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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

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

Imperforate anus, malrotation and Hirschsprung's disease: a rare association.

The association of imperforate anus with anomalies of rectal innervation is very rare. Moreover, malrotation only rarely accompanies these malformations. We report 2 patients with this unusual triple association and its impact on their management. Retrospectively both patients presented at birth with the same radiological picture of distended distal colon and right-sided small bowel location. We discuss the importance of a systematic search for associated intestinal malformations in cases of imperforate anus in order to avoid serious complications and to choose the optimal operative strategy.

Anastomosis, Surgical↗
PubMed1995

Phagocytosis of individual CD4+ T cells by HIV-induced T cell syncytia.

Transmission electron microscopic analysis of HIV-induced syncytia of the CD4+ SupT1 cell line has revealed profiles of whole T cells in the syncytium cytoplasm. Serial sections demonstrate that these T cells are completely enveloped by a second membrane in the syncytium cytoplasm and represent phagosomes. Pycnosis of engulfed T cell nuclei, vacuolation of the cytoplasm of engulfed T cells, and the association of engulfed T cells with dense vesicular clusters in the syncytium cytoplasm support the conclusion that they represent phagosomes. In addition, transmission electron micrographs of the syncytium surface reveal giant pseudopodial extensions wrapping around T cells, in a fashion similar to bacterial and yeast phagocytosis by professional phagocytes. These results suggest that phagocytosis is a characteristic acquired during HIV-induced syncytium formation, and that it may represent an avenue of T cell death in addition to fusion in HIV-infected SupT1 cell cultures.

CD4-Positive T-Lymphocytes↗
PubMed1995

Self-reported tooth loss and bone mineral density in older men and women.

It has been reported that postmenopausal women with osteoporosis have a higher than expected number of dentures and fewer teeth than women without osteoporosis. The relationship between self-reported tooth loss and bone mineral density (BMD) at the hip and spine in 608 men and 874 women, aged 65-76 years, was examined in a cross-sectional study. BMD was measured using dual X-ray absorptiometry. Twenty-four per cent of men and 27% of women had no natural teeth. There was a consistent decrease in BMD with increasing numbers of teeth lost in men. This relationship was independent of age, body mass index and smoking habit (trochanter r = -0.14, p < 0.0005; Ward's triangle r = -0.1, p < 0.005; and lumbar spine r = -0.07, p < 0.05) with between 5% and 9% difference in mean BMD at various sites between men who had all their teeth and men who had no teeth. There was no significant association between self-reported tooth loss and BMD in women. Tooth loss is associated with lower BMD in men; this relationship is less consistent in women.

Aged↗
PubMed1995

Life-style factors associated with winter serum 25-hydroxyvitamin D levels in elderly adults.

A cross-sectional survey of community-dwelling elderly volunteers (104 women, 87 men, mean age 70 years) was carried out in winter to determine whether cardiovascular and other potentially modifiable lifestyle factors were associated with serum levels of 25-hydroxyvitamin D during this period. Mean winter levels of serum 25-hydroxyvitamin D were higher in men than in women (14.2 vs. 12.2 ng/ml, p = 0.021), higher in those who used margarine daily compared with less often (14.4 vs. 11.9 ng/ml, p = 0.005), and higher in those who holidayed overseas in the last 6 months at a lower latitude than in Great Britain or Germany (14.9 vs. 12.4 ng/ml, p = 0.044), after controlling for other confounders. Serum 25-hydroxyvitamin D levels were not related to the number of hours spent outdoors during the previous month (r = 0.04, p > 0.05). When participants were classified by tertile of low-density lipoprotein (LDL) cholesterol, mean serum 25-hydroxyvitamin D was raised in the highest (14.3 ng/ml, p = 0.011) and middle (13.3 ng/ml, p = 0.15) tertiles compared with the lowest tertile (11.9 ng/ml), after controlling for other confounders. All other cardiovascular risk factors, including total- and HDL-cholesterol, blood pressure, BMI, smoking and leisure physical activity, were unrelated to serum vitamin D. These results suggest that body vitamin D levels in elderly people during winter are related to diet and overseas holidays within the last 6 months, but not to UK winter sun exposure, nor to the major cardiovascular risk factors apart from LDL cholesterol.

Aged↗
PubMed1995

Extravasation rates and complications of intraosseous needles during gravity and pressure infusion.

OBJECTIVE: To compare the extravasation rates and insertion complications under gravity and 300 mm Hg (40 kPa) pressure infusion of threaded (SurFast and Sussmane-Raszynski intraosseous needles, Cook Critical Care, Bloomington, IN); and nonthreaded needles (16-gauge disposable intraosseous needle with 45 degrees trocar Cook Critical Care, Bloomington, IN; Jamshidi bone marrow needle; Baxter Health Care Corp, Valencia, CA). DESIGN: A prospective, randomized study. SETTING: An animal laboratory at a university center. SUBJECTS: Five healthy mix breed piglets, weighing 15 to 15.5 kg. INTERVENTIONS: Piglets were anesthetized and ventilated. Tibial, femoral, and humeral osseous sites were exposed by dissection of overlying tissue. All bleeding points were cauterized and oozing was prevented by sealing with cyanoacrylate. Intraosseous access devices then were inserted one at a time in random order and rated for difficulty of insertion. Normal saline solution was infused under gravity or 300 mm Hg (40 kPa) pressure. Extravasation rates then were calculated from the increase in weight of a gauze sponge wrapped tightly at the base of the needle during infusion. MEASUREMENTS AND MAIN RESULTS: No significant (p > .05) differences in extravasation rates were noted among the different types of needles, either under gravity or pressure infusions. The Sussmane-Raszynski needle was significantly more difficult to insert than the others (rated difficult to insert and control in 16 of 34 attempts). Inadvertent penetration of both cortices occurred with nonthreaded needles only (three of 66 attempts). The SurFast needle provided greatest penetration control and was most resistant to accidental dislodgement. CONCLUSIONS: Under ideal conditions, needle type does not influence extravasation rates. However, difficulty with insertion and penetration of both cortices occur commonly and may lead to extravasation during stressful emergency situations or when performed by unskilled personnel.

Animals↗
PubMed1995

Bone mineral density and its relationship to skin colour in Caucasian females.

Low bone mineral density (BMD) is associated with a high risk of osteoporosis and fracture. While women with darker skin, such as women of American African origin, are reputed to have lower risk osteoporosis and fractures compared with women with fair skin such as Caucasian women, with Oriental women having intermediate levels of risk, the reasons for these differences are not clear. We examined the relationship between BMD and skin colour in a population based study of 2005 Caucasian women with a mean age of 58.1 years, resident in Cambridge and categorized into fair, medium and dark complexions by self-report. There was no difference between the three categories of skin colour with regard to body size or life-style characteristics. Women with self-reported fair skin had lowest BMD values, women with self-reported dark skin had highest BMD values, and women with self-reported medium skin colour had intermediate values at all sites. These differences were significant at the trochanter and Ward's triangle of the hip (P values of 0.01 and 0.03, respectively). These associations were independent of age and weight. The associations remained after stratifying for smoking habit and years since menopause. In a cohort of Caucasian women resident at latitude 52 degrees North, fair-skinned women have lower BMD values than darker-skinned women. This association between skin colour and BMD may reflect sunlight exposure times and underlying vitamin D status.

Bone Density↗
PubMed1995

Teicoplanin or vancomycin in the treatment of gram-positive infections?

The glycopeptide antibiotics vancomycin and teicoplanin have similar mechanisms of action on bacterial cell wall synthesis. Their spectra of activity are limited to Gram-positive bacteria, with the degree of bactericidal activity depending on the species of micro-organism. Staphylococcus aureus, Staphylococcus epidermis, enterococci and Clostridium difficile are generally sensitive, including methicillin-resistant strains of S. aureus and S. epidermidis. Glycopeptide resistance has recently emerged in staphylococci and enterococci. Vancomycin has a shorter half-life than teicoplanin and requires multiple dosing to maintain adequate serum levels. It can only be given by prolonged intravenous infusion over 1 h. In contrast, the pharmacokinetics of teicoplanin allow for once-daily dosing, either by rapid intravenous infusion or by the intramuscular route. The latter offers reliable absorption for patients with limited venous access and is also of benefit for out-patient therapy. Teicoplanin is a safer drug than vancomycin. It is associated with a lower incidence of nephrotoxicity or ototoxicity. Compared to vancomycin, the availability of the intramuscular route and the absence of a requirement for routine serum monitoring, together with the reduced need to treat drug-related side-effects make teicoplanin more cost-effective. It is as effective as vancomycin for most indications, is safe, easy to administer and an important agent for treating Gram-positive infections. Its role in hospitals is likely to increase if the price of drug acquisition is kept low.

Cell Wall↗
PubMed1995

Proximal sequence element-binding transcription factor (PTF) is a multisubunit complex required for transcription of both RNA polymerase II- and RNA polymerase III-dependent small nuclear RNA genes.

The proximal sequence element (PSE), found in both RNA polymerase II (Pol II)- and RNA Pol III-transcribed small nuclear RNA (snRNA) genes, is specifically bound by the PSE-binding transcription factor (PTF). We have purified PTF to near homogeneity from HeLa cell extracts by using a combination of conventional and affinity chromatographic methods. Purified PTF is composed of four polypeptides with apparent molecular masses of 180, 55, 45, and 44 kDa. A combination of preparative electrophoretic mobility shift and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analyses has conclusively identified these four polypeptides as subunits of human PTF, while UV cross-linking experiments demonstrate that the largest subunit of PTF is in close contact with the PSE. The purified PTF activates transcription from promoters of both Pol II- and Pol III-transcribed snRNA genes in a PSE-dependent manner. In addition, we have investigated factor requirements in transcription of Pol III-dependent snRNA genes. We show that in extracts that have been depleted of TATA-binding protein (TBP) and associated factors, recombinant TBP restores transcription from U6 and 7SK promoters but not from the VAI promoter, whereas the highly purified TBP-TBP-associated factor complex TFIIIB restores transcription from the VAI but not the U6 or 7SK promoter. Furthermore, by complementation of heat-treated extracts lacking TFIIIC activity, we show that TFIIIC1 is required for transcription of both the 7SK and VAI genes, whereas TFIIIC2 is required only for transcription of the VAI gene. From these observations, we conclude (i) that PTF and TFIIIC2 function as gene-specific as gene-specific factors for PSE-and B-box-containing Pol III genes, respectively, (ii) that the form of TBP used by class III genes with upstream promoter elements differs from the from used by class III genes with internal promoters, and (iii) that TFIIIC1 is required for both internal and external Pol III promoters.

Base Sequence↗
PubMed1995

Interobserver variation in respiratory signs of severe malaria.

Respiratory abnormalities are common presentations of malaria and acute respiratory tract infection, both of which are major causes of childhood mortality and morbidity in sub-Saharan Africa. Appropriate management depends on accurate assessment of disease severity which for the majority of children must be based on clinical signs alone. Choosing which signs best serve this purpose remains a considerable problem particularly in malaria endemic areas. As part of a prospective study to define clinical signs indicative of life threatening malaria video recordings were used to examine the level of agreement between clinicians for potentially important respiratory signs in 51 children. Overall agreement was good for recession, severe recession, and nasal flaring (kappa = 0.57, 0.50, and 0.60 respectively) and substantial for deep breathing and the summary impression of respiratory distress (kappa = 0.70 and 0.69 respectively). However, within this substantial variation in interpretation was apparent between individual observers from slight to almost perfect agreement (kappa values 0.10-0.92). Video is a useful tool to demonstrate interobserver variation and it may also allow training in recognition of signs and a means of standardising clinical signs between centres.

Child↗
PubMed1995

Alcohol consumption and bone mineral density in older men.

It is well documented that alcohol abuse is associated with an increased risk of fracture in men, but the relationship of moderate alcohol intake to bone mineral density (BMD) is not as clear. We examined the relationship between self-reported alcohol intake and BMD measured at the hip and spine using dual X-ray absorptiometry in a population-based cohort of men. The men were categorized as (1) non-drinkers and drinkers and (2) as having no, low, medium, and high alcohol intake (units/week). 458 men aged 69.1 +/- (SD) 2.8 (range 64-76) years were studied. Drinkers were significantly younger (p = 0.01), had lower recorded caffeine intake (p = 0.02), and had fewer pack years of smoking (p = 0.04) than non-drinkers. The mean BMD at the hip was significantly higher in drinkers as compared with non-drinkers (p = 0.02) before and after adjusting for age and weight. However, after further adjusting for pack years of smoking, caffeine intake, and physical activity, the difference remained significant at the trochanter only. Men categorized in the highest tertiles of alcohol intake (> 11 units/week) were younger (p = 0.3), had lower caffeine intake (p = 0.008), and had significantly higher gamma-glutamyltransferase levels (p = 0.002) than the other categories. The crude mean BMD at femoral neck, trochanter, and Ward's triangle was significantly higher in men who drank 1-4 units of alcohol per week. However, most of this association disappeared when BMD was adjusted for age and weight except at the trochanter.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Aerosolized beta 2-agonists do not induce bronchial hyperreactivity in healthy adults.

OBJECTIVE: To determine whether regular administration of beta 2-agonists could induce bronchial hyperreactivity in nonasthmatic volunteers. DESIGN: A prospective, randomized, double-blind, placebo-controlled, crossover clinical trial of 2 weeks therapy with a 2-week washout period between each treatment period. Treatments were albuterol or matching placebo as 2 inhalations 4 times daily. SUBJECTS: Ten healthy, nonsmoking women 27-37 years old. SETTING: General clinical research center of a tertiary care university hospital. MAIN OUTCOME MEASURES: Baseline spirometry and methacholine bronchoprovocation studies were performed immediately prior to, 12 hours following, and 1 and 2 weeks following each treatment period. RESULTS: No change was detected in either baseline spirometry or methacholine responsiveness. CONCLUSIONS: This suggests that if beta 2-agonists induce a rebound bronchial hyperreactivity, it is not the result of the production of tolerance or a direct effect on bronchial smooth muscle.

Adrenergic beta-2 Receptor Agonists↗
PubMed1995

Parasite viability during treatment of severe falciparum malaria: differential effects of artemether and quinine.

The effect of artemether (AR) and quinine (QN) on parasite viability ex vivo was compared in children being treated for severe Plasmodium falciparum malaria. Parasitized blood taken at intervals during treatment was cultured in vitro, and parasite development was assessed microscopically. Parasite viability (defined as the proportion of circulating rings developing to early schizonts) was 56.8% in the AR group (n = 7) 6 hr after the start of treatment, compared with 93.3% for QN (n = 6; P = 0.015). Even after 24 hr of QN treatment, parasite viability was not significantly reduced in five patients. These ex vivo findings, which confirm previous observations of the stage-specific effects of these drugs against P. falciparum, suggest that AR may be superior to QN in the treatment of severe malaria.

Animals↗
PubMed1995

Acetabular reconstruction using structural grafts in total hip replacement: a 12 1/2 year follow-up.

We reviewed 34 patients who had structural acetabular grafts used in conjunction with total hip replacement. Two patients died and eight were lost to follow-up, leaving 24 patients with 24 grafts who were followed-up for a minimum of 10 years and an average of 12 1/2 years. There were 8 primary hips and 16 revisions. Twenty-two (92%) of the grafts united. The two non-unions were in patients with sepsis. Six grafts (26%) failed. Two failed because of sepsis and four were aseptic failures. All the aseptic failures were the results of technical errors. Two grafts were of poor quality and all of the aseptic failures had transverse trabeculae and transverse screws. There were 10 (41%) loose acetabular components. Two were loose because of sepsis. Of the eight aseptic failures, four were caused by failure of the graft and in the other four, the graft remained intact but the cemented acetabular components loosened. There was no correlation between the percentage of component coverage by the graft and component failure. The average preoperative Harris rating was 43 and the postoperative rating was 81, including the failures. If the failures were eliminated, the rating of the remaining patients was 93. Structural acetabular grafts are rarely necessary. However, they do work and their success is clearly related to technique. Important technical factors include: the graft must be of good quality, the trabecula must be oriented in the line of weight-bearing forces, the graft must accurately fit the defect, the graft must be supported by a host buttress, and the graft should be fixed with lag screws that are oriented in a line of weight-bearing. If these criteria are met, early weight-bearing is important to stimulate graft healing and remodeling.

Acetabulum↗
PubMed1995

Effect of winter oral vitamin D3 supplementation on cardiovascular risk factors in elderly adults.

OBJECTIVE: A possible role for vitamin D deficiency in contributing to the winter increase in cardiovascular disease mortality was investigated by testing the effect of vitamin D supplementation on blood pressure and other cardiovascular risk factors during winter. DESIGN: Randomised double-blind trial of vitamin D supplementation in winter. SUBJECTS: Men and women, mean age 70 years (range 63-76) recruited from general practitioner age-sex registers in Cambridge (UK). INTERVENTION: 95 people received a single oral dose of 2.5 mg cholecalciferol and 94 received the placebo at baseline interviews during December 1991. Follow-up assessment was 5 weeks later during January 1992. RESULTS: Comparing follow-up with baseline assessment, serum 25-hydroxyvitamin D increased in the treated group and decreased slightly in the placebo group [mean (s.d.) change: 7.2 (+/- 3.8) vs -1.4 (+/- 1.1) ng/ml, P = 0.0001]; while parathyroid hormone decreased in the treated, and increased in the placebo, group [-0.27 (+/- 0.78) vs 0.13 (+/- 0.75) pmol/l, P = 0.0004]. However, the mean change in blood pressure was similar in both groups: systolic -5 (+/- 13) vs -5 (+/- 16) mmHg, P = 0.81; diastolic -1 (+/- 9) vs -1 (+/- 9), P = 0.92; as was the mean change in serum cholesterol [-0.07 (+/- 0.52) vs -0.05 (+/- 0.60) mmol/l, P = 0.81]. In contrast, the mean change in radial pulse was significantly decreased in the treated group compared with placebo [-2 (+/- 9) vs 1 (+/- 7) beats per min, P = 0.030]. CONCLUSIONS: The failure of vitamin D supplementation to change blood pressure or serum cholesterol suggests that the winter increase in these factors is not caused by decreased vitamin D levels.

Aged↗
PubMed1995

The management of severe malaria in children: a review.

We have attempted to summarise an approach to management of severe malaria from our experience and that of others from published data in this review. This represents our current state of knowledge and practices which may change as research continues in this field. It also represents what we feel should be the minimum aim in treating severe malaria even at district hospital level. It focuses on practical issues encountered when admitting such patients: initial assessment, immediate supportive management, use of transfusion, appropriate anti-malarial treatment and ongoing management.

Child↗
PubMed1994

Duration of expression of inducible nitric oxide synthase in glial cells.

Lipopolysaccharide (LPS) or a combination of interleukin (IL)-1 beta and interferon (IFN)-gamma cause transcriptional induction of a calcium-independent nitric oxide synthase (NOS) in astrocytes and C6 glioma cells. LPS induction of NOS in C6 cells was evidenced by a small amount of nitrite accumulation as compared with cells exposed to IL-1 beta/IFN-gamma, but the maximal NOS activity achieved (as revealed by cGMP formation) was the same. The NOS activity induced by LPS in C6 cells was maximal at 4 to 8 hr and then rapidly decreased, while NOS activity induced by IL-1 beta/IFN-gamma slowly decreased after 4 hr. In addition, the effects of re-presenting IL-1 beta/IFN-gamma to both astrocytes and C6 cells after maximal induction of activity of the inducible form of NOS were studied. The re-addition of cytokines prolonged both NOS mRNA expression and also enzyme activity, suggesting effects at either the transcriptional (further induction) or translational level (mRNA stability). These results imply that the time course of NO production by induced astrocytes depends both upon the nature of the inducing stimulus and the frequency of the cells' exposure to it.

Amino Acid Oxidoreductases↗