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Biomedical subjects

D A Morgan

Publications and source records attributed to D A Morgan.

At least 127 records · Page 7Linked to original sources

Revision total hip arthroplasty with osseous allograft reconstruction. A clinical and roentgenographic analysis.

One hundred twelve irradiation-sterilized, -70 degrees frozen allografts have been used in 72 patients who were available for follow-up study in a prospective analysis of allograft revision total hip arthroplasty. Clinical objectives were achieved in 85% of patients with a follow-up period ranging from six to 72 months. Based on clinical and roentgenographic analysis, specific recommendations are made to further improve the success rate of revision total hip arthroplasty associated with protrusio, shelf, acetabular, calcar, and large fragment femoral allografts.

Acetabulum↗

Cardiac sensory receptors in Dahl salt-resistant and salt-sensitive rats.

The Dahl strain of genetically salt-resistant (DR) and salt-sensitive (DS) rats affords an opportunity to explore mechanisms responsible for salt resistance and sensitivity. Dahl sensitive rats exhibit abnormalities in sympathetic neural control of the circulation and in renal sodium handling. Since cardiac baroreflexes participate in regulation of sympathetic nerve activity and sodium excretion, we have evaluated cardiac baroreflex function in DR and DS rats. This article briefly reviews evidence that cardiac sensory endings with vagal afferents are reset to a higher threshold in DS rats before elevation of arterial or cardiac filling pressures, as a result of this resetting, cardiac baroreflex inhibition of sympathetic nerve activity during volume expansion is impaired in prehypertensive DS rats, a high-sodium diet enhances the gain of cardiac baroreflex inhibition of sympathetic nerve activity in DR but not DS rats, and atrial natriuretic factor stimulates cardiac sensory receptors with vagal afferents. Taken together, these studies prompt speculation that humoral factors released during intake of a high-sodium diet may sensitize cardiac baroreflexes and thereby protect against sodium retention and hypertension. An absence of this compensatory adjustment or plasticity in cardiac baroreflex function in DS rats may predispose to salt-induced hypertension.

Animals↗

Efficacy and tolerability of vindesine in the treatment of small-cell lung cancer. A phase II study.

Eighteen patients suffering from small-cell lung cancer, all with measurable lesions, were treated with vindesine (3 mg/m2 i.v. on days 1 and 8 of a 21-day cycle). Partial responses (PR) were seen in six patients (three of whom had been previously heavily treated). Most patients tolerated the drug extremely well, an important consideration when expected cure rates are very poor.

Carcinoma, Small Cell↗

Isolated intrathoracic relapse in small-cell lung cancer: incidence and implications.

Between 1978 and 1983, 56 patients with limited-stage small-cell lung cancer (SCLC) were treated by combination chemotherapy and moderate-dose thoracic irradiation (30 Gy). There are four survivors beyond 4 years; other patients were followed up until death, and sites of relapse documented, with five exceptions. Nine patients died with disease apparently confined to the chest. This suggests that treatments aimed at achieving better local control warrant prospective evaluation.

Carcinoma, Small Cell↗

131I and 111In-labelled monoclonal antibody imaging of primary lung carcinoma.

Preliminary clinical studies have been carried out to determine whether the monoclonal antibody 791T/36 would localize in primary lung cancer to an extent sufficient for external detection by gamma scintigraphy. Radiolabelling of the antibody with 131I permitted visualization of three out of eight (38%) tumours using planar imaging with 99Tcm-labelled blood pool subtraction. Radiolabelling of the same antibody with 111In permitted visualization of tumour uptake in nine out of 13 (69%) tumours, without the need for image subtraction. Single photon emission computed tomography (SPECT) studies of seven patients demonstrated concentration of 111In-labelled antibody at the tumour site in each case, four of which were visualized on the planar images. The present study demonstrates localization of the 791T/36 antibody in primary lung carcinoma and confirms the superiority of 111In over 131I as a radiolabel for antibody imaging, especially when emission tomography is performed. These data indicate that further work will be required to determine whether this antibody will be a suitable carrier for cytotoxic agents in the therapy of lung cancer.

Aged↗

Activation of vagal depressor reflexes by atriopeptins inhibits renal sympathetic nerve activity.

Atrial natriuretic factor decreases arterial pressure but the hypotensive response is not accompanied by the expected reflex tachycardia. The absence of reflex tachycardia might reflect a stimulating effect of atrial natriuretic factor [atriopeptins (AP)] on cardiac-sensory receptors with vagal afferents. To test the hypothesis that AP inhibit sympathetic nerve activity by activating vagal afferents we measured changes in renal sympathetic nerve activity (SNA), heart rate, and arterial pressure during injection of APII and APIII in anesthetized Sprague-Dawley rats in the intact state, after sinoaortic denervation, and after sinoaortic denervation plus bilateral vagotomy. In intact, anesthetized rats APIII (50 micrograms/kg) lowered mean arterial pressure [-31 +/- 8 (SE) mmHg] without the expected reflex increase in renal SNA and heart rate. In contrast, infusion of sodium nitroprusside in a dose that produced a similar decrease in mean arterial pressure (-29 +/- 9 mmHg) evoked a significant increase in renal SNA (+38 +/- 8%) and heart rate (+17 +/- 5 beats/min). In rats with sinoaortic denervation, APIII induced a greater fall in mean arterial pressure (-44 +/- 8 mmHg). This hypotensive response was associated with a decrease in renal SNA (-26 +/- 2%) that was abolished by bilateral vagotomy. Atropine did not attenuate the decrease in renal SNA with APIII. We conclude that APII and APIII increase the activity of vagal afferents and thereby inhibit the increases in renal SNA and heart rate, which would be expected to result from the fall in arterial pressure. We speculate that this action might facilitate reflexly the renal vasodilator and natriuretic actions of APs.

Animals↗

High salt diet sensitizes cardiopulmonary baroreflexes in Dahl salt-resistant rats.

Compared with Dahl salt-resistant (R) rats, Dahl salt-sensitive (S) rats on a low salt diet have impaired cardiopulmonary baroreflex control of sympathetic nerve activity. The purpose of this study was to examine the sensitivity of cardiopulmonary baroreflex function in both strains of Dahl rats when they are challenged with a high salt diet. We studied Dahl R and S rats after 6 weeks of low and high salt diets. To assess cardiopulmonary baroreflex function, we measured decreases in splanchnic sympathetic nerve activity produced by increases in left ventricular end-diastolic pressure during graded volume expansion (dextran 75) after bilateral sinoaortic denervation. A given amount of infused volume produced comparable increases in left ventricular end-diastolic pressure in Dahl R rats on low and high salt diets but significantly greater decreases in sympathetic nerve activity in the high salt group than in the low salt group. Thus, the high salt diet augmented the sympathoinhibitory response to volume expansion in the Dahl R rats. In contrast, among the Dahl S rats equivalent increases in left ventricular end-diastolic pressure during volume expansion produced smaller sympathoinhibitory responses in the high salt group than in the low salt group. The gain of the cardiopulmonary baroreflex, expressed as the percentage decrease in sympathetic nerve activity per mm Hg increase in left ventricular end-diastolic pressure, was significantly increased by a high salt diet in Dahl R rats but tended to be decreased by a high salt diet in Dahl S rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radiation therapy of squamous carcinoma of the tonsil: an analysis of prognostic factors and of treatment failures.

A retrospective analysis of the results of treatment by primary irradiation of 87 cases of squamous-cell carcinoma of the tonsil at one institution over a 20-year period is presented. Survival at 5 years for all patients was 20%. The major determinants of survival were tumour size (T) and nodal status (N) at presentation. Degree of histological differentiation had no prognostic significance. Initial failure occurred in the primary tonsil site or in cervical lymph nodes in almost all cases. It is clear that treatments that increase loco-regional control are needed if the prognosis for the more advanced tumours is to be improved and it is suggested that a combined-modality approach (surgery plus irradiation) needs to be explored. For early lesions, primary radiation therapy remains the treatment of choice.

Adult↗

Patterns of flap recurrence following mastectomy.

Flap recurrence after mastectomy is divisible into three distinct entities: spot recurrence, multiple spot recurrence and field change. Spot recurrence and multiple spot recurrence are usually controlled by local measures and are not associated with any particular characteristics of the primary tumour. The field change type of flap recurrence is difficult to control and is associated with aggressive primary tumours (grade III, node positive, oestrogen receptor negative) and a very poor prognosis. The appearance of field change type of flap recurrence is an indication for systemic therapy.

Breast Neoplasms↗

The prediction of local or regional recurrence after simple mastectomy for operable breast cancer.

Both the histological grade of the primary tumour and lymph node status have been found to contribute significantly towards the development of a local or regional recurrence after simple mastectomy for operable breast cancer. No other factor, from a series of seven studied, has been found to be of independent significance. A small group of patients with grade III tumours, lymph node positive at mastectomy, has been identified in whom more than 40 per cent of all symptomatic local or regional recurrences occurred. The chance a patient in this group has of developing a local or regional recurrence requiring treatment within 4 years approaches 50 per cent.

Breast Neoplasms↗

Novel peripheral blood-derived human cell lines with properties of megakaryocytes.

For 18 mo, we derived 18 cell lines from 11 donors with various clinical profiles ranging from normal to leukemic. Suspension cultures were initiated with 1 X 10(6) mononuclear blood cells/ml of nutrient medium containing 10% human serum and 10% lectin-stimulated human lymphocyte conditioned medium. The cultures were monitored weekly by morphological analyses of Wright-Giemsa-stained cell preparations. All successful cultures showed a significant decline in viability during the first 3-4 wk with rate "lymphoid" cells observed in mitosis. Within the next 2 wk, the proliferating cells gave rise to a rapidly expanding population of mononuclear cells. As the cultures expanded, cell morphology became heterogeneous with respect to cell size and nuclear ploidy, with an accumulation of giant multinuclear cells that were suggestive of megakarocytes. Even though the cells did not have the classical morphology of mature platelet-forming megakaryocytes, 90% of the cells within a cell line were positive by direct or indirect immunofluorescence for the platelet membrane glycoproteins IIb and IIIa; for surface markers HLA-Dr and B2-microglobulin; for intracellular platelet-derived growth factor and platelet factor IV; and for membrane affinity or binding with serum platelet-derived growth factor and platelet factor IV. These results suggest that a blood precursor cell, most likely a primitive megakaryoblast, was isolated from the peripheral blood and was provided with an optimal culture environment for sustained growth. These cells did not mature to a more differentiated stage, perhaps owing to regulatory factor deficiencies in this in vitro system. The remarkable frequency of obtaining cell lines with megakaryocyte properties from normal peripheral blood and the capacity of some normal donors to repeatedly yield these cell lines make this cell culture system indeed unique by being selective for putative megakaryocyte precursors.

Antigens, Viral↗

An experimental study of iatrogenically induced operating theatre burns.

An experimental study was undertaken to investigate the rate of decay of heat from standard orthopaedic mallets post-autoclaving. A temperature-specific burn analysis was performed using a laboratory animal model, and in combination with the results of the heat decay study, the identification of a 'critical zone' has been made. It is during this 'critical zone' that iatrogenic burns can occur. Two economically viable, practical solutions are offered. One is an autoclavable thermometer which can be included in the instrument tray. The second is a 'new design' orthopaedic mallet. The most reliable preventative measure, however, is constant vigilance. Iatrogenic burns can and do occur.

Burns↗

Heterogeneity of human natural killer cells.

The cell surface antigens and specificity of cultures of human natural killer (NK) cells, propagated in the presence of interleukin 2, were analyzed at the single-cell level. With the use of a micropipette isolation procedure, clones were initiated from cells of defined phenotype. The cell surface markers on the resultant clones were not stable and often diverged from those on the cells selected for initiation. Clones manifesting NK activity had low expression of T4 and T8 and most had some expression of T10, whereas clones without detectable cytotoxic activity had a considerable proportion of cells expressing T4 and/or T8 antigens. Within a cytotoxic clone, single cells shown to have killer activity were shown to express often T10 and infrequently T8; T4 was not detected on any of the reactive cells examined. The NK, reactive cells were found to express also antibody-dependent cell-mediated cytotoxicity and lectin-dependent cell-mediated cytotoxicity (LDCC), and some of the individual NK cells were shown to have the ability to lyse more than one type of target cell. However, there appeared to be considerable heterogeneity among the cells in the clones, with only 50-60% of cells displaying lytic activity against K562 cells at a given time. In addition, one cytotoxic clone appeared to have specific immune alloreactivity as well as NK and LDCC activities. The results of this study indicated that the cell surface phenotype and specificity of cytotoxic reactivity of cultured human NK cells were heterogeneous and suggested that such heterogeneity may be due to variations in the levels of differentiation and/or activation.

Cell Differentiation↗

Germ cell tumours confined to the supra-clavicular fossa: a report of two cases.

Two cases of germ cell tumours in males presenting as a left supra-clavicular mass, with no evidence of disease in other sites, are reported. Biopsy showed seminoma in one case and teratoma in the other. Supra-clavicular germ cell tumour as an isolated finding after intensive investigations has not previously been reported.

Adult↗