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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 163 records · Page 9Linked to original sources
PubMed1997

Noncirrhotic hepatoma presenting with paraneoplastic neurologic manifestations: two cases.

Hepatocellular carcinoma usually occurs in patients with cirrhosis and is rarely associated with paraneoplastic neurologic disorders. We describe two young patients with hepatomas occurring in noncirrhotic livers, both of whom presented with neurologic symptoms. A 19-yr-old man who presented with coma and a 23-yr-old woman with a 3-month history of progressive hemiparesis, dysarthria, and altered affect were each found, at autopsy, to have hepatocellular carcinoma occurring in a noncirrhotic liver. Neuropathologic examinations revealed widespread multifocal necrotizing leukoencephalopathy in the man and occlusive noninflammatory cerebral vasculopathy with widespread cortical and subcortical infarcts in the woman. It is unlikely that the neuropathologic findings in these patients are explicable on the basis of antibody-mediated tissue injury.

Adult↗
PubMed1996

Chronic salicylate poisoning and severe malaria.

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.

Acidosis↗
PubMed1996

Effect of hypoxia and reoxygenation on regional activity of nitric oxide synthase in brain of newborn piglets.

The activity of nitric oxide synthase (NOS) was measured in homogenates from cortex, striatum, hippocampus, cerebellum, pons, thalamus and midbrain of the brain of newborn piglets and the effects of hypoxia and posthypoxic period on this activity was evaluated. The control activities were 19.7, 31.5, 26.8, 16.7, 33.6, 19.3 and 39.4 pmol/mg protein per min, respectively. A 1 h period of hypoxia (an FiO2 of 7%) resulted in statistically significant decreases in the activity of NOS in every region of the brain except for the cortex, where the activity was not significantly altered compared to control. By 2 h of reoxygenation following such a hypoxic episode, the NOS activities increased to above control levels in all regions of the brain, but this increase was statistically significant compared to control only in thalamus. Since hypoxia induced the greatest decrease in NOS activity in the cerebellum, the kinetic constants of the enzyme were measured in homogenates from this region of brain. The decreased activity following the hypoxic episode was associated with an approximately four-fold increase in the apparent affinity (KM) for arginine with no significant change in the maximal rate of reaction (Vmax). The decrease in NOS activity subsequent to a hypoxic episode may contribute to the disturbances in cellular metabolism in the immature brain induced by episodes of hypoxia-reoxygenation.

Animals↗
PubMed1996

Alterations in CNS gene expression in a rodent model of moderate traumatic brain injury complicated by acute alcohol intoxication.

The combined effects of acute alcoholic intoxication and moderate traumatic brain injury (TBI) on zif/268, glial fibrillary acidic protein (GFAP), and preproenkephalin (PPE) mRNA expression were examined. Adult male Wistar rats received ip injections of a 5% alcohol solution (2.4 g/kg in a final volume of 20 ml isotonic saline) 10 min prior to fixed-head, mechanical injury. Using Northern analysis, a transient three- to fourfold induction of zif/268 mRNA levels was observed 45 min after injury in both TBI and alcohol-treated rats. This induction occurred in regions close to the impact site, namely, the olfactory bulb (OB) and frontal cortex (FTCTX) but not in the more distal piriform/amygdala cortex (P/A). No PPE mRNA changes were observed at 45 min for any experimental group. By 6 h, zif/268 transcript levels returned to or fell below basal levels in the OB and FTCTX while GFAP mRNA levels began to increase in TBI rats. At 24 h, GFAP mRNA levels were greatly increased in all three brain regions of TBI rats. However, alcohol inhibited the temporal induction of GFAP mRNA in the FTCTX and P/A triggered by TBI at 6 and 24 h. These results suggest that although acute alcohol intoxication prior to TBI does not influence gene expression patterns immediately after injury, it may minimize the transcriptional activation of astrocytes particularly in more distant brain regions that were influenced by the impact in nonintoxicated rats.

Alcoholic Intoxication↗
PubMed1996

Expression of nitric oxide synthase type II in the spinal cord under conditions producing thermal hyperalgesia.

There is evidence supporting spinal cord nitric oxide (NO) production in the mechanisms underlying hyperalgesia, presumed to arise from the activity of neuronal nitric oxide synthase type I (NOS I). Intrathecal administration of interleukin-1 beta and interferon-gamma to rats results in a thermal hyperalgesia which peaks at 2 h post-injection but which is undetectable 8 h post-injection. Expression of mRNA for nitric oxide synthase type II (NOS II) was detected by reverse transcription-polymerase chain reaction followed by Southern hybridization utilizing specific oligonucleotides in spinal cord tissue from animals 4 h and 8 h after cytokine injection, but not at longer time points. NOS II protein was detected in soluble fractions of spinal cords from animals 4 h and 8 h after cytokine injection. In situ hybridization for NOS II mRNA revealed positive cells bilaterally in the spinal cord 4 h after cytokine injection in a perivascular distribution and scattered throughout the gray and white matter. Immunohistochemistry for NOS II showed a similar distribution which could only be partially accounted for by macrophages/microglia. These results provide evidence for induction of NOS II expression under conditions producing thermal hyperalgesia and suggest a possible role in this behavior for the production of NO by a variety of cell types in the CNS.

Animals↗
PubMed1996

Rates of bone loss in peri- and postmenopausal women: a 4 year, prospective, population-based study.

1. Age-related bone loss is well established but reported rates of bone loss in the spine and femur vary widely. The aim of the present study was to investigate changes in bone mineral density in the lumbar spine and proximal femur in healthy postmenopausal women. 2. One hundred and thirty-eight population-based women, aged 45-65 years, recruited from general practice registers in 1990, were assessed at baseline; 108 returned for repeat assessment 4 years later, of whom 31 had taken hormone replacement therapy for 12 months or more of the 4-year study period. Bone densitometry of the lumbar spine and proximal femur was performed by dual-energy X-ray absorptiometry. Serum 25-hydroxyvitamin D and oestradiol were measured by RIA and serum intact parathyroid hormone by radio-immunometric assay. 3. The mean age at follow-up was 62 years (mean of 13.6 years after menopause). Lumbar spine bone mineral density was significantly higher in women who had received hormone replacement therapy for more than 12 months during the study period than in those who had not (P < 0.01). There was no difference between these two groups in the femoral neck or trochanteric bone mineral density. In the lumbar spine, the annual change in bone mass in untreated women was -0.39% (95% confidence intervals -0.60 to -0.09; P < 0.02) whereas there was a small gain in women receiving hormone replacement therapy [+0.36% (-0.12 to 0.84; P not significant)]. The annual change in bone mass in the femoral neck and trochanter was -0.51 and -0.45 respectively in untreated women (P < 0.01 and P < 0.02), and -0.16 and -0.15 in those receiving hormone replacement therapy (P not significant). 4. Our results demonstrate relatively low rates of bone loss in the spine and proximal femur in these healthy, population-based peri- and postmenopausal women. Hormone replacement therapy appeared to be associated with a significant protective effect on spinal, but not femoral, bone mineral density.

Absorptiometry, Photon↗
PubMed1996

Nitric oxide synthase type II mRNA stability is translation- and transcription-dependent.

Nitric oxide synthase (NOS) type II is induced in many cell types in response to cytokines or endotoxin. The duration of type II NOS mRNA expression in astroglial cells and macrophages in vitro is brief, even in the continuous presence of inducers, and their removal dramatically accelerates mRNA decay. Addition of cycloheximide, in the presence or absence of actinomycin D, protected the mRNA from degradation. Whereas type II NOS mRNA was partially stabilized by actinomycin D, manganese superoxide dismutase mRNA was almost completely stabilized. This suggests that type II NOS mRNA stability is regulated via transcription- as well as translation-dependent processes and that the effect of actinomycin D is mRNA specific.

Animals↗
PubMed1996

A multicenter inspection of the swirling phenomenon in platelet concentrates prepared in routine practice. Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion.

BACKGROUND: In a previous multicenter study, the absence of the swirling phenomenon correlated well with platelet disc-to-sphere transformation, a morphology feature associated in the past with poor platelet viability. STUDY DESIGN AND METHODS: In 13 centers, 5366 platelet concentrates (PCs) were prepared and stored under routine conditions and evaluated for the presence of swirling. PCs found not to have swirling were evaluated for pH and platelet and white cell counts in parallel with an equal number of PCs with swirling that were studied as controls. RESULTS: In 13 participating centers, swirling was reported to be absent after 3 and 5 days of storage in 0 to 3.8 percent and in 0 to 18 percent of PCs, respectively. In 94 percent of units with swirling, pH was 6.7 to 7.5; this is a range of values associated with adequate in vivo survival. In 69 percent of PCs without swirling, pH was lower than 6.4 or higher than 7.6; these values are associated with reduced platelet viability. Three-quarters of the cases in which the absence of swirling was associated with pH values between 6.7 and 7.5 were reported from 2 out of the 13 participating centers. CONCLUSION: In PCs prepared and stored under routine conditions, the presence of swirling correlated well with pH values associated with adequate platelet in vivo viability. In about 20 percent of PCs without swirling, this was not due to a low or high pH value, and it would be useful to investigate whether this lack of swirling is associated with poor platelet viability. These data support the possibility that the evaluation of swirling by visual inspection might replace invasive and more cumbersome assays currently used for routine PC quality control.

Blood Platelets↗
PubMed1996

An investigation into the physical stability of a neonatal parenteral nutrition formulation.

The physical stability of a neonatal parenteral nutrition formulation has been examined using differential interference contrast (DIC) microscopy. In vitro studies indicated that particle size increases occur immediately after mixing the Intralipid emulsion with the amino acid/glucose solution, while simulation of clinical administration indicated that larger droplets were observed at the end of the catheter approximately 1 h after administration commenced. Microscopic observation of adjacent droplets of the two fluids showed reversible aggregation occurring almost immediately. It was concluded that the current method of administering this neonatal emulsion does not prevent droplet coalescence.

Drug Stability↗
PubMed1996

General practitioners' immediate management of men presenting with urethral symptoms.

OBJECTIVES: To describe the immediate reported management, by general practitioners (GPs), of men presenting with symptoms of urethral discharge, or dysuria only. SUBJECTS: All 692 GPs in practice in Brent, Harrow, Ealing, Hammersmith, and Hounslow (UK). METHOD: Data were collected using a GP completed questionnaire concerning the management of the last male patient seen, aged less than 40 years, complaining of urethral discharge, and the last male patient under 40 years complaining of dysuria only. RESULTS: The response rate among GPs was 52%. Fifty three per cent of men with urethral symptoms, 86% of men with a urethral discharge and 24% with dysuria only, were identified by GPs and referred without investigation or treatment to a genitourinary medicine clinic. Of men with dysuria only, 93% of investigations by GPs were reported to include a mid-stream urine (MSU) specimen for bacteriology, and 19% a urethral swab for chlamydia. Seventy eight per cent of GPs reported using treatments with a broad spectrum antibiotic, 53% with trimethoprim, whilst 14% of GPs reported using a tetracycline in common use to treat non-gonococcal urethritis. Urine specimens were reported to be "culture positive" in 41% of men who had an MSU specimen tested, and 15% of men who had a urethral swab tested were reported to be chlamydia positive. CONCLUSION: The GPs included in this study were not a full sample, or representative of all the GPs, and the data are retrospective. Nevertheless, we found a large difference in GPs reported management for men with urethral symptoms according to whether or not urethral discharge was a reported complaint. Reported management is likely to be, at least, indicative of actual management. Therefore, the results suggest that assessment by GPs of men presenting with dysuria should be explored and more appropriate management strategies defined.

Adolescent↗
PubMed1996

The Nottingham Study of Neurotic Disorder: influence of cognitive therapists on outcome.

BACKGROUND: In previously published papers from the Nottingham Study of Neurotic Disorder a short treatment package of cognitive-behaviour therapy was no more effective than placebo drug treatment after 10 weeks' assessment in a cohort of 210 patients with neurotic disorders. This paper examines the outcome over two years of the patients treated by cognitive-behaviour therapy separated into two therapist groups, those who were competent in administering treatment and those of uncertain competence. METHOD: The therapists (mainly community psychiatric nurses) of 70 patients with an original DSM-III diagnosis of either dysthymic, panic or generalised anxiety disorder were separated into two groups on the basis of their perceived competence by their supervisor (DK). Ratings of psychopathology were made at regular intervals over two years by assessors blind to knowledge of treatment or therapist. RESULTS: The patients treated by competent therapists (n = 30) generally showed greater improvement than those allocated to therapists of uncertain competence (n = 40), mainly with respect to depressive symptoms, and the difference persisted over two years, long after the cognitive-behaviour therapy had been completed. CONCLUSIONS: Cognitive-behaviour therapy given by competent therapists over a 10 week period is of lasting benefit in neurotic disorder.

Adult↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1996

Improved survival for children with B-cell acute lymphoblastic leukemia and stage IV small noncleaved-cell lymphoma: a pediatric oncology group study.

PURPOSE: In an effort to improve outcome for children with advanced B-cell malignancies, a treatment plan based on a published regimen that consists of four courses of fractionated cyclophosphamide (cyclo) given with doxorubicin (doxo) and vincristine (VCR) was intensified by alternating with sequential high-dose methotrexate (MTX) and cytarabine (Ara-C), given in conjunction with intrathecal (IT) MTX and Ara-C. PATIENTS AND METHODS: From October 1986 to October 1992, 133 eligible patients were enrolled: 74 with B-cell (surface immunoglobulin-positive [Slg+] acute lymphoblastic leukemia (B-ALL) and 59 with stage IV small noncleaved-cell lymphoma (SNCCL). The median age was 8 years; there were 103 males and 30 females. Abdominal tumor masses were prominent in 63 cases (33 B-ALL and 30 stage IV SNCCL). RESULTS: Complete remission (CR) was achieved in 66 B-ALL and 57 stage IV patients (93% overall). At 4 years, the estimated event-free survival (EFS) rate is 65% +/- 8% for patients with B-ALL and 79% +/- 9% for those with stage IV SNCCL. Among patients with CNS involvement, 23 of 36 remain in CR (4-year EFS rate, 64% +/- 13%). Relapses occurred early; only 3 patients relapsed after completion of therapy. Thirteen relapses occurred in the marrow, three in the CNS, and six in other sites. Of 11 CNS-positive patients who relapsed, only two recurred primarily in the CNS. CONCLUSION: The results of this study indicate that with intensified chemotherapy an increasing potential for cure exists for patients with B-ALL and stage IV SNCCL.

Adolescent↗