Observations on the iron metabolism as related to the influence of a low oxygen tension at high altitudes, and after the disappearance of this factor upon return to sea level, have been made in human subjects. They consisted mainly of studies of intestinal absorption and turnover rate of iron by means of the radioactive isotope of this metal (Fe-59). Additional observations were made on blood volume, reticulocytosis, bone marrow cytology, life span of the red cells and hemoglobin breakdown pigments. The data obtained seem to justify the following conclusions: 1. There is an increase of intestinal iron absorption during the early period of exposure to an altitude of 14,900 feet. After 48 hours of exposure, this was estimated to be about 3 times higher than the absorption observed in subjects at sea level and in native residents at the above-mentioned altitude. 2. There is an increase of plasma and red cell iron turnover rates after 2 hours of arrival to 14,900 feet, indicating that the increase in the production of red cells, to compensate for hypoxia, is a very early response. 3. The highest increase in plasma and red cell iron turnover rate takes place 7 to 14 days after exposure to high altitude begins. After six months of exposure, there is still an elevated iron turnover rate. The native residents of high altitudes (14,900 feet) have a red cell iron turnover rate of approximately 30 per cent higher than healthy subjects at sea level. 4. A progressive decrease in the plasma and red cell iron turnover rate is observed in native residents of high altitudes when brought down to sea level, the maximum of which is reached after two to five weeks, indicating a great degree of depression on red cell production. After that, a gradual return to normal rate is observed in the weeks that follow. 5. The degree of reticulocytosis is in close relationship with changes in the red cell iron turnover rates. 6. Changes in the total blood volume, either during ascent or descent, take place only after several weeks. The red cell mass variations which occur during the early periods of environmental change, are compensated by proportional changes in the plasma volume. The increase or decrease of the total blood volume after this period is due exclusively to red cell mass modifications. 7. The bone marrow cytologic studies carried out in subjects temporarily exposed or living permanently at high altitudes show a hyperplastic condition. The reverse, or an inhibition of red cell production, takes place when high altitude polycythemic subjects are brought down to sea level. This constitutes the cytologic counter-proof for the iron turnover studies. 8. The life span of the red blood cells, after descent from high altitudes to sea level, falls within normal patterns. However, by the method employed it is not possible to determine if there is an increased destruction of red cells during the first week. But if there is a greater destruction, this would be of a small degree, affecting only the older elements. The increase in the hemoglobin breakdown pigments, which occurs under the influence of environmental factors, is also discussed. 9. In native residents of high altitudes the amount of free erythroprotoporphyrins is higher than in residents at sea level. The erythroprotoporphyrins in newcomers to high altitudes rise and reach a peak at the end of the second month, followed by a gradual decline. On the other hand, when high altitude natives are brought down to sea level, a marked decrease in erythroprotoporphyrins is noted. The rate of decrease is highest within the first months.

The investigation reported in this paper is concerned with the effects of desoxycorticosterone acetate (DCA), hydrocortisone and dietary potassium depletion on the elaboration of an osmotically concentrated urine in the hydropenic state. Loeb and his associates (1, 2) demonstrated that dogs maintained on large amounts of DCA develop a diabetes insipidus-like picture. Since then, renal function studies in man (3-5), dogs (6) and rats (7,8) have shown that the ability of the kidney to concentrate the urine is markedly reduced in states of adrenal hyperfunction and potassium deficiency. The mechanism by which polyuria is produced under these conditions has not been established. In particular, the role of potassium deficiency is still a matter of controversy. Thus, contrary to Loeb and co-workers (1, 2), who were unable to prevent the development of polyuria in their DCA-treated animals by feeding potassium chloride, some authors maintain (9) that the increased loss of potassium following the administration of adrenal steroids is responsible for the impairment of water conservation. Also, there is no agreement on the sensitivity of the kidney to vasopressin (Pitressin®) during various states of potassium depletion (7, 9).The present study is an attempt to clarify some of these points. We have, in particular, studied the formation of a concentrated urine during osmotic diuresis in the hydropenic state. According to current concepts, an osmotically concentrated urine can be visualized as being made up of an isosmotic portion less the amount of water abstracted from it to produce hypertonicity ( 10, 11 ). * Aided by a grant from the National Heart Institute, Bethesda, Md.t This work was done during the tenure of an Established Investigatorship of the American Heart Association. This latter moiety has been designated TCHEO (10,11) or water economy (12) and direct evidence indicates that the collecting duct system is the site where the process of final water abstraction occurs (13,14). Contrary to findings obtained on control animals in which variations of TCH,0 are fairly small over a wide range of urine flows, our results show that DCA administration produces a significant and progressive reduction of that amount of water as urine flow increases. Also, at higher flow rates the occurrence of marked hypotonicity was a frequent finding, thus indicating that the fluid reaching the site of final water abstraction was not rendered isosmotic during its passage along the distal tubule and collecting duct (13,14). METHODSThirty-eight experiments were performed on nine female mongrel dogs ranging in weight from 17 to 25 Kg.' Anesthesia was induced and maintained by appropriate amounts of sodium pentobarbital given intravenously. In all animals data on osmolality of urine and plasma at low urine flow rates and during osmotic diuresis were obtained before and after treatment with various hormones and diets. Thus, each animal served as its own control. Since, in particular, variations in the protein intake have been shown to influe...

When compared with sea-level residents, the healthy natives living at an altitude of 4,540 m show a 12% reduction in the glomerular filtration rate, a 37% reduction in effective renal plasma flow, a 12% reduction in effective renal blood flow, and an increase of 39% in the filtration fraction. The corresponding values in patients with chronic mountain sickness living at 4,300 m above sea level are: glomerular filtration rate, 32% reduction; effective renal plasma flow, 57% reduction; effective renal blood flow, 9% increase; and filtration fraction, 56% increase. The mean hematocrit values of the healthy and sick natives investigated were 59 and 79%, respectively. The possible relationships between cardiac output, hematocrit values, and renal hemodynamics are discussed. altitude stress; blood flow, kidney; glomerular filtration Submitted on October 5, 1964

To determine the possible changes in semen quality of Venezuelan men from 1981 to 1995, a retrospective analysis of semen volume and sperm concentrations was carried out for 2313 men from infertile couples. According to the sperm counts the sample was categorized in four groups: A, 0 sperm; B, <20 x 10(6) sperm/mL; C, 20-200 x 10(6) sperm/mL; D, 2200 x 10(6) sperm/mL. The percentage of men in each group was 9.1, 18.8, 63. 1, and 9.0%, respectively. The frequency of azoospermia and oligozoospermia (groups A and B) did not change over the last 15 years. On the contrary, the frequency showed a significant increase in group C and a decrease in group D. The range of the means of semen volume was 2.6-3.6 mL, linear regression analysis did not show a decrease in seminal fluid volume over time. The range of the means of sperm concentrations were 6.2-12.0 x 10(6) sperm/mL, 73-100 x 10(6) sperm/mL), and 230-340 sperm x 10(6)/mL in groups B, C, and D, respectively. Linear regression analysis revealed a significant reduction in the means of sperm concentrations only in group D. Excluding the azoospermic group, the analysis of pooled data (B + C + D), did not show a significant change in the means of sperm density throughout time. In the semen samples with sperm counts below 200 x 10(6)/mL the means of sperm concentration did not change in the 15-year period of observation.

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