The effect of high altitude on platelet counts, thrombopoietin and erythropoietin levels in young Bolivian airmen visiting the Andes.

Recognition of thrombosis as a complication of exposure to high altitude has stimulated interest in rheological changes resulting from hypobaric hypoxia. Previous studies of platelet counts at high altitude have yielded conflicting results and have not been studied in conjunction with potential mediating cytokines. We studied the effects of high-altitude exposure on platelet numbers, thrombopoietin (tpo) and erythropoietin (epo) levels in man. A group of 28 volunteers from the Bolivian Airforce stationed at Santa Cruz (600 m altitude) were studied 48 h and 1 week after their ascent to La Paz (3600 m). In addition 105 volunteers based at Santa Cruz for at least 1 year were compared with 175 age- and sex-matched residents at El Alto (4200 m). Platelet counts were measured immediately after sampling and serum samples assayed for tpo and epo. In the ascending group, mean platelet counts were 251 x 10(9), 367 x 10(9) and 398 x10 (9)/l at 600 m and following 48 h and 1 week at 3600 m respectively. Mean tpo levels were 132.5, 76 and 92 pg/ml with epo values of 2.98, 11.6 and 7.9 mIU/ml respectively. In the resident populations mean platelet counts were 271 x 10(9)/l in the low- and 471 x 10(9)/l in the high-altitude groups. Mean tpo and epo levels measured 69.3 pg/ml and 4.5 mIU/ml respectively at 600 m and 58.5 pg/ml and 5.1 mIU/ml at 4200 m. In conclusion we have demonstrated a significant and sustained elevation in platelet numbers within 48 h of ascent to high altitude. Our findings do not support a role for tpo as a mediator of the increased platelet count. However, these data do not discount epo as a potential candidate.

Density of intimal smooth muscle cells in the coronary arteries of Bolivians.

OBJECTIVE: To test an equation that uses measurements of fibroplastic intimal thickening and foam cell infiltrates, precursors for necrotic cores of atherosclerotic plaques in coronary arteries, to compute anticipated amounts of atheronecrosis. Data from New Orleans, La, and La Paz, Bolivia, afforded the opportunity to test the precision of the equation by comparing findings in separate populations. METHODS: Coronary arteries retrieved at autopsy in La Paz, Bolivia, were processed into hematoxylin-eosin-stained paraffin sections along with a parallel series in New Orleans. RESULTS: The Bolivian data fit the equation without modification. Findings showed the precursors of atheronecrosis to progress at the slowest rate in Bolivians, at the fastest rate in New Orleans men, and at an intermediate rate in New Orleans women. CONCLUSIONS: The population with the most extensive atheronecrosis in aging subjects also had the greatest degrees of precursor changes in young adults. An equation that describes these principles precisely applies equally well to all three of the populations examined here, which are the only ones studied to date.

Biochemical epidemiology of gallbladder cancer.

To evaluate the a priori hypotheses that an increased level of glyco and tauro lithocholic acid, perhaps because of a decreased capacity for hepatic sulfation, contributed to the biochemical epidemiology of gallbladder cancer, a case-control study was undertaken at four hospitals in La Paz, Bolivia, and at one hospital in Mexico City, Mexico. Eighty-four cases with newly diagnosed histologically confirmed gallbladder cancer were compared with 264 controls with cholelithiasis or choledocholithiasis in the absence of cancer and with 126 controls with normal biliary tracts. All study subjects were undergoing abdominal surgery. Interview data were collected for all study subjects, as well as blood, bile, and gallstone specimens when feasible. Sera were analyzed for carcinoembryonic antigen, cholesterol concentration, and total bile acids. Bile specimens were analyzed for carcinoembryonic antigen; and for concentration of bile salts; cholesterol; phospholipids; and the glycine and taurine conjugates of cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic, and lithocholates; sulfoglycolithocholate; and sulfotaurolithocholate. Gallstone specimens were analyzed for the percentage of cholesterol content, the percentage of calcium bilirubinate content, and the percentage of calcium carbonate content. Serum bile acids were increased in cases versus the two control groups (median 11.7 nmol/mL vs. 9.3 nmol/mL for stone controls and 8.2 nmol/L for nonstone controls, P < or = .02 for each pairwise comparison). Biliary bile acids were markedly decreased in the cases (median 3.98 micromol/mL vs. 33.09 micromol/mL, and 154.0 micromol/L, respectively, P < or = .0001 for each comparison), even after excluding those with a serum bilirubin higher than 2.0 mg/dL. Bile cholesterol was lower for the cases as well (median 1.70 micromol/mL vs. 4.90 micromol/mL, and 16.81 micromol/ mL, respectively, P < or = .02), as was the concentration of bile phospholipids (median 2.97 micromol/mL vs. 6.26 micromol/mL, and 52.69 micromol/mL, P = .1 and .0004, respectively). Contrary to our a priori hypothesis, there was no difference between the cases and either control group in their bile concentrations of lithocholate, the proportion of bile acids which were sulfated, or the concentration of nonsulfated lithocholate. However, the cases had a higher concentration of ursodeoxycholate (UDC) (P < .004 for both control groups), especially glycoursodeoxycholate (P < .001 for both control groups). A previously published suggestion that gallstone size differed between cases and controls was not confirmed. In conclusion, cases with gallbladder cancer differed from controls with stones and from controls with normal biliary tracts in their serum and bile biochemistries. These findings may be a reflection of the disease process, or may provide useful clues to its pathogenesis.

Curso de patología: patología general / sss

Este texto tiene por finalidad el proporcionar, a los alumnos de las Facultades de Medicina de Bolivia, nociones tanto de Patología General como especial tratando de dar énfasis en las enfermedades que son frecuentes en el país. Para ello se consultó, pese a las dificultades de la investigación bibliográfica en nuestro medio, tanto de la literatura médica nacional, dispersa y poco conocida, como de la universal. Sin embargo, este aporte a docencia universitaria, destinado a dar a conocer las alteraciones morfológicas más importantes de las enfermedades en general, asimismo trata de uniformizar la enseñanza de la materia en las universidades del país y, al mismo tiempo, dar a los alumnos una publicación que esté más a su alcance

Rarity of hypertensive stigmata in aging renocortical arteries of Bolivians.

Numerous reports have accumulated from around the world throughout the twentieth century of small, remote, self-sufficient populations that do not show a rise of blood pressure with age. Knowing that renocortical arteriosclerosis, a defining feature of hypertensive nephrosclerosis, is a close commensurate of blood pressure, it can be predicted that the elderly members of such populations should fail to show arteriosclerosis of hypertensive degree in the renal cortex. Emigrants from such populations sometimes come to medical attention in places like La Paz, Bolivia. Reported here are findings in autopsy samples of kidney tissue examined in La Paz. These samples have revealed remarkably little renovasculopathy at all ages up to 80 years, a phenomenon that has not previously been observed. Because of these findings, it can now be seen as biologically possible for a whole population of elderly persons to avoid renovasculopathy of hypertensive degree, and by implication, perhaps never experience hypertensive cardiovascular disease.

Pulmonary endocrine cells of Aymara Indians from the Bolivian Andes.

INTRODUCTION: There is evidence to suggest that life at high altitude causes changes in the population of pulmonary endocrine cells, possibly because of exposure to chronic hypoxia. A study was made of the populations of pulmonary endocrine cells in three Aymara Indians and three Mestizos of La Paz (3600 m), Bolivia, which were compared with those in four white lowlanders. METHODS: Pulmonary endocrine cells were immunolabelled for neurone specific enolase and their two major secretory products, gastrin releasing peptide and calcitonin, and their numbers expressed per cm2 of tissue section. RESULTS: No differences in morphology, number, content, or distribution of immunoreactive cells were found when the native highlanders were compared with the lowlanders. CONCLUSIONS: If chronic hypoxia as such exerts an influence on human pulmonary endocrine cells it was not apparent in this morphological study. There was no increase in gastrin releasing peptide containing pulmonary endocrine cells, such as have previously been seen in patients with pulmonary hypertension characterised by plexogenic pulmonary arteriopathy. This may be due to the fact that in plexogenic pulmonary arteriopathy there is free migration of smooth muscle cells. Although three of the highlanders in this present study showed pulmonary vascular remodelling, this was in contrast only modest.

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz.

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600-3800 m, were significantly larger than those in age-matched controls from sea level (15.3 g vs 10.4 g; P less than 0.001) and appeared hyperplastic. The pituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P less than 0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

Small pulmonary arterial vessels of Aymara Indians from the Bolivian Andes.

A study was made of the qualitative histological features of the small pulmonary arterial vessels of 25 adult citizens of La Paz, Bolivia (altitude 3600 m) coming to necropsy. Abnormalities found included muscularization of pulmonary arterioles, the development of longitudinal muscle in the intima of pulmonary arteries and arterioles, and the formation of muscular tubes lining the longitudinal muscle which extended through arterioles into the precapillaries of the lung. Arteriolar muscularization was found in three of the 13 Aymaras and in two of the 12 Mestizos studied. Intimal longitudinal muscle was present in four Aymaras and five Mestizos. Muscular tubes were found in only one case, a young Aymara. The features were very similar to those found in chronic obstructive airways disease. The appearances are consistent with a growth of new vascular smooth muscle in response to alveolar hypoxia as opposed to hypoxic vasoconstriction.

Serum CEA and CA 19-9: potential future diagnostic or screening tests for gallbladder cancer?

The poor prognosis of gallbladder cancer and the presence of high-risk populations make the identification of a screening test for this disease very desirable. As part of an ongoing case-control study of gallbladder cancer being conducted in Mexico City, Mexico, and in La Paz, Bolivia, blood specimens were sought from all patients with cancer of the gallbladder and on controls of similar age and sex undergoing upper abdominal surgery. Each sample was analyzed for carcino-embryonic antigen (CEA) and CA 19-9. Using the specimens from Bolivia, a serum CEA cutoff of 4.0 ng/ml yielded a sensitivity of 50.0% and a specificity of 92.7%, while a serum CA 19-9 cutoff of 20.0 units/ml yielded a sensitivity of 79.4% and a specificity of 79.2%. Using ROC curve analysis, the latter was a much better test than the former (p less than 0.05). Using the tests in series or in parallel did not substantively improve the results. The specimens from Mexico were used for validation purposes, and yielded very similar results. In conclusion, serum CA 19-9 and CEA are fairly good tests for discriminating patients with gallbladder cancer from patients with gallstones and no cancer, the former being a better test than the latter. These tests may be useful in identifying disease recurrences. In addition, if a sufficiently high-risk population could be identified, this could potentially become a useful screening test for this serious disease, allowing early intervention. However, additional data are needed prior to recommending this clinically.

Cancer of the gallbladder in Bolivia: suggestions concerning etiology.

In order to investigate the very high incidence of gallbladder cancer in Bolivia, a series of patients with gallbladder cancer and/or cholelithiasis from a hospital in La Paz was compared to a series of patients with cholelithiasis from Philadelphia. Each group demonstrated a similar female predilection. Bolivian patients with gallbladder cancer were older than patients with cholelithiasis who, in turn, were older than the general population (p less than 0.001). Racial differences demonstrated previously were confirmed. Bolivian gallstones were uniformly cholesterol in type, in contrast to the US series, in which 27% of patients had black pigment stones. Bile specimens obtained from Bolivian patients with cholelithiasis had a lower concentration of bile salts, phospholipids, and cholesterol than bile specimens from US cholelithiasis patients (p less than 0.01, less than 0.001, and less than 0.001, respectively). These biochemical differences may help to explain the differing incidence of cholelithiasis and gallbladder cancer in the US and Bolivia.

The epidemiology of cancer of the extra-hepatic biliary tract in Bolivia.

Data on patients with cancer of the gall bladder and cancer of the extra-hepatic bile ducts were obtained from the tumour registry in La Paz, Bolivia. Incidence rates were calculated using the Bolivian census data and compared to US incidence data from the Third National Cancer Survey. The age and population standardized incidence rates for cancer of the gall bladder in Bolivia were 5.3/100,000 males/year and 10.3/100,000 females/year. Comparable US rates were 1.0/100,000 males/year and 2.1/100,000 females/year. The age and population standardized incidence rates for cancer of the extra-hepatic bile ducts in Bolivia were 1.1/100,000 males/year and 4.1/100,000 females/year. Comparable US rates were 1.6/100,000 males/year and 1.0/100,000 females/year respectively. Both diseases occurred at younger ages in Bolivia than in the US and both showed marked racial variation. Differences in disease incidence between Bolivia and the US could not be fully explained by differences in age, sex, or racial distributions. Studies designed to investigate the causes of this remarkable variation in disease incidence could provide important clues to disease aetiology.

Megacolon at high altitude.

Megacolon occurs frequently in high altitude areas. This report describes observations made in 60 cases seen in La Paz, Bolivia (3,600 meters above sea level). Motility of both the large and small bowel was found to be increased and the feces had a low pH. No histologic abnormalities were noted in the nervous plexus or smooth muscle. It is assumed that megacolon in these circumstances is acquired and not congenital.

Megacolon at high altitude.

El megacolon es una alteracion frecuentemente encontrada en las grandes alturas.En esta publicacion describimos y analizamos sesenta casos de megacolon encontrados en el Hospital Obrero en La Paz, Bolivia a 3.600 m de altura sobre el nivel del mar. Se ha encontrado el transito intestinal acelerado tanto en intestino delgado como en colon. El pH de las materias fecales acido. En el estudio histopatologico no se encuentran alteraciones ni en los plexos nerviosos ni en la musculatura lisa. Se propone que el megacolon de las grandes alturas es una alteracion adquirida, producida por una mayor distencion de los gases en colon bajo una presion atmosferica mas baja que al nivel del mar, 490 mm Hg a esta altura comparada con los 760 mm Hg al nivel de mar

Incidencia de litiasis biliar y cancer del tracto biliar extra hepatico en autopsias. / Incidence of biliary lithiasis and biliary tract cancer in necropsies

La incidencia de litiasis biliar encontrada en 327 autopsias de adultos efectuadas en el Hospital. No 1 de la CNSS fue 31.19% Los calculos biliares fueron mas frecuentes en mujeres (45,93%) que en varones (22,56%). Por otra parte, el cancer de via biliar fue el mas frecuentemente encontrado en autopsias de ninos y adultos realizadas en el mismo periodo de tiempo, haciendo el 15,9% de los canceres encontrados en dichos estudios post-mortem

Colecistitis xantogranulomatosa. / Xanthogranulomatous cholecystitis

Se analizan las caracteristicas clinicas y patologicas de 20 casos colecistitis xantogranulomatosa que constituyen solo el 0,56% de las colecistitis con estudio anatomopatologico. Se enfatiza el hecho de que pueden ser confudidas macroscopicamente, tanto por el cirujano como por el patologo, con el carcinoma de vesicula biliar. Se revisan publicaciones sobre su etiopatogenia que consideran que esta lesion es secundaria a un dano tisular, posiblemente por agentes bacterianos o litiasis, en tejidos donde hay acumulos de lipidos biliares

Megacolon at high altitude.

El megacolon es una alteracion frecuentemente encontrada en las grandes alturas.En esta publicacion describimos y analizamos sesenta casos de megacolon encontrados en el Hospital Obrero en La Paz, Bolivia a 3.600 m de altura sobre el nivel del mar. Se ha encontrado el transito intestinal acelerado tanto en intestino delgado como en colon. El pH de las materias fecales acido. En el estudio histopatologico no se encuentran alteraciones ni en los plexos nerviosos ni en la musculatura lisa. Se propone que el megacolon de las grandes alturas es una alteracion adquirida, producida por una mayor distencion de los gases en colon bajo una presion atmosferica mas baja que al nivel del mar, 490 mm Hg a esta altura comparada con los 760 mm Hg al nivel de mar

Megacolon at high altitude.

Megacolon occurs frequently in high altitude areas. This report describes observations made in 60 cases seen in La Paz, Bolivia (3,600 meters above sea level). Motility of both the large and small bowel was found to be increased and the feces had a low pH. No histologic abnormalities were noted in the nervous plexus or smooth muscle. It is assumed that megacolon in these circumstances is acquired and not congenital.

Morbidity from cancer in La Paz, Bolivia.

Data from a population-based Cancer Registry in La Paz, Bolivia, are presented. The city is located at approximately 4,000 meters above sea level and has a strong cultural influence consisting of Aymará Indians immigrating from the altiplano. Incidence rates in females are high for cancer of the cervix, the gallbladder and the thyroid gland. Males display unusually high rates of testicular cancer. Stomach cancer rates are lower than among other Andean populations. Smoking-related cancer and cancers related to sex-hormones are lower than average in incidence. Cancer of the nasal mucosa and paranasal sinuses is unusually high in frequency.

Small pulmonary arteries in some natives of La Paz, Bolivia.

A histological study was made of the small pulmonary blood vessels in pieces of lung obtained at necropsy from 19 long-term residents of La Paz, Bolivia (3800 m). There was variation in the response of the pulmonary vasculature of these subjects to the chronic hypoxia of high altitude. The most characteristic finding, seen in seven of the 16 cases beyond infancy, was distal extension of vascular smooth muscle into pulmonary arterioles as small as 20 micrometer in diameter. Medial hypertrophy of the muscular pulmonary arteries occurred in only three of these seven subjects. Intimal fibrosis was seen in eight of the 19 cases and was ascribed to age; such fibrotic proliferation may affect the reversibility of hypoxic pulmonary hypertension and associated vascular changes in highlanders.

Diseases of the colon and rectum in Bolivia.

A review of the surgical and autopsy records from two general hospitals in La Paz, Bolivia, discloses an incidence of colon and rectal disease, excluding hemorrhoids, of 0.6 per cent (138 of 22,361 surgical cases) and 2.5 per cent (16 of 640 consecutive autopsies). Acquired megacolon complicated by volvulus represented more than half of all cases in the surgical series. Ulcerative colitis, diverticular disease, and neoplastic polyps represented less than 10 per cent of the cases of colonic disease. Only ten cases of carcinoma of the colon were seen, whereas five cases of granulomatous colitis or ileocolitis were detected in the same surgical material. Among sixty-four lesions of the rectum, so-called retention polyps accounted for 54.5 per cent of the cases, with carcinoma next in frequency (25 per cent), and the remainder being different varieties of inflammatory conditions. In the autopsy material almost half of the cases were infectious conditions, followed by congenital malformations and complicated acquired megacolon. No case of diverticular disease of the colon or neoplastic polyps was seen, and there was only one case of cancer of the large bowel. Because of the high incidence of acquired megacolon and the low incidence of cancer, ulcerative colitis, adenomatous polyps, and diverticular disease of the colon, possible etiopathogenic factors of these conditions are discussed in comparison with their incidence in other developed and developing countries of the world.