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Biomedical subjects

D L Murray

Publications and source records attributed to D L Murray.

At least 19 recordsLinked to original sources

Screening maternal serum alpha-fetoprotein levels and human parvovirus antibodies.

The association between gestational infection with human parvovirus (B19) and fetal loss has increased interest in this virus and demand for diagnostic testing. However, serological assays for B19 are not yet widely available. Maternal serum alpha-fetoprotein (MSAFP) testing is commonly used during the second trimester to screen for various fetal defects. We attempted to determine whether an elevated level of MSAFP would be an appropriate indication for B19-specific tests. Over a 26-month period, MSAFP tests were performed at Michigan State University for 21 392 women. Sera remaining after that testing were stored frozen. Of these, 22 cases samples--from women with MSAFP levels greater than 3.0 multiples of the median (MOM) and pregnancies that ended in fetal loss--and 44 matched control samples--from women with MSAFP levels greater than 0.4 and less than 2.2 MOM and live births at term--were tested for B19 antibodies. None of the 66 samples was IgM positive, while 33 (50 per cent) were IgG positive. The presence of IgG was not significantly associated with case or control status (matched odds ratio = 0.77, 95 per cent confidence interval 0.28-2.11). These findings are consistent with other studies indicating prior infection in approximately half of adults and suggest that elevated screening MSAFP levels, in the absence of other evidence of B19 infection, should not prompt B19-specific testing.

Adult

Hazards of closed pesticide mixing and loading systems: the paradox of protective technology in the Third World.

In studies in developing countries, closed systems for mechanically mixing and loading hazardous pesticides have been shown to reduce exposure to workers. To evaluate the efficacy of closed systems in preventing worker exposure in the developing world, a cross sectional study was conducted at rural crop dusting airports in the cotton growing region of Nicaragua. Worker exposure was evaluated by measuring the activity of erythrocyte cholinesterase in the field with a new design battery operated colorimeter. The 10 mixer loaders at four airstrips with closed systems were compared with the 16 mixer loaders at four airstrips where pesticides were hand poured. Paradoxically, cholinesterase activity was 1.1 IU/ml blood (95% Cl 0.49-1.8) lower (inhibited) among workers in airstrips with closed systems than among workers hand pouring insecticides, after adjusting for weight of organophosphates sprayed in the past 14 days, and for prior training in safe use of pesticides. Mixer loaders with prior training had cholinesterase activity 0.83 IU (95% Cl 0.30-1.4) higher than untrained workers, and the weight of organophosphates sprayed was also a statistically significant predictor in the model. Unfortunately, management viewed the closed systems primarily as a production tool, rather than as a way to protect workers. Airstrips with closed systems were able to apply an average of 3250 lb organophosphates per worker in the 14 days before the survey compared with 849 lb per worker in airstrips without closed systems. Only three of 10 mixer-loaders at airstrips with closed systems had received formal training in safer use of pesticides. Because of shortage of personnel and transport, it was difficult for the responsible government agencies to train workers adequately and to enforce pesticide health and safety standards at multiple dispersed worksites.

Cholinesterase Inhibitors

Chloroplasts of Arabidopsis thaliana homozygous for the ch-1 locus lack chlorophyll b, lack stable LHCPII and have stacked thylakoids.

We are interested in the mechanism of insertion of proteins into the chloroplast thylakoid membrane and the role that accessory pigments may play in this process. For this reason we have begun a molecular analysis of mutant plants deficient in pigments that associate with thylakoid membrane proteins. We have characterized plants that are homozygous for the previously isolated, recessive mutation chlorina-1 (ch-1) of Arabidopsis thaliana. Despite the lack of chlorophyll b and light-harvesting proteins of photosystem II (LHCPII) near normal levels of LHCPII mRNA are found in the mutant, in contrast to LHCPII mRNA levels in carotenoid-deficient mutants. The LHCPII mRNA of chlorina-1 plants can be translated in vitro so it is likely that LHCPII is not stable in ch-1 plants. Moreover, the thylakoid membranes of ch-1 plants remain appressed even though LHCPII levels are drastically reduced.

Chlorophyll

Age-related cysteine uptake as rate-limiting in glutathione synthesis and glutathione half-life in the cultured human lens.

The study included human lenses of ages ranging from newborn to 92 years. Protein-free reduced glutathione decreased 14-fold, whereas protein-free oxidized glutathione increased 2.6-fold with increasing age. L-Cyst(e)ine uptake g-1 lens of very old cultured lenses decreased 70% from that exhibited in newborn lenses, demonstrating a marked decline of L-cyst(e)ine uptake as a function of age. In these same lenses the synthesis of reduced glutathione (mumol g-1 lens) decreased 73% with age. It was concluded that the glutathione decrease observed in the aging human lens was associated with decreased uptake of L-cyst(e)ine, decreased glutathione synthesis and possibly an increase in protein-free oxidized glutathione. The high correlation of L-cyst(e)ine uptake and glutathione synthesis supports the hypothesis that L-cyst(e)ine uptake is a rate-limiting factor of glutathione synthesis in the intact human lens. By the use of buthionine sulfoximine, the half-life of glutathione was estimated to be 90 hr in the cultured human lens.

Adolescent

Preretinal pH changes in the rabbit under conditions of light and dark.

Preretinal pH was measured in the avascular region of 19 rabbit retinas during alternating cycles of light and dark, using a miniature, needle-type pH electrode. In 14 experiments with the rabbits breathing room air, cyclic changes in pH, decreasing in the dark and increasing in the light, were observed. The transition from light to dark caused a mean pH decrease of 0.047 +/- 0.029 U (n = 14). An inversion of the light/dark pH response was observed in five experiments. In three of these, the effect was induced by having the rabbits breathe 100% O2. In the five rabbits showing a reversed response, a mean pH increase of 0.034 +/- 0.025 pH U was observed in the dark; light-ON caused a decrease of 0.035 +/- 0.025 pH U. The direction of the preretinal pH change is thought to be the net effect of light/dark-induced changes in the metabolism of the photoreceptors and inner retinal layers (defined for the purpose of this paper as the region between the outer synaptic layer and the inner limiting membrane). In six separate experiments, retinal metabolism was assessed by measuring preretinal PO2 during alternating cycles of light and dark while the rabbits breathed room air. Oxygen tension declined from a mean of 14.5 +/- 6.2 (S.D.) mmHg in the light to 10.1 +/- 5.4 (S.D.) mmHg in darkness, and increased from a mean of 10.9 +/- 5.1 (S.D.) mmHg in darkness to 15.4 +/- 5.8 (S.D.) mmHg in the light. The time courses of the pH and the PO2 changes were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of timolol on human retinal, choroidal and optic nerve head circulation.

In a double-masked, randomized, placebo-controlled study, we evaluated the effect of topical timolol maleate 0.5% on the retinal, choroidal, and optic nerve head circulation in 5 healthy volunteer subjects. Changes in the pulsatile component of choroidal blood flow (PCBF) were determined from measurements of the ocular pulse wave. Changes in the retinal arterial blood flow rate (RBF) and optic nerve head capillary blood speed (CBS) were determined by laser Doppler velocimetry and monochromatic photography. In timolol-treated eyes, PCBF decreased by 32 +/- 12% (p = 0.0007). Changes in RBF and CBS were not statistically significant. In the contralateral placebo-treated eyes, PCBF decreased by 15 +/- 8% (p = 0.006) and RBF increased by 18 +/- 10% (p = 0.002). The change in CBS was not statistically significant.

Administration, Topical

Triage decisions in child care for sick children.

Child-care centers for children with mild, acute communicable, and noncommunicable illnesses are beginning to evolve. Few states have enacted regulations concerning the policies and procedures under which child-care centers for sick children operate. These centers should have policies regarding the triage and care of ill children that promote the safety of all children and staff at the center. As part of the establishment of regulations for the Michigan Department of Social Services, Lansing, a triage model has been developed that provides a means of standardizing the screening process used to admit mildly ill children to such centers. We present pilot guidelines for use by center personnel, discuss considerations inherent in formulating triage policy for child-care centers for sick children, and provide a starting point for those attempting to standardize regulations governing child-care centers for sick children.

Child Day Care Centers

Cysteine and glutathione metabolism in organ-cultured rat corneas.

The capability of organ-cultured rat corneas to metabolize cysteine and synthesize glutathione was assessed by use of radioactive L-cyst(e)ine. Metabolites from protein-free tissue extracts were separated and quantified by HPLC, using radioisotope and ultraviolet detectors. Most of the radioactivity detected in the rat cornea was found in three areas of the HPLC elution profile: 1) reduced glutathione, 2) cystine and 3) in a rapidly eluting area (the 'five-minute' area) consisting of several unidentified peaks. The proportion of radioactivity found within the five-minute area increased with time of incubation and became the dominant radioactive peak area by 48 hours of incubation. In contrast to rat lens extracts, the synthesis of glutathione in rat cornea formed a minor portion of the L-cysteine metabolic products. The unlabeled reduced glutathione concentration was relatively stable over a 48-hour incubation period. Synthesis of glutathione was prevented by 0.3 mM buthionine sulfoximine, resulting in more than 90% of the radioactivity being contained in the five-minute peak area. Inhibition of glutathione synthesis allowed the estimation of glutathione's half-life to approximate 10.5 hours in the organ-cultured rat cornea.

Animals

Glutathione synthesis and glutathione redox pathways in naphthalene cataract of the rat.

This investigation examined many parameters during the course of early development of naphthalene-induced cataract in a time span of 0 to 79 days of treatment. Feeding naphthalene daily to Black-Hooded rats resulted in gradual progressive development of cataract. The first faint opacities were detectable after 7 days. Free soluble total glutathione (oxidized and reduced) of these lenses was shown to gradually decrease to a maximum loss of about 20%, a value reached by day 30 of treatment. No activity loss of either enzyme required for glutathione synthesis (gamma-glutamylcysteine synthetase or glutathione synthetase) was observed in homogenates of naphthalene versus control lenses. There was also neither impairment of [35S]-L-cystine uptake nor of [35S]-glutathione synthetic capacity in lenses cultured from rats after 12, 24 or 36 days of naphthalene feeding when compared to control lenses. Hence, glutathione loss cannot be explained by a damaged glutathione synthesis system. Progressive activity loss of glutathione peroxidase and glutathione reductase was observed. The loss of glutathione peroxidase activity was especially remarkable. Thus, the defense system against oxidative damage is impaired and may be a significant factor in naphthalene-induced cataract of the rat.

Animals

Conditions for maximizing and inhibiting synthesis of glutathione in cultured rat lenses: an application of HPLC with radioisotope detection.

This investigation was concerned with factors which would maximize and inhibit L-cyst(e)ine uptake and glutathione synthesis of rat lenses cultured for 24 hours in a medium containing [35S]-L-cystine. The lenticular protein-free extract was separated and quantified by use of HPLC equipment which included an in-line radioisotope detector coupled with extensive post-run computer analysis. Six thiols were assessed for their ability to increase the uptake of L-cyst(e)ine and its utilization for glutathione synthesis. The most successful was 2-mercaptoethanol, which increased the L-cyst(e)ine uptake 3.6-fold and glutathione synthesis 2.9-fold. This work demonstrated that the rate of glutathione synthesis was directly proportional to the rate of uptake of L-cyst(e)ine. An inhibitor of glutathione synthesis, buthionine sulfoximine, in a concentration range of 0.11-3 mM, decreased uptake of the [35S]-label by one-third. The 3.0 mM concentration inhibited glutathione synthesis 98.7% and decreased glutathione 51% in 24 hours. The data indicate that half the glutathione disappeared in 23 hours in these cultured rat lenses. Because determination of this value did not depend upon the variable rate of cysteine transport, the value may approximate the in vivo value.

Animals

Oral clomiphene citrate and vaginal progesterone suppositories in the treatment of luteal phase dysfunction: a comparative study.

Oral clomiphene citrate (CC) and vaginal progesterone suppositories (PS) are common treatment modalities in luteal phase dysfunction (LPD). Little is known regarding the relative efficacy of these agents. To study the use of CC and PS in the management of LPD, a retrospective cohort study of patients presenting with infertility was undertaken. Sixty-five patients in whom LPD was diagnosed and corrected, as judged by endometrial biopsies, were studied; 35 were treated with PS and 30 with CC. Using Student's t-tests and chi-square analyses, the two treatment groups were demographically comparable. Using life-table analysis, no one therapeutic approach proved superior. Clomiphene citrate and PS are comparable treatment modalities in the setting of LPD given correction of endometrial lag.

Administration, Oral

Comparative study of cephalexin hydrochloride and cephalexin monohydrate in the treatment of skin and soft tissue infections.

In two prospective, randomized multicenter double-blind studies with a dosage of either 250 mg given four times a day (study A) or 500 mg given two times a day (study B), the comparative efficacy and safety of cephalexin hydrochloride (LY061188; Keftab) and cephalexin monohydrate (Keflex) for treatment of skin and soft tissue infections were determined. In study A, 97 patients received cephalexin hydrochloride and 101 patients received cephalexin monohydrate. In study B, 75 patients received cephalexin hydrochloride and 70 patients received cephalexin monohydrate. Diagnoses included abscesses, cellulitis, wound infections, and infected dermatitis, and were comparable in the different treatment groups. Pathogens were isolated from 82% of patients enrolled; the majority of isolates were of Staphylococcus aureus, Streptococcus pyogenes, other staphylococcal species, and a few gram-negative bacteria. In study A, 68 of 71 (95.7%) evaluable patients who received cephalexin hydrochloride responded satisfactorily; 73 of 81 (90%) patients who received cephalexin monohydrate also responded satisfactorily. In study B, 56 of 58 (96.5%) evaluable patients who received cephalexin hydrochloride responded satisfactorily; 47 of 50 (94%) patients who received cephalexin monohydrate also responded satisfactorily. An adverse clinical event leading to discontinuation of the treatment drug developed in 17 of 343 (4.95%) patients in both studies. No differences were noted between the two drugs. Skin eruptions, pruritus, and mild gastrointestinal symptoms were the common adverse effects. These data suggest that cephalexin hydrochloride, a new formulation of cephalexin, is a safe and effective antimicrobial agent for treatment of a variety of skin and subcutaneous infections in a dosage of either 250 mg four times a day or 500 mg twice a day.

Adult

Determination of immune status to measles, rubella, and varicella-zoster viruses among medical students: assessment of historical information.

We examined the serological susceptibility of entering medical students to measles, rubella, and varicella-zoster (VZV) viruses over a four-year period. Serological results were then compared to historical information to ascertain whether undocumented histories of disease or vaccination could be used to identify students who may not need serological testing. For measles, historical information was of no benefit in predicting immunity. For VZV and, to a greater extent, rubella, a higher seropositive rate was seen in students claiming a positive history.

Antibodies, Viral