Effect of sugars on transport of alanine in intestine.

The eflect of glucose and galactose on transport of alanine by rabbit ileum has been investigated. Transmural transport and cellular ac cumulation of the amino acid were in hibited by the sugars, but alanine in flux across the mucosal border of the cells was unaltered.

Subhuman primate pregnancy complicated by streptozotocin-induced diabetes mellitus.

Polydipsia, polyuria, polyphagia, and glucosuria followed the administration of streptozotocin to 6 nonpregnant and 15 pregnant monkeys (Macaca mulatta) in the first trimester of pregnancy. The diabetogenic action of the drug was also reflected in an induced but variable deterioration in maternal intravenous glucose tolerance and a marked attenuation of maternal plasma insulin responsiveness to intravenous glycemic stimuli. The products of conception were examined in 29 pregnancies. The neonates and the placentas of the streptozotocin-treated pregnant animals were significantly heavier than average for the period of gestation, polyhydramnios was consistently present, and there was an increase in the incidence of third trimester stillbirths. The fetal and maternal plasma glucose, insulin, and growth hormone concentrations were examined after the intravascular administration of glucose or a solution of mixed amino acids to the fetus in the third trimester. The neonatal plasma responses to similar insulinogenic stimuli were also examined.Fetal and neonatal base line plasma insulin concentrations were significantly elevated compared to those of the controls. The administration of intravascular glucose to the fetus, mother, or neonate was associated with a prompt 2-to 5-fold increase in fetal or neonatal plasma insulin concentrations. These findings contrast to the unresponsiveness of the pancreatic islet tissue we reported in normal subhuman primate pregnancy. The intravascular infusion of a relatively low concentration of mixed amino acids (2 mg/min) to the conceptii from the streptozotocin-treated pregnancies was associated with an elevation in fetal and neonatal plasma insulin levels, whereas normal monkey fetuses and neonates required a 10-fold greater concentration of amino acids in the infusate for similar responses. The induced hyperaminoacidemia or hyperglycemia did not consistently alter plasma growth hormone concentrations in the conceptii from normal or streptozotocin-treated pregnancies. These data provide evidence that maternal glucose intolerance during pregnancy is associated with enhanced fetal and neonatal pancreatic islet cell responsiveness to glucose and mixed amino acids. Although the specific mechanism(s) that alters both the sensitivity and responsiveness of the normal pancreatic fetal islet to insulinogenic stimuli remains unclear, the data do indicate that insulin-dependent maternal hyperglycemia and hyperaminoacidemia, separately or in combination could contribute to the fetal hyperinsulinemia of pregnancies complicated by diabetes mellitus. Moreover, the overall experiences with these streptozotocin-treated animals suggest that a subhuman primate model may be available to examine directly the antenatal pathophysiology of abnormal carbohydrate metabolism.

Fetal insulin and growth hormone metabolism in the subhuman primate.

The concentrations of plasma glucose, insulin, growth hormone, and immunoreactive growth hormone-like substance in subhuman primate fetal and maternal plasma were examined after the intravascular administration of glucose, arginine, or tolbutamide to the fetus. Cannulation of interplacental vessels permitted studies on the fetus in utero without disruption of fetal-placental-maternal anatomic integrity. Single glucose injections, glucose infusions, and arginine infusions into the fetus did not alter fetal plasma insulin concentrations. In contrast, tolbutamide injections elicited an immediate 3-4-fold increase in fetal plasma insulin concentrations. A bidirectional placental transfer of insulin was demonstrated with the use of simultaneously injected insulin-(125)I to the mother and insulin-(131)I to the fetus. Simian fetal plasma contained a substance which cross-reacted with immunologic identity to human growth hormone. In contrast, simian maternal plasma and amniotic fluid reacted with immunologic nonidentity to human growth hormone. Although glucose administration to the fetus did not suppress nor did arginine infusion consistently augment fetal plasma growth hormone levels, the latter were observed to vary in individual experiments. The plasma responses to the same stimuli in the neonate were also examined. In contrast to the fetal experiments, glucose injection in the neonate elicited a delayed rise in the concentration of plasma insulin. Similar to the fetus, the plasma concentration of insulin increased after tolbutamide injection and did not change in response to arginine infusion. The initial concentrations of neonatal plasma growth hormone were significantly lower when contrasted with the initial fetal plasma levels. There was no difference in the responsiveness of the fetal and neonatal growth hormone-releasing mechanisms when challenged by glucose or arginine infusion. The data indicate that the fetal plasma concentration of growth hormone is labile, that fetal growth hormone metabolism may differ from that in the neonate, and that pancreatic islet cell responsiveness rapidly changes after delivery.

Factors affecting the response to insulin in the normal subhuman pregnant primate.

The concentrations of plasma glucose, free fatty acids, insulin, growth hormone, and placental prolactin in subhuman primate fetal and maternal plasma were examined following intravascular administration of insulin and glucagon to the fetus and mother. The neonatal plasma responses to these same stimuli were also examined. Fetal plasma glucose concentrations were minimally altered by direct fetal insulin injections, whereas neonatal glucose levels declined with similar injections. In both instances, however, plasma free fatty acid levels declined following insulin. When the amount of insulin given the fetus was increased, fetal plasma glucose concentrations did decline. Combined intravascular insulin injections and infusions in the mother were associated with a disappearance of the initial maternal to fetal plasma glucose concentration gradient and a nearly parallel fall in both maternal and fetal plasma glucose levels. It was concluded that insulin was biologically active in the fetus. Obtunded fetal plasma glucose responses to direct fetal insulin administration may be a function of placental transfer of glucose from the maternal pool. Maternal plasma placental prolactin and fetal plasma growth hormone levels were unchanged in the presence of sustained maternal and fetal hypoglycemia. However, neonatal plasma growht hormone levels did increase in response to hypoglycemia. The observed bidirectional placental barrier to transfer of radioisotopically labeled growth hormone indicated that fetal plasma growth hormone was solely of fetal origin. These data suggested further that a change in the growth hormone-releasing mechanism may occur from fetal to neonatal life. Direct maternal intravascular glucagon administration led to augmentation in both maternal and fetal plasma insulin and glucose levels. Direct fetal glucagon injections enhanced both maternal and fetal plasma insulin levels. These simultaneous changes in both plasma pools were consistent with the demonstration of a bidirectional placental transfer of radioisotopically labeled glucagon. The role of endogenously produced glucagon in these studies remains to be clarified.

Kinetic relations of the Na-amino acid interaction at the mucosal border of intestine.

The relation between unidirectional influxes of Na and amino acids across the mucosal border of rabbit ileum was studied under a variety of conditions. At constant Na concentration in the mucosal bathing solution, amino acid influx followed Michaelis-Menten kinetics permitting determination of maximal influx and the apparent Michaelis constant, K(t). Reduction in Na concentration, using choline as substitute cation, caused an increase in K(t) for alanine but had no effect on maximal alanine influx. The reciprocal of K(t) was a linear function of Na concentration. Similar results were obtained for valine and leucine and these amino acids competitively inhibited alanine influx both in the presence and in the absence of Na. These results lead to a model for the transport system which involves combination of Na and amino acid with a single carrier or site leading to penetration of both solutes. The model predicts that alanine should cause an increase in Na influx and the ratio of this extra Na flux to alanine flux should vary with Na concentration. The observed relation agreed closely with predicted values for Na concentrations from 5 to 140 mM. These results support the hypothesis that interactions between Na and amino acid transport depend in part on a common entry mechanism at the mucosal border of the intestine.

Alanine and sodium fluxes across mucosal border of rabbit ileum.

Unidirectional influxes of L-alanine and Na from the mucosal solution into the epithelium of in vitro rabbit ileum have been determined. In the presence of 140 mM Na, alanine influx is approximately 2.2 micromoles/hr cm(2), but is inhibited if the NaCl in the mucosal solution is replaced by choline Cl, Tris-Cl, mannitol, LiCl, or KCl. Although alanine influx is strongly dependent upon Na in the mucosal solution, it is uninfluenced by marked reduction of intracellular Na pools. In addition, alanine influx is unaffected by intracellular alanine concentration. Na influx is markedly inhibited by the presence of Li. Evidence is presented that Na transport across the mucosal border cannot be attributed to simple diffusion even though the net flux across this surface is in the direction of the electrochemical potential difference.

Effect of inhibitors on alanine transport in isolated rabbit ileum.

The effects of metabolic inhibitors and ouabain on alanine transport across rabbit ileum, in vitro, have been investigated. Net transport of alanine and Na across short-circuited segments of ileum is virtually abolished by cyanide, 2,4-dinitrophenol, iodoacetate, and ouabain. However, these inhibitors do not markedly depress alanine influx from the mucosal solution, across the brush border, into the intestinal epithelium, and they do not significantly affect the Na dependence of this entry process. The results of this investigation indicate that: (a) the Na dependence of alanine influx does not reflect a mechanism in which the sole function of Na is to link metabolic energy directly to the influx process; and (b) the inhibition of net alanine transport across intestine is, in part, the result of an increased rate coefficient for alanine efflux out of the cell across the brush border. Although these findings do not exclude a direct link between metabolic energy and alanine efflux, the increased efflux may be the result of the increased intracellular Na concentration in the presence of these inhibitors. The results of these studies are qualitatively consistent with a model for alanine transport across the brush border which does not include a direct link to metabolic energy.

Hypothalamic-pituitary control of perinatal prolactin secretion in Macaca mulatta.

Sequential changes in maternal and fetal plasma and amniotic fluid concentrations of prolactin (PRL) and growth hormone (GH) were examined after these intravascular administration of thyrotropin releasing hormone (TRH) or L-dopa alone or combined directly to the near-term Rhesus fetus. The neonatal plasma responses to these same stimuli were also examined. Fetal and neonatal plasma PRL levels increased immediately after TRH injection and remained elevated from baseline levels (102-800%) throughout the 45 min sampling period. Maternal plasma PRL levels also increased markedly. Although amniotic fluid concentrations were more variable, the trend was an increase. After L-dopa injection, fetal and neonatal plasma PRL values declined 26-62% from baseline levels. Maternal plasma PRL concentrations also declined 30-50%, but amniotic fluid PRL concentrations progressively increased. When L-dopa and TRH were administered together, fetal plasma PRL levels declined 14-40% from initial levels, but maternal plasma PRL levels did not change in a consistent manner, and amniotic fluid PRL levels remained stable. There was no change from baseline fetal or neonatal plasma GH concentrations in these experiments. The plasma PRL responses of the primate conceptus to these stimuli are consistent with those found in the adult; the unresponsiveness of plasma GH is not. The direction and magnitude of changes in both maternal plasma and amniotic fluid PRL concentrations provide indirect evidence of placental transfer of TRH and L-dopa in some experiments, and require a biophysical explanation not apparent in others.

Fetal lung lecithin metabolism in the glucose-intolerant Rhesus monkey pregnancy.

Fetal lung lecithin metabolism was examined in rhesus monkey gestations complicated by glucose intolerance secondary to maternal streptozotocin (STZ) administration. Fetuses of STZ-treated mothers were delivered at 85% to 89% of term and were compared to two control groups of fetuses from normal pregnancies--one group age-matched to the STZ pregnancies, and the other composed of fetuses delivered in the final 10% of gestation. In the glucose-intolerant pregnancies, two measures of fetal lung lecithin biosynthesis--the amniotic fluid lecithin-to-sphingomyelin (L/S) ratio and the rate of 14C-choline incorporation into lecithin in fetal lung slices--were significantly greater than in age-matched normal gestations and were similar to results in late-gestation controls. However, lung lecithin concentrations in the glucose-intolerant group were comparable to the age-matched controls, and both were significantly less than in the late-gestation controls. Since the gestational age, mode of delivery, and fetal acid-base status were the same in the age-matched groups, we conclude that these changes in fetal lung lecithin metabolism are due to the effects of maternal glucose intolerance.

Acute grief and mourning: one obstetrician's experience.

Perinatal death is a fact of our workplace. Most losses are unexpected. The acute nature of the loss is associated with grief and mourning lasting for many months. The emotional impact on the family and the physician, both initially and during the bereavement period, is intense and potentially negative. The clinical interactions that occur during this time speak to the art of medicine and the privilege of being a physician.

Ketonuria in normal pregnancy.

Nine low-risk, clinically normal pregnant women tested their urine for ketone bodies at three- to four-day intervals throughout gestation. Eight of the women had acetoacetonuria present on two to 15 days each. This finding was not related to length of gestation or time of day. Ketonuria probably occurs sporadically in most normal pregnancies.

Magnesium sulfate, maternal hypothermia, and fetal bradycardia with loss of heart rate variability.

BACKGROUND: Fetal bradycardia and decreased heart rate variability can indicate a nonreassuring fetal status. However, there can be iatrogenic, physiologic, or pathologic causes. CASE: A patient in premature labor received toxic levels of magnesium sulfate for tocolysis. Elevated maternal serum magnesium levels correlated inversely with maternal temperature and both fetal heart rate and fetal heart rate variability. There was also a relative decrease of the maternal heart rate from baseline. When the magnesium levels returned to normal, these vital signs returned to normal. CONCLUSION: Magnesium sulfate therapy can result in maternal hypothermia and a decrease in fetal heart rate and heart rate variability. Maternal hypothermia might be the cause of fetal bradycardia. A direct action of magnesium on the fetal heart might be the cause of heart rate variability.

Amniotic fluid copper and zinc concentrations in human pregnancy.

Amniotic fluid concentrations of zinc and copper were measured in human pregnancy of 12 to 44 weeks' gestation. Although mean values for both metals are relatively flat throughout pregnancy, there appears to be a relative increase in copper levels between 26 and 33 weeks' gestation, and increasing levels of zinc after 34 weeks. Correlations with fetal age or fetal-maternal disease are not apparent in specimens from this heterogenous population.

Variations of biologic activity of low-dose prostaglandin E2 on cervical ripening.

The effect of low-dose prostaglandin E2 vaginal gel specially prepared from commercially available materials, on subsequent indicated oxytocin induction of labor, was investigated in a randomized, double-blind, placebo-controlled clinical trial. The stability of the gel after preparation was documented by radioimmunoassay in vitro. No differences between the treated and placebo groups were noted in subsequent modified Bishop scores, length of labor, use of analgesia or anesthesia, success of induction, mode of delivery, or perinatal outcome. Comparisons of this clinical trial with those previously reported are offered.

Maternal weight gain patterns and birth weight outcome in twin gestation.

OBJECTIVE: To evaluate the association between maternal weight gain patterns, based on pregravid body mass index (BMI) and birth weight outcome in twins, and to make specific recommendations for maternal weight gain during twin gestation. METHODS: One hundred eighty-nine twin pregnancies were reviewed retrospectively. Weekly rates of maternal weight gain before 20 weeks, from 20 weeks to delivery, and for total gestation were calculated. Thresholds of weekly maternal weight gain were determined for underweight and normal-weight women. RESULTS: In underweight women, a higher weekly rate of gain before 20 weeks was associated with the birth of both twins weighing at least 2500 g (1.13 versus 0.70 lb/week, P = .017), when compared with mothers of at least one twin weighing less than 2500 g. A higher rate of weight gain from 20 weeks to delivery was associated with the delivery of twins weighing at least 2500 g in both underweight (1.92 versus 1.29 lb/week, P = .031) and normal weight (1.63 versus 1.29 lb/week, P = .046) women. No significant differences in weight gain patterns were found between overweight women delivering twins weighing less than 2500 g or at least 2500 g. A weekly rate of gain from 20 weeks' gestation to delivery of at least 1.75 lb/week in underweight women and at least 1.50 lb/week in normal-weight women was associated with the birth of both twins weighing at least 2500 g. After controlling for other potential determinants of birth weight, the threshold of 1.75 lb/week in underweight women showed a trend toward significance as an independent predictor of both twins weighing at least 2500 g (P = .06). CONCLUSION: Certain maternal weight gain patterns during twin pregnancy are associated with the birth of each twin weighing at least 2500 g. As with singletons, recommendations for maternal weight gain during twin pregnancy can be based on pregravid BMI.

Herpes gestationis. An update.

Advances in the immunopathology of blistering diseases now provide increased accuracy in the diagnosis of herpes gestationis in pregnancy. Guidelines are presented in this review to determine the presence of the disease. Exogenous corticosteroids will effectively alleviate symptoms and prevent formation of new lesions.

Complementary and alternative medicine. Part I: Clinical studies in obstetrics.

Studies in which complementary and alternative medicine (CAM) interventions were used in the care of obstetric patients were identified by searching The National Library of Medicine's electronic database. This paper is a selected review of both randomized and nonrandomized clinical trials. There are a number of CAM therapeutic practices that may have potential benefit for patients. Additional clinical research with appropriate scientific methodology is warranted to determine the merit and value of integrating some CAM modalities into conventional medical obstetric care.

Complementary and alternative medicine. Part II: Clinical studies in gynecology.

This review describes randomized and nonrandomized clinical studies in which complementary and alternative interventions were used to treat gynecologic illness and disease. The articles were identified through the use of The National Library of Medicine's electronic database. Statistically significant clinical benefit could not be identified for most practices. However, additional scientific investigation with appropriate research methods would help clarify a number of provocative insights and suggestions of potential clinical effectiveness.

Cervimetry: a review of methods for measuring cervical dilatation during labor.

Several different methods of measuring cervical dilatation have been described. In this article, we review those methods and examine findings from studies using them. Although many instruments have been developed to measure cervical dilatation during labor and their use as a research tool has been established, no device has yet been successfully used for clinical obstetrics. The ideal device has not yet been developed; however, because repeated digital cervical examinations are time consuming for the clinician, are poorly reproducible, and are uncomfortable for the patient, continued efforts to develop a cervimeter suitable for clinical use is a worthwhile endeavor.

Carbohydrate metabolism studies after one year of using an oral contraceptive containing gestodene and ethinyl estradiol.

UNLABELLED: The objective of the study is to evaluate the effects of a gestodene-containing oral contraceptive on carbohydrate metabolism. The design of the study is prospective. The setting is at University of South Florida Outpatient Unit. The patients consisted of twenty-three normal women desiring contraception. Serum glucose and insulin levels were measured during a three-hour glucose tolerance test at control time and after one year of drug use. RESULTS: All of the one-year glucose values were significantly elevated as well as the fasting and three-hour insulin values. These changes were mostly confined to women over 26 years of age and not in the younger 18 to 23 year olds. An oral contraceptive containing 75 micrograms of gestodene and 30 micrograms of ethinylestradiol can significantly alter carbohydrate metabolism in older women.

PIP: In Tampa over a 1-year period, health workers followed 23 normal 18-34 year old women, who came to the University of South Florida Outpatient Unit for an oral contraceptive (OC) prescription, to examine the carbohydrate metabolic effects of an OC containing 75 mcg gestodene and 30 mcg ethinyl estradiol. No one conceived. All the glucose values increased significantly over the 12-month study period (p = .002). The significant increase was restricted to only women in the 26-34 year old group at fasting and 0.5, 1, and 2 hours (p .05), however. The fasting and 3 hour insulin values were significantly elevated (p .001 and .002, respectively). The elevated insulin values were largely confined to the 26-34 year old group (at 0.5, 1, and 3 hours), but they were also elevated at fasting and 3 hours in the 18-23 year old group. Even though the values of carbohydrate metabolic parameters were significantly elevated, the values were in the normal physiologic range. Since gestodene has little estrogen binding capacity and estrogen improves carbohydrate metabolism, this combined OC tends to have adverse effects on carbohydrate metabolism, particularly in older women. Longer and larger duration studies are needed to examine whether these effects increase or reverse with time.