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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
PubMed1986

Uterine metabolism of the pregnant rabbit under chronic steady-state conditions.

The study of uterine metabolism in pregnancy under chronic steady-state conditions has been confined to large mammals and, more recently, to the guinea pig. The pregnant rabbit is of interest because of its short gestation and large litter size. We developed an indirect approach involving retrograde catheterization of the uterine venous drainage, permitting measurement of both uterine metabolic quotients and uterine uptakes. Radioactive microspheres were used to measure blood flow. A large lactate and ammonia efflux from the uterus was found. In the fed state, ketogenic substrates were taken up in small amounts. However, during starvation a significant increase in ketoacid uptake was observed with a concurrent fall in acetate uptake. There was a large glucose/oxygen quotient across the uterus, but the glucose plus lactate/oxygen quotient was comparable to that found in the sheep and guinea pig (0.6 +/- 0.1). It is apparent that in all three species studied under chronic steady-state conditions (sheep, guinea pig, and rabbit) there is a large glucose uptake associated with a net lactate production, and fuels other than glucose and lactate must be used by the uterus.

Acetates↗
PubMed1986

Increased muscle tone during etretinate therapy.

A 40-year-old man with severe psoriasis developed painless muscle stiffness coinciding with four successive courses of etretinate therapy. Peripheral nerve block extinguished the increased muscle tone. Our patient's symptoms resembled those of the stiff-man syndrome. Increased muscle tone is a potential side effect of etretinate treatment and must be distinguished from the common musculoskeletal symptoms observed in patients taking retinoid therapy.

Adult↗
PubMed1986

Stereoselective disposition of mexiletine in man.

The pharmacokinetics of S-(+)- and R-(-)-mexiletine and of the corresponding conjugates were investigated in six healthy young volunteers after administration of a single 200 mg oral dose of racemic mexiletine hydrochloride. The values for the distribution rate constants as well as for the elimination half-lives of the two enantiomers were similar but the AUC of the S-(+)-enantiomer was always significantly higher (P less than 0.01) than that of the opposite enantiomer. The mean R/S ratios for unchanged mexiletine in serum and in urine were 0.78 +/- 0.12 (s.d.) and 0.80 +/- 0.21, respectively. Urinary excretion of mexiletine conjugates consisted mainly of the R-(-)-enantiomer; the mean R/S enantiomeric ratio over 48 h was 9.65 +/- 3.10. Serum concentrations of the conjugates were measured in three subjects. The mean R/S AUC ratio was 2.94 +/- 0.48 and the renal clearance of the R-(-)-enantiomer was significantly higher (P less than 0.02) than that of the S-(+)-enantiomer.

Adult↗
PubMed1986

Enoxacin compared with vancomycin for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis.

Enoxacin administered orally was compared with vancomycin administered intravenously for the treatment of experimental methicillin-resistant Staphylococcus aureus endocarditis. The MICs and MBCs of both enoxacin and vancomycin for an inoculum of 5.0 X 10(5) CFU of the methicillin-resistant S. aureus strain per ml were 1.56 microgram/ml. With an inoculum of 10(8) CFU/ml, enoxacin at 6 micrograms/ml and vancomycin at 180 micrograms/ml resulted in similar decreases in numbers of methicillin-resistant S. aureus in broth. Methicillin-resistant S. aureus endocarditis in rabbits was treated with enoxacin at 100 mg/kg orally every 12 h or vancomycin at 30 mg/kg intravenously every 12 h for 3 or 5 days. Enoxacin treatment for 3 or 5 days and vancomycin treatment for 5 days significantly reduced bacterial counts of vegetations compared with those in untreated control rabbits after 1 day of infection. Bacterial counts of vegetations after vancomycin treatment for 3 days did not differ significantly from those of untreated controls. Bacterial counts of vegetations in the four therapeutic groups did not differ significantly from one another. In uninfected rabbits single doses of vancomycin at 30 mg/kg administered intravenously achieved much higher concentrations in serum than did single doses of enoxacin at 100 mg/kg administered orally. Enoxacin had an elimination half-life in serum that was approximately 1.5 times longer than that of vancomycin. This study demonstrated that enoxacin administered orally is as effective as vancomycin administered intravenously for the treatment of experimental methicillin-resistant S. aureus endocarditis.

Animals↗
PubMed1986

Net substrates balance across hindlimb in conscious rabbit during late pregnancy.

The present work performed in rabbits was designed to investigate whether changes in skeletal muscle metabolism could contribute to glucose homeostasis during late pregnancy a time at which there is a large glucose demand of the gravid uterus. We therefore studied the net substrate balance of glucose, lactate, free fatty acids, and ketone bodies across the hindlimb of pregnant animals (days 24 and 30) and virgin animals. Our data show that on day 24 the basal rate of glucose uptake is similar to that observed in virgin rabbits, but it decreases by approximately 60% on day 30 despite comparable levels of blood glucose and plasma insulin at both gestational ages. A moderate hyperglycemia (20% above basal level) and hyperinsulinemia (2- to 3-fold above basal level) sustained for 80 min failed to increase glucose uptake except in virgin animals. Estimates of the contribution of substrates to oxidative metabolism indicate that free fatty acids could represent the major fuel in all groups, whereas glucose would be of minor importance especially at term. It is concluded that in pregnancy a) under normoglycemia there is a reduced insulin effect on glucose uptake and b) under moderate hyperglycemia and hyperinsulinemia the insulin resistance results from an impaired stimulation of glucose uptake. Sparing glucose from the skeletal muscle, the mother can direct more glucose toward the uterus without marked increase in her production rate.

Animals↗
PubMed1986

Lack of skeletal radiographic changes during short-term etretinate therapy for psoriasis.

We prospectively analyzed radiographic skeletal surveys of eight patients who received etretinate therapy for psoriasis at doses ranging from 0.5 to 1.2 mg/kg/day for 6-18 months. Although subtle skeletal changes could have been obscured by some of our patients' other radiographic abnormalities, no bony changes that could be attributed to etretinate were detected in any of these patients.

Adult↗
PubMed1986

The contribution of salivary amylase to glucose polymer hydrolysis in premature infants.

To determine whether salivary amylase of premature infants can function as a surrogate for pancreatic amylase, we evaluated its production in the infant, acid resistance, and hydrolytic potency in a simulated oropharyngeal, gastric, and intestinal environment. The activity of salivary amylase in 11 prematures varied between 1 and 33 U/ml; the isozymic profile and acid resistance of the premature salivary amylase were identical to those of the enzyme of adults. A "modular" formula containing 7 g/dl of a 14C labeled long chain glucose polymer with degrees of polymerization ranging between 18 and 29 glucose units was prepared. Salivary amylase, 1.1 U/ml, was added to this formula. The progressive breakdown of the 14C polymers as the milk was subjected to oropharyngeal, gastric, and intestinal phase environments was evaluated by quantifying the liberation of short-chain oligomers from the 14C labeled substrates. The gastric pH was varied between 2 and 5 and the gastric incubation time was either 5 or 180 min. Substantial gastric phase breakdown only occurred after 3 h of exposure at the higher pHs of 4 (12%) and 5 (32%). During the intestinal phase, salivary amylase activity resumed. Prior gastric phase pH affected ultimate intestinal phase breakdown, p less than 0.001; after 5-min gastric phases at pHs ranging from 2 to 5, the intestinal phase breakdown ranged from 17 to 55%. We conclude that the limited salivary amylase in the saliva of premature infants can produce significant glucose polymer digestion in both the stomach and small intestine but the digestion falls substantially short of that accomplished by usual concentrations of pancreatic amylase.

Adult↗
PubMed1985

Epileptiform burst responses in ventral vs dorsal hippocampal slices.

Field potentials from area CA1 evoked by stimulation of the Schaffer collaterals were compared in dorsal and ventral hippocampal slices of rat brain. Responses were categorized into 5 response types on the basis of their morphology, ranging from simple (single spike component) to complex (multiple spike components). A higher percentage of ventral slices, compared to dorsal slices, responded with a complex morphology under normal and increased K+ concentrations. Thus, there was a significantly greater tendency for cells within the ventral hippocampus to generate burst responses.

Animals↗
PubMed1985

Fluorescent phosphonate labels for serine hydrolases. Kinetic and spectroscopic properties of (7-nitrobenz-2-oxa-1,3-diazole)aminoalkyl methylphosphonofluoridates and their conjugates with acetylcholinesterase molecular forms.

The synthesis, kinetic, and spectral characterization of (7-nitrobenz-2-oxa-1,3-diazole)aminoethyl and (7-nitrobenz-2-oxa-1,3-diazole)aminopentyl methylphosphonofluoridate are described. These homologous organophosphorous agents contain the environmentally sensitive 7-nitrobenz-2-oxa-1,3-diazole chromophore. They inhibit acetylcholinesterase from Torpedo at rates exceeding 10(7) M-1 min-1 to form long-lived conjugates with one chromophore/80-kilodalton subunit. The intensity, position, and line width of the absorption spectra of the conjugates and reactivation kinetics in the presence and absence of the bisquaternary oxime 1,1'-trimethylene-bis(4-formylpyridinium bromide) dioxime indicate that these agents form conjugates in which the NBD-aminoalkyl moieties experience distinctive microscopic environments within the active center. NBD-aminoethyl methylphosphono-acetylcholinesterase undergoes oxime-induced as well as spontaneous reactivation at rates that are 3.6 and 35 times faster, respectively, than the corresponding rates measured for the NBD-aminopentyl conjugate. Hence, reactivation exhibits a marked dependence on structure of the methylphosphonate. Fluorescence emission at wavelengths greater than 520 nm is highly quenched and exhibits quantum efficiencies of less than 5%. Absorption maxima for the covalent NBD-aminoethyl methylphosphono-acetylcholinesterase appear at 475-480 nm while those for the corresponding NBD-aminopentyl methylphosphono-acetylcholinesterase appear at 485-490 nm. Bandwidths of the absorption maxima are substantially broader for the acetylcholinesterase adduct with NBD-aminoethyl methylphosphonofluoridate (3870 cm-1) than for the enzyme adduct with NBD-aminopentyl methylphosphonofluoridate (2870 cm-1). The CD spectrum of NBD-aminopentyl methylphosphono-acetylcholinesterase shows optical activity coincident with the shape and position of the absorption spectrum. In contrast, in addition to optically active transitions at the absorption maxima, the CD spectrum of NBD-aminoethyl methylphosphono-acetylcholinesterase shows intense optical activity at 430 nm, a wavelength region coincident with the region of spectral broadening. The spectral properties of alpha-chymotrypsin conjugates formed by reaction with the two probes are different, and the respective spectra differ also from those observed for the acetylcholinesterase conjugates. These results indicate that there is a reciprocal relationship between the structure of the probe and the structure of the active center.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗
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↗