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Biomedical subjects

M Tomlinson

Publications and source records attributed to M Tomlinson.

33 records · Page 2Linked to original sources
PubMed1994

Piccadilly Circus legionnaires' disease outbreak.

BACKGROUND: An outbreak of legionnaires' disease occurred in central London in January and February 1989. An Infection Control Committee was established to investigate the outbreak and institute control measures. The objective of this paper is to describe the investigation and control of the outbreak. METHODS: An epidemiological survey and case-control study were carried out. The subjects were cases of community acquired pneumonia associated with central London with onset of illness in January and February 1989. RESULTS: Thirty-three confirmed cases, including five deaths, and ten suspected cases, including three deaths, were identified with dates of onset from 1 January to 11 February. A clustering of visits by cases to the vicinity of Piccadilly Circus was noted, and a case-control study demonstrated a strong association between illness and visits to this area in the two weeks before onset of symptoms. The causative organism, Legionella pneumophila serogroup 1, was isolated from six patients. Legionella pneumophila of the same serogroup was isolated from water samples from five wet cooling systems (cooling towers) in the area under investigation, but in only two systems was the organism indistinguishable by subtyping from the patients' strains. Many of the cooling towers examined were inadequately maintained, including one of the two above a building adjacent to Piccadilly Circus from which a strain indistinguishable from the outbreak strain was isolated. All cooling towers in the area were shut down until inspected, and only allowed to restart after appropriate maintenance had been instigated. CONCLUSIONS: This outbreak showed the continuing risk of legionnaires' disease posed by wet cooling systems, including cooling towers, and highlighted the need to assess this risk so that appropriate maintenance is carried out. Regulations have recently been introduced, under the Health and Safety at Work Act, requiring notification of all wet cooling systems to the local authority to facilitate the investigation of outbreaks of legionnaires' disease.

Adolescent↗
PubMed1992

A clinical audit of patients on an orthopaedic waiting list for greater than two years.

AIMS: the aims of this paper were to review a group of 142 patients who had been on an orthopaedic waiting list for more than two years, both by postal audit and by clinical assessment, and to determine the fates of these patients. METHOD: all patients who had been on the orthopaedic waiting list for more than two years were written to, asking them to attend a preadmission clinic if they still required surgery. Those who attended the clinic were reassessed with regard to their orthopaedic problem and general state of health. Preadmission summaries, radiographs and waiting list details were analysed with respect to time spent on the waiting list, changes in clinical and radiographic findings and changes in diagnosis or proposed operation. The number of patients removed from the waiting list and the reason for removal was noted. RESULTS: One hundred and thirty-four of 142 patients replied. One hundred and three attended the preadmission clinic. A change of diagnosis was made for four patients and nine patients underwent a different operation than that originally proposed. Thirty-four patients were removed from the waiting list after reassessment. Of the 142 original patients only 69 (49%) remained on the waiting list. A number of patients deteriorated significantly while on the waiting list. CONCLUSION: a significant number of patients on a long orthopaedic waiting list may no longer require surgery. A number of patients can be expected to deteriorate significantly while on the waiting list. Postal audits alone are insufficient to determine who on the waiting list still requires surgery.

Adult↗
PubMed1992

In-vitro stimulation of TNF-alpha from human whole blood by cell-free supernatants of gram-positive bacteria.

Gram-positive bacteria are being recognized increasingly as the cause of shock-like syndromes, clinically indistinguishable from those seen in association with Gram-negative endotoxic shock. Much clinical and experimental data link tumour necrosis factor-alpha (TNF-alpha) with the pathogenesis of endotoxic shock, and a number of studies of individual Gram-positive species have also implicated TNF-alpha. We report here the first systematic study of the ability of cell-free supernatants of common Gram-positive bacteria to induce TNF-alpha from human peripheral blood monocytes in vitro. Almost all the 63 strains were able to induce TNF-alpha, although the levels were substantially lower than those obtained from supernatants of Gram-negative bacteria, used as controls. Streptococcus pneumoniae, S. pyogenes, viridans streptococci and coagulase-negative staphylococci were consistently more active than group B and D streptococci. TNF-alpha induction did not correlate with conventional markers of pathogenicity; amongst strains of Staphylococcus aureus, commensal and blood culture isolates did not induce significantly different amounts of TNF. We conclude that cell-free supernatants of most Gram-positive bacteria are capable of inducing TNF-alpha from human peripheral blood monocytes in vitro, but the significance of this finding remains to be determined.

Bacterial Toxins↗
PubMed1988

Effect of rapid normalization of plasma glucose levels on microvascular dysfunction and polyol metabolism in diabetic rats.

Effects of rapid normalization of plasma glucose levels (by insulin infused via Alzet pumps implanted intraperitoneally) on plasma insulin-like growth factor I (IGF-I) levels, granulation tissue polyol levels, and vascular permeation by 125I-labeled albumin were examined in male Sprague-Dawley rats with streptozocin-induced (60-65 mg/kg) diabetes. Two days after implantation of pumps, plasma insulin levels were twice normal levels and remained elevated (1.4-2.5 times normal) throughout the remainder of the study. Plasma glucose levels and granulation tissue polyol levels were normalized within 2 days after initiation of insulin treatment. Plasma IGF-I levels were significantly increased (2 times) by 2 days, but were not normalized until 7 days. In contrast, 125I-albumin permeation normalized at a much slower relatively linear rate and was still not completely normal after 14 days of insulin treatment. In view of 1) previous studies demonstrating that diabetes-induced increases in 125I-albumin permeation in this tissue are linked to increased metabolism of glucose to sorbitol and 2) the rapid normalization of tissue polyol levels in this study, the relatively linear rate of normalization of vascular permeability over 14 days in these studies suggests that impaired vascular barrier functional integrity in this model is mediated by structural and/or functional vascular alterations associated with sustained increased polyol metabolism rather than by increased polyol levels per se and/or by readily reversible functional and metabolic alterations associated with acute increases in polyol metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Galactose ingestion increases vascular permeability and collagen solubility in normal male rats.

In view of the similarity of cataracts and neuropathy in galactose-fed and diabetic rats, the present experiments were undertaken to determine whether consumption of galactose-enriched diets (10, 25, or 50% by weight) also increases collagen crosslinking and permeation of vessels by 125I-albumin analogous to that observed in diabetic rats. The observations in these experiments: demonstrate that consumption of galactose-enriched diets for 3 wk selectively increases 125I-albumin permeation of the same vascular beds affected in diabetic rats and by diabetic vascular disease in humans (i.e., the aorta and vessels in the eye, kidney, sciatic nerve, and new tissue formed in the diabetic milieu); demonstrate that the susceptibility of the vasculature to aldose reductase-linked injury (increased permeability) varies greatly in different tissues; indicate that collagen solubility (crosslinking) changes in galactose-fed rats differ sharply from those in diabetic rats; and provide new evidence that consumption of galactose-enriched diets induces a hypogonadal state in male rats.

Aldehyde Reductase↗
PubMed1986

Diabetes-induced increases in vascular permeability and changes in granulation tissue levels of sorbitol, myo-inositol, chiro-inositol, and scyllo-inositol are prevented by sorbinil.

In a recently developed animal model, we investigated the pathogenesis of diabetic vascular disease and demonstrated that 125I-albumin permeation is markedly increased in new "granulation tissue" vessels formed in subcutaneous tissue after the onset of diabetes. The studies described in this report were undertaken to examine the effects of an aldose reductase inhibitor on diabetes-induced increases in vascular permeability in this animal model. 125I-albumin permeation was assessed 3 weeks after the subcutaneous implantation of sterile preweighed polyester fabric (to stimulate angiogenesis) in diabetic male Sprague-Dawley rats, in controls, and in diabetic rats given sorbinil approximately 12 or approximately 25 mg/kg/d mixed in ground rat chow. Sorbinil administration prevented the diabetes-induced increase in vascular permeability by approximately 60% at the lower dose and by approximately 80% at the higher dose without affecting body weight or plasma glucose levels. Diabetes-induced changes in tissue levels of sorbitol, myo-inositol, scyllo-inositol, and chiro-inositol were also prevented by the high dose of sorbinil (data were not obtained for the lower dose). These observations are consistent with evidence linking diabetic cataracts and neuropathy to imbalances in sorbitol/inositol metabolism and support the hypothesis that diabetic vascular disease as well as neuropathy and cataracts are mediated by excess metabolism of glucose through the polyol pathway. Furthermore, these observations suggest that increased vascular permeability associated with diabetic microangiopathy in humans may be prevented by inhibitors of aldose reductase without the need to normalize blood glucose levels.

Adolescent↗
PubMed1986

Sex steroid dependency of diabetes-induced changes in polyol metabolism, vascular permeability, and collagen cross-linking.

The effects of castration on diabetes-induced increases in collagen cross-linking and vascular permeability and on polyol levels in new granulation tissue formed after induction of streptozocin (STZ) diabetes were examined in male Sprague-Dawley rats. New granulation tissue formation was induced by implanting sterile polyester fabric subcutaneously (s.c.) at the time of STZ injection 3 wk before assessment of vascular permeability and collagen cross-linking. Castration was performed 10 days before implanting the fabric. The characteristic increases in collagen cross-linking (manifested by decreased solubility in 0.5 M acetic acid) and in albumin permeation of the vasculature seen in intact diabetic rats were completely prevented by castration. Net collagen accumulation was not affected by diabetes or castration. Castration also markedly diminished diabetes-induced increases in tissue levels of sorbitol and completely prevented the decreases in tissue levels of myo-inositol and scyllo-inositol observed in intact diabetic rats, but had no effect on serum glucose levels, nonenzymatic glycosylation of plasma and granulation tissue proteins, or plasma somatomedin-C levels. The demonstration that castration prevents diabetes-induced increases in vascular permeability and collagen cross-linking as well as imbalances in tissue levels of sorbitol, myo-inositol, and scyllo-inositol in this model indicates that all of these changes are sex steroid-dependent phenomena. While the pathogenesis of these vascular permeability and collagen cross-linking changes is clearly multifactorial, these new findings: indicate that the role of sex steroids in the development of late complications of diabetes may be far more important than hitherto suspected, and suggest an explanation for the clinical observation that diabetic complications are uncommon in prepubertal diabetic subjects regardless of duration of diabetes.

Animals↗
PubMed1985

Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking.

In recent studies we have demonstrated a marked increase in albumin permeation of new vessels formed by angiogenesis (in subcutaneous tissue) in the diabetic milieu. Likewise, lysyl oxidase-mediated collagen cross-linking is markedly increased in the scar tissue associated with angiogenesis. The present studies were undertaken to determine whether sorbinil, a chemical inhibitor of aldose reductase that has been shown to prevent and reverse diabetic cataracts and neuropathy, also could prevent the vascular permeability and collagen cross-linking changes in this model. Vascular permeation by 125I-BSA, collagen cross-linking, and tissue levels of sorbitol, myo-inositol, and scyllo-inositol were assessed in male Sprague-Dawley rats 3 wk after injection of streptozocin and induction of angiogenesis and collagen synthesis in polyester fabric implanted subcutaneously. Sorbinil (approximately 25 mg/kg/day) added to the diet of diabetic rats reduced the diabetes-induced increases in albumin permeation by 80%, completely prevented diabetes-induced changes in tissue levels of sorbitol and myo-inositol, and markedly reduced diabetes-induced changes in tissue levels of scyllo-inositol. In contrast, sorbinil had no effect on plasma glucose levels or collagen solubility (an index of collagen cross-linking). These observations indicate that increased vascular permeability associated with diabetes is linked to imbalances in sorbitol/inositol metabolism. These findings also indicate that diabetes-induced increases in vascular permeability and in collagen cross-linking are independent phenomena and diabetes-induced increases in vascular permeability are largely preventable by treatment with an aldose reductase inhibitor in the face of high plasma glucose levels.

Albumins↗
PubMedDate not supplied

Vascular disruption birth defects and history of prenatal cocaine exposure: a case control study.

OBJECTIVE: To test the hypothesis that prenatal cocaine exposure is associated with a 3-fold increased risk for vascular disruption among malformations. STUDY DESIGN: A retrospective case-control study was based upon >68,000 delivery records at Hutzel Hospital for a 9-year period. Ascertainment was based upon ICD-9 codes for limb defects, abdominal wall defects, and facial clefts. Transverse limb defects and gastroschisis were defined as cases, and nondisruption anomalies served as controls. Statistical analysis for history of maternal cocaine use reported during pregnancy was performed by chi(2) analysis and the odds ratio determined. RESULTS: A total of 190 cases of limb anomalies, abdominal wall defects, and cleft lips were identified after exclusion criteria. Statistical analysis was performed on the 119 cases informative for maternal cocaine use during pregnancy. Seven of 34 vascular disruption cases had cocaine exposure reported versus 12 of 85 other malformations controls. The odds ratio for cocaine exposure and vascular disruption is 1.58 (95% confidence interval = 0.55-4.47). CONCLUSION: The putative association of prenatal cocaine exposure and vascular disruption birth defects remains unresolved, but the attributable risk is very likely less than the 3-fold odds ratio previously reported.

Abdominal Muscles↗