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Biomedical subjects

R M Pitkin

Publications and source records attributed to R M Pitkin.

At least 73 records · Page 4Linked to original sources

Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura.

The optimal method of infant delivery for gravida women with immunologic thrombocytopenic purpura (ITP) is controversial because of the unpredictability of the fetus developing thrombocytopenia and the uncertainty of the relation between vaginal birth and intracranial hemorrhage in thrombocytopenic infants. We have employed the technique of platelet counts on fetal scalp blood obtained prior to or early in the course of labor in 12 patients with ITP. A count of 50,000/cu mm, selected on the basis of literature review and retrospective analysis of our own experience, was used to define fetal thrombocytopenia. Three thrombocytopenic fetuses were delivered by cesarean section. Trial labor was permitted in the other nine cases in which fetal scalp platelet count exceeded 50,000/cu mm. The outcome was good in all instances. If cesarean section is to be employed in ITP patients to obviate the potential danger of fetal hemorrhage with vaginal delivery, the use of platelet counts of fetal scalp blood seems to provide the most rational basis for management at present.

Blood Platelets↗

Altered maternal calcium homeostasis in diabetic pregnancy.

Twenty-one diabetic gravidas were studied with serial measurements of serum concentrations of total and ionized calcium, magnesium, phosphorus, albumin, and parathyroid hormone and plasma levels of calcitonin. Pregnant diabetics had significantly lower serum magnesium concentrations throughout pregnancy than did nondiabetics. They also had significantly lower parathyroid hormone levels after midpregnancy, because the progressive increase in parathyroid hormone concentration observed in control subjects did not occur in diabetics. There was no significant difference between pregnant diabetics and nondiabetics in serum concentrations of total calcium, ionized calcium, phosphorus, or albumin or in plasma levels of calcitonin.

Calcitonin↗

Maternal and fetal parathyroid hormone responsiveness in pregnant primates.

Maternal and fetal parathyroidd hormone (PTH) responsiveness to hypocalcemia induced by EDTA infusion (50 mg/kg over 2 h) was studied in rhesus monkeys in late pregnancy. Although baseline serum total calcium (Ca) levels in the fetus exceeded those in the mother (4.83 +/- 0.13 vs. 4.28 +/- 0.15 meq/liter; P < 0.001), PTH values were not significantly different (5.62 +/- 0.37 vs. 6.18 +/- 0.33 muleq/ml; P > 0.05). EDTA infusion directly to five fetuses produced significant hypocalcemia (maximal decline averaging 19 +/- 2%) and PTH response (maximal increase averaging 46 +/- 5%). In contrast, in four control studies involving fetal saline infusion, there were no significant changes in fetal Ca or PTH levels. Four maternal control infusions produced no significant changes in either Ca or PTH levels. A comparison of maternal and fetal PTH responses indicated considerable similarity, although fetal PTH levels tended to return to baseline somewhat more gradually after cessation of the hypocalcemic stimulus than did maternal levels. These studies indicate that fetal PTH secretion, both baseline and in response to hypocalcemia, is quantitatively similar to that of the adult, and thus, the fetal parathyroid does not appear to be suppressed by the relative hypercalcemia of late fetal life.

Animals↗

Fetal calcitropic hormones and neonatal calcium homeostasis.

Ionic calcium (Ca2+), total calcium, magnesium, phosphorus, albumin, immunoreactive parathyroid hormone (PTH), and immunoreactive calcitonin (CT) were measured in maternal and cord blood at term delivery of 96 women near term with predominantly normal pregnancies. Calcium, magnesium, phosphorus, and albumin were measured in the infants at 24 hours of age. Umbilical Ca2+ levels exceeded maternal values significantly (2.82 +/- 0.15 vs 2.23 +/- 0.09 mEq/liter, P < .001), as did calcium, magnesium, phosphorus, and albumin levels. The relative fetal hypercalcemia was associated with significantly higher CT levels in fetus than in mother (248 +/- 68 vs 209 +/- 54 pg/ml, P < .05) but PTH concentrations did not differ significantly between the two circulations. Within the fetal circulation, levels of each component did not differ except for PTH which was in higher concentration in venous than in arterial blood (5.50 +/- 1.81 vs 4.93 +/- 1.71 microliter-eq/ml, P < .05). Stepwise multiple regression analysis, utilizing neonatal Ca level as the dependent variable, identified one clinical feature (duration of pregnancy) and six laboratory data as significant independent variables, account in sum for 35% of the variation in neonatal calcium level. The significant laboratory variables, in order of entry into the model, were maternal PTH, umbilical venous PTH, maternal phosphorus, umbilical venous magnesium, neonatal albumin, and neonatal magnesium. These results indicate that the normal fetus responds to hypercalcemia in late intrauterine life by increasing CT secretion but not by suppressing PTH output. The umbilical PTH level is one of several factors at birth which correlates significantly with calcium concentration at 24 hours of age.

Calcitonin↗

Effects of magnesium sulfate treatment on perinatal calcium metabolism. II. Neonatal responses.

To evaluate the effects of maternal magnesium sulfate treatment on neonatal magnesium and calcium homeostasis, the authors studied 23 term neonates whose mothers had received intravenous magnesium sulfate for pre-eclampsia and compared them with 14 control neonates. Total and ionized calcium, magnesium, phosphorus, and albumin were measured in maternal and umbilical blood; total calcium, magnesium, phosphorus, and albumin were measured serially in the newborn infants. Magnesium levels were higher in treated than in control infants in umbilical venous and arterial blood samples and in the neonatal blood samples 2, 12, and 24 hours after delivery. However, at 48 hours and beyond there was no difference in serum magnesium levels between treated infants and controls. Calcium levels were not significantly different in treated versus control subjects in umbilical blood or in any neonatal samples. There was no correlation between the maternal magnesium concentration at delivery and the levels of calcium in umbilical or neonatal blood. These data indicate that maternal magnesium sulfate therapy does not cause neonatal hypocalcemia and that the induced neonatal hypermagnesemia is resolved within the first 48 hours of life.

Calcium↗

Platelet and leukocyte counts in pregnancy.

Platelets and leukocytes in venous blood were counted with automated methodology in 23 women studied longitudinally throughout pregnancy and at six weeks after delivery. The average platelet count declined monotonically in a manner consistent with the gestational increase in blood volume. Total leukocyte count rose early in gestation and remained elevated, with neutrophils accounting for the changes. Absolute neutrophil counts during gestation were nearly twice those of the same women postpartum (5.76 vs 3.13/cu mm x 10(-3).) The monocyte count also tended to increase, whereas lymphocytes, eosinophils, and basophils declined in number.

Basophils↗

Effects of magnesium sulfate treatment on perinatal calcium metabolism. I. Maternal and fetal responses.

Serial maternal and cord blood determinations of the ions and hormones involved in calcium homeostasis were made in pre-eclamptic women treated with intravenous magnesium sulfate. A 4 gm loading dose followed by 1 to 2 gm/hr caused maternal serum magnesium concentrations to rise 150%, to levels of 3.3 to 4.5 mEq/L, and ionized calcium levels to fall 16%, to 1.89 mEq/L. The hypocalcemia etly altering calcitonin. Changes in total calcium paralleled those of ionized calcium; phosphorus levels were not affected by magnesium infusion. At the time of delivery the offspring of these women were hypermagnesemic and relatively hypocalcemic, although less so than their mothers. Fetal ionized calcium levels, although lower with magnesium treatment than in control subjects, were within the lower limits of the normal range, which perhaps explains why the fetus did not respond with increased PTH or decreased calcitonin output. These results indicate that the principal maternal response to magnesium-induced hypocalcemia involves increased parathyroid hormone secretion which tends to preserve maternal calcium homeostasis, while the fetus is partially protected from hypermagnesemia and hypocalcemia by the placenta.

Adult↗

Calcium metabolism in normal pregnancy: a longitudinal study.

Total and ionic calcium, magnesium, phosphorus, albumin, and immunoreactive parathyroid hormone (iPTH) and calcitonin (iCT) were measured in serum or plasma from 30 women throughout pregnancy (beginning before 12 weeks' gestation) and the puerperium. Total calcium levels declined during gestation, paralleling a progressive fall in albumin concentration, whereas ionic calcium values declined only very slightly. Although iPTH levels in early pregnancy were lower than postpartum values (suggesting that iPTH may decline initially following conception), the major portion of gestation was characterized by progressively increasing concentrations which at term averaged 53% above early pregnancy levels and 33% above puerperal values. Thus, the principal adjustment during pregnancy is "physiologic hyperparathyroidism" which acts to preserve maternal homeostasis by maintaining the concentration of calcium ions in extracellular fluid in the presence of expanding fluid volume, increased renal function, and placental transfer. iCT levels were not affected consistently by pregnancy and exhibited highly variable patterns; half of the subjects demonstrated an increase during the first and second trimesters and then a decline in the third trimester and the remaining half was equally divided between those with no change and those with progressively falling levels.

Adult↗

Maternal-perinatal calcium relationships.

Serum concentrations of total and ionic calcium, magnesium, phosphorus, and albumin were measureed in maternal and cord blood of 115 near-term deliveries. The same measurements (except for ionic calcium) were made in blood obtained from corresponding newborns at 24 hours of age. Cord levels of all components exceeded maternal values, and maternal and cord levels correlated significantly with each other. In the case of calcium, the cord-maternal difference involved both ionic and protein-bound forms. Significant umbilical arterio-venous differences were found only in the case of total calcium, and this difference reflected variation in the protein-bound form only. During the first 24 hours postpartum, total calcium concentration fell (by an average of 0.75 mEq/liter), phosphorus levels rose (by an average of 0.63 mg/dl), and magnesium and albumin did not change significantly. Cord levels of all agents correlated significantly with corresponding neonatal values. In view of the significant positive relationships demonstrated between maternal and cord levels and between cord and neonatal levels, these results substantiate the importance of the maternal serum ionic calcium concentration in normal perinatal calcium homeostasis.

Calcium↗

Urinary urea-nitrogen ratio as an index of protein nutrition in diabetic pregnancy.

Urinary urea nitrogen-total nitrogen ratio (UN/TN) was measured at intervals throughout pregnancy in 12 normal women and in 10 with insulin-dependent diabetes mellitus and the results were related to protein ingestion estimated by dietary history. While urea and nitrogen correlated significantly with each other in both normal and diabetic subjects, the relationship between UN/TN and protein intake was quite different in the two groups. Nondiabetic patients exhibited generally close correlation between UN/TN and protein intake with statistically significant correlation coefficients (r = 0.74-0.99) in 11 of 12 subjects. In none of the 10 diabetic patients, however, was significant correlation found. While the reliability of the index in diabetic patients tended to improve as hyperglycemia lessened, even under conditions considered clinically to indicate excellent metabolic control (mean plasma glucose less than or equal to 125 mg/dl), UN/TN still did not correlate significantly with protein intake. These observations suggest that the unstable carbohydrate metabolism characteristic of diabetes mellitus may be responsible for altered protein retention during pregnancy. From a clinical point of view, the utility of urinary urea studies as a simple and objective index of protein intake in the normal pregnant women does not apply in the diabetic patients.

Adult↗

Laminaria as an adjunct in induction of labor.

The safety and efficacy of laminaria tents as an adjunct to labor induction near term were examined in a prospective, controlled, and randomized study involving insertion of laminaria into the cervical canal the evening prior to planned induction. Six of 35 subjects in whom laminaria were used entered labor spontaneously and delivered overnight, compared with 1 of 39 controls. Of the remainder, the Bishop score increased an average of 3.7 points, a highly significant change, in the laminaria-treated group compared with no change in the controls. Labor, induced primarily by amniotomy with intravenous oxytocin then given to patients in whom regular contractions did not begin within 8 hours, was shorter with laminaria use than in controls, though the amniotomy-to-delivery interval did not differ significantly. However, comparison of the subgroup with cervices relatively unfavorable for induction, indicated by an initial Bishop score of 5 or less, showed both length of labor and amniotomy-to-delivery interval to be significantly shorter (each by an average of 3 hours) in the laminaria-treated group compared with controls. Complications, including febrile morbidity, did not differ. We conclude that laminaria tents are both effective and safe as an adjunct to labor induction, acting by accelerating the preparatory changes in the cervix which normally occur in late pregnancy.

Dilatation↗

Calcium-regulating hormones during the menstrual cycle.

Calcium metabolism during the menstrual cycle was studied in seven women from whom fasting blood samples were drawn daily or every other day throughout ovulatory cycles. Total calcium (Ca), ionic calcium (Ca++), magnesium (Mg), phosphorus (P), and immunoreactive parathyroid hormone (PTH) and calcitonin (CT) were measured. LH levels were used to date each cycle and progesterone levels were used to confirm ovulation. Plasma estradiol was measured in two of the subjects. In six subjects with cycle lengths of 27-31 days, PTH levels rose progressively through the follicular phase to a peak at or slightly before the LH surge, then fell progressively through the luteal phase; peak PTH levels were 30-35% above early follicular and late luteal values. CT levels were also highest at midcycle, but the CT pattern was somewhat more variable than that of PTH. Ca++ tended to fall until 3-4 days before ovulation and then to increase, while Ca, Mg, and P exhibited no particular pattern. One subject experienced a prolonged (44 day) ovulatory cycle characterized by three distinct PTH peaks, each of which coincided with elevations in plasma estradiol level. These results represent the first report of menstrual cyclicity in calcium-regulating hormones. The timing suggest an estrogen effect and it is hypothesized that estrogen inhibits PTH-induced bone resorption, lowering serum Ca++, which in turn provokes a compensatory PTH output. With the decline of the preovulatory estrogen peak, Ca++ levels rise and PTH secretion falls. Alternatively, it is possible that the primary action may be an estrogen-induced rise in CT release, causing hypocalcemia and consequent PTH output. Cyclic changes in PRL release or vitamin D metabolism might also be involved.

Calcitonin↗

Radioimmunoassay of calcitonin in the plasma of rhesus monkey and man.

We describe a radioimmunoassay for rhesus monkey and human immunoreactive calcitonin, in which a selected goat anti-human calcitonin antiserum, 131I-labeled synthetic human calcitonin tracer, and purified synthetic human calcitonin standards were used. The mean basal concentration of calcitonin in normal monkey plasma (254 microgram/liter) was not significantly different from that in normal human plasma (217 microgram/liter). The data indicate that the method is sensitive (lower limit of detection, 5 ng/liter), specific, accurate, and reproducible (coefficient of variation, 1-11% over a wide range of concentrations). Monkey calcitonin response to changes in plasma calcium concentration is similar to that in man, with significant correlation between calcium and calcitonin concentrations. Use of this radioimmunoassay for monkey and human calcitonin allows the monkey to be used in further studies of factors regulating secretion, function, and metabolism of calcitonin under various experimental conditions that would not be feasible in man.

Animals↗

Serum calcium concentrations in human pregnancy.

Total and ionic calcium concentrations were measured in maternal serum from nonpregnant (N=30), pregnant (N=137), and early puerperal (N=17) women. In this cross-sectional study, total calcium levels (measured by atomic absorption spectrophotometry) exhibited the previously described pattern of a decline beginning in the first trimester and continuing until approximately 32 weeks, with a slight terminal rise from thence to term. Mean (+/-SD) values for the three trimesters were 4.80 (+/- 0.13), 4.56 (+/- 0.14), and 4.46 (+/-0.16) mEq. per liter, respectively, with all differences statistically significant. Ionic calcium levels (measured by calcium flow-through electrode) declined to a lesser (though still statistically significant) degree; mean (+/- S.D.) values for the three trimesters were 2.33 (+/-0.07), 2.28 (+/-0.08), and 2.24 (+/-0.06) mEq. per liter, respectively. Because of the differential rates of fall, the proportion of total calcium represented by the ionic component increased progressively during gestation. The results indicate that the major portion of the characteristic decline in maternal serum total calcium concentration with pregnancy reflects changes in the nonionized (albumin-bound) fraction while the ionic portion declines only slightly. The concentration of calcium ions in serum is maintained within a very narrow physiologic range throughout gestation.

Calcium↗

Nutritional influences during pregnancy.

Maternal nutrition represents one of the important influences on the course and outcome of pregnancy and attention to nutritional factors (i.e., assessment of nutritional status, dietary advice, and follow-up evaluation) properly constitute an essential component of prenatal care. Nearly all nutrients are required in increased amounts during gestation but the magnitude of the increase varies from nutrient to nutrient. Caloric needs increase by 300 kcal per day, representing an addition of 15 per cent, and should be sufficient to support a weight gain averaging 350 to 400 gm per week during the last two trimesters. Total protein intake during pregnancy should be 1.3 gm per kg for the mature woman and somewhat higher for the adolescent. Gestational needs for iron cannot be met by diet and supplementation (in the form of simple ferrous salts, 30 to 60 mg daily) should be provided. Folate requirements are doubled during pregnancy and, while these can be met by diet, supplementation may be considered as an option. Provision of the gestational calcium allowance from food sources is readily possible if (and only if) daily products are consumed. The generally increased need for other nutrients can be provided readily by the properly selected diet. Thus, with respect to supplements, iron and perhaps folate should be advised routinely while other vitamin-mineral supplements are probably neither helpful nor harmful. Prescription of vitamin-mineral supplements cannot be expected to compensate for poor dietary habits. Dietary restriction of nutrients in general, and energy and sodium in particular, has the potential for impairing the maternal capacity to make the required physiologic adjustments of pregnancy and interfering with fetal development. Restriction of any nutrient to levels below the guidelines provided by the Recommended Dietary Allowances is rarely if ever advisable.

Ascorbic Acid↗