Biomedical subjects
M D Lindheimer
Publications and source records attributed to M D Lindheimer.
Pregnancy in the renal transplant patient.
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Osmotic and volume control of vasopressin release in pregnancy.
This article, a review of factors controlling vasopressin (AVP) release in pregnancy, extends our contribution to a symposium in this journal published in 1987 (vol X, pp 270-275). Body tonicity decreases (approximately 10 mOsm/kg) very early in pregnancy due to decrements in the osmotic thresholds for AVP release and thirst. In addition, the metabolic clearance rate (MCR) of AVP markedly increases between gestational week 10 and midpregnancy, and is paralleled by the appearance and increase of circulating cystine aminopeptidase (vasopressinase), while the MCR of 1-deamino-8-D-AVP (DDAVP), an analogue resistant to inactivation by the enzyme, changes little in pregnancy. These increases (MCR of AVP and plasma vasopressinase) may explain certain syndromes of transient diabetes insipidus (DI) that complicate gestation. Finally, mechanisms responsible for the altered osmoregulation in pregnancy are obscure, but chorionic gonadotropin may be involved in the changes during human gestation.
Hypertension in pregnancy: advances and controversies.
Advances in prenatal care have resulted in a substantial decline in the number of serious complications associated with high blood pressure during pregnancy. Nevertheless, the hypertensive disorders remain a significant cause of maternal and fetal morbidity, and even mortality [Rochat et al. 1988]. In addition, hypertension in pregnancy is a topic that generates considerable controversy, ranging from the correct manner to measure blood pressure in gravidas, to major disputes concerning management considerations. The pervasiveness of such controversies [Cunningham and Pritchard 1984, Ferris 1984, Disdale 1988, Kaplan et al. 1988] led the United States' National Institutes of Health, through its National High Blood Pressure Education Program, to convince a working group whose "consensus" report has just been published (1990), and is recommended reading for physicians who manage gravidas. This review focuses on preeclampsia, and includes observations concerning the pathogenesis of this disorder as well as strategies to prevent its occurrence. Conflicting opinions regarding the management of preeclamptic women will also be discussed, highlighting the recommendations made by the NIH consensus group (NHBPEP 1990). Space considerations limit the references cited, and the reader is referred to a chapter [Barron 1991] and several texts [Chesley 1978, Rubin 1988] for a more complete survey of the literature.
Regulation of blood pressure in pregnancy: pressor system blockade and stimulation.
Contributions of the autonomic nervous system (ANS), renin-angiotensin system (RAS), and arginine vasopressin (AVP) to basal mean arterial pressure (MAP) were evaluated in near-term pregnant and virgin rats as follows. MAP and heart rate (HR) were measured before and after ganglionic, alpha-adrenoreceptor, RAS, and/or AVP blockade. In addition, pressor responses to angiotensin II (ANG II), norepinephrine, phenylephrine, or AVP were determined in ganglionic-blocked animals. In both groups decrements in MAP were greatest after ganglionic or alpha-blockade, intermediate after RAS blockade, and negligible after AVP-V1 antagonism ([d(CH2)5Tyr(Me)]AVP). Recovery of MAP was also similar in the two groups except after phentolamine when MAP and HR remained lower in gravid rats. Superimposition of RAS or AVP blockade during phentolamine infusion suggested that ANG II and AVP were less effective in supporting MAP during alpha-blockade in pregnancy. Pressor responses to ANG II and norepinephrine during ganglionic blockade were markedly blunted during pregnancy; however, those to phenylephrine and AVP were unchanged. We conclude that contributions of ANS, RAS, and AVP to basal MAP are similar in pregnant and virgin rats; neural mechanisms dominating in both groups. However, recovery during alpha-blockade is impaired during gestation, apparently due to blunted HR responses and decreased pressor contributions of ANG II and AVP. This may be explained, in part, by decreased vascular reactivity to ANG II, although a similar mechanism cannot be invoked for AVP.
Desoxycorticosterone in normal pregnancy. II. Cortisol-dependent fluctuations in free plasma desoxycorticosterone.
Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.
Effect of general anaesthesia on renal haemodynamics in the rat.
1. The effect of sodium pentobarbital and Inactin anaesthesia on renal haemodynamics in the rat was evaluated with radioactive microspheres 15 micrometer in diameter. 2. Both anaesthetic agents caused substantial decrements in total renal blood flow (sodium pentobarbital, -34%; Inactin, -24%) compared with unanaesthetized animals. 3. Measurements of renal function obtained in rats anaesthetized with either of these anaesthetic agents should be interpreted with caution.
Postural effects on renal function and volume homeostasis during pregnancy.
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A simple method for determining the free cortisol index in plasma: measurements in human pregnancy.
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Desoxycorticosterone in normal pregnancy. I. Sequential studies of the secretory patterns of desoxycorticosterone, aldosterone, and cortisol.
Plasma concentrations of desoxycorticosterone (DOC) and aldosterone are markedly elevated in pregnancy. Although DOC secretion in nongravid women has been assumed to be dependent mainly on adrenocorticotropic hormone (ACTH), in a previous study of women in the third trimester of pregnancy it was found to be unresponsive to ACTH, dexamethasone, and variations in salt intake. In this study plasma DOC, aldosterone, and cortisol levels, as well as their responses to ACTH stimulation and overnight dexamethasone suppression, were observed sequentially in seven normal women during the course of pregnancy and at three months post partum. Plasma DOC, aldosterone, and cortisol levels rose substantially during gestation, but increments in DOC did not necessarily coincide with those of the other two. Responses of all three corticosteroids to ACTH were enhanced during the first two trimesters compared to the nongravid state; DOC became unresponsive in the third trimester, while aldosterone and cortisol rose to an even greater extent. Elevated maternal DOC was not decreased significantly by dexamethasone at any stage of pregnancy, while plasma cortisol was suppressed. Nonsuppressibility of DOC with dexamethasone and also the lack of correlation of the rise in DOC with the increase in cortisol during the course of pregnancy suggest that increased DOC secretion in pregnancy does not arise from ACTH-dependent pathways of the maternal adrenal. The loss of responsiveness of DOC to ACTH in the third trimester suggests that the maternal adrenals have undergone an alteration in their steroidogenic response to ACTH, but also may indicate that their output of DOC has reached a maximal rate.
Nephrolithiasis during pregnancy.
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Renal disease in pregnant women.
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Plasma angiotensin converting enzyme activity in mother and fetus.
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Nephrotic proteinuria with pre-eclampsia.
During a retrospective study of 100 patients who underwent renal biopsy because of pregnancy complicated by hypertension, we found 19 patients whom proteinuria exceeded 5.0 Gm. per 24 hours and an additional eight patients in whom excretion ranged between 3.5 and 5 Gm. per day. Of these 27 patients, 23 had the kidney lesion of pre-eclampsia, and three of them had superimposed hypertensive changes in the vasculature. The remaining four had other renal diseases. We located and re-examined 10 of the 23 pre-eclamptic women, 12 to 104 (mean, 36) months after delivery. Serum creatinine levels were normal in all but one, who was discovered to have polycystic kidney disease. During the same time period, we located the records of six women who had heavy proteinuria during gestation but were normotensive. Thus, at our institution, pre-eclampsia is the most common cause of the nephrotic syndrome in pregnancy. The frequency of nephrotic proteinuria in pre-eclampsia appears higher than previously suspected, but, despite this fact, recovery was complete in most instances.
Maternal primary hyperparathyroidism of pregnancy. Successful treatment by parathyroidectomy.
Primary hyperparathyroidism of pregnancy may result in spontaneous abortion, neonatal hypocalcemia, or neonatal tetany if appropriate treatment is not instituted. Of great importance in prevention of these complications is an awareness by physicians that this disease exists and is of clinical importance. Parathyroidectomy performed during the second trimester of pregnancy offers the best chance for fetal and neonatal survival. This operation results in little risk to either the mother or the fetus. Normal calcium homeostasis is restored to the fetus and the risk of hypocalcemia in the neonatal period is virtually eliminated.
Uremia in rats with normal kidneys: a model for the study of renal function in a uremic environment.
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Actions of hormones on the kidney.
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The optimum pH of renal adenosine triphosphatase and its variation with the type of ATP.
The in vitro optimum pH of renal (Na+, K+)-ATPase, assumed to be 7.8, depends on the type of ATP used. The accepted value is obtained with 'grade II' ATP but with purer ATP ('Sigma grade') it lies close to the intracellular pH in rat medulla and cortex (pH 7.0, 7.2). Values were identical in rats subjected to dietary potassium depletion for 2-4 weeks. The optimal Mg2+ concentration was also influenced by the type of ATP but Mg ATPase activity was unaffected. Both types of ATP were hydrolysed by trichloracetic acid. Where the purer ATP is used the assay conditions need to be modified accordingly.