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Biomedical subjects

J Leggett

Publications and source records attributed to J Leggett.

15 recordsLinked to original sources
PubMed2001

Opioid and GABA receptors involved in mediation and modulation of tonic and stimulus-evoked inhibition of a spinal reflex in the decerebrated and spinalized rabbit.

The purposes of this study were to investigate: (i) the identity of the opioid peptide(s) mediating tonic and stimulus-evoked inhibition of the sural-medial gastrocnemius reflex of the decerebrated, spinalized rabbit and (ii) the modulation of these processes by endogenous GABA. The selective delta receptor antagonist naltrindole (100 nmol kg(-1) i.v.), the GABA(A) blocker bicuculline (300 nmol intrathecal, i.th.), and the GABA(B) antagonist CGP 35348 (1 micromol i.th.) increased gastrocnemius reflexes to 150-160% of pre-drug values, whereas a sub-maximal dose of naloxone (30 nmol kg(-1) i.v.) augmented reflexes to >500% of controls. Kelatorphan, an inhibitor of enkephalin metabolism (2 micromol i.th.), depressed gastrocnemius responses by 50% and potentiated the inhibitory effects of methionine enkephalin. Repetitive electrical stimulation of the superficial or common peroneal nerves inhibited reflexes for 15-20 min. This effect was significantly reduced by naltrindole and CGP 35348. It was not reduced by a low dose (30 nmol kg(-1) i.v.) of naloxone or by bicuculline. When naloxone and naltrindole were combined at 30 nmol kg(-1) each, stimulus-evoked inhibition was blocked. Given after bicuculline, naloxone at 100 nmol kg(-1) i.v. abolished peroneal-evoked inhibition, but a dose of 300 nmol kg(-1) was required to produce the same effect after CGP 35348. Kelatorphan augmented the depth and duration of inhibition evoked by peroneal nerve stimulation. These data are consistent with the involvement of enkephalin-like peptides in tonic and stimulus-evoked inhibition of the sural-gastrocnemius reflex. Tonic inhibition in rabbit spinal cord is dominated by opioids acting through mu receptors, whereas co-activation of delta, mu and GABA(B) receptors mediates stimulus-evoked inhibition. It is possible that GABA(B) receptors inhibit the release of spinal opioids while simultaneously supporting their actions at post-synaptic targets.

Animals↗
PubMed1999

Validity of three measures of severity of AIDS for use in health services research studies.

Policy makers and hospital managers often use severity adjustments as a control for patient mix differences when evaluating outcomes of care. Unfortunately, few indices are carefully examined and therefore the evaluations based on these methods of severity adjustment are suspect. This paper examines the accuracy of three indices for measuring the severity of illness of AIDS patients. We examine the Diagnosis-Based Severity Index (DBSI), a modified version of DBSI referred to as MDBSI and the Composite Laboratory Index (CLI) in predicting survival of AIDS patients at one medical centre. We analysed the correlation between indices and months of survival. We also examined the percentage of variance in survival months explained by each index separately and together. Finally, we used survival analysis to examine whether DBSI classifies patients in groups with distinct patterns of survival. Only patients who had died were included in the analysis so that information on the patients' full course of illness was available. Of the 91 patients abstracted, 81 cases had date of AIDS, date of death, and the CLI. These 81 cases were the focus of the analysis. Both CLI and DBSI were predictive of months of survival but were not correlated to each other. Predictions of months of survival were improved if both indices were used together rather than separately. Survival analysis confirmed that patients classified by DBSI had distinctly different survival patterns. Each index measures different aspects of the severity of the patient's condition and when possible both indices should be used together. When laboratory data are not available, e.g. in Medicaid administrative files, the use of DBSI may be reasonable.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Reality of glove use and handwashing in a community hospital.

BACKGROUND: Since the advent of universal precautions and body substance isolation, few studies have examined the relationship between glove use and handwashing. METHODS: During a 5-month period in 1991, 477 structured observations were conducted on 19 patients care units at a community teaching hospital during each of three shifts. Patient care contacts were defined as either high level or low level according to potential for blood or body fluid contact. RESULTS: Health care workers were potentially exposed to body fluids (high-level contact) on 152 occasions. Eighty-eight percent of all high-level contacts were limited to the hands; 47% of these contacts occurred during the night shift. Handwashing occurred after 32% of high-level contacts. Health-care workers wore gloves in 57% of high-level contacts. Rates of handwashing and glove use varied markedly among patient care units. Correct handwashing (> or = 9 seconds) occurred after 20% of contacts when health care workers wore gloves but after only 3% of high-level contacts when gloves were not used (p = 0.004). CONCLUSIONS: Despite universal precautions or body substance isolation, educational efforts, and written policies, rates of handwashing and glove use are inadequate in cases of potential blood and body fluid contact. The perceived need for gloves may encourage handwashing.

Blood↗
PubMed1993

Correlation of tobramycin-induced inhibition of protein synthesis with postantibiotic effect in Escherichia coli.

Scant data exist on intracellular events during aminoglycoside-induced postantibiotic effect (PAE). We examined DNA, RNA, and protein syntheses after tobramycin exposure using [3H]thymidine, [14C]uracil, and [14C]alanine incorporation in a clinical Escherichia coli strain. Late-log-phase bacteria in oxygenated minimal salts medium at 37 degrees C were exposed to tobramycin (7.5 micrograms/ml) (twice the MIC) for 30 min. Tobramycin caused a kill of 2 log10 CFU/ml prior to drug removal by filtration and a 5-h PAE, measured by viable counts. Excess amounts of labelled precursors were added to tobramycin-exposed organisms during, immediately after, and at various intervals following exposure. In the presence of tobramycin, DNA, RNA, and protein syntheses were sequentially inhibited within 1 generation time. Following drug removal, both DNA and RNA syntheses promptly resumed, suggesting readily dissociable nonspecific binding to DNA and RNA. However, total protein synthesis did not resume until 4 h later. beta-Galactosidase activity, a measure of functional enzymatic protein synthesis, was also inhibited for 4 h after drug removal. Bacterium length, measured by confocal microscopy, increased during PAE. Two distinct populations eventually emerged: one that returned to control dimensions and one that remained excessively elongated by the end of PAE (2.5 microns versus 4.0 microns; P < 0.05). We hypothesize that only viable cells return to the control morphology. Flow cytometry showed enhanced DNA complexity during PAE, consistent with either impaired cellular protein synthesis in viable cells or perturbations in dying cells. In summary, duration of PAE correlated with inhibition of total and functional protein synthesis but not DNA or RNA synthesis.

Bacterial Proteins↗
PubMed1993

Quantum leap into continuous quality improvement.

Prior to a JCAHO accreditation visit, Southeast Georgia Regional Medical Center implemented a program for improved prevention and treatment of nosocomial pressure ulcers. Forms were developed for monitoring skin integrity and therapy beds were tried from a vendor, which also provided a computerized assessment tool. Results included 15 percent pressure ulcer prevention in addition to enhanced collaborative nursing practice.

Cross Infection↗
PubMed1991

Randomized controlled trial of prophylactic rifampin for peritoneal dialysis-related infections.

Staphylococcal infections are a major cause of catheter infections and peritonitis in peritoneal dialysis patients. Since catheter-related infections are associated with nasal carriage of Staphylococcus aureus in this population, we studied the effect of intermittent rifampin, an antibiotic known to decrease S aureus nasal carriage, on catheter-related infections and peritonitis. We randomly assigned 64 patients to receive either rifampin 300 mg twice daily for 5 days every 3 months or no treatment. The rifampin-treated patients had a significant delay in time to first catheter-related infection (P less than 0.015) and significantly fewer catheter-related infections overall (P less than 0.001). The catheter-related infection rate in rifampin-treated patients was .26 per patient-year versus .93 per patient-year in untreated patients. Multivariate analysis defined baseline colonization of nares or catheter exit-site and prior renal transplant as risk factors for catheter-related infections. There was no significant difference in peritonitis rates between groups, although the trend was for a delayed time to first episodes and fewer episodes in rifampin-treated patients. Adverse effects necessitated withdrawal of rifampin in four patients. We conclude that intermittent rifampin administration is effective in decreasing catheter-related infections in a peritoneal dialysis population.

Adult↗
PubMed1991

Factors affecting duration of in-vivo postantibiotic effect for aminoglycosides against gram-negative bacilli.

A murine thigh-infection model was used to determine the effect of certain host- and drug-related factors on the duration of the in-vivo postantibiotic effect (PAE) observed with aminoglycosides against Gram-negative bacilli. The role of neutrophils (PMNs), pharmacokinetics and variation among species and strains were studied. PAEs were quantitated after a single injection of gentamicin or amikacin. PAEs were several hours longer in normal mice than in neutropenic mice, in mice with renal impairment than in those with normal renal function, and with strains of Klebsiella pneumoniae than with strains of Escherichia coli, Serratia marcescens and Enterobacter cloacae. Among the 15 strains of Enterobacteriaceae studied, the duration of the in-vivo PAE did not correlate with MIC, duration of in-vitro PAE, and extent of in-vivo bactericidal activity. We conclude that prolonged PAEs are consistently observed in vivo with aminoglycosides against Enterobacteriaceae, and that this duration is enhanced in the presence of PMNs and by pharmacokinetic properties simulating those observed in humans.

Amikacin↗
PubMed1991

Correlation between in vitro and in vivo activity of antimicrobial agents against gram-negative bacilli in a murine infection model.

We studied the relationship between in vitro susceptibility tests (MICs, MBCs) and in vivo activity of tobramycin, pefloxacin, ceftazidime, and imipenem against 15 gram-negative bacilli from five different species in a murine thigh infection model. Complete dose-response curves were determined for each antimicrobial agent against each strain, and three parameters of in vivo activity were defined: maximal attainable antimicrobial effect (i.e., reduction in log10 CFU per thigh compared with untreated controls) at 24 h (Emax), total dose required to reach 50% of maximal effect (P50), and total dose required to achieve a bacteriostatic effect (static dose). Pefloxacin demonstrated the greatest Emax (P less than 0.05). Tobramycin was the most potent antimicrobial agent, as indicated by its having the lowest static dose/MIC ratio (P less than 0.002). Log10 P50s and static doses correlated significantly with log10 MICs or MBCs for the 15 strains of each antibiotic (P less than 0.01) except imipenem (P greater than 0.50). The greater potency of imipenem against the three Pseudomonas aeruginosa strains than against strains of the family Enterobacteriaceae (P less than 0.01) explained this lack of correlation. A longer duration of postantibiotic effect for imipenem against P. aeruginosa (P = 0.02) contributed to its increased potency against these strains. We conclude that in vitro susceptibility tests correlated well with in vivo activity in this animal model and that variations in potency among the four antimicrobial agents could be explained by differences in pharmacokinetics or pharmacodynamic activity.

Animals↗
PubMed1988

In vivo postantibiotic effect in a thigh infection in neutropenic mice.

The postantibiotic effect (PAE) is the suppression of bacterial growth that persists after limited exposure of organisms to antimicrobial agents. We demonstrated and standardized the in vivo PAE in a thigh infection model in neutropenic mice. Inhibitors of protein and nucleic acid synthesis induced PAEs of 1.4-7.5 h against aerobic gram-negative bacilli, whereas beta-lactam antibiotics did not induce significant PAEs. Against aerobic gram-positive cocci, cell wall-active agents and inhibitors of protein and nucleic acid synthesis induced PAEs of 1.2-7.1 h, except for penicillins, which did not induce PAEs against streptococci. With few exceptions the in vivo PAE correlated well with the PAE reported in prior in vitro studies. Residual drug in thigh tissue did not cause the PAE. Theoretically, the presence of a PAE may allow antimicrobial agents to be given more intermittently without organism regrowth after drug levels fall below the minimal inhibitory concentration.

Agranulocytosis↗
PubMed1988

Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model.

Current antimicrobial dosing regimens are designed to maintain active drug levels for most of the dosing interval and are based on 40-y-old observations. With use of numerous multiple-dosing regimens in an animal model, this study is the first to successfully minimize the interdependence between pharmacokinetic parameters and thereby determine, by stepwise multivariate regression analysis, that the time that serum levels exceeded the minimum inhibitory concentration (MIC) was the most significant parameter determining efficacy for beta-lactams and erythromycin against various pathogens, whereas the log area under the curve was the major parameter for aminoglycosides. Optimal dosing intervals were no greater than the time that serum levels exceeded the MIC plus the duration of the postantibiotic effect. Careful application of these concepts should allow other investigators to use more optimally dosed regimens than those previously used in preclinical trials and to design studies to improve on current dosing regimens for humans.

Animals↗
PubMed1978

Hypoglycemia: an overview.

Hypoglycemia was not described as a human clinical syndrome until exogenous insulin was discovered. Much of our current knowledge of the symptoms of hypoglycemia derived from the reactions of schizophrenics to insulin coma therapy in the late 1920's. The diagnosis of hypoglycemia cannot be made simply on the basis of a blood glucose level since many asymptomatic persons have levels below 50 mg/100 ml. The diagnosis should be made only if symptoms occur at the glucose nadir and are relieved by the administration of glucose. The most common organic cause of hypoglycemia is functioning islet-cell tumor. By far the most prevalent type of hypoglycemia is idiopathic (function), a condition whose pathophysiology is not understood and which has given rise to a popular lay "mythology."

Adenoma, Islet Cell↗