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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 235 records · Page 13Linked to original sources
PubMed1994

Phosphatidic acid promotes phosphoinositide metabolism and DNA synthesis in cultured cortical astrocytes.

The addition of exogenous phosphatidic acid (PA) to cultured cortical astrocytes prelabelled with [3H]inositol resulted in the accumulation of intracellular [3H]inositol phosphates (IP) in a concentration-dependent (EC50 = 20 microM) manner. Analysis of the individual IPs formed following a PA challenge revealed a rapid but transient generation of [3H]inositol trisphosphate (IP3) indicating the involvement of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown in this response a fact which was confirmed when the recovery of radiolabel in membrane phosphoinositides was assessed. PA's ability to stimulate IP3 accumulation was found to be dependent upon its acyl-chain length. Dioleoyl-PA (C18:1) was equally as effective as PA from egg yolk lecithin in this respect whilst dipalmitoyl-PA (C16:0) was less so and dimyristoyl-PA (C14:0) and dilauroyl-PA (C12:0) were without effect. In subconfluent, serum-deprived cultures, PA was found to increase DNA synthesis following a 48 h exposure period. This effect was observed over the same concentration range used to measure phosphoinositide breakdown and was found to be mediated by the activation of protein kinase C. As with its effect on phosphoinositide metabolism, PA's ability to promote DNA synthesis was correlated with its acyl-chain length. These data show that PA is capable of stimulating both phosphoinositide metabolism and DNA synthesis in cultured astrocytes possibly via the activation of specific membrane receptors. However, the precise relationship between these events remains to be elucidated.

Animals↗
PubMed1994

Mothering on crack cocaine: a grounded theory analysis.

Mothers who use crack cocaine are commonly believed to be selfish, uncaring, and neglectful of their children. For this paper, the grounded theory method was used to analyze 68 semi-structured depth interviews with cocaine-using mothers. These women's views of motherhood, the strategies they used to manage mothering on cocaine, and the contextual influences on mothering outcomes were explored. Contrary to popular assumptions, the women highly valued motherhood and held firm standards for childrearing. Mothers were concerned about the possible risks to their children and used a process of defensive compensation to protect both their children and their maternal identities from the negative influences of crack cocaine. When unable to fulfil their maternal responsibilities by other means, some mothers placed their children with family members, and others lost custody involuntarily. When children were forcibly removed, mothers often increased their drug use to cope with the loss. Social and economic conditions influenced the outcomes of mothering on crack.

Adult↗
PubMed1994

Muscarinic cholinergic stimulation of the nitric oxide-cyclic GMP signaling system in cultured rat sensory neurons.

Acetylcholine or carbachol stimulated cyclic GMP production in neuronal cultures from embryonic rat dorsal root ganglia but not in non-neuronal dorsal root ganglia cultures. Acetylcholine stimulation of cyclic GMP production was mediated by muscarinic receptors and required extracellular Ca2+. Basal cyclic GMP production and acetylcholine-evoked cyclic GMP production were attenuated by Methylene Blue, suggesting the involvement of soluble guanylate cyclase and nitric oxide synthase. L-NG-Monomethyl arginine attenuated basal, acetylcholine or carbachol-stimulated cyclic GMP production; this inhibition of acetylcholine and carbachol stimulation of cyclic GMP was reversed by L-arginine. These results suggest that a nitrosyl factor mediates basal, as well as acetylcholine- and carbachol-stimulated, cyclic GMP production. Selective destruction of small diameter neurons by capsaicin pretreatment of dorsal root ganglion neuronal cultures abolished acetylcholine and capsaicin stimulation of cyclic GMP, but did not affect sodium nitroprusside stimulation of cyclic GMP. These results suggest that acetylcholine evoked production of a nitrosyl factor in capsaicin-sensitive (small diameter) sensory neurons, which subsequently stimulated a soluble guanylate cyclase and cyclic GMP production in adjacent neuronal and/or non-neuronal cells. These results demonstrate that muscarinic agonists stimulate the nitric oxide-cyclic GMP signaling system in capsaicin-sensitive sensory neurons. Thus, the noxious character of acetylcholine when administered peripherally may be mediated by nitric oxide-cyclic GMP.

Acetylcholine↗
PubMed1994

alpha-Phenyl-tert-butyl-nitrone inhibits free radical release in brain concussion.

Traumatic brain injury (TBI) is one of the important causes of mortality and morbidity. The pathogenesis of the underlying brain dysfunction is poorly understood. Recent data have suggested that oxygen free radicals play a key role in the primary and secondary processes of acute TBI. We report direct electron spin resonance (ESR) evidence of hydroxyl (.OH) radical generation in closed-head injury of rats. Moderate brain concussion was produced by controlled and reproducible mechanical, fixed, closed-head injury. A cortical cup was placed over one cerebral hemisphere within 20 min of the concussion, perfused with artificial cerebrospinal fluid (aCSF) containing the spin trap agent pyridyl-N-oxide-tert-butyl nitrone (POBN, 100 mM), and superfusate samples collected at 10 min intervals for a duration up to 130 min post brain trauma. In addition, POBN was administered systemically (50 mg/kg body wt.) 10 min pretrauma and 20 min posttrauma to improve our ability to detect free radicals. ESR analysis of the superfusate samples revealed six line spectra (alpha N = 15.4 G and alpha beta H = 2.5 G) characteristic of POBN-OH radical adducts, the intensity of which peaked 40 min posttrauma. The signal was undetectable after 120 min. Administration of alpha-phenyl-tert-butyl-nitrone (PBN), a spin adduct forming agent systemically (100 mg/kg body wt. IP 10 min prior to concussion) alone or along with topical PBN (100 mM PBN in aCSF), significantly (p < 0.001) attenuated the ESR signal, suggesting its possible role in the treatment of TBI.

Animals↗
PubMed1994

Secretory leukocyte protease inhibitor and lung inflammation in developing bronchopulmonary dysplasia.

OBJECTIVE: To investigate secretory leukocyte protease inhibitor (SLPI) concentrations in tracheal lavage fluids of neonates with an endotracheal tube in place during the first month of life, and to evaluate the relationship of SLPI to neutrophil counts and elastase activity in patients in whom bronchopulmonary dysplasia (BPD) developed versus those in whom it did not. DESIGN: A prospective, inception cohort study. SETTING: University children's hospital neonatal intensive care unit. PATIENTS: Fifty-three neonates who weighed < 2000 gm at birth, and who had an endotracheal tube in place, were enrolled. Forth-one patients survived to 28 days; BPD developed in 24 but not in 17 patients. MAIN OUTCOME MEASURES: Tracheal lavage was performed on days 1, 2, 4, 7, 14, 21, and 28, and analyzed for neutrophils, elastase activity, and SLPI. Results were evaluated longitudinally for 28 days, and were compared between BPD and no-BPD groups during the first week. RESULTS: SLPI concentrations increased significantly for all patients during the study period. During the first week, SLPI concentrations were similar between BPD and no-BPD groups; neutrophil counts and elastase activity were higher in the BPD group. CONCLUSIONS: Patients in whom BPD ultimately developed had early evidence of increased pulmonary inflammation and a significantly less favorable protease-antiprotease balance. If elastase-induced injury contributes to the development of BPD, early therapy with recombinant SLPI might be beneficial by increasing the antielastase capacity of epithelial lining fluid.

Bronchoalveolar Lavage Fluid↗
PubMed1994

Lumbar vertebral and femoral neck bone mineral density are higher in postmenopausal women with the alpha 2HS-glycoprotein 2 phenotype.

alpha 2HS-glycoprotein (AHSG) is a plasma protein which becomes concentrated in the organic matrix of bone. The two most common alleles, AHSG*1 and AHSG*2, give rise to three common phenotypes. A recent report showed that a group of postmenopausal white North American women with different AHSG phenotypes differed significantly with respect to their oestrogen status. We have studied variations in bone mineral density, measured by DEXA, and levels of sex hormones and biochemical markers of bone metabolism in a group of 88 post-menopausal women unselected as to their health status. Lumbar vertebral and femoral neck bone mineral density (BMD), and the free oestradiol index were all significantly higher (P < 0.05) in women with the AHSG 2 phenotype. Values of these three parameters were lowest in the AHSG 1 phenotype and intermediate in the AHSG 2-1 phenotype. Because the differences in BMD between the AHSG 2 and 1 phenotypes represent at least a 40% difference in fracture risk, the AHSG phenotype may be of some clinical relevance as a risk factor for osteoporosis.

Aged↗
PubMed1994

A multicenter evaluation of reproducibility of swirling in platelet concentrates. Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion.

BACKGROUND: Eleven laboratories participated in a study investigating whether swirling can be used in monitoring platelet discoid morphology in platelet concentrates (PCs). STUDY DESIGN AND METHODS: In each laboratory, two readers observed the swirling pattern in 1- to 5-day-old PCs, in PCs containing spherical platelets obtained by 4 degrees C storage (spherical PCs), and in PCs containing known proportions of spherical and discoid platelets. Swirling was reported as positive, intermediate, or negative. Moreover, platelet morphology was evaluated by oil-phase microscopy. RESULTS: Swirling of spherical PCs was found to be positive and negative in 5 and 68 percent of cases, respectively. Conversely, swirling of fresh PCs was positive and negative in 83 and 2 percent of cases, respectively. Results in PCs containing known amounts of added spherical platelets were intermediate between those in fresh and spherical PCs. The observed agreement between the two readers (number of concordant readings/total readings) was 67 percent. Most disagreements concerned positive versus intermediate or intermediate versus negative evaluations, whereas a positive versus negative disagreement was observed in only 1 percent of cases. The percentages of discs found by microscopy showed greater variation among the different laboratories, indicating that this measurement should be better standardized. CONCLUSION: Evaluation of swirling seems promising for large-scale quality control of PCs. Further studies are needed to confirm this hypothesis.

Blood Platelets↗
PubMed1994

The prevalence and morbidity of snake bite and treatment-seeking behaviour among a rural Kenyan population.

Snake-bite mortality among a rural population in Kenya was estimated to be 6.7/100,000 people each year, representing 0.7% of all deaths. A community-based retrospective survey of 4712 households provided estimates of the incidence of snake bite in this population. Although 151/100,000 people are bitten each year, only 19% of these are bitten by potentially venomous snakes. When those who had been bitten were shown photographs of a range of locally prevalent snakes, most indicated that both venomous and non-venomous snakes were capable of causing death. Most (68%) of bite cases sought treatment from a traditional healer who invariably used local herbal preparations applied to the bite site and/or in a ring around the bitten limb. Local skin incisions were also commonly practised. The use of traditional medicine for snake bite is a feature of most areas of the developing world where venomous snakes are prevalent. Improvements in early referral and appropriate care will only occur when traditional healers are integrated into primary health care and hospital-based health systems.

Adolescent↗
PubMed1994

Histopathologic consequences of moderate concussion in an animal model: correlations with duration of unconsciousness.

Although duration of unconsciousness is commonly used as a prognostic index following traumatic brain injury (TBI), few controlled studies have statistically evaluated the relationship between unconsciousness and histologic pathology, particularly after moderate head injury. Using a pendulum-striker concussive device, a reproducible model of TBI in rats was developed. This model is uncomplicated by skull fractures, contusions, or experimenter-induced craniotomies. In the present study, the severity of the histopathology observed in this model of moderate closed-head injury at 48 h posttrauma is linearly related to the duration of unconsciousness (p < 0.0001). The pathology, assessed with a silver stain for neurodegeneration, is particularly striking if unconsciousness persists for 4 minutes or more. These data suggest that the initial period of unconsciousness may be a useful predictor of clinical brain histopathology associated with moderate closed-head injury, predicting either the degree of pathology and/or the rate it progresses if left untreated.

Animals↗
PubMed1994

Age-associated bone loss in men and women and its relationship to weight.

The relationship of bone mineral density (BMD) to age and weight was investigated in a cross-sectional study of 942 community-dwelling men and women aged 65-74 years. BMD continues to decline after the age of 65 at a similar rate in men and women. BMD was positively associated with weight in both men and women with similar regression slopes; approximately one third of the decline in BMD with age could be explained by the associated age-related decline in weight. Maintaining weight in later life may prevent some of the age-related loss of bone. Whatever factors are responsible for the age-related decline in bone mass apply similarly in men and women at these older ages: there is no evidence for accelerated decline in women in this age group.

Aged↗
PubMed1994

Single-dose cholecalciferol suppresses the winter increase in parathyroid hormone concentrations in healthy older men and women: a randomized trial.

A randomized double-blind controlled trial of a single oral dose of 2.5 mg (100,000 IU) cholecalciferol (vitamin D3) was conducted in the winter in 189 healthy free-living men and women aged 63-76 y. The mean baseline serum concentration for 25-hydroxyvitamin D was 34.5 nmol/L and for parathyroid hormone 3.18 pmol/L. After 5 wk, mean serum 25-hydroxyvitamin D concentrations were 60% higher in the treated than in the placebo group (P < 0.001). There was a 12% difference in parathyroid hormone concentrations in the treated compared with the placebo group (P < 0.001). No differences in serum calcium were seen. Findings suggest that 25-hydroxyvitamin D has a physiological role in the regulation of parathyroid secretion independent of serum calcium in healthy elderly people. Parathyroid concentrations rise and 25-hydroxyvitamin D concentrations decline with age. These results may have implications for the prevention of osteoporotic fractures that occur with increased frequency in winter and in elderly people.

Aged↗
PubMed1994

Comparison of pH and carbon dioxide tension values of central venous and intraosseous blood during changes in cardiac output.

OBJECTIVE: To compare the pH and PCO2 values determined from of simultaneously corrected samples of central venous and intraosseous blood during sequential changes in cardiac output. DESIGN: Prospective, descriptive study. SETTING: An animal laboratory in a university medical center. SUBJECTS: Fourteen mixed breed 4-wk-old piglets. INTERVENTIONS: Animals were anesthetized with ketamine hydrochloride and neuromuscular blockade was induced by the administration of pancuronium bromide. After endotracheal intubation and the institution of mechanical ventilation, a 4-Fr pulmonary artery catheter and a carotid artery cannula were inserted via a cutdown into the right neck of each piglet. A 16-gauge intraosseous needle was inserted into the anteromedial surface of the right tibia. MEASUREMENTS AND MAIN RESULTS: Central venous and intraosseous blood gas samples were obtained simultaneously with thermodilution cardiac output measurements. Cardiac output measurements were as follows: during steady state (0.80 +/- 0.14 L/min), after volume loading of 15 mL/kg (1.00 +/- 0.25 L/min), after three successive bleeds of 15 mL/kg each at 30-min intervals (0.70 +/- 0.28, 0.54 +/- 0.22, and 0.43 +/- 0.16 L/min, respectively) and at exsanguination (unrecordable). Paired t-tests demonstrated no significant differences in pH and PCO2 values between intraosseous and central venous samples under all study conditions. Limits of agreement for difference in PCO2 between sites, within the range of cardiac outputs studied, were -12.86 to 11.38 torr (-1.71 to 1.46 kPa) and for pH were -0.09 to 0.15. CONCLUSIONS: Intraosseous blood samples can be obtained without difficulty even during extreme hypovolemia. The pH and PCO2 values of intraosseous and central venous blood samples were similar under all study conditions. Intraosseous blood may be a useful alternative to central venous blood to assess tissue acid-base status during hemorrhagic shock and other low-flow states.

Animals↗
PubMed1994

Systemic lupus erythematosus: considerations for a genetic approach.

There is a powerful evidence suggesting that etiology and pathogenesis of systemic lupus erythematosus has both genetic and environmental components. Unfortunately, understanding the genetics of lupus has been impeded by knowing the pattern of inheritance. Indeed, a complex mode of inheritance for the lupus disease phenotype is suggested by the known characteristics of this disorder. Twenty-five multiplex pedigrees for lupus have been enrolled and have been used to evaluate power to reveal linkage. The power to find linkage in these pedigrees is greater for autosomal recessive than for autosomal dominant modes of inheritance. Once 100 similar pedigrees are available for analysis our results predict that linkage is likely to be present for genetic models with relatively relaxed requirements. At loci operating by autosomal recessive inheritance linkage should be detectable despite genetic homogeneity as low as 40% and penetrance as low as 50%. For loci operating by autosomal dominant inheritance genetic homogeneity must be 60% or more when penetrance is as low as 50% to be able to establish linkage. Available preliminary data are also consistent with a possible genetic linkage of Fc gamma RIIIPMN with lupus in American Black pedigrees multiplex for lupus.

Alleles↗
PubMed1994

A formative evaluation of the Welsh Heartbeat Award Scheme.

This paper presents findings from a study which examined the experiences of Environmental Health Officers and catering establishments with the Welsh Heartbeat Award Scheme, and their views on its future direction. Data were obtained via self-completion questionnaires from 26 Environmental Health Officers and 117 catering establishments across Wales between November 1991 and May 1992. The results show that the scheme is valued by both groups. Suggested improvements included leaflets to promote the scheme to caterers, and hygiene guidance notes and a healthy catering recipe book for caterers. One key problem highlighted by the study was effective monitoring of the scheme, a solution to which may lie with District Health Authority commissioners.

Awareness↗
PubMed1994

Renal function and proteinuria after cardiopulmonary bypass: the effects of temperature and mannitol.

We studied three groups of patients without previous renal impairment, undergoing elective coronary artery bypass surgery. Group H (n = 7) underwent open heart surgery using moderate hypothermia (28 degrees C); Groups N and M (n = 8, each) were managed at normothermia. The extracorporeal circuit was primed with Hartmann's solution 2.5 L with the addition of mannitol 0.5 g/kg in Group M. Serum concentrations of sodium and creatinine, and the urinary concentrations of microalbumin and N-acetyl-beta-D-glucosaminidase (NAG) were measured in each patient at six different time intervals: T0, 6 h prior to surgery; T1, between sternotomy and 45 min into cardiopulmonary bypass (CPB); T2, in the interval from 45 min into, to prior to weaning off CPB; T3, from coming off CPB to skin closure; T4, in the first 6 h in the intensive care unit; and T5, at 6 days postoperatively. Creatinine clearance (CCR) and fractional sodium excretion (FENA) were calculated at each time point. Urine output during CPB at Interval T2 was significantly higher in Group H compared to Group N (P = 0.03) but not Group M. We found no significant differences in CCR, FENA, microalbuminuria, and urinary NAG among the three groups at any time. However, there were overall significant changes in measured variables over time compared to baseline. We conclude that CPB is associated with a significant alteration in renal function as shown by increased FENA, microalbuminuria, and urinary NAG. The use of hypothermic or normothermic CPB and the use of prophylactic mannitol did not produce any significant modification of these changes.

Coronary Artery Bypass↗