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Biomedical subjects

J J Cook

Publications and source records attributed to J J Cook.

48 records · Page 3Linked to original sources

Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes.

A double-blind controlled trial of azathioprine (2 mg.kg-1.day-1) was conducted with 49 patients aged 2-20 yr (mean 10.8 yr) who had newly diagnosed type I (insulin-dependent) diabetes. Patients were randomly assigned to receive either azathioprine (n = 24) or placebo (n = 25) for 12 mo, beginning within the 20-day period after diagnosis. Baseline clinical and metabolic characteristics did not differ between the two groups. No patient experienced complete remission, defined as restoration of normal carbohydrate tolerance without other treatment. Partial remission, defined as good metabolic control (hemoglobin A1c less than or equal to 7.9%, preprandial blood glucose less than or equal to 8 mM with an insulin dose of less than 0.5 U.kg-1.day-1), occurred in 10 placebo (40%) and 7 azathioprine (29%) patients at 6 mo and in 4 placebo (16%) and 4 azathioprine (17%) patients at 12 mo (differences not significant). Fasting plasma C-peptide was significantly greater in the azathioprine-treated group at 3 and 6 mo, but this difference was not sustained. C-peptide responses to a standard meal and the frequency of islet cell and insulin antibodies did not differ between the two groups over the 12-mo period. Azathioprine caused no significant side effects. We conclude that in the dosage used, and despite early effects on endogenous insulin secretion, azathioprine alone does not influence the remission phase in children with newly diagnosed type I diabetes.

Azathioprine↗

Mitogenic effects of growth hormone in cultured human fibroblasts. Evidence for action via local insulin-like growth factor I production.

We examined human growth hormone's (hGH) effect on mitogenesis in cultured human fibroblasts, and the role of local insulin-like growth factor I (IGF-I). With 0.5% human hypopituitary serum (HPS), hGH increased thymidine incorporation (TI) over serum-free medium dose responsively, with half-maximal effect at 10 ng/ml (0.5 nM) (hGH 127 +/- 8.8%; IGF-I 107 +/- 1.7% [SEM]) (n = 10). Similarly, with 0.5% HPS, hGH and IGF-I increased cell replication by 172 +/- 8.2% and 169 +/- 25%, respectively (n = 4). Specific IGF-I monoclonal antibody (Sm1.2) dose dependently blunted TI stimulated by 10 ng/ml hGH or IGF-I (at 1:1000, 38 +/- 6.5% and 30 +/- 14% reduction, respectively). Sm1.2 also reduced cell replication by both 10 ng/ml hGH and IGF-I, respectively, to 32% and 42% of stimulated values. Dexamethasone (0.1 microM) synergistically enhanced TI by both IGF-I and hGH. A 28-h time course for TI showed that hGH stimulated a similar peak to IGF-I, lagging in its effect by 4-10 h. We have provided further evidence that hGH stimulates growth of cultured human fibroblasts via local IGF-I production, consistent with IGF-I's paracrine-autocrine role.

Adult↗

Detection of insulin antibodies in newly-diagnosed type 1 diabetic children after "acid-stripping" of sera.

A sensitive microassay using sera from which endogenous bound insulin was removed by acid-stripping was employed to screen for insulin antibodies in 48 newly-diagnosed Type 1 diabetic children and 20 age-matched controls. Using intact diabetic sera, the binding of 125I-insulin exceeded the upper control range in 16/48 (33%); when the sera were acid-stripped at pH 4.2 for 30 minutes at 4 degrees C, binding to the 16 positive sera increased further and in another five sera became significant, making a total of 21/48 positive (44%). Children 5 years of age or less had a higher prevalence of insulin antibodies. Islet cell antibodies, assayed by indirect immunofluorescence, were detected in equal fractions of insulin antibody-positive and -negative sera (76% versus 77%). Assay of insulin antibodies using acid-stripped sera under the conditions described significantly increases the sensitivity of insulin antibody detection. Insulin antibodies appear to be a specific marker of islet autoimmunity, but compared to islet cell antibodies are relatively insensitive, and may be a marker for a particular subgroup of diabetics.

Adolescent↗

Ipratropium and fenoterol in the treatment of acute asthma.

A double-blind, randomized trial was carried out in 48 children to assess the effects of inhaled ipratropium bromide, fenoterol or a combination of both drugs in treating their moderately severe acute asthma. Doses were adjusted according to the age of the patients and administered by nebulizer. Measurements of pulse rate and respiratory rate and assessment of the severity of symptoms were made at fixed intervals during the first 2 hours on treatment. Repeat nebulizations were given, if necessary, at 2-hourly intervals. The results suggested that fenoterol provided the most adequate treatment and there was no evidence to indicate that the addition of ipratropium produced any improved benefit.

Acute Disease↗

Antimicrobial prescribing errors in children.

During a 120 day period, the charts of patients who had received antimicrobial agents were examined. This group numbered 255 and comprised 52% of children admitted with infections. Patients treated by family doctors and/or hospital staff predominantly had respiratory infections and the ampicillin/amoxycillin group of drugs was most commonly prescribed. Of the 203 antimicrobial agents prescribed by hospital staff, 64% were considered to be prescribed appropriately. The major errors related to dosage, the most potentially serious relating to the prescribing of aminoglycosides and chloramphenicol. Of the 203 antimicrobial agents prescribed for 171 children in the community, 11% were considered to be appropriately prescribed or without error. The major error was the prescribing of these drugs for syndromes of known viral aetiology. Errors were also frequent in relation to dosage, duration and choice of antimicrobial agents.

Anti-Bacterial Agents↗

Effect of endotoxin shock on skeletal muscle cell membrane potential.

Transmembrane potential changes were monitored in 21 dogs that were shocked by intravenous injectin of Difco purified endotoxin (055:B5). Corresponding serial measurements of electrolyte concentration in plasma and muscle biopsies were obtained to assess fluid and electrolyte changes. During shock the transmembrane potential was found to become significantly less negative (-55.2 mv.) from a control of -87.5 mv. (p less than 0.001). A significant efflux of K+ (p less than 0.02) from the cell was recorded, but intracellular Na+ and Cl- concentration rose. A plausable explanation for the fluid and electrolyte shifts, possibly due to a decrease in the muscle temperature and a resultant decline in metabolism, has been offered.

Animals↗