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Biomedical subjects

B Johnston

Publications and source records attributed to B Johnston.

At least 19 recordsLinked to original sources

Discriminant analysis when all variables are ordered.

Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria in obtaining the equation, the illustrative examples use absolute distance. This paper compares the prediction procedures obtained from NPD with those from linear discriminant analysis, linear regression (with and without transformed variables), and logistic regression. We show that NPD is analogous to regression tree analysis with incorporation of ordered variables and monotonicity. We use various prediction functions to predict the example data, the data using the leave-one-out technique, and a verification set. Consistently, non-parametric discriminant analysis performs as good as or better than the tested alternatives.

Craniocerebral Trauma

Rate-corrected mean velocity of fiber shortening-stress at peak systole as a load-independent measure of contractility.

The relation of mean velocity of fiber shortening-stress at end-systole is a good load-independent index of left ventricular contractility, but involves simultaneous M-mode echocardiography, carotid tracing and blood pressure determination, which may be impractical in children. As stress at peak systole and end-systole are closely related, this study examined whether the relation of mean velocity of fiber shortening-stress at peak systole could be used as a simpler method of assessing left ventricular contractility in a normal population of children. In addition, the cross-sectional normal range for a pediatric population was obtained. In 25 normal children aged 4 to 17 years (mean age 11), rate-corrected mean velocity of fiber shortening (MVCFc), stress at peak systole (sigma PS), and end-systolic stress (sigma ES) were determined using echocardiography, carotid pulse tracing and blood pressure measurement. Six patients with cardiomyopathy (mean age 8 years) were also studied. The relation of stress at peak systole and end-systolic stress was sigma PS = 1.004 sigma ES + 12.0 (r = 0.91, SEE = 4.98; p less than 0.001) for the normal group, and sigma PS = 1.083 sigma ES + 7.7 (r = 0.99, SEE = 4.07; p less than .001) for the cardiomyopathic group. This slope of the regression line was slightly higher and the difference was statistically significant. The slope of MVCFc = 0.0066 sigma PS + 1.55 (SEE = 0.131, r = -0.52) was nearly identical to that of MVCFc = 0.0065 sigma ES + 1.46, (SEE = 0.135, r = -0.46), with no difference in the regression coefficients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Inhaled steroids in patients with bronchiectasis.

The effect of inhaled beclomethasone diproprionate (1500 micrograms day-1) on symptoms, pulmonary function and sputum production was examined in a double-blind, placebo-controlled, cross-over study in 20 patients with bronchiectasis. An 18% reduction in daily sputum production (P less than 0.003) was observed on treatment with inhaled steroid compared to placebo. A small, significant, improvement in morning peak expiratory flow rate (P less than 0.03) and forced expiratory volume in 1 s (P less than 0.03) was seen but the absolute changes are unlikely to be of clinical importance. Symptom scores for cough improved significantly (P less than 0.02). Inhaled steroids may have a role in the management of bronchiectasis by reducing cough and sputum production.

Administration, Inhalation

Pharmacologic, toxicologic, and marrow transplantation studies in dogs given succinyl acetone.

A novel immunosuppressant, succinyl acetone (4,6-dioxoheptanoic acid), was studied in dogs. Results with bolus intravenous injections at doses ranging from 50 to 1600 mg/kg showed dose-dependent alpha and beta half-lives, ranging from 30 to 80 min and 7 to 27 hr, respectively. Results suggested that continuous i.v. infusion was necessary to maintain constant plasma levels. Four dogs were given 9.2 Gy total-body irradiation and autologous marrow transplants along with continuous i.v. infusion of succinyl acetone at 50, 100, 200, or 400 mg/kg/day for 21 days, and all four had rapid, sustained hematopoietic engraftment. However, two of the four dogs receiving 200 and 400 mg succinyl acetone/kg/day, respectively, developed bilateral hind-limb ataxia, with histologically confirmed cerebellar lesions in the dog given the higher dose, thus establishing a potential dose-limiting neurotoxicity. Prevention of graft-versus-host disease was studied in recipients of allogeneic marrow. Dogs were given 9.2 Gy TBI, followed by hematopoietic grafts from unrelated DLA-nonidentical or DLA-haploidentical littermate dogs. Succinyl acetone was given as continuous infusion for 21 days after transplant at doses of 100-300 mg/kg/day. Starting succinyl acetone on the day of marrow infusion in four dogs failed to prevent rapid onset of acute GVHD, and dogs survived no longer than controls. Starting succinyl acetone 3 days before transplant delayed the onset of acute GVHD and prolonged survival significantly compared with that of dogs not given postgrafting immunosuppression (P = 0.008); survival was comparable to that in previously reported dogs given either methotrexate or cyclosporine as postgrafting immunosuppression (P = 0.88 and 0.99, respectively). Seven of the sixteen allogeneic recipients developed evidence of neurotoxicity during succinyl-acetone infusion. Neurological dysfunctions were manifested by hind-limb ataxia and posterior paresis. In conclusion, succinyl acetone significantly delayed the onset of GVHD and prolonged survival of DLA-nonidentical marrow graft recipients but did not induce graft-host tolerance and was associated with dose-limiting neurotoxicity.

Animals

Relevance of pH dependency on in vitro release of bromocriptine from a modified-release formulation.

Since pH profiles of the dissolution rate are thought to be predictive for the in vivo performance of oral modified-release formulations with respect to bioavailability and dose dumping with food, these pH profiles were established for a new modified-release (MR) formulation for bromocriptine (Parlodel SRO). The results show a marked decrease of bromocriptine dissolution with increasing pH of the dissolution medium. However, when measured in native human duodenal juice (pH 8.1), dissolution was significantly higher than when measured in buffer of comparable pH. In a human pharmacokinetic study, this MR formulation showed good bioavailability and no food effect on the pharmacokinetic profile. Therefore, pH profiles alone seem to have only a limited predictive power for the in vivo performance of this MR formulation for bromocriptine.

Bromocriptine

Inter-observer agreement in assessing comatose children.

Inter-observer agreement was evaluated for twelve items used in the neurological assessment of comatose children. Data were obtained prospectively on fifteen patients examined independently by two observers in a double-blind fashion. Observer variability was measured by using the Disagreement Rate and Kappa statistic. The Disagreement Rate ranged from 0.01 to 0.12 for all items. Values for Kappa statistic were generally in accordance with those for Disagreement Rate. The data suggest fair to almost perfect inter-observer agreement for the items used to assess comatose children in this study.

Adolescent

Coma scales in pediatric practice.

Interobserver variability for six coma scales was assessed prospectively on a sample of 15 comatose children, by two physicians, in a double-blind fashion. The six scales were the Glasgow Coma Scale, the Simpson and Reilly Scale, the Children's Coma Score, the Children's Orthopedic Hospital and Medical Center Scale, the Jacobi Scale, and the 0 to IV Scale. Interobserver variability was measured by using disagreement rate and the kappa statistic. The results from both methods were generally concordant. The disagreement rate for the various items in the different scales ranged from a high of 0.20 to a low of 0.03. The disagreement rate was greater than 0.10 for verbal responses in the Children's Coma Score and Glasgow Coma Scale and for both items in the Children's Orthopedic Hospital and Medical Center Scale. The disagreement rate was 0.10 or less for the 0 to IV Scale and for all items in the Simpson and Reilly and Jacobi scales. The relatively high interobserver agreement for these scales makes them more suitable for the pediatric setting than the other three scales, since good agreement is essential for interpreting data reliably, both in clinical practice and for research.

Adolescent

Recurrent hypertonic dehydration due to selective defect in the osmoregulation of thirst.

A 6-year-old girl with recurrent episodes of hypertonic dehydration was studied. She denied thirst even with a plasma osmolality as high as 421 mosmol/kg. The hypernatremia was associated with an ability to concentrate urine (854 mosmol/kg). Volume expansion with water corrected hypernatremia (162 to 148 mEq/l) and resulted in an increased urine flow and urinary dilution (137 mosmol/kg) because of suppression of endogenous vasopressin (AVP) release (5.1 pg/ml). Hypertonic saline infusion raised the plasma AVP level (25.6 pg/ml) in response to changes in plasma osmolality (305 to 330 mosmol/kg) and led to a maximal urine osmolality of 818 mosmol/kg. With chronic forced fluid intake, the patient maintained a normal serum sodium concentration (range, 135-145 mEq/l) with a urine osmolality as low as 65 mosmol/kg. These findings are consistent with an isolated defect in the osmoregulation of thirst as the cause of the chronic hypertonic dehydration without deficiency in AVP secretion.

Arginine Vasopressin

Equestrian injuries: a comparison of professional and amateur injuries in Berkshire.

A retrospective study of horse riding injuries in Berkshire was undertaken over a one year period from November 1983. The information was obtained from the Ambulance Service, the Jockey Club and the St. John Ambulance Brigade. There was a total of 103 injured persons with no deaths. Information from the Jockey Club was compared with the other two groups, the former sustaining more limb injuries and the latter more head injuries. A questionnaire was sent to all 42 ambulance patients. Thirty-eight had radiographs taken, 16 of which showed a fracture. Forty-one were wearing some form of hard hat, but if a safety strap was available it was attached in 24 cases. The dangers of riding are highlighted and the importance of adequate protective clothing emphasised.

Adolescent

Expression of the c-myc protooncogene in human prostatic carcinoma and benign prostatic hyperplasia.

We have examined the level of c-myc transcripts in prostate tissue obtained from patients with both benign prostatic hyperplasia and adenocarcinoma of the prostate. A significantly higher level of c-myc transcripts is observed in patients with adenocarcinoma (P less than 0.05). In addition, a subset of patients with adenocarcinoma had levels of c-myc transcripts 2-fold higher than the mean level for this group. These preliminary results indicate that the investigation of c-myc levels as a prognostic indicator in prostatic carcinoma is warranted.

Acid Phosphatase