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Biomedical subjects

R M Pitkin

Publications and source records attributed to R M Pitkin.

At least 91 records · Page 5Linked to original sources

Placental transfer of glucose-amino acid complexes present in parenteral solutions.

Intravenous infusion of glucose-amino acid complexes, formed during heat sterilization of mixtures of glucose and amino acids or protein hydrolysates, has been associated with mild dehydration in infants, and with excessive trace metal ion excretion in both infants and adults. When parenteral solutions containing these glucose-amino acid complexes were infused into pregnant rhesus monkeys, the compounds accumlated in the maternal plasma and were transported to the fetal circulation. Although all of the compounds studied crossed the placenta, fetal levels were consistently lower than maternal levels. Amniotic fluid concentrations of these compounds increased progressively with the length of maternal infusion, presumably through fetal urination into the amniotic sac. In animals infused with solutions not heat sterilized, levels of these compounds could not be detected in maternal plasma and urine, fetal plasma and urine, or in amniotic fluid. In view of possible toxicity of the glucose-amino acid complexes, parenteral solutions containing these compounds should probably be avoided in the intravenous nutrition of the pregnant woman.

Amino Acids↗

Radioimmunoassay of parathyroid hormone (parathyrin) in monkey and man.

A radioimmunoassay for rhesus monkey and human immunoreactive parathyrin was developed in which a selected anti-bovine parathyrin antiserum, radioiodinated purified bovine parathyrin tracer, and human parathyroid tissue-culture media standards were used. The resulting data indicate that (a) the method is sensitive, specific, accurate and reproducible; (b) it is valid for both the rhesus monkey and the human; (c) the serum immunoreactive parathyrin concentration of the monkey is essentially the same as that in man; (d) monkey immunoreactive parathyrin responds to changes in serum calcium concentration similarly to that in man; and (e) the rhesus monkey is therefore a suitable species in which to study parathyroid physiology, from which conclusions can be applied to the human.

Adult↗

Drugs and the fetus.

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Drug-Related Side Effects and Adverse Reactions↗

Vaginal hysterectomy in obese women.

The influenced of obesity in vaginal hysterectomy was examined by comparing the characteristics and outcome in 108 patients who weighed 200 pounds or more with matched controls weighing less than 200 pounds. Obese and nonobese subjects were similar in age and surgical indications, though overweight patients, who averaged nearly 60% above standard weight for height and age, were more likely to have hypertension and diabetes mellitus. Both operating time and operative blood loss were greater in obese patients, presumably because of more frequent employment of vaginal repair in this group. However, obese and nonobese patients did not differ significantly with respect to mortality (none in either group), postoperative febrile morbidity (62 and 56%, respectively), or postoperative hospitalization in excess of 12 days (19 and 16%, respectively). Thus, obesity does not seem to impose additional risks in vaginal hysterectomy, in contrast to abdominal hysterectomy in which the increased morbidity relates to wound infection.

Female↗

Mercury in human maternal and cord blood, placenta, and milk.

Total mercury concentration was measured by atomic absorption spectrophotometry in 100 maternal-umbilical cord blood pairs, 39 placentae, and 32 breast milk samples, all from patients at the University of Iowa Hospitals. The mean maternal and cord blood levels were 1.01 and 1.24 parts per billion (ppb), respectively. Though the difference between maternal and cord values was not statistically significant, the two were significantly correlated with each other, and maternal blood level increased significantly with maternal age. Mean placental and milk concentrations were 2.28 and 0.93 ppb, respectively. The mercury levels in this study were lower than those reported from elsewhere, probably reflecting a combination of methodological refinement and relatively low mercury exposure in a rural population whose diet is low in fish consumption. These low levels suggest that the risk of perinatal mercury damage is small in such a population.

Age Factors↗

Abdominal hysterectomy in obese women.

During a 25 year period in a university hospital gynecology service, 300 obese women, weighing 200 pounds or more, underwent abdominal total hysterectomy. In comparison with nonobese controls, the overweight patients were more likely to have carcinoma of the endometrium, hypertension and diabetes mellitus. Postoperatively, the most striking difference between the obese and nonobese groups was in the incidence of wound complications, with no significant difference in the occurrence of other disorders. The incidence of wound complications was 29 per cent with obesity, seven times that in patients of normal weight, and all types of wound disorders, except evisceration, occurred more frequently in obese patients. Among identifiable factors potentially responsible for wound infection were an increased incidence of diabetes, longer operating time and greater blood loss in overweight patients. The increased incidence of wound infection was responsible for greater febrile morbidity and the more frequent need for prolonged hospitalization. The mortality rate was 1 per cent in the obese group and zero per cent in the control group, a statistically insignificant difference. Since abdominal hysterectomy in obese women is associated with increased risk of morbidity, although not necessarily of mortality, obesity per se should rarely, if ever, contraindicate necessary surgical therapy. In situations in which surgical treatment is more elective, its complications should be borne in mind.

Adult↗

Acute polyhydramnios recurrent in successive pregnancies. Management with multiple amniocenteses.

A patient with acute polyhydramnios in two successive pregnancies is described. In both this case and the only previously reported similar one, management by frequent transabdominal removal of relatively small amniotic fluid volumes was associated with prolongation of pregnancy and a living infant, suggesting that multiple amniocenteses can improve the otherwise hopeless prognosis associated with acute polyhydramnois.

Acute Disease↗

Fetal ingestion and metabolism of amniotic fluid protein.

Fetal swallowing, digestion, and utilization of amniotic fluid protein were studied in near-term rhesus monkeys in which 35S-protein, synthesized biologically from 35S-methionine, was injected into the amniotic sac. The half-time of the injected protein in amniotic fluid was 1.1 days, a figure consistent with findings of others that fetal swallowing represents the principal mechanism of clearance of amniotic fluid protein. On delivery at timed intervals up to 7 days after injection, evidence of progressive proteolysis along the fetal alimentary tract was found. The amnio acids liberated from protein hydrolysis were apparently utilized in protein synthesis in the gut wall as well as absorbed in fetal plasma, where they equilibrated rapidly with maternal plasma and amniotic fluid. Maximal amino acid radioactivity in these three compartments occurred 3 days after injection and was followed 1 day later by maximal fetal plasma protein radioactivity. Incorporation into protein of amino acids absorbed after hydrolysis was found in fetal lung, liver, skeletal muscle, and brain. The results indicate that ingested amniotic fluid protein undergoes proteolysis in the fetal alimentary tract and the amino acids thus made available are utilized in protein synthesis by the developing fetus. While this mechanism can provide only a relatively minor proportion (estimated at 10 to 15 per cent) of fetal nitrogen requirements, it may represent an important aspect physiologically by preparing the fetus for extrauterine nutrition. Moreover, the use of intra-amniotic nutrition as a mode of fetal therapy, while speculative at present, offers possibilities for the furture.

Amino Acids↗

Placental transfer of glutamate and its metabolites in the primate.

When radioactive glutamate was infused into pregnant rhesus monkeys, 69 to 88 per cent of radioactivity in the maternal plasma remained in association with glutamate while 10 to 22 per cent was converted to glucose. In the fetal plasma, glucose and lactate accounted for more than 80 per cent of radioactivity, with less than 2 per cent of the label found in glutamate. Maternal glutamate infusions resulting in a ten- to twenty-fold increase in maternal plasma glutamate levels (60 to 100 mumoles per 100 ml.) had no effect upon fetal glutamate levels. Infusions producing maternal glutamate levels 70 times normal (280 mumoles per 100 ml.) did result in some transfer of glutamate to the fetal circulation. Labeled glutamate administered to the fetus at 1.5 to 2.4 Gm. per kilogram of fetal weight did not result in glutamate transfer to the maternal circulation. Infusion of glutamate to the fetus at 5 Gm. per kilogram of fetal weight increased fetal plasma glutamate levels to 2, 000 mumoles per 100 ml. and resulted in some transfer of glutamate to maternal circulation. Glutamate metabolites (lactate and glucose) were readily transferred across the placenta in either direction. These studies indicate that the primate placenta is virtually impermeable to glutamate unless extreme elevations of plasma glutamate are induced.

Amino Acids↗

Calcium metabolism in pregnancy: a review.

Calcium metabolism in pregnancy is a complex process involving calcium, phosphorus, vitamin D, parathyroid hormone (PTH), and calcitonin (CT). Calcium absorption is enhanced in pregnancy, and increased storage in the maternal skeleton probably occurs as well. Adequate amounts are provided by the current Recommended Dietary Allowance of 1,200 mg. daily which can be met readily by natural foods, specifically milk. If supplemental calcium is given, a nonphosphate salt is probably advisable, since some evidence suggests that excessive phosphate intake may be related to leg cramps in pregnancy. Vitamin D is necessary for optimal calcium utilization in pregnancy, although the possibility of fetal toxicity with overdosage has been suggested. From a review of available information with respect to maternal-perinatal calcium interrelationships, I propose the following hypothesis: While total maternal serum calcium declines during pregnancy because of the physiologic hypoalbuminemia, the level of ionic calcium remains constant, in part, at least, because of increasing maternal PTH output. The placenta plays a primary role in fetal calcium metabolism by transporting calcium ions from the mother to the fetus against a concentration gradient. Relatively high fetal ionic calcium levels cause suppression of PTH and stimulation of CT in the fetus, facilitating growth of the fetal skeleton. With sudden loss of the placental source of calcium at birth, the newborn infant becomes functionally hypoparathyroid and/or hypercalcitonemic, and the serum calcium level declines until 3 to 4 days of life when PTH rises and CT falls with a resultant slight rise in calcium.

Animals↗

Calcitonin effects in primate pregnancy.

The acute effects of calcitonin (CT), a hypocalcemic hormone to act by inhibiting bone resorption, were studied in rhesus monkeys in late pregnancy. Salmon CT was injected intravenously into either mother or fetus and the concentration of total calcium and inorganic phosphorus in maternal plasma, fetal plasma, and amniotic fluid measured. Maternal CT administration produced a gradual fall in maternal plasma calcium levels and, to a lesser extent, in maternal plasma phosphorus levels. Both depth and duration of maternal hypocalcemia were related to dose. In addition, the dbree of hypocalcemic response was greater in pregnant than in nonpregnant animals at equivalent dosage levels. Hypocalcemia induced in the mother by CT injection was not reflected in fetal hypocalcemia. Fetal CT administration produced a triphasic response in fetal plasma calcium, consisting of a prompt initial drop followed by a return to or above the baselineand then a more gradual decline. Bth the initial and the secondary hypocalcemic responses in the fetus were dose-related in terms of depth and duration. These observations suggest that CT MAY BE AN IMPORTANT HORMONE IN BOTH MATERNAL AND FETAL PHYSIOLOGY.

Amniotic Fluid↗

Creatinine exchange between mother, fetus, and amniotic fluid.

Creatinine exchange between mother, fetus, and amniotic fluid was investigated in rhesus monkeys in late pregnancy in which a different radioactive-labeled form of creatinine was injected simultaneously into either of two of the three possible compartments. Creatinine specific activity was then determined for each isotope in each compartment over the ensuing 4-6 h. A rapid and extensive bidirectional exchange occurred between all three compartments. Maternal-fetal flux, while bidirectional, seemed to be predominately from mother to fetus. Approximately 35% of labeled creatinine originally injected into the fetus and 25% of labeled creatinine originally injected into the mother were present in the amniotic sac within 2 h. Creatinine pool size was calculated to be approximately 6 mg/kg in both mother and fetus. Comparison of experiments involving living had dead fetuses indicated that the route of creatinine transfer from mother to amniotic fluid was through the living fetus and directly across the chorioamnion in the dead fetus. In addition, the time required for 'mixing' of creatinine injected into the amniotic sac was longer with a dead than with a living fetus but its half-life averaged 4.5 h regardless of fetal status.

Amnion↗

Monosodium glutamate metabolism in the neonatal monkey.

Monosodium glutamate (MSG) administered by gastric tube to 10 infant monkeys at doses of 1-4 g/kg produced rapid increases in plasma glutamate (17- to 33-fold) and aspartate (50- to 90-fold) levels. The degree of elevation was proportional to the dose administered. Levels of other amino acids were unaffected. Two of the monkeys exhibited high fasting glutamate levels and abnormal glutamate tolerance curves. Despite this apparent decreased ability to metabolize glutamate, neither these animals nor any of the others for whom morphologic studies have been previously reported demonstrated neurotoxicity. Studies using 14-C-labeled glutamated indicated conversion of administered glutamate to two ninhydrin-negative compounds identified as glucose and lactate, as well as to asparate.

Amino Acids↗

Transplacental passage of methylmercury and its uptake by primate fetal tissues (38576).

Radioactive methylmercury given to rhesus monkeys in late pregnancy crossed the placenta slowly from mother to fetus. The maternal-fetal ratio in both plasma and erythrocytes was as low as 10:1 serveral hours after maternal administration. Transfer from fetus to mother was even slower with the concentration gradient remaining above 25:1. Organic mercury was generally distributed throughout fetal tissues in a similar manner regardless of the routine of administration. The placenta and blood-brain barrier each appear to represent partial impediments to acute transfer of organic mercury, probably because of extensive erythrocyte binding. While the hemochorial placenta, by virtue of its limited permeability to organic mercury, appears to afford the fetus some degree of protection of acute mercury poisoning the fact that mercury moves out of the fetel circulation even more slowly than into it probably accounts for the fetal hazard with chronic exposure.

Animals↗