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Biomedical subjects

S Zamudio

Publications and source records attributed to S Zamudio.

At least 37 records · Page 2Linked to original sources

Women at altitude: changes in carbohydrate metabolism at 4,300-m elevation and across the menstrual cycle.

We hypothesized that, in women, the blood glucose response to a meal (BGR) would be lower after exposure to 4,300 m compared with sea level (SL) and that BGR would be reduced in the presence of estrogen plus progesterone (E+P) relative to estrogen alone (E). Sixteen women were studied in both the E and E+P conditions at SL and in either the E or E+P condition at 4,300 m. On day 9 in each condition, blood was sampled before, and every 30 min for 2 h after, the subjects ate a high-carbohydrate meal. At 4,300 m, BGR peaked at a lower value (5.73 +/- 0.94 mM) than at SL (6.44 +/- 1.45 mM) and returned to baseline more slowly (P < 0.05). Plasma insulin values were the same but C peptide was slightly higher at 4,300 m (P < 0. 05). At SL, BGR returned to baseline more slowly in E+P condition (5. 13 +/- 0.89 and 5.21 +/- 0.91 mM at 60 and 90 min, respectively) relative to E condition (4.51 +/- 0.52 and 4.69 +/- 0.88 mM, respectively) (P < 0.05). Insulin and C peptide were not different between E and E+P conditions. The data indicate that BGR is lower in women at high altitude compared with the SL, possibly due to greater suppression of hepatic glucose production or stimulation of peripheral glucose uptake by insulin. BGR was lower in E condition relative to E+P condition at SL and possibly at 4,300 m, but the relative concentrations of ovarian hormones do not appear to alter the magnitude of the change in BGR when women are exposed to high altitude.

Adult↗

Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy.

Blood pressure decreases during early pregnancy in association with a decrease in peripheral vascular resistance and increases in renal plasma flow and glomerular filtration rate. These early changes suggest a potential association with corpora lutea function. To determine whether peripheral vasodilation occurs following ovulation, we studied 16 healthy women in the midfollicular and midluteal phases of the menstrual cycle. A significant decrease in mean arterial pressure in the midluteal phase of the cycle (midfollicular of 81.7 +/- 2.0 vs. midluteal of 75.4 +/- 2.3 mmHg, P < 0.005) was found in association with a decrease in systemic vascular resistance and an increase in cardiac output. Renal plasma flow and glomerular filtration rate increased. Plasma renin activity and aldosterone concentration increased significantly in the luteal phase accompanied by a decrease in atrial natriuretic peptide concentration. Serum sodium, chloride, and bicarbonate concentrations and osmolarity also declined significantly in the midluteal phase of the menstrual cycle. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion increased in the luteal compared with the follicular phase, whereas no changes in urinary cGMP or NO2/NO3 excretion were found. Thus peripheral vasodilation occurs in the luteal phase of the normal menstrual cycle in association with an increase in renal plasma flow and filtration. Activation of the renin-angiotensin-aldosterone axis is found in the luteal phase of the menstrual cycle. These changes are accompanied by an increase in urinary cAMP excretion indicating potential vasodilating mediators responsible for the observed hemodynamic changes.

Adult↗

Breathing and brain blood flow during sleep in patients with chronic mountain sickness.

Chronic mountain sickness (CMS) patients have lower arterial O2 saturation (SaO2) during sleep compared with healthy high-altitude residents, but whether nocturnal arterial O2 content (CaO2) and brain O2 delivery are reduced is unknown. We measured SaO2, CaO2, sleep-disordered breathing (SDB), and internal carotid artery flow velocity in 8 CMS patients, 8 age-matched healthy CMS controls, 11 healthy younger-aged Han, and 11 healthy younger-aged Tibetan male residents of Lhasa, Tibet (3,658 m). CMS patients spent a greater portion of the night in SDB (total no. of episodes of apnea, hypopnea, and hypoventilation) than did the CMS controls, young Han, or young Tibetans (15% vs. 5, 1, and 1%, respectively; P < 0.05) because of more frequent apnea and hypoventilation episodes and longer duration of all types of episodes. SDB and unexplained arterial O2 desaturation caused nocturnal SaO2 to be lower and more variable in CMS patients than in CMS controls or in younger-aged Han or Tibetan men. Average CaO2 was similar, but the CMS patients spent 29%, whereas the other groups spent < 4%, of the night at values < 18 ml O2/100 ml whole blood. Internal carotid artery flow velocity during wakefulness was similar in CMS patients and CMS controls despite higher end-tidal PcO2 values in the CMS patients. When contiguous sleep stages are compared, flow velocity rose from stage 2 to rapid-eye-movement sleep in both groups. Whereas flow velocity remained elevated from awake to rapid-eye-movement sleep in the CMS controls, it fell in the CMS patients. During episodes of SDB, internal carotid flow velocity increased in CMS controls but did not change in the CMS patients such that values were lower in the CMS patients than in CMS controls at the end and after SDB episodes. We concluded that SDB and episodes of unexplained desaturation lowered nocturnal SaO2 and CaO2, which, together with a lack of compensatory increase in internal carotid artery flow velocity, likely decreased brain O2 delivery in CMS patients during a considerable portion of the night.

Adult↗

Potentiation of the immobility response elicited by bandaging and clamping in mesencephalic rats.

In earlier work, we showed that adult rats exhibit immobility response (IR) if a clamp is fastened to the skin of the nape of the neck, but not at other areas of the body, and not by bandaging. The present study characterizes IR in adult rats with complete mesencephalic transections. In the mesencephalic rats, the duration of the IR not only increased, but the stimuli capable of eliciting it were more diverse. All head and body areas clamped or bandaged were capable of inducing a profound IR. In contrast, the IR in intact rats was of shorter duration, and was only induced by clamping the neck, or by bandaging the upper or the lower torso. Furthermore, unlike the mesencephalic rats the ability of the bandaging to induce IR is reduced after the first trial and finally disappears. Only clamping the neck was able to persistently induce IR in intact rats. These data support the hypothesis that the IR control system is in the midbrain, hindbrain or spinal cord, and that systems above the mesencephalon modulate the IR. Such modulation appears to involve the ability to discriminate amongst tactile stimuli, and to integrate previous experience.

Animals↗

Increased risk of craniosynostosis with higher antenatal maternal altitude.

BACKGROUND: During the 1980s, the Colorado Department of Health received reports from several high-altitude communities of clusters of the malformation craniosynostosis. In a population-based, case-control study, we examined the association between overall and trimester-specific maternal antenatal altitude exposure and the occurrence of infant craniosynostosis. METHODS: We identified case children through a statewide registry and randomly sampled control children from birth records. By telephone interview, each mother provided data on the locations of all antenatal residences and places of employment as well as other factors. Staff mapped all locations and abstracted the corresponding altitudes. RESULTS: The odds ratio (OR) of any synostosis for a time-weighted mean antenatal altitude of > or = 2000 metres (high altitude) versus < 2000 metres (low altitude) was 1.4 (lower bound of the one-sided 95% test-based confidence interval (CI): 0.9). The OR was elevated in smokers but not in non-smokers. As compared to non-smokers, the OR of any synostosis for high-altitude smokers was 4.6 (lower bound of the 95% one-sided exact CI: 1.7). Particularly elevated were the corresponding OR of coronal (18.1, 4.4) and metopic synostosis (16.3, 2.8), and OR for high-altitude exposure during the second trimester (any synostosis: 6.4, 1.99; coronal: 28.6, 6.1; metopic: 26.7, 4.1). CONCLUSIONS: Antenatal maternal high-altitude exposure and smoking are associated with increased risk of infant craniosynostosis, perhaps through generation of intermittent hypoxaemia.

Altitude↗

Alterations in uteroplacental blood flow precede hypertension in preeclampsia at high altitude.

High-altitude residence during pregnancy is associated with an increased incidence of preeclampsia. To determine whether uteroplacental blood flow was reduced and pelvic blood flow distribution altered before the onset of hypertension, we measured common iliac (CI), uterine (UA), and external iliac (EI) artery flow velocities (FV), indexes of flow distribution, and blood volume (BV) at week 12, 24, and 36 of pregnancy and 6 mo postpartum in 23 normotensive, 7 preeclamptic, 5 transiently hypertensive, and 3 chronically hypertensive residents of 3,100 m. Normotensive women had a progressive increase in CIFV and UAFV, decrease in EIFV, redistribution of CIFV from the EI to the UA, and increase in BV with advancing pregnancy. Preeclamptic women attained maximal UAFV and redistribution of CIFV from the EI to the UA well before the onset of hypertension and, unlike normotensive women, showed no further increases near term. Plasma volume increment with pregnancy related to the fall in the EIFV/CIFV ratio. Transiently hypertensive women resembled normotensive subjects in the parameters measured, whereas chronically hypertensive subjects resembled preeclamptic subjects. We concluded that preeclamptic vs. normotensive pregnant residents of high altitude had less redistribution of CI flow to the UA and no increase in UA blood flow near term. That these differences were present before the onset of hypertension supports the concept that preeclampsia is characterized by an incomplete vascular adjustment to pregnancy.

Adult↗

Effect of altitude on uterine artery blood flow during normal pregnancy.

To determine whether uterine blood flow was reduced and indexes of pelvic blood flow distribution altered in normotensive pregnancy at high (3,100 m) compared with low altitude (1,600 m), we measured uterine, common iliac, and external iliac artery blood flow velocities and diameters in women during pregnancy and again postpartum. Pregnancy increased uterine artery diameter, blood flow velocity, and volumetric flow at both altitudes. Uterine artery blood flow velocity was greater (69.0 +/- 2.2 vs. 59.4 +/- 3.0 cm/s; P < 0.005) but diameter was smaller at 3,100 m than at 1,600 m (2.5 +/- 0.3 mm vs. 3.4 +/- 0.2 mm; P < 0.005), resulting in volumetric flow that was one-third lower at week 36 of pregnancy (203 +/- 48 vs. 312 +/- 22 ml/min, respectively; P < 0.01). Pregnancy increased common iliac blood flow velocity and decreased external iliac artery blood flow velocity at both altitudes. The uterine artery received a smaller percent of common iliac flow at 3,100 than at 1,600 m (46 +/- 7 vs. 74 +/- 6%; P < 0.005). Gestational age was similar but birth weight was lower at 3,100 m than at 1,600 m. Among subjects at 1,600 m, variation in uterine blood flow velocity correlated positively with infant birth weight. We concluded that reduced uterine blood flow and altered pelvic blood flow distribution during pregnancy at high altitude likely contributed to the altitude-associated reduction in infant birth weight.

Adult↗

Mitochondrial DNA analysis in Tibet: implications for the origin of the Tibetan population and its adaptation to high altitude.

Mitochondrial DNAs (mtDNAs) of 54 Tibetans residing at altitudes ranging from 3,000-4,500 m were amplified by polymerase chain reaction (PCR), examined by high-resolution restriction endonuclease analysis, and compared with those previously described in 10 other Asian and Siberian populations. This comparison revealed that more than 50% of Asian mtDNAs belong to a unique mtDNA lineage which is found only among Mongoloids, suggesting that this lineage most likely originated in Asia at an early stage of the human colonization of that continent. Within the Tibetan mtDNAs, sets of additional linked polymorphic sites defined seven minor lineages of related mtDNA haplotypes (haplogroups). The frequency and distribution of these haplogroups in modern Asian populations are supportive of previous genetic evidence that Tibetans, although located in southern Asia, share common ancestral origins with northern Mongoloid populations. This analysis of Tibetan mtDNAs also suggests that mtDNA mutations are unlikely to play a major role in the adaptation of Tibetans to high altitudes.

Adaptation, Physiological↗

Protection from intrauterine growth retardation in Tibetans at high altitude.

Intrauterine growth retardation has long been recognized at high altitude. Since growth-retarded babies have a decreased chance of survival, intrauterine growth retardation would be expected to have been selected against in populations long resident at high altitude. We have previously reported that Tibetan babies born at 3,658 m weighed more than their North or South American altitude counterparts. This study sought to determine whether Tibetans were protected from altitude-associated intrauterine growth retardation. We compared birth weights in Tibetans living at low altitude in Kathmandu, Nepal (elevation 1,200 m), or at high altitude in Lhasa, Tibet Autonomous Region, China (elevation 3,658 m). Birth weights were similar in 45 low-altitude and 34 high-altitude Tibetan births regardless of whether all infants or only full-term births were considered, or whether birth weight was adjusted for variation in maternal parity, gestational age, and infant sex. In comparison with literature observations, the altitude-associated difference in birth weight was smallest in Tibetans, intermediate in South America, and greatest in North America. These data support the hypothesis that Tibetans are protected from altitude-associated intrauterine growth retardation and suggest that selection for optimization of birth weight at high altitude has occurred in Tibetans.

Adult↗

Blood volume expansion, preeclampsia, and infant birth weight at high altitude.

Low blood volume (BV) during pregnancy is associated with intrauterine growth retardation and preeclampsia, which are more common at high altitude (HA) than at low altitude. We hypothesized that reduced BV expansion during pregnancy predisposed some women to develop preeclampsia and/or have lower-birth-weight infants at HA. BV was lower in 34 HA residents (3,100 m) than in 22 moderate-altitude residents (1,600 m) while nonpregnant (58.3 +/- 1.2 vs. 72.3 +/- 1.3 ml/kg; P < 0.001) and 36 wk pregnant (69.9 +/- 1.9 vs. 83.3 +/- 3.6 ml/kg; P < 0.01). BV fell between weeks 24 and 36 of pregnancy, and total BV increment with pregnancy was less in women who developed preeclampsia or transient hypertension at HA (n = 12). At HA, total blood and plasma volume expansion and arterial O2 saturation correlated negatively with the highest mean arterial pressure recorded during pregnancy (r = -0.73, P < 0.01 and r = -0.58, P < 0.01, respectively). Total BV and late pregnancy change in BV correlated positively with infant birth weight. We concluded that BV expansion in normotensive pregnancy at HA vs. moderate altitude was similar but that nonpregnant BV was less among HA women, accounting for the low BV in pregnancy. HA women who developed preeclampsia or transient hypertension had less BV expansion, particularly during the third trimester, which was associated with smaller infants.

Adult↗

[Chylous ascites: report of a case and review of the literature].

A patient presenting chylous ascitis due to an epithelial originated malignancy is reported. The primary focus of the malignancy could not be precise in spite of all diagnoses procedures available including explorer laparatomy. As this is a very unusual occurrence in the clinical practice, a review of reported literature has been made on ethological, physiopathological and therapeutical aspects.

Aged↗

Are Tibetans better adapted?

Evidence is reviewed from our recent (1987-1991) investigations which demonstrate better high-altitude adaptation among Tibetans than in acclimatized newcomers or other lifelong high-altitude residents. Characteristics of oxygen transport contributing to the Tibetans' remarkable exercise performance are described.

Acclimatization↗

Quantitative estimation of human uterine artery blood flow and pelvic blood flow redistribution in pregnancy.

OBJECTIVE: To determine the contributions of uterine artery diameter and mean flow velocity to the increase in volumetric flow during human pregnancy. METHODS: Volunteers (18 pregnant and six not pregnant) were studied using both a commercially available Doppler instrument with imaging ultrasound and an improved Doppler instrument with software that can determine instantaneous true mean blood flow velocity. Diameter and mean flow velocity measurements were combined to yield volumetric flows in the common iliac, external iliac, and uterine arteries during and after pregnancy. RESULTS: Compared with the nonpregnant state, uterine artery diameter doubled by week 21 (from 1.4 +/- 0.1 to 2.8 +/- 0.2 mm; P < .05), did not change between weeks 21 and 30 (2.9 +/- 0.1 mm), and increased between weeks 30 and 36 (to 3.4 +/- 0.2 mm). Uterine artery mean flow velocity rose progressively from nonpregnant values to attain at week 36 a velocity nearly eight times faster (8.4 +/- 2.2 versus 61.4 +/- 3.0 cm/second; P < .05). Unilateral uterine artery blood flow at week 36 was 312 +/- 22 mL/minute. CONCLUSIONS: Compared with nonpregnant values, common iliac artery flow increased and external iliac artery flow decreased during pregnancy, suggesting that redistribution of pelvic flow to favor the uterus contributed to the pregnancy-associated rise in uterus artery flow. Early in pregnancy, the increase in uterine artery blood flow was due in equal parts to changes in uterine artery diameter and mean flow velocity, whereas late in pregnancy, the rise was due mainly to faster mean flow velocity.

Adult↗

The cystic fibrosis heterozygote--advantage in surviving cholera?

Cystic fibrosis (CF) is the most common fatal genetic disorder of caucasians. While it has been hypothesized that there is a CF heterozygote advantage which allowed the gene to achieve such high prevalence, the nature of that advantage remains a mystery. The recent identification and sequencing of the CF gene has increased the probability that the CF heterozygote advantage will be discovered. In this hypothesis we review the information which is known about the selection of the CF mutation and its cellular consequences, and present evidence which suggests that resistance to cholera may have been the environmental factor which selected CF heterozygotes over their 'normal' homozygote cohort. Future lines of experimentation and possible clinical applicability to therapy of secretory diarrhea are presented.

Chloride Channels↗

Indicators of biotin status: a study of patients on prolonged total parenteral nutrition.

Plasma biotin concentration and lymphocyte propionyl CoA carboxylase (PCC) and its activation index (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were compared as markers of biotin status in patients on biotin-free prolonged total parenteral nutrition (TPN). Five patients had been on biotin-free TPN for over 1 month when the study was started, and had already developed clinical signs that may be caused by this vitamin deficiency. They had markedly reduced levels of both biotin and carboxylase levels, which increased to near normal levels 4 months after biotin was added to the TPN. They initially presented subnormal plasma zinc concentrations which were normal at the end of the study. Another 4 patients also received biotin-free TPN. After 1 month propionyl CoA carboxylase, which was already below normal in 3 of them at admission, further decreased and became undetectable in 1 of them, who presented clinical deficiency manifestations. The enzyme activation index increased more than twice, although plasma biotin remained normal. When the vitamin was added to the TPN solution, PCC activity increased and its activation index decreased to normal. Plasma zinc concentrations remained normal throughout in this other group of patients indicating that changes of biotin markers are not likely to be related to zinc status variation. Plasma biotinidase, a key enzyme in biotin endogenous recycling, was already subnormal at admission and had become normal at the end of the study, but was not associated with the biotin status.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Biotin deficiency in protein-energy malnutrition.

Several of the clinical and biochemical manifestations of biotin deficiency also occur in severe protein-energy malnutrition (PEM). Average plasma biotin concentrations were lower in 16 malnourished children (10 with marasmus, 3 with kwashiorkor and 3 with marasmic kwashiorkor) than in 31 controls. Lymphocyte mitochondrial carboxylase activities were studied in 11 controls and in 10 patients with PEM; on the average, they were lower in the patients. Their activation indices (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were higher in PEM. All these differences were statistically significant. None of these parameters were age-dependent in a range between 3 and 72 months. Carboxylase activities and plasma biotin levels increased to normal during nutritional recovery in two malnourished patients who were further studied. These results suggest that there is biotin deficiency in severe PEM. Urinary biotin concentrations, expressed per g of creatinine, were higher in the patients than in the controls; this may have been caused by increased renal clearance or by the reduced creatinine excretion which occurs in malnourished individuals. It will be important in future studies to determine the relative contribution of biotin deficiency to the malnourished phenotype.

Biotin↗

Tibetan protection from intrauterine growth restriction (IUGR) and reproductive loss at high altitude.

Chronic hypoxia at high altitude restricts fetal growth, reducing birth weight and increasing infant mortality. We asked whether Tibetans, a long-resident high-altitude population, exhibit less altitude-associated intrauterine growth restriction (IUGR) and prenatal or postnatal reproductive loss than Han (ethnic Chinese), a group that has lived there for a shorter period of time. A population sample was obtained, comprising 485 deliveries to Tibetan or Han women over an 18-month period at 8 general hospitals or clinics located at 2,700-4,700 m in the Tibet Autonomous Region, China. Birth weight, gestational age, and other information were recorded for each delivery. Prenatal and postnatal mortality were calculated using information obtained from all pregnancies or babies born to study participants. Tibetan babies weighed more than the Han, averaging 310 g heavier at altitudes 2,700-3,000 m (95% CI = 126, 494 g; P < 0.01) and 530 g heavier at 3,000-3,800 m (210, 750 g; P < 0.01). More Han than Tibetan babies were born prematurely. Prenatal and postnatal mortality rose with increasing elevation and were 3-fold higher across all altitudes in the Han than the Tibetans (P < 0.05). Tibetans experience less altitude-associated IUGR than Han and have lower levels of prenatal and postnatal mortality. When the relationships between birth weight and altitude are compared among these and other high-altitude populations, those living at high altitude the longest have the least altitude-associated IUGR. This may suggest the occurrence of an evolutionary adaptation.

Adult↗