Fatal rupture of a subcapsular liver haematoma in a patient treated with anisolylated plasminogen streptokinase activated complex.
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Biomedical subjects
Publications and source records attributed to R M Wilson.
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In 35 thyrotoxic patients and 35 patients receiving thyroxine replacement therapy mean serum intact parathyroid hormone concentrations were lower than in euthyroid normal volunteer controls. In 20 hypothyroid patients intact PTH was increased relative to euthyroid controls. Mean serum adjusted calcium was increased in thyrotoxic patients relative to euthyroid controls and in 8 toxic patients with elevated serum adjusted calcium (greater than 2.60 mmol/l) intact PTH was below the assay detection limit (less than 0.5 pmol/l). Indices of PTH activity were consistent with intact PTH measurements in thyrotoxic patients with nephrogenous cyclic adenosine monophosphate lower, tubular maximum reabsorption of phosphate higher, and urinary calcium creatinine ratio higher than controls. In hypothyroid patients these indices of PTH activity suggest relative end organ resistance to PTH with nephrogenous cyclic adenosine monophosphate similar, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio lower than in controls. In treated hypothyroid patients nephrogenous cyclic adenosine monophosphate was higher, tubular maximum reabsorption of phosphate similar, and calcium creatinine ratio higher than in controls. These results are compatible with the hypothesis that thyroid status modifies the renal responses to PTH (1-84).
This study examines whether an aldose reductase inhibitor (statil, ICI) can enhance neutrophil oxidative killing by diabetic neutrophils. We have examined a radiometric assay of phagocytosis and killing of Candida albicans by neutrophils from 20 controls and 20 subjects with insulin-dependent diabetes under various in vitro glucose concentrations. Glucose was present at 5, 10 and 20 mM in the presence and absence of statil (11 microM). Phagocytosis was unaffected by raised glucose levels in controls and in diabetic subjects. Killing by the diabetic cells was inhibited by increasing concentrations of glucose, killing was 18.9 +/- 2.0, 16.9 +/- 2.4 and 14.8 +/- 2.0% (mean +/- s.e.m.) at 5, 10 and 20 mM glucose, respectively (P less than 0.05). With the addition of statil under the same conditions killing improved to 19.3 +/- 2.0, 23.2 +/- 2.2 and 23.6 +/- 2.4 (P less than 0.01), these values were similar to the controls (P greater than 0.01). We conclude therefore that aldose reductase inhibition restores oxidative killing to normal.
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To develop care of diabetes further a specialist nurse established contact with general practices in Sheffield Health District and identified difficulties in providing a service for diabetics. One hundred and thirty practices were visited, and full data were collected from 104. Each practice agreed to establish a register of diabetics, and information and support were subsequently provided to help in developing services. In collecting information from each practice the nurse covered specific points on staff, facilities, and organisation. Over two years the service offered in 60 practices considerably improved, allowing a minimum standard of diabetic care to be achieved. This allowed coordinated and effective referral of certain patients from hospital diabetic clinics and improved services to those not attending any clinics.
The cases of two patients with vesiculobullous lesions were diagnosed clinically and histopathologically as pemphigus foliaceus; unexpectedly, both revealed intercellular IgA, but not IgG, in the upper epidermis by direct immunofluorescence. Such histologic and immunofluorescence findings have been reported in eight other cases. In our cases no circulating IgA or IgG intercellular antibodies could be detected; in four of eight other reported cases IgA antibodies showed intercellular staining like that of pemphigus antibodies. Subcorneal acantholytic lesions occurred in both our cases; of the other cases reported, five had essentially identical histopathologic findings. The clinical and histopathologic features of pemphigus, as well as the recent findings of circulating IgA intercellular antibodies alone or with IgG antibodies, appear to place this disease into the spectrum of pemphigus. The 10 IgA pemphigus cases reported to date fall into one of two groups, the IgA pemphigus foliaceus (including our two cases) and IgA pemphigus of the intraepidermal neutrophilic type, which seems to be less common.
Authentic stable standards of 7H-dibenzo[c,g]carbazole (DBC), a potent environmental carcinogen, were synthesized in order to study the compound's metabolism and mutagenesis in whole cell systems. Complete characterization of 2-OH-DBC, 3-OH-DBC, 4-OH-DBC, 13c-OH-DBC and N-methyl-DBC was accomplished by UV, IR, fluorescence and high resolution NMR spectra, and by high resolution mass spectrometric procedures. Metabolites of DBC were isolated and separated by HPLC from extracts of rat liver microsomal incubations and the medium of primary cultures of rat liver cells. Identification of metabolites was accomplished by comparisons between the authentic standards and isolated metabolites by UV and fluorescence spectroscopy, mass spectral analyses, and by co-chromatographic techniques. 2-OH-DBC and 3-OH-DBC were found in all rat liver preparations as well as three other unidentified phenols. 4-OH-DBC, 13c-OH-DBC or N-methyl-DBC were not isolated under any conditions. The rates of appearance of DBC metabolites in cultures of rat liver cells were compared to those for benzo[a]pyrene (BaP) at 10, 25, 50 and 100 microM substrate. At 25 microM substrate or greater, DBC metabolites appeared in the culture medium at significantly faster rates than those of BaP. At 100 microM substrate, DBC metabolites appeared at a rate approximately 4-times the rate observed for BaP. When the mutagenic potential of DBC was compared to that of BaP under identical conditions in a co-cultivation system of rat liver cells and an epithelial cell line, DBC was found to produce significantly higher rates of mutagenesis than BaP at concentrations of 0.4, 4.0 and 40.0 microM in the culture medium. The mutagenic potential of DBC was compared to that of several derivatives of the parent compound. 3-OH-DBC, 13c-OH-DBC and N-methyl-DBC were found to be mutagenic in the co-cultivation system at 40 microM, with mutation frequencies of 4.4 +/- 0.8, 8.0 +/- 3.1 and 12.9 +/- 5.4 mutants per 10(5) survivors, respectively. The parent compound induced 8.0 +/- 2.8 mutants per 10(5) survivors at the same concentration. 2-OH-DBC and 4-OH-DBC were not mutagenic under the same conditions. The studies have shown that metabolism of 7H-DBC leads predominantly to phenols in rat liver cells. The results of the mutagenesis experiments indicate that, of the derivatives studied, those associated by induction to the nitrogen are mutagenic. The latter studies suggest that the nitrogen is involved in the activation of the parent compound through inductive mechanisms.
Cerebral nocardiosis is an uncommon but increasingly diagnosed infection in Australia. We report three cases. One occurred in an immunosuppressed male in whom the diagnosis was made at autopsy, one in an otherwise healthy elderly woman with subcutaneous nocardiosis, and the third was a posterior fossa nocardial abscess without systemic involvement occurring in a previously healthy woman after surgical excision of a meningioma. Primary cerebral nocardiosis is rare, with only two cases of primary posterior fossa nocardiosis reported. The cases highlight the difficulty of diagnosis and the need for aggressive treatment with a combined approach of surgical drainage and antibiotic therapy. The antibiotic regime of choice is the subject of controversy. Rifampicin, cephalosporins, imipenem, sulphonamides and other agents were used with varying success in our patients. Cerebral nocardiosis should be considered in any patient with a cerebral space occupying lesion.
Clinical and immunological features suggesting Type 1 diabetes were assessed in 202 patients treated with oral hypoglycaemic agents for presumed Type 2 diabetes. Islet cell antibodies (ICA) were detected at a level exceeding 5 JDF units in 5.9% of patients, and complement-fixing ICA were detected in 3.4%. IgG insulin autoantibodies were detected in 8.8% of insulin-naive patients, none of whom were ICA positive. ICA were detected more frequently in patients with shorter duration of diabetes (p = 0.02). Age and relative body weight were similar in ICA positive and negative groups. ICA positive patients were more likely to have lost weight (p less than 0.02) than ICA negative patients, although this may have been attributable to the differing duration of diabetes in the two groups. Other individual clinical features suggesting Type 1 diabetes were not significantly more frequent in ICA positive patients. However, a higher proportion of ICA positive than ICA negative patients had one or more features suggestive of Type 1 diabetes irrespective of the duration of diabetes. Clinical features suggesting Type 2 diabetes were present in a similar proportion of ICA positive and ICA negative patients. Fasting and glucagon stimulated C-peptide levels were similar in ICA positive and matched ICA negative patients.
We assessed the prevalence of hypoglycemic symptoms in patients (aged 40-65 yr) treated with oral hypoglycemic agents (OHAs) attending routine diabetes clinics at our hospital. Symptoms were experienced during the previous 6 mo in 41 of 203 (20.2%) patients treated with sulfonylureas but in none of the 16 patients treated with metformin alone. Hypoglycemic symptoms were experienced at least monthly in 5.9% and less frequently in 14.3% of patients. The prevalence of symptoms decreased with increasing duration of sulfonylurea administration (P less than .01). Mean glycosylated hemoglobin and postprandial plasma glucose were significantly lower in patients reporting hypoglycemic symptoms than in those without symptoms (P less than .001). The prevalence of hypoglycemic symptoms was significantly higher in patients treated with glyburide than in patients treated with gliclazide (P less than .01) or chlorpropamide (P less than .05). The prevalence of symptoms was higher in patients taking medications in addition to OHAs (P less than .01). Ten (24%) of the patients who experienced hypoglycemic symptoms were taking drugs that may potentiate sulfonylureas.
We introduce a large equivalence class of graph properties, all of which are shared by so-called random graphs. Unlike random graphs, however, it is often relatively easy to verify that a particular family of graphs possesses some property in this class.
Two cases of toxic shock syndrome following chemical face peel are reported. Toxic shock syndrome is a severe toxin-mediated multisystem disease. The major signs are fever, rash, desquamation, and hypotension. It can occur in males as well as females and is not necessarily related to menstruation. The surgical wound does not usually appear infected. Early recognition is the hallmark of successful treatment. Therapy is symptomatic, with aggressive administration of fluids. Antistaphylococcal agents are used. Prophylactic antibiotics are not necessarily recommended.
Most textbooks advise that newly diagnosed insulin-dependent diabetics be admitted to the hospital. Nevertheless, if they are not acutely ill, we start insulin treatment on an outpatient basis. We report herein the logistics, efficacy, and safety of our system. Over two years, 115 newly diagnosed insulin-dependent diabetics were seen in our hospital. Fifteen (66% of them ketoacidotic) were admitted. The other 100 were treated as outpatients by a nurse specialist with a starting dosage of 6 to 10 units of intermediate-acting insulin twice daily. Hemoglobin A1 concentration at diagnosis was 15.2% +/- 2.7% (mean +/- SD); at six months, 10.9% +/- 2.9%; and at one year, 10.6% +/- 2.8%. Only three outpatient starters were hospitalized in the first year, one for hypoglycemia and two with respiratory tract infections. Our findings suggest that outpatient stabilization is both safe and cost-effective.
The oxygen washin method has been shown to be a practical way to measure functional residual capacity (FRC) in the intensive care unit. The ventilator oxygen concentration is increased and measurements of respiratory flow and oxygen concentration at the mouth are made with the patient monitoring system. No additional personnel, bedside equipment or ventilator attachments are required. A feasibility study was performed to determine if this method could be used to estimate a continuous distribution of ventilation with respect to ventilation to volume ratio VA/V. Due to gas mixing in the ventilator, the inspired oxygen fraction does not increase instantaneously to its new value. An equation was derived which models the lung as 50 discrete compartments and accounts for the transient change in mean inspired oxygen fraction. A digital computer simulation demonstrated good distribution recovery for one and two mode ventilation distributions. Continuous distributions were computed for four post cardiac surgery patients at four levels of positive end expiratory pressure (PEEP). In these patients a linear increase in the amount of ventilation in the normal VA/V range occurred with increasing PEEP, i.e., slow and fast spaces tended to move centrally toward a more normal VA/V range. At zero PEEP 26% of the ventilation occurred in the normal range and this increased to 49% at 15 PEEP. Dead space fraction was poorly estimated and spurious modes occurred in the high VA/V range.
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Neutrophil phagocytosis and killing of Candida albicans were examined using a radiometric assay in 25 patients with insulin-dependent diabetes and 17 controls under various in vitro metabolic conditions. Glucose was present at 5, 10 and 50 mM, beta-hydroxybutyrate at 1, 5 and 20 mM and glucose with beta-hydroxybutyrate in combinations of 10 with 5 and 50 with 20 mM, respectively. Phagocytosis occurred at similar levels in diabetics and controls at all the glucose and beta-hydroxybutyrate concentrations used. The ability to neutrophils from diabetics to kill candida was inhibited by increased concentrations of glucose and beta-hydroxybutyrate, both independently and in combination. Candida killing (mean +/- s.e.) was 20 +/- 2.4, 19 +/- 2.3 and 13 +/- 2.7% at glucose concentrations of 5, 10 and 50 mM; and 20 +/- 3.4, 20 +/- 3 and 13 +/- 3% at beta-hydroxybutyrate concentrations of 1, 5 and 20 mM, respectively, and in glucose and beta-hydroxybutyrate combinations of 10 with 5 and 50 with 20 mM was 20 +/- 2.8 and 10 +/- 2.8%, respectively. Inhibition was not observed with control neutrophils. These data indicate that although phagocytosis occurs at similar levels in diabetics and controls, killing of candida by the diabetic neutrophil is impaired under conditions of hyperglycaemia and ketosis. The biochemical basis for this effect is discussed.
A new method for the measurement of phagocytosis of Candida albicans by human polymorphonuclear leucocytes (PMN) is described using a fluorescence activated cell sorter. We have used acridine orange to discriminate between PMN which have internalised yeast particles and those which have not. This method allows accurate measurement of particle phagocytosis as an event distinct from particle adherence. It also permits detailed examination of the kinetics of phagocytosis, the study of which is likely to be of value in the investigation of diseases where abnormalities of PMN function are suspected.
Twenty-six Type 1 diabetic patients previously treated for 10-20 months with twice daily conventional bovine isophane insulin (containing at least 1000 ppm proinsulin) were changed to highly purified (less than 1 ppm proinsulin) bovine isophane for 6 months (Switch group). Insulin antibody levels fell significantly from a geometric mean of 14.9 to 9.1 micrograms/l. Thirty-two patients with newly diagnosed Type 1 diabetes were treated with the same highly purified bovine isophane insulin twice daily for 6 months (Starter group). Their insulin antibody levels rose from a geometric mean of 1.9 to 8.2 micrograms/l in contrast to values of 1.4 rising to 16.3 micrograms/l in an age and sex matched historical control group treated from diagnosis only with twice daily conventional bovine isophane insulin. Lipoatrophy at injection sites developed in three (9%) in the Starter group treated with highly purified bovine isophane compared to 7 (22%) of those on conventional bovine isophane. Insulin dose and diabetic control did not differ between the groups. Starter and Switch groups were subsequently treated with semi-synthetic human isophane insulin for 6 months during which insulin antibody levels fell significantly from a geometric mean of 8.5 to 4.4 micrograms/l (p less than 0.001). We conclude that bovine insulin purified to less than 1 ppm proinsulin is significantly less immunogenic than its conventional proinsulin contaminated counterpart but even at this level of purity is still more immunogenic than human insulin of equivalent purity.