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Biomedical subjects

M Murphy

Publications and source records attributed to M Murphy.

At least 325 records · Page 18Linked to original sources
PubMed1993

Molecular regulation of neural crest development.

The neural crest is a transient embryonic structure that gives rise to a multitude of different cell types in the vertebrate. As such, it is an ideal model to study the processes of vertebrate differentiation and development. This review focuses on two major questions related to neural crest development. The first question concerns the degree and time of commitment of the neural crest cells to different cell lineages and the emerging role of the homeobox containing genes in regulating this process. Evidence from the cephalic crest suggests that the commitment process does start before the neural crest cells migrate away from the neural tube and gene ablation experiments suggest that different homeobox genes are required for the development of neural and mesenchymal tissue derivatives. However, clonal analysis of neural crest cells before migration suggests that many of the cells remain multi-potential indicating that the final determinative steps occur progressively during migration and in association with environmental influences. The second question concerns the nature of the environmental factors that determine the differentiation of neural crest cells into discrete lineages. Evidence is provided, mainly from in vitro experiments, that purified growth factors selectively promote the differentiation of neural crest cells down either sympathetic, adrenal, sensory, or melanocytic cell lineages.

Animals↗
PubMed1993

Lactate dehydrogenase levels during MACOP-B chemotherapy for non-Hodgkin's lymphoma.

Lactate dehydrogenase (LD) levels rose consistently during MACOP-B chemotherapy for intermediate and high-grade non-Hodgkin's lymphoma (NHL). Levels peaked at week nine and fell to normal within six weeks of completion of therapy. Isoenzyme patterns, studied prospectively in seven patients, showed a parallel rise in LD1 and LD2 suggesting a source other than tumour tissue for the rise in total LD. In the absence of evidence of myocardial or renal damage, haematopoietic tissue was the most likely source. With no evidence of haemolysis, normal serum levels of vitamin B12 and folate and normal red cell folate, dyserythropoiesis was considered to be the underlying mechanism. A rising mean corpuscular volume further reinforced this suggestion. Intensive use of methotrexate along with co-trimoxazole as prophylaxis against pneumoycystis carinii is considered the most likely cause of marrow dysfunction. Failure to recognise that rising LD levels during such therapy is treatment-related, rather than of tumour origin, may lead to inappropriate change or abandonment of therapy.

Adult↗
PubMed1993

3H-thymidine uptake by the rat urinary bladder after induction of diabetes mellitus.

Streptozotocin-induced diabetes mellitus causes diuresis, increases in bladder mass and changes in micturition. Temporal changes in micturition and bladder mass after induction of diabetes with streptozotocin were monitored and correlated with DNA synthesis and 3H-thymidine incorporation. There were increases in water consumption, urine excretion, urinary frequency, and mean and maximal micturition volume within 1 day after induction of diabetes. These parameters reached maximal values within 6 to 11 days and were maintained at 30 and 60 days. Bladder mass was significantly elevated by 7 days and did not increase further with increasing duration of diabetes. DNA concentration was decreased in bladders from 4, 7 and 14 day diabetics. 3H-thymidine incorporation into DNA increased within 2 days after induction of diabetes, reached maximal values at 4 to 7 days and declined to control values by 14 days. Autoradiography showed intense labelling of the urothelium one day after induction of diabetes, with labelling remaining high up to day 7. Connective tissue and smooth muscle labelling were slower to develop. Labelling of smooth muscle was transient, appearing only on days 4 and 7. The time course of the events was consistent with the hypothesis that bladder distension or increasing micturition volume stimulates thymidine incorporation into DNA, resulting in an increase in bladder mass.

Animals↗
PubMed1993

How much heparin? A simple in vitro test.

A simple in vitro test to calculate the dose of heparin required to achieve optimal in vivo anticoagulation during surgery has been assessed in 15 patients who subsequently underwent vascular surgery. Heparin was added to four aliquots of patients blood in vitro to give five solutions with heparin concentrations ranging from 0-0.8 units/ml of plasma. The activated partial thromboblastic times (APTT) of each of these samples was then measured and the natural log (ln) of the APTT calculated. The natural log of the APTT in vitro was then plotted against the in vitro heparin concentration. From this linear correlation the concentration of heparin required to achieve an APTT 2.5 times the normal in vitro (Hc) for the 15 different patients was calculated and ranged from 0.4-0.75 units/ml (median 0.47). Based on an estimate of the plasma volume (PV), the bolus dose of heparin given intravenously to each patient to produce an equivalent anticoagulant response in vivo was calculated (Hc x PB). Heparin boli administered ranged from 1000-2000 units (median 1500). The mean in vivo APTT achieved was 77% of the predicted value (range 62%-123%). Such an estimation of an in vivo response, by means of an in vitro test, should help to more accurately predict the effects of heparin in vivo and individualise anticoagulation dosage.

Aged↗
PubMed1993

Method for studying drug-warfarin interactions.

The potential effects of extended-release felodipine on the pharmacokinetics and pharmacodynamics of warfarin were studied in a double-blind crossover study in 12 healthy men. Warfarin dosage was adjusted to achieve stable subtherapeutic anticoagulation. Subjects were then randomized to receive 2 weeks of treatment with 10 mg extended-release felodipine or placebo once daily, and warfarin dosage was adjusted if necessary to maintain stable international normalized ratio. The pharmacokinetics of R- and S-warfarin and the warfarin dose requirement did not differ importantly between periods of treatment with felodipine and placebo. The design of this study is suitable for general use in the identification of possible effects of other drugs on the pharmacokinetics and pharmacodynamics of warfarin. A different approach is needed if there is any reason to expect that warfarin may alter the pharmacokinetics or pharmacodynamics of the test drug.

Adult↗
PubMed1993

Identification of mycoplasmas in urine from persons infected with human immunodeficiency virus.

Voided urine samples from persons with and without human immunodeficiency virus (HIV) infection were examined for mycoplasmas. Mycoplasma hominis organisms were identified in cultures of urine from 32 (18%) of 180 HIV-positive individuals and from 8 (21%) of 38 HIV-negative individuals. In contrast, glucose-utilizing mycoplasmas were identified in the urine of 30 (17%) of the HIV-positive individuals and in none of those who were HIV-negative. Assays of growth inhibition around disks containing specific antisera identified 14 of the 30 glucose-utilizing mycoplasmas as Mycoplasma fermentans. Four isolates were presumptively identified as Mycoplasma pirum. Growth on solid media was insufficient to permit the identification of the species of the other 12 isolates by growth inhibition.

Adult↗
PubMed1993

Factors affecting the efficacy of a community-based quit smoking program.

Community-based Fresh Start courses have been running at local community centres throughout Victoria since February 1983. This paper describes the key features of this program and identifies the factors which relate to smoking cessation. Data were collected from 3298 participants who attended a program between February 1983 and June 1988. All participants were asked to complete three short questionnaires: on arrival at the course, at the conclusion of the course and a year after finishing the course. Although most participants had made previous unsuccessful quit attempts and perceived quitting to be difficult, attendance at the course had a major impact on their reported smoking. At the conclusion of the course at least 51% of participants had quit smoking and the remaining participants had reduced their smoking by an average of 50%. At the 1 year follow-up, at least 23% of participants were non-smokers and the remaining participants had reduced their smoking by an average of 21%. Successful quitting at the end of the course and at the 12 month follow-up was positively related to the number of sessions attended and the perceived likelihood of quitting, and negatively related to initial cigarette consumption.

Adolescent↗
PubMed1993

Rodenticide-induced coagulopathy in a young child. A case of Munchausen syndrome by proxy.

PURPOSE: To present the diagnosis and management of superwarfarin ingestion, a cause of serious and prolonged coagulopathy. METHODS: Specific identification of the anticoagulant was made by high-pressure liquid chromatography. RESULTS: A 24 month-old child developed bruises and a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) after receiving multiple doses of brodifacoum, a superwarfarin rodenticide. The coagulopathy was treated successfully with large doses of parenteral and oral vitamin K1; fresh frozen plasma was administered as a precautionary measure on two occasions. After the first 10 days of the child's hospitalization, the mother was identified as the source of brodifacoum, exemplifying the behavior described as Munchausen syndrome by proxy. Oral vitamin K1 was initiated and continued in an outpatient setting with tapering doses over nine months, using the PT as a guide for therapy. CONCLUSIONS: This report emphasizes the necessity of recognizing rodenticide poisoning and investigating its source. Frequent monitoring of the PT is essential to prevent hemorrhagic complications due to repeat exposure, inadequate vitamin K1 therapy, or noncompliance.

4-Hydroxycoumarins↗
PubMed1993

Prevalence of the fragile X anomaly amongst autistic twins and singletons.

Early screening studies of autistic individuals suggested that up to one-quarter of cases were associated with the Fragile X anomaly. Recent studies find that the usual behavioural phenotype of the Fragile X anomaly is distinct from autism as usually defined, and that a variety of methodological factors contribute to the variability of the prevalence estimates. We report the prevalence of the Fragile X anomaly, using strict cytogenetic criteria, in a large sample of autistic individuals whose diagnosis was confirmed using a standardised diagnostic instrument. The anomaly was detected in 1.6% of tested autistic individuals from a combined sample of: autistic twins; clinic attenders; and, individuals from families multiplex for autism or related cognitive phenotypes. The anomaly was not detected in greater than 2.5% of any of the constituent samples and accounted for only a small proportion of the genetic influences amongst concordant twins and multiplex families. The anomaly was detected in 5% of the 40 tested autistic females, confirming reports that the prevalence of the anomaly is similar amongst autistic individuals of both sexes.

Adult↗
PubMed1993

Clinical trials with velnacrine: (PROPP) the physician reference of predicted probabilities--a statistical model for the estimation of hepatotoxicity risk with velnacrine maleate.

Safety observations during the clinical development of Mentane (velnacrine maleate) have included the occurrence of generally asymptomatic liver enzyme elevations confined to patients with Alzheimer's disease (AD). The clinical presentation of this reversible hepatocellular injury is analogous to that reported for tetrahydroaminoacridine (THA). Direct liver injury, possibly associated with the production of a toxic metabolite, would be consistent with reports of aberrant xenobiotic metabolism in Alzheimer's disease patients. Since a patient related aberration in drug metabolism was suspected, a biostatistical strategy was developed with the objective of predicting hepatotoxicity in individual patients prior to exposure to velnacrine maleate. The method used logistic regression techniques with variable selection restricted to those items which could be routinely and inexpensively accessed at screen evaluation for potential candidates for treatment. The model was to be predictive (a marker for eventual hepatotoxicity) rather than a causative model, and techniques employed "goodness of fit", percentage correct, and positive and negative predictive values. On the basis of demographic and baseline laboratory data from 942 patients, the PROPP statistic was developed (the Physician Reference Of Predicted Probabilities). Main effect variables included age, gender, and nine hematological and serum chemistry variables. The sensitivity of the current model is approximately 49%, specificity approximately 88%. Using prior probability estimates, however, in which the patient's likelihood of liver toxicity is presumed to be at least 30%, the positive predictive value ranged between 64-77%. Although the clinical utility of this statistic will require refinements and additional prospective confirmation, its potential existence speaks to the possibility of markers for idiosyncratic drug metabolism in patients with Alzheimer's disease.

Age Factors↗
PubMed1993

Inhibition of herpes simplex virus type 1 DNA polymerase activity by peptides from the UL42 accessory protein is largely nonspecific.

To identify regions in the UL42 protein of herpes simplex virus type 1 which affect viral DNA polymerase activity, a series of 96 overlapping pentadecapeptides spanning the entire 488 amino acids of the UL42 protein were synthesized and tested for their ability to inhibit polymerase activity on a primed single-stranded M13 DNA template. Two assays were used: formation of full-length double-stranded M13 molecules and rate of incorporation of deoxyribonucleoside triphosphates. Peptides from five noncontiguous regions of the UL42 protein were found to inhibit herpes simplex virus type 1 polymerase activity in both the presence and absence of UL42 protein. The most active peptides from each region correspond to amino acids 23 to 38 (peptide 6), 64 to 78 (peptide 14), 89 to 102 (peptide 19), 229 to 243 (peptide 47), and 279 to 293 (peptide 57). By two different methods (DNA mobility shift and DNA precipitation), peptides 14, 19, 47, and 57 were found to bind DNA; they most probably inhibit enzyme activity by this mechanism. Peptide 6 did not bind DNA and must act by some mechanism other than competing for DNA. The inhibitory peptides were also tested for activity against mammalian polymerase alpha and the Klenow fragment of Escherichia coli polymerase. Although some limited specificity was demonstrated (up to 10-fold for peptide 6), all the peptides showed significant activity against both polymerase alpha and E. coli polymerase.

Amino Acid Sequence↗
PubMed1993

Attitudes of British psychiatrists to the diagnosis of somatisation disorder. A questionnaire survey.

A postal questionnaire was sent to 195 senior British psychiatrists who were asked about their attitudes towards the DSM-III-R diagnosis of somatisation disorder (SD) and the ICD-10 diagnosis of multiple somatisation disorder. Of the 148 respondents, 98 (66%) had experience of liaison psychiatry, and these psychiatrists used the diagnosis significantly more often than those without liaison sessions. More than half the respondents perceived SD as both a personality disorder and a mental state disorder, although 27% thought that patients with SD had an undiagnosed physical disease. The marked discrepancy between British and North American psychiatrists in diagnostic practices was perceived to be a consequence of both the difference in health care systems and the interest shown in the disorder by North American psychiatrists, rather than a reflection of genuine differences in prevalence.

Attitude of Health Personnel↗