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Biomedical subjects

M L Murray

Publications and source records attributed to M L Murray.

At least 19 recordsLinked to original sources

Mycophenolate mofetil therapy for moderate to severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that can be refractory to topical and systemic corticosteroids, phototherapy, topical immunomodulators and systemic immunosuppressive drugs. Recent studies have shown promise for the use of mycophenolate mofetil (MMF) to treat recalcitrant AD. AIM: To assess the effectiveness and adverse effects of MMF used for moderate to severe AD in a university outpatient dermatology clinic. METHODS: A retrospective chart review of 20 patient charts was conducted for patient age, gender, duration of disease, prior therapies, concomitant therapy, clinical response and adverse side-effects. RESULTS: Of the 20 patients, 17 improved within 4 weeks of starting MMF therapy. Ten patients had disease remission and were subsequently able to discontinue MMF. Seven attained satisfactory control of their AD using MMF as maintenance therapy. Overall, MMF was well tolerated, with mild headaches, gastrointestinal complaints and fatigue as the commonest side-effects. During therapy, herpes zoster developed in four patients, Staphylococcus aureus cutaneous infections in two, and herpes simplex in one. One patient discontinued MMF because of insufficient control of pruritus. CONCLUSION: MMF can be rapidly effective and well tolerated in patients with moderate to severe AD resistant to conventional therapies. The limitations of this retrospective study include no control group and a lack of a standardized scoring index to assess improvement, and the concomitant use of adjuvant therapies makes the contribution of MMF alone difficult to assess. Larger controlled studies are needed.

Adult↗

Increased prescribing trends of paediatric psychotropic medications.

Psychotropic medication use by children in the USA has increased. We used the IMS MIDAS Prescribing Insights to examine prescribing trends in nine countries between the years 2000 and 2002. Trends in seven countries rose significantly from year 2000 to 2002; the UK had the highest increase (68%).

Adolescent↗

A drug utilisation study of antidepressants in children and adolescents using the General Practice Research Database.

AIMS: To characterise prescribing patterns of antidepressants (ATDs) to children and adolescents aged < or =18 years in the UK. METHODS: Subjects issued at least one ATD prescription between 1 January 1992 and 31 December 2001 were identified from the UK General Practice Research Database. Prescribing patterns, annual prevalence, morbidity patterns, and time to discontinuation of ATD use were identified. RESULTS: A total of 24,976 subjects received 93,091 prescriptions; 51,868 (55.7%), 38,429 (41.3%), and 2708 (2.9%) prescriptions were for tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and other ATDs respectively. ATD prevalence increased 1.7-fold from 1992 to 2001. TCA prevalence decreased by 30% from 3.6 to 2.5 per 1,000; SSRI prevalence increased 10 times from 0.5 to 4.6 per 1,000. In new ATD users aged < or =10 years, the most common diagnosis associated with TCA use was nocturnal enuresis (75.1%); in those aged > or =15 years, it was depression (45.8%). Depression was also associated with SSRI use (69.0%). For new users with depression, the median treatment durations for TCAs and SSRIs were 30 and 58 days respectively. TCA users were more likely to terminate treatment than SSRI users (TCAs v fluoxetine: 1.40, 95% CI 1.32 to 1.47; non-fluoxetine SSRIs v fluoxetine: 1.01, 95% CI 0.96 to 1.07). CONCLUSIONS: SSRIs have gained popularity for the treatment of depression compared with TCAs. TCAs are still used despite their lack of efficacy in prepubertal depression and their moderate effect in adolescents. However, >50% of subjects discontinue treatment after two months, with TCA users stopping earlier than SSRI users.

Adolescent↗

Self-esteem, social support, and satisfaction differences in women with adequate and inadequate prenatal care.

This descriptive, retrospective study examined levels of self-esteem, social support, and satisfaction with prenatal care in 193 low-risk postpartal women who obtained adequate and inadequate care. The participants were drawn from a regional medical center and university teaching hospital in New Mexico. A demographic questionnaire, the Coopersmith self-esteem inventory, the personal resource questionnaire part 2, and the prenatal care satisfaction inventory were used for data collection. Significant differences were found in the level of education, income, insurance, and ethnicity between women who received adequate prenatal care and those who received inadequate care. Women who were likely to seek either adequate or inadequate prenatal care were those whose total family income was $10,000 to $19,999 per year and high school graduates. Statistically significant differences were found in self-esteem, social support, and satisfaction between the two groups of women. Strategies to enhance self-esteem and social support have to be developed to reach women at risk for receiving inadequate prenatal care.

Adult↗

Estimation of long-term risk from Canadian uranium mill tailings.

A methodology is presented for assessing the risk from Canadian uranium mill tailings piles. The methodology is based on the "set of triplets" concept and uses an event tree to identify various scenarios representing the performance of a pile over its 1,000-year design life. Compartment-type mathematical models are used to quantify the movement of hazardous substances through the environment. Numerical examples are given of both "level 1" (straight probabilistic) and "level 2" (probability of frequency) type analyses.

Canada↗

Mutagenic activity from nitrosation of oligoamines.

To determine structural features necessary for the production of direct mutagenic activity from oligoamine-nitrate reaction mixtures, we systematically tested a group of aliphatic amine substrates for comutagenic action with nitrite. The ability to react with nitrite and form direct-acting mutagenic derivatives was common to a reasonably well defined class of aliphatic polyamines. In general, primary-secondary diamino compounds were mutagenic in the Ames Salmonella tester system when reacted with nitrite, whereas primary and secondary amines produced no direct mutagenic activity when tested separately. In combination with teritary amino groups, primary amines were inactive; one secondary-tertiary amine was tested, and this substrate produced mutagenic activity.

Diamines↗

Interaction of mutagenic spermidine-nitrous acid reaction products with uvr- and recA-dependent repair systems in Salmonella.

It has been observed previously that the mutagenic action of nitrous acid may be potentiated by polyamines. We examined the cellular response of two deoxyribonucleic acid repair systems to treatment with spermidine-nitrite reaction products. uvrB- deficient mutants of Salmonella typhimurium LT2 showed enhanced lethal and mutagenic response to the reaction products. Lethal activity was further enhanced in a uvrB recA double mutant, whereas mutagenic activity was not detectable. Dependence of mutagenesis on the recA gene implicates the action of an error-prone repair system in the fixation of a premutagenic lesion as a mutation. From consideration of the substrate characteristics of the two repair systems studied, it is suggested that the deoxyribonucleic acid lesion formed by the reaction products of spermidine and nitrite is an intrastrand cross-link.

DNA Repair↗

Substrate-specificity of uvr excision repair.

The substrate specificity of the uvr endonuclease, the product of the uvrA, uvrB, and uvrC genes is reviewed. It is suggested that the relatively well-defined substrate specificity of this repair enzyme is useful as a guide in determining the nature of the DNA-lesion caused by a given mutagen.

DNA Polymerase I↗

Effect of protein synthesis on plasmid maintenance in Streptococcus faecalis.

Plasmid-to-chromosome ratios in Enterobacteriaceae, upon interruption of protein synthesis by chloramphenicol, are either conserved or increased when measured by dye buoyant density centrifugation. We have found, on the other hand, that the effect of inhibition of protein synthesis on the amount of covalently closed circular deoxyribonucleic acid visualized by this method in two strains of Streptococcus faecalis appears to differ from these established systems. A three- to sixfold decrease in covalently closed circular deoxyribonucleic acid was observed when lysates of chloramphenicol-treated cultures were submitted to dye buoyant density centrifugation. A loss of covalently closed circular deoxyribonucleic acid was also evident from electrophoretic profiles of these lysates. Several conditions which could account for the apparent loss of covalently closed circular deoxyribonucleic acid upon inhibition of protein synthesis are discussed.

Bacterial Proteins↗

Analysis of increasing antibiotic resistance of Klebsiella pneumoniae relative to changes in chemotherapy.

Three antibiotic-resistant strains of Klebsiella pneumoniae responsible for outbreaks of systemic infection in a hospital nursery were analyzed. Each organism emerged after prolonged use of a drug to which it was resistant. The first strain (RO16) produced neomycin phosphotransferase and contained three plasmids with molecular weights of 24, 25, and 30 X 10(6) daltons, respectively. Resistance to ampicillin, carbenicillin, neomycin, and kanamycin was transferred by conjugation at a frequency of 10(-6). The second strain of K. pneumoniae (RO106) produced gentamicin adenyltransferase and maintained aminoglycoside resistance only when propagated in antibiotic-containing medium. DNA analyses revealed eight species of plasmid DNA: one species with a molecular weight of 70 X 10(6) daltons apparently accounted for conjugal transfer of resistance to ampicillin, carbenicillin, chloramphenicol, and streptomycin. The third strain (RO180) was resistant primarily to colistin and lacked plasmids. Control of the outbreak due to this strain was achieved by aminoglycoside therapy.

Aminoglycosides↗

Restriction enzyme analysis of plasmids from Haemophilus influenzae.

Examination of Haemophilus influenzae strains isolated in New Orleans revealed ampicillin-resistant strains with plasmids of size classes not previously detected in North America. The molecular weight of plasmids in five ampicillin-resistant strains ranged from 0.8 x 10(6) daltons (0.8 Mdal) to 36 Mdal. The molecular weights of the plasmids were determined by sucrose gradient centrifugation, electron microscopy, and agarose gel electrophoresis. Plasmids of the previously detected 30-Mdal size class were found in three of the five ampicillin-resistant strains. Restriction enzyme analysis is consistent with a close relationship between these three 30-Mdal plasmids. Of the two remaining ampicillin-resistant strains, one contained a single plasmid of 36 Mdal and the other contained two plasmids of 0.8 and 2.3 Mdal.

Centrifugation, Density Gradient↗

Genetic map position of the gluconate-6-phosphate dehydrogenase gene in Salmonella typhimurium.

Gluconate-6-phosphate dehydrogenase (GND) is genetically determined in Salmonella typhimurium by a locus (gnd) mapping between the somatic antigen (rfb) and histidine (his) operons. The enzyme is constitutive. Strains of Salmonella carrying an F' genetic element which contains the gnd(+) gene have GND activity two to three times that of the wild type. This gene dosage effect was used to determine that the GND reaction is not rate-limiting for the metabolism of glucose by the pentose shunt in S. typhimurium.

Chromosome Mapping↗