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Biomedical subjects

M A Simmons

Publications and source records attributed to M A Simmons.

At least 55 records · Page 3Linked to original sources
PubMed1984

Actions of 4-aminopyridine on mammalian ganglion cells.

The effects of 4-aminopyridine (4-AP) on membrane electrical properties and synaptic transmission in neurons of the isolated rabbit superior cervical ganglion were investigated. 4-AP (0.03-0.1 mM) increased the amplitude of the fast excitatory postsynaptic potential (f-EPSP) without affecting appreciably either the acetylcholine (ACh) depolarization induced by iontophoresis of ACh or the passive and active membrane properties of the neurons. At concentrations of 1-5 mM, 4-AP reversibly depressed the amplitude of the f-EPSP as well as the ACh depolarization; a slight to moderate prolongation of the action potential duration was observed. In addition to the effects on evoked synaptic potentials, 4-AP induced spontaneous discharges which were abolished reversibly by curare, low Ca solution or Co. The results indicate that 4-AP at low concentrations facilitated evoked as well as spontaneous release of ACh by a presynaptic mechanism, whereas at higher concentrations it exerted a curare-like effect on the postsynaptic membrane.

4-Aminopyridine↗
PubMed1984

Carbonic acid dissociation constant (pK1) in critically ill newborns.

In the Henderson-Hasselbalch equation, the apparent first dissociation constant for carbonic acid in plasma, pK1, is 6.10 +/- 0.01 (+/- SD) in healthy adults. In contrast, values for pK1 in sick adults and in sick infants and children have been reported to vary widely. Because of the far reaching implications of these findings, we repeated the measurements in 19 newborns in a neonatal intensive care unit. Two measurements were made in each infant, one while the infant was acutely ill and another after recovery. We found that neither the mean value nor the range of pK1 values was affected by the infants' clinical status. The values during the acute phase of the hospitalization (range, 6.01-6.12; mean +/- SD, 6.08 +/- 0.03) did not differ from those after recovery (6.02-6.17; 6.08 +/- 0.04). A second study was performed in order to see if the wide range of pK1 values seen in other studies might be the result of an unstable state accompanying acute changes in acid-base status similar to those that might be encountered in clinical situations. However, data in seven lambs showed no significant difference when pK1 before an acute alteration in acid-base status (6.10 +/- 0.04) was compared with that 10 min after (6.09 +/- 0.03). In newborn intensive care units, nomograms are used to calculate total CO2 from pH and PCO2 assuming a pK1 = 6.10. Our data support this practice.

Acid-Base Equilibrium↗
PubMed1982

Oxygen delivery to the brain before and after birth.

We studied the relationship between cerebral oxygen consumption and cerebral oxygen delivery (cerebral blood flow x arterial oxygen content) in fetal, newborn, and adult sheep, Relative to the amount of oxygen consumed, cerebral oxygen delivery in the fetus exceeds that in the lamb and adult by 70 percent. This may represent a protective advantage for the fetus or simply a necessary adaptation to the low arterial oxygen pressure in the intrauterine environment.

Animals↗
PubMed1982

Enkephalinergic modulation of non-cholinergic transmission in mammalian prevertebral ganglia.

The non-cholinergic excitatory potential elicited in neurons of the isolated inferior mesenteric ganglia was depressed by bath application of Met- or Leu-enkephalin and enhanced by naloxone or naltrexone. The membrane depolarization induced by exogenously applied putative transmitter substance P was not appreciably affected by either enkephalin (Enk) or opiate antagonists. Our results indicate that the non-cholinergic excitatory transmission which may be mediated by substance P in prevertebral ganglia is modulated presynaptically by endogenously released Enk in a manner that may resemble the interaction between these two peptides in the spinal cord.

Animals↗
PubMed1982

Parenteral galactose therapy in the glucose-intolerant premature infant.

Blood galactose concentrations were measured in 55 neonates consuming at least 80 ml/kg/day of lactose-containing formula. The range of galactose concentration immediately after feeding was 0.8 to 4.2 mg/dl, with a mean of 1.5 +/- 0.2 mg/dl. Galactose concentration fell rapidly after feeding, and normal values for the population fell with a half-life of 45 minutes. Considering galactose as a potential intravenous nutrient, six glucose-intolerant premature infants were given galactose-containing solutions intravenously using a double-blind randomized crossover protocol. Infants were chosen who had sustained hyperglycemia (150 mg/dl) and glucosuria (2+ Clinitest) requiring glucose infusion at a rate below 7 mg/kg/minute for more than 24 hours. Compared to the control glucose period, intravenous alimentation with a solution containing carbohydrate as 50% glucose and 50% galactose resulted in a 65% increase in total carbohydrate infusion rate, normalization of the blood glucose concentration, and decreased glucosuria. Blood galactose concentration averaged 15 mg/dl, and no clinical or biochemical evidence of galactose toxicity was noted.

Blood Glucose↗
PubMed1982

Response of cerebral blood flow to changes in PCO2 in fetal, newborn, and adult sheep.

Developmental effects on the response of cerebral blood flow (Qc) and cerebral O2 consumption (CMRO2) to changes in CO2 tension were assessed in unanesthetized fetal, newborn, and adult sheep. Blood flow was measured using the radioactive microsphere technique. CMRO2 was calculated as the product of Qc and the difference in O2 content between arterial and sagittal sinus blood (CaO2 -- CVO2). The response of Qc to changes in arterial CO2 tension increased from fetus [3.53 +/- 0.56 ml.100 g-1.min-1.mmHg PaCO2(-1) (SE)] to newborn (5.16 +/- 0.59) to adult (6.20 +/- 0.63). Only the fetal-adult difference was significant (P less than 0.05). It has been suggested that developmental differences in CO2 responsiveness of cerebral blood flow are the result of differences in CMRO2. We corrected for differences in CMRO2 by looking at the response to CO2 of the variable 1/(CaO2--CVO2). According to the Fick principle 1/(CaO2--CVO2) = Qc/CMRO2, i.e., blood flow per unit O2 consumption. The fetal response was not significantly different from the newborn, but the adult was significantly different from both (P less than 0.05). Thus the difference in CO2 response of cerebral blood flow between fetus and adult cannot be explained by differences in CMRO2.

Animals↗
PubMed1981

Effects of changes in arterial O2 content on cerebral blood flow in the lamb.

The effect of variations in arterial O2 content (CaO2) on the cerebrovascular bed of seven unanesthetized newborn lambs was studied as the hematocrit and arterial PO2 (PaO2) were varied. Each subject was studied at a high hematocrit [44 +/- 3% (SD)] and a low hematocrit [24 +/- 3%]. At each hematocrit level the PaO2 was changed over a range of 30-150 mmHg. The relationship between cerebral blood flow and PO2 depended on hematocrit and vice versa. To the contrary, the relationship of blood flow to CaO2 was independent of hematocrit and/or PO/. As CaO2 fell, regardless of whether this was due to a fall in PO2 hematocrit or both, there was a reciprocal increase in cerebral blood flow such that cerebral O2 delivery (cerebral blood flow x CaO2) was constant. These data show that CaO2 is a variable of fundamental importance to the regulation of cerebral blood flow. Changes in CaO2 are accompanied by reciprocal changes in cerebral blood flow to maintain constant cerebral O2 delivery. Data among species with differing cerebral O2 consumption show that cerebral O2 delivery, in turn, is regulated according to cerebral O2 consumption.

Animals↗
PubMed1981

Ontogeny of erythrocyte insulin binding in the sheep.

The ontogeny of insulin binding in the sheep was studied using the erythrocytes (RBCs) of 31 fetuses, 10 lambs, and 5 adult animals. Six fetuses were studied on three occasions over a 2-week period from 120--135 days of gestation to provide longitudinal data on changes in insulin binding. Maximal percent binding of [125I]iodoinsulin and receptor concentration decreased significantly as the age of the animal increased (r = 0.76, P less than 0.001 and r = --0.49, P less than 0.001, respectively). Total loss of insulin binding to RBCs was estimated to occur in the second postnatal month, and the RBCs from the adult sheep showed no specific insulin binding. The osmotic fragility of RBCs in each developmental group of animals was also studied to assess possible differences in RBC membrane properties. RBC osmotic fragility was significantly lower in fetuses than in adult sheep (osmotic fragility 50 = 0.55% phosphate-buffered saline vs. 0.76% phosphate-buffered saline, respectively; P less than 0.001). The data suggest that fetal RBCs of lower osmotic fragility and high insulin binding capacity are progressively replaced during late prenatal and early postnatal life by adult-type RBCs of increased osmotic fragility and lacking binding capacity for insulin. The timing of the disappearance of insulin binding to RBCs coincides with the final transition in the animals from a monogastric to a ruminant metabolic state, and may reflect a change in the need for insulin with age.

Aging↗
PubMed1981

Lethal chylothoraces due to superior vena caval thrombosis in infants.

An unusual etiology, probably iatrogenic, for chylothoraces in the newborn period was recently noted. Three tiny premature infants, all of whom subsequently died, developed massive bilateral chylothoraces. These infants had had prolonged hyperalimentation using jugular central venous catheters for severe gastrointestinal problems and malnutrition. All developed superior vena caval thrombosis, two with overt superior vena caval syndromes. Two had venograms that showed extension of thrombus into the innominate veins to the confluence of the jugular and subclavian veins, at the site of drainage of the lymphatic channels of the thorax. The relationship between superior vena caval an innominate vein thrombosis and chylothoraces in discussed and an important pitfall in the radiologic evaluation is emphasized.

Chylothorax↗
PubMed1981

Premature rupture of membranes and preterm labor: neonatal infection and perinatal mortality risks.

The purpose of this study was to analyze neonatal infection rates and perinatal mortality in births complicated by premature rupture of membranes (PROM) and spontaneous labor before term (less than 37 weeks' gestation). Neonatal infection occurred more commonly in preterm compared with term infants. The risk of infection due solely to PROM was insignificant compared with the risk attributable to preterm birth. Perinatal mortality and cause-specific mortality varied inversely with gestational age. These rates were not significantly different between groups with or without PROM or with or without associated development of maternal endometritis. Although the mortality due to infection was higher in preterm compared with term groups, most preterm deaths were attributed to other factors, particularly anoxia and respiratory causes. The diverse fetal risks associated with PROM and the associated maternal infection risks analyzed support expectant management when PROM occurs preterm.

Endometritis↗
PubMed1980

The effect of serotonin depletion on the discriminability of LSD.

Nine groups of rats were trained to discriminate LSD (0.12 mg/kg) from saline in a two-lever, water-reinforced, drug discrimination procedure. After stable discriminative performance was obtained (>95% correct), groups were administered one of several treatments which lower the concentration of serotonin (5-HT) in brain: (1) 12.5, 25, 50, 100 or 200 microgram of 5,7-dihydroxytryptamine (5,7-DHT) intraventricularly (IVT); (2) 3 X 100 mg/kg of p-chlorophenylalanine (PCPA) intraperitoneally (IP); or (3) 20 mg/kg of p-chloroamphetamine (PCA) IP. Control rats received either IVT injections of 5,7-DHT vehicle or IP injections of PCA or PCPA vehicles. Beginning 12 days after treatment, lever preference following various doses of LSD was determined. The results indicated that only the 200 microgram dose of 5,7-DHT and PCPA caused a significant potentiation of LSD-lever responding at the 0.03 mg/kg dose of LSD while all treatments except 12.5 and 25 microgram of 5,7-DHT resulted in significant depletion of 5-HT. Moreover, amount of 5-HT and percent LSD responding following 0.03 mg/kg LSD were not significantly correlated. It was concluded that 5-HT depletion, per se, cannot account for supersensitivity to the behavioral effects of LSD.

5,7-Dihydroxytryptamine↗
PubMed1980

Pharmacology of furosemide in the premature newborn infant.

The pharmacokinetic parameters of furosemide were measured in 14 premature newborn infants, one to 20 days of age, and in 12 older infants, aged one to 4 months, following a single intravenous dose of 1 mg/kg of furosemide. Furosemide levels were determined by a high pressure liquid chromatographic method which required 3 microliter of plasma. The volume of distributuion for furosemide was calculated to be 0.24 +/- 0.03 l/kg (mean +/- SE) in all infants studied, regardless of postnatal age. The half-life in the first three weeks of life was found to be 19.9 +/- 3.0 hours. Thus, the half-life of furosemide in the premature infant is considerably longer than in adults or older children, but the volume of distribution is similar. The bioavailability of oral furosemide in infants appeared to be low. The findings of this study indicate that furosemide, 1 mg/kg parenterally, given with a frequency of more than twice daily to the premature infant in the immediate neonatal period, or in parenteral dosages in excess of 2 mg/kg, may lead to plasma levels associated with ototoxicity.

Biological Availability↗
PubMed1979

Coagulation studies in extremely premature infants.

Evidence of developmental evolution of coagulation can be seen when the studies of 10 thriving extremely premature (EPT) infants are compared to normal full-term (FT) infants. The prothrombin time, partial thromboplastin time, and thrombin time all became shorter with increasing gestational age. Fibrinogen levels and platelet counts appear to be comparable to term infant and adult levels. Fibrin degradation products (FDP) of 10 micrograms/ml or less were found in the thriving EPT infants. When compared to healthy full-term infants, there is a definite gestational dependency of anti-thrombin III levels. Factors II and VII appear to be related to intrauterine maturation after the age of viability (24 wk), but factor VII-X complex does not. The contact factors XI, XII, high molecular weight kininogen (Fitzgerald factor), and prekallikrein (Fletcher factor) are all markedly decreased in thriving EPT infants. The mean factor V level is lower than that found in FT infants. This study confirms a gestational age dependency of factor VIII activity. The ratio of factor VIII antigen to factor VIII clotting activity is increased (2.8 vs 1.01 in FT and adults). Thriving small for gestational age (SGA) infants had coagulation studies which were not statistically different from those of thriving EPT infants. The coagulation changes which occurred in severely ill EPT were mainly in the factors which decrease during intravascular coagulation (factors I, V, and VIII). The present study suggests that because of the high antigen to activity ratio seen in thriving EPT infants, a dysfunctional or fetal factor VIII may have been produced. However, the further elevation of this ratio in the severely ill EPT infants is in keeping with a pathologic proteolysis or increased endothelial release of factor VIII antigen.

Blood Coagulation Factors↗
PubMed1979

Metabolic requirements for fetal growth.

Table 1 outlines a metabolic balance sheet for the sheep fetus. It is clear that maternal substrate concentrations as well as placental function are important in assuring the provision of adequate substrate to meet fetal metabolic and growth requirements. It is intriguing that the fetus appears to use substrates not usually regarded as important in extrauterine diets (lactate) and to use substrates for catabolic purposes normally thought to be primarily anabolic substrates (amino acids). This information emphasizes the hazards of extrapolating metabolic and nutritional patterns seen in extrauterine life in reaching conclusions concerning the fetus. It likewise emphasizes the importance of ongoing studies in maternal and fetal nutrition and metabolism.

Animals↗