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Biomedical subjects

M Gilbert

Publications and source records attributed to M Gilbert.

At least 199 records · Page 11Linked to original sources
PubMed1985

Cardiac output distribution and uteroplacental blood flow in the pregnant rabbit: a comparative study.

This study presents data on cardiac output distribution and uterine and placental blood flows in pregnant rabbits under chronic steady-state conditions. Ten liters and 67 fetuses were studied at 29 days of gestation, by means of radioactive microspheres. Five nonpregnant female animals were also studied for comparison. Mean cardiac outputs were 747.16 +/- 55.7 and 613.80 +/- 63.76 ml/min in the pregnant and nonpregnant states, respectively. In the pregnant animals, uterine and mammary blood flows were 6.7% +/- 0.7% and 5.1% +/- 0.5% of cardiac output, respectively. Within litters, the highest placental blood flows occurred at the ovarian and vaginal ends of the uterine horn. Placental blood flow per gram of fetus was 0.106 +/- 0.008 ml X min-1 X gm-1. A comparison with analogous data in the guinea pig and sheep demonstrates that toward the end of pregnancy placental blood flow per gram of fetus is approximately 2.5-times higher in sheep than in rabbits and guinea pigs. Expressed as a percentage of cardiac output, near-term uterine blood flow is significantly less in rabbits than in guinea pigs and sheep, whereas mammary blood flow is significantly higher. These interspecies differences are related to differences in placental structure, fetal/maternal mass ratio, and maturity at birth.

Animals↗
PubMed1985

Effect of cigarette smoking on mexiletine kinetics.

The effect of cigarette smoking on the kinetics of a single, 200 mg, oral dose of the antiarrhythmic drug mexiletine was investigated in healthy subjects. Cigarette smoking had no effect on absorption or distribution of the drug, but it significantly reduced the elimination t1/2 from 11.1 +/- 3.4 to 7.2 +/- 1.8 hours; the effect on clearance was less significant. Determination of the urinary concentrations of the three major metabolites of mexiletine (mexiletine glucuronide conjugate, hydroxymethylmexiletine, and p-hydroxymexiletine) indicated that cigarette smoking selectively induced conjugation of mexiletine with glucuronic acid as well as aliphatic hydroxylation to yield hydroxymethylmexiletine, but that it had no effect on the formation of p-hydroxymexiletine.

Adult↗
PubMed1985

Efficient storage system for breath hydrogen.

Recommended materials for breath hydrogen collection (plastic syringes with twist lock closure) are only adequate for relatively brief periods because of gradual hydrogen loss and considerable variability between duplicate samples. To document the most favorable storage conditions for breath hydrogen, we compared hydrogen retention in plastic syringes using a conventional twist-in-lock closure versus a simple, inexpensive syringe closure, a Critocap. Hydrogen retention was studied at 25, 5, and -20 degrees C in two different syringe brands over 72 h of storage. An analysis of variance confirms the superiority of Critocaps over twist-in-lock closures (p less than 0.001). Reliability was maximal when samples were placed in environments less than 5 degrees C. When storage time was extended to 7 days, mean hydrogen retention was 86 +/- 6% (means +/- SD).

Breath Tests↗
PubMed1985

Effects of fasting on glucose turnover rate and metabolite levels in conscious pregnant guinea pigs.

The effect of fasting during pregnancy is of particular interest in the guinea pig because of the large fetal mass carried to term. The present studies examined the effect of acute and chronic starvation on maternal glucose turnover in the guinea pig. In the first experiment, 7 near-term pregnant guinea pigs were fasted for 6 h. The maternal glucose concentration and glucose production decreased rapidly, falling to about 65-70% of fed levels at 4 h of starvation. Mothers demonstrated a 2.6-fold elevation in ketoacids after 2, 4 and 6 h starvation. In a second experiment, 5 non-pregnant and 11 near-term pregnant animals were studied in the control period and after 24 h of fasting. The maternal glucose concentration in the control state was independent of fetal mass. The maternal glucose turnover rate in the fed state correlated linearly with fetal mass. After 24 h of fasting, the glucose concentration and glucose turnover rate both decreased, with the magnitude of each decrease proportional to fetal mass. We conclude that, in the pregnant guinea pig, the fetal mass impacts significantly on maternal glucose metabolism in the fed and fasting states.

Acetates↗
PubMed1985

The use of computed tomography of the spine to identify patients at high risk for epidural metastases.

The usefulness of spinal computed tomography (CT) in predicting the presence of epidural tumor was evaluated in cancer patients undergoing CT myelography for suspected epidural tumor. Two hundred ninety two vertebral levels were evaluated in 30 patients. Spinal CT demonstrated cortical disruption surrounding the epidural space from metastatic cancer in 109 vertebrae. Eighty-five (78%) of these vertebral levels had tumor extension into the adjacent epidural space. The incidence of epidural tumor adjacent to vertebrae which had normal spinal CT or metastatic tumor without cortical disruption was 11%. Eighty-six percent of the epidural tumor adjacent to these vertebrae were a result of craniocaudal tumor extension in the epidural space from adjacent vertebral levels with cortical disruption. Twenty-one of 23 patients (91%) with cortical disruption at more than one vertebral level on spinal CT had epidural tumor. Synchronous noncontiguous epidural lesions were observed in 38% of patients with epidural tumor. Spinal CT is an important diagnostic test in determining which patients are at high risk for epidural tumor. Myelography should be performed in all patients with suspected epidural tumor to accurately define the full extent of tumor.

Adult↗
PubMed1985

The specificity and stability of the triton-extracted cytoskeletal framework of gerbil fibroma cells.

Cellular meshworks and topography of gerbil fibroma cells can be preserved by gentle extraction procedures using Triton X-100. We determined the stability and specificity of these cytoskeletal frameworks by measuring extraction rate and its sensitivity to exogenous protein. Two buffers were used, which mimicked the intracellular and extracellular ionic environments. With both buffers, extraction was nearly complete at 5 min. This pattern of extraction was seen both in 5- and 9-day-old cultures. The same pattern of extraction was seen when three different dilutions of cells were examined the second day after plating. Thus, extraction rate was largely independent of minor variations in ionic composition, age in culture, or cell density. Specificity of the cytoskeletal frameworks so produced was determined by competition with two different exogenous proteins (bovine serum albumin or ovalbumin), which did not remove any additional material from the cytoskeletal frameworks, even with over 10% exogenous protein in the extraction buffer. This pattern of extraction is not unique to gerbil fibroma cells. A similar pattern of extraction was seen for a series of cells: mouse 3T3 cells, 3T6 cells and SVPY 3T3 cells. These experiments indicate that the cytoskeletal framework produced by Triton extraction under appropriate conditions is stable after extraction for a period of 10 min or longer, and that the structures are specific, in that they are not disrupted by the presence of exogenous proteins.

Animals↗
PubMed1985

Tissue plasminogen activator release in vivo in response to vasoactive agents.

Release of tissue plasminogen activator into the circulation of rats in response to intravascular injections of vasoactive agents is studied by using a sensitive and specific clot lysis assay. Intra-arterial bradykinin elicits a rapid and transient rise in circulating plasminogen activator, which is maximum within one minute and is cleared within four to eight minutes. The plasminogen activator is fibrin dependent and is neutralized by an antiserum to human tissue-type plasminogen activator. Bradykinin is 1,000-fold more potent than the other agonists tested, which include histamine, norepinephrine, epinephrine, eledoisin-related peptide, arginine-vasopressin, lysine-vasopressin, desmopressin acetate, carbachol, and acetylcholine. Potency of bradykinin is related to its amino acid sequence. Sequential infusions of bradykinin produce a tachyphylactoid response that could be overcome by increasing the dose of the sequential bradykinin challenge. It is concluded that the characteristics of the responses to bradykinin and other agents in vivo differ significantly from those observed in isolated tissue preparations.

Animals↗
PubMed1985

Presence of natural autoantibodies in hyperimmunized mice.

Mice were immunized with various antigens in complete Freund's adjuvant following various injection schedules. Hybridomas were produced from the spleens of these immunized mice and examined for production of antibodies directed against the antigen injected and against a panel of self (tubulin, actin, myosin, DNA) and non-self antigens (myoglobin, spectrin, peroxidase, trinitrobenzene). Two to five percent of the hybrids were found to secrete polyspecific antibodies able to react with two or more antigens of the panel. Several of these hybrids were subcloned and expanded into ascites. The monoclonal immunoglobulins they secreted were isolated and shown to be IgM (kappa) and to possess the polyspecific antibody function. Several hybrids were also found to secrete antibodies reacting with the immunizing antigen as well as one or more antigens of the panel. The antibody secreted by one subclone which reacts with both the immunizing antigen, prolactin and one of the panel antigens, TNP, has been isolated using a DNP-immunoadsorbent. The isolated antibody was found to be a monoclonal IgM (kappa) immunoglobulin and to react both with prolactin and TNP. The hypothesis is advanced that cells carrying polyspecific natural antibodies as receptors after a given antigenic stimulation proliferate into cells producing highly specific antibodies for epitopes of that given antigen; the cells with polyspecific receptors will be continuously replaced by new cells probably on bone-marrow origin.

Animals↗
PubMed1984

The hippocampus, context, and information processing.

Two experiments are described in which groups of rats with bilateral hippocampal lesions, cortical lesions, and operated controls are compared on tests of discrimination learning, retention, and reversal learning. Experiment 1 examined the effects of varying prior training and context on new learning. Experiment 2 used a transfer paradigm to compare extent of original learning by hippocampal and control groups in a discrimination task involving multiple discriminanada . The major findings were that rats with hippocampal damage were less efficient at processing information and were more constrained by contextual influences than control rats.

Animals↗
PubMed1984

High pressure liquid chromatographic assay for mexiletine in serum.

A highly sensitive, rapid, and specific high pressure liquid chromatographic assay for the analysis of the antiarrhythmic agent mexiletine is reported. The method involves extraction of mexiletine with organic solvent followed by analysis using fluorescence detection. The minimum measurable limit is 1 ng and inter- and intra-day coefficients of variation are less than 5.8%. The method is useful for pharmacokinetic studies and routine serum monitoring of mexiletine.

Chromatography, High Pressure Liquid↗
PubMed1984

Uterine blood flow and substrate uptake in conscious rabbit during late gestation.

The aim of this study was the quantitation of the metabolic demands of the uterus in rabbits between days 24 and 30 of gestation, a time at which there is a fourfold increase in fetal weight. Serial measurements of substrate concentrations in maternal artery and uterine vein were performed over this period. Uterine blood flow was measured on days 24 and 30. Uterine substrate uptake was calculated by application of the Fick principle. Over the gestation range studied, the absolute uterine blood flow increased proportionally to the uterine weight gain. The uterine arteriovenous differences for glucose (G), lactate (L), free fatty acids (FFA), ketone bodies (KB), and oxygen (O2) were constant throughout the study. At both gestational ages, the weight-specific uterine substrate consumption (G, FFA, KB, O2) and production (L) were respectively similar. On days 24 and 30 the amount of G directed to the gravid uterus represented approximately 13 and approximately 36% of the maternal glucose turnover rate, respectively. The maximum contributions of G and FFA to the uterine oxygen consumption on day 24 were 80 and 30%, respectively. We have thus confirmed that at term the gravid uterus is a site of high glucose consumption. Finally, we demonstrated that in a nonruminant species, FFA would be a substantial source of carbon.

Animals↗
PubMed1984

Glucose turnover rates in chronically catheterized non-pregnant and pregnant rabbits.

Glucose turnover rates have been measured in conscious, chronically catheterized, non-pregnant and pregnant rabbits. Non-pregnant rabbits were studied weekly for 4 wk. Pregnant animals were studied once while non-pregnant and then weekly for up to 4 wk during pregnancy. Glucose turnover rate was measured using a primed-constant infusion of [U-14C]glucose and [6-3H]glucose. The weight of the rabbits did not vary throughout the 4-5 wk of study in either the non-pregnant or pregnant group. Seven pregnant rabbits delivered pups which weighed an average of 61 g each. In non-pregnant rabbits, blood glucose concentration did not vary with time. In the pregnant rabbits, blood glucose concentration fell by the end of gestation to an average value of 74.6 +/- 2.7 mg/dl, significantly less (P less than 0.01) than the glucose concentration in the same animals before pregnancy, 88.2 +/- 2.4 mg/dl. The weight specific glucose turnover rate did not vary with time in either the non-pregnant (4.38 +/- 0.16 mg X min-1 X kg-1) or pregnant rabbits (3.89 +/- 0.29 mg X min-1 X kg-1). Blood glucose clearance did not change over time in the non-pregnant rabbits but did increase in the pregnant rabbits in late pregnancy. Blood glucose clearance was inversely related to the fall in blood glucose concentration.

Animals↗
PubMed1984

Some aspects of maternal metabolism throughout pregnancy in the conscious rabbit.

Studies of maternal metabolism during pregnancy have focused principally upon the latter half of gestation. However, maternal metabolic adaptations to pregnancy may occur at all stages of pregnancy. To study maternal metabolism throughout pregnancy, we developed a chronically catheterized rabbit model in which animals could be studied under conscious, stress-free conditions when nonpregnant and then serially throughout pregnancy. Anesthesia produced marked hyperglycemia. In contrast, chronic catheterization and daily handling did not affect blood concentrations of glucose, lactate, ketone bodies, or free fatty acids, or food intake. Glucose concentration decreased with pregnancy to a value at term equal to 85% of the prepregnancy value. Lactate concentration rose significantly in the second half of pregnancy but changes in free fatty acids and ketoacid levels were not significant. These results are discussed from a comparative physiologic point of view, emphasizing the unique aspects of rabbit metabolism during pregnancy and the importance of performing such studies under conscious, stress-free conditions.

Anesthesia↗
PubMed1984

Glucagon and insulin secretion and their biological activities in hypothermic rats.

To clarify the impact of hypothermia on the hormonal control of glucose metabolism, rats were rendered hypothermic (25 C) after catheterization of the portal vein. Glucose, insulin, glucagon, and catecholamine concentrations were serially monitored, and the regional blood flows were measured, allowing the estimation of hormone outputs. Hypothermia reduced the portal blood flow by 50% without changing arterial blood pressure, blood gases, or pH. Portal plasma insulin secretion dropped (0.05 +/- 0.01 vs. 0.23 +/- 0.04 mU/min), and glucagon secretion increased (0.81 +/- 0.18 vs. 0.38 +/- 0.10 ng/min). The B cell responses to glucose, arginine, and glucagon were abolished, while the A cell response to arginine was not significantly affected. Glucose intolerance was apparent after iv glucose or arginine loads. Haloperidol and to a lesser extent phentolamine suppressed the cold-induced glucagon rise. Phentolamine and to a lesser extent haloperidol alleviated the cold-induced suppression of insulin release. Propranolol, naloxone, and atropine were relatively inactive. The cold-induced glucose intolerance was not corrected by phentolamine treatment. A marked resistance to iv insulin was apparent in these rats, which is in contrast to a normal sensitivity to iv glucagon.

Animals↗
PubMed1984

Effect of insulin on glucose uptake by the maternal hindlimb and uterus, and by the fetus in conscious pregnant sheep.

Previous studies have demonstrated the presence of insulin receptors on the maternal surface of the placenta in several species and the specific binding of insulin to the placenta in sheep. However, both in-vitro and in-vivo studies have produced conflicting evidence concerning the effect of insulin on placental glucose uptake. To clarify this problem, we measured maternal hindlimb, uterine and fetal glucose and oxygen extractions and glucose/oxygen quotients in chronically catheterized, non-stressed, late-gestation pregnant sheep over 1 h at a constant concentration of arterial plasma glucose, and again during the next 2 h at the same glucose level but at a higher insulin concentration using glucose 'clamp' methodology. Insulin produced a 4.9-fold increase in glucose extraction and a 3.5-fold increase in glucose/oxygen quotient across the hindlimb; in contrast, insulin did not significantly affect uterine or fetal glucose extraction or glucose/oxygen quotient. We conclude that in contrast to other tissues of the pregnant ewe, placental glucose uptake and transfer are insensitive to variations in maternal insulin concentration.

Animals↗