typical case of CFP diagnosed it correctly (7). As a result of considerable education and outreach efforts by the Florida Department of Health during the past decade, accuracy of CFP diagnosis in that state has improved. However, in other nonendemic regions, diagnostic recognition remains low.
An interstate comparison of reports to PCCs revealed additional trends, beyond the increased number of NYC CFP cases. Unpublished data from CFP-related calls to the American Association of Poison Control Centers during 2000–2010 were analyzed for trends and changes in geographic distribution. The data revealed that the rate of CFP-related calls per capita during 2010, compared with the previous 10 years, was 55% higher in NYC but 44% lower in Florida. Although this data set might not be representative of individual state CFP records, the rate per capita of U.S. cases remained relatively constant throughout the preceding 11 years. This increase of reported cases in NYC might reflect changing sources and diversity of fish species marketed in NYC and elsewhere. The increase might also indicate improved awareness and capacity for investigation by the medical and public health community. The decrease in CFP reports from Florida likely was the result of improved awareness of CFP after extensive long-term outreach and education efforts and specific guidance on the harvest of high-risk fish in this endemic region.
CFP is considered a highly underreported illness, with only an estimated 10% of cases reported to health authorities (7). Increasing awareness among health-care providers might improve reporting and investigation. However, CFP prevention is complicated by difficulty in identifying high-risk fishing grounds and inadequate industry knowledge and compliance with the FDA seafood Hazard Analysis and Critical Control Point (HACCP) regulations.† Premarket testing of fish for CTX is not feasible because of the lack of rapid field methods and the sporadic distribution of toxic fish, even in endemic areas. Coordinated tracebacks of implicated fish by federal and state agencies to specific fishing grounds remains the primary strategy for managing CFP.
The findings in this report are subject to at least three limitations. First, meal remnant samples were available only in three of the six CFP outbreaks. Second, where physician reports to the PCC were unavailable, the symptoms were based entirely on self-report or secondhand reports from family members. Finally, additional cases might have occurred but were unrecognized because of lack of physician awareness to make an appropriate diagnosis and the need to report.
This investigation demonstrates the value of CFP-implicated fish traceback along with updated information on emerging CFP risks, including new harvest areas and species. Prevention through education alone might be limited by seafood mislabeling. Reports indicate that 20%–25% of all seafood products are mislabeled (8). A recent assessment of seafood purchased at retail stores and restaurants in New York, New Jersey, and Connecticut indicated that >20% of 190 specimens were mislabeled, incompletely labeled, or misidentified by employees (8). Methods for fish species identification using DNA barcoding have been validated (9) and are being implemented in several U.S. state and federal laboratories, as well as academic institutions. These methods have been applied to multiple CFP cases. Ongoing collaborative efforts with federal, state, and local agencies tasked with consumer protection and food safety might be useful in controlling CFP and mislabeling of fish (10). Until accurate and cost-effective means of premarket testing become available, prevention of additional cases will continue to be dependent on HACCP compliance by the seafood industry and CFP diagnosis and reporting by health-care providers, warranting additional outreach and education.
Acknowledgment
Munerah Ahmed, MPH, New York City Dept of Health and Mental Hygiene, New York.References
- Food and Drug Administration. FDA fish and fishery products hazards and controls guidance. 4th ed. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration; 2011. Available at http://www.fda.gov/downloads/food/guidancecomplianceregulatoryinformation/guidancedocuments/seafood/ucm251970.pdf
.
- CDC. Cluster of ciguatera fish poisoning—North Carolina, 2007. MMWR 2009;58:283–5.
- Thomson Reuters (Healthcare). Ciguatera fish poisoning. POISINDEX System [database]. Greenwood Village, Colorado: Thomson Reuters (Healthcare); 2012.
- Friedman MA, Fleming LE, Fernandez M, et al. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs 2008;6:456–79.
- Achaibar KC, Moore S, Bain PG. Ciguatera poisoning. Pract Neurol 2007;7:316–22.
- Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy. Neurology 2002;58:873–80.
- McKee D, Fleming LE, Tamer R, Weisman R, Blythe DG. Physician diagnosis and reporting of ciguatera fish poisoning in an endemic area. In: Hallegraeff GM, Blackburn SI, Bolch CJ, Lewis RJ, eds. Harmful algal blooms 2000. Paris, France: Intergovernmental Oceanographic Commission of United Nations Educational, Scientific, and Cultural Organization; 2001:451–3.
- Consumers Union. Mystery fish: the label said red snapper, the lab said baloney. Consum Rep 2011;76:18–22.
- Handy SM, Deeds JR, Ivanova NV, et al. A single laboratory validated method for the generation of DNA barcodes for the identification of fish for regulatory compliance. J AOAC Int 2011;94:201–10.
- Government Accountability Office. Seafood fraud—FDA program changes and better collaboration among key federal agencies could improve detection and prevention. Washington, DC: Government Accountability Office; 2009. Available at http://www.gao.gov/new.items/d09258.pdf
* Additional information on CFP signs and symptoms available at http://www.nyc.gov/html/doh/downloads/pdf/cd/2010/10md25.pdf 
.
.
† Additional information, including advisories and guidance related to high-risk species and endemic regions, is available at http://www.fda.gov/food/foodsafety/hazardanalysiscriticalcontrolpointshaccp/seafoodhaccp/default.htm.
.
sumber :
Ciguatera Fish Poisoning — New York City, 2010–2011
Weekly
February 1, 2013 / 62(04);61-65During August 2010–July 2011, the New York City Department of Health and Mental Hygiene (DOHMH) received reports of six outbreaks and one single case of ciguatera fish poisoning (CFP), involving a total of 28 persons. CFP results from consumption of certain large, predatory, tropical reef fish that have bioaccumulated ciguatoxins (CTX). CFP is characterized by various gastrointestinal, cardiovascular, and neurologic symptoms. A prolonged period of acute illness can result, and the neurologic symptoms can last months, with variable asymptomatic and symptomatic periods. The first two outbreaks and the single case, involving 13 persons, were reported during August 6–September 13, 2010. DOHMH distributed a health alert in November 2010 requesting health-care providers be alert for CFP signs and symptoms. The health alert resulted in identification of 11 more cases that month and an additional two outbreaks involving four persons in July 2011. In comparison, only four CFP outbreaks, involving 21 persons total, had been reported in New York City (NYC) during the preceding 10 years (2000–2009). DOHMH's investigation revealed that 13 persons became ill after eating barracuda, and 15 became ill after eating grouper. Although specific and highly sensitive laboratory analyses can detect and confirm CTX in fish, no practical field tests are available for fish monitoring programs. CFP prevention depends on educating the public, seafood suppliers, and distributors about known CFP endemic areas and high-risk fish species. Traceback investigations of fish associated with outbreaks provide valuable information regarding fishing areas associated with CFP. Not all fish from CFP endemic areas are ciguatoxic, but persons who eat fish from endemic regions are at higher risk for CFP. If an illness is suspected to be CFP, public health authorities should be notified and informed of the case history for possible investigation and intervention measures.
On August 6, 2010, an adolescent female aged 16 years, and her mother aged 47 years went to a hospital emergency department (ED) with diarrhea, light-headedness, and perioral tingling after eating barracuda purchased at a fish market in Queens, New York. Hours later, an additional four family members (three males and one female) who had eaten the same fish, reported tingling in their extremities. Two of the four also visited the ED. Later, the four who had gone to the ED experienced abdominal cramps, dizziness, headache, faintness, nausea, and vomiting. Hypotension and bradycardia persisted, despite volume resuscitation with normal saline. The treating physician suspected a link between the barracuda consumption and neurologic and gastrointestinal symptoms (Table 1), subsequently diagnosed CFP,* and contacted the NYC Poison Control Center (PCC). The PCC reported the incident to DOHMH, and a DOHMH inspector collected samples of barracuda from the fish market and the patients' home. The inspector also embargoed barracuda sale at the fish market.
Samples were analyzed for CTX at the Gulf Coast Seafood Laboratory of the Food and Drug Administration (FDA) using methods developed by FDA to confirm CFP cases. These methods included an in vitro mouse neuroblastoma cell assay for sodium channel toxins to provide a semiquantitative measure of composite ciguatoxicity in fish (1). Extracts that were positive by this method were subsequently analyzed by liquid chromatography–tandem mass spectrometry for unequivocal confirmation of ciguatoxins (1). One meal remnant was confirmed to contain Caribbean CTX-1 and -2 at a toxicity level of 1.1 µg/kg total C-CTX-1 equivalents, more than 10 times the FDA guidance level of 0.1 µg/kg total C-CTX-1 equivalents. The patients reported that some of their neurologic symptoms persisted for 2–5 months (Table 1).
During August–September 2010, an additional seven CFP cases were reported to DOHMH. These consisted of two outbreaks (outbreaks 2 and 3; Table 1) and a single case. All patients experienced symptoms consistent with CFP after eating barracuda purchased from fish markets in three different NYC boroughs and one restaurant (Table 2). On the evening of November 19, 2010, after reading the health alert about CFP, a physician reported a suspected CFP outbreak in Queens (outbreak 4). This new outbreak involved 11 persons from three families who had eaten fish labeled as grouper that was purchased from a Queens supermarket. Five hours after eating the fish, one family member visited the ED with vomiting, nausea, hypotension, and leg cramping. Shortly thereafter, other members of the family reported experiencing numbness and tingling, and two had bradycardia diagnosed several days after fish consumption. In contrast with previously reported cases, four patients experienced tooth pain or paradoxical dysesthesias (Table 1). New York State Department of Agriculture and Markets completed their traceback investigation and identified the same distributor involved in the barracuda-related CFP outbreak reported earlier that year.
On July 12, 2011, two separate outbreaks and an additional four cases that were associated with eating grouper at Manhattan restaurants were reported to DOHMH. One of the patients was a physically active man who swam >2 miles per day before his illness. After the onset of acute CFP symptoms, he had difficulty walking that persisted for several months. A sample of leftover fish was confirmed by FDA to contain 1.9 µg/kg total C-CTX-1 equivalents, exceeding the FDA guidance level by almost 20 times. Before this most recent outbreak, the implicated vendor was inspected by FDA and issued a warning letter detailing violations.
Reported by
Nathan Graber, MD, Faina Stavinsky, MS, Robert Hoffman, MD, Jessica Button, Nancy Clark, MA, New York City Dept of Health and Mental Hygiene; Scott Martin, MD, Stony Brook Univ Medical School, Stony Brook, New York. Alison Robertson, PhD, Food and Drug Administration. John Hustedt, MPH, Public Health Prevention Svc, CDC. Corresponding contributor: John Hustedt, johnhustedt@gmail.com, 212-788-4290.Editorial Note
CTX are naturally occurring toxins that can accumulate in commonly consumed coral reef fish (e.g., barracuda, grouper, snapper, amberjack, and surgeonfish). Precursors of CTX are derived from marine dinoflagellates (microalgae) that live on the surfaces of seaweeds and denuded corals. These microalgae are consumed by herbivorous fish and undergo bioconversion to the more potent CTX as they move through the food chain. CTX can accumulate in reef fish that eat other fish, reaching levels that can cause CFP among humans when consumed. The toxins are colorless, odorless, tasteless, and temperature-stable, making them difficult to detect or destroy. Consequently, CFP occurrence is not attributable to incorrect food handling, storage, preparation, or procurement methods. The attack rate can be 80%–90% among persons who have eaten a toxic fish, depending on the concentration of CTX in the fish, the total amount of fish consumed, and the consumer's body weight and health status (2). As in the outbreaks described in this report, symptomatology is variable.Initial treatment options for CFP are limited and supportive only. The majority of patients experience symptoms within 6–48 hours after eating contaminated fish. In an acutely symptomatic patient, any vital sign instability or electrolyte imbalance should be treated in accordance with the normal standard of care (3). Administration of intravenous mannitol was thought to reduce neuronal edema; however, a randomized double-blind, clinical trial found no evidence of mannitol being superior to normal saline, and mannitol can cause additional side effects, including hypotension, requiring caution during administration (4–6). Treatment of CFP symptoms (e.g., neuropathy, fatigue, and headache) with amitriptyline, sodium channel blockers, and pain medications all have been tried with variable success (4). Consultation with the local PCC is recommended and in NYC fulfills the reporting requirement.
This report reflects the importance of surveillance and outreach networks in responding to patients' histories, including food consumption, that are indicative of CFP, and highlights prevention challenges. Reports made to the NYC PCC allowed expeditious and effective action when the first cases of CFP were reported. Investigators notified other jurisdictions, consulted local health departments with expertise in CFP prevention and case management, and conducted outreach to NYC health-care providers. In southern Florida, where CFP is endemic, 68% of physicians who were presented with a typical case of CFP diagnosed it correctly (7). As a result of considerable education and outreach efforts by the Florida Department of Health during the past decade, accuracy of CFP diagnosis in that state has improved. However, in other nonendemic regions, diagnostic recognition remains low.
An interstate comparison of reports to PCCs revealed additional trends, beyond the increased number of NYC CFP cases. Unpublished data from CFP-related calls to the American Association of Poison Control Centers during 2000–2010 were analyzed for trends and changes in geographic distribution. The data revealed that the rate of CFP-related calls per capita during 2010, compared with the previous 10 years, was 55% higher in NYC but 44% lower in Florida. Although this data set might not be representative of individual state CFP records, the rate per capita of U.S. cases remained relatively constant throughout the preceding 11 years. This increase of reported cases in NYC might reflect changing sources and diversity of fish species marketed in NYC and elsewhere. The increase might also indicate improved awareness and capacity for investigation by the medical and public health community. The decrease in CFP reports from Florida likely was the result of improved awareness of CFP after extensive long-term outreach and education efforts and specific guidance on the harvest of high-risk fish in this endemic region.
CFP is considered a highly underreported illness, with only an estimated 10% of cases reported to health authorities (7). Increasing awareness among health-care providers might improve reporting and investigation. However, CFP prevention is complicated by difficulty in identifying high-risk fishing grounds and inadequate industry knowledge and compliance with the FDA seafood Hazard Analysis and Critical Control Point (HACCP) regulations.† Premarket testing of fish for CTX is not feasible because of the lack of rapid field methods and the sporadic distribution of toxic fish, even in endemic areas. Coordinated tracebacks of implicated fish by federal and state agencies to specific fishing grounds remains the primary strategy for managing CFP.
The findings in this report are subject to at least three limitations. First, meal remnant samples were available only in three of the six CFP outbreaks. Second, where physician reports to the PCC were unavailable, the symptoms were based entirely on self-report or secondhand reports from family members. Finally, additional cases might have occurred but were unrecognized because of lack of physician awareness to make an appropriate diagnosis and the need to report.
This investigation demonstrates the value of CFP-implicated fish traceback along with updated information on emerging CFP risks, including new harvest areas and species. Prevention through education alone might be limited by seafood mislabeling. Reports indicate that 20%–25% of all seafood products are mislabeled (8). A recent assessment of seafood purchased at retail stores and restaurants in New York, New Jersey, and Connecticut indicated that >20% of 190 specimens were mislabeled, incompletely labeled, or misidentified by employees (8). Methods for fish species identification using DNA barcoding have been validated (9) and are being implemented in several U.S. state and federal laboratories, as well as academic institutions. These methods have been applied to multiple CFP cases. Ongoing collaborative efforts with federal, state, and local agencies tasked with consumer protection and food safety might be useful in controlling CFP and mislabeling of fish (10). Until accurate and cost-effective means of premarket testing become available, prevention of additional cases will continue to be dependent on HACCP compliance by the seafood industry and CFP diagnosis and reporting by health-care providers, warranting additional outreach and education.
Acknowledgment
Munerah Ahmed, MPH, New York City Dept of Health and Mental Hygiene, New York.References
- Food and Drug Administration. FDA fish and fishery products hazards and controls guidance. 4th ed. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration; 2011. Available at http://www.fda.gov/downloads/food/guidancecomplianceregulatoryinformation/guidancedocuments/seafood/ucm251970.pdf
- CDC. Cluster of ciguatera fish poisoning—North Carolina, 2007. MMWR 2009;58:283–5.
- Thomson Reuters (Healthcare). Ciguatera fish poisoning. POISINDEX System [database]. Greenwood Village, Colorado: Thomson Reuters (Healthcare); 2012.
- Friedman MA, Fleming LE, Fernandez M, et al. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs 2008;6:456–79.
- Achaibar KC, Moore S, Bain PG. Ciguatera poisoning. Pract Neurol 2007;7:316–22.
- Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy. Neurology 2002;58:873–80.
- McKee D, Fleming LE, Tamer R, Weisman R, Blythe DG. Physician diagnosis and reporting of ciguatera fish poisoning in an endemic area. In: Hallegraeff GM, Blackburn SI, Bolch CJ, Lewis RJ, eds. Harmful algal blooms 2000. Paris, France: Intergovernmental Oceanographic Commission of United Nations Educational, Scientific, and Cultural Organization; 2001:451–3.
- Consumers Union. Mystery fish: the label said red snapper, the lab said baloney. Consum Rep 2011;76:18–22.
- Handy SM, Deeds JR, Ivanova NV, et al. A single laboratory validated method for the generation of DNA barcodes for the identification of fish for regulatory compliance. J AOAC Int 2011;94:201–10.
- Government Accountability Office. Seafood fraud—FDA program changes and better collaboration among key federal agencies could improve detection and prevention. Washington, DC: Government Accountability Office; 2009. Available at http://www.gao.gov/new.items/d09258.pdf
* Additional information on CFP signs and symptoms available at http://www.nyc.gov/html/doh/downloads/pdf/cd/2010/10md25.pdf .
.
† Additional information, including advisories and guidance related to high-risk species and endemic regions, is available at http://www.fda.gov/food/foodsafety/hazardanalysiscriticalcontrolpointshaccp/seafoodhaccp/default.htm.
.
sumber :
Ciguatera Fish Poisoning — New York City, 2010–2011
Weekly
February 1, 2013 / 62(04);61-65During August 2010–July 2011, the New York City Department of Health and Mental Hygiene (DOHMH) received reports of six outbreaks and one single case of ciguatera fish poisoning (CFP), involving a total of 28 persons. CFP results from consumption of certain large, predatory, tropical reef fish that have bioaccumulated ciguatoxins (CTX). CFP is characterized by various gastrointestinal, cardiovascular, and neurologic symptoms. A prolonged period of acute illness can result, and the neurologic symptoms can last months, with variable asymptomatic and symptomatic periods. The first two outbreaks and the single case, involving 13 persons, were reported during August 6–September 13, 2010. DOHMH distributed a health alert in November 2010 requesting health-care providers be alert for CFP signs and symptoms. The health alert resulted in identification of 11 more cases that month and an additional two outbreaks involving four persons in July 2011. In comparison, only four CFP outbreaks, involving 21 persons total, had been reported in New York City (NYC) during the preceding 10 years (2000–2009). DOHMH's investigation revealed that 13 persons became ill after eating barracuda, and 15 became ill after eating grouper. Although specific and highly sensitive laboratory analyses can detect and confirm CTX in fish, no practical field tests are available for fish monitoring programs. CFP prevention depends on educating the public, seafood suppliers, and distributors about known CFP endemic areas and high-risk fish species. Traceback investigations of fish associated with outbreaks provide valuable information regarding fishing areas associated with CFP. Not all fish from CFP endemic areas are ciguatoxic, but persons who eat fish from endemic regions are at higher risk for CFP. If an illness is suspected to be CFP, public health authorities should be notified and informed of the case history for possible investigation and intervention measures.
On August 6, 2010, an adolescent female aged 16 years, and her mother aged 47 years went to a hospital emergency department (ED) with diarrhea, light-headedness, and perioral tingling after eating barracuda purchased at a fish market in Queens, New York. Hours later, an additional four family members (three males and one female) who had eaten the same fish, reported tingling in their extremities. Two of the four also visited the ED. Later, the four who had gone to the ED experienced abdominal cramps, dizziness, headache, faintness, nausea, and vomiting. Hypotension and bradycardia persisted, despite volume resuscitation with normal saline. The treating physician suspected a link between the barracuda consumption and neurologic and gastrointestinal symptoms (Table 1), subsequently diagnosed CFP,* and contacted the NYC Poison Control Center (PCC). The PCC reported the incident to DOHMH, and a DOHMH inspector collected samples of barracuda from the fish market and the patients' home. The inspector also embargoed barracuda sale at the fish market.
Samples were analyzed for CTX at the Gulf Coast Seafood Laboratory of the Food and Drug Administration (FDA) using methods developed by FDA to confirm CFP cases. These methods included an in vitro mouse neuroblastoma cell assay for sodium channel toxins to provide a semiquantitative measure of composite ciguatoxicity in fish (1). Extracts that were positive by this method were subsequently analyzed by liquid chromatography–tandem mass spectrometry for unequivocal confirmation of ciguatoxins (1). One meal remnant was confirmed to contain Caribbean CTX-1 and -2 at a toxicity level of 1.1 µg/kg total C-CTX-1 equivalents, more than 10 times the FDA guidance level of 0.1 µg/kg total C-CTX-1 equivalents. The patients reported that some of their neurologic symptoms persisted for 2–5 months (Table 1).
During August–September 2010, an additional seven CFP cases were reported to DOHMH. These consisted of two outbreaks (outbreaks 2 and 3; Table 1) and a single case. All patients experienced symptoms consistent with CFP after eating barracuda purchased from fish markets in three different NYC boroughs and one restaurant (Table 2). On the evening of November 19, 2010, after reading the health alert about CFP, a physician reported a suspected CFP outbreak in Queens (outbreak 4). This new outbreak involved 11 persons from three families who had eaten fish labeled as grouper that was purchased from a Queens supermarket. Five hours after eating the fish, one family member visited the ED with vomiting, nausea, hypotension, and leg cramping. Shortly thereafter, other members of the family reported experiencing numbness and tingling, and two had bradycardia diagnosed several days after fish consumption. In contrast with previously reported cases, four patients experienced tooth pain or paradoxical dysesthesias (Table 1). New York State Department of Agriculture and Markets completed their traceback investigation and identified the same distributor involved in the barracuda-related CFP outbreak reported earlier that year.
On July 12, 2011, two separate outbreaks and an additional four cases that were associated with eating grouper at Manhattan restaurants were reported to DOHMH. One of the patients was a physically active man who swam >2 miles per day before his illness. After the onset of acute CFP symptoms, he had difficulty walking that persisted for several months. A sample of leftover fish was confirmed by FDA to contain 1.9 µg/kg total C-CTX-1 equivalents, exceeding the FDA guidance level by almost 20 times. Before this most recent outbreak, the implicated vendor was inspected by FDA and issued a warning letter detailing violations.
Reported by
Nathan Graber, MD, Faina Stavinsky, MS, Robert Hoffman, MD, Jessica Button, Nancy Clark, MA, New York City Dept of Health and Mental Hygiene; Scott Martin, MD, Stony Brook Univ Medical School, Stony Brook, New York. Alison Robertson, PhD, Food and Drug Administration. John Hustedt, MPH, Public Health Prevention Svc, CDC. Corresponding contributor: John Hustedt, johnhustedt@gmail.com, 212-788-4290.Editorial Note
CTX are naturally occurring toxins that can accumulate in commonly consumed coral reef fish (e.g., barracuda, grouper, snapper, amberjack, and surgeonfish). Precursors of CTX are derived from marine dinoflagellates (microalgae) that live on the surfaces of seaweeds and denuded corals. These microalgae are consumed by herbivorous fish and undergo bioconversion to the more potent CTX as they move through the food chain. CTX can accumulate in reef fish that eat other fish, reaching levels that can cause CFP among humans when consumed. The toxins are colorless, odorless, tasteless, and temperature-stable, making them difficult to detect or destroy. Consequently, CFP occurrence is not attributable to incorrect food handling, storage, preparation, or procurement methods. The attack rate can be 80%–90% among persons who have eaten a toxic fish, depending on the concentration of CTX in the fish, the total amount of fish consumed, and the consumer's body weight and health status (2). As in the outbreaks described in this report, symptomatology is variable.Initial treatment options for CFP are limited and supportive only. The majority of patients experience symptoms within 6–48 hours after eating contaminated fish. In an acutely symptomatic patient, any vital sign instability or electrolyte imbalance should be treated in accordance with the normal standard of care (3). Administration of intravenous mannitol was thought to reduce neuronal edema; however, a randomized double-blind, clinical trial found no evidence of mannitol being superior to normal saline, and mannitol can cause additional side effects, including hypotension, requiring caution during administration (4–6). Treatment of CFP symptoms (e.g., neuropathy, fatigue, and headache) with amitriptyline, sodium channel blockers, and pain medications all have been tried with variable success (4). Consultation with the local PCC is recommended and in NYC fulfills the reporting requirement.
This report reflects the importance of surveillance and outreach networks in responding to patients' histories, including food consumption, that are indicative of CFP, and highlights prevention challenges. Reports made to the NYC PCC allowed expeditious and effective action when the first cases of CFP were reported. Investigators notified other jurisdictions, consulted local health departments with expertise in CFP prevention and case management, and conducted outreach to NYC health-care providers. In southern Florida, where CFP is endemic, 68% of physicians who were presented with a typical case of CFP diagnosed it correctly (7). As a result of considerable education and outreach efforts by the Florida Department of Health during the past decade, accuracy of CFP diagnosis in that state has improved. However, in other nonendemic regions, diagnostic recognition remains low.
An interstate comparison of reports to PCCs revealed additional trends, beyond the increased number of NYC CFP cases. Unpublished data from CFP-related calls to the American Association of Poison Control Centers during 2000–2010 were analyzed for trends and changes in geographic distribution. The data revealed that the rate of CFP-related calls per capita during 2010, compared with the previous 10 years, was 55% higher in NYC but 44% lower in Florida. Although this data set might not be representative of individual state CFP records, the rate per capita of U.S. cases remained relatively constant throughout the preceding 11 years. This increase of reported cases in NYC might reflect changing sources and diversity of fish species marketed in NYC and elsewhere. The increase might also indicate improved awareness and capacity for investigation by the medical and public health community. The decrease in CFP reports from Florida likely was the result of improved awareness of CFP after extensive long-term outreach and education efforts and specific guidance on the harvest of high-risk fish in this endemic region.
CFP is considered a highly underreported illness, with only an estimated 10% of cases reported to health authorities (7). Increasing awareness among health-care providers might improve reporting and investigation. However, CFP prevention is complicated by difficulty in identifying high-risk fishing grounds and inadequate industry knowledge and compliance with the FDA seafood Hazard Analysis and Critical Control Point (HACCP) regulations.† Premarket testing of fish for CTX is not feasible because of the lack of rapid field methods and the sporadic distribution of toxic fish, even in endemic areas. Coordinated tracebacks of implicated fish by federal and state agencies to specific fishing grounds remains the primary strategy for managing CFP.
The findings in this report are subject to at least three limitations. First, meal remnant samples were available only in three of the six CFP outbreaks. Second, where physician reports to the PCC were unavailable, the symptoms were based entirely on self-report or secondhand reports from family members. Finally, additional cases might have occurred but were unrecognized because of lack of physician awareness to make an appropriate diagnosis and the need to report.
This investigation demonstrates the value of CFP-implicated fish traceback along with updated information on emerging CFP risks, including new harvest areas and species. Prevention through education alone might be limited by seafood mislabeling. Reports indicate that 20%–25% of all seafood products are mislabeled (8). A recent assessment of seafood purchased at retail stores and restaurants in New York, New Jersey, and Connecticut indicated that >20% of 190 specimens were mislabeled, incompletely labeled, or misidentified by employees (8). Methods for fish species identification using DNA barcoding have been validated (9) and are being implemented in several U.S. state and federal laboratories, as well as academic institutions. These methods have been applied to multiple CFP cases. Ongoing collaborative efforts with federal, state, and local agencies tasked with consumer protection and food safety might be useful in controlling CFP and mislabeling of fish (10). Until accurate and cost-effective means of premarket testing become available, prevention of additional cases will continue to be dependent on HACCP compliance by the seafood industry and CFP diagnosis and reporting by health-care providers, warranting additional outreach and education.
Acknowledgment
Munerah Ahmed, MPH, New York City Dept of Health and Mental Hygiene, New York.References
- Food and Drug Administration. FDA fish and fishery products hazards and controls guidance. 4th ed. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration; 2011. Available at http://www.fda.gov/downloads/food/guidancecomplianceregulatoryinformation/guidancedocuments/seafood/ucm251970.pdf
- CDC. Cluster of ciguatera fish poisoning—North Carolina, 2007. MMWR 2009;58:283–5.
- Thomson Reuters (Healthcare). Ciguatera fish poisoning. POISINDEX System [database]. Greenwood Village, Colorado: Thomson Reuters (Healthcare); 2012.
- Friedman MA, Fleming LE, Fernandez M, et al. Ciguatera fish poisoning: treatment, prevention and management. Mar Drugs 2008;6:456–79.
- Achaibar KC, Moore S, Bain PG. Ciguatera poisoning. Pract Neurol 2007;7:316–22.
- Schnorf H, Taurarii M, Cundy T. Ciguatera fish poisoning: a double-blind randomized trial of mannitol therapy. Neurology 2002;58:873–80.
- McKee D, Fleming LE, Tamer R, Weisman R, Blythe DG. Physician diagnosis and reporting of ciguatera fish poisoning in an endemic area. In: Hallegraeff GM, Blackburn SI, Bolch CJ, Lewis RJ, eds. Harmful algal blooms 2000. Paris, France: Intergovernmental Oceanographic Commission of United Nations Educational, Scientific, and Cultural Organization; 2001:451–3.
- Consumers Union. Mystery fish: the label said red snapper, the lab said baloney. Consum Rep 2011;76:18–22.
- Handy SM, Deeds JR, Ivanova NV, et al. A single laboratory validated method for the generation of DNA barcodes for the identification of fish for regulatory compliance. J AOAC Int 2011;94:201–10.
- Government Accountability Office. Seafood fraud—FDA program changes and better collaboration among key federal agencies could improve detection and prevention. Washington, DC: Government Accountability Office; 2009. Available at http://www.gao.gov/new.items/d09258.pdf
* Additional information on CFP signs and symptoms available at http://www.nyc.gov/html/doh/downloads/pdf/cd/2010/10md25.pdf .
.
† Additional information, including advisories and guidance related to high-risk species and endemic regions, is available at http://www.fda.gov/food/foodsafety/hazardanalysiscriticalcontrolpointshaccp/seafoodhaccp/default.htm.
.
sumber : centers for deseases control and prevention
di tayangkan ulang oleh : dr.Erick Supondha (hyperbaric& diving medicine consultant) hiperbarik oksigen terapi >RS bethsaida , jakarta indonesia, (dokter hiperbarik/ahli hiperbarik/dokter kesehatan penyelaman)
021 99070050
Senin, 26 November 2012
Barodontalgia &Diving
Barodontalgia
Karena Hukum Boyle, (dengan meningkatnya tekanan, penurunan volume dan sebaliknya), Melakukan penyelaman dengan adanya udara penuh pada lubang di gigi akan menyebabkan masalah, karena lubang di dalam gigi tidak dapat berubah ukurannya baik bertambah ataupun berkurang sesuai dengan kedalaman di bawah permukaan air. Saas dipermukaan air kita berada pada tekanan satu ATM dan jika kita menyelam sampai kedalamanan 99 FSW maka akan meningkatkan tekanan di dalam lubang gigi tadi sebesar 4 atm absolut, dan menimbulkan tekanan sebesar 58,6 lb / sq.in
peningkatan tekanan ini akan menyebabkan nyeri atau barodontalgia dan sangat mungkin membatasi kegiatan penyelam dari bawah air.
-------------------------------------------------- ------------------------------
Kondisi kondisi yang dapat memungkinkan udara masuk ke bagian dalam gigi dapat menyebabkan barodontalgia, termasuk karies, cacat margin restorasi, abses periodontal,Sumbatan sinus maksilaris, lesi pulpa dan terapi endodontik.
Gigi yang telah dibuka untuk perawatan endodontik dan untuk sementara ditutup pernah diketahui meledak akibat dari udara yang terperangkap disana dan ekspansi saat ke permukaan. Hal ini disebut sebagai odontocrexis dan ditemukan lebih umum pada penyelam dalam yang menggunakan campuran heliox. Penggunaan porselen utuh pada mahkota gigi juga dapat hancur pada penyelaman yang relatif dangkal, 65 meter. Hal ini diduga bahwa udara yang terperangkap adalah remover mahkota sangat efisien yang mana ikatan semen gagal. Kesehatan mulut sangat penting dan disarankan untuk penyelam yang aktif dalam scuba diving dan untuk menghindari barodontalgia, semua lesi karies harus diperbaiki, mahkota yang rusak diganti, lesi periodontal aktif diobati dan semua terapi endodontik disempurnakan.
Senin, 19 November 2012
Lightning and diving
Oceans Rarely Hit By Lightning
NASA has shown with satellite imaging that the oceans rarely get hit with lightning. Apparently the surface water does not heat up enough to cause the positive charge needed for lightning to occur. Potentially, lightning is the biggest weather danger for divers. Every year, lightning kills more people in the US than tornadoes or hurricanes. Only floods are more deadly. During the last three decades, floods killed an average of 139 people a year, lightning 87, tornadoes 82 and hurricanes 27 in the US, according to national Weather Service figures.
The question should be "what cautionaries should the scuba diver take?" Should he get out of the water? Is he safer in the water than in the boat? If shore diving - stay in the water or go ashore?
Over the years around ten percent of the lightning deaths in the US have been in or near the water- the statistics don't show how manyvictims were diving or swimming, how many were on boats and how many were on beaches. Lightning is likely to strike the highest thing around, which is why we're told not to take shelter under trees during thunderstorms. If you're in a boat during a thunderstorm, the boat and everyone in it are the highest things around; they're prime targets for lightning bolts. While people on land can take shelter in buildings or vehicles, those aboard a dive boat that's caught by a thunderstorm far from shore have no place to take shelter. Diving underwater may not be an option. Lightning that hits the water could be deadly because its electricity flows through water.
Scientists know little about what happens when lightning hits water. The electrical current probably spreads in all directions, weakening as it spreads out. Since large numbers of dead fish aren't found after thunderstorms move across bodies of water, the current probably weakens in short distances.
Still, a diver who happens to be underwater when a lightning bolt hits nearby could become part of an unintended scientific experiment on just how quickly the current weakens.
I can find nothing about a possible stand off distance, probably since a prediction cannot be made regarding the location of the strike. Assume that it will hit the highest point, however, and the answer would be to get out of the boat or stay in the water if shore diving. We just don't know the answer.
Ron Holle, research meteorologist, NOAA National Severe Storms Laboratory, Norman, Okla. has this to say about lightning and water:
"Large numbers of lightning flashes strike oceans, lakes, rivers, and ponds. If there is nothing protruding higher than a body of water or flat ground, then a flat surface is hit.
The area of a swimming pool is small, so it's not usually directly hit. However, the area affecting a pool is quite large. This area includes the surrounding power and telephone lines, and the plumbing around the pool and inside the bathhouse and other structures. These are usually unsafe places during a thunderstorm because the current from a lightning strike will travel easily through the standing water, showers and other plumbing. Since the pump, lights and other facilities have power lines linked to the plumbing, a hit to any part of a pool complex can affect all of it.
Water does not "attract" lightning. It does, however, conduct current very well. It's not clear how far lightning travels through water. People have been killed or injured by direct or indirect strikes while in or on the water, boats, docks, piers, surf, surfboards, canoes, while fishing, and so on. In most cases, it appears that the strike was within a few tens of yards of the person. But the current can extend farther through plumbing or wiring so the distance of influence can be greater.
In general, there is less lightning per area over water than over land. This is due to the fact that water bodies are usually cooler than land during summer. For this reason thunderstorms are less likely to build or continue to develop over water than over heated land.
The current in a lightning bolt is as high as 30,000 amperes --- about 150 times more than ordinary house current of 200 amps. It's easy to see how this much electricity is deadly. Fortunately, many lightning victims aren't hit directly, if all the charge doesn't go through them. This is why about six out of every seven persons hit by lightning survive, although sometimes with serious injuries and lasting ill effects.
Lightning will often hit something, such as a tree, a wire fence or a boat mast. Most of the electricity flows through the object that it hits, but some jumps to hit a person or people. This is called a 'side flash'. Such side flashes have killed people talking on the telephone or taking a shower inside otherwise safe buildings, following through phone lines or water pipes after hitting the ground. People are also sometimes injures when lightning hits the ground and follows it to where they are standing.
Lightning can affect all parts of the body, but the usual cause of deaths is heart stoppage. The electrical charge disrupts the heart's rhythm, stopping it. Usually, however, the heart will quickly resume beating. The electricity is more likely to paralyze the brain's respiratory center. The victim will die from lack of oxygen unless someone nearby can quickly perform artificial respiration to get the victim's breathing going again. This may have to continue for hours before the victim begins to breath normally.
A Lightning Safety Group, which met at the 1998 American Meteorolgical Society convention to update safety recommendations, noted in it's report: "Generally speaking, if an individual can see lightning and/or hear thunder, he or she is already at risk. Louder or more frequent thunder indicates that lightning activity is approaching, increasing the risk for lightning injury or death."
The report also notes that "many lightning casualties occur in the beginning, as the storm approaches --- Also, many lightning casualties occur after the perceived threat has passed." In fact, the danger can persist as long as thirty minutes after the storm has passed and the last thunder is heard.
Lightning always comes from a thunderstorm cloud, but has been known to hit as far as 20 miles from the nearest cloud, far from the storm's rain. This is why the group says seeing just one lightning bolt or hearing one clap of thunder should be a warning to get into a safe place.
If you're caught in a boat, about all you can do is crouch down in the boat's center and stay as far away from any metal surfaces, and radios or other electrical gear that might be attached to an antenna.
If you see lightning, knowing which way the wind is pushing the clouds will make a big difference. If the wind is pushing the clouds your way, it's time to head for shore. If you see lightning, the flash to bang method can also help determine whether lightning is moving closer. ( sound travels about one mile every five seconds).
--------------------------------------------------------------------------------
If caught at sea in a thunderstorm:
-Stay in the center of the cabin
--Keep arms and legs in the boat - do not dangle in the water.
--Discontinue all water activities
--Disconnect and do not touch any electronic equipment.
--Lower, remove or tie down the radio antenna and other protruding devices if not part of the lightning protection system
--Avoid making contact with any part of the boat connected to the lightning protection system. Avoid touching two components that are connected to the system at the same time, such as the gear lever and spotlight handle.
NOAA has this to say about lightning and water:
-Get out of the water, it's a great conductor of electricity.
-Stay off the beach and out of small boats or canoes.
-If caught in a boat, crouch down in the center away from metal hardware.
-Swimming, wading, snorkeling and scuba diving are NOT safe.
-Lightning can strike the water and travel some distance beneath and away from its point of contact.
-Don't stand in puddles of water.
The US Navy Manual does not address the problem, that I can find.
So-- what to do? If I were diving in a thunderstorm, I'd get out of the water. Before diving? I'd not dive during and for thirty minutes after the storm.
However, we might want to alter our recommendations considering this answer to a question to Science Update posed about lightning and fish kills. This was sent to us by Jeff Wiberg.
"Does lightning fry fish? I'm Bob Hirshon and this is Science Update.
Today's question comes from Matthew Dabney of Longmont, Colorado.
Matt:
"Why is it that we're directed to get out of water during a lightning storm to avoid electrocution? Do fish get electrocuted when the lightning strikes a lake?"
We asked Don MacGorman, a physicist at the National Severe Storms Laboratory in Norman, Oklahoma. He says that as long as the fish are underwater, they're probably okay.
Don:
"Basically lightning stays more on the surface of the water rather than penetrating it. That's because water is a reasonably good conductor, and a good conductor keeps most of the current on the surface."
So, when lightning hits the water, the current zips across the surface in all directions. And if you're swimming anywhere in the vicinity, it'll probably hit you. But below the surface, most of the electricity is instantly neutralized. So the fish are generally spared.
Of course, if the fish happen to be surfacing, they're at risk just like you are. And Dr. MacGorman adds that some electricity does penetrate the water, right at the strike point.
Don:
"So fish under a lightning strike can be killed, if it's close enough to the surface. But it has to be much closer than you do on the surface of the water."
Considering this answer - and if you have diving gear and adequate air - the best place for you to be would be underwater (not on the surface swimming).
--------------------------------------------------------------------------------
Links for Further Reading
Lightning Safety, National Weather Service, Melbourne, FL
Lightning Injuries, eMedicine, Mary Ann Cooper, MD
Lightning Injuries, eMedicine, Scott Bjerke, MD FACS
Lightning Injury Research Program
sumber: scubadoc.com
ditayangkan ulang oleh : dr.erick Supondha (hyperbaric&diving medicine Consultant) jakarta, indonesia , hiperbarik oksigen terapi RS. Bethsaida 021 99070050
NASA has shown with satellite imaging that the oceans rarely get hit with lightning. Apparently the surface water does not heat up enough to cause the positive charge needed for lightning to occur. Potentially, lightning is the biggest weather danger for divers. Every year, lightning kills more people in the US than tornadoes or hurricanes. Only floods are more deadly. During the last three decades, floods killed an average of 139 people a year, lightning 87, tornadoes 82 and hurricanes 27 in the US, according to national Weather Service figures.
The question should be "what cautionaries should the scuba diver take?" Should he get out of the water? Is he safer in the water than in the boat? If shore diving - stay in the water or go ashore?
Over the years around ten percent of the lightning deaths in the US have been in or near the water- the statistics don't show how manyvictims were diving or swimming, how many were on boats and how many were on beaches. Lightning is likely to strike the highest thing around, which is why we're told not to take shelter under trees during thunderstorms. If you're in a boat during a thunderstorm, the boat and everyone in it are the highest things around; they're prime targets for lightning bolts. While people on land can take shelter in buildings or vehicles, those aboard a dive boat that's caught by a thunderstorm far from shore have no place to take shelter. Diving underwater may not be an option. Lightning that hits the water could be deadly because its electricity flows through water.
Scientists know little about what happens when lightning hits water. The electrical current probably spreads in all directions, weakening as it spreads out. Since large numbers of dead fish aren't found after thunderstorms move across bodies of water, the current probably weakens in short distances.
Still, a diver who happens to be underwater when a lightning bolt hits nearby could become part of an unintended scientific experiment on just how quickly the current weakens.
I can find nothing about a possible stand off distance, probably since a prediction cannot be made regarding the location of the strike. Assume that it will hit the highest point, however, and the answer would be to get out of the boat or stay in the water if shore diving. We just don't know the answer.
Ron Holle, research meteorologist, NOAA National Severe Storms Laboratory, Norman, Okla. has this to say about lightning and water:
"Large numbers of lightning flashes strike oceans, lakes, rivers, and ponds. If there is nothing protruding higher than a body of water or flat ground, then a flat surface is hit.
The area of a swimming pool is small, so it's not usually directly hit. However, the area affecting a pool is quite large. This area includes the surrounding power and telephone lines, and the plumbing around the pool and inside the bathhouse and other structures. These are usually unsafe places during a thunderstorm because the current from a lightning strike will travel easily through the standing water, showers and other plumbing. Since the pump, lights and other facilities have power lines linked to the plumbing, a hit to any part of a pool complex can affect all of it.
Water does not "attract" lightning. It does, however, conduct current very well. It's not clear how far lightning travels through water. People have been killed or injured by direct or indirect strikes while in or on the water, boats, docks, piers, surf, surfboards, canoes, while fishing, and so on. In most cases, it appears that the strike was within a few tens of yards of the person. But the current can extend farther through plumbing or wiring so the distance of influence can be greater.
In general, there is less lightning per area over water than over land. This is due to the fact that water bodies are usually cooler than land during summer. For this reason thunderstorms are less likely to build or continue to develop over water than over heated land.
The current in a lightning bolt is as high as 30,000 amperes --- about 150 times more than ordinary house current of 200 amps. It's easy to see how this much electricity is deadly. Fortunately, many lightning victims aren't hit directly, if all the charge doesn't go through them. This is why about six out of every seven persons hit by lightning survive, although sometimes with serious injuries and lasting ill effects.
Lightning will often hit something, such as a tree, a wire fence or a boat mast. Most of the electricity flows through the object that it hits, but some jumps to hit a person or people. This is called a 'side flash'. Such side flashes have killed people talking on the telephone or taking a shower inside otherwise safe buildings, following through phone lines or water pipes after hitting the ground. People are also sometimes injures when lightning hits the ground and follows it to where they are standing.
Lightning can affect all parts of the body, but the usual cause of deaths is heart stoppage. The electrical charge disrupts the heart's rhythm, stopping it. Usually, however, the heart will quickly resume beating. The electricity is more likely to paralyze the brain's respiratory center. The victim will die from lack of oxygen unless someone nearby can quickly perform artificial respiration to get the victim's breathing going again. This may have to continue for hours before the victim begins to breath normally.
A Lightning Safety Group, which met at the 1998 American Meteorolgical Society convention to update safety recommendations, noted in it's report: "Generally speaking, if an individual can see lightning and/or hear thunder, he or she is already at risk. Louder or more frequent thunder indicates that lightning activity is approaching, increasing the risk for lightning injury or death."
The report also notes that "many lightning casualties occur in the beginning, as the storm approaches --- Also, many lightning casualties occur after the perceived threat has passed." In fact, the danger can persist as long as thirty minutes after the storm has passed and the last thunder is heard.
Lightning always comes from a thunderstorm cloud, but has been known to hit as far as 20 miles from the nearest cloud, far from the storm's rain. This is why the group says seeing just one lightning bolt or hearing one clap of thunder should be a warning to get into a safe place.
If you're caught in a boat, about all you can do is crouch down in the boat's center and stay as far away from any metal surfaces, and radios or other electrical gear that might be attached to an antenna.
If you see lightning, knowing which way the wind is pushing the clouds will make a big difference. If the wind is pushing the clouds your way, it's time to head for shore. If you see lightning, the flash to bang method can also help determine whether lightning is moving closer. ( sound travels about one mile every five seconds).
--------------------------------------------------------------------------------
If caught at sea in a thunderstorm:
-Stay in the center of the cabin
--Keep arms and legs in the boat - do not dangle in the water.
--Discontinue all water activities
--Disconnect and do not touch any electronic equipment.
--Lower, remove or tie down the radio antenna and other protruding devices if not part of the lightning protection system
--Avoid making contact with any part of the boat connected to the lightning protection system. Avoid touching two components that are connected to the system at the same time, such as the gear lever and spotlight handle.
NOAA has this to say about lightning and water:
-Get out of the water, it's a great conductor of electricity.
-Stay off the beach and out of small boats or canoes.
-If caught in a boat, crouch down in the center away from metal hardware.
-Swimming, wading, snorkeling and scuba diving are NOT safe.
-Lightning can strike the water and travel some distance beneath and away from its point of contact.
-Don't stand in puddles of water.
The US Navy Manual does not address the problem, that I can find.
So-- what to do? If I were diving in a thunderstorm, I'd get out of the water. Before diving? I'd not dive during and for thirty minutes after the storm.
However, we might want to alter our recommendations considering this answer to a question to Science Update posed about lightning and fish kills. This was sent to us by Jeff Wiberg.
"Does lightning fry fish? I'm Bob Hirshon and this is Science Update.
Today's question comes from Matthew Dabney of Longmont, Colorado.
Matt:
"Why is it that we're directed to get out of water during a lightning storm to avoid electrocution? Do fish get electrocuted when the lightning strikes a lake?"
We asked Don MacGorman, a physicist at the National Severe Storms Laboratory in Norman, Oklahoma. He says that as long as the fish are underwater, they're probably okay.
Don:
"Basically lightning stays more on the surface of the water rather than penetrating it. That's because water is a reasonably good conductor, and a good conductor keeps most of the current on the surface."
So, when lightning hits the water, the current zips across the surface in all directions. And if you're swimming anywhere in the vicinity, it'll probably hit you. But below the surface, most of the electricity is instantly neutralized. So the fish are generally spared.
Of course, if the fish happen to be surfacing, they're at risk just like you are. And Dr. MacGorman adds that some electricity does penetrate the water, right at the strike point.
Don:
"So fish under a lightning strike can be killed, if it's close enough to the surface. But it has to be much closer than you do on the surface of the water."
Considering this answer - and if you have diving gear and adequate air - the best place for you to be would be underwater (not on the surface swimming).
--------------------------------------------------------------------------------
Links for Further Reading
Lightning Safety, National Weather Service, Melbourne, FL
Lightning Injuries, eMedicine, Mary Ann Cooper, MD
Lightning Injuries, eMedicine, Scott Bjerke, MD FACS
Lightning Injury Research Program
sumber: scubadoc.com
ditayangkan ulang oleh : dr.erick Supondha (hyperbaric&diving medicine Consultant) jakarta, indonesia , hiperbarik oksigen terapi RS. Bethsaida 021 99070050
Senin, 12 November 2012
Senin, 05 November 2012
Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke.
Abstract
Background
Recovery after stroke correlates with non-active (stunned) brain regions, which may persist for years. The current study aimed to evaluate whether increasing the level of dissolved oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke.
Methods and Findings
A prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6–36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to "treated" or "cross" groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (5 days/week), 90 minutes each, 100% oxygen at 2 ATA. We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group. Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) – regions of noticeable discrepancy between anatomy and physiology.
Conclusions
The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.
Trial Registration
ClinicalTrials.gov NCT00715897
Citation: Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, et al. (2013) Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients - Randomized, Prospective Trial. PLoS ONE 8(1): e53716. doi:10.1371/journal.pone.0053716
Editor: Jens Minnerup, University of Münster, Germany
Received: June 17, 2012; Accepted: December 5, 2012; Published: January 15, 2013
Copyright: © 2013 Efrati et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was supported by the research fund of Assaf-Harofeh medical center, by the Tauber Family Foundation and the Maguy-Glass Chair in Physics of Complex Systems at Tel Aviv University and by Joseph Hackmey. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors herby declare that, although Prof. Eshel Ben-Jacob is a PLOS ONE Editorial Board member, this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
* E-mail: efratishai@013.net
Introduction
Intensive functional therapy and rehabilitation programs for post stroke patients are considered essential for maximizing the patients' quality of life [1], [2]. Unfortunately, these programs are often just partially successful, and additional therapeutic approaches towards metabolic recovery of affected cerebral tissues are called for. While a considerable amount of preclinical research supports the use of hyperbaric oxygen therapy (HBOT) for post-stroke damaged brain tissue, so far, only 5 articles reported controlled clinical trials of HBOT for stroke patients. These studies, in which the treatment started during the early-acute phase immediately after stroke, yielded non conclusive and somewhat contradicting results [3], [4], [5], [6], [7]. In contrast, a recent phase-I study evaluating the effect of HBOT on chronic neurological deficiencies (due to traumatic brain injury) revealed promising results [8]. However, to date the effects of HBOT on neurological deficiencies due to stroke during the late-chronic phase (the focus of the current report) have not yet been investigated in a prospective randomized trial.
Years of clinical experience revealed that the dramatic spontaneous recovery from stroke occurs mainly within the first 30 days, though moderate and severe stroke survivors continue to improve for at least 90 days [9]. Most of the recovery involves brain regions rendered dysfunctional, but not dead [10]. Accumulated data from visualizations of these non-active (stunned) regions indicates that they may persist alive but dysfunctional for months, even years, after the acute injury [11], [12], [13]. It was proposed that the oxygen supply to these under-active neurons was low due to stroke damage to blood vessels in these regions, leading to oxygen deficiency, anaerobic metabolism and ATP depletion [14], [15]. The decreased oxygen level not only causes reduction in the neuronal activity but also prevents angiogenesis to replace the stroke-damaged blood vessels and the generation of new synaptic connections. Since 1 cm3 of normal brain tissue contains about 1 km of blood vessels, high oxygen supply is essential for repair of the stunned regions. Indeed, as has been demonstrated by previous studies, an increase in dissolved oxygen has several beneficial effects in damaged brain tissues [13], [16], [17], [18], [19], [20]. Transport of oxygen to glial mitochondria, the main sites of oxygen utilization, follows oxygen release from erythrocytes into the plasma and then diffusion of the blood-dissolved oxygen across the Blood-Brain Barrier (BBB). Breathing oxygen under hyperbaric conditions has been shown to be a potent means of increasing arterial oxygen tension and consequently the brain oxygen tension [20], [21], [22]. For example, at 2ATA (atmospheres absolute), the plasma O2 partial pressure rises above 1,110 mmHg. Hence, it is reasonable to expect that HBOT can be an efficient (and clinically feasible) method for increasing tissue/cellular oxygenation and thus effectively evoking neuroplasticity in the chronically non-active areas during the late post-stroke phase.
Many physiological pathways, each with a different characteristic time, are spontaneously activated following the onset of stroke. Therefore, a challenging question to be addressed considers the optimal time lapse after stroke to start the HBOT procedure. It should also be kept in mind that signals and chemical cues associated with cell death during the acute stage of stroke might, in fact, promote repair during recovery [23] and can be negatively affected by premature application of HBOT. Unlike the case of preclinical animal studies, in clinical practice it is not feasible to apply the HBOT immediately at the stroke onset. Thus, HBOT procedure can practically begin either at the degenerative or at the regenerative stage. One can assume that any added energy during the degenerative stage could further increase the unwanted, post-injury damage. On the other hand, elevated oxygen supply during the regenerative stage would supply the energy needs for the innate brain repair processes. The differences in the time lapse between stroke onset and HBOT application in previous studies are likely to be the reason for the contradictive results obtained for HBOT application during the acute phase after stroke [3], [4], [5], [6], [7]. The aim of the current study was to evaluate the effects of HBOT started at the late-chronic phase after the acute stroke.
Methods
The study was performed as a prospective, randomized, controlled, two-group trial. The population included patients of ages 18 years or older, who had either ischemic or hemorrhagic stroke 6–36 months prior to their inclusion. All patients had to have at least one motor dysfunction. Exclusions were based on chest pathology incompatible with HBOT, inner ear disease, claustrophobia and inability to sign informed consent. Additional exclusions were based on dynamic neurologic improvements during the last month (based either on objective measurements by external evaluator or on subjective statement by the patients). Smoking was not allowed during the study. All patients signed written informed consent; the protocol was approved by the local Helsinki committee. The study was conducted in the hyperbaric and research units of Assaf-Harofeh Medical Center, Israel.
Protocol and End Points
After signing an informed consent form, the patients were invited for baseline evaluations. Included patients were randomized into two groups (1:1 randomization): a treated group and a cross group. The neurologic functions as evaluated by National Institutes of Health Stroke Scale (NIHSS) [24], [25], ability to perform activities of daily living (ADL) [26], and brain metabolism as visualized SPECT were the primary endpoints of the study. The secondary end point of the study included Quality of life evaluation. The patients in the treated group were evaluated twice – at baseline and after 2 months of HBOT treatment. Patients in the cross group were evaluated three times: baseline, after 2 months control period of no treatment, and after consequent 2 months of HBOT sessions (Figure 1). The post-HBOT neurological evaluations as well as the SPECT scans were performed more than 1 week (1–3 weeks) after the end of the HBOT protocol. The following HBOT protocol was practiced: 40 daily sessions, 5 days/week, 90 minutes each, 100% oxygen at 2ATA. The detailed clinical study protocol (Protocol S1), randomization and placebo consideration (Text S1), copy of the informed consent (Form S1), as well as CONSORT 2010 checklist of information (Checklist S1) are attached as supporting information.
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Figure 1. Flowchart of the patients in the study.
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Neurologic Evaluation
The clinical severity of the stroke was blindly assessed by a trained physician according to the NIHSS [24], [25]. The ADL were evaluated by a questionnaire covering the following functions: bathing, dressing, grooming, oral care, toileting, walking, climbing stairs, eating, shopping, cooking, managing medications, using phone, housework, doing laundry, driving and managing finances [26]. For each criterion, the patient defined whether he/she is independent, needs help, dependent or does not do at all (range: 0(best)-51(worst)).
Brain Functional Imaging and Analysis
Brain single photon emission computed tomography (SPECT) was conducted with 925–1,110 MBq (25–30 mCi) of technetium-99methyl-cysteinate-dimmer(Tc-99m-ECD)at40–60 min post injection using a dual detector gamma camera (ECAM or Symbia T, Siemens Medical Systems) equipped with high resolution collimators. Data was acquired in 3-degree steps and reconstructed iteratively with Chang method (μ = 0.12/cm) attenuation correction [27]. Visual analysis was conducted by fusing pre- and post-treatment studies that were normalized to pre-treatment whole brain activity. SPECT images were reoriented into Talairach space using NeuroGam (Segami Corporation) for identification (based on visual inspection) of abnormal perfusion regions and in order to compute volume rendered brain images.
More specifically, the assessment was done independently by two nuclear medicine physicians who compared the scans and graded them as either: 1 = no change, 2 = mild change and 3 = significant change. This was done “blindly” (without pre-conditioned information about the patients). “No change” was assigned to no visual difference in the number or size of perfusion deficits; “mild change” to a reduction in number or size of perfusion defects; “significant change” to a global perfusion increment in addition to diminution of defect numbers or size. Differences in evaluation were resolved after mutual reviewing. A comparison of the SPECT results with anatomical imaging CT was conducted in order to evaluate the extent of perfusion deficit in relation to the anatomical lesion. All SPECT analysis were done while blinded to the laboratory and clinical data.
Quality of Life Evaluation
Quality of life was evaluated by the EQ-5D questionnaire [28]. EQ-5D essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D descriptive system covers mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-VAS records the respondent’s self-rated health on a vertical, visual analogue scale (range: 0(worst)-100(best)).
Statistical Analysis
The statistical analysis considerations are detailed in Appendix A. SAS software (version 9.1; SAS Inc.) was used. Continuous data is expressed as means ± STD (standard deviation) and compared by unpaired t-test for inter-group comparison and by paired t-test for intra-group comparison. Categorical data is expressed in numbers and percentages and compared by chi-square test. P values<0 .05="" all="" allocated="" analyses.="" analysis="" and="" assessment="" considered="" efficacy="" had="" in="" included="" patients="" post-baseline="" randomly="" safety="" significant.="" statistically="" the="" those="" were="" who="">
Scatter Plot Analysis of the Clinical Scores
The analysis aims to better quantify and compare changes in the clinical scores, while taking into consideration the high patient-to-patient variability. The idea was to inspect, for each patient at each time stage, the scaled relative differences in each of the clinical scores. More specifically, we calculated for a specific patient (j) the scaled relative difference SRDj, defined as:
Where SFj is the value of a clinical score at the end of the time stage (either treatment or control), and SIj is the score at the beginning of the time stage. We note that the symbol<> indicates average over the values of the patients in the group. For example,means the average of SFj over all patients (j) that belong to the group. The abbreviation STD means the standard deviation between the values of the patients in the group. This analysis enables quantitative inspection of the changes in the clinical scores as is further explained and illustrated in Text S2. We note that the results can be further signified when the averaged difference () is not divided by STD(SFj–SIj).
Results
The study included 74 patients (August 2008-October 2010). 7 patients from the treated group and 8 patients from the cross group were excluded: 8 refused the SPECT, 3 had no measurable paresis, 1 had a medical problem, 1 had a stroke during the control period, and 2 refused to quit smoking (Figure 1).
Twenty four patients (80%) from the treated group had a history of ischemic stroke; of those, 17(71%), 3(13%), 2(8%) and 2(8%) patients were classified as TOAST 1, 2, 3 and 4, respectively. Twenty five patients (86%) from the cross group had ischemic stroke; of those, 18(72%), 3(12%), 2(8%) and 2(8%) patients were classified as TOAST 1, 2, 3 and 4, respectively; p = 0.8 for comparison of the TOAST classification between the groups. Of the 6 patients (20%) in the treated group that had hemorrhagic stroke, 5(83%) had anterior circulation stroke; and of the 4 patients with hemorrhagic stroke in the cross group, 3(75%) had anterior stroke. Baseline patients’ characteristics are summarized in Table 1.
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Table 1. Baseline patients' characteristics.
doi:10.1371/journal.pone.0053716.t001
Neurologic Evaluation
The results of the neurological evaluations, including the NIHSS and the ADL and the quality of life estimates EQ-5D and EQ-VAS, are summarized in Table 2. Details of the parameter estimates, significance levels and confidence intervals for NIHSS and ADL are presented in Figure 2.
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Figure 2. The results of the neurological evaluation. Each point represents a patient.
(A–C) NIHSS score: (A) Scores of the treated group patients before and after the HBOT period (B) Scores of the cross group before and after the control (no treatment) period. (C) Scores of the cross group after the HBOT period. (D–F) The same as (A)-(C) for the activities of daily living (ADL) scores. We note that the lines indicate the diagonal. Abbreviation: NIHSS = National Institutes of Health Stroke Scale; ADL = Activities of Daily Living.
doi:10.1371/journal.pone.0053716.g002
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Table 2. Summary of the results of the National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) and quality of life questionnaire (EQ-5D and EQ-VAS).
doi:10.1371/journal.pone.0053716.t002
NIHSS.
Clinical evaluations revealed statistically significant improvements in the NIHSS measures following treatment both in the HBOT-treated group (Figure 2a; p = 0.004 compared to control) and in the HBOT-treated cross group (Figure 2c; p<0 .0001="" 2b="" all="" at="" baseline.="" change="" compared="" control="" cross="" did="" during="" further="" group="" igure="" improvements="" is="" non-treatment="" not="" noticeable="" of="" p="0.43" period="" pre-hbot="" scores="" significance="" the="" these="" to="" when="" which="">
ADL.
Clinical evaluations revealed statistically significant improvements in the ADL score following treatment both in the HBOT-treated group (Figure 2d; p<0 .001="" 2e="" 2f="" adl="" after="" and="" baseline="" change="" compared="" control="" cross="" during="" further="" group="" hbot-treated="" igure="" improvements="" in="" is="" no="" non-treatment="" noticeable="" of="" p="0.42" period="" pre-hbot="" scores="" significance="" the="" there="" these="" to="" was="" when="" which="">
Scatter Plot Analysis of the Neurological Evaluations
The statistical significance of the improvements following the treatment periods is noticeable in the scatter plot analysis represented in Figure 3 and further detailed in Appendix B. In particular, the results show that the combined score of all patients improved following HBOT, while remaining unchanged during the control period.
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Figure 3. Scatter plot analysis of the changes in the combined neurological evaluations.
The scatter plot shows changes in the NIHSS and ADL scores in terms of the scaled relative differences as is defined in the methods section (averaged difference () is not divided by STD(SFj−SIj)). The color code is – changes during the treatment periods for the HBOT treated group (red diamonds), changes during for the HBOT-treated cross group (red circles) and changes during the control (non-treatment) period of the HBOT-treated cross group (blue circles).
doi:10.1371/journal.pone.0053716.g003
Quality of Life
The effect on the quality of life is summarized in Table 2. The EQ-5D score significantly improved following treatment, both for the HBOT-treated group (p<0 .0001="" 2.="" and="" as="" baseline="" between="" both="" compared="" comparison="" control="" cross="" eq-vas="" evaluations="" following="" for="" group="" groups="" hbot-treated="" improved="" improvement="" in="" is="" more="" no="" obtained="" p="0.016" period="" pre-hbot="" results="" score="" significant="" significantly="" similar="" specifically="" summarized="" table="" the="" there="" to="" treatment="" was="" were="" while="">
Brain Functional Imaging- rCBF SPECT Imaging
All brain SPECT evaluations were completed for 29 patients in the treated group and for 28 in the cross group. Comparison of brain activity improvement following the HBOT revealed that 55% of the treated group had significant improvement after HBOT and 35% had mild improvement. In the cross group, during the first (control) period 36% had mild improvement and only 6.2% had significant improvement (p<0 .001="" 29="" 43="" after="" and="" cross="" data="" demonstrated="" group="" hbot="" improvement="" in="" mild="" not="" p="" shown="" significant="" tables="" the="">
The improvements in the SPECT were mostly in regions showing noticeable discrepancy between the CT and SPECT–the earlier mentioned stunned regions of low activity living cells. The following examples of three typical patients illustrate the associations between the improvements in the patients’ clinical conditions and evaluations and the changes in their brain activity (indication of the activation of neuroplasticity) as reflected by changes in their corresponding SPECT images:
Example-1.
Baseline brain SPECT images demonstrating hypoperfusion in the right fronto-parietal region, right postero-medial frontal and posterior-parietal perfusion lesions with no significant changes after the control period (Figure 4). In comparison, the SPECT after HBOT demonstrated disappearance of the perfusion lesions. Global cortical and subcortical perfusion improvement was seen (Figure 5).
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Figure 4. Volume rendered Brain SPECT perfusion maps of Example 1.
The results are of a patient in the cross group, suffering from left hemiparesis due to ischemic stroke that occurred 1 year prior to inclusion in the study. Baseline and control volume rendered brain perfusion views show diffuse hypoperfusion in the right hemisphere involving the fronto-parietal region and right postero-medial frontal (right motor cortex), right medial parietal and posterior-parietal (sensory cortex and associative motor cortex) (red circles). The HBOT SPECT scan done at the end of HBOT treatments shows disappearance of the perfusion deficits that were still demonstrated at the end of the control period. In addition, a significant global cortical and subcortical (basal ganglia and thalamic nuclei) perfusion improvement is seen.
doi:10.1371/journal.pone.0053716.g004
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Figure 5. Volume rendered Brain SPECT perfusion maps of Example 2.
The results are of a patient in the treated group, suffering from right hemiparesis due to ischemic stroke that occurred 14 months prior to her inclusion in the study. Comparison of pre- and post-hyperbaric treatment SPECT scans. These SPECT images demonstrate significant improvement of perfusion deficits in the left hemisphere involving the medial and posterolateral frontal area (motor cortex, red circles) and lateral inferior frontal region (Broca's area, blue circles) in comparison to the baseline SPECT. HBOT SPECT findings correlate positively with the patient's improved motor and verbal functions.
doi:10.1371/journal.pone.0053716.g005
These SPECT images are of a 61y old woman from the cross group, suffering from left hemiparesis due to ischemic stroke that occurred 1 year prior to inclusion. Baseline NIHSS showed minor facial paresis, no ability to hold her left hand against gravity, some ability to hold her left leg against gravity for less than 5 seconds and mild-to-moderate sensory loss. In ADL, she needed help in bathing, dressing and climbing stairs. She was unable to do any housework. After HBOT, she was able to hold her hand and leg against gravity without significant sensory loss. She could move her fingers, was independent in bathing, dressing, shopping and cooking.
Example-2.
SPECT images at the end of HBOT demonstrating significant improvement of perfusion deficit in the left hemisphere (Figure 5) involving the medial and posterolateral frontal area (motor cortex) and lateral inferior frontal area (Broca's area). These images are from a 62y old woman from the treated group suffering from right hemiparesis due to ischemic stroke that occurred 14 months prior to inclusion. Baseline NIHSS showed no movement in her right arm, some effort against gravity in her right leg, mild-moderate aphasia, alexia and mild-moderate dysarthria. In ADL, she was completely dependent in bathing and dressing and needed help in transferring, walking, climbing stairs and eating. After HBOT, she could move her right hand against gravity, move fingers, and hold her leg against gravity. She regained speech (almost fluent) and reading capabilities. In ADL, she was able to walk, climb stairs and eat by herself. She was not dependent in bathing and dressing.
Example-3.
SPECT images demonstrating improvement in the peri-infarct region following HBOT. The images are of a 64y old woman from the treated group suffering from right hemiparesis due to ischemic stroke that occurred 26 months prior to inclusion. After treatment, the leg hemiparesis was resolved, her hand function improved significantly but she did not regain all fine motor skills. Figure 6 shows improvement in the peri-infarct region.
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Figure 6. Volume rendered Brain SPECT perfusion maps of Example 3.
The results are of a patient in the treated group suffering from left hemiparesis due to ischemic stroke that occurred 26 months prior to inclusion in the study. The brain perfusion maps (upper two images) show the infracted brain (deep blue color) involving the right antero-postero-lateral frontal, right superior-parietal and right parieto-occipital regions. Curved sagittal view in CT MIP reconstruction of the brain shows the anatomical stroke area (left lower image, V = posterior horn of right ventricle). The peri-infarct region show improved perfusion as demonstrated by HBOT image (right upper image). Quantitation of the cerebral blood flow (CBF) change (delta between baseline and HBOT) is demonstrated in the right lower image.
doi:10.1371/journal.pone.0053716.g006
Safety
Six patients had mild-moderate barotrauma of the middle ear. After several days of rest they returned and completed the protocol. Two patients with a history of epileptic seizures prior to their inclusion in the study had mild episodes of convulsion (consciousness was fully maintained) during the study. Both patients were already treated with anti-epileptic drugs prior to their inclusion.
Discussion
In the current study, the effect of HBOT on chronic neurological deficiency due to stroke was evaluated in a prospective, randomized controlled study. Statistically significant improvements were obtained following treatment for almost all treated patients from both the HBOT-treated group and the HBOT-treated cross group (with no false negative), as was evaluated by NIHSS, ADL, brain SPECT and life quality. The significance of the improvements in this chronically debilitated population of patients is further noticeable when compared to the lack of improvement during the control (no-treatment) period of the cross group (with no false positive).
This is the first prospective, randomized clinical study evaluating the effect of HBOT in the late post-stroke period (6 months to 3 years after the acute event). There are two major reasons for selecting this study population. First, by carefully selecting patients with chronic stable neurological deficiency we were able to avoid unexpected changes in their condition. In this regard, the selection proved very useful since the control group demonstrated neurological stability with no outliers. The second reason was, as discussed in the introduction, to test our hypothesis that the optimal time for the HBOT procedure should be during the regenerative and not during the degenerative stage. While it is not possible to mark a clear line between the regenerative and the degenerative phases [23], it is quite clear that 6 months after the acute event in a stable patient the degenerative process has ended. As mentioned in the introduction, the differences in initiation times and protocols of HBOT may explain contradictive results in previous studies, where HBOT was used in the early phase after stroke [3], [4], [5], [6], [7]. The recent publication by Harch et al., evaluating the effect of HBOT on chronic neurological deficiencies due to traumatic brain injury, also supports the use of HBOT in the late stage after the acute insult [8].
The issue of “how to handle the control group” was discussed by a multidisciplinary team including physicians specializing in hyperbaric medicine, physicists specializing in neuronal-glia interactions and the ethics committee. The patients can tell if pressure is increased or not, so the pressure must be increased also in the control group. The only way to administer “placebo” of HBOT is to bring the patients to the hyperbaric chamber and to increase the environmental pressure to an extent that the patients will feel it in their ears. The minimal pressure needed to gain such a feeling should be 1.3 ATM. Henry’s law states: “the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the pressure of that gas in equilibrium with that liquid”. Thus, hyperbaric environment significantly increases the dissolved oxygen pressure even if a person holding his breath [29]. Compressed air at 1.3 ATA increases the plasma oxygen tension by at least 50% and that is certainly notable. There are many case reports illustrating significant effects following small increase in air pressure [30], [31], [32]. Moreover, even a slight increase in partial pressure, such as, for example, to 1.05 ATM at altitude 402 m below sea level (the Dead Sea), can lead to noticeable physiological effects [33], [34], [35], [36], [37]. However, it should be kept in mind that oxygen is not a drug, and because it is metabolized mainly in the mitochondria, there is no simple dose-response curve.
Since increasing the pressure even without adding oxygen can also increases the dissolved oxygen partial pressure, the only way to maintain normal (placebo) levels of dissolved oxygen is to supply air with lower than normal level of oxygen, which we deemed unethical. To partially compensate for this inherent limitation, the patients in the cross group started with a two-month control period of no treatment, at the end of which they were crossed to two months of HBOT sessions. To gain better validity of the results, we used the scatter plot analysis of the changes in the combined neurological evaluations. The scatter plots (figure 3) show changes in the NIHSS and ADL scores in terms of the scaled relative differences, as is defined in the methods section. In that analysis, summarized in figures 2 & 3, the correlation between changes NIHSS & ADL after HBOT is clearly demonstrated. Moreover, the analysis evidently demonstrates that the effect of HBOT on these “not completely blinded evolution” was the same in the treated group and the control group after blind randomization. The correlation between the improvement in NIHSS and ADL and the improvement in the brain SPECT results, which was done in a completely blinded fashion, further substantiates the clinical findings. Moreover, the consistency between the anatomical locations of the changes in the brain metabolism, as demonstrated by the SPECT, with the finding in the neurological evaluation provides important validation of the neurological evaluation.
During most of the 20th century, there was an ongoing debate about the time window available for induction of neuroplasticity. The improvements in the chronic late stage reported here support the view that neuroplasticity can be activated months to years after the acute event when a proper brain stimulation (such as HBOT) is applied. More specifically, the current study included patients that underwent stroke more than 6 months prior to treatment and after their condition reached a steady state (no improvements were monitored for at least a month). These important and unexpected findings arein agreement with other recent findings revealing that many aspects of the brain remain plastic even at adulthood [38]. They are also consistent with several other studies in post stroke patients [39], [40], [41]. In the current study, patients were treated only with HBOT without any additional guided training and/or practice. This was done in order to demonstrate the therapeutic potential of this treatment. It is reasonable to expect that exploiting the HBOT in conjunction with other rehabilitation intervention can lead to even better results leading to optimal future practice. The current study paved the way for future investigations of this promising direction, which should be one of the aims of upcoming more elaborated clinical studies.
Current imaging technologies reveal that the stunned brain areas (regions of high anatomy-physiology mismatch) may persist for months and years after an acute brain event [11], [12], [13]. The changes in SPECT images after treatment demonstrate that the HBOT procedure led to reactivations of neuronal activity in the stunned areas. While SPECT imaging has limited spatial resolutions (in comparison, for example, to fMRI), the changes in activity were sufficiently robust to be clearly detected by the SPECT images. However, a future, more detailed study using fMRI (along with direct observations on animal model) will be able to provide additional valuable insights, in particular regarding the operative underlying mechanisms that activate the neuroplasticity (e.g. the putative role of glial cells). We note that patients were not selected based on their anatomical and functional brain imaging evaluation. It might be possible that the results would have been even better had the study included only patients with high SPECT/CT mismatch. This issue of the preferred population for HBOT should be further investigated in future clinical trials. We also note that in the current pioneering study aimed at “proof of concept”, all patients underwent 40 HBOT sessions. Based on our current clinical experience, more sessions of HBOT may be needed, at least for some patients, in order to obtain the maximal improvement effect.
In any case, the observed reactivation of neuronal activity in the stunned areas imply that increasing the plasma oxygen concentration with hyperbaric oxygenation is a potent means of delivering to the brain sufficient oxygen for tissue repair: HBOT might initiate a cellular and vascular repair mechanism and improve cerebral vascular flow [8], [13], [16], [17]. At the cellular level, HBOT can improve mitochondrial function (in both neurons and glial cells) and cellular metabolism; improve BBB and inflammatory reactions; reduce apoptosis; alleviate oxidative stress; increase levels of neurotrophins and nitric oxide, and up-regulate axon guidance agents [13], [16], [17], [20]. Moreover, the effects of HBOT on neurons can be mediated indirectly by glial cells, including asrocytes [18]. HBOT may also promote neurogenesis of the endogenous neural stem cells [19]. The major limitation of the above-mentioned data is that it has been tested in different types of models and includes different protocols of HBOT. However, it is well noticed that there is at least one common denominator to all repair/regeneration mechanisms: they are all energy/oxygen dependent. It might be possible that HBOT enables the metabolic change simply by supplying the missing energy/oxygen needed for those regeneration processes.
To conclude, in this study we provide, for the first time, convincing results demonstrating that HBOT can induce significant neurological improvement in post stroke patients. The neurological improvements in a chronic late stage demonstrate that neuroplasticity can be operative and activated by HBOT even long after acute brain insult. Thus, the findings have important implications that can be of general relevance and interest in neurobiology. Although this study focused on stroke patients, the findings bear the promise that HBOT may serve as a valuable therapeutic practice in other neurological disorders exhibiting discrepancy between the anatomical and functional evaluation of the brain.
Supporting Information
Protocol S1.
Clinical Study Protocol.
(DOCX)
Checklist S1.
CONSORT 2010 checklist.
(DOCX)
Form S1.
Informed consent form (English translation).
(PDF)
Text S1.
Statistical, Randomization and Placebo Considerations.
(DOCX)
Text S2.
Scatter plot analysis of the clinical scores.
(DOCX)
Acknowledgments
We are thankful Dr. Alexander Vol and Dr. Orna Gribova for enlightening discussions regarding the neurophysiology and oxygen related processes in brain recovery. Special thanks to Dr. Hanna Levi for valuable help with the statistics and data analysis. We thank Michal Ben-Jacob for her significant help in editing the manuscript. We thank the following individuals for their important contribution in patients’ management during this study: Alona Esterin, Mazi Aski-Sela, Angela Chanimov, Malca Katovski, Lea Shkolnic, Eyal Malca. Vitali Triban.
Author Contributions
Conceived and designed the experiments: SE GF IK NG HG. Performed the experiments: SE GF YB JB MF. Analyzed the data: SE OV KK EB-J HG. Wrote the paper: SE EB-J HG. Performed the experiments (brain SPECT): OV. Performed the experiments (neurological evaluation part): IK. Performed the experiments (brain imaging part): HG.
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di tayangkan ulang oleh dr.Erick Supondha (hyperbaric & Diving Medicine Consultant) Jakarta, indonesia
hiperbarik oksigen terapi RS. Bethsaida 021 99070050
sumber :http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053716
Background
Recovery after stroke correlates with non-active (stunned) brain regions, which may persist for years. The current study aimed to evaluate whether increasing the level of dissolved oxygen by Hyperbaric Oxygen Therapy (HBOT) could activate neuroplasticity in patients with chronic neurologic deficiencies due to stroke.
Methods and Findings
A prospective, randomized, controlled trial including 74 patients (15 were excluded). All participants suffered a stroke 6–36 months prior to inclusion and had at least one motor dysfunction. After inclusion, patients were randomly assigned to "treated" or "cross" groups. Brain activity was assessed by SPECT imaging; neurologic functions were evaluated by NIHSS, ADL, and life quality. Patients in the treated group were evaluated twice: at baseline and after 40 HBOT sessions. Patients in the cross group were evaluated three times: at baseline, after a 2-month control period of no treatment, and after subsequent 2-months of 40 HBOT sessions. HBOT protocol: Two months of 40 sessions (5 days/week), 90 minutes each, 100% oxygen at 2 ATA. We found that the neurological functions and life quality of all patients in both groups were significantly improved following the HBOT sessions while no improvement was found during the control period of the patients in the cross group. Results of SPECT imaging were well correlated with clinical improvement. Elevated brain activity was detected mostly in regions of live cells (as confirmed by CT) with low activity (based on SPECT) – regions of noticeable discrepancy between anatomy and physiology.
Conclusions
The results indicate that HBOT can lead to significant neurological improvements in post stroke patients even at chronic late stages. The observed clinical improvements imply that neuroplasticity can still be activated long after damage onset in regions where there is a brain SPECT/CT (anatomy/physiology) mismatch.
Trial Registration
ClinicalTrials.gov NCT00715897
Citation: Efrati S, Fishlev G, Bechor Y, Volkov O, Bergan J, et al. (2013) Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients - Randomized, Prospective Trial. PLoS ONE 8(1): e53716. doi:10.1371/journal.pone.0053716
Editor: Jens Minnerup, University of Münster, Germany
Received: June 17, 2012; Accepted: December 5, 2012; Published: January 15, 2013
Copyright: © 2013 Efrati et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The study was supported by the research fund of Assaf-Harofeh medical center, by the Tauber Family Foundation and the Maguy-Glass Chair in Physics of Complex Systems at Tel Aviv University and by Joseph Hackmey. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors herby declare that, although Prof. Eshel Ben-Jacob is a PLOS ONE Editorial Board member, this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
* E-mail: efratishai@013.net
Introduction
Intensive functional therapy and rehabilitation programs for post stroke patients are considered essential for maximizing the patients' quality of life [1], [2]. Unfortunately, these programs are often just partially successful, and additional therapeutic approaches towards metabolic recovery of affected cerebral tissues are called for. While a considerable amount of preclinical research supports the use of hyperbaric oxygen therapy (HBOT) for post-stroke damaged brain tissue, so far, only 5 articles reported controlled clinical trials of HBOT for stroke patients. These studies, in which the treatment started during the early-acute phase immediately after stroke, yielded non conclusive and somewhat contradicting results [3], [4], [5], [6], [7]. In contrast, a recent phase-I study evaluating the effect of HBOT on chronic neurological deficiencies (due to traumatic brain injury) revealed promising results [8]. However, to date the effects of HBOT on neurological deficiencies due to stroke during the late-chronic phase (the focus of the current report) have not yet been investigated in a prospective randomized trial.
Years of clinical experience revealed that the dramatic spontaneous recovery from stroke occurs mainly within the first 30 days, though moderate and severe stroke survivors continue to improve for at least 90 days [9]. Most of the recovery involves brain regions rendered dysfunctional, but not dead [10]. Accumulated data from visualizations of these non-active (stunned) regions indicates that they may persist alive but dysfunctional for months, even years, after the acute injury [11], [12], [13]. It was proposed that the oxygen supply to these under-active neurons was low due to stroke damage to blood vessels in these regions, leading to oxygen deficiency, anaerobic metabolism and ATP depletion [14], [15]. The decreased oxygen level not only causes reduction in the neuronal activity but also prevents angiogenesis to replace the stroke-damaged blood vessels and the generation of new synaptic connections. Since 1 cm3 of normal brain tissue contains about 1 km of blood vessels, high oxygen supply is essential for repair of the stunned regions. Indeed, as has been demonstrated by previous studies, an increase in dissolved oxygen has several beneficial effects in damaged brain tissues [13], [16], [17], [18], [19], [20]. Transport of oxygen to glial mitochondria, the main sites of oxygen utilization, follows oxygen release from erythrocytes into the plasma and then diffusion of the blood-dissolved oxygen across the Blood-Brain Barrier (BBB). Breathing oxygen under hyperbaric conditions has been shown to be a potent means of increasing arterial oxygen tension and consequently the brain oxygen tension [20], [21], [22]. For example, at 2ATA (atmospheres absolute), the plasma O2 partial pressure rises above 1,110 mmHg. Hence, it is reasonable to expect that HBOT can be an efficient (and clinically feasible) method for increasing tissue/cellular oxygenation and thus effectively evoking neuroplasticity in the chronically non-active areas during the late post-stroke phase.
Many physiological pathways, each with a different characteristic time, are spontaneously activated following the onset of stroke. Therefore, a challenging question to be addressed considers the optimal time lapse after stroke to start the HBOT procedure. It should also be kept in mind that signals and chemical cues associated with cell death during the acute stage of stroke might, in fact, promote repair during recovery [23] and can be negatively affected by premature application of HBOT. Unlike the case of preclinical animal studies, in clinical practice it is not feasible to apply the HBOT immediately at the stroke onset. Thus, HBOT procedure can practically begin either at the degenerative or at the regenerative stage. One can assume that any added energy during the degenerative stage could further increase the unwanted, post-injury damage. On the other hand, elevated oxygen supply during the regenerative stage would supply the energy needs for the innate brain repair processes. The differences in the time lapse between stroke onset and HBOT application in previous studies are likely to be the reason for the contradictive results obtained for HBOT application during the acute phase after stroke [3], [4], [5], [6], [7]. The aim of the current study was to evaluate the effects of HBOT started at the late-chronic phase after the acute stroke.
Methods
The study was performed as a prospective, randomized, controlled, two-group trial. The population included patients of ages 18 years or older, who had either ischemic or hemorrhagic stroke 6–36 months prior to their inclusion. All patients had to have at least one motor dysfunction. Exclusions were based on chest pathology incompatible with HBOT, inner ear disease, claustrophobia and inability to sign informed consent. Additional exclusions were based on dynamic neurologic improvements during the last month (based either on objective measurements by external evaluator or on subjective statement by the patients). Smoking was not allowed during the study. All patients signed written informed consent; the protocol was approved by the local Helsinki committee. The study was conducted in the hyperbaric and research units of Assaf-Harofeh Medical Center, Israel.
Protocol and End Points
After signing an informed consent form, the patients were invited for baseline evaluations. Included patients were randomized into two groups (1:1 randomization): a treated group and a cross group. The neurologic functions as evaluated by National Institutes of Health Stroke Scale (NIHSS) [24], [25], ability to perform activities of daily living (ADL) [26], and brain metabolism as visualized SPECT were the primary endpoints of the study. The secondary end point of the study included Quality of life evaluation. The patients in the treated group were evaluated twice – at baseline and after 2 months of HBOT treatment. Patients in the cross group were evaluated three times: baseline, after 2 months control period of no treatment, and after consequent 2 months of HBOT sessions (Figure 1). The post-HBOT neurological evaluations as well as the SPECT scans were performed more than 1 week (1–3 weeks) after the end of the HBOT protocol. The following HBOT protocol was practiced: 40 daily sessions, 5 days/week, 90 minutes each, 100% oxygen at 2ATA. The detailed clinical study protocol (Protocol S1), randomization and placebo consideration (Text S1), copy of the informed consent (Form S1), as well as CONSORT 2010 checklist of information (Checklist S1) are attached as supporting information.
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Figure 1. Flowchart of the patients in the study.
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Neurologic Evaluation
The clinical severity of the stroke was blindly assessed by a trained physician according to the NIHSS [24], [25]. The ADL were evaluated by a questionnaire covering the following functions: bathing, dressing, grooming, oral care, toileting, walking, climbing stairs, eating, shopping, cooking, managing medications, using phone, housework, doing laundry, driving and managing finances [26]. For each criterion, the patient defined whether he/she is independent, needs help, dependent or does not do at all (range: 0(best)-51(worst)).
Brain Functional Imaging and Analysis
Brain single photon emission computed tomography (SPECT) was conducted with 925–1,110 MBq (25–30 mCi) of technetium-99methyl-cysteinate-dimmer(Tc-99m-ECD)at40–60 min post injection using a dual detector gamma camera (ECAM or Symbia T, Siemens Medical Systems) equipped with high resolution collimators. Data was acquired in 3-degree steps and reconstructed iteratively with Chang method (μ = 0.12/cm) attenuation correction [27]. Visual analysis was conducted by fusing pre- and post-treatment studies that were normalized to pre-treatment whole brain activity. SPECT images were reoriented into Talairach space using NeuroGam (Segami Corporation) for identification (based on visual inspection) of abnormal perfusion regions and in order to compute volume rendered brain images.
More specifically, the assessment was done independently by two nuclear medicine physicians who compared the scans and graded them as either: 1 = no change, 2 = mild change and 3 = significant change. This was done “blindly” (without pre-conditioned information about the patients). “No change” was assigned to no visual difference in the number or size of perfusion deficits; “mild change” to a reduction in number or size of perfusion defects; “significant change” to a global perfusion increment in addition to diminution of defect numbers or size. Differences in evaluation were resolved after mutual reviewing. A comparison of the SPECT results with anatomical imaging CT was conducted in order to evaluate the extent of perfusion deficit in relation to the anatomical lesion. All SPECT analysis were done while blinded to the laboratory and clinical data.
Quality of Life Evaluation
Quality of life was evaluated by the EQ-5D questionnaire [28]. EQ-5D essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ-VAS). The EQ-5D descriptive system covers mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-VAS records the respondent’s self-rated health on a vertical, visual analogue scale (range: 0(worst)-100(best)).
Statistical Analysis
The statistical analysis considerations are detailed in Appendix A. SAS software (version 9.1; SAS Inc.) was used. Continuous data is expressed as means ± STD (standard deviation) and compared by unpaired t-test for inter-group comparison and by paired t-test for intra-group comparison. Categorical data is expressed in numbers and percentages and compared by chi-square test. P values<0 .05="" all="" allocated="" analyses.="" analysis="" and="" assessment="" considered="" efficacy="" had="" in="" included="" patients="" post-baseline="" randomly="" safety="" significant.="" statistically="" the="" those="" were="" who="">
Scatter Plot Analysis of the Clinical Scores
The analysis aims to better quantify and compare changes in the clinical scores, while taking into consideration the high patient-to-patient variability. The idea was to inspect, for each patient at each time stage, the scaled relative differences in each of the clinical scores. More specifically, we calculated for a specific patient (j) the scaled relative difference SRDj, defined as:
Where SFj is the value of a clinical score at the end of the time stage (either treatment or control), and SIj is the score at the beginning of the time stage. We note that the symbol<> indicates average over the values of the patients in the group. For example,
Results
The study included 74 patients (August 2008-October 2010). 7 patients from the treated group and 8 patients from the cross group were excluded: 8 refused the SPECT, 3 had no measurable paresis, 1 had a medical problem, 1 had a stroke during the control period, and 2 refused to quit smoking (Figure 1).
Twenty four patients (80%) from the treated group had a history of ischemic stroke; of those, 17(71%), 3(13%), 2(8%) and 2(8%) patients were classified as TOAST 1, 2, 3 and 4, respectively. Twenty five patients (86%) from the cross group had ischemic stroke; of those, 18(72%), 3(12%), 2(8%) and 2(8%) patients were classified as TOAST 1, 2, 3 and 4, respectively; p = 0.8 for comparison of the TOAST classification between the groups. Of the 6 patients (20%) in the treated group that had hemorrhagic stroke, 5(83%) had anterior circulation stroke; and of the 4 patients with hemorrhagic stroke in the cross group, 3(75%) had anterior stroke. Baseline patients’ characteristics are summarized in Table 1.
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Table 1. Baseline patients' characteristics.
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Neurologic Evaluation
The results of the neurological evaluations, including the NIHSS and the ADL and the quality of life estimates EQ-5D and EQ-VAS, are summarized in Table 2. Details of the parameter estimates, significance levels and confidence intervals for NIHSS and ADL are presented in Figure 2.
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Figure 2. The results of the neurological evaluation. Each point represents a patient.
(A–C) NIHSS score: (A) Scores of the treated group patients before and after the HBOT period (B) Scores of the cross group before and after the control (no treatment) period. (C) Scores of the cross group after the HBOT period. (D–F) The same as (A)-(C) for the activities of daily living (ADL) scores. We note that the lines indicate the diagonal. Abbreviation: NIHSS = National Institutes of Health Stroke Scale; ADL = Activities of Daily Living.
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Table 2. Summary of the results of the National Institutes of Health Stroke Scale (NIHSS), activities of daily living (ADL) and quality of life questionnaire (EQ-5D and EQ-VAS).
doi:10.1371/journal.pone.0053716.t002
NIHSS.
Clinical evaluations revealed statistically significant improvements in the NIHSS measures following treatment both in the HBOT-treated group (Figure 2a; p = 0.004 compared to control) and in the HBOT-treated cross group (Figure 2c; p<0 .0001="" 2b="" all="" at="" baseline.="" change="" compared="" control="" cross="" did="" during="" further="" group="" igure="" improvements="" is="" non-treatment="" not="" noticeable="" of="" p="0.43" period="" pre-hbot="" scores="" significance="" the="" these="" to="" when="" which="">
ADL.
Clinical evaluations revealed statistically significant improvements in the ADL score following treatment both in the HBOT-treated group (Figure 2d; p<0 .001="" 2e="" 2f="" adl="" after="" and="" baseline="" change="" compared="" control="" cross="" during="" further="" group="" hbot-treated="" igure="" improvements="" in="" is="" no="" non-treatment="" noticeable="" of="" p="0.42" period="" pre-hbot="" scores="" significance="" the="" there="" these="" to="" was="" when="" which="">
Scatter Plot Analysis of the Neurological Evaluations
The statistical significance of the improvements following the treatment periods is noticeable in the scatter plot analysis represented in Figure 3 and further detailed in Appendix B. In particular, the results show that the combined score of all patients improved following HBOT, while remaining unchanged during the control period.
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Figure 3. Scatter plot analysis of the changes in the combined neurological evaluations.
The scatter plot shows changes in the NIHSS and ADL scores in terms of the scaled relative differences as is defined in the methods section (averaged difference (
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Quality of Life
The effect on the quality of life is summarized in Table 2. The EQ-5D score significantly improved following treatment, both for the HBOT-treated group (p<0 .0001="" 2.="" and="" as="" baseline="" between="" both="" compared="" comparison="" control="" cross="" eq-vas="" evaluations="" following="" for="" group="" groups="" hbot-treated="" improved="" improvement="" in="" is="" more="" no="" obtained="" p="0.016" period="" pre-hbot="" results="" score="" significant="" significantly="" similar="" specifically="" summarized="" table="" the="" there="" to="" treatment="" was="" were="" while="">
Brain Functional Imaging- rCBF SPECT Imaging
All brain SPECT evaluations were completed for 29 patients in the treated group and for 28 in the cross group. Comparison of brain activity improvement following the HBOT revealed that 55% of the treated group had significant improvement after HBOT and 35% had mild improvement. In the cross group, during the first (control) period 36% had mild improvement and only 6.2% had significant improvement (p<0 .001="" 29="" 43="" after="" and="" cross="" data="" demonstrated="" group="" hbot="" improvement="" in="" mild="" not="" p="" shown="" significant="" tables="" the="">
The improvements in the SPECT were mostly in regions showing noticeable discrepancy between the CT and SPECT–the earlier mentioned stunned regions of low activity living cells. The following examples of three typical patients illustrate the associations between the improvements in the patients’ clinical conditions and evaluations and the changes in their brain activity (indication of the activation of neuroplasticity) as reflected by changes in their corresponding SPECT images:
Example-1.
Baseline brain SPECT images demonstrating hypoperfusion in the right fronto-parietal region, right postero-medial frontal and posterior-parietal perfusion lesions with no significant changes after the control period (Figure 4). In comparison, the SPECT after HBOT demonstrated disappearance of the perfusion lesions. Global cortical and subcortical perfusion improvement was seen (Figure 5).
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Figure 4. Volume rendered Brain SPECT perfusion maps of Example 1.
The results are of a patient in the cross group, suffering from left hemiparesis due to ischemic stroke that occurred 1 year prior to inclusion in the study. Baseline and control volume rendered brain perfusion views show diffuse hypoperfusion in the right hemisphere involving the fronto-parietal region and right postero-medial frontal (right motor cortex), right medial parietal and posterior-parietal (sensory cortex and associative motor cortex) (red circles). The HBOT SPECT scan done at the end of HBOT treatments shows disappearance of the perfusion deficits that were still demonstrated at the end of the control period. In addition, a significant global cortical and subcortical (basal ganglia and thalamic nuclei) perfusion improvement is seen.
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Figure 5. Volume rendered Brain SPECT perfusion maps of Example 2.
The results are of a patient in the treated group, suffering from right hemiparesis due to ischemic stroke that occurred 14 months prior to her inclusion in the study. Comparison of pre- and post-hyperbaric treatment SPECT scans. These SPECT images demonstrate significant improvement of perfusion deficits in the left hemisphere involving the medial and posterolateral frontal area (motor cortex, red circles) and lateral inferior frontal region (Broca's area, blue circles) in comparison to the baseline SPECT. HBOT SPECT findings correlate positively with the patient's improved motor and verbal functions.
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These SPECT images are of a 61y old woman from the cross group, suffering from left hemiparesis due to ischemic stroke that occurred 1 year prior to inclusion. Baseline NIHSS showed minor facial paresis, no ability to hold her left hand against gravity, some ability to hold her left leg against gravity for less than 5 seconds and mild-to-moderate sensory loss. In ADL, she needed help in bathing, dressing and climbing stairs. She was unable to do any housework. After HBOT, she was able to hold her hand and leg against gravity without significant sensory loss. She could move her fingers, was independent in bathing, dressing, shopping and cooking.
Example-2.
SPECT images at the end of HBOT demonstrating significant improvement of perfusion deficit in the left hemisphere (Figure 5) involving the medial and posterolateral frontal area (motor cortex) and lateral inferior frontal area (Broca's area). These images are from a 62y old woman from the treated group suffering from right hemiparesis due to ischemic stroke that occurred 14 months prior to inclusion. Baseline NIHSS showed no movement in her right arm, some effort against gravity in her right leg, mild-moderate aphasia, alexia and mild-moderate dysarthria. In ADL, she was completely dependent in bathing and dressing and needed help in transferring, walking, climbing stairs and eating. After HBOT, she could move her right hand against gravity, move fingers, and hold her leg against gravity. She regained speech (almost fluent) and reading capabilities. In ADL, she was able to walk, climb stairs and eat by herself. She was not dependent in bathing and dressing.
Example-3.
SPECT images demonstrating improvement in the peri-infarct region following HBOT. The images are of a 64y old woman from the treated group suffering from right hemiparesis due to ischemic stroke that occurred 26 months prior to inclusion. After treatment, the leg hemiparesis was resolved, her hand function improved significantly but she did not regain all fine motor skills. Figure 6 shows improvement in the peri-infarct region.
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Figure 6. Volume rendered Brain SPECT perfusion maps of Example 3.
The results are of a patient in the treated group suffering from left hemiparesis due to ischemic stroke that occurred 26 months prior to inclusion in the study. The brain perfusion maps (upper two images) show the infracted brain (deep blue color) involving the right antero-postero-lateral frontal, right superior-parietal and right parieto-occipital regions. Curved sagittal view in CT MIP reconstruction of the brain shows the anatomical stroke area (left lower image, V = posterior horn of right ventricle). The peri-infarct region show improved perfusion as demonstrated by HBOT image (right upper image). Quantitation of the cerebral blood flow (CBF) change (delta between baseline and HBOT) is demonstrated in the right lower image.
doi:10.1371/journal.pone.0053716.g006
Safety
Six patients had mild-moderate barotrauma of the middle ear. After several days of rest they returned and completed the protocol. Two patients with a history of epileptic seizures prior to their inclusion in the study had mild episodes of convulsion (consciousness was fully maintained) during the study. Both patients were already treated with anti-epileptic drugs prior to their inclusion.
Discussion
In the current study, the effect of HBOT on chronic neurological deficiency due to stroke was evaluated in a prospective, randomized controlled study. Statistically significant improvements were obtained following treatment for almost all treated patients from both the HBOT-treated group and the HBOT-treated cross group (with no false negative), as was evaluated by NIHSS, ADL, brain SPECT and life quality. The significance of the improvements in this chronically debilitated population of patients is further noticeable when compared to the lack of improvement during the control (no-treatment) period of the cross group (with no false positive).
This is the first prospective, randomized clinical study evaluating the effect of HBOT in the late post-stroke period (6 months to 3 years after the acute event). There are two major reasons for selecting this study population. First, by carefully selecting patients with chronic stable neurological deficiency we were able to avoid unexpected changes in their condition. In this regard, the selection proved very useful since the control group demonstrated neurological stability with no outliers. The second reason was, as discussed in the introduction, to test our hypothesis that the optimal time for the HBOT procedure should be during the regenerative and not during the degenerative stage. While it is not possible to mark a clear line between the regenerative and the degenerative phases [23], it is quite clear that 6 months after the acute event in a stable patient the degenerative process has ended. As mentioned in the introduction, the differences in initiation times and protocols of HBOT may explain contradictive results in previous studies, where HBOT was used in the early phase after stroke [3], [4], [5], [6], [7]. The recent publication by Harch et al., evaluating the effect of HBOT on chronic neurological deficiencies due to traumatic brain injury, also supports the use of HBOT in the late stage after the acute insult [8].
The issue of “how to handle the control group” was discussed by a multidisciplinary team including physicians specializing in hyperbaric medicine, physicists specializing in neuronal-glia interactions and the ethics committee. The patients can tell if pressure is increased or not, so the pressure must be increased also in the control group. The only way to administer “placebo” of HBOT is to bring the patients to the hyperbaric chamber and to increase the environmental pressure to an extent that the patients will feel it in their ears. The minimal pressure needed to gain such a feeling should be 1.3 ATM. Henry’s law states: “the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the pressure of that gas in equilibrium with that liquid”. Thus, hyperbaric environment significantly increases the dissolved oxygen pressure even if a person holding his breath [29]. Compressed air at 1.3 ATA increases the plasma oxygen tension by at least 50% and that is certainly notable. There are many case reports illustrating significant effects following small increase in air pressure [30], [31], [32]. Moreover, even a slight increase in partial pressure, such as, for example, to 1.05 ATM at altitude 402 m below sea level (the Dead Sea), can lead to noticeable physiological effects [33], [34], [35], [36], [37]. However, it should be kept in mind that oxygen is not a drug, and because it is metabolized mainly in the mitochondria, there is no simple dose-response curve.
Since increasing the pressure even without adding oxygen can also increases the dissolved oxygen partial pressure, the only way to maintain normal (placebo) levels of dissolved oxygen is to supply air with lower than normal level of oxygen, which we deemed unethical. To partially compensate for this inherent limitation, the patients in the cross group started with a two-month control period of no treatment, at the end of which they were crossed to two months of HBOT sessions. To gain better validity of the results, we used the scatter plot analysis of the changes in the combined neurological evaluations. The scatter plots (figure 3) show changes in the NIHSS and ADL scores in terms of the scaled relative differences, as is defined in the methods section. In that analysis, summarized in figures 2 & 3, the correlation between changes NIHSS & ADL after HBOT is clearly demonstrated. Moreover, the analysis evidently demonstrates that the effect of HBOT on these “not completely blinded evolution” was the same in the treated group and the control group after blind randomization. The correlation between the improvement in NIHSS and ADL and the improvement in the brain SPECT results, which was done in a completely blinded fashion, further substantiates the clinical findings. Moreover, the consistency between the anatomical locations of the changes in the brain metabolism, as demonstrated by the SPECT, with the finding in the neurological evaluation provides important validation of the neurological evaluation.
During most of the 20th century, there was an ongoing debate about the time window available for induction of neuroplasticity. The improvements in the chronic late stage reported here support the view that neuroplasticity can be activated months to years after the acute event when a proper brain stimulation (such as HBOT) is applied. More specifically, the current study included patients that underwent stroke more than 6 months prior to treatment and after their condition reached a steady state (no improvements were monitored for at least a month). These important and unexpected findings arein agreement with other recent findings revealing that many aspects of the brain remain plastic even at adulthood [38]. They are also consistent with several other studies in post stroke patients [39], [40], [41]. In the current study, patients were treated only with HBOT without any additional guided training and/or practice. This was done in order to demonstrate the therapeutic potential of this treatment. It is reasonable to expect that exploiting the HBOT in conjunction with other rehabilitation intervention can lead to even better results leading to optimal future practice. The current study paved the way for future investigations of this promising direction, which should be one of the aims of upcoming more elaborated clinical studies.
Current imaging technologies reveal that the stunned brain areas (regions of high anatomy-physiology mismatch) may persist for months and years after an acute brain event [11], [12], [13]. The changes in SPECT images after treatment demonstrate that the HBOT procedure led to reactivations of neuronal activity in the stunned areas. While SPECT imaging has limited spatial resolutions (in comparison, for example, to fMRI), the changes in activity were sufficiently robust to be clearly detected by the SPECT images. However, a future, more detailed study using fMRI (along with direct observations on animal model) will be able to provide additional valuable insights, in particular regarding the operative underlying mechanisms that activate the neuroplasticity (e.g. the putative role of glial cells). We note that patients were not selected based on their anatomical and functional brain imaging evaluation. It might be possible that the results would have been even better had the study included only patients with high SPECT/CT mismatch. This issue of the preferred population for HBOT should be further investigated in future clinical trials. We also note that in the current pioneering study aimed at “proof of concept”, all patients underwent 40 HBOT sessions. Based on our current clinical experience, more sessions of HBOT may be needed, at least for some patients, in order to obtain the maximal improvement effect.
In any case, the observed reactivation of neuronal activity in the stunned areas imply that increasing the plasma oxygen concentration with hyperbaric oxygenation is a potent means of delivering to the brain sufficient oxygen for tissue repair: HBOT might initiate a cellular and vascular repair mechanism and improve cerebral vascular flow [8], [13], [16], [17]. At the cellular level, HBOT can improve mitochondrial function (in both neurons and glial cells) and cellular metabolism; improve BBB and inflammatory reactions; reduce apoptosis; alleviate oxidative stress; increase levels of neurotrophins and nitric oxide, and up-regulate axon guidance agents [13], [16], [17], [20]. Moreover, the effects of HBOT on neurons can be mediated indirectly by glial cells, including asrocytes [18]. HBOT may also promote neurogenesis of the endogenous neural stem cells [19]. The major limitation of the above-mentioned data is that it has been tested in different types of models and includes different protocols of HBOT. However, it is well noticed that there is at least one common denominator to all repair/regeneration mechanisms: they are all energy/oxygen dependent. It might be possible that HBOT enables the metabolic change simply by supplying the missing energy/oxygen needed for those regeneration processes.
To conclude, in this study we provide, for the first time, convincing results demonstrating that HBOT can induce significant neurological improvement in post stroke patients. The neurological improvements in a chronic late stage demonstrate that neuroplasticity can be operative and activated by HBOT even long after acute brain insult. Thus, the findings have important implications that can be of general relevance and interest in neurobiology. Although this study focused on stroke patients, the findings bear the promise that HBOT may serve as a valuable therapeutic practice in other neurological disorders exhibiting discrepancy between the anatomical and functional evaluation of the brain.
Supporting Information
Protocol S1.
Clinical Study Protocol.
(DOCX)
Checklist S1.
CONSORT 2010 checklist.
(DOCX)
Form S1.
Informed consent form (English translation).
(PDF)
Text S1.
Statistical, Randomization and Placebo Considerations.
(DOCX)
Text S2.
Scatter plot analysis of the clinical scores.
(DOCX)
Acknowledgments
We are thankful Dr. Alexander Vol and Dr. Orna Gribova for enlightening discussions regarding the neurophysiology and oxygen related processes in brain recovery. Special thanks to Dr. Hanna Levi for valuable help with the statistics and data analysis. We thank Michal Ben-Jacob for her significant help in editing the manuscript. We thank the following individuals for their important contribution in patients’ management during this study: Alona Esterin, Mazi Aski-Sela, Angela Chanimov, Malca Katovski, Lea Shkolnic, Eyal Malca. Vitali Triban.
Author Contributions
Conceived and designed the experiments: SE GF IK NG HG. Performed the experiments: SE GF YB JB MF. Analyzed the data: SE OV KK EB-J HG. Wrote the paper: SE EB-J HG. Performed the experiments (brain SPECT): OV. Performed the experiments (neurological evaluation part): IK. Performed the experiments (brain imaging part): HG.
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hiperbarik oksigen terapi RS. Bethsaida 021 99070050
sumber :http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053716
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