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Biomedical subjects

H C Knowles

Publications and source records attributed to H C Knowles.

At least 19 recordsLinked to original sources

Spontaneous abortion among insulin-dependent diabetic women.

A prospective study was undertaken to evaluate the frequency of spontaneous abortion in clinically apparent pregnancies among insulin-dependent diabetic women evaluated prior to pregnancy. The study was done in 132 pregnancies occurring in 91 diabetic women. The spontaneous abortion rate was 30%; 70% of the pregnancies progressed beyond 20 weeks. The abortion rates for Classes B, C, D, and F through RT were 0%, 25%, 44%, and 22%, respectively. Initial serum levels of the beta-subunit of human chorionic gonadotropin above 6000 mIU were usually associated with favorable outcome while levels below 6000 mIU were not predictive of outcome. Data from this study suggest that the risk of spontaneous abortion among insulin-dependent diabetic women may be substantially higher than for the general population. Higher abortion rates were generally associated with more advanced White classification of diabetes. Age at diagnosis was the only factor which showed a significant contribution to the risk of abortion.

Abortion, Spontaneous↗

High malformation rates and decreased mortality in infants of diabetic mothers managed after the first trimester of pregnancy (1956-1978).

Over a period of 23 years we accumulated data on 182 pregnant juvenile diabetic subjects during pregnancy, labor, and delivery. Diabetic subjects were evaluated generally after the first trimester of pregnancy. Data examined included diabetic class, maternal complications of pregnancy, and infant morbidity and mortality. Data were analyzed in two periods-before and after 1970. In the second period, maternal polyhydramnios and acidosis rates improved, neonatal problems of homeostasis did not change significantly, and combined fetal and neonatal losses fell from 34.7% to 16.4%. The neonatal malformation rate, however, increased from 1.4% to 16.8% and was not influenced by maternal age or diabetic class.

Adolescent↗

Clinical experience with one hundred seven diabetic pregnancies.

Clinical experience with 45 pregnancies in women with Class A diabetes and 62 pregnancies in women with insulin-requiring diabetes is described. The perinatal mortality rates were 0, 16.1, and 9.3, respectively, among the Class A, insulin-requiring, and total diabetic populations. Diabetic mothers experienced significantly higher prevalences of cesarean section and ketoacidosis than did the overall population. There were no other significant differences in maternal complications. Diabetic mothers demonstrated high rates of abnormal estriol levels and relatively low rates of positive contraction stress tests. Positive contraction stress tests were highly correlated with abnormal outcome. Delivery occurred either at or after 37 weeks in 93% of the Class A and in 81% of the insulin-requiring women. In comparison to infants in the general population, those of diabetic mothers experienced significantly elevated rates of being large for gestational age, macrosomia, and hypoglycemia. Congenital abnormalities were significantly higher in the Class A, but not in the insulin-requiring population. Neonatal morbidity could not be related to maternal diabetic control and was only minimally related to gestational age.

Blood Glucose↗

A pathophysiologic study of the hypertension associated with burn injury in children.

Measurements of cardiac output, blood volume, plasma renin activity (PRA), serum aldosterone, plasma and urinary catecholamine levels, serum and urinary electrolyte levels, and of transfusion and fluid therapy have been made in eight hypertensive and seven normotensive burned children. Studies were conducted during the acute phase of burn injury when hypertension was first diagnosed and were repeated just before discharge from the hospital. Hypertensive patients perfused at an inappropriately high total peripheral resistance and hypervolemia was demonstrated in the hypertensive patients. No differences could be demonstrated between hypertensive or normotensive patients in PRA, aldosterone, catecholamine, or electrolyte levels. These data indicate that both the hypervolemia and the vasoconstrictor activity of PRA and/or catecholamines are present when hypertension develops in these patients. These data suggest that the renin-angiotension-aldosterone system is directly stimulated as part of the neuroendocrine response to trauma.

Acute Disease↗

Pituitary hormone response to head injury.

Measurements of the serum levels of pituitary hormones were made in six patients with uncomplicated head injury. Samples were obtained at 4-hour intervals for 72 hours to evaluate diurnal rhythms. Three of the six patients revealed elevations of serum growth hormone (GH) and prolactin, but no trends could be established. Likewise, three patients had marked elevations of luteinizing hormone and lesser elevations of follicle-stimulating hormone, but no pattern was discernible. The level of thyroid-stimulating hormone was stable and remained in the normal range throughout. GH was measured after intravenous glucose loading. A paradoxical rise reverted to normal at the late follow-up evaluation. It is suggested that the abnormal levels were related to abnormal hypothalamic function rather than to pituitary damage.

Adolescent↗

Insulin, obesity, and triglyceride interrelationships in sixteen children with familial hypertriglyceridemia.

Sixteen children with familial hypertriglyceridemia were studied to determine whether there were any distinctive insulintriglycerid-obesity relationships in pediatric familial hypertriglyceridemia. Eleven of 16 children had calculated fat mass greater than the 97th percentile for age, height, and sex. When compared with 16 normal control subjects matched for degree of obesity immunoreactive insulin and glucose response during oral glucose tolerance was similar for normal and hypertriglyceridemic children. By either simple correlation or multiple regression analysis, plasma, triglycerides did not correlate significantly with measurements of insulin or obesity in hypertriglyceridemic or normal children. Within the limits of a small sample size, and in the presence of obesity, insulin does not appear to play a predominant role in the genesis of hypertriglyceridemia in children with familial hypertriglyceridemia. With a small mean weight loss of 1.8 kg and adherence to a diet with 20% of calories as protein, 40% each as fat and carbohydrate, polyunsaturate to saturate ratio of 1.5:1, mean plasma triglycerides were reduced from 238 to 140 mg/100 ml in the 11 obese children with familial hypertriglyceridemia (P less than 0.02). Speculation In spite of the complicating role of obesity, adolescence, and the small sample size, it is interesting to note that the correlation coefficients between triglyceride and insulin/glucose area (0.36), and insulin area (0.30), although not significant (P less than 0.1), were considerably higher in hypertriglyceridemic children than in normal subjects in whom comparable correlation coefficients were 0.08 and 0.08. This infers that the potential role of insulin in triglyceride metabolism in children with familial hypertriglyceridemia might be discerned with longitudinal follow-up into adulthood.

Adolescent↗

Low-dose intravenous insulin infusion versus subcutaneous insulin injection: a controlled comparative study of diabetic ketoacidosis.

Fourteen paients, 5 to 17 years old, with 18 episodes of uncomplicated diabetic ketoacidosis were randomly allocated and studied prospectively. The study group received 0.1 units of insulin per kilogram of body weight per hour as a continuous intravenous infusion; the control group received insulin subcutaneously. In both groups, a gradual fall in serum glucose and ketone levels was achieved. Serum ketones persisted longer in the intravenous group. No complications were encountered. The study suggests that both regimens of insulin administration are equally effective, but a low-dose constant infusion may provide more simplified and controlled management than the standard subcutaneous regimen.

Adolescent↗

The effects of diethylstilbestrol and medroxyprogesterone acetate on kinetics and production of testosterone and dihydrotestosterone in patients with prostatic carcinoma.

Alterations in the metabolism of testosterone (T) and dihydrotestosterone (DHT) induced by diethylstilbestrol (DES) or medroxprogesterone acetate (MPA) could account for the beneficial therapeutic effect of these agents in prostatic carcinoma. To investigate this possibility we sutdied plasma kinetics of T and DHT in 17 elderly patients with prostatic carcinoma, before and after treatment with DES (1 or 5 mg/d) or MPA (10 or 30 mg/d) for 30 days. Metabolic clearance rates (MCR) were determined with the single injection technique and by use of two compartment model, plasma concentrations (PC) of T and DHT by radioimmunoassay, the per cent of T bound to plasma protein (T-binding) by charcoal adsorption of the unbound steroid. Production rate (PR) and PC of T were lower, PR and PC of DHT were higher in our patients than in normal men. With both DES regimens, PR, PC and MCR of either androgen declined; however, T was suppressed to a much greater extent than DHT. In either instance, the decrease may have been caused by direct suppression of testicular androgen synthesis and/or by decreased gonadotropin stimulation. Enhanced T-binding played an additional role in reducing the free testosterone index. High and low dose of DES were equally effective. The low dose regimen of MPA did not influence androgen metabolism. MPA in the higher dose suppressed PR and PC of T and DHT, possibly due to effects on testicular synthesis or by gonadotropin suppression as suggested for DES. In contrast to DES, MPA failed to cause profound changes in MCR of either androgen or in T-binding. When judged by its influence on the metabolism of T and DHT in prostatic carcinoma, MPA in higher doses is much less effective than either dose regimen of DES.

Aged↗