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Biomedical subjects

W R Cohen

Publications and source records attributed to W R Cohen.

At least 19 recordsLinked to original sources

Growth hormone treatment after cesarean delivery in rats increases the strength of the uterine scar.

OBJECTIVE: We sought to determine whether postcesarean treatment of rats with growth hormone (GH) affected the strength of the uterine incision in the puerperium and in a subsequent pregnancy. STUDY DESIGN: Forty-eight near-term pregnant rats were delivered by cesarean section. Half received subcutaneous recombinant human GH (2.0 mg x kg(-1) x d(-1)) for 7 days; control animals received saline injections. Four weeks after delivery, the uterine bursting pressure was determined in 5 treated and 5 control animals. Eight rats in each group were used to study uterine hydroxyproline concentrations and the histologic characteristics of the scar. Twenty-two animals were rebred 30 to 40 days after their cesarean sections. After repeat cesarean delivery, on day 19, the bursting pressure and hydroxyproline concentrations of the previous hysterotomy scar were determined. RESULTS: The uterine horn bursting pressure in the GH-treated animals was significantly greater than that in the control animals both 28 days postpartum and near term in a subsequent pregnancy. The uterine hydroxyproline concentrations followed the same pattern. Histologic study of the scars showed they were thicker and had less cellularity in the treated animals than in the control animals. CONCLUSION: Postcesarean treatment with GH increased the bursting strength of rat uterine incisions. This effect was accompanied by a significant increase in collagen content and persisted through a subsequent pregnancy.

Animals↗

Control of fetal insulin secretion.

In this study, we investigated the way in which fetal insulin secretion is influenced by interrelated changes in blood glucose and sympathoadrenal activity. Experiments were conducted in late gestation sheep fetuses prepared with chronic peripheral and adrenal catheters. The fetus mounted a brisk insulin response to hyperglycemia but with only a minimal change in the glucose-to-insulin ratio, indicating a tight coupling between insulin secretion and plasma glucose. In well-oxygenated fetuses, alpha(2)-adrenergic blockade by idazoxan effected no change in fetal insulin concentration, indicating the absence of a resting sympathetic inhibitory tone for insulin secretion. With hypoxia, fetal norepinephrine (NE) and epinephrine secretion and plasma NE increased markedly; fetal insulin secretion decreased strikingly with the degree of change related to extant plasma glucose concentration. Idazoxan blocked this effect showing the hypoxic inhibition of insulin secretion to be mediated by a specific alpha(2)-adrenergic mechanism. alpha(2)-Blockade in the presence of sympathetic activation secondary to hypoxic stress also revealed the presence of a potent beta-adrenergic stimulatory effect for insulin secretion. However, based on an analysis of data at the completion of the study, this beta-stimulatory mechanism was seen to be absent in all six fetuses that had been subjected to a prior experimentally induced hypoxic stress but in only one of nine fetuses not subjected to this perturbation. We speculate that severe hypoxic stress in the fetus may, at least in the short term, have a residual effect in suppressing the beta-adrenergic stimulatory mechanism for insulin secretion.

Adrenergic alpha-Antagonists↗

Sex differences in the adrenal catecholamine response to hypoglycemia in rats.

We studied the influence of sex on the adrenal catecholamine response to acute insulin-induced hypoglycemia in Sprague-Dawley rats. Eight male and seven female adult rats were anesthetized with pentobarbital, and a microdialysis probe was placed in the left adrenal. Dialyzed epinephrine and norepinephrine levels were measured by high-performance liquid chromatography during a control period and for 1 hour after insulin administration. The blood glucose level was measured every 15 minutes. The same protocol was applied to 23 adult females at various stages of the estrus cycle. The pattern of blood glucose changes during insulin-induced hypoglycemia was similar in both sexes, but males exhibited a significantly greater increase in epinephrine than females (261% v 52%, P = .001) in the sex-comparison experiment. A similar trend was observed for norepinephrine (73% v 0%, P = .075). The adrenal response in females for both catecholamines was not significantly affected by the estrus cycle phase (P = .989 for epinephrine and P = .424 for norepinephrine). We conclude that sex influences the magnitude of the adrenal catecholamine counterregulatory response to hypoglycemia. Males had a significantly greater increase in epinephrine release than females exposed to the same pattern of hypoglycemia. Female responses to hypoglycemia were not influenced by estrus cyclicity.

Adrenal Glands↗

The adrenal secretion of catecholamines during systemic metabolic acidosis in fetal sheep.

This study was undertaken to determine whether or not metabolic acidemia per se stimulates catecholamine (CA) secretion from the adrenal medulla in fetal sheep. The potential confounding effect of low O2 content, occasioned by the right shift in the oxyhemoglobin dissociation curve with acidemia, was taken into account in experimental design. Hemodynamic values, blood gases, O2 content, lactate and glucose concentrations and adrenal CA secretion rates and plasma CA levels were studied in fetal sheep at baseline and during control (saline infusion) and acidemic (15 and 30% lactic acid infusion) periods. Experiments were conducted after recovery from preparative operations performed under general anesthesia. Arterial pH did not change with saline infusion. During 15 and 30% lactic acid infusions, pH fell to 7.23 and 7.09, respectively, as lactate concentrations increased 4.7 and 10 times. Arterial PCO2 increased from 50 to 58 torr during 30% lactic acid infusion. Fetal CA secretion and plasma concentrations did not change during saline, or 15 or 30% lactic acid infusions. Moreover, hemodynamic parameters did not indicate increased CA secretion. In conclusion, we found no evidence for stimulation of adrenal CA secretion by metabolic acidosis.

Acidosis↗

[Postpartum hemorrhage].

Postpartum hemorrhages are observed in 2 to 10% of all deliveries. They are severe in 1% of the pregnancies. However, they remain a major cause of maternal morbidity and mortality. Post-partum hemorrhages are generally separated in 2 categories. Acute hemorrhage occurs in the 24 hours following the delivery and is mainly caused by uterine atony, retained secondines, placenta accreta, birth canal trauma and uterine inversion. The delayed hemorrhage occurs after 1 day to 6 weeks after the delivery and is often related to uterine infection or abnormal involution of the placental bed. The management requires uterine massage and ocytocine or prostaglandins. Surgical or radiological selective ligation or embolization of the internal iliac arteries can be required. The hysterectomy is proposed in the most severe cases.

Acute Disease↗

Using and archiving the labor curves.

Optimal interpretation of the events of labor requires integration of information about cervical changes, fetal descent, uterine contractions, fetal position and attitude, as well as fetal heart rate monitoring and maternal condition. The use and understanding of labor curves is a vital part of this process. The complexity and diversity of labor data lend itself to computer storage and analysis.

Cervix Uteri↗

Hyperglycemia suppresses the adrenal medullary response to hypoxemia.

An in vivo microdialysis technique was used to study adrenal medullary function in 6 euglycemic and 6 hyperglycemic anesthetized Sprague-Dawley rats exposed to hypoxia. After stabilization of an adrenal dialysis probe, dialyzable adrenal epinephrine and norepinephrine were measured in response to 15 min of 7.8% oxygen breathing in both groups. In euglycemic rats, hypoxia increased epinephrine and norepinephrine by 650 and 320% above baseline, respectively. During hyperglycemia, (mean plasma glucose level 30.0 mM) epinephrine and norepinephrine rose only 119 and 104%, respectively. The catecholamine increase in the hyperglycemic rats was significantly attenuated in comparison to euglycemic controls (epinephrine, P = 0.0232; norepinephrine, P = 0.0079). These data demonstrate that acute hyperglycemia has the capacity to suppress the normal adrenal medullary response to hypoxemia.

Adrenal Medulla↗

Short labor: characteristics and outcome.

OBJECTIVE: To determine the characteristics and consequences of short labor. METHODS: Ninety-nine term pregnancies with singleton vertex presentation and labor lasting 3 hours or less were compared with controls with longer labor, matched to the index cases by maternal age, parity, and birth weight. RESULTS: Short labor occurred mostly in multiparas. Both the first and second stages of labor were found to be shortened in these cases. There was significantly more placental abruption, uterine tachysystole, and maternal cocaine use among short-labor cases. Major perineal lacerations, postpartum hemorrhage, birth trauma, and low Apgar scores were distributed approximately equally between cases and controls. A preponderance of the bad outcomes in the short labors occurred in the subgroup of those with rates of dilatation and descent that exceeded established 95th percentile limits. CONCLUSIONS: Labors of 3 hours or less in duration were strongly associated with placental abruption, but were otherwise not major contributors to maternal and fetal morbidity.

Abruptio Placentae↗

Phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase activity in rat uterus. Cyclic and steroid-induced changes.

PURPOSE: The activity of phenylethanolamine-N-methyl-transferase (PNMT) and catechol-O-methyl-transferase (COMT) was studied in uterine homogenates from adult female Wistar rats with normal cycles and that had been ovariectomized, adrenalectomized, and steroid-treated. RESULTS: Activities of the two enzymes changed significantly during the normal estrus cycle. Both peaked during metestrus, with COMT showing a secondary peak of activity at proestrus. Progesterone treatment significantly increased and estradiol decreased PNMT activity in comparison to untreated controls. Hydrocortisone administration had no effect on uterine PNMT activity. COMT activity was not affected significantly by any of the steroid treatments. CONCLUSION: The data confirm that uterine tissues possess the enzymatic machinery to synthesize epinephrine from norepinephrine, and suggest the activity of this pathway may be mediated by variations in the sex hormone environment of the uterus.

Animals↗

Pregnancy in women aged 40 and older.

Counseling patients about pregnancy at advanced maternal age is a difficult process. This is true both because our knowledge of the attendant risks is incomplete and still evolving, and because of the difficulties of assigning risks and addressing counterbalancing benefits for individual patients. There are a number of social and personal considerations involved in a decision to become a parent after the age of 40. Generally, older parents tend to be more mature, to be in stable and healthy marriages, and to have more financial and family resources to assist with the process of child rearing. Parents in their fifth decade, however, may complain of having less energy to devote to young children or may be at a stage in their careers in which they have less time for family participation than when they were younger. Also, grandparents, who can play a critical role in early childhood development, often have become too old to participate in that role or have died. All of these issues must be considered by parents contemplating late childbearing. A great deal has been written, much of it positive, even enthusiastic, about the quality of pregnancy and childbirth among older women. Nevertheless, much of the literature is difficult to interpret because of problems in controlling for confounding variables. In addition, much of the focus on so-called older women has been on those older than 35 years. In fact, the great majority of the medical literature concerning late childbearing relates to women between the ages of 35 and 40. The data that directly concern women in their fifth decade suggest that risks that began to accelerate after the age of 35 become considerably greater and increase more rapidly after the age of 40. Obviously, couples must decide what risks they are willing to accept and how these potential risks might be countervailed by the presumed advantages of parenthood relatively late in the reproductive years. There is convincing evidence to show that fecundity is decreased with advancing maternal age, and various forms of early pregnancy loss are increased. Thus, to delay childbearing results in a significant decrease in the likelihood of becoming pregnant or carrying a pregnancy to term. The possibility of genetic disorders is, as has been discussed previously, relatively easy to quantitate, and most age-related anomalies are amenable to prenatal diagnosis. It seems clear that women with underlying medical diseases, particularly hypertension and diabetes mellitus, contribute heavily to the excess morbidity and mortality associated with late childbearing.(ABSTRACT TRUNCATED AT 400 WORDS)

Female↗

Local heat and cold application after eastern cottonmouth moccasin (Agkistrodon piscivorus) envenomation in the rat: effect on tissue injury.

We studied the effect of local application of heat or cold on the development of tissue necrosis in envenomated rats. Anesthetized animals had 6 mg/kg venom from Agkistrodon piscivorus injected subcutaneously into the lateral aspect of a hind limb. Heat or cold was applied to the site of envenomation in the experimental groups for 4-6 hr, and the injected area was examined histologically after 24 hr. Neither local treatment, with or without the presence of systemic antivenin, significantly affected the severity of tissue necrosis induced by the venom in comparison to a control group left at ambient temperature.

Animals↗

The effect of hyperglycemia on acid-base and sympathoadrenal responses in the hypoxemic fetal monkey.

We investigated the influence of hyperglycemia on the fetal acid-base and sympathoadrenal responses to hypoxemia (maternal FIO2 9%) in rhesus monkey fetuses. In chronic preparations, we determined PO2, O2 content, PCO2, pH, lactate, glucose, insulin, catecholamines, heart rate, and arterial pressure. Combined hyperglycemia and hypoxemia resulted in a decrease in fetal pH and an increase in lactate; however, the magnitude of these changes was only modestly, and not significantly, greater than those observed during euglycemic hypoxemia. These effects were much less striking than expected, based on earlier work in sheep (Shelley, Bassett & Milner, 1975; Robillard, Sessions, Kennedy & Smith, 1978). Although catecholamines increased significantly in response to hypoxemia both in hyperglycemic and euglycemic fetuses, the increase was less in the hyperglycemic group, possibly resulting from a modulating effect of the high glucose concentration on catecholamine release from the adrenal medulla. Finally, a significant fetal insulin response to hyperglycemia was seen which, suggestively, was partially inhibited in the presence of hypoxemia and its associated increase in sympathoadrenal activity.

Acid-Base Equilibrium↗

Sympathoadrenal responses during hypoglycemia, hyperinsulinemia, and hypoxemia in the ovine fetus.

Interrelations of sympathoadrenal function and changes in glucose and insulin homeostasis were studied in chronically cannulated late gestation fetal sheep. Catecholamine secretory rates (based on direct adrenal sampling) and plasma concentrations were determined in the fetus during 2 h of insulin-induced hypoglycemia, during a period of hypoxemia, and during hyperinsulinemia per se (i.e., without hypoglycemia). Fetal insulin infusion (5-10 mU.kg-1.min-1) resulted in hypoglycemia and a significant rise in secretion of epinephrine but not of norepinephrine. By contrast, fetal hypoxemia caused a prompt and significant increase in adrenal secretion of both norepinephrine and epinephrine. Changes in peripheral plasma catecholamine levels were usually, but not always, qualitatively similar to those in adrenal secretion; the latter was a far more sensitive indicator of adrenal function. Hyperinsulinemia per se caused no change in adrenal secretory rates or plasma concentrations of catecholamines. Nevertheless, insulin infusion caused a fetal tachycardia even in the absence of hypoglycemia and hypoxemia, suggesting either a direct effect on the heart or stimulation of sympathetic nerves.

Adrenal Medulla↗

Catastrophic complications of previous cesarean section.

Of 711 patients who were delivered after one or more previous cesarean sections, 17 (2.4%) had an extremely serious complication. Uterine rupture and placenta previa or placenta accreta with accompanying hemorrhage were the major contributors to mortality and major morbidity. Nine uterine ruptures occurred, including five associated with labor with a low transverse uterine scar and one with an unknown scar (1.4% of trials of labor). There were two cases of placenta previa and five with varying degrees of placenta accreta. The nature and frequency of the observed complications emphasize the potentially serious remote consequences of cesarean section.

Adult↗

Labor patterns in women with previous cesareans.

Little information exists to help determine the presence or significance of labor abnormalities in women attempting vaginal birth after previous cesarean. A case-control study was performed to obtain information on patterns of labor progress and the incidence of dysfunctional labor in patients having a trial of labor after previous cesarean delivery. Sixty-eight such women were matched to nulliparous and multiparous controls. Labor-curve characteristics for the group of women with previous cesarean differed significantly from those of both the nulliparas and multiparas. When stratified by history of previous vaginal birth, however, those with no previous vaginal birth were indistinguishable from nulliparous controls and those with a previous vaginal birth were indistinguishable from multiparous controls. Parity-specific criteria for the diagnosis of dysfunctional labor were thus indicated. Labor disorders were present most frequently in the previous-cesarean group with no previous vaginal birth (41.9%). This incidence did not differ significantly from that in the control nulliparas (27.1%) (P = .15), but did differ from that in the multiparas (15.8%) (P less than .01). Previous-cesarean patients with a previous vaginal birth had a frequency of labor disorders (14.3%) not significantly different from that of multiparous controls. We conclude that trial of labor in women with a previous cesarean should be evaluated by standard criteria for nulliparas if there has been no previous vaginal birth, and by criteria for multiparous women if there has been any previous infant born vaginally.

Adult↗

Influence of presentation on neonatal outcome of vaginally delivered low birthweight infants. A matched pair analysis.

Neonatal outcome of 30 low birthweight (800 to 2000 g) breech infants delivered vaginally was compared with a matched sample of vaginally delivered vertex infants. Using a multiple regression analysis, presentation was found to be significantly related only to the Apgar score at 1 minute. No effect of presentation was found on Apgar score at 5 minutes, length of stay in the nursery, need for ventilatory support, or incidence of neonatal death, seizures, or intracranial hemorrhage. Thus, vaginal delivery of low birthweight breech fetuses was associated with short-term infant outcomes comparable to those of similar fetuses delivered vaginally from vertex presentations. The findings suggest that prevailing assumptions about the risks of premature breech vaginal delivery need to be evaluated critically.

Apgar Score↗