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Biomedical subjects

L McCoy

Publications and source records attributed to L McCoy.

At least 19 recordsLinked to original sources
PubMed2001

Technique of right laparoscopic donor nephrectomy: a single center experience.

The majority of laparoscopic donor nephrectomies (LDNs) are limited to the left side due to technical and allograft concerns in using the right. We review our experience with right LDNs. Since June 1997, 15 right LDNs were performed and the records retrospectively reviewed for demographics, operative time, transfusions, complications, and length of stay. Recipient records were also reviewed for delayed graft function, complications, and serum creatinine levels. Overall donor, recipient and graft survivals at 6 months are 100%. Mean operative time was 317 +/- 11.0 min, length of stay was 4.2 +/- 0.2 d, and mean serum creatinine levels at discharge, 1, 3, and 6 months were 1.74 +/- 0.19, 1.59 +/- 0.13, 1.72 +/- 0.13, and 1.68 +/- 0.13 mg/dL, respectively. No transfusions were required. There were no operative or hospital complications. Two recipients (13.3%) experienced delayed graft function, defined as requiring hemodialysis post-transplantation. With hand-assisted laparoscopy, the right laparoscopic donor nephrectomy is safe and allows excellent allograft function.

Adult↗
PubMed2000

Global assessment of functioning (GAF) ratings: determinants and role as predictors of one-year treatment outcomes.

OBJECTIVE: To assess the adequacy of global ratings of patients' psychosocial functioning, which are an integral part of the current system for obtaining multidimensional psychiatric diagnoses and are embodied by the Global Assessment of Functioning (GAF) Scale as AXIS V of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (American Psychiatric Association, 1994). METHOD: We identified a sample of 1,688 patients with substance use disorders, many of whom also had psychiatric disorders; examined the determinants of GAF ratings; and focused on how well these ratings predicted patients' one-year symptom and psychosocial functioning outcomes. RESULTS: Patients' clinical diagnoses and psychiatric symptoms were stronger predictors of GAF ratings than was their social and occupational functioning. Moreover, GAF ratings were only minimally associated with patients' one-year psychological, social, and occupational functioning outcomes. CONCLUSIONS: These findings raise serious questions about the conceptual and clinical value of the current standard method of assessing psychiatric and substance abuse patients' global functioning.

Adult↗
PubMed1998

Antipsychotic drug regulation of AMPA receptor affinity states and GluR1, GluR2 splice variant expression.

We recently reported that chronic administration of antipsychotic drugs dramatically elevated [3H]AMPA binding, with minimal elevation of [3H]CNQX binding in rat brain. The aim of the current study was to examine the mechanism of this effect. Chronic haloperidol minimally increased the total number of binding sites (total Bmax) compared to saline-injected animals. Specifically, haloperidol dramatically increased the proportion of high-affinity-site AMPA receptors (approximately 30% increase) without inducing a significant change in the low-affinity constant. In situ hybridization for flip and flop isoforms of GluR1 and GluR2 (AMPA receptors) was not altered in a pattern or degree that compared to the changes seen in AMPA receptor binding. These findings suggest that the long-term action of antipsychotic drugs may be to regulate AMPA receptor responsiveness to agonist stimulation via posttranscriptional means, and is unlikely to be related to GluR1 or GluR2 splice variant expression. This effect may have relevance to both the therapeutic effects and side effects of antipsychotic drugs in humans.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1998

The cellular intake kinetics and acute biological effects of various oxovanadium species: a comparative study.

It is well known that different oxovanadium species can have significantly different biopotencies, including hypoglycemic actions. The basis for the observed differences in the biopotency of different oxovanadium species: vanadate, vanadyl, 1,10-phenanthroline bisperoxovanadate (phen-bpv), 4-methyl 1,10-phenanthroline bisperoxovanadate (mpv) and 4,7-dimethyl 1,10-phenanthroline bisperoxovanadate (dpv), was examined in this study. The cellular uptake kinetics for these oxovanadium species was measured. Phen-bpv and vandyl had the most rapid cellular uptake. Mpv, dpv and vanadate exhibited a much slower uptake kinetics. Stimulation of protein tyrosine phosphorylation (PTP), both the time dependency and the dose dependency, was used as an index for biopotency. Although phen-bpv and vanadyl had the same cellular uptake kinetics, they differed markedly in their ability to stimulate PTP. Structurally similar oxovanadium species, phen-bpv, mpv and dpv demonstrated different uptake kinetics and effects on stimulating PTP. Bioavailability, both in term of cellular uptake and migration or transport to the active site, has been shown to be an important factor, in addition to intrinsic activity of the oxovanadium species, in determining the overall biopotency. Finally, this study demonstrates that variation of the chelating ligand has a profound effect on the physiochemical properties and biological effects of the oxovanadium species.

Kinetics↗
PubMed1997

Time course and regional basis of Pb-induced changes in MK-801 binding: reversal by chronic treatment with the dopamine agonist apomorphine but not the D1 agonist SKF-82958.

In the present study we attempted to further define the time course and regional specificity of lead (Pb)-induced changes in the NMDA receptor complex and the influence of dopaminergic system modulations on these changes. Autoradiographic measurements of alterations in MK-801 binding, as evaluated under four different activation conditions (none, spermidine, glycine, or maximal activation), were performed in medial frontal cortex, dorsal striatum, and nucleus accumbens of male rats after 2 weeks or 8 months of chronic postweaning (from 21 days of age on) exposure to 0, 50, or 150 ppm Pb acetate in drinking water. The 8-month groups also received chronic intermittent intraperitoneal injections of saline, or of the dopamine (DA) agonist apomorphine or the D1 agonist SKF-82958 2-3 times per week beginning at 60 days of age. Two weeks of 50 ppm Pb exposure resulted in small but significant increases in MK-801 binding under conditions of glycine or spermidine activation, whereas decreases were observed in response to 150 ppm under conditions of no or maximal activation in all regions. After 8 months of Pb, concentration-dependent decreases in MK-801 binding were observed across regions under all activation conditions. These effects were noted at blood Pb concentrations averaging as low as 16 microg/dl. Pb-induced decreases in MK-801 binding were either partially or fully reversed by chronic intermittent treatment with the DA agonist apomorphine but not by the D1 agonist SKF-82958, implicating D2-based mechanisms in this reversal. Combined findings from this and previous studies based on this exposure protocol indicate a Pb-induced pattern of widespread hypoglutamatergic function accompanied by increased DA function in mesolimbic systems, a pattern of changes reminiscent of those proposed to underlie schizophrenia. Such findings suggest that Pb exposure, even at current environmental levels, could be a risk factor for behavioral and/or neurological disturbances arising from imbalances of glutamate/dopamine function in mesocorticolimbic systems.

Animals↗
PubMed1997

Regional decreases in alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) and 6-[3H]cyano-7-nitroquinoxaline-2,3-dione ([3H]CNQX) binding in response to chronic low-level lead exposure: reversal versus potentiation by chronic dopamine agonist treatment.

This study evaluated the hypotheses that in vivo lead (Pb) exposure would alter alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor binding and, based on known glutamate-dopamine interactions and Pb-induced changes in dopamine (DA) systems, that AMPA binding might be differentially influenced by DA agonist treatment under conditions of Pb exposure. Alterations in high-affinity ([3H]AMPA) versus total AMPA [6-[3H]cyano-7-nitroquinoxaline-2,3-dione ([3H]CNQX)] receptor binding were determined in medial frontal cortex, dorsal striatum, and nucleus accumbens of rats exposed to 0, 50, or 150 ppm of Pb acetate for 2 weeks or 8 months. Additional 8-month groups received chronic intermittent treatment with saline, the D1 agonist SKF82958, or the general DA agonist apomorphine. Two-week exposures increased AMPA receptor densities, whereas robust decreases occurred after 8 months of Pb; at the latter time point changes were more pronounced for high-affinity than total AMPA receptor binding, with high-affinity effects expressed preferentially in dorsal striatum and nucleus accumbens. DA agonist treatments almost fully reversed Pb-related declines in [3H]AMPA binding but either had no effect (apomorphine) or even further potentiated (SKF82958) the decreases in [3H]CNQX binding. One possible basis for the long-term (8-month) decrease in AMPA binding is a postsynaptic glutamatergic stimulation of non-NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Chronic treatment with typical and atypical antipsychotics increases the AMPA-preferring form of AMPA receptor in rat brain.

We assessed the effects of chronic (21 day) administration of antipsychotic drugs on the density of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in rat brain. We used two typical antipsychotic drugs, haloperidol and pimozide, and two atypical antipsychotic drugs, risperidone and clozapine. Antipsychotic drugs as a group significantly elevated the density of the AMPA receptor measured with an AMPA receptor agonist ([3H]AMPA), but not with an AMPA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione ([3H]CNQX). In all regions studied, the magnitude of the increase seen with chronic typical antipsychotic drugs was significantly greater than that seen with chronic atypical antipsychotic drugs. In frontal cortex and striatum, typical antipsychotics but not atypical antipsychotics elevated AMPA receptor binding over control. These findings suggest that antipsychotic drugs alter the agonist affinity of the AMPA receptor without altering the number of AMPA receptors. Typical antipsychotic drugs may be more potent in this effect than atypical antipsychotic drugs, especially in critical corticostriatal circuits.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Chronic antipsychotic treatment alters glycine-stimulated NMDA receptor binding in rat brain.

In this study the chronic effect of antipsychotic drugs (APDs) on N-methyl-D-aspartate (NMDA) receptor binding was evaluated. Rats were treated for 21 days with i.p. injections of haloperidol (0.5 mg/ kg), pimozide (0.5 mg/kg), clozapine (20 mg/kg), risperidone (1 mg/kg) or water vehicle (1 ml/kg). Brain tissue sections underwent different [3H]MK-801 assay conditions. Following a short preincubation wash, there were no effects of APDs on either unenhanced or agonist enhanced [3H]MK-801 binding. Following a prolonged preincubation wash, APDs resulted in a reduction in both unenhanced binding and glycine enhanced binding. The attenuation of glycine stimulation in the APD treated animals was selective as neither NMDA nor spermidine enhanced binding was significantly affected. The present data suggest specific actions at the glycine regulatory site on the NMDA receptor as part of the chronic effects of APDs.

Analysis of Variance↗
PubMed1996

Washable endogenous substances and regional heterogeneity in agonist enhanced [3H]MK-801 binding in rat brain.

NMDA receptor/ion channel function is modulated through a number of distinct sites that regulate channel opening. Published studies report widely varying results in modulatory site agonist effects due to assay conditions and technique. Also, NMDA receptor regulation at these sites by endogenous substances remains poorly characterized. The objectives of the present study in Sprague-Dawley rat forebrain sections were: (i) determine the contribution of various prewash variables on agonist stimulation of the NMDA receptor, (ii) compare regional differences in functional glycine, spermidine and NMDA binding sites under optimized prewash conditions, and (iii) define the influence of endogenous substances at each modulatory site by analyzing changes in binding at different prewash durations. We demonstrate that prewash conditions have a critical influence on [3H]MK-801 binding in rat tissue sections and that this effect was differentially expressed across brain regions. An extended prewash duration caused a regionally specific decrease in unenhanced [3H]MK-801 binding, while a short prewash caused a regionally specific biphasic effect on enhanced [3H]MK-801 binding. After prolonged prewash, binding was restored to previous (unwashed) binding levels with exogenously added glycine, NMDA, or spermidine alone or combinations of agonists. These data suggest that washable endogenous substances contribute to the full functionality of the NMDA receptor and the regional heterogeneity in [3H]MK-801 binding is dependent on the interaction of receptor protein subtypes and the presence of one or more endogenous substances.

Animals↗
PubMed1993

Clinical correlates of valproate augmentation in refractory bipolar disorder.

We examined the clinical correlates of valproate (VPA) therapy in refractory bipolar disorder. Retrospective chart review was used to collect demographic and clinical data including present diagnosis, diagnosis at illness onset, duration of illness, number of hospitalizations, VPA dose, side effects, and maximum serum concentration. Global response was rated once patients serum VPA exceeded 50 mg/dL. The charts of all inpatients admitted over a two-year period and treated with VPA for acute episodes of bipolar disorder in manic, mixed, or depressed phase were reviewed. Seventeen of these patients began VPA augmentation while hospitalized and became the cohort for review. Patients were excluded if VPA was started prior to admission or the patient was discharged less than one week after drug initiation. Patients were not excluded on the basis of EEG, CT, or neurological exam findings. Overall, 12 of 17 (71%) of the patients showed a moderate or marked improvement while 5 of 17 (29%) showed mild or no response. Responders were older and had a longer duration of illness with an increased number of hospitalizations. There was a strong trend for responders to achieve a higher serum VPA level. A significant positive correlation was found between response in acute mania and psychotic symptoms at first episode of illness.

Adult↗
PubMed1991

Beneficial effects of isovolemic hemodilution using a perfluorocarbon emulsion in a stroke model.

In a clinically applicable cat stroke model, 16 purpose-bred adult animals were used to evaluate the beneficial effects of two treatment regimens: isovolemic hemodilution with either a perfluorocarbon emulsion or dextran 40 (a glucose polymer). Animals that received these treatment regimens were then compared with a control group of untreated animals. Focal cerebral infarctions were produced by transorbital ligation of the left middle cerebral artery. The randomly allocated treatment arms of the study were instituted 3 hours after ligation of the middle cerebral artery, thereby simulating a human clinical situation. In vivo mitochondrial metabolic activity of the peri-infarct cerebral tissue was continually assessed by means of a multiwavelength near-infrared spectrophotometer. This allowed measurement of cellular oxygenation at the cytochrome aa3 level, the terminal member of the cytochrome chain. Sequential proton-based magnetic resonance imaging was used to measure intracerebral water in vivo. Cardiac output, oxygen consumption/delivery, chemical, histologic, and rheologic parameters were also assessed. The data collected were analyzed by group means and standard statistical analyses, which revealed that the group treated with the perfluorocarbon emulsion had both less brain edema in the early post-infarct period (p less than 0.05), as well as a higher level of oxidation of cytochrome aa3 (p less than or equal to 0.025). This evidence supports the premise that isovolemic hemodilution with an oxygen-carrying hemodiluent may be beneficial in the treatment of ischemic strokes.

Animals↗
PubMed1988

Development of bronchiolar epithelium: time course of response to oxygen and recovery.

Hyperoxia (greater than 95% O2) reversibly suppresses the early postnatal development of rat bronchiolar epithelium. We now show that blunting of the normal increase in nuclear numerical density per centimeter cubed of Clara and ciliated cells becomes apparent within 24 h of exposure to O2 (age 2 days) and reaches a maximum on the last day of hyperoxia (age 7 days). The intergroup differences began to disappear within 48 h after removal from O2. During air breathing, Clara cell mitosis increased sixfold between the ages of 1 and 2 days and returned to day 1 values by age 7 days. During O2 breathing, Clara cell mitosis increased threefold between age 1 and 2 days, returned to day 1 values by day 4, but exhibited a second peak 24 h post-O2 (day 8) not present in unexposed pups. The onset of differences in the volume of Clara cell organelles and glycogen was variable, but the differences were partly or completely eliminated 48 h post-O2 exposure. We conclude hyperoxia reversibly impairs mitosis by Clara cells.

Animals↗
PubMed1988

Postnatal undernutrition slows development of bronchiolar epithelium in rats.

The lung's small conducting airways are sites of dysfunction early in the course of chronic lung diseases that are prevalent in humans; furthermore, there is evidence that aspects of childhood environment may adversely influence small airway function in adulthood. Because there is considerable early postnatal morphological maturation of the bronchiolar epithelium in rats, these considerations led to the present study in which we assessed the effect of early postnatal undernutrition in rats on the anatomic development of the bronchiolar epithelium. We found undernutrition, produced by increasing rat litter size shortly after birth, led to delayed development of the mitochondria and rough endoplasmic reticulum of bronchiolar Clara cells. Of particular interest, underfeeding resulted in considerably diminished mitosis by Clara cells, decreased nuclear numerical density of bronchiolar ciliated cells, evidence of diminished conversion of Clara cells to ciliated cells, and an abnormal cellular composition of the small airway epithelium that persisted well beyond the period of underfeeding. We conclude that early neonatal events can have long-term effects on the bronchiolar epithelium.

Aging↗
PubMed1986

Biogenesis and cell cycle relationship of poly(A)- actin mRNA in mouse ascites cells.

A variety of rapidly growing mammalian cells contain a substantial portion of their actin mRNA in a poly(A)- form. We have used DNA-driven hybridization of a cloned actin cDNA-containing plasmid with pulse-labeled RNA from mouse S-180 ascites cells to examine newly synthesized actin mRNA. Our results indicate that the same proportion of newly synthesized and steady-state actin mRNA (approx. 40%) exists in a poly(A)- deficient form. This suggests that the poly(A)- form arises by some process other than slow cytoplasmic de-adenylation of a poly(A)+ precursor. We have also examined cell cycle-enriched populations of S-180 ascites cells for the presence of poly(A)- actin mRNA. Results from these experiments indicate that cells in G1 phase of the cell cycle contain predominantly poly(A)+ actin mRNA, while the poly(A)- form is restricted to late-S and post-S phase cells.

Actins↗
PubMed1986

Hyperoxia reversibly suppresses development of bronchiolar epithelium.

The bronchiolar epithelium of rats is anatomically immature at birth. We now ask whether postnatal hyperoxia impairs the normal development of bronchiolar epithelium; and, if development is impaired, is the impairment permanent? To answer these questions, we exposed newborn rats to hyperoxia (greater than 95% O2, 1 atm) or air for 7 days and killed the rats at age 7 or 30 days. We used ultrastructural and morphometric means to assess maturation of the bronchiolar epithelium. Hyperoxia substantially diminished the postnatal increase in nuclear numerical density of bronchiolar Clara cells and ciliated cells. Hyperoxia also markedly delayed the rise in volume density of Clara cell secretory granules and rough endoplasmic reticulum but accelerated the increase in volume density of Clara and ciliated cell mitochondria. When rats exposed to hyperoxia from age 1 to 7 days were thereafter allowed to breathe air, by age 30 days all the differences were eliminated that were detected between the air- and O2-breathing groups at age 7 days. We conclude hyperoxia causes a marked but nonpermanent suppression of maturation of the bronchiolar epithelium.

Aging↗
PubMed1985

Determination of fezolamine and its desmethyl metabolite in human plasma and urine by high-performance liquid chromatography. Intravenous pharmacokinetics in the beagle hound.

Sensitive and selective high-performance liquid chromatographic methods for the quantitation of the experimental antidepressant fezolamine and its desmethyl metabolite in plasma and urine have been developed. Both assays are linear between 0 and 500 ng/ml in both plasma and urine and have calculated minimum quantifiable levels of less than 10 ng/ml. Statistical evaluation of analytical parameters under single-blind conditions demonstrated an overall precision within +/- 4% of nominal for both compounds in either biological medium. The overall accuracies of the assays were within +/- 5% of nominal values in urine and +/- 10% of nominal values in plasma. Following intravenous administration of fezolamine fumarate to beagle hounds, a biexponential decline in drug plasma levels was observed with the first phase having a half-life of about 11 min and the second phase about 2.6 h. Peak plasma levels of the metabolite were observed at 2 h. Recovery of the parent drug in urine was less than 5% of the administered dose and less than 1% for the desmethyl metabolite.

Animals↗