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Biomedical subjects

M Ryan

Publications and source records attributed to M Ryan.

At least 199 records · Page 11Linked to original sources
PubMed1995

Inducible expression of the P, V, and NP genes of the paramyxovirus simian virus 5 in cell lines and an examination of NP-P and NP-V interactions.

The P, V, and NP genes of the paramyxovirus simian virus 5 (SV5) were cloned such that their expression was regulated by the tetracycline-controlled transactivator (M. Gossen and H. Bujard, Proc. Natl. Acad. Sci. USA 89:5547-5551, 1992), and mammalian cell lines that inducibly expressed individually the P, V, or NP protein or coexpressed the P plus NP or V plus NP proteins were isolated. A plasmid that expresses the tetracycline-controlled transactivator linked, via the foot-and-mouth disease virus 2A cleavage peptide sequence, to the neomycin aminoglycoside phosphotransferase gene was constructed. Cells were cotransfected with this plasmid, and the appropriate responder plasmids and clonies were selected on the basis of their resistance to Geneticin (via the neomycin aminoglycoside phosphotransferase gene). The properties of these cell lines, in terms of the induction of the P, V, and NP genes, are described in detail. Both the P and V proteins were phosphorylated when expressed alone. In immunoprecipitation studies using a monoclonal antibody that recognizes both the P and V proteins, a nonphosphorylated host cell protein with an estimated molecular weight of 150,000 was coprecipitated with V but not P. Immunofluorescence data demonstrated that when expressed separately, the P protein had a diffuse cytoplasmic distribution, but the related V protein had both a nuclear and cytoplasmic distribution. The NP protein had a granular cytoplasmic distribution, giving rise to punctate and granular fluorescence. Coexpression of the NP and P proteins resulted in the accumulation of large cytoplasmic inclusion aggregates, similar to those visualized at late times in SV5-infected cells. Coexpression of V with NP led to a partial redistribution of the NP protein in that the NP protein had both a diffuse cytoplasmic and nuclear distribution in the presence of V, but no NP-V aggregates or inclusion bodies were visualized. Direct binding studies also revealed that NP bound to both P and V. For SV5, these studies suggest that V may have a role in keeping NP soluble prior to encapsidation.

Animals↗
PubMed1995

Economics in sample size determination for clinical trials.

In the design of clinical trials, sample size determination is usually undertaken by statisticians and clinicians. It is rare for health economists to be involved in this aspect of trial design. However, there are a number of outcome changes that are of 'economic significance', and it is important for trial designers and funders to be aware of these before planning, funding and mounting a trial. In this paper we demonstrate through the use of three examples (prevention of osteoporosis, management of infertility, and endometriosis) how economics can be used to influence the size of a clinical trial. Trials that are too small or too large waste research resources; health economics can lead to more efficient trial designs.

Adult↗
PubMed1994

A case control study of infection with an epidemic strain of multiresistant Salmonella typhimurium DT104 in England and Wales.

Laboratory reports of a multiresistant strain of Salmonella typhimurium definitive type (DT) 104 rose in 1993; this led the Public Health Laboratory Service to investigate cases and identify possible risk factors for infection. Information derived from questionnaires, and details of previous isolations of S. typhimurium DT104 from food and animals, were used to design an unmatched case control study. Eighty-three cases whose isolations were of the same plasmid profile type (the 'epidemic strain') and 235 controls were included in the analysis. Illness was independently associated with the consumption of several food items and contact with animals, particularly ill farm animals. The number of isolations of this organism continues to rise, and control measures may include reducing infection in animals used for food, reducing the risk of contamination at all stages of the food chain, and raising awareness of measures to prevent food poisoning among food handlers and the general public.

Adolescent↗
PubMed1994

Hysterectomy experience among mid-aged Australian women.

OBJECTIVES: To determine the rate of oophorectomy in, use of hormone replacement therapy by, and health, social and lifestyle factors of, mid-aged Australian women who have undergone hysterectomy. DESIGN AND PARTICIPANTS: A community-based cross-sectional survey by telephone interview of a random sample of 2001 Australian-born Melbourne women aged between 45 and 55 years. MAIN OUTCOME MEASURES: The health status, sociodemographic and lifestyle correlates of women who had undergone hysterectomy compared with women in the natural menopause transition. RESULTS: Twenty-two per cent of the women had undergone hysterectomy. Of these, 21% had had one ovary removed, and 20% both. Mean age at hysterectomy was 40.4 years. There was no trend in the bilateral oophorectomy rate over the last two decades. Current hormone replacement therapy use increased significantly with surgery, from 17% of non-hysterectomised women to 31% of hysterectomised women, and 49% for women who had undergone hysterectomy and bilateral oophorectomy. Hysterectomised women were significantly more likely to be of lower educational level, and to report a history of troublesome premenstrual complaints, more dilatation and curettage procedures and nongynaecological operations, and use of prescription medications. CONCLUSIONS: Social and pre-existing health problems influence hysterectomy rates. Many women undergo oophorectomy at hysterectomy despite limited evidence of benefit.

Australia↗
PubMed1994

Human t(4;11)(q21;q23) acute lymphoblastic leukemia in mice with severe combined immunodeficiency.

Mice with severe combined immunodeficiency (SCID) were injected intravenously with primary bone marrow blasts from 12 children with newly diagnosed t(4;11)(q21;q23) acute lymphoblastic leukemia (ALL). Blasts from eight patients caused overt disseminated leukemia, whereas blasts from the other four patients produced occult leukemia that was detectable only by the polymerase chain reaction (PCR) technique. Only one patient among eight whose blasts caused disseminated leukemia in SCID mice remains alive and disease-free at 48.4 months postdiagnosis. In contrast, three of the other four patients whose blasts did not cause overt leukemia in SCID mice remain alive and disease-free at 6.1, 23.6, and 35.9 months, respectively. Thus, the occurrence of overt leukemia in SCID mice may be a predictor of patients' disease-free survival. The described SCID mouse model system may prove useful for designing more effective treatment strategies against therapy-refractory t(4;11) ALL.

Adolescent↗
PubMed1994

Dependence of electroosmotic flow in capillary electrophoresis on Group I and II metal ions.

The effect of Group I and II metal ions on electroosmotic flow in capillary electrophoresis in fused-silica capillaries is characterized. The electroosmotic mobility of aqueous mobile phases of lithium, sodium, potassium, calcium and barium acetates in fused-silica capillaries is measured as a function of pH at constant voltage. Cross contamination is avoided by using separate columns for each study and pH control is maintained with the aid of He sparging. The shape of a plot of pH vs. electroosmotic mobility depends on the particular cation used which in turn depends on the surface sorption properties of the ions. Column history is demonstrated to have an effect on electroosmotic flow and therefore retention times. The resolution of a test mixture is optimal in the lithium-based buffer.

Buffers↗
PubMed1994

Uterine and umbilical blood flow velocity during epidural anaesthesia for caesarean section.

The purpose of this study was to use colour Doppler to determine the effect of epidural anaesthesia on the uterine and umbilical blood flow velocities. After determining the precision of the technique, Doppler insonation of the uterine and umbilical arteries was performed in consenting non-labouring patients requesting epidural anaesthesia for Caesarean section. Patients in Group I were normal and those in Group II were at high risk for uteroplacental blood flow abnormalities. The pulsatility indexes (PI) of both uterine and umbilical arteries were compared at the following times: control, after fluid and after anaesthesia using repeated measure analysis of variance. In Group I (n = 30) the PI increased from 0.72 to 0.82 in the left uterine artery and from 0.71 to 0.85 in the right uterine artery (P < 0.05). In Group II (n = 10) the PI increased from 0.67 to 0.85 in the left uterine artery (NS) and from 0.98 to 1.38 in the right uterine artery (P < 0.05). There was no change in the PI in the umbilical artery. We conclude that the PI of the uterine arteries increases after epidural anaesthesia with lidocaine, epinephrine and fentanyl but there is no change in the umbilical PI. While these changes do not appear to be clinically important in the low-risk population, further studies are required to determine the impact on fetuses at high risk for in utero hypoxaemia.

Adult↗
PubMed1994

Prevalence of Corynebacterium urealyticum in urine specimens collected at a university-affiliated medical center.

Corynebacterium urealyticum (formerly Corynebacterium group D2) has been implicated as a cause of alkaline-encrusted cystitis and urinary tract struvite calculi. Despite preselecting urine specimens with neutral and alkaline pHs and using prolonged incubation on a selective medium, isolation of this organism was rarely observed in a population of hospitalized patients. We do not recommend routine cultures for this organism unless the urine is alkaline and struvite crystals, leukocytes, and erythrocytes are present.

Academic Medical Centers↗
PubMed1994

The electrocardiogram is a more sensitive indicator than echocardiography of hypertrophic cardiomyopathy in families with a mutation in the MYH7 gene.

BACKGROUND: Mutations in the cardiac beta myosin heavy chain gene causing hypertrophic cardiomyopathy have been identified, and to assist both diagnosis and prediction of outcome attempts have been made to correlate phenotype and genotype. Two new mutations in codon 403 of the gene in three unrelated families are described and attention drawn to variable or even absent phenotypic expression in different family members. METHODS AND RESULTS: The polymerase chain reaction and heteroduplex analysis on Mutation Detection Enhancement gels were used to search for mutations in the globular head of the beta myosin heavy chain gene in families with hypertrophic cardiomyopathy. Two mutations were found in exon 13 (codon 403) of the gene. In two unrelated Polish families the mutation resulted in the conversion of arginine to tryptophan (CGG: >TGG). A second mutation, found in a British family, converted the same arginine to leucine (CGG: >CTG). These mutations were detected in family members who had electrocardiographic and echocardiographic features typical of hypertrophic cardiomyopathy; however, they were also detected in 7 other adult relatives with an abnormal electrocardiogram but a normal echocardiogram. Two unrelated adult relatives had completely normal clinical findings but carried the gene mutation. CONCLUSIONS: Identification of a specific mutation gives no guide to the clinical phenotype. There is considerable variability in the phenotypic expression of hypertrophic cardiomyopathy. Mutations were detected in adults previously regarded as normal or in whom the diagnosis was questionable. The fact that the clinical significance of the mutation in these people is still unknown emphasises the dilemma facing screening programmes. Isolated, unexplained electrocardiographic abnormalities in first degree relatives in a family with a definitive diagnosis of hypertrophic cardiomyopathy should be regarded as evidence of a carrier state.

Adult↗
PubMed1994

The Homeless Prenatal Program: a model for empowering homeless pregnant women.

The Homeless Prenatal Program (HPP) is one of the first programs in the country to provide comprehensive prenatal services to homeless pregnant women. A formative evaluation was conducted in 1992, indicating that HPP is achieving its program goals of improving birth outcomes and transforming the lives of its clients. Results of the qualitative evaluation are presented, including HPP's service model and approach to empowerment. In this model, empowerment has two central tenets, derived from the special needs of women who are pregnant and homeless: the "mother-child connection," and the principle of "giving back."

Child↗
PubMed1994

Dispensing physicians and prescribing pharmacists: economic considerations for the UK.

Recent years have seen an increase in the number of dispensing physicians in the UK. There have also been suggestions that legislation restricting certain drugs to prescription-only availability should be relaxed and that pharmacists should take a more active role in the provision of drugs. General medical practitioners and pharmacists have common ancestry in the medieval spicers, who dispensed medicines and offered medical advice. Rural practitioners have been allowed to dispense drugs since 1911. Physician dispensing can benefit patients via savings in time and the monetary cost of visiting a pharmacist, but it restricts drug choice, can compromise safety, and encourages overprescribing except for physicians with drugs budgets. The effects of physician dispensing on government costs are not yet clear. Over-the-counter (OTC) purchase can save patients the cost of a physician visit and reduce drug costs to some patients, but it can also provide an incentive to pharmacists to profit twice from a drug, at government expense. Switching drugs from prescription-only to OTC reduces the government drug bill, but provides an incentive to pharmacists to overprescribe, and may not be as safe for patients. Liberalising prescribing by doctors would discourage community pharmacies which provide an advisory service to patients. Liberalising OTC switches would reduce opportunistic assessment of patients by doctors and could compromise patient safety. Separation of physician and pharmacist functions is probably safer for patients. It is concluded that the current situation in the UK, whereby most dispensing is done by pharmacists, is the preferred option other than for those patients who do not live within easy access of a pharmacy. A reassessment of the legal status of drugs and subsequent OTC switch of drugs used to treat minor self-limiting illnesses is also favoured.

Cost-Benefit Analysis↗