Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 163 records · Page 9Linked to original sources

PubMed1996

Participation of nucleoside-diphosphate kinase in muscarinic K+ channel activation does not involve GTP formation.

Agonist-bound muscarinic receptors open atrial K+ channels through a GTP-dependent pathway mediated by the G protein Gk. However, nucleotides other than GTP are also able to support channel activity, even in the absence of agonists. This process was proposed to be mediated by nucleoside-diphosphate (NDP) kinase, which would transfer phosphate from nucleotide triphosphates to the GDP bound to Gk, producing Gk-GTP without the need for receptor-induced GDP-GTP exchange. We examined the effect of antibodies to NDP kinase on the ATP-supported activity of atrial muscarinic K+ channels and the corresponding GIRK1/CIR channels expressed in HEK 293 cells. Inhibitory antibodies reduced ATP-induced channel openings, but this effect displayed an absolute requirement for agonist and was also seen with antibodies that do not inhibit the enzyme. Both types of antibodies also reduced agonist-dependent channel activity in the presence of GTP, ruling out a role for NDP kinase in GDP rephosphorylation. Channel activity was not affected by the antibodies in preparations where ATP-induced muscarinic channels are not under tight receptor control, namely pertussis toxin-treated atrial patches and membranes from cells expressing KACh channel subunits. Thus, participation of NDP kinase in this pathway requires activated receptors and has a function distinct from phosphate transfer between nucleotides.

Adenosine Triphosphate↗

PubMed1996

Cortexillins, major determinants of cell shape and size, are actin-bundling proteins with a parallel coiled-coil tail.

Cortexillins I and II of D. discoideum constitute a novel subfamily of proteins with actin-binding sites of the alpha-actinin/spectrin type. The C-terminal halves of these dimeric proteins contain a heptad repeat domain by which the two subunits are joined to form a two-stranded, parallel coiled coil, giving rise to a 19 nm tail. The N-terminal domains that encompass a consensus actin-binding sequence are folded into globular heads. Cortexillin-linked actin filaments form preferentially anti-parallel bundles that associate into meshworks. Both cortexillins are enriched in the cortex of locomoting cells, primarily at the anterior and posterior ends. Elimination of the two isoforms by gene disruption gives rise to large, flattened cells with rugged boundaries, portions of which are often connected by thin cytoplasmic bridges. The double-mutant cells are multinucleate owing to a severe impairment of cytokinesis.

Actins↗

PubMed1996

Children on hunger strike: child abuse or legitimate protest?

The issue of children on hunger strike (voluntary total fasting) has not been reported before. The World Medical Association Declaration of Tokyo 1975 and the Declaration of Malta 1991 (revised 1992) provide clinicians with guidelines for the management of adult patients on hunger strike but do not mention children. We report the management of 14 Vietnamese children, aged 1 to 12 years, who took part in a hunger strike at a refugee detention centre in Hong Kong.

Child↗

PubMed1996

Effect of caffeine on recognition of and physiological responses to hypoglycaemia in insulin-dependent diabetes.

BACKGROUND: For the patient with diabetes, hypoglycaemia unawareness--ie, the warning signs of falling blood glucose are missing--is potentially dangerous. One study has suggested that, in healthy volunteers, caffeine might be a helpful treatment. Our study looked at two effects of caffeine ingestion (250 mg) on the brain--namely, a decrease in cerebral blood flow and an increase in brain glucose use--to see if the recognition of and physiological responses to hypoglycaemia were altered in patients with insulin-dependent diabetes mellitus (IDDM). METHODS: 12 patients were studied twice. A hyperinsulinaemic glucose clamp was used to maintain plasma glucose at 5 mmol/L for 90 min, followed by 60 min at 3.8 mmol/L, and then 2.8 mmol/L for a further hour. After 30 min at 5 mmol/L, patients consumed, in a double-blind, crossover design, 250 mg caffeine or matched placebo. We recorded middle cerebral artery velocity (VMCA), counterregulatory hormone levels, and cognitive function, and patients recorded hypoglycaemia symptoms on a visual analogue scale. RESULTS: Caffeine caused an immediate and sustained fall in VMCA of 10 cm/s, from 60 to 50 cm/s (95% CI -5 to -15 cm/s; p < 0.001). At a blood glucose of 3.8 mmol/L, plasma adrenaline levels were twice as high after caffeine than after placebo (difference 524 pmol/L). When glucose was lowered to 2.8 mmol/L, caffeine ingestion was associated with: greater awareness of hypoglycaemia in 9 patients, significantly more intense autonomic and neuroglycopenic symptoms, and higher levels of adrenaline, cortisol, and growth hormone. Cognitive function (latency of P300 evoked potentials) deteriorated to the same extent in both studies at this glucose level. INTERPRETATION: The sustained fall in VMCA and augmented sympathoadrenal and symptomatic responses during moderate hypoglycaemia suggest caffeine as a potentially useful treatment for diabetic patients who have difficulty recognising the onset of hypoglycaemia.

Adult↗

PubMed1996

Epidemiology of AIDS among Hispanics in Chicago.

The purpose of this study was to describe the epidemiology of AIDS among Hispanics in Chicago. These data are needed to tailor prevention and treatment programs across diverse Hispanic ethnic subgroups. To pursue Hispanic origin for the 1,289 Hispanic persons diagnosed with AIDS in Chicago, death certificates for those cases contained in Chicago's AIDS Reporting System (ARS) file that were decreased were examined for information on national origin; the AIDS case reporting form was modified in January 1994 to collect data on Hispanic ethnic origin; care providers were contacted for further information; and medical records were investigated to determine Hispanic ethnic origin. Ethnic origins obtained from all sources are according to patient self-report. All reference to Hispanic ethnic subgroups in this study include U.S.-born and foreign-born Hispanics. Ethnic subgroup was identified for 989 Hispanic persons (77% of the 1,289 Hispanic cases) in the ARS. Data collected indicate that for all races and across Hispanic ethnic subgroups, Puerto Ricans have had the highest annual AIDS case rate since 1987. The mode of transmission for Puerto Rican males is predominantly through injection drug use (IDU), whereas for Mexican males the predominant mode of transmission is through males having sex with other males (MSM). For all Hispanic females, heterosexual contact was the predominant mode of transmission, with the largest proportion being sex partners of IDUs. The descriptive epidemiology of AIDS across Hispanic ethnic subgroups in Chicago highlights the need to target specific interventions among Puerto Ricans. In particular, culturally sensitive interventions tailored for Puerto Rican IDUs and their sex partners are needed, as are interventions for all Hispanic females who are at increased risk for heterosexual transmission.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Primary penile lymphoma: the case for combined modality therapy.

A patient with non-Hodgkin's lymphoma with a penile mass as the only apparent site of clinical involvement is presented, and the literature reviewed. Our patient was treated initially with partial penile amputation. A year later the lymphoma recurred in the chest and the right tonsil. Further chemotherapy failed to salvage the patient, who died of disseminated lymphoma. We suggest that, for patients presenting with a lymphomatous penile mass as the initial manifestation of non-Hodgkin's lymphoma, chemotherapy with or without radiotherapy as the initial treatment. Surgery should be reserved only for failures.

Aged↗

PubMed1996

The impact of the technological care environment on the nursing role.

Proliferation of acute health care technology creates problems and benefits for nurses and patients. In this paper the impact of technology on the nursing work role is reviewed through the international literature. The thrust of the nursing literature has, not surprisingly, matured over time as the use of technology has become well established in the acute care environment, and three themes can be identified. The implications for acute care nurse specialists, including their educational needs, are set in context of the Australian health care system, with particular reference to the cardiac care environments.

Australia↗

PubMed1996

Glycolipids of human primary testicular germ cell tumours.

The glycolipid content of human non-seminomatous germ cell tumour cell lines correlates with their differentiation lineage. To analyse whether this reflects the situation in primary tumours, we studied five embryonal carcinomas, five yolk sac tumours and nine (mixed) non-seminomas, using thin-layer chromatography and carbohydrate immunostaining. We also analysed the glycolipid content of 19 seminomas to reveal their relationship with non-seminomas. Lactosylceramide (CDH) was detected in all embryonal carcinomas, but in fewer than half of the seminomas. Seminomas and embryonal carcinomas contained globoseries glycolipids, including globotriosylceramide (Gb3), globoside (Gb4), galactosy globoside (Gb5) and sialy1 galactosyl globoside (GL7). The lacto-series glycolipid Le(x) was found in all embryonal carcinomas, but only in one seminoma. Gangliosides GD3 and GT3 were detected in many seminomas, but rarely in embryonal carcinomas. Yolk sac tumours displayed a heterogeneous glycolipid profile. Compared with seminomas and pure embryonal carcinomas, differentiated non-seminomas had reduced levels of globo-series glycolipids, especially Gb3 and Gb5, whereas CDH, Le(x), GD3 and GT3 were found in the majority of cases. Thus, the glycolipid content of non-seminoma cell lines reflects the situation in primary tumours. Globo-series glycolipids are similarly expressed in seminomas and embryonal carcinomas. The expression of Gb3 and Gb5 is reduced in non-seminomas upon differentiation. Le(x) expression in non-seminomas, including embryonal carcinomas, allows discrimination from seminomas. Expression of gangliosides in seminomas might indicate their maturation from ganglioside-negative precursor cells. Reprogramming of these precursors would result in the formation of Le(x)-expressing embryonal carcinomas.

Carbohydrate Sequence↗

PubMed1996

Specific suppression of human tumor necrosis factor-alpha synthesis by antisense oligodeoxynucleotides.

Recent clinical studies using neutralizing antibodies point to a key role for tumor necrosis factor-alpha (TNF-alpha) in chronic inflammatory diseases. Antisense technique is a recent approach aiming at inhibition of single proteins. Previously, we described nonspecific induction of TNF by phosphorothioate oligonucleotides. In this study, we established an in vitro model that allows specific inhibition of TNF synthesis, bypassing TNF induction. Freshly isolated human monocytes were incubated with oligonucleotides and the cationic lipid lipofectin in different ratios. TNF synthesis was stimulated with lipopolysaccharide and quantified by a specific radioimmunoassay (RIA). Among all sequences tested, one of the antisense oligonucleotides complementary to the translation initiation region of TNF mRNA (5'-CAT GCT TTC AGT CAT-3') revealed highest efficacy. At 2 microM, the antisense oligonucleotide inhibited TNF synthesis by up to 79%. A concentration as low as 250 nM of the antisense oligonucleotide was effective. Scrambled controls and controls with different, defined degrees of mismatches confirmed a sequence-specific action. Examination with confocal fluorescence microscopy showed a marked difference comparing lipofectin-mediated vs. spontaneous uptake. This study defines criteria that from the prerequisite necessary for design and application of antisense oligonucleotides against TNF in vivo.

Fluorescent Dyes↗

PubMed1996

Event-related potential prolongation in Alzheimer's disease signifies frontal lobe impairment: evidence from SPECT imaging.

BACKGROUND: The N2 and P3 components of auditory event-related potentials (ERPs) and single-photon emission computed tomographic (SPECT) images are separate independent biological markers of cerebral function and are abnormal in Alzheimer's disease (AD). The relationship between ERP N2 and P3 latencies and regional cerebral perfusion abnormalities in AD is unknown. METHODS: ERP and SPECT data were obtained one week apart in 18 patients with "probable" AD of mild or moderate severity, and 12 healthy age-matched elderly controls. Average premotor frontal, anterior temporal, inferior parietal, and occipital cortical/cerebellar perfusion ratios were calculated from the SPECT data and correlations with ERP N2 and P3 latencies derived for AD and control groups separately. RESULTS: ERP N2 latency was correlated significantly with the average frontal perfusion ratio (r = -.59; p < .009), but correlations with average temporal, parietal, and occipital ratios were nonsignificant in the AD group. Similarly, ERP P3 latency was correlated significantly with the average frontal perfusion ratio (r = -.65; p < .004), but not with the other perfusion ratios in the AD group. In the control group, a partial correlation between the average frontal perfusion ratio and the ERP N2 latency was noted (r = -.52; p < .09), but no other ERP/SPECT correlations approached statistical significance. CONCLUSION: ERP N2 and P3 latency delay in AD is a function of differential frontal lobe hypoperfusion.

Aged↗

PubMed1996

A case-control study of risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I) in Jamaica.

BACKGROUND: We investigated behavioural and environmental risk factors for seropositivity to human T-lymphotropic virus type I (HTLV-I). METHODS: A nested case-control study of 201 HTLV-I seropositive subjects and 225 age- and sex-matched seronegative controls was performed using questionnaire data from the enrollment visit of a cohort study in 1987-1988. HTLV-I serostatus was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot. RESULTS: Among women, the number of lifetime sexual partners (P < 0.05, chi 2 trend) and the number of different men fathering a child by the woman (P < 0.06, chi 2 trend) were associated with HTLV-I seropositivity. Use by the female subject of an intrauterine device (IUD) was associated with an increased risk of seropositivity (odds ratio (OR) = 2.67, 95% confidence interval (CI): 1.13-6.23); condom use was rare in this population. Among male subjects, a larger number of lifetime sexual partners was also associated with HTLV-I seropositivity (P < 0.05, chi 2 trend). No association was found between HTLV-I seropositivity and educational attainment, income, or occupation. Having been breastfed as a child or receipt of a blood transfusion had elevated but imprecise OR due to very high and low prevalence of the risk factors, respectively. Several variables relating to insect or animal exposure showed no association with HTLV-I seropositivity. CONCLUSIONS: These data confirm that heterosexual intercourse is a major route of HTLV-I transmission, but do not support suggestions of insect or environmental vectors.

Adult↗

PubMed1996

Health effects of human T-lymphotropic virus type I (HTLV-I) in a Jamaican cohort.

BACKGROUND: Other than adult T-cell leukaemia (ATL) and HTLV-I associated myelopathy (HAM), the health effects of infection with human T-lymphotropic virus type I (HTLV-I) are not well defined. METHOD: A cohort of 201 confirmed HTLV-I seropositive Jamaican food service workers and 225 seronegative controls of similar age and sex from the same population was examined. A health questionnaire, physical examination, and laboratory tests were performed at enrollment into the cohort in 1987-1988. RESULTS: One of 201 HTLV-I seropositives, but no controls were diagnosed with HAM, for a prevalence of 0.5% (95% confidence interval) (CI) 0.01-2.7%); no cases of ATL were diagnosed. While there was no difference in current symptoms, the HTLV-I seropositive group was more likely to report a past medical history of hepatitis or jaundice (OR = 3.49, 95% CI: 0.93-13.08), malaria (OR = 2.13, 95% CI: 0.96-4.73), and dengue fever (OR = 1.37, 95% CI: 0.82-2.29); however, these differences were of borderline statistical significance. Low income HTLV-I seropositive women had lower body weight (P < 0.01) and body mass index (P < 0.009) than their seronegative counterparts; similar differences were seen in the smaller male group. A trend toward higher prevalence of severe anaemia (haemoglobin < 10 g/dl) (12.6% versus 7.7%, P < 0.105) and a significantly lower prevalence of eosinophilia (1.0% versus 6.3%, P < 0.004) was seen among HTLV-I seropositives compared to controls. CONCLUSIONS: Although most HTLV-I seropositives are asymptomatic, HAM may be diagnosed in approximately 0.5% of carriers. Chronic HTLV-I infection may also exert subtle effects on body mass and haematological parameters.

Adult↗

PubMed1996

Modulation of lysyl oxidase by dietary copper in rats.

Lysyl oxidase levels were estimated in rat tissues using an enzyme-linked immunosorption assay (ELISA) and a functional assay standardized against known amounts of purified lysyl oxidase. High concentrations of lysyl oxidase (> or = 150 micrograms/g of tissue or packed cells) were detected in connective tissues, such as tendon and skin. Values for aorta, kidney, lung and liver ranged from 30 to 150 micrograms/g of tissue; values for skeletal muscle and diaphragm were < 30 micrograms/g tissue. Purified rat skin lysyl oxidase catalyzed the release of 50-100 Bq of tritium per micrograms enzyme in assays that used 3H-elastin-rich substrates. In dense connective tissues, good agreement was obtained for the values from ELISA and those derived from measurements of functional activity in aorta, lung, skin and tendon (r2 > 0.9). When egg white-based experimental diets containing 2 or 10 micrograms/g added copper were fed to weanling rats, values for skin lysyl oxidase functional activity in the group fed 2 micrograms/g added copper were one-third to one-half the values for skin lysyl oxidase functional activity in rats fed 10 micrograms/g copper. This reduction in lysyl oxidase activity, however, had minimal effect on indices of collagen maturation in rat skin, e.g., collagen solubility in neutral salt and dilute acid or the levels of acid stable cross-links. Moreover, copper deficiency did not influence the steady-state levels of lysyl oxidase specific mRNA in rat skin or the apparent amounts of lysyl oxidase in rat skin as determined by ELISA. These observations underscore that the concentration of lysyl oxidase is relatively high in dense corrective tissues, and although decreasing dietary copper influences functional activity, there is little apparent effect on the production of lysyl oxidase protein.

Administration, Oral↗

PubMed1996

Transesophageal echocardiographic guidance of transseptal left heart catheterization during radiofrequency ablation of left-sided accessory pathways in humans.

UNLABELLED: Radiofrequency ablation (RFA) of left-sided accessory pathways can be achieved using catheters introduced by a retrograde or transseptal approach. Transesophageal echocardiography (TEE) has previously been demonstrated to be safe and efficacious in guiding transseptal puncture in patients during mitral valvuloplasty (MV). This study was undertaken to assess the feasibility, safety, and clinical utility of TEE during transseptal puncture and RFA of left-sided accessory pathways. METHODS: TEE was performed during transseptal puncture in 30 patients (41 +/- 12 years, 19 females), 15 patients during attempted RFA of a left-sided accessory pathway and 15 patients during attempted balloon MV. RESULTS: There was no difference in age, sex distribution, or procedural complications when MV patients were compared to RFA patients. At baseline, left atrial dimension was increased and congestive heart failure was more common when MV patients were compared to RFA patients (P < 0.05) Adequate baseline two-dimensional and Doppler TEE images were obtained in all patients. One patient sustained mild esophageal bleeding during the TEE. Positioning of the transseptal catheter in the fossa ovalis was facilitated and confirmed by TEE in 29 of 30 cases. One case of cardiac perforation occurred and was associated with inadequate TEE localization of the fossa ovalis. Thrombus was detected on the transseptal catheter by TEE in two cases prior to systemic heparinization. In both cases, thrombus was removed without embolic event. CONCLUSIONS: TEE safely guides transseptal puncture in patients undergoing RFA of left-sided accessory pathways. TEE markers of the fossa ovalis facilitate puncture and may reduce the risk of cardiac perforation particularly in patients with a normal size left atrium. TEE may be especially valuable for identifying thrombus during transseptal puncture.

Adolescent↗

PubMed1996

Blood cultures in adult patients released from an urban emergency department: a 15-month experience.

OBJECTIVE: To determine the frequency of positive blood cultures obtained from adult patients with potential occult bacteremia released from an urban ED and how often these positive cultures alter the subsequent patient course or management. METHODS: This retrospective case series study was conducted at the ED of a large, urban teaching hospital. The study population consisted of a convenience sample of adult patients who presented to the ED with evidence of fever or other clinical conditions suggesting the possibility of bacteremia. The records of all patients who had blood cultures done and who were not admitted to an inpatient service were reviewed. Follow-up was obtained for all patients for whom culture results were positive. A substantial influence on the medical management or clinical course by a (noncontaminant) positive blood culture result was defined as a positive result that directly led to: further diagnostic testing, hospital admission, initiation or alteration of antibiotic therapy, or a different diagnosis. Culture-positive patients who were noncompliant with requested ED follow-up were included in this estimate. An estimate of the laboratory charges per diagnosis of bacteremia also was derived. RESULTS: Only 24 of 1,350 patients (1.8% of the study population; 95% CI 1.1-2.5%) had true-positive blood cultures. Only 7 patients (0.52% of the population; 95% CI 0.14-0.90%) potentially had their medical management affected by the positive blood culture results. Based on the laboratory charges associated with all blood cultures for this patient group, the cost per clinically significant positive blood culture result was $ 11,570. CONCLUSIONS: The prevalence of bacteremia was 1.8% among the released patients who had blood cultures obtained in the ED. Furthermore, only 0.52% of the patients had positive blood cultures that potentially affected their medical management. Further study is warranted to identify specific criteria for selecting ambulatory patients for whom the use of blood cultures may be cost-effective.

Adult↗

PubMed1996

Comparative effects of intravesical versus extravesical administration of ZD6169 and cromakalim on the response of the in vitro rat whole bladder to field stimulation.

Potassium channel openers are currently being evaluated for their inhibitory effect on hyperreflexia. Increasing potassium permeability results in a hyperpolarization of the smooth muscle membrane and a reduction in calcium entry. This stabilizes the membrane and should result in the reduction of spontaneous contractile activity. Potassium channel agonists have been shown to be effective in the reduction of hyperreflexia secondary to outlet obstruction in rats, and certainly have been shown to reduce the contractile response of isolated tissues to a number of different agonists. In addition, intravesical administration of potassium channel openers have been shown to be effective against hyperreflexia (in rabbits) using intravesical administration, although relatively high concentrations had to be employed. Using an in vitro whole bladder model (rat), our current study compares the potency and efficacy of intravesical versus extravesical administration of two potassium channel openers for the inhibition of field-stimulated contraction. The results demonstrate that (1) the extracellular administration of ZD6169 and cromakalim were equally effective inhibitors of the contractile response to field stimulation, (2) low frequency stimulation was inhibited to a significantly greater degree than high frequency stimulation, (3) intravesical administration of ZD6169 was equally effective at inhibiting the response to low frequency field stimulation when compared to extravesical administration, (4) intravesical administration was less effective than extravesical administration at high frequency stimulation (although the inhibition was still statistically significant), and (5) intravesical administration of cromakalim did not inhibit field stimulation.

Amides↗

PubMed1996

Are butter and cheese rich in monounsaturates beneficial in hyperlipidaemic patients?

BACKGROUND: Reduction in intake of dairy products has long been recommended to reduce blood lipids. The value of monounsaturated fatty acids is increasingly recognized. METHODS: We evaluated the effects of a monounsaturate-rich butter and cheese (B) produced by modifying the bovine diet on blood lipid levels of patients with type IIa hyperlipidaemia. We compared their effects with those of normal butter and cheese (A) and polyunsaturate-rich spread and cheese (C). Using a double cross-over design, we studied 30 patients of mean age 56.4 years (23 men, one woman excluded) over 6-week periods. RESULTS: Approximately 35.5 g/day butter/cheese were consumed; no changes in serum total cholesterol, triglycerides, low-density lipoprotein, lipoprotein (a) or cholesterol: high-density lipoprotein (HDL) ratio were observed. HDL levels were higher in B(1.31 mmol/l) than in C (1.22 mmol/l; P < 0.05) and similar to those in A (1.28 mmol/l). HDL2 levels were higher in patients fed diet A(0.23 mmol/l) than they were in those fed diet C (0.19 mmol/l; P < 0.05) and similar to those in patients fed diet B (0.20 mmol/l). Serum HDL3 was significantly higher in patients fed diet B (1.11 mmol/l) than in those fed diet C (1.03 mmol/l; P < 0.05) but similar to that in patients fed diet A (1.06 mmol/l). CONCLUSIONS: Moderate intake of modified dairy products may be of value and deserves further evaluation.

Butter↗

PubMed1996

Specification and initial evaluation of a multiple application teleradiology system.

The digitization and transmission of medical images is becoming increasingly more important and available. The selection of appropriate clinical applications for teleradiology systems is an important factor in determining the success of such ventures. In this paper, the selection of such applications and the evaluation of the teleradiology system is described. The system (LIAISON, CAPTEC Ltd, Malahide, Ireland) is PC based and is capable of digitization and transmission of three categories of medical images: (1) plain film radiographs; (2) CT film data and (3) video sequences such as ultrasound scans. A comprehensive technical evaluation was carried out on the acquisition and display station in which various parameters such as spatial resolution, signal-to-noise ratio (SNR), and distortion were investigated. Results showed that the system performed well within specifications. An exploratory clinical evaluation was performed using a case mix of subtle fractures, chests and dislocations, and CT scans. Here the system performed well with a diagnostic accuracy of 95% for the digital image compared with the analogue image.

Computer Communication Networks↗