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Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 199 records · Page 11Linked to original sources

Immune and serologic profiles of HIV-infected and noninfected hemophilic children and adolescents. Hemophilia Growth and Development Study Group.

OBJECTIVES: To assess relationships among the effects of HIV on hemophilic children and adolescents' immunologic parameters and vaccine-related serology. METHODS: We analyzed data from extensive baseline immunologic evaluations of 207 HIV antibody-positive (HIV+) and 126 HIV antibody-negative (HIV-) hemophilic children and adolescents. RESULTS: HIV+ and HIV- participants differed significantly in T-lymphocyte subpopulation numbers, immunoglobulin levels, and seroprevalence rates for diphtheria toxoid, measles, and mumps antigens, IgG levels, IgM levels, and serologic titers to vaccine antigens showed little correlation with T-cell parameters. Proportionately more HIV+ participants were nonreactive to each and all of a panel of 7 skin test antigens (71% vs 28% anergic, RR 2.6). The odds of anergy increased 1.6 times for every decline of 200 CD4+ cells/microliters. CONCLUSIONS: HIV had significant, largely independent T- and B-lymphocyte effects on this pediatric cohort.

Adolescent↗

High-dose methotrexate for gestational trophoblastic disease.

Eighty patients with low-risk and 5 patients with intermediate-risk gestational trophoblastic neoplasia (GTN) (WHO classification) were treated with single-agent high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI classification, 65 patients had nonmetastatic GTN, 13 patients had low-risk metastatic GTN, and 7 patients had high-risk metastatic GTN. Seventy-one (84%) patients achieved remission (beta HCG < or = 5 IU/liter) with MTX/FAR, whereas 14 (16%) failed to achieve remission with MTX/FAR alone. All failures were salvaged with second-line therapies. Patients successfully treated with MTX/FAR required a median of 4 courses to achieve remission, and a median of 2 consolidative courses. Factors found predictive of failure with MTX/FAR were pretreatment beta HCG (P = 0.003), prior history of GTN (P < 0.04), and time from termination of antecedent pregnancy to initiation of treatment (P < 0.05). No significant difference was noted between the "success" and "failure" groups with respect to MTX dose or infusion time, the timing and dosage of folinic acid rescue, the number of courses of MTX, or the mean interval between courses. Multivariate analysis revealed that the pretreatment beta HCG (P < 0.01) and short time from termination of antecedent pregnancy to initiation of treatment (P < 0.03) were independently significant for failure. No significant (grade 3/4) hematologic or gastrointestinal toxicity occurred, and no treatment delays or dose reductions were required. This regimen is both effective and well tolerated; however, the theoretical advantages of high-dose methotrexate do not appear to offer any clinical advantage over conventional dose MTX in low- and intermediate-risk GTN.

Biomarkers, Tumor↗

The importance of fixation procedures on DNA template and its suitability for solution-phase polymerase chain reaction and PCR in situ hybridization.

Conventional solution-phase polymerase chain reaction (PCR) and in situ PCR/PCR in situ hybridization are powerful tools for retrospective analysis of fixed paraffin wax-embedded material. Amplification failure using these techniques is now encountered in some centres using archival fixed tissues. Such 'failures' may not only be due to absent target DNA sequences in the tissues, but may be a direct effect of the type of fixative, fixation time and/or fixation temperature used. The type of nucleic acid extraction procedure applied will also influence amplification results. This is particularly true with in situ PCR/PCR in situ hybridization. To examine these effects in solution-phase PCR, beta-globin gene was amplified in 100 mg pieces of tonsillar tissue fixed in Formal saline, 10% formalin, neutral buffered formaldehyde, Carnoy's Bouin's, buffered formaldehyde sublimate, Zenker's, Helly's and glutaraldehyde at 0 to 4 degrees C, room temperature and 37 degrees C fixation temperatures and for fixation periods of 6, 24, 48 and 72 hours and 1 week. DNA extraction procedures used were simple boiling and 5 days' proteinase K digestion at 37 degrees C. Amplified product was visible primarily yet variably from tissue fixed in neutral buffered formaldehyde and Carnoy's, whereas fixation in mercuric chloride-based fixatives produced consistently negative results. Room temperature and 37 degrees C fixation temperature appeared most conducive to yielding amplifiable DNA template. Fixation times of 24 and 48 hours in neutral buffered formaldehyde and Carnoy's again favoured amplification.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

Intracellular calcium signalling in peripheral cells of patients with bipolar affective disorder.

Consistent with previous studies, elevated free intracellular calcium ion concentrations ([Ca2+]i) were found in blood platelets and lymphocytes of patients with mania and bipolar depression. Incubation with an ultrafiltrate of plasma from patients with bipolar illness had no effect on intracellular calcium ion concentration in platelets from normal subjects, suggesting that elevated [Ca2+]i is not due to a circulating factor. As was true in an earlier study of the effect of lithium on platelets, incubation with therapeutic levels of carbamazepine lowered [Ca2+]i in lymphocytes from affectively ill patients but not controls. Increased [Ca2+]i in peripheral cells may reflect a diffuse change in cellular homeostasis and may contribute to mixtures as well as rapid alternations of activity of affective, behavioral and physiologic systems in bipolar illness. Correction of the abnormality may at least be a marker of a relevant therapeutic action if it is not the action itself.

Bipolar Disorder↗

Peripheral blood hairy cell leukemia cells express only low affinity IL-2 receptors.

Purified leukemia cells from three patients with hairy cell leukemia were studied for IL-2 receptor status. All samples expressed the p55IL-2 receptor subunit. However, none demonstrated sensitivity to the IL-2-diphtheria toxin conjugate, DAB486IL-2, which shows selective cytotoxicity for high affinity IL-2 receptor-bearing cells. In the one case studied with 125I-IL-2 binding, only low affinity IL-2 receptors were noted. These data suggest that hairy cell leukemia cells express only low affinity IL-2 receptors and are insensitive to DAB486IL-2.

Diphtheria Toxin↗

PHA induces IL-2 receptors on B-CLL cells and is a potential biological response modifier for the LIL-2-diphtheria toxin, DAB486IL-2.

DAB486IL-2 is an IL-2-diphtheria toxin conjugate which was developed to be specifically cytotoxic to cells bearing high affinity IL-2 receptors. The high affinity IL-2 receptor is a heterodimer comprising p55 and p75 subunits. While the p75 subunit appears to be ubiquitously expressed among the common North American leukemias and lymphomas, the p55 subunit is more restricted in its expression. To broaden the therapeutic relevance of the DAB486IL-2 we have sought physiologically feasible inducers of the p55 IL-2 receptor subunit. This report describes that PHA, in vitro, induces the p55 IL-2 receptor subunit on initially p55-negative B-CLL cells and converts toxin-insensitive leukemia cells to a toxin-sensitive state.

Diphtheria Toxin↗

The evolution of undergraduate medical informatics programmes.

This article summarizes developments in the teaching of medical informatics to undergraduate health care professionals. Whilst clinical schools are adopting quite different approaches to informatics education and training, there seem to be a number of common factors shaping educational policies and the resultant programmes. Different professional schools face similar problems in relation to resources and staff development. At the same time, examination of different syllabuses suggests the existence of divergent models as to what medical informatics should encompass, as well as different views as to what elements of the domain should be included in preliminary or undergraduate courses. The relevance of these trends to health libraries is briefly considered.

Attitude to Computers↗

Paravaginal female adnexal tumor of probable wolffian origin.

Female adnexal tumor of wolffian origin (FATPWO) is a lesion that predominantly occurs in the broad ligament. Its occurrence in the right paravaginal area is rare; only one other case has been reported to occur at this site. The authors report a case of paravaginal FATPWO in a 20-year-old woman that recurred twice during a 5-year period. The microscopic and ultrastructural features of this lesion were identical to other cases of FATPWO reported in the literature. This tumor must be recognized, especially at this site, so that it is not confused with vaginal adenocarcinoma related to diethylstilbestrol exposure in utero.

Adenoma↗

Treatment with GHRH(1-29)NH2 in children with idiopathic short stature induces a sustained increase in growth velocity.

OBJECTIVE: Therapy with GHRH in patients with mild GH insufficiency appears to be more effective than in those with severe insufficiency. We, therefore, studied the clinical response of children with idiopathic short stature to treatment with GHRH(1-29)NH2 (GHRHa) for a period of 12 months. DESIGN: Eighteen short pre-pubertal children (aged 4.3-11.0 years, 17 male) with idiopathic short stature (height < 3rd centile, peak GH to provocative testing > 20 mU/l) were recruited to receive GHRHa 20 micrograms/kg by twice daily s.c. injection for one year. One patient was non-compliant and was withdrawn prior to 3 months of therapy. Pretreatment height velocity was calculated for 12 months and subjects were measured 3-monthly during therapy. Overnight GH profiles and s.c. GHRH tests (20 micrograms/kg) were performed at 0, 3, 6 and 12 months of therapy. In addition, an i.v. GHRH test (1 microgram/kg) was performed at the start and after 1 month of therapy. MEASUREMENTS: Overnight GH profiles were analysed using the Pulsar program. RESULTS: Mean (SD) height velocity (HV) increased from 4.8(0.9)cm/year pre-treatment to 7.2(1.6)cm/year after 12 months of therapy (P = 0.001). The children growing slowly (HV < 25th centile) before treatment had a greater growth response than those growing normally (HV > or = 25th centile) before treatment. Final height prediction increased by a mean (SD) of 3.4(2.6)cm. Overnight GH levels and GH responses to GHRH testing fell during the 12 months of therapy. Fasting blood glucose and insulin levels increased during therapy, as did IGF-I. Cessation of GHRHa was followed by catch-down growth during the first 3 months off therapy: mean (SD) HV 3.89(1.82)cm/year (P < 0.04), although the HV after 6 months (4.9(1.0))cm/year) and 12 months (4.4(1.0)cm/year) was not different from pretreatment values. CONCLUSIONS: Short-term therapy with twice-daily s.c. injection of GHRHa (20 micrograms/kg) promoted linear growth in short children who were not GH-insufficient. The improved height velocity was sustained throughout the 12 months of treatment, followed by catch-down growth, and returned to pretreatment velocity after cessation of therapy.

Blood Glucose↗

Commitments to caring.

Home care agencies eager to embrace the future should not lose sight of what makes their agencies so effective: the dedicated staff who strive to fulfill the agency's mission. It is vitally important for agencies to clarify their missions and to create open and honest environments for employees.

Communication↗

Evaluation of Mesalt dressings and continuous wet saline dressings in ulcerating metastatic skin lesions.

The care of chronic ulcerating metastatic skin lesions is not well established or supported by research. Because these cancerous lesions may be present for many years, patients and their caregivers are confronted with ongoing dressing care to control and prevent odor, bleeding, drainage, and infection. Eleven patients in this study compared Mesalt dressings (Sancella Incorporated, Oakville, Ontario, Canada) with continuous wet saline dressings using a crossover design. Results indicated that Mesalt dressings received significantly higher ratings when compared with continuous wet saline dressings for ease of application and odor control and were significantly preferred by patients. No significant differences were found for ease of removal and comfort of the dressing. Neither were there any significant differences in the occurrence of clinical infection, number of dressing changes, and time spent for the care of the lesion. Mesalt dressings were more expensive than continuous wet saline dressings, but benefits may outweight the costs.

Aged↗

The discriminant value of semiquantitative SPECT data in mild Alzheimer's disease.

UNLABELLED: In most semiquantitative SPECT studies, overlap between groups of patients with Alzheimer's disease (AD) and age-matched elderly controls is such that single posterior cortical perfusion measurements lack sensitivity. In the present study, the value of a combination of semiquantitative temporoparietal SPECT parameters was examined. METHODS: Supratentorial transaxial perfusion measurements were obtained in frontal, anterior temporal, posterior temporoparietal and occipital cortical areas in both hemispheres, in a baseline population of 10 healthy elderly controls and 30 mild to moderately impaired AD patients, as well as in a prospective group of 15 patients with mild cognitive impairment, 12 patients with a diagnosis of probable AD and individual cases of multi-infarct dementia, dementia-frontal type and paranoid psychosis. A linear discriminant function (LDF) was calculated from the baseline subjects' data to classify control and AD subjects individually. RESULTS: Highly significant hypoperfusion was noted in both the anterior temporal and posterior temporoparietal regions of interest in the AD group compared with controls, but with significant overlap. Using an LDF incorporating these perfusion measurements in both hemispheres, 10/10 (100%) controls and 26/30 (87%) AD baseline subjects were correctly classified. Using the baseline LDF in the prospective 15 mildly impaired cases, 11/12 new mild AD cases and none of the 3 non-AD cases were classified in the AD group. CONCLUSION: These results support the use of a combination of semiquantitative SPECT perfusion estimates from cortical areas with predictable pathological involvement in AD in a linear discriminant format in the clinical assessment of patients with suspected AD.

Aged↗

Superior mesenteric venous thrombosis masquerading as Crohn's disease.

Superior mesenteric venous (SMV) thrombosis is an uncommon cause of mesenteric ischemia, frequently presenting with nonspecific and subacute symptoms. We report a case of a 28-yr-old man presenting with symptoms and radiographic changes suggestive of Crohn's disease who, upon further evaluation, was found to have SMV thrombosis. A search for a precipitating condition revealed a strong family history of thromboembolic disease and deficiency of protein C. The patient responded to supportive therapy and anticoagulation.

Adult↗