Neuropsychological functioning following craniopharyngioma removal.

The neuropsychological functioning of patients who had undergone surgical removal of craniopharyngiomas was compared to that of an endocrine control group composed of patients with nontumor hypopituitarism, an obese control group, and a normal control group. Neuropsychological assessments consisting of measures of intelligence, memory, attention, and executive functioning were carried out. The craniopharyngioma group had lower Performance IQ than did the normal control group, but their Performance IQ was comparable to that of the hypopituitarism and obese control groups. The craniopharyngioma patients did not differ in Verbal or Full Scale IQs from the remaining groups. There were no group differences on measures of verbal or nonverbal memory, ability to sustain attention, or executive functioning including measures of verbal or figural fluency, nonverbal problem solving, ability to copy a complex geometric figure, and visual motor and visual sequencing skills. The group mean scores on the measures of intelligence and neuropsychological abilities for the craniopharyngioma patients were in the low-average to average range. While craniopharyngioma patients can have significant morbidity including endocrine and visual deficits as well as obesity resulting from hyperphagia, neuropsychological deficits are not always present. Their neuropsychological outcome is more benign than some previous studies have suggested.

Clinical course of pediatric and adolescent Graves' disease treated with radioactive iodine.

The use of radioactive iodine (RAI) therapy in children and adolescents with Graves' disease is increasing; however, few data exist to guide dosing in this population. We aimed to determine the clinical course, failure rate and factors associated with failure of RAI for pediatric Graves' disease. A retrospective chart review from a tertiary care pediatric endocrinology clinic (1990-2003) identified 22 patients (12.7 +/- 4.0 years at diagnosis) with Graves' disease treated with RAI after initial pharmacological therapy. Patients received a calculated dose of RAI (0.1 mCi/g thyroid tissue, adjusted for 6-h radio-iodine uptake). Twenty-seven percent (95% CI 11-50%) remained hyperthyroid and required a second dose. If the first RAI was successful, the average time to hypothyroidism was 2.96 +/- 1.05 months. There were no statistically significant differences between those successfully treated with one dose and those requiring re-treatment. This high failure rate indicates a need to examine dosing of RAI in this age group.

Hypertension control: results from the Diabetes Care Program of Nova Scotia registry and impact of changing clinical practice guidelines.

BACKGROUND: The objective of this study was to determine the rate of blood pressure control according to 4 sets of Canadian guidelines published over a decade in patients with diabetes mellitus attending Diabetes Centres in the province of Nova Scotia. METHODS: One hundred randomly selected charts from each of 13 Diabetes Centres audited between 1997 and 2001 were extracted from the Diabetes Care Program of Nova Scotia Registry. Multivariate logistic regression analyses examined the relationship between individual characteristics and self-reported antihypertensive use. Included were 1132 adults, mean age 63 years (48% male), with 9 years mean time since diagnosis of diabetes. RESULTS: According to the 1992 guidelines, 63% of the patients and according to the 2003 guidelines, 84% of patients were above target blood pressure or receiving antihypertensive medications. Forty-seven percent of patients are considered to be hypertensive and not on treatment according to 2003 guidelines. The results of the multivariate analyses showed that the only factors independently associated with anti-hypertensive use was oral anti-hyperglycemic use. CONCLUSION: Hypertension is an additional risk factor in those with diabetes mellitus for macrovascular and microvascular complications. The health and budgetary impacts of addressing the treatment gap need to be further explored.

Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia.

Familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism (NSHPT), and autosomal dominant hypocalcemia (ADH), in which calcium homeostasis is disordered, are associated with mutations in the calcium-sensing receptor (CASR). Six unrelated kindreds with FHH and/or NSHPT and two unrelated kindreds with ADH were studied. Direct sequence analysis of the exons of the CASR gene identified heterozygous mutations in six of the kindreds with FHH and in one of those with ADH. We performed functional analyses on the novel missense and insertion/frameshift mutants by transiently transfecting wild-type and mutant CASRs tagged with a c-Myc epitope in human embryonic kidney (HEK293) cells. All mutant receptors were expressed at a similar level to that of the wild type; however, whereas mutants R220W and A835T (the ADH mutant) were fully glycosylated and were visualized on the cell surface, glycosylation of mutants G549R and C850-851 ins/fs was impaired, resulting in reduced cell surface staining. In fura-2-loaded HEK293 cells expressing the wild-type or mutant receptors, the inactivating R220W mutant produced a significant shift to the right relative to the wild-type CASR in the cytosolic calcium response to increasing extracellular calcium concentrations and the G549R and C850-851 ins/fs mutants were without detectable activity. The activating A835T mutation resulted in a shift to the left in the cytosolic calcium response to extracellular calcium concentrations relative to the wild type. Our studies have identified novel CASR mutations that alter the function of the CASR in several different ways.