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Biomedical subjects

C B Wilson

Publications and source records attributed to C B Wilson.

At least 775 records · Page 43Linked to original sources

Positron emission tomography for tumour assessment.

As positron emission tomography (PET) is outside of the main theme of this conference, it is necessary to outline what it offers as a method for assessing tissue function in vivo. This is followed by illustrations of how PET has and is being used to study the physiology and biochemistry of tumours and pharmacokinetics and pharmacology of anticancer agents. Strategies are offered as to how PET may be used for the development of new chemotherapeutic agents.

Fluorouracil↗

Development of an in vitro colony formation assay for the evaluation of in vivo chemotherapy of a rat brain tumor.

An in vitro colony formation assay for the evaluation of in vivo brain tumor therapy has been developed. When plated, disaggregated cells derived from solid tumors proliferated to form relatively homogeneous colonies after a latency period of 2 to 6 days. Increasing concentrations of fetal calf serum enhanced colony-forming efficiency (CFE) with a plateau between 7 and 16%. Supplementation with either irradiated feeder cells (10(3) to 10(5) cells per dish), or medium conditioned by 1 to 3 days of in vitro incubation with the same cell line, doubled the CFE. The density of tumor cells (untreated or previously treated with chemotherapeutic agents) did not affect the CFE when a minimum of 10(4) total cells (tumor plus feeder) were plated. Therefore, in this system the optimal experimental conditions for evaluating chemotherapy and radiotherapy require incubation of disaggregated tumor cells for 12 days in medium containing 10% of fetal calf serum and enough feeder cells to provide a minimum of 10(4) cells per dish. The CFE for untreated tumors was 18 +/- 10% (+/-S.D.), demonstrating that there is significant biological variation. The assay appeared sensitive, with reproducible results, when applied to individual chemically treated tumors. An estimate of the percentage of clonogenic cells affected by in vivo chemotherapy may be obtained by comparing the CFE of cells from treated and untreated tumors. This assay can measure up to a 5 log(10) cell kill, and it should prove to be valuable in developing more effective regimens for the treatment of solid tumors in animals and man.

Animals↗

Immunopathologic mechanisms of renal disease.

Anti-GBM antibodies and glomerular deposition of circulating immune complexes are responsible for the immunopathogenesis of about 5% and 75% of human glomerulonephritides, respectively. Anti-GBM antibodies most frequently cause rapidly progressive glomerulonephritides, respectively in about half of the patients with pulmonary hemorrhage, the Goodpasture's syndrome. Immune complexes cause a wide variety of glomerulonephritides, including diffuse and focal proliferative, membranous, membranproliferative and rapidly progressive morphologic varieties often accompanied by nephrotic syndrome. Immune complexes cause a wide variety of glomerulonephritides, including diffuse and focal proliferative, membranous, membranoproliferative and rapidly progressive morphologic varieties often accompanied by nephrotic syndrome. Immunopathologic tubulo-interstitial renal injury can be caused by antibodies reacting with TBM or by deposition of immune complexes in tubulo-interstitial tissue. Immunofluorescence studies of renal tissue supplemented by detection of circulating anti-basement membrane antibodies and immune complexes are essential in differentiating the immunopathologic mechanisms of glomerular and tubular injury, and are necessary adjuncts in evaluating patients with glomerulo- and tubulo-interstitial nephritis.

Anti-Glomerular Basement Membrane Disease↗

Bone and joint infections caused by Kingella kingae: six cases and review of the literature.

Six cases of Kingella kingae arthritis, osteomyelitis, and diskitis were studied, and data were reviewed from an additional 23 cases in the English-language literature. K. kingae is a slow-growing, fastidious, gram-negative microorganism that colonizes mucous membranes of the upper respiratory tract. Infections were predominantly seen in infants and young children (86% of cases) and were preceded by an upper respiratory tract infection in 31% of patients. Low-grade fever (38 degrees C-39 degrees C) and pain or swelling involving the affected limb developed insidiously. However, 76% of the infections were diagnosed within 1 week after the onset of symptoms. The knee was involved in 47% and the hip in 33% of cases of arthritis. Osteomyelitis mainly involved the femur (36%); four cases of osteomyelitis (29%) were diagnosed as diskitis. The erythrocyte sedimentation rate was greater than 20 mm/h in all patients. Gram stains of aspiration fluid were positive in 19% of cases, whereas blood cultures yielded growth in only 5%. Radiographic signs indicating the presence of osteomyelitis were observed in 93% of patients. All patients recovered completely. K. kingae is an important causative agent in indolent bone, joint, and intervertebral disk infections.

Arthritis, Infectious↗

Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection.

The human neonate is unduly susceptible to infection with viruses and other pathogens, such as Toxoplasma and Listeria, that survive and replicate within cells. Cellular immunity is the major mechanism of host defense against these intracellular pathogens. Selective immaturity in certain functions of T lymphocytes appears to be a major factor in the neonate's susceptibility to these infections. Particularly striking is the deficiency in production of interferon-gamma. We review the data regarding the deficiency in the production of interferon-gamma by cells of healthy and infected neonates, discuss what is known regarding the cellular and molecular mechanisms for this deficiency, and review the unique role played by interferon-gamma in host defense against intracellular pathogens. The response of the neonate's effector cells to the immunoenhancing effects of interferon-gamma appears to be variable; diminished enhancement by interferon-gamma of cytotoxic cell function and the production of tumor necrosis factor by macrophages may further compound the effects of diminished production of interferon-gamma.

Disease Susceptibility↗

Ontogeny of T lymphocyte function in the neonate.

T cell precursors are first detected in the thymus at eight weeks of gestation. By 15 to 20 weeks of gestation, T-cell precursors expressing alpha beta and gamma delta T-cell receptors are present in the thymus in numbers relatively similar to those found in postnatal life. However, recent data suggest that T-cell receptor diversity is more limited during fetal and neonatal life than in adults. Additionally, the functional capacity of T cells in the fetus and neonate is immature, in that neonatal T cells express a limited repertoire of lymphokines in response to activation. Specifically, the production of the lymphokines, interferon-gamma and interleukin-4, which participate in the maturation of cytotoxic cells, activation of macrophages, and the maturation and modulation of B cell function and isotype expression, is reduced more than tenfold compared to cells from adults. This appears to result primarily from the lack of memory T cells in the fetus and neonate, reflecting their antigenic naivete. The difference in lymphokine expression is due to diminished transcription of these genes in neonatal T cells in response to activation. Preliminary data indicate that differences in essential promoter elements regulating transcription of these lymphokine genes plays a role in their differential expression in T cells.

Animals↗

Glomerular hemodynamics in moderate Goldblatt hypertension in the rat.

Glomerular hemodynamics were studied by micropuncture technique in the unclipped kidney in rats in which modest two kidney Goldblatt hypertension was maintained for 4 weeks and in normotensive controls. Both groups ingested less than 2 mEq Na+/day. In hypertensive rats at micropuncture, mean hydrostatic pressure was elevated both systematically (128 +/- 5 vs 113 +/- 3 mm Hg, p less than 0.05) and within glomerular capillaries (55 +/- 2 vs 48 +/- 1 mm Hg, p less than 0.05), resulting in an increase in the transglomerular hydrostatic pressure gradient (40 +/- 2 vs 33 +/- 1 mm Hg, p less than 0.05). The glomerular capillary permeability coefficient, however, was decreased in the hypertensive rats (0.063 +/- 0.017 vs 0.115 +/- 0.011 nl/s/g kw/mm Hg, p less than 0.05), resulting in no change in nephron filtration rate 38.9 +/- 2.3 vs 39.0 +/- 2.5 nl/min/g kw). Nephron plasma flow also remained unchanged (154 +/- 10 vs 140 +/- 7 ml/min/g kw). In separate studies in this model of hypertension, saralasin infusion demonstrated a peripheral effect of circulating angiotensin II which was increased over controls. Kidney mass and GFR were not different between clipped and unclipped kidneys. No consistent abnormalities were observed by light or electron microscopy either in glomeruli or in vessels in the unclipped kidney. This study demonstrates that glomerular hemodynamics may be altered early in the course of modest hypertension in this model without altering blood flow or filtration rate. The decrease in glomerular capillary area and/or permeability (LpA) in the hypertensive rats could be either a result of the increased effect of circulating angiotensin II or the direct effect of glomerular capillary hypertension.

Animals↗

Metered-dose inhaler technique and quality of life with airways disease: assessing the value of the Vitalograph in educational intervention.

The efficacy of delivering medicines by metered-dose inhaler (MDI) is well established, and the patient's technique with MDIs is related directly to achieving the desired clinical outcome. The present study was designed to assess and improve MDI technique by using a Vitalograph Aerosol Inhalation Monitor (VAIM) in an airways disease education programme. Baseline measurements were made immediately prior to educational intervention incorporating feedback from a VAIM unit. At 6 weeks' follow-up, MDI technique was found to have regressed to the sub-optimal measures recorded at baseline prior to educational intervention. However, patients reported a significant improvement in physical function between baseline and follow-up as measured by the Rand 36-Item Health Survey (SF-36), Version 1.0. The results reinforce the need for a longitudinal educational programme for patients prescribed medications delivered by MDI. The VAIM unit provided health educators and patients with both a visual and a quantitative assessment of patients' MDI technique, and was thus of positive value as part of the intervention process.

Adult↗

Microsurgical treatment of neurovascular disease. Part I. Personnel, equipment, extracranial-intracranial anastomosis.

This study was prepared with the objective of directing the attention of the medical community to advances during the last decade in the operative treatment of cerebral ischemia, intracranial aneurysms, and cerebral and spinal vascular malformations. The requirements for specialized personnel, facilities, and instrumentation are detailed for those who are unfamiliar with the complexities of microneurosurgery. The importance of adequate training in the intricacies of extracranial-intracranial anastomotic procedures is stressed. Reported results of this operation are discussed. It is anticipated that a recently organized cooperative study will provide the data necessary for evaluation of long term benefits. Attention is given to grading the clinical status of patients with intracranial aneurysms in advance of surgery and the importance of operating upon good risk patients. How to manage the relatively large numbers of poor risk patients with aneurysms unsuitable for immediate operation is discussed. Sophisticated radiological procedures utilized in the diagnosis, management, and evaluation of therapy are described. The role and significance of properly administered anesthesia are discussed in relation to the performance of complicated and time-consuming microsurgery on the brain and spinal cord. The study group has tried to present this material objectively and to urge those individuals working in this difficult field to acquire the special skills and instrumentation of microneurosurgery, to implement the "team-of-experts" concept in the operating room, and to enlist the support of related disciplines.

Arteriovenous Shunt, Surgical↗

Safer handling practice for nurses: a review of the literature.

The lifting and handling of people is an integral part of nursing care and has been blamed for a high incidence of back injuries to nurses. Changes to nursing practice have been dictated by this level of injury following the passing of health and safety legislation in 1992. This review seeks to evaluate the growing body of research from a range of disciplines in order to establish an evidence base for the moving and handling of patients. It identifies that studies considering the impact of changes in practice on patient outcomes are lacking. The term 'safer handling practice' has been used by the author to indicate a new way of thinking in relation to moving and handling people in health and care settings. A definition of safer handling practice has been derived from the literature with concomitant implications for training. Using this body of knowledge alongside studies investigating mobility of older people, the literature was used deductively to ascertain that safer handling practice has the potential to influence positively the mobility of older people. The author suggests further research to be conducted in the field of safer handling practice.

Activities of Daily Living↗