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Biomedical subjects

M P Golden

Publications and source records attributed to M P Golden.

At least 19 recordsLinked to original sources

Activation of human immunodeficiency virus by herpes simplex virus.

Heterologous viruses have been examined for their ability to accelerate the course of infection with the human immunodeficiency virus (HIV) type 1. In this study, ACH-2 cells persistently infected with HIV-1 exhibited augmented HIV-1 replication as a result of superinfection with herpes simplex virus (HSV) type 1. Using HSV-1 mutants with deletions in the genes encoding immediate-early proteins ICP0, ICP4, and ICP27, it was found that ICP0 and ICP27, but not ICP4, were essential for up-regulation of HIV replication. Northern blot analysis showed that this activation of HIV was characterized by an initial rise in the level of the small, subgenomic (2.0 and 4.3 kb) mRNA species, followed by an increase in the level of unspliced genomic (9.2 kb) mRNA. Such a shift in transcriptional phase recapitulates the early-to-late transition seen in single-step growth curves of acute HIV-1 infection. Thus, HSV can activate HIV-1 from latency in ACH-2 cells, this activation of HIV is independent of productive HSV replication since the delta ICP4 deletion mutant is replication-incompetent, and this activation is evident as an increase in the steady-state levels of HIV transcripts.

CD4-Positive T-Lymphocytes

Twice-daily humulin ultralente insulin decreases morning fasting hyperglycemia.

OBJECTIVE: To test whether a two-injection regimen of HUL/R would improve FBG and metabolic control in pediatric IDDM patients with a dawn rise in FBG compared with our standard twice-daily therapy, HL/R. RESEARCH DESIGN AND METHODS: Seventy-seven patients with fasting hyperglycemia (prebreakfast mean FBG greater than or equal to 8.3 mM (150 mg/dl) during the preceding 2 wk) were evaluated with twice-weekly midsleep (0230-0330) FBG for 2 wk. Forty-seven patients (61%) had a mean dawn rise between midsleep and prebreakfast of greater than or equal to 2.8 mM (50 mg/dl). Patients continued on HL/R for an additional 4 wk, after which 31 patients were then randomized into a double-blind 12-wk trial of either HUL/R (n = 14) or HL/R (n = 17) administered before breakfast and the evening meal. Midsleep FBG was obtained twice weekly with weekly insulin adjustment as needed to optimize glycemic control. FBG was monitored and verified with memory glucometers (Glucometer M). HbA1c levels were measured at the time of physician visits at 0, 6, and 12 wk. RESULTS: Prebreakfast FBG was lower in the HUL/R-treated patients (10.6 +/- 0.6 vs. 12.6 +/- 0.6 mM [191 +/- 6.4 vs. 227 +/- 11.2 mg/dl], P less than 0.02). The dawn rise was diminished in the HUL/R patients (0.5 +/- 0.5 vs. 2.6 +/- 0.7 mM [9 +/- 8.3 vs. 46 +/- 11.7 mg/dl], P less than 0.02). FBG at lunch, dinner, bedtime, and midsleep were similar in both groups, and HbA1c did not differ between groups or change significantly in either group during the 12-wk trial. Insulin dose, percentage R, day-night dosage split, and episodes of hypoglycemia (FBG less than 3.3 mM [60 mg/dl]) were similar in both groups. CONCLUSIONS: A 12-wk trial of twice-daily HUL/R improved fasting glycemia in pediatric patients with a dawn rise but did not improve metabolic control as measured by HbA1c.

Blood Glucose

Pediatrics residents' attitudes about insulin-dependent diabetes mellitus and children with diabetes.

Nationwide, pediatricians provide a substantial portion of the health care of children with diabetes. Their beliefs and attitudes about diabetes and children with the illness have an important influence on their treatment decisions. The attitudes and beliefs of a 1988 sample of pediatrics residents were compared with data from a 1987 national survey of practicing pediatricians' beliefs and attitudes about children with insulin-dependent diabetes mellitus and about the disease itself. Pediatrics residents in their second and third years of training were considerably more negative about diabetes and diabetic children than were either the members of the national sample of practicing pediatricians or the residents' first-year colleagues.

Attitude of Health Personnel

Management of diabetes in pediatric resident continuity clinics.

General pediatricians provide comprehensive care for many children with insulin-dependent diabetes mellitus. To assess and improve our ambulatory training program, we first evaluated diabetes-specific care behaviors by residents in their continuity clinics and then introduced a structured visit encounter form. Based on established guidelines provided to the residents, a chart audit indicated appropriate measurement of glycosylated hemoglobin 40% of the time, cholesterol 90% of the time, urine protein 50% of the time, and thyroxine 66.7% of the time. Height was plotted 23% of the time, blood pressure was noted 66% of the time, and ophthalmologic referrals were documented 60% of the time. Requests for assistance from nonphysician members of a multidisciplinary diabetes team were minimal. After introduction of the structured visit encounter form, care behaviors did not improve. New training approaches to prepare general pediatric residents to provide excellent diabetes care are needed.

Ambulatory Care Facilities

Longitudinal relationship of asymptomatic hypoglycemia to cognitive function in IDDM.

Early-onset insulin-dependent diabetes mellitus (IDDM) is linked to subsequent learning deficits. To investigate the relationship of learning deficits to metabolic control, 23 children with IDDM (age at testing 71 +/- 21 mo, age at diagnosis 35 +/- 15 mo) diagnosed before 5 yr of age were followed for periods of 6-78 mo. Mean glycosylated hemoglobin (HbA1), episodes of severe hypoglycemia, and frequency of self-monitoring blood glucose (SMBG) measurements less than 2.8 mM (50 mg/dl, asymptomatic hypoglycemia) were recorded every 3 mo. Six subjects entered the study 12.3 +/- 6.7 mo after diagnosis, and only severe hypoglycemia was present before entry. For the remaining 17 subjects, HbA1 and severe and asymptomatic hypoglycemia were present from the time of diagnosis of diabetes. Mean HbA1 level was 10.1 +/- 1.0%, and mean severe hypoglycemic episodes per patient was 2.9, but the frequency was highly skewed; one patient had 37 episodes, and 14 had none. The mean percentage of SMBG readings less than 2.8 mM was 2.4 +/- 2.1. On the revised Stanford-Binet Intelligence Scale there was no correlation between any subscale and severe hypoglycemia. However, the relative frequency of asymptomatic hypoglycemia correlated with scores on the abstract/visual reasoning scale (r = -.39, P = .037). This relationship was primarily accounted for by the relationship of asymptomatic hypoglycemia to performance on the copying subscale (r = -.42, P = .022). Children with frequent asymptomatic hypoglycemic episodes had lower mean copying scores and abstract reasoning scores than those with infrequent episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose Self-Monitoring

Clinical evaluation of computer-assisted self-monitoring of blood glucose system.

The Glucometer M Diabetes Management System includes a glucose-reflectance meter with memory that can interface with a microcomputer for data manipulation and analysis. We evaluated the system in a short-term randomized control trial to determine its impact on metabolic control, self-monitoring of blood glucose (SMBG) testing behaviors, regimen self-adjustment, understanding of insulin-dependent diabetes mellitus (IDDM) treatment, attitudes about SMBG, and perceived quality of patient-physician interaction. Twenty-nine adolescent subjects (experimental) with IDDM were randomly assigned the Glucometer M system for 4 mo. Twenty-eight control subjects used meters without memory. All subjects returned twice to the clinic at 2-mo intervals during the study. At clinic visits, both groups reviewed their SMBG data with their physician. Reviews on experimental subjects were conducted with computer-generated data formats. Control subject reviews used traditional logbooks. Both groups showed a significant drop in glycosylated hemoglobin during the study period (P less than .001); however, there were no between-group differences. There were also no differences in SMBG testing behavior or self-reported regimen self-adjustment between groups or within groups compared with baseline. Compared with control subjects, experimental subjects indicated a significant increase in self-reported understanding of IDDM treatment (P = .002), perceived importance of testing (P = .006), and the quality of interaction with their physician (P less than .001). These data suggest that use of computer-assisted SMBG systems in the outpatient setting does not improve metabolic control over 4 mo. It may, however, contribute to improving communication between the patient and health-care providers.

Blood Glucose Self-Monitoring

Pediatric endocrinologic recommendations, pediatric practice, and current pediatric training regarding care of children with diabetes.

Many pediatric diabetes patients are cared for by community-based pediatricians. Training for pediatricians in optimal diabetes care should be based on both the recommendations of pediatric endocrinologists regarding optimal care and the practices of general pediatricians. Pediatric endocrinologists, general pediatricians, and pediatric residency coordinators were surveyed to assess the consonance of current recommendations, practices, and training in pediatric diabetes care. Not surprisingly, pediatric endocrinologists recommended more subspecialty care than pediatricians reported practicing. A major difference between endocrinologists and pediatricians emerged in the area of psychosocial support. A total of 85% of endocrinologists answered that there should be a mental health diabetes team member, but only 37% of pediatricians reported often or sometimes working with one to develop care plans. Pediatricians who provide complete diabetes care for most of their patients measure frequent glycosylated hemoglobin levels, obtain yearly lipid measurements marginally less often, and use urinary glucose measurements more often than recommended by pediatric endocrinologists. According to the descriptions of most pediatric residency training programs, multidisciplinary teams include a pediatrician, an endocrinologist, and a dietician. However, 25% do not include a social worker or nurse and 70% do not include a psychologist. Although most training programs operate on the assumption that their trainees will ultimately share responsibility with a subspecialist for diabetes care, in 26% of programs residents saw no diabetics in their continuity clinics. Most residents do not participate in providing diabetes education.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Improving compliance with exercise in adolescents with insulin-dependent diabetes mellitus: results of a self-motivated home exercise program.

In this project we investigated the impact of a 12-week at-home aerobic fitness program on aerobic capacity and metabolic control of ten adolescents (four girls and six boys 12 to 14 years of age) with insulin-dependent diabetes mellitus. The adolescents had no prior experience with exercise training. The 45-minute program, designed by a physical therapist, consisted of a stretching, calisthenics, and "cool-down" routine set to popular music. It was taught to the youngsters in group sessions. Each adolescent was given audio- and videocassettes of the routine for home use that emphasized self-motivation in maintaining training. The youngsters were asked to exercise three times per week and were also taught how to adjust their insulin and diet for exercise. Aerobic fitness was determined by maximal oxygen uptake following a vigorous, continuous progressive cycling test; metabolic control was measured by glycosylated hemoglobin values. All of the adolescents reported greater than 85% completion of the program. The youngsters displayed a correspondingly significant increase in aerobic fitness as measured by maximal oxygen uptake: 40.39 +/- 8.87 v 44.86 +/- 12.89 mL/kg/min. Glycosylated hemoglobin levels (mean +/- SD) for the entire group were significantly reduced after the program (11.41 +/- 4.47% v 10.01 +/- 3.21%). Results of this study indicate that nonathletic adolescents with insulin-dependent diabetes mellitus can engage in self-motivated exercise training at home. If properly designed, such programs can improve aerobic fitness and may contribute to improvement in diabetes control.

Adolescent

Cognitive maturity and self-management among adolescents with insulin-dependent diabetes mellitus.

The ability of adolescents with insulin-dependent diabetes mellitus (IDDM) to assume responsibility for self-management is complicated by normal psychosocial developmental tasks, including establishing independence from authority. We evaluated self-managerial behavior and its relation to cognitive maturity. Forty-one adolescents with IDDM (age range 12 to 21 years) and their parents, who were trained to self-adjust insulin on compensatory and anticipatory bases, participated. The data indicated that parents withdrew from the insulin adjustment process as their adolescents grew older. Parental participation had virtually ceased by the time the child reached age 15 years. Parental withdrawal, however, was not always balanced by the adolescent's assumption of responsibility for insulin adjustments. Older adolescents were statistically no more likely than younger adolescents to self-adjust insulin doses. Both self-adjustment and metabolic control (HbA1 values) among adolescents were, however, related to cognitive maturity. More cognitively mature adolescents were also more likely to perceive themselves as being in control of their illness. Thus, older adolescents who are less cognitively mature than their peers are sometimes given responsibility for self-managerial behaviors that they are unable to assume.

Achievement

Management of diabetes mellitus in children younger than 5 years of age.

Optimal treatment for children younger than 5 years of age with insulin-dependent diabetes mellitus is not well defined. Nineteen young children with this disease were treated with a program in which frequent home blood-glucose monitoring was used as the basis for an educational program emphasizing parental adjustment of insulin in response to current glucose levels and anticipated diet and exercise. Eleven children were treated from diagnosis (group I) and another eight (group D) were referred after less intensive treatment. The mean duration of observation of group I children was 13.6 months (range, six to 24 months). For group D, the mean time between diagnosis and referral was 14.9 months (range, seven to 24 months) and 14.6 months (range, six to 24 months) after referral. Before referral, there were 11 hospitalizations in group D. During the intensified program there were two hospitalizations in group D and one in group I. There were 3.3 episodes of severe hypoglycemia per child per 18 months in group D before referral, 1.7 episodes after referral, and 0.4 episodes in group I. Ten of 14 severe hypoglycemic episodes during intensified treatment occurred when there was no or infrequent home blood-glucose monitoring. Only four episodes seemed to have been unpredictable and unpreventable. Mean glycosylated hemoglobin levels were higher in group D patients when compared with both the duration of insulin-dependent diabetes mellitus and the time of initiation of intensified treatment. Mean daily insulin doses increased progressively in group I patients following diagnosis, and were comparable with those in group D patients at 15 and 18 months' duration of illness. Thus, frequency of hospitalization and severe hypoglycemia can be decreased in young children. Frequent home blood-glucose monitoring is required and extensive educational and psychosocial support is necessary for families to implement this intensive approach. The long-term effects on psychoneurological development need evaluation.

Age Factors

Obesity in lower and middle socio-economic status mothers and their children.

To identify potential nursing interventions for obesity in lower socioeconomic status populations, the relationships between maternal and child obesity, socioeconomic status, maternal nutritional knowledge, and locus of control for maternal weight in 144 children and their mothers were studied. Subjects were recruited from two clinic populations; Clinic 1 was of lower socioeconomic status than Clinic 2. As compared with those from Clinic 2, mothers from Clinic 1 were heavier, had less nutritional knowledge, and were more external with respect to locus of weight control. There was a trend for Clinic 1 children to be heavier than those in Clinic 2 but this finding was not statistically significant. The lower socioeconomic status children significantly resembled their mothers' adiposity (possibly foreshadowing adult obesity), however, the middle socioeconomic status children did not resemble their mothers.

Adult

Insulin resistance in total lipodystrophy: evidence for a pre-receptor defect in insulin action.

The cause of insulin resistance in lipodystrophic diabetes is unknown but has generally been ascribed to dysfunction at either the receptor or post receptor level. In a 14 year-old girl with total acquired lipodystrophy, subcutaneous and intravenous insulin requirements approximated 600 units daily. However, circulating total and free insulin levels were not increased, and during testing by the euglycemic clamp method, the glucose response to increasing free insulin concentrations was within the range found in eight subjects with insulin-dependent diabetes. Insulin clearance during the euglycemic clamp was 43, 98, 115, and 116 mL/kg/min at each of four insulin infusion rates compared to means of 13, 13, 12, and 11 in the control subjects with diabetes. No detectable degrading activity was present in serum, and serum inhibited insulin degradation normally. Binding of insulin to IgG, IgM, and IgE was not increased, insulin binding to monocytes and erythrocytes was not sufficiently abnormal to account for the the insulin resistance, and insulin receptor increased insulin clearance or accelerated degradation of insulin by tissues.

Adolescent

An approach to prevention of recurrent diabetic ketoacidosis in the pediatric population.

In 1982 we introduced a program designed to prevent recurrent diabetic ketoacidosis (RDKA), based on the assumption that diabetes education in conjunction with appropriate use of and adherence to insulin therapy should eliminate all RDKA. A hierarchical set of medical, educational, and psychosocial interventions was used. The rate of RDKA was lower after initiation of the program even though patients seen during this period came from lower socioeconomic and more one-parent families (each independently associated with RDKA) than patients seen prior to intervention. In 44 patients with a history of RDKA, insulin omission was documented in 31, inadequate education in 13. Overall, the rate of RDKA decreased from a prereferral mean of 25.2 episodes to a postreferral mean of 2.6 episodes per 100 patient-months (P less than 0.0001). Metabolic control improved after intervention as documented by a decrease in mean hemoglobin A1 from 14.1% to 10.7% (P less than 0.0001). RDKA ceased whether or not psychotherapy was used. Although RDKA is causally related to a variety of social, economic, and family dysfunctions, its prevention requires recognition that its proximate cause is omission of insulin and assurance that a support system exists to ensure adherence.

Adolescent

Inherited abnormal thyroid hormone-binding protein causing selective increase of total serum thyroxine.

A 9-yr-old boy is described in whom increased serum T4 concentration, increased T3 uptake, and increased free T4 index were associated with a euthyroid clinical state with normal total serum T3. T4-binding globulin (TBG), measured by RIA, was decreased. Reverse flow paper electrophoresis of serum proteins after reaction with radioactively labeled T4 demonstrated increased binding of T4 to a protein with electrophoretic mobility corresponding to albumin. Displacement of serum protein-bo-nd [125I]T4 activity by increasing concentrations of T4 revealed the presence of a low affinity, high binding capacity system with an association constant similar to that of T4-binding prealbumin. This low affinity binding protein cochromatographed with TBG on a DEAE-Sephadex column which normally separates TBG from T4-binding prealbumin. At free T4 concentrations equivalent to those present in the plasma of normal individuals, the T4 bound to free ratio is higher in the patient than in normals and the total serum T4 level is increased in the presence of normal free T4 concentrations. The relative affinity of this abnormal T4-binding protein for T3 is low compared to that of TBG. The patient's father had the same abnormal binding protein, which was not found in his mother or fraternal twin brother. These data suggest an autosomal dominant mode of inheritance of an aberration leading to synthesis of a new protein instead of normal TBG. The new protein is different from TBG in electrophoretic mobility, T4 and T3 binding, and antigenic properties.

Child

Management of congenital adrenal hyperplasia using serum dehydroepiandrosterone sulfate and 17-hydroxyprogesterone concentrations.

Simultaneous serum concentrations of dehydroepiandrosterone sulfate (DHEA-S) and 17-hydroxyprogesterone (17-OHP) were compared with urinary 17-ketosteroid (17-KS) and pregnanetriol (PT) excretion during therapy in 18 prepubertal patients with the 21-hydroxylase deficiency form of congenital adrenal hyperplasia (CAH). Patients were classified into those in good, poor, or questionable control on the basis of clinical examination, skeletal age, and 17-KS and PT excretion. During therapy, use of serum steroid concentrations was found to be nearly as accurate in judging adequacy of control as use of urine steroid concentrations. Of 34 evaluations, a definite assessment of adequacy of control could be arrived at 25 times using urinary values and 22 times using both serum DHEA-S and 17-OHP concentrations. DHEA-S concentration responded sluggishly when treatment was not adequate, being greater than 100 microgram/dl only in patients significantly undertreated. It was never elevated in well-controlled patients. Mid-afternoon 17-OHP concentrations were less than 200 ng/dl in well-controlled patients but readily escaped suppression and could not be used to differentiate poor from borderline control or from temporary noncompliance. Therefore, an increases DHEA-S concentration indicated poor control and a suppressed 17-OHP concentration indicated good control. The combination of normal DHEA-S level with elevated 17-OHP level, however, did not permit exact evaluation of the degree of control. Of significance is that not all patients with CAH present with an elevated DHEA-S concentration, and only in those in whom an elevated level has been documented can DHEA-S level be used as an index of control during therapy.

17-Ketosteroids