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Biomedical subjects

D Daneman

Publications and source records attributed to D Daneman.

At least 55 records · Page 3Linked to original sources
PubMed1994

Plasma prorenin as an early marker of nephropathy in diabetic (IDDM) adolescents.

We studied a group of 50 adolescents, average age 16 years, with diagnosed IDDM present for about seven years. Twenty-five had microalbuminuria (MA) averaging 111.0 +/- 34.0 (SEM) micrograms/min albumin excretion rate versus 6.7 +/- 7.4 micrograms/min in the 25 without MA. In other respects, such as sex ratio, age, body mass index, duration of IDDM, hemoglobin A1c, and normotensive systolic, diastolic and mean blood pressures (BP), these subgroups were closely matched. We compared them with a control group of 39 normotensive adolescents, of whom 18 were carefully matched siblings of the IDDM subjects with MA and 21 were similarly matched siblings of the IDDM non-MA subjects. Plasma renin concentration was determined by a direct radioimmunoassay method (Sanofi-Pasteur) and found to be virtually the same in the control and IDDM adolescents as a whole. There was also no real difference between the MA and non-MA subgroups. In contrast, plasma prorenin was significantly higher in the combined IDDM group (197.5 +/- 9.3 vs. control, 134.0 +/- 7.9 pg/ml, P < 0.0001). It was also higher in the MA subgroup than in the non-MA subgroup (226.4 +/- 13.6 vs. 168.5 +/- 10.1 pg/ml, P < 0.001). Interestingly, the 18 control siblings matching the MA subgroup had higher plasma prorenin than the 21 control siblings matching the non-MA subgroup (P < 0.001), suggesting a familial predisposition that precedes detectable diabetes and nephropathy. Our findings confirm and extend reports by other workers that elevated plasma prorenin is associated with incipient nephropathy, manifested by MA. The exclusive renal origin of this prorenin, its role in plasma, and the mechanism responsible for its elevation in IDDM with MA, are yet to be demonstrated, as is the general applicability of these findings to different populations of diabetics, with a higher incidence and severity of complications.

Adolescent↗
PubMed1994

The endocrine outcome after surgical removal of craniopharyngiomas.

The postoperative course of children undergoing surgery for craniopharyngioma was reviewed. Typically they were below height at presentation. All had an attempt at radical surgical resection of the tumor. Most developed diabetes insipidus in the postoperative period, which was permanent in all but 1 child. 94% required thyroid replacement therapy, and sex steroids were administered in 100% when they reached the age of puberty. 91% required maintenance corticosteroids. 54% required growth hormone replacement, but some children showed continued growth despite apparent growth hormone deficiency. Postoperative obesity develops in one half of patients, and may be improved with administration of growth hormone; a controlled trial is underway.

Adolescent↗
PubMed1994

Sodium-lithium transport in adolescents with IDDM. Relationship to incipient nephropathy and glycemic control.

OBJECTIVE: The aims of this study were to examine genetic and environmental influences in the development of early diabetic nephropathy and to assess the value of measuring membrane sodium transport as a marker for early nephropathy. RESEARCH DESIGN AND METHODS: We measured erythrocyte sodium-lithium (Na-Li) countertransport, blood pressure (BP), HbA1c, and microalbuminuria (MA) in 84 adolescents with insulin-dependent diabetes mellitus (IDDM), 29 of whom had MA. Twenty-nine non-MA patients were selected and matched for age, sex, and IDDM duration with the 29 diabetic subjects with MA. The 84 diabetic adolescents were also compared with 85 nondiabetic siblings. RESULTS: The erythrocyte Na-Li countertransport was significantly greater in the IDDM group than in the sibling group (mean +/- SD, 0.41 +/- 0.14 vs. 0.30 +/- 0.11 mmol Li.liters of erythrocytes-1.h-1, respectively, P < 0.0001), but a significant correlation was noted between the results in IDDM subjects and their siblings (r = 0.42, P < 0.0008). Na-Li countertransport was not different in the diabetic subjects with or without MA (0.43 +/- 0.13 vs. 0.37 +/- 0.13 mmol Li.liters of erythrocytes-1.h-1, respectively). There was a significant correlation in the IDDM group between recent diabetic control (HbA1c) and Na-Li countertransport (r = 0.37, P < 0.003). Diastolic BP was significantly higher in the IDDM group with MA than in those without MA (60 +/- 6 vs. 55 +/- 6 mmHg, respectively, P < 0.03). CONCLUSIONS: These results suggest that erythrocyte Na-Li countertransport is influenced by the diabetic milieu. However, there was also evidence in our subjects of a genetic contribution to Na-Li countertransport as seen by the correlation between levels in the IDDM subjects and their siblings. Using Na-Li countertransport, we were not able to segregate those IDDM adolescents with and without early nephropathy.

Adolescent↗
PubMed1993

Psychologic and psychoeducational consequences of thyroxine therapy for juvenile acquired hypothyroidism.

The observation of severe behavioral reactions or learning problems in three teenagers treated with L-thyroxine for juvenile acquired hypothyroidism prompted us to conduct a prospective study of achievement and behavioral characteristics of patients with newly diagnosed juvenile acquired hypothyroidism. On diagnosis of juvenile acquired hypothyroidism and before treatment with L-thyroxine, 23 children and adolescents underwent a comprehensive battery of psychoeducational tests, which was repeated after 3, 12, and 24 months of replacement therapy. Results revealed that adverse behavioral reactions and learning problems were relatively rare in these children, although symptoms of juvenile acquired hypothyroidism were associated with increased distractibility, hyperactivity, and poorer achievement. The least gain in achievement was made by children with more severe hypothyroidism at diagnosis; children with the best psychologic outcome were those who achieved euthyroidism more slowly. We conclude that severe behavioral manifestations of L-thyroxine therapy for juvenile acquired hypothyroidism are uncommon, but mild behavioral symptoms and poorer school achievement may occur in about 25% of patients, who represent the most severe cases at diagnosis.

Adolescent↗
PubMed1992

Sonography of multinodular thyroid gland in children and adolescents.

Multinodular disease of the thyroid gland is uncommon in children and adolescents, and has received little attention in the recent literature. This article reviews the clinical, sonographic, and pathologic findings in 16 children with multinodular disease of the thyroid gland, and draws attention to the high incidence of other associated clinical findings. This condition was associated with a triad including renal and digital anomalies in three patients, with McCune-Albright syndrome in two patients, with Hashimoto's thyroiditis in three patients, and with thyroid carcinoma in four patients. Three of five patients with a history of previous radiation therapy had thyroid carcinoma. Sonography is a proven valuable imaging modality for the study of thyroid disease in children and has contributed to our understanding of multinodular disease of the thyroid gland in this age group.

Adolescent↗
PubMed1992

Drug-induced hypothyroidism: the thyroid as a target organ in hypersensitivity reactions to anticonvulsants and sulfonamides.

Inherited defects in detoxification of reactive metabolites of drugs predispose patients to "hypersensitivity" reactions. Covalent interaction of metabolites with cell macromolecules leads to cytotoxic and immunologic outcomes, manifested clinically by multisystem syndromes with variable organ involvement. Hypothyroidism developed in 5 of 202 patients (age range, 1 to 81 years) we investigated for hypersensitivity reactions to anticonvulsants or sulfonamides shortly after their reaction. None had previous personal or family histories of autoimmune disease. All had low thyroxine levels, elevated levels of thyroid stimulating hormone, and autoantibodies including antimicrosomal antibodies. Patients were 2 to 18 years of age at presentation, and two were male. All returned to a euthyroid state within a year of presentation, and all remain well. The demographics, clinical presentation, and course of the patients is atypical of idiopathic lymphocytic thyroiditis. We investigated the pathogenesis of thyroid toxicity using the hydroxylamine metabolite of sulfamethoxazole as a model. The hydroxyalmine was toxic to thyroid cells in vitro, which did or did not express thyroid peroxidase activity, whereas the parent sulfonamide was toxic only to cells with active thyroid peroxidase. The purified enzyme converted sulfamethoxazole to the hydroxylamine. Formation of reactive drug metabolites by thyroid peroxidase in a host who is genetically unable to detoxify the metabolites may lead directly to cytotoxicity. Covalent binding to macromolecules, including thyroid peroxidase, also may lead to expression of neoantigens and formation of autoantibodies. Patients who have sustained hypersensitivity reactions to drugs should be investigated for possible involvement of the thyroid.

Adolescent↗
PubMed1992

Sonography in thyroid carcinoma in children.

This paper reviews the clinical, sonographic and pathological findings of 20 children with thyroid carcinoma in an attempt to determine the value and limitations of sonography in thyroid neoplasms in this age group. Although sonography is an excellent technique for the evaluation of thyroid disorders and masses, certain limitations must be kept in mind. Microscopic foci of tumour might be missed and sonography cannot predictably differentiate benign from malignant disease. Previous radiation exposure should increase the level of suspicion for malignancy.

Adenocarcinoma↗
PubMed1992

Insulin-stimulated glucose transport in circulating mononuclear cells from nondiabetic and IDDM subjects.

The objectives of this study were 1) to evaluate glucose transport and its regulation by insulin in easily accessible human cells, 2) to investigate the glucose transporter isoforms involved, and 3) to establish whether a defect in glucose transport is associated with peripheral insulin resistance, which is common in insulin-dependent diabetes mellitus (IDDM) patients. We measured 2-deoxyglucose (2-DG) uptake in circulating mononuclear cells from 23 nondiabetic adults, 16 adults with IDDM, and 10 children with IDDM. Circulating mononuclear cells were separated from whole blood by Ficoll gradients and incubated with +/- 1 nM insulin. 2-DG uptake was measured after incubation with [3H]2-DG and cell separation through corn oil-phthalate. Cytochalasin B-inhibitable 2-DG uptake (basal and insulin stimulated) was higher in control than in IDDM subjects (P less than 0.001). Insulin significantly increased 2-DG uptake or 3-O-methylglucose uptake in both groups. Basal and insulin-stimulated 2-DG uptake was similar for adults and children with IDDM and did not correlate with age or body mass index in any group or disease duration, insulin dosage, or HbA1c in IDDM. In separated monocytes and lymphocytes, 2-DG uptake increased in response to insulin only in the monocyte population. Insulin dose-response curves indicated maximal stimulation of hexose uptake at 1-2 nM insulin for both control and diabetic subjects and demonstrated a significant decrease in maximal insulin response in the latter. Immunoblotting with specific antibodies revealed that circulating mononuclear cells and separated monocytes express the GLUT1 but not the GLUT4 isoform of the glucose transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Relationship of self-efficacy and binging to adherence to diabetes regimen among adolescents.

OBJECTIVE: To test the hypothesis that poorer adherence to diabetes care is related to four variables associated with self-concept in adolescents with diabetes: self-esteem, self-efficacy, depression, and binging behavior. In addition, we expected adolescent females to be less adherent to diabetes care. RESEARCH DESIGN AND METHODS: We recruited 193 consecutive patients (aged 13-18 yr) with insulin-dependent diabetes mellitus during their regular quarterly visit to a diabetes clinic in a large urban hospital. Participants completed the Rosenberg Self-Esteem Scale, the Children's Depression Inventory, an assessment of the frequency of binging in the past 3 mo, and parallel forms of an adherence scale and a self-efficacy scale that were developed for use in this study. RESULTS: Adolescents who reported lower adherence tended to report lower self-esteem (r = 0.45, P less than 0.001) and self-efficacy (r = 0.57, P less than 0.001), more depressive symptoms (r = -0.50, P less than 0.001), more binging (r = -0.36, P less than 0.001), and had higher HbA1c (r = -0.24, P less than 0.001) than those with higher adherence scores. Together, the psychological variables accounted for 50% of the variance in adherence. There was no sex difference in reported binging, but, as expected, adolescent females reported less adherence overall (F[7,184] = 2.5, P = 0.018). CONCLUSIONS: Treatment adherence in adolescents with insulin-dependent diabetes mellitus is associated with behavioral and psychological variables. These findings suggest that specific behavioral and cognitive interventions could be used to improve adherence in those individuals who lack confidence in their ability to perform diabetes-related tasks.

Adolescent↗
PubMed1992

Eating disorders and IDDM. A problematic association.

IDDM and eating disorders are common conditions in young women. Whether a specific association exists between these two disorders remains controversial. Some studies have suggested an increased incidence of eating disorders in young women with IDDM, whereas others have not detected such an increase. These differences may be attributable, at least in part, to methodological issues in study design, measurement tools, and relatively small sample sizes. Whether the prevalence of eating disorders in IDDM is increased will be resolved only by larger studies that use standardized diagnostic interviews. We suspect that certain aspects of IDDM and its management may trigger the expression of an eating disorder in susceptible individuals. Required dietary restraint and weight gain related to diabetes management are the factors most likely to be implicated. Eating disorders are relatively common in young women with IDDM and may contribute to impaired metabolic control with hypoglycemia and DKA, and to long-term microvascular complications of diabetes. Omission or reduction of required insulin, an extremely common means of weight control in these young women, is likely an important factor in this regard. Further research is required to determine more precisely the relationship between IDDM and eating disorders, and the effects of eating disorders on metabolic control and chronic complications of IDDM.

Bulimia↗
PubMed1991

Familial hyperinsulinism: successful conservative management.

A large family in whom 4 of 13 children were affected with hyperinsulinism of variable severity is described. The oldest affected child required subtotal pancreatectomy to control the hypoglycemia, but the three younger children were managed successfully with prolonged conservative therapy with maintenance oral doses of diazoxide. The three affected school-age children in the family have deficits in the areas of visuomotor integration and short-term memory. The three youngest children have normal intelligence compared with four unaffected siblings; only the oldest child, who has undergone pancreatectomy, has low-average intelligence (IQ80). We conclude that in infants with persistent but asymptomatic hyperinsulinemic hypoglycemia every effort should be made to treat conservatively with antihypoglycemic agents such as diazoxide for as long as possible to allow for spontaneous remission and thereby avoid pancreatectomy.

Adolescent↗
PubMed1991

Eating disorders and intentional insulin undertreatment in adolescent females with diabetes.

Intentional undertreatment with insulin was found to be a common method of inducing weight loss or preventing weight gain in female adolescents with insulin-dependent diabetes mellitus (IDDM) and eating disorders. More than half of those with eating disorders intentionally omitted insulin to produce hyperglycemia and weight loss. Individuals with eating disorders were also less compliant with other aspects of IDDM management and had poorer metabolic control than the rest of the sample. It is suggested here that intentional undertreatment with insulin in some individuals with IDDM may be regarded as an equivalent to purging, with similar purpose and consequences.

Adolescent↗
PubMed1991

Milk proteins in the etiology of insulin-dependent diabetes mellitus (IDDM).

The etiology of insulin-dependent diabetes mellitus (IDDM) is multifactorial. The final cause of the disease, the specific destruction of the islet beta-cells, is the result of a cellular/humoral autoimmune process that operates in individuals with a particular genetic background in response to an external triggering factor(s). The most likely environmental triggers are virus infections and dietary factors. Among the latter group dietary proteins, mainly cow milk proteins, have been found to be important. Elimination of intact cow milk proteins from the diet significantly reduced the incidence of IDDM in the spontaneously diabetic BB rat, the elimination being most effective when it occurs during the pre-weaning period. Conversely, in newly discovered diabetics (both rats and children) increased levels of antibodies to cow milk proteins as compared with non-diabetic controls were found. These higher titres of antibodies were against beta-lactoglobulin and anti-bovine serum albumin. In further studies we found that antibodies to bovine serum albumin cross-react with a beta-cell membrane protein of Mr 69,000 and that this protein is likely induced by interferon. At the molecular level, a region of the bovine serum albumin has distinct homology to the beta-subunits of the MHC class II proteins Ia, DQ and DR, and antibodies raised against this bovine serum albumin region identified the same 69K beta cell membrane protein, in the same manner as antibodies to the third hypervariable region of DR-beta did. Our hypothesis is that bovine milk proteins (mainly bovine serum albumin) might be an important environmental factor providing specific peptides that share antigenic epitopes with host cell proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The relationship between insulin autoantibodies and islet cell histology in the diabetes prone BB rat.

The relationship between insulin autoantibodies (IAA) and pancreatic islet cell histology was examined in 71 diabetes prone BB rats from the Toronto colony. Twenty-seven of the 71 became diabetic and of these, 18 (67%) were IAA positive by ELISA. IAA were also detected in 39/44 (89%) which did not develop diabetes, but in none of six control animals at 50-140 days of age. All 27 which became diabetic showed some evidence of lymphocytic infiltration scored + to ++++ histometrically and 26/27 evidence of beta cell degranulation. The frequency of diabetes increased with both intensity of insulitis and degree of beta cell degranulation, but there was no correlation between either and IAA. IAA are a marker for the BB strain of Wistar rat, but do not correlate with islet cell histology and do not predict clinical diabetes.

Animals↗
PubMed1990

Distinct antibody specificities to a 64-kD islet cell antigen in type 1 diabetes as revealed by trypsin treatment.

Type 1 diabetes is associated with antibodies that immunoprecipitate a 64-kD islet cell membrane protein from detergent extracts of pancreatic islets. In this study we have determined whether mild trypsin treatment of islet membranes can release fragments of the antigen that bind antibodies in the serum of Type 1 diabetic patients. Partial tryptic proteolysis of [35S]methionine-labeled 64-kD antigen immunoprecipitated from detergent extracts of rat islets resulted in the formation of 50-, 40-, and 37-kD fragments. Similar sized fragments were recovered when sera from diabetic patients were employed to immunoprecipitate polypeptides solubilized by mild trypsin treatment of a particulate fraction of radiolabeled rat islets. Of 27 diabetic patients, 22 possessed antibodies to the 50-kD polypeptide and 21 to the 40- and 37-kD polypeptides. A positive association was found between 64k antibodies and antibodies to the 50-kD fragment but not between 64k antibodies and antibodies to the 40- or 37-kD fragments. Some 64k antibody negative patients possessed antibodies that efficiently immunoprecipitated the latter fragments. Serum from 25 of 27 (93%) diabetic patients immunoprecipitated at least one of the three tryptic polypeptides. One of 20 nondiabetic controls immunoprecipitated a 50-kD polypeptide and all controls were negative for antibodies to 40- and 37-kD fragments. Thus, Type 1 diabetes is associated with the presence of at least two antibody reactivities to distinct determinants of the 64-kD antigen, and some patients may possess antibodies to a cryptic epitope on the detergent-solubilized molecule. These data suggest that the detection of antibodies (present in 93% of patients) to epitopes on tryptic polypeptides of the 64-kD antigen may be of even greater diagnostic value for the onset of Type 1 diabetes than analyses of antibodies reactive with the intact 64-kD antigen.

Adolescent↗