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Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 271 records · Page 15Linked to original sources

Prognostic factors for healing of bone lesions in histiocytosis X.

Healing characteristics and rates of resolution were retrospectively reviewed in 38 bone lesions in 18 patients with histiocytosis X. Signs which tended to indicate future healing were a change from a nontrabecular pattern to a trabecular pattern by 10 weeks, a nonsclerotic lesion to one with sclerosis by 13 weeks, and loss of distinct margins by 24 weeks. Complete healing then occurred within 36 to 40 weeks after development of these favorable signs. The earliest occurrence of a favorable sign was 6 weeks. A trabecular pattern was found in 90% of the lesions, outside the skull, which eventually healed. Fifty-eight percent (22 of 38) of the lesions completely healed in an average of 13.6 months. Five months was the most rapid occurrence of healing in any of our cases.

Bone Diseases↗

Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies.

A subset of B cells expressing the CD5 marker, a 67 KD molecule, has been implicated in the pathogenesis of autoimmune disease. To study the immunoglobulin repertoire of CD5+ B cells we investigated chronic lymphocytic leukemic (CLL) cells, since the majority of the malignant clones express CD5. CLL were induced to secrete their IgM in vitro by phorbol 12-myristate 13-acetate (PMA) and the supernatants screened for binding to a panel of autoantigens. Twelve out of 14 CLL clones were autoreactive, binding to Fc of IgG, ssDNA, dsDNA, histones, cardiolipin, or cytoskeletal components. Many also bound to more than one antigen tested for, showing multispecificity. Our data suggest that a high proportion of CD5+ B cells are programmed to secrete multispecific autoantibodies.

Antibodies, Neoplasm↗

Characteristics of emergency medicine fellowships.

Little has been reported in the literature on the characteristics of existing and planned emergency medicine fellowships. To help answer important questions about fellowships, a 28-question survey was developed by representatives from the University Association for Emergency Medicine education and fellowship committees, the Emergency Medicine Residents' Association, and a health services researcher. This questionnaire was sent to all emergency medicine residency directors and known emergency medicine fellowship programs. The results of our survey indicate that there are 18 current and 11 planned fellowships. The fellowships primarily last one year, are research oriented, and place a large emphasis on toxicology, emergency medical services, and critical care. They are based mostly in university or university-affiliated hospitals, and will graduate physicians who stay in academic emergency medicine. The major problems with fellowships include inadequate funding and lack of adequate candidates.

Emergency Medicine↗

Henoch-Schönlein purpura and Hodgkin's disease.

A 39 year old man who presented with classical Henoch-Schönlein purpura was shown to have mediastinal nodular sclerosing Hodgkin's lymphoma. The Henoch-Schönlein purpura resolved after treatment of the lymphoma.

Adult↗

Protection against complement-mediated cell damage by Ca2+ and Zn2+.

Ca2+ and Zn2+ prevent antibody-dependent complement-induced permeability changes in tonsil lymphocytes and Lettre cells. Lactate dehydrogenase leaks out from Lettre cells at high complement:cell ratios, under which conditions higher concentrations of Ca2+ and Zn2+ are required for protection. Ca2+ and Zn2+ do not inhibit complement activation or C9 binding to Lettre cells, and prevent leakage through preformed lesions. It is concluded that the extent of complement-induced membrane damage depends on the concentration of extracellular Ca2+, and may be modulated by changes in extracellular Ca2+ or Zn2+.

Animals↗

The current status of typhoid vaccine development and clinical trials with typhoid vaccines.

The killed whole cell typhoid vaccines, although protective, have limited usefulness because of the adverse reactions they evoke. In contrast, new typhoid vaccines protect without reactogenicity. Attenuated oral vaccine Ty2la has been evaluated in field trials of efficacy in Santiago, Chile. Three doses of Ty2la in an enteric-coated formulation given within one week provided 69% efficacy for at least four years. Ty2la has reached the stage of being a practical public health tool. Two double auxotrophic (Aro-, Pur-) mutant strains of S. typhi (541Ty and 543Ty) were well-tolerated and stimulated cell-mediated immune responses but evoked little serological response. Parenteral purified Vi polysaccharide of S. typhi (single 25 mcg dose) was safe and immunogenic and provided 64-72% protection (for at least 17-21 months) in controlled field trials in Nepal and South Africa.

Adult↗

Cortisol responses to cholinergic drugs in Alzheimer's disease.

Patients with Alzheimer's disease participated in a trial of two sessions in which they received physostigmine and neostigmine in a double-blind crossover design. Most of these patients subsequently participated in a scopolamine vs saline double-blind crossover trial using a similar design. Physostigmine increased plasma cortisol relative to neostigmine, with the greatest difference at time points greater than 90 min post drug oral administration. Physostigmine also significantly decreased plasma cholinesterase (ChE). There was a significant positive correlation between the effects of physostigmine on increasing cortisol and decreasing ChE; there was no correlation between the increase in cortisol of cholinesterase inhibitor following neostigmine administration, but neither of these chemical parameters is related to the drug's effects on cognitive functioning.

Aged↗

The relation of predicted structure to observed conformation and activity of glucagon analogs containing replacements at positions 19, 22, and 23.

Six new analogs of glucagon have been synthesized containing replacements at positions 19, 22, and 23. They were designed to study the correlation between predicted conformation in the 19-27 segment of the hormone and the conformation calculated from circular dichroism measurements and the observed activation of adenylate cyclase in the liver membrane. The analogs were [Val19]glucagon, [Val22]glucagon, [Glu23]glucagon, [Val19,Glu23]glucagon, [Glu22,Glu23]glucagon, and [Ala22,Ala23]glucagon. The structures predicted for the 19-27 segment ranged from strongly alpha helical to weakly beta sheet. The observed conformations varied as functions of amino acid composition, solvent, concentration, pH, and temperature but did not correlate well with prediction. There was, however, a correlation between predicted structure and activation of adenylate cyclase in rat liver membranes.

Adenylyl Cyclases↗

Use of sodium restriction and enalapril in persons with moderate to severe hypertension.

One hundred and seventy-four patients who were receiving drug therapy for hypertension were asked to restrict their sodium intake for three months. At the end of that time their drug therapy was replaced with enalapril and the dose of the drug "titrated" to obtain a diastolic blood pressure of less than 90 mmHg. Sodium restriction caused a small fall in blood pressure and could be used as sole therapy in only 6% of patients. Enalapril therapy was instituted without problems and control of blood pressure below 90 mmHg was achieved in 62% of persons with monotherapy. The number of tablets of enalapril that were taken was reduced from 5.9 to 2.7; in most patients these were taken once a day. There were few side-effects and no depression of white cell count, no proteinuria and no deterioration of renal function. Seventy-six per cent of patients preferred the new regimen either because they felt better than with their previous therapy (52%) or because of the more simple regimen (24%). Enalapril was an effective, well tolerated antihypertensive agent and potentially has a major role to play in the management of patients with high blood pressure.

Antihypertensive Agents↗

Abnormal distribution of the helper-inducer and suppressor-inducer T-lymphocyte subsets in the rheumatoid joint.

T lymphocytes can be divided into two main phenotypic populations, CD4 and CD8. These can be further subdivided into 2H4, 4B4, or UCHL1 subsets by appropriate monoclonal antibodies. We have investigated these subsets in the synovial fluid of patients with rheumatoid arthritis and have found (i) a virtual absence of CD4+ 2H4+ and the marked reduction of CD8+ 2H4+ T cells; (ii) a marked increase of CD4+ 4B4+ and CD8+ 4B4+ T cells; and (iii) a marked increase of CD4+ UCHL1+ and CD8+ UCHL1+ T cells compared with peripheral blood. Although the functions of the CD8 subsets are not known, the virtual absence of CD4+ 2H4+ suppressor-inducer T cells and the marked increase of CD4+ 4B4+ helper-inducer T cells and of CD4+ UCHL1+ memory T cells may help to explain the many known functional immunological properties of synovial T cells.

Antibodies, Monoclonal↗

Evaluation of a perinatal grief support team.

An analysis of the effects of intervention from a perinatal grief support team was begun in 1982. Seventy-eight women experiencing stillbirth or early perinatal death were randomly assigned to either the grief support team's protocol of care or to the control group who received routine hospital care. Assessment was carried out on 34 participants, 16 from the control group and 18 from the treatment, 6 months after delivery. A three-part self-administered, self-rating grief index questionnaire was used. There was no statistical difference on overall grief scores between the two matched groups. The treatment group reported significantly lower scores than the control group on the two grief subscales of anger-hostility and physical symptoms. Women who reported more life changes before the perinatal death tended to have fewer problems with the symptomatology of grief. Social support was an important variable in explaining grief symptomatology. Women reporting low levels of social support who were in the treatment group had significantly lower mean scores on the grief subscales of anger-hostility, somatic experience, physical symptoms, and problems with vigor.

Counseling↗

The effect of perindopril on blood pressure in humans on different sodium intakes.

Perindopril is a new inhibitor of converting enzyme activity with a prolonged half-life. Thirty-two patients with essential hypertension and a diastolic blood pressure greater than 95 mm Hg were stratified into two groups according to their 24 h urine sodium excretion. They were randomized in a double-blind fashion to placebo or perindopril and a dose titration made in steps of 2, 4, 6, and 8 mg given once daily at weekly intervals. The goal diastolic blood pressure was 90 mm Hg. Goal blood pressure was achieved in 11 of 16 patients on perindopril and 3 of 6 patients on placebo. Perindopril caused a fall in BP of 22/11 (supine) and 27/14 (erect) mm Hg while the placebo group had falls of 3/2 (supine) and 3/0 (erect) mm Hg. Most of the blood pressure fall occurred in the first week of therapy with 2 mg/day. Side effects were few and occurred mainly in the placebo phase. There was no alteration in urine protein, white cell count, plasma urea, or creatinine. The fall in blood pressure achieved at the end of the titration or with 2 mg did not differ between the two groups. There was no correlation between blood pressure response and 24 h urine sodium or plasma renin activity. These results indicate that perindopril is an effective antihypertensive drug that appears to work equally well in patients on high or low sodium intake.

Aged↗

Direct effect of interleukin 2 on chronic lymphocytic leukaemia B cell functions and morphology.

The functional and morphological changes induced by recombinant interleukin 2 (IL-2) were studied in purified B cells from patients with untreated B chronic lymphocytic leukaemia (B-CLL). In eight of nine patients, purified B-CLL cells increased their DNA synthesis in response to IL-2 without preactivation in vitro. This response, studied in detail in three patients, was dose dependent and reached a maximum on day 5 or 6. IL-2 induced or increased IgM secretion in cultures from five of the nine patients studied. Two of this responsive group were particularly interesting as IL-2 not only stimulated IgM secretion but also induced the secretion of IgG. Immunoglobulin production was invariably monoclonal. B CLL cells incubated with IL-2 showed distinct morphological changes including an increase in the size of cytoplasm and enlargement of nuclei together with the appearance of nucleoli. These changes were present in all IL-2 treated cultures but were more pronounced in those containing immunoglobulin secreting cells. None of the IL-2 induced changes appeared to correlate with the clinical stage of the disease or the level of Tac antigen expression on the freshly isolated CLL B cells.

Aged↗