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area academica
medicina de grandes montañas
la OMS (Organización Mundial de la Salud) resalta que de los "mil 300 millones de fumadores existentes, unos 650 millones morirán prematuramente".
Volume 339:1603-1608 November 26, 1998 Number 22
Carbon Monoxide Poisoning
Armin Ernst, M.D., and Joseph D. Zibrak, M.D.
Sources of Carbon Monoxide
Carbon monoxide is a product of the incomplete combustion of hydrocarbons. The concentration of carbon monoxide in the atmosphere is usually less than 0.001 percent. The levels are higher in urban areas than in rural areas. Endogenous carbon monoxide production from the catabolism of hemoglobin is a component of normal biochemical processes. A low base-line level of carboxyhemoglobin is detectable in every person. Tobacco smoke is an important source of carbon monoxide. Blood carboxyhemoglobin commonly reaches a level of 10 percent in smokers and may even exceed 15 percent, as compared with 1 to 3 percent in nonsmokers.
The sources of exogenous carbon monoxide that cause poisoning include motor vehicle exhaust fumes, poorly functioning heating systems, and inhaled smoke. Propane-operated forklifts have been implicated as a cause of headache in warehouse workers. "Cleaner" fuels such as propane and methane undergo more complete combustion but have also been reported to be sources of carbon monoxide poisoning.
The carbon monoxide in motor vehicle exhaust fumes accounts for the majority of deaths from carbon monoxide poisoning in the United States. Of the 11,547 accidental carbon monoxide deaths reported between 1979 and 1988, motor vehicle exhaust accounted for 57 percent. In a series of 56 motor vehicle–associated deaths reported from 1980 to 1995, 43 percent were due to faulty exhaust systems, 39 percent to operation in an improperly ventilated structure, and 18 percent to the use of a fuel-burning heating device in the passenger compartment. Lethal concentrations of carboxyhemoglobin can be achieved within 10 minutes in the confines of a closed garage. Carbon monoxide from motor vehicles can also cause death in semienclosed spaces or in working or living quarters adjacent to garages.
An often overlooked source of carbon monoxide poisoning is methylene chloride, a common component of paint remover and other solvents. Methylene chloride is readily absorbed through the skin and lungs as a vapor and circulates to the liver, where its metabolism results in the generation of carbon monoxide.
Carbon monoxide is a colorless, odorless, and nonirritant toxic gas that is easily absorbed through the lungs. The amount of gas absorbed is dependent on the minute ventilation, the duration of exposure, and the relative concentrations of carbon monoxide and oxygen in the environment. Carbon monoxide is principally eliminated by the lungs as an unchanged gas. Less than 1 percent is oxidized to carbon dioxide. Ten to 15 percent of carbon monoxide is bound to proteins, including myoglobin and cytochrome-c oxidase. Less than 1 percent of the absorbed gas exists in solution.
Carbon monoxide toxicity appears to result from a combination of tissue hypoxia and direct carbon monoxide–mediated damage at the cellular level. Carbon monoxide competes with oxygen for binding to hemoglobin. The affinity of hemoglobin for carbon monoxide is 200 to 250 times as great as its affinity for oxygen. The consequences of this competitive binding are a shift of the oxygen–hemoglobin dissociation curve to the left and its alteration to a more hyperbolic shape. These alterations result in impaired release of oxygen at the tissue level and cellular hypoxia. The binding of carbon monoxide to hemoglobin alone does not account for all of the pathophysiologic consequences observed. In studies in animals, transfusion of blood with highly saturated carboxyhemoglobin but minimal free carbon monoxide does not reproducibly result in clinical symptoms. This observation suggests that the small fraction of free carbon monoxide dissolved in plasma has an important role….
Volume 318:347-351 February 11, 1988 Number 6
Pulmonary hazards of smoking marijuana as compared with tobacco
To compare the pulmonary hazards of smoking marijuana and tobacco, we quantified the relative burden to the lung of insoluble particulates (tar) and carbon monoxide from the smoke of similar quantities of marijuana and tobacco. The 15 subjects, all men, had smoked both marijuana and tobacco habitually for at least five years. We measured each subject's blood carboxyhemoglobin level before and after smoking and the amount of tar inhaled and deposited in the respiratory tract from the smoke of single filter-tipped tobacco cigarettes (900 to 1200 mg) and marijuana cigarettes (741 to 985 mg) containing 0.004 percent or 1.24 percent delta 9-tetrahydrocanabinol. As compared with smoking tobacco, smoking marijuana was associated with a nearly fivefold greater increment in the blood carboxyhemoglobin level, an approximately threefold increase in the amount of tar inhaled, and retention in the respiratory tract of one third more inhaled tar (P less than 0.001). Significant differences were also noted in the dynamics of smoking marijuana and tobacco, among them an approximately two-thirds larger puff volume, a one-third greater depth of inhalation, and a fourfold longer breath-holding time with marijuana than with tobacco (P less than 0.01). Smoking dynamics and the delivery of tar during marijuana smoking were only slightly influenced by the percentage of tetrahydrocanabinol. We conclude that smoking marijuana, regardless of tetrahydrocannabinol content, results in a substantially greater respiratory burden of carbon monoxide and tar than smoking a similar quantity of tobacco.
High-Altitude Illness
Buddha Basnyat, M.D.
Nepal International Clinic
Katmandu, Nepal
Altitude sickness is common in the Himalayas, where thousands of people come for trekking every fall and spring. For those of us who offer health care in Nepal to travelers at high altitude (which Peter Hackett helped to start many years ago) the review by Hackett and Roach (July 12 issue)1 was fascinating, but I do have a few comments.
More than overhydration, the great danger in the mountains is dehydration due to the general unavailability or poor quality of water or to the lack of thirst. Dehydration may simulate acute mountain sickness, as the authors suggest. It may also interfere with proper acclimatization2 and aid in the pathogenesis of acute mountain sickness.3 Hence, at our clinic we advise drinking adequate water (without going to extremes) so that the urine is clear. Epidemiologic studies have shown that respiratory infections may predispose persons to acute mountain sickness and not only to high-altitude pulmonary edema.3,4 Therefore, persons with symptoms of a cold or influenza before a trek or a climb must be more cautious.
In the Himalayas, we caution people not to sleep more than 400 m above their sleeping altitude of the previous night, when this is logistically possible, although data regarding the effect of changes in sleeping altitude are lacking; 600 m may be too large a change. Finally, impaired cerebral autoregulation may contribute to high-altitude cerebral edema, as suggested, but my colleagues and I were amazed to find in a study we conducted that even healthy, well-adapted Sherpas had impaired cerebral autoregulation at 4300 m.5

Peter H. Hackett, M.D., and Robert C. Roach, Ph.D.
Everest or bust: a cross sectional, epidemiological study of acute mountain sickness at 4243 meters in the Himalayas.
Basnyat B, Lemaster J, Litch JA.

Himalayan Rescue Association/Nepal International Clinic/Patan Hospital, Nepal.
BACKGROUND: Thousand of tourists trek in the Himalayas every season and risk acute mountain sickness (AMS). Prior studies have shown that the rate of ascent is one of the primary risk factors for the development of AMS but the role of body hydration, age, gender, alcohol and medication usage, body weight, and altitude of residence continues to be in question. This study estimates the incidence of AMS at 4234 m at Pheriche in the Everest region, explores a number of risk factors predisposing trekkers to a diagnosis of AMS and attempts to quantify the relationship between the Lake Louise AMS diagnostic criteria and oxygen saturation. METHODS: Demographic data and information about risk factors felt to place trekkers at increased risk of AMS was collected from 550 trekkers for 1 mo in the fall of 1996 at 4234 m in the Everest region. RESULTS: Diagnosis of AMS was made in 29.8% (159 trekkers) of the study population. Low water intake (odds ratio 1.57; 95% confidence interval,1.02-2.40), the presence of respiratory symptoms (odds ratio 2.21; 95% confidence interval, 1.43-3.40), and an oxygen saturation below 85% at 4243 m (odds ratio 2.35; 95% confidence interval, 1.55-3.56) were identified as independent risk factors for AMS diagnosis in this sample. In addition, AMS risk decreased 18.7% (95% confidence interval, 3.8-31.2%) for each additional night spent between Lukla (2804 m) and the study site at 4243 m. CONCLUSION: Increased reported fluid intake decreased the risk of AMS in this cross sectional prospective study. Further studies need to be done to confirm this finding before recommendations can be made. In addition the rise in the risk of AMS as the rate of ascent increased along this popular Everest trek was quantified for the first time. Finally, AMS was also associated with respiratory symptoms and with a lower oxygen saturation.

PMID: 10503751 [PubMed - indexed for MEDLINE]
referencia adicional
Aclimatarse a las alturas
Revisión Bibliográfica: Mal de Montaña
Dr. Peter H. Hackett, The American Alpine Club, Inc., New York
medicina tropical
A Vaccine against Rotavirus — When is Too Much Too Much?
Volume 337:1228-1229 October 23, 1997 Number 17
The development of the quadrivalent rotavirus vaccine evaluated in the study by Pérez-Schael et al., reported in this issue of the Journal,1 represents the culmination of a long and highly creative process of research and development at the National Institutes of Health.2 Today, just 25 years after rotavirus was discovered,3 the use of a modified Jennerian approach has resulted in a quadrivalent vaccine that combines a naturally attenuated serotype 3 rhesus rotavirus with reassortants composed of 10 genomic segments of rhesus rotavirus RNA plus 1 of human origin encoding the VP7 neutralization specificity of serotype 1, 2, or 4 rotavirus.4 As with any new vaccine, the issues that need to be addressed before introducing it into use are safety, efficacy, impact, and cost. In the case of rotavirus, these issues need to be considered separately for developed and developing countries.

A century ago, morbidity and mortality due to diarrheal disease in the United States were similar in magnitude to the situation in many developing countries today. Now, except for public concern about the Shiga-toxin–producing strains of Escherichia coli, diarrheal disease in the United States is no longer considered to be a serious threat. Diarrhea remains common, but its severity has diminished so that the number of deaths caused by this illness has been reduced to around 300 per year.5 These deaths occur primarily in the winter, when rotavirus is the predominant cause of diarrhea and is responsible for around one third of deaths.6 Peak rates of hospitalization for diarrheal disease also occur in the winter months, especially among children between 4 and 35 months of age — the range of ages at which they are at greatest risk for rotavirus infection.7 Studies in the United States indicate that the rhesus rotavirus–based quadrivalent vaccine is safe and can prevent nearly half of all rotavirus infections, 80 percent of severe episodes, and virtually all cases of dehydrating rotavirus illness.8

An effective program of vaccination against the severe forms of rotavirus in the United States could significantly reduce mortality due to diarrheal disease, hospitalizations, and associated direct medical costs (estimated to be $500 million to $600 million yearly),9 as well as the indirect costs associated with the hospitalization of infants and children, including lost wages for parents and the cost of unexpected and unbudgeted child care. When is too much too much? One hundred preventable deaths per year are too many, and $500 million in direct charges to the health care system is too high. Therefore, a safe and efficacious rotavirus vaccine, even one costing an estimated $250 million yearly (when priced at $30 per dose9), can be recommended for introduction into routine infant-immunization schedules in the developed countries.

The study by Pérez-Schael et al.,1 conducted in Venezuela, shows that the rotavirus vaccine has similar efficacy against severe rotavirus infection in a developing country — with an 88 percent reduction in cases of severe diarrhea, a 75 percent reduction in episodes of dehydrating illness, and a 70 percent reduction in hospital admissions. About 1 million deaths annually are due to rotavirus in developing countries, and the authors suggest that this vaccine will be useful in reducing the burden of disease if it is introduced into routine immunization programs in developing countries. The implication is that such a policy should be implemented now. We do not concur at this time, on the basis of the data at hand on efficacy and the estimated costs of immunization.

First, the same vaccine, albeit at a dose containing 1 log fewer viral copies, was much less impressive in earlier trials in Peru and Brazil, although in both studies there was some protection against severe disease.10,11 Are the better results in Venezuela due simply to the increase in antigenic load? The background rate of diarrheal disease was considerably lower in Venezuela than in Peru or Brazil, suggesting a greater risk of all enteric infections in the latter two countries. Given the differences in the incidence of diarrhea, we wonder whether the lower rates of seroconversion in Peru and Brazil were due to viral interference under conditions of enhanced transmission of all enteric organisms or to the poorer nutritional status of the infants. Although Pérez-Schael et al. classified the socioeconomic status of their study population, neither they nor the investigators in Peru or Brazil provided sufficient data to permit comparisons among the three populations. Given their lower rates of diarrhea, we suspect that the Venezuelans live under better sanitary conditions, have better nutritional status, and may respond better to the rotavirus vaccine than children who live in a more contaminated environment. Wherever there is substantial fecal contamination of water and food and a high burden of diarrheal disease is exactly where the morbidity and mortality from rotavirus are the highest. And in the most adverse environments, the vaccines may be the least effective. However, these studies also do not tell us whether enhanced horizontal spread of the vaccine virus in less hygienic settings leads to increases in herd immunity, which would be a hidden bonus of the use of the vaccine.

Another consideration relates to the logistics of immunization in developing countries. If it is ever to be used in developing countries, the rotavirus vaccine must be compatible with the schedule of the World Health Organization's Expanded Program on Immunization (EPI), which includes oral poliovirus vaccine. In all three studies of the efficacy of this rhesus rotavirus–based vaccine in the developing world,1,10,11 care was taken to avoid giving the rotavirus vaccine together with oral poliovirus vaccine because of the lingering concern that the response to one vaccine or the other would be inhibited. These studies either used inactivated poliovirus vaccine9 or gave the rotavirus vaccine at extra visits scheduled between regular EPI immunization days.4,10 Although there are data to show that the rotavirus vaccine does not inhibit the serologic response to the oral poliovirus vaccine,12 it is not known whether the converse is true.

Finally, the rate of seroconversion as measured in terms of neutralizing antibody was not impressive in Venezuela, especially for the reassortant viruses in the vaccine, and seroconversion was not boosted by a third dose. If neutralizing antibody is not a surrogate for protection, then we cannot determine whether or not a third immunization increases protection. If it does not, and if this dose were eliminated, the cost of immunization could be reduced by one third.

Even if all these issues are resolved and this vaccine is considered ready for the Third World, we still need to ask whether the Third World is ready for this vaccine. The issue is the cost of the vaccine. And unfortunately, the question is, When is too much too much? If the vaccine is priced at $30 per dose,9 it is simply too costly for most poor countries with total per capita health expenditures of $5 to $20 per year. The vaccine will not be used at that price, even if 1 million children die each year from potentially preventable rotavirus infections. Health budgets in poor countries do not increase when new forms of technology come along. Instead, priorities for action are reordered, and some programs are discontinued. The current alternative to the prevention of rotavirus by vaccination is further implementation of oral-rehydration-therapy programs. It has been known for 20 years that, if properly prepared and administered, oral rehydration therapy is an inexpensive and effective treatment for serious, dehydrating rotavirus diarrhea.13 The vaccine will have to be very inexpensive before ministries of health can justify adding it to their EPI programs. Even with the recent drop in the cost of the hepatitis B vaccine and the relatively low cost of the conjugate vaccines against Haemophilus influenzae type b, they are still priced too high for many poor countries. The same will be true of the quadrivalent rotavirus vaccine. We will once again be faced with a situation in which a technological advance cannot be used in the populations most in need, while elsewhere it is rapidly put to use to protect populations at far lower risk for illness and death.

Unfortunately, unless we change the moral imperatives in health care, financial considerations will continue to dominate in all global public health initiatives, even for such common illnesses as diarrhea and respiratory infections. The challenge to the public health establishment that is posed by this vaccine goes beyond the science involved in its development and evaluation. The greater challenge is to address the moral imperative of bringing it to those who need it most.
Safety, immunogenicity, and protective efficacy of one and three doses of the tetravalent rhesus rotavirus vaccine in infants in Lima, Peru.
Lanata CF, Midthun K, Black RE, Butron B, Huapaya A, Penny ME, Ventura G, Gil A, Jett-Goheen M, Davidson BL.
Instituto de Investigacion Nutricional, Lima, Peru.
J Infect Dis. 1996 Aug;174(2):268-75.
An oral rhesus-human rotavirus tetravalent (RRV-TV) vaccine (10(4) pfu of rhesus rotavirus [type G3] and of 3 human-rhesus reassortants [G1, G2, and G4]) was evaluated in a field trial in Lima, Peru. At 2, 3, and 4 months of age, infants received either a dose of RRV-TV, an initial dose of vaccine followed by a dose of placebo at 3 and 4 months, or a dose of placebo. Rotavirus-specific IgA responses were detected by ELISA in 75% of the three-dose vaccine group, 59% of the one-dose vaccine group (P = .05), and 24% of the placebo group (P < .001): 64%, 48%, and 12% of each group, respectively, had a neutralizing antibody response to at least 1 serotype. Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea; however, they did provide some protection (range, 35%-66%) against more severe rotavirus diarrhea, especially for episodes caused by type G1.
A randomized controlled trial comparing mebendazole and albendazole against Ascaris, Trichuris and hookworm infections.
Albonico M, Smith PG, Hall A, Chwaya HM, Alawi KS, Savioli L.

Programme of Intestinal Parasitic Infections, World Health Organization, Geneva, Switzerland.
The efficacies and side effects of single dose treatments with 500 mg mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg mebendazole (Janssen) was compared with a generic version of the drug, 500 mg mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied.
Physical activity and growth of Kenyan school children with hookworm, Trichuris trichiura and Ascaris lumbricoides infections are improved after treatment with albendazole.
Adams EJ, Stephenson LS, Latham MC, Kinoti SN.

Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853-6301.
Growth, activity, appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm (93% prevalence), T. trichiura (84% prevalence) and A. lumbricoides (29% prevalence) before and 9 wk after treatment with three 400-mg doses of albendazole (Zentel) or placebo. Fecal samples were examined for helminth eggs using a modified Kato technique. Activity was measured during free-play with motion recorders on the dominant thigh. Children rated their appetites on a 5-point scale. After baseline measurements, children were randomly allocated to the albendazole-treated (n = 28) and placebo (n = 27) groups, treated, and re-examined 9 wk later. At follow-up, egg counts were significantly lower than at baseline in the albendazole-treated group (P < or = 0.002), and gains in activity, reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group. We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity.

Terapeútica antiparasitaria
Aparicio, Pilar y col.
Preventive anthelmintic treatment...
Jorgensen RG et. al.
una buena noticia:

...Thank you for the note. I will look for my reference. I will be back in Macusani in November with Quechua Benefit and the dental team... We'll be in Mosoq Runa in the first or second week of november...

Mike Safley

Traducción Libre -vwtv-:
...Gracias por su nota. buscaré mis referencias (bibliográficas, le pedimos unas). Nosostros regresaremos a Macusani en noviembre con la Beneficencia Quechua y el equipo odontológico...estaremos en Mosoq Runa la primera o segunda semana de noviembre...

Mike Safley