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Biomedical subjects

M J Hayes

Publications and source records attributed to M J Hayes.

At least 37 records · Page 2Linked to original sources

Chemical stress relaxation of polyglycolic acid suture.

Chemical stress relaxation methods are employed to study chemical and mechanical factors influencing the degradation of uncoated polyglycolic (PG) sutures. Specially constructed instrumentation is used to study the kinetics of the load bearing capability of PG (Dexon¿) 3-0 sutures in hydrolytic solution. The effects of pH, temperature, strain rate, and initial load on the rate of chemical stress relaxation are presented. Data show how mechanical factors such as the rate of loading (related to the speed of knot tying), as well as the final tension, are related to the rate of structural degradation. Maximum stability is observed at approximately 40 degrees C, with slower degradation both above and below this point. Results show that the slower and tighter the suture is pulled, the greater its ability to sustain tensile loads during hydrolysis.

Biodegradation, Environmental↗

Neonatal desipramine treatment alters free-running circadian drinking rhythms in rats.

Neonatal treatment with monoamine reuptake inhibitors results in a constellation of neurobehavioral alterations in adult rats that may model human depression. Since alterations in circadian rhythmicity have been reported in both depressed patients and in animal depression models, the present study examined the effects of neonatal desipramine treatment (5.0 mg/kg SC from postnatal day 7 through 22) on free-running circadian drinking rhythms. Rhythmicity was examined in constant darkness (DD), constant light (LL), and during adult desipramine treatment (0.25 mg/ml via the drinking water). Compared with saline-treated controls, neonatal desipramine lengthened free-running period in DD, blunted the period-altering effect of LL, and potentiated the period-altering effect of adult desipramine treatment. Neonatal desipramine treatment also increased circadian amplitude and spectral magnitude, but did not modify the effects of light or adult desipramine on these parameters. These results provide further evidence that behavioral depression is associated with alterations in circadian rhythmicity, and are consistent with the hypothesis that such relationships are mediated by brain monoaminergic systems.

Alcohol Drinking↗

Pneumocystis carinii pneumonia after liver transplantation in adults.

Proven Pneumocystis carinii pneumonia (PCP) occurred in 8 (5.2%) of 154 adult liver transplant recipients between January 1986 and December 1992. The interval between transplantation and PCP ranged from 69 to 131 days with a mean of 95 days (SD 20 days). The PaO2 breathing room air at diagnosis ranged from 40 mmHg to 75 mmHg with a mean of 59.6 mmhg (SD 13 mmHg). Bronchial washings taken at bronchoscopy stained positively for Pneumocystis carinii and confirmed the diagnosis. Transbronchial biopsy was unnecessary for diagnosis. One patient died from PCP while the remainder recovered. Patients transplanted immediately before the index patients served as controls. Patients who developed PCP had more episodes of rejection (p < 0.05), received more OKT3 (p < 0.05), and were receiving more prednisone (p < 0.05) than controls. They also had lower levels of albumin (p < 0.01), and higher levels of alkaline phosphatase (p < 0.05), alanine (p < 0.01), and aspartate aminotransferase (p < 0.001), and gamma-glutamyltranspeptidase (p < 0.02). This study raises the possibility of selecting patients at risk of PCP for chemoprophylaxis.

Adult↗

Spontaneous motility in premature infants: features of behavioral activity and rhythmic organization.

The spontaneous motor activity of clinically stable premature infants, 26-36 weeks gestational age, was investigated. Movements were recorded using a pressure-sensitive transducer positioned below the infant's head and torso. Behavior samples were digitized every 0.5 s during 2 and 3-hr continuous recording sessions. Time-series analyses revealed prominent motility cycles of circa 80 min and circa 30 min. These results are consistent with periodicities in motility and REM activation observed in full-term neonates. The longer rhythms of 70-100 min of motility found in this study establish that these periods are present at this stage of development independent of maternal zeitgebers. Developmental changes in motility rhythms and movement burst durations were also observed. Bout durations became somewhat longer in older (> 30 weeks) infants, but the relative time devoted to movement per session was comparable in older and younger (< or = 30 weeks) infants.

Age Factors↗

The metabolism of CGS 15873 in man using stable isotope pattern recognition techniques.

CGS 15873 is a relatively specific dopamine agonist with preferential activity at the presynaptic autoreceptor and therefore may represent a novel agent for the treatment of schizophrenia and/or Parkinson's disease. Several metabolites have been identified in the rat and monkey using an isotopically enriched dosing solution and pattern recognition techniques coupled with GC/MS and LC/MS. In this study, the metabolism of CGS 15873 was investigated in man using these same techniques. In urine, specific isotope clusters were found that matched the dosing solution pattern. Three metabolites were identified: an O-glucuronide conjugate of the parent drug, N-despropyl CGS 15873, and a keto metabolite of CGS 15873. Thermospray LC/MS allowed for the direct confirmation of the conjugated metabolite. GC/MS required derivatization but afforded greater sensitivity compared to LC/MS.

Adult↗

Quantitative determination of arecoline in plasma by gas chromatography chemical ionization mass spectrometry.

A capillary gas chromatography/mass spectrometry (GC/MS) method for the quantitative analysis of arecoline in plasma has been developed for concentrations in the range 1-50 ng ml-1. Hexadeuterated arecoline was utilized as the internal standard. The removal of drug from plasma was accomplished by a two-step liquid/liquid extraction procedure involving a wash step followed by extraction with 5% triethyl amine in ethyl acetate. The GC/MS determinations were carried out with temperature-programmed capillary GC and ammonia chemical ionization mass spectrometry. The [M + H]+ ions of both analyte and internal standard were monitored at m/z 156 and 162, respectively. The method is linear and has sufficient sensitivity, precision, accuracy and selectivity for analysis of drug levels in human plasma.

Arecoline↗

Trial of early nifedipine in acute myocardial infarction: the Trent study.

Over 30 months 9292 consecutive patients admitted to nine coronary care units with suspected myocardial infarction were considered for admission to a randomised double blind study comparing the effect on mortality of nifedipine 10 mg four times a day with that of placebo. Among the 4801 patients excluded from the study the overall one month fatality rate was 18.2% and the one month fatality rate in those with definite myocardial infarction 26.8%. A total of 4491 patients fulfilled the entry criteria and were randomly allocated to nifedipine or placebo immediately after assessment in the coronary care unit. Roughly 64% of patients in both treatment groups sustained an acute myocardial infarction. The overall one month fatality rates were 6.3% in the placebo treated group and 6.7% in the nifedipine treated group. Most of the deaths occurred in patients with an in hospital diagnosis of myocardial infarction, and their one month fatality rates were 9.3% for the placebo group and 10.2% for the nifedipine group. These differences were not statistically significant. Subgroup analysis also did not suggest any particular group of patients with suspected acute myocardial infarction who might benefit from early nifedipine treatment in the dose studied.

Adolescent↗

Rapidly developing tolerance to transdermal nitroglycerin in congestive heart failure.

We have reported early attenuation of hemodynamic effects of transdermal nitroglycerin in patients with heart failure. We now report nitroglycerin plasma levels in those same patients. We administered transdermal nitroglycerin, 60 mg/24 h, to eight patients or placebo to seven patients in a double-blind fashion, and monitored pulmonary wedge pressure and nitroglycerin plasma levels for 24 hours. After placebo administration, nitroglycerin plasma levels and pulmonary wedge pressure remained unchanged. During transdermal nitroglycerin administration, the plasma nitroglycerin level rose from 0.04 +/- 0.12 ng/mL at baseline to near peak levels at 2 hours (7.43 +/- 7.21 ng/mL). Between 2 and 24 hours, levels fluctuated at a steady state. Pulmonary wedge pressure fell from 22 +/- 7 mm Hg at control to a nadir of 14 +/- 5 mm Hg at 4 hours (p less than 0.01). Despite persistently high plasma nitroglycerin levels, by 18 hours pulmonary wedge pressure was no longer significantly reduced (20 +/- 9 mm Hg). These results indicate that rapid development of tolerance is the cause of attenuated hemodynamic efficacy of transdermal nitroglycerin.

Administration, Topical↗

Isolation and structural identification of 1,25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis.

Hypercalcemia and hypercalciuria in sarcoidosis are thought to result from the endogenous overproduction of an active vitamin D metabolite. We employed primary cultures of pulmonary alveolar macrophages from two patients with biopsy-proven pulmonary sarcoidosis and a recent or current clinical abnormality in calcium metabolism to synthesize in vitro a 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-like metabolite from 25-hydroxyvitamin D3 (25OHD3). The macrophage metabolite cochromatographed with [3H]1,25-(OH)2D3 on normal phase and reverse phase high performance liquid chromatography and was bound with high affinity by the chick intestinal receptor for 1,25-(OH)2D3. On UV spectroscopy, the metabolite possessed the carbon-5,7,10 (19) cis-triene chromophore characteristic of a vitamin D sterol. Electron impact mass spectrometry of trimethylsilyl ether derivatives of the metabolite revealed a mass fragmentation pattern similar to that of the trimethylsilyl ether derivative of authentic 1,25-(OH)2D3. The incubation of cultured macrophages from two patients with idiopathic pulmonary fibrosis and two with scleroderma with [3H]25OHD3 did not result in production of a metabolite with the chromatographic identity of 1,25-(OH)2D3. These data indicate that the metabolite of 25OHD3 synthesized by sarcoid macrophages in vitro is 1,25-(OH)2D3 and that the macrophage is a synthetic source of the sterol metabolite in sarcoidosis.

Adult↗

Gas chromatography-mass spectrometry characteristics of methylated perfluoroacyl derivatives of cytosine and 5-methylcytosine.

Pentafluorobenzoyl and heptafluorobutyryl derivatives of cytosine and pentafluorobenzoyl-5-methylcytosine have been examined by mass spectrometry following permethylation. Electron impact mass spectra were used to confirm the structures of the derivatives. The permethylated pentafluorobenzoyl derivatives of cytosine and 5-methylcytosine are sensitive for quantitative analysis by capillary gas chromatography-mass spectrometry. Under negative ion chemical ionization conditions 1 femtogram of each is detected.

5-Methylcytosine↗

Saliva as a chemical cue in the development of social behavior.

Throughout development, Mongolian gerbils engage in conspicuous naso-oral investigations of their social partners' mouth areas. The behavioral contribution of saliva-related stimuli in regulating oral-directed responses was studied during several important phases of the gerbil's social life. Weanlings were preferentially attracted to their mother's saliva, subadults at puberty preferred saliva of littermates to that of nonlittermates, and sexually experienced males preferred the saliva of estrous females to that of nonestrous females. The use of saliva as a discriminative cue during various developmental periods suggests that oral chemostimuli have a perennial role in regulating social interchanges.

Animals↗

Immediate and latent effects induced by the antiallatotropin precocene 2(P2) on embryonic Dermacentor variabilis (Say) (Acari: Ixodidae).

Fumigation of eggs with the antiallatotropin precocene 2(P2) disrupted development late in embryogenesis in the American dog tick Dermacentor variabilis. An age (time) gradient of responses in embryos was noted. Subsequent developmental effects included partial failure of stadia to attach, feed, ecdyse and partial-to-complete sterility in adult females. No precocious metamorphosis or adultiformes were observed, but a change in sex ratio of surviving adults was noted. A subsequent application of juvenile hormone 3 (JH 3) to P2-sterilized females enabled them to feed and successfully complete the gonadotrophic cycle. Restoration of gonadotrophic function by exogenous JH 3 suggested the possibility of a naturally occurring JH in D. variabilis.

Animals↗

Randomised trial comparing buprenorphine and diamorphine for chest pain in suspected myocardial infarction.

Buprenorphine, a new powerful analgesic agent, was used to treat chest pain in patients with suspected myocardial infarction. Initial studies showed no significant changes in systemic or pulmonary artery blood pressure or in heart rate after intravenous buprenorphine. Sublingual buprenorphine also appeared effective in relieving pain, but its onset of action was considerably delayed compared with the intravenous route. A randomised double-blind controlled trial of equivalent doses of buprenorphine and diamorphine showed no significant difference between the drugs in terms of pain relief and duration of action. The occurrence of nausea, vomiting, and other side effects was similar in the two groups. The onset of action of buprenorphine was slightly but significantly slower than that of diamorphine. Since buprenorphine seems to be comparable with diamorphine in action and is not a controlled drug, it may prove useful in both general and hospital practice.

Buprenorphine↗

Chemoimmunotherapy of cancer. 3. Analytical measurement of chemical half-lives of monofunctional alkylators.

The objective of this study is the measurement of the rates of hydrolysis of a series of chloroethyl sulfide derivatives, under stimulated physiological conditions. Interferences encountered with the conventional spectrophotometric method prompted the use of a rapid-response, chloride selective electrode. This probe was readily capable of monitoring the hydrolytic rate, which is identical with the rate of chloride ion formation. Since the desired subsecond half-lives were not achieved by any of the compounds, factors influencing the rates were investigated. The results suggest that the rate-controlling cyclization step may be inhibited, due to coordination of undissociated protonic functional groups on the aromatic portions of the structures with the lone-pair electrons on sulfur.

Chemical Phenomena↗

Changes in the plasma clearance and protein binding of carbenoxolone with age, and their possible relationship with adverse drug effects.

Comparison by equilibrium dialysis of plasma protein binding sites for carbenoxolone in people under 40 years of age and in people over 65 years of age showed that the number of binding sites was reduced in the elderly and that this fall was associated with a reduction in plasma albumin levels. Although carbenoxolone has some aldosterone-like effects, these properties could not be shown to be due to displacement of aldosterone from its protein binding sites by competitive protein binding of carbenoxolone. Single doses of carbenoxolone were found to be removed considerably more slowly from the plasma of elderly individuals than from the young. The results of these three series of experiments suggest that the side-effects of carbenoxolone in the elderly may in part be caused by reduced protein binding, leaving more free drug in the active unbound form, and in part by reduced hepatic clearance mechanisms.

Adult↗