Robert G. Thompson

Integrated Concentration of Growth Hormone in Juvenile-onset Diabetes

Twenty-four-hour patterns of plasma growth hormone concentrations were evaluated during 50 studies of 42 subjects with juvenile-onset diabetes mellitus. Blood was sampled continuously over 24 h using a portable peristaltic pump under conditions in which subjects remained ambulatory and maintained their daily dietary and insulin regimens. All diabetics showed diurnal patterns characterized by frequent episodes of secretion of growth hormone. The mean 24-h concentration of growth hormone, designated the integrated concentration, was significantly higher among juvenile-onset diabetics (P < 0.001) than it was in ageand sex-matched nondiabetic populations. Juvenileonset diabetics younger than 20 yr had significantly higher (P < 0.005) growth hormone integrated concentrations than did older juvenile-onset diabetics. There was no statistically significant correlation between the integrated concentrations of glucose and growth hormone; thus, the study failed to provide us with support for the hypothesis that elevated growth hormone concentrations in diabetics are a consequence of hyperglycemia. Variability of diurnal glucose concentrations was positively correlated (P < 0.015) with the growth hormone integrated concentration among juvenile-onset diabetics. Our observations indicate that rapid declines in plasma glucose concentration or episodes of absolute hypoglycemia were significant factors, contributing to both the elevated integrated concentration and the secretory spiking of growth hormone observed in the diabetic population,

Growth Hormone: Metabolic Clearance Rates, Integrated Concentrations, and Production Rates in Normal Adults and the Effect of Prednisone

A constant withdrawal pump was used to determine the integrated concentration of growth hormone (ICGH) which was used in conjunction with the metabolic clearance rate (MCR) of growth hormone (GH) to calculate the GH production rates (GHPR) in normal adults, acromegalics, and normal controls receiving prednisone. The mean ICGH for 22 premenopausal females on no medication was 3.0+/-1.6 ng/ml (sd) which is significantly lower (P < 0.005) than the mean of 6.6+/-2.9 for 10 women receiving oral contraceptives and significantly higher than the means of 1.5+/-0.75 for 5 postmenopausal females (P < 0.05) and 1.8+/-1.0 for 16 adult males (P < 0.01) which are comparable. The mean GHPRs in mg/24 hr per m(2) for the four groups are: normal females = 0.52+/-0.24 (sd), females receiving contraceptive pills = 1.65+/-0.58 (P < 0.005), postmenopausal females = 0.26+/-0.12 (P < 0.025), and adult males 0.35+/-0.23 (P < 0.025).Three untreated acromegalic patients had ICGHs of 59, 82, and 93 ng/ml and GHPRs ranging from 14.5 to 17.9 mg/24 hr. Prednisone in a dose of 20 mg t.i.d. for 8 days significantly decreased both the ICGH and GHPR. Alternate day prednisone (60 mg in a single q.o.d. dose) resulted in less consistent inhibition of GH release which may play a role in the more normal growth seen in children receiving q.o.d. prednisone.

Verbal Fluency and Naming Performance in Type I Diabetes at Different Blood Glucose Concentrations

The effect of serum glucose alterations on selected verbal skills was examined in a group of diabetic men between 18 and 35 yr of age. An artificial insulin infusion system was used to set and maintain glucose concentrations during testing at each of three levels: hypoglycemia (55 mg/dl), euglycemia (110 mg/dl), and hyperglycemia (300 mg/dl). Subjects were used as their own controls, with performance at euglycemia serving as the comparison standard. A double-blind crossover design was employed as described in Holmes et al. (see ref. 14). Results showed significantly disrupted naming or labeling skills at hypoglycemia, with a trend toward poorer performance at hyperglycemia. During hypoglycemia, rate of responding was slowed from 6% to 18%, compared with euglycemic performance, but accuracy was not impaired. In contrast, word recognition skills were not affected by deviations in glucose. These performance effects were not correlated with duration of disease except for one of the five tests administered. This one exception, on the most difficult task, was less notable than the general finding of no relation between disease duration (from 6 mo to 17.5 yr) and test performance. Thus, in addition to considering long-term consequences of blood glucose alterations, clinicians and diabetic patients may wish to consider acute neuropsychological consequences of disrupted euglycemia.

Social and school competencies in children with short stature: longitudinal patterns.

Longitudinal evaluation of 47 children with short stature secondary to growth hormone deficiency (GHD), constitutional delay (CD), and Turners syndrome (TS) was undertaken approximately 3 years after initial assessment. Parent ratings of social and school competence indicated a developmental trend of poorer adjustment during early adolescence (ages 12 and 14), which was preceded (age 9) and followed (age 17) by age-appropriate functioning. Evaluation of social competence scores suggested that large organized group activities were avoided, although children had close friends with whom they interacted regularly. Children with short stature obtained age-expected scores for their involvement in solitary activities (i.e., hobbies and household chores) and tended to participate in individual sports (i.e., fishing, swimming), consistent with a pattern of withdrawal from large groups. Younger children with CD evidenced academic functioning at least 1 SD higher than children from all other groups, and this age-related effect may explain performance inconsistencies reported previously with other groups of CD children. Of the children studied, girls with TS experienced the greatest academic difficulty.

A new method of patellectomy for patellofemoral arthritis.

Total patellectomy, although it has a biomechanical disadvantage in that it may lead to a degree of quadriceps weakness, is frequently indicated in selected patients. Numerous different techniques of performing patellectomy have been described. In this paper, we present a technique of performing a patellectomy in which the continuity of the quadriceps mechanism is not disrupted and the vastuc medialis is advanced. Twenty-six patients (twenty-nine knees) in whom the procedure was performed were studied retrospectively. The findings in this series showed 90 per cent good or excellent results, two cases of extensor lag, an average of 118 degrees of knee flexion, minimum quadriceps atrophy with good strength, and minimum postoperative immobilization. The method presented has the important advantage of an easier, smoother postoperative knee-rehabilitation period, which is extremely advantageous in elderly patients.

Validity of urine glucose measurements for estimating plasma glucose concentration.

Both physicians and diabetic patients have traditionally relied on measurement of glycosuria as an indirect method of estimating plasma glucose concentration to guide adjustment of insulin and diet therapy. Our observations on the correlation between mean plasma glucose concentration with simultaneous urine glucose concentration or excretion rate re-emphasize the limitations of this approach. Although our observations show a significant correlation (P < 0.0001) between plasma glucose concentration and urine glucose concentration or urine glucose excretion rate, the wide confidence limits [95% confidence limits (minimum) ± 150 mg/dl] on plasma glucose concentration estimated from urine glucose measurements limit the clinical applicability of such estimates. Differences among subjects in the renal resorption of glucose contribute to the wide variance of estimates. However, significant variability in renal glucose resorption within individuals is documented, further reinforcing the limitations of urine glucose determinations for reliable estimates of plasma glucose concentrations. Diabetologists need to reconsider the applicability of urine glucose measurements in evaluation of adequacy of therapy and in adjustment of insulin dosage.

Cervical-Spine Injuries in Children

Some children up to the age of nine years, who are normal otherwise, may show a partial anterior subluxation of the second on the third cervical vertebra. This is considered a normal variant in the appearance of lateral roentgenograms of the flexed cervical spine. A survey of forty-seven children in three different childrens hospitals, all without symptoms or clinical evidence of neck disability, revealed that five children had marked subluxation of the second on the third cervical vertebra, and that three had borderline dislocations. Children who have these normal variations should not be subjected to extensive orthopaedic treatment, unless there has been a history of sufficient injury to the neck and clinical examination bears out the probability that these are pathological subluxations.

Glucose and Insulin Responses to Diet: Effect of Variations in Source and Amount of Carbohydrate

The influence of variations in amount of carbohydrate in the diet (45 per cent or 65 per cent of total calories) and source (sucrose or corn syrup) on plasma insulin and glucose concentrations was evaluated in eight normal men. Four diets, which were alternated in a Latin square design, were consumed for 10 days. Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test and over a 24-hour period while the test diets were consumed. The 24-hour study was completed with a portable, constant withdrawal pump, which allowed samples to be collected as a series of 48 consecutive, integrated, 30-minute samples. Thus, the 24-hour mean, or integrated, concentration as well as fluctuations during the day could be determined. The 24-hour integrated concentration of glucose did not vary significantly with the dietary changes tested. In contrast, two of the three methods used, to evaluate the glucose tolerance test results indicated that high carbohydrate diets improve glucose tolerance. Glucose fluctuations were significantly greater during ingestion of diets containing corn syrup than during those containing sucrose. The percentage of dietary energy supplied as carbohydrate did not influence glucose fluctuations significantly. Diets containing corn syrup were associated with significantly higher integrated concentrations of insulin than the sucrose diets. Insulin-integrated concentrations did not vary significantly with changes in the percentage of dietary carbohydrate. The insulin response to the glucose tolerance test did not vary with the source of carbohydrate and did not accurately reflect the 24-hour mean insulin concentrations. We concluded that (1) a change in the percentage of energy supplied as carbohydrate does not significantly influence the concentration of either glucose or insulin in normal subjects; (2) concentrations of glucose throughout the day are more stable when the dietary carbohydrate is sucrose than when it is corn syrup; (3) sucrose-containing diets require significantly lower insulin concentrations to maintain euglycemia than do corn syrup–containing diets; (4) glucose and insulin responses to an oral glucose tolerance test do not accurately reflect the 24-hour glucose and insulin concentrations obtained during ingestion of the test diets.

Amputation and Rehabilitation for Severe Foot Ischemia

Definitive amputation for foot ischemia secondary to arteriosclerosis with or without diabetes, should always be considered an important first step in the process of rehabilitation. If the patient can have a below-knee amputation, the end product is a great deal more satisfactory than if the patient has an above-knee amputation. Ultimate ambulatory status can be achieved only by preserving both knee joints.

Relationship of the adrenergic nervous systemand growth hormone release in normal adults and children with various growth disorders

The influence of alpha receptor stimulationduring beta blockade has been evaluated using epinephrine and propranolol in normal adults and patients with growth problems. These drugs were administered independently, together, and concurrently with arginine, insulin, and synthetic ACTH in a group of eight normal adults. Significant release of growth hormone accurred after arginine, insulin, ACTH, or simultaneous epinephrine and propranolol administration, as well as after administration of epinephrine and propranolol with arginine, insulin or ACTH. Significantly greater release occurred in normal adults and among the patients with familial short stature, intrauterine growth retardation, and constitutional delay after arginine-insulin-epinephrine-propranolol administration than with arginine-insulin alone. No release occurred after either test among idiopathic and organic hypopituitary patients except in three patients with idiopathic hypopituitarism with a partial but inadequate response to arginine and insulin. These patients released growth hormone after epinephrine and propranolol administration and to a greater extent after arginine-insulin-epinephrine-propranolol administration and hence may have a defect in adrenergic receptors. Epinephrine and propranolol also enhanced growth hormone release after insulin among the psychosocial dwarfs.