Biomedical subjects
Publications and source records attributed to G Davidson.
Radiological and clinical evidence of acute necrosis in a meningioma following one cycle of chemotherapy with 5-fluorouracil, folinic acid, and levamisole was observed in a patient being treated for invasive rectal carcinoma. The possible mechanisms and implications of this occurrence are discussed.
Venous access devices connected to jugular vein catheters were implanted SC in 2 groups of 6 White Carneau pigeons (Columba livia). Total parenteral nutrition (TPN), or a control solution (lactated Ringer's solution) was infused as a bolus 4 times daily. Physiologic, hematologic, and biochemical variables were monitored over 5 days. Complications in the TPN-treated pigeons included 8.7% weight loss during the 5-day trial, hyperglycemia for up to 90 minutes after infusion, and glucosuria after infusion. Control pigeons lost 1.3% of their body weight and did not become hyperglycemic or glucosuric after infusion. Hematocrit in both groups of pigeons decreased to a value slightly below published reference values for pigeons. Five pigeons developed venous thrombosis in the proximal part of the cranial vena cava. Results indicated that intermittent administration of TPN is possible in birds; however, further research is required to develop better techniques for administration of TPN solutions. Additionally, it is important to determine, more specifically, the caloric and nutrient requirements of pigeons under stress and receiving TPN.
We describe two patients who developed devastating strokes due to intracranial arterial occlusion 15 weeks and 97 weeks following high dose stereotactic iodine-125 brachytherapy for glioblastoma multiforme. In both cases the occlusion was within the implant volume at points receiving 110-281 Gy and there was no other evidence of significant atherosclerosis in the patients. We therefore conclude that these complications were a direct result of the brachytherapy. The phenomenon of radiation-induced occlusion of large cerebral arteries is reviewed.
To assess the possible relationship between maternal drug use during pregnancy and subsequent sudden infant death syndrome (SIDS), we identified 1760 cases of SIDS from a population of more than 1.2 million infants (1.45/1000) born in New York City between 1979 and 1989. The SIDS rate in drug-exposed infants was 5.83 per 1000 infants, compared with 1.39 per 1000 infants who were not drug exposed. With control for known associated high-risk variables, the risk ratio for SIDS in each individual drug group (methadone, 3.6; heroin, 2.3; methadone and heroin, 3.2; cocaine, 1.6; cocaine and methadone or heroin, 1.1) was higher than in the non-drug-exposed group. Higher rates of SIDS were found in infants exposed to opiates alone than in cocaine-exposed infants, but increasing rates of SIDS in cocaine-exposed infants toward the end of the decade suggested that "crack" cocaine may be linked to these increasing rates. Declines in the overall rate of SIDS during the decade were observed for both the drug-exposed (11.28 to 4.09 per 1000) and the nonexposed groups (1.70 to 1.05 per 1000). Differences in rates of SIDS between major racial-ethnic groups in nonexposed infants were not apparent if the mothers used drugs during pregnancy. Seasonal variation and distribution of ages at time of SIDS death did not differ between the drug-exposed group and the nonexposed group, suggesting that drug-associated SIDS may provide clues as to the cause or causes of SIDS.
The dose effect of deferoxamine treatment in attenuation of ischemia-induced reperfusion injury in the skin and muscle of latissimus dorsi myocutaneous flaps was studied in pigs weighing 19.7 +/- 0.5 kg. The latissimus dorsi myocutaneous flaps were subjected to 4, 6, or 8 hours of warm global ischemia. The length and area of viable and nonviable skin and muscle were assessed 48 hours after the ischemic insult by using the fluorescein and nitroblue tetrazolium dye tests, respectively. It was observed that perioperative deferoxamine treatment (250 mg/kg IV) was effective (p < 0.05) in attenuation of ischemia-induced reperfusion injury in the skin but not in the muscle of latissimus dorsi myocutaneous flaps subjected to 4, 6, or 8 hours (n = 10) of ischemia compared with the saline-treated control (n = 10). In a separate study, it was observed that preoperative deferoxamine treatment (250 mg/kg per day x 2 days, IM) plus perioperative deferoxamine treatment (250 mg/kg IV) was effective (p < 0.05) in attenuation of muscle ischemia-induced reperfusion injury in latissimus dorsi myocutaneous flaps subjected to 4 hours of ischemia and 48 hours of reperfusion (n = 10) compared with the saline treated control (n = 10). Morphologic studies with light and electron microscopy also provided evidence to indicate that preoperative plus perioperative deferoxamine treatment, but not perioperative deferoxamine treatment alone, remarkably reduced ischemia-induced reperfusion injury in the skeletal muscle of latissimus dorsi myocutaneous flaps compared with the saline-treated control. It is concluded that deferoxamine is effective in the attenuation of ischemia-induced reperfusion injury in the skin and muscle of pig latissimus dorsi myocutaneous flaps, but a longer period and/or higher dose of deferoxamine treatment is required for the muscle than for the skin. The pharmacologic actions and metabolism of deferoxamine relating to mitigation of ischemia-induced reperfusion injury in the pig skin and muscle are discussed.
A 27 year old man with intestinal pseudo-obstruction who developed parenteral nutrition induced hyperlipidaemia and who also had ophthalmoplegia and an undifferentiated myopathy is described. Histological examination of biopsy specimens and molecular analysis show that this patient had both familial visceral myopathy and a mitochondrial myopathy, suggesting that a mitochondrial DNA mutation is the molecular lesion in familial visceral myopathy.
OBJECTIVES--To assess the knowledge, attitudes, and perceptions of risk of occupational HIV transmission in hospital in relation to existing guidelines. DESIGN--Cross sectional anonymous questionnaire survey of all occupational groups. SETTING--One large inner city teaching hospital. SUBJECTS--All 1530 staff working in the hospital in October 1991 and 22 managers. MAIN MEASURES--Knowledge of safe working practices and hospital guidelines; attitudes towards patients with AIDS; perception of risk of occupational transmission of HIV; availability of guidelines. RESULTS--The response rate in the questionnaire survey was 63% (958/1530). Although staff across all occupational groups knew of the potential risk of infection from needlestick injury (98%, 904/922), significantly more non-clinical staff (ambulance, catering, and domestic staff) than clinical staff (doctors, nurses, and paramedics) thought HIV could be transmitted by giving blood (38%, 153/404 v 12%, 40/346; chi 2 = 66.1 p < 0.001); one in ten clinical staff believed this. Except for midwives, half of staff in most occupational groups and 19% (17/91) of doctors and 22% (28/125) of nurses thought gloves should be worn in all contacts with people with AIDS. Most staff (62%, 593/958), including 38% (36/94) of doctors and 52% (67/128) of nurses thought patients should be routinely tested on admission, 17% of doctors and 19% of nurses thought they should be isolated in hospital. One in three staff perceived themselves at risk of HIV. Midwives, nurses, and theatre technicians were most aware of guidelines for safe working compared with only half of doctors, ambulance, and paramedical staff and no incinerator staff. CONCLUSIONS--Policy guidelines for safe working practices for patients with HIV infection and AIDS need to be disseminated across all occupational groups to reduce negative staff attitudes, improve knowledge of occupational transmission, establish an appropriate perception of risk, and create a supportive and caring hospital environment for people with HIV. IMPLICATIONS--Managers need to disseminate policy guidelines and information to all staff on an ongoing basis.
A healthy 22-year-old woman developed respiratory failure and brain death within 48 h of bilateral tibial fractures. Autopsy showed fat embolism in the lung and brain, and a large patent foramen ovale that may have contributed to massive cerebral fat embolism.
Since 1984 there have been reports of a destructive spondyloarthropathy occurring in patients on long-term hemodialysis. The primary abnormality appears to be an accumulation of beta 2-microglobulin, which is not adequately removed by dialysis, and forms amyloid deposits in articular and periarticular tissues. We report a case of this disease in a patient treated only by peritoneal dialysis. While this form of treatment may delay the development of arthropathy, as compared to hemodialysis, it does not prevent it. An increasing incidence of this disorder may be expected, since increasing numbers of patients have been on long-term peritoneal dialysis.
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OBJECTIVE: Candoxatril (UK79,300) is an orally available inhibitor of the neutral endopeptidase (E.C.3.4.24.11) which degrades atrial natriuretic factor (ANF). This study was designed to establish initial safety and efficacy data in essential hypertension for this novel class of drug. DESIGN: A prospective, double-blind, placebo-controlled, single-dose comparison of candoxatril with placebo in a crossover manner. Three doses of candoxatril (10, 50 and 200 mg) were used, with four subjects at each dose level. SETTING: The Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow, UK (a hospital clinical research unit). PATIENTS: Twelve patients with untreated essential hypertension. Diastolic blood pressure was greater than 95 mmHg on three separate occasions before entry to the study. INTERVENTION: Candoxatril or matching placebo was administered orally in the fasting state. Serial measurements of urinary volume and electrolyte excretion were taken (on each hour, urine volume was replaced with an equivalent volume of water by mouth). Blood pressure and heart rate were recorded for 12 h after drug administration and serial blood samples were taken for measurement of plasma ANF and neurohormone concentrations. MAIN OUTCOME MEASURES: Urine volume and electrolyte concentration; blood pressure; heart rate; plasma atrial natriuretic factor. RESULTS: Plasma ANF concentrations rose significantly in all patients within 2 h of candoxatril administration compared with placebo although peak and integrated ANF levels were similar at all three doses. A significant natriuresis was only seen after 200 mg candoxatril, with a greater cumulative urine sodium excretion over 12 h compared with placebo; this was associated with a greater diuresis over 12 h compared with placebo. After a single oral dose of candoxatril, blood pressure and heart rate remained unchanged. CONCLUSIONS: Candoxatril in a single dose caused no adverse effects in essential hypertension. The drug caused a rise in basal ANF levels at all doses, but natriuresis was only seen with the highest dose used. No change in blood pressure was recorded after acute dosing, and the results of chronic studies with this compound are awaited. Oral inhibitors of ANF degradation may have therapeutic potential in cardiovascular disorders.
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Discontinuous non-circumferential lesions of tunica media were observed in four cases of traumatic rupture of the vertebral artery. We hypothesize that these lesions were due to mechanical disruption of smooth muscle cells and the liberation of catabolic enzymes with subsequent degradation of the arterial media. To test this hypothesis, healthy vertebral arteries were incubated with crude extracts of bovine smooth muscle cytosol in attempt to reproduce the histological changes of the arterial media in traumatized vertebral arteries. We observed cytosol-induced degradation of tunica media, characterized by pallor of staining with the Masson's Trichrome method, which was due to catabolic enzyme activity that was effectively inhibited by heat inactivation of the cytosol. The cytosol-induced tinctorial changes were similar to the lesions of the tunica media in naturally-occurring cases of traumatic vertebral artery rupture. We conclude that although vertebral arteries can be ruptured by physical distortion alone, associated lesions of the tunica media are due to in situ trauma-associated release of heat-labile catabolic enzymes.
1. The following question can be successfully answered with a well developed quantitative assessment model: Is more money likely to be saved from the services of an on-site occupational health nursing program than is expended in providing these services? 2. The focus of this evaluation should be restricted to the net cost savings from the direct substitution of on-site for off-site provision of occupational health nursing services by such programs. 3. The evaluation model requires estimates of five separate factors for each occupational health nursing service provided by such programs that directly substitute for its off-site provision.
1. A primary management use of this quantitative assessment model is to estimate the overall net cost savings from operating an entire on-site occupational health nursing program. 2. Another management use of this model is to estimate the net cost savings contributed by individual occupational health nursing services included in the on-site program. 3. The exclusive focus of the model on the net cost savings arising from the direct substitution of on-site for off-site occupational health nursing services can be extended with the application of a break even analysis. 4. A sensitivity analysis can be applied to factors of the model to help overcome the effects of substantial uncertainty concerning their estimates.
Functional receptors for melatonin have been localized and characterized on the pars tuberalis (PT) of a number of mammalian species, but the cell-type responsive to melatonin is unknown. The ultrastructure of the ovine pars tuberalis has been examined and these findings correlated with the functional response of the gland to melatonin. This study revealed that two secretory cell types predominate in the ovine PT, which differ in the abundance of dense-core granules. The most abundant of the cells are either agranular or very sparsely granulated and represent 90% of the total population, with the remaining 10% being composed of cells with abundant dense-core vesicles. Few follicular cells were observed. This ratio of secretory cell-types persisted in primary culture, with the two types non-separable by Percoll gradient centrifugation. Using forskolin, as a non-specific stimulant of adenylate cyclase, melatonin was shown to inhibit the formation of cyclic AMP by 80-90% in cells both before and after Percoll centrifugation. The results demonstrate that the agranular secretory cells of the ovine pars tuberalis are the melatonin responsive cell-type of this gland.
A 12-year-old boy was investigated for knee pain and contractures, and was found to have an intraspinal tumor of a lumbar nerve root and a tumor in the tectal region, both low-grade astrocytomas. We postulated that the tectal region astrocytoma metastasized to the lumbar intraspinal region. After surgery, the child underwent focal irradiation to the posterior fossa supplemented by craniospinal irradiation and a boost dose to the region of the lumbar spinal tumor. A low-grade astrocytoma rarely presents as spinal metastasis. This case may represent the first of a primary tectal low-grade astrocytoma manifesting as a symptomatic spinal mass.