Is familial hyperparathyroidism a unique disease?

BACKGROUND: Familial hyperparathyroidism is a rare condition reported to behave more aggressively than sporadic hyperparathyroidism. METHODS: A retrospective (1975 to 1995) analysis was performed on 30 such patients. All patients had at least one first-degree relative with surgically treated hyperparathyroidism and no personal or family history of multiple endocrine neoplasia. RESULTS: There were 19 women and 11 men with a mean age of 39 years (range, 13 to 78 years). Fourteen patients (47%) had nephrolithiasis. The mean serum calcium level was 11.6 mg/dl (range, 10.5 to 15.3 mg/dl). Twenty-three primary and 15 repeat explorations (eight recurrent and seven persistent disease) were performed during the study period. Follow-up was obtained on all patients and ranged from 1 to 21 years (mean, 12 years). At the conclusion of the study, hypercalcemia (five recurrent and one persistent) was present in six patients (20%). CONCLUSIONS: Familial hyperparathyroidism is a distinct and unique entity. Patients are diagnosed at a young age and have a high incidence of nephrolithiasis. Long-term follow-up is mandatory because of the high incidence of both recurrent and persistent hyperparathyroidism. Surgical treatment should include subtotal parathyroidectomy and routine transcervical thymectomy performed in centers with experience in the management of multiple-gland parathyroid disease.     

Lovastatin decreases de novo cholesterol synthesis and LDL Apo B-100 production rates in combined-hyperlipidemic males

The effect of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, on the kinetics of de novo cholesterol synthesis and apolipoprotein (apo) B in very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) was investigated in five male patients with combined hyperlipidemia. Subjects were counseled to follow a Step 2 diet and were treated with lovastatin and placebo in randomly assigned order for 6-week periods. At the end of each experimental period, subjects were given deuterium oxide orally and de novo cholesterol synthesis was assessed from deuterium incorporation into cholesterol and expressed as fractional synthesis rate (C-FSR) and production rate (C-PR). Simultaneously, the kinetics of VLDL, IDL, and LDL apo B-100 were studied in the fed state using a primed-constant infusion of deuterated leucine to measure fractional catabolic rates (FCR) and production rates (PR). Drug treatment resulted in significant decreases in total cholesterol (-29%), VLDL cholesterol (-40%), LDL cholesterol (-27%), and apo B (-16%) levels and increases in HDL cholesterol (+13%) and apolipoprotein (apo) A-I (+11%) levels. Associated with these plasma lipoprotein responses was a significant reduction in both de novo C-FSR (-40%; P = .04) and C-PR (-42%; P = .03). Treatment with lovastain in these patients had no significant effect on the FCR of apoB-100 in VLDL, IDL, or LDL, but resulted in a significant decrease in the PR of apoB-100 in IDL and LDL. Comparing the kinetic data of these patients with those of 10 normolipidemic control subjects indicates that lovastatin treatment normalized apoB-100 IDL and LDL PR. The results of these studies suggest that the declines in plasma lipid levels observed after treatment of combined hyperlipidemic patients with lovastatin are attributable to reductions in the C-FSR and C-PR of de novo cholesterol synthesis and the PR of apoB-100 containing lipoproteins. The decline in de novo cholesterol synthesis, rather than an increase in direct uptake of VLDL and IDL, may have contributed to the decline in the PR observed.     

Which lifestyle parameters discriminate high- from low-risk participants for coronary heart disease risk factors. Longitudinal analysis covering adolescence and young adulthood

BACKGROUND: The purpose of this study was to analyse which lifestyle parameters (daily physical activity, dietary intake, smoking habits and alcohol consumption) discriminate between participants at high-risk and those at low-risk for coronary heart disease (CHD) [systolic and diastolic blood pressure (SBP/DBP), total serum cholesterol (TC), high-density lipoprotein cholesterol (HDL), the TC: HDL ratio, body fatness (sum of skinfolds [SSF]) and cardiopulmonary fitness (VO2-max)]. METHODS: The data were derived from the Amsterdam Growth and Health Study (AGHS); an observational longitudinal study in which six repeated measurements were carried out over a period of 15 years on 181 participants aged 13 years at entry to the study. To assess possible discriminating factors, generalized estimating equations were used. This method makes use of risk group changing behaviour over time by using all available longitudinal data. RESULTS: For DBP no significant relationships were found; high risk for SBP was inversely related to smoking habits (OR=0.52; P<0.01). No significant relationships were found for TC; high risk for HDL was positively related to the intake of carbohydrates (OR=1.2; P=0.02) and to smoking habits (OR=1.6; P=0.04); high risk for the TC:HDL ratio was positively related to the intake of carbohydrates (OR=1.3; P=0.01). High risk for SSF was positively related to the intake of protein (OR=1.5; P<0.01) and smoking habits (OR=1.8; P=0.01) and inversely related to daily physical activity (OR=0.81; P=0.01). High risk for VO2-max was inversely related to daily physical activity (OR=0.67; P<0.01). CONCLUSIONS: In the relative young and healthy population of the AGHS during adolescence and young adulthood, physical inactivity was the most important lifestyle parameter related to high risk for CHD.     

Mite allergen (Der p 1) concentration in houses and its relation to the presence and severity of asthma in a population of Sydney schoolchildren

The murine L5178Y (LY) lymphoma sublines, LY-R (radiation resistant) and LY-S (radiation sensitive) display a difference in susceptibility to camptothecin (CPT): LY-S cells are less sensitive to killing by this inhibitor of topoisomerase I than LY-R cells. Post-treatment (CPT present until 3 h after irradiation) sensitizes only LY-S cells. In agreement with this, only in LY-S cells is the relative number of DNA-protein cross-links formed after treatment with CPT + X higher than expected for additivity of X-ray and CPT-induced damage. The pattern of changes in the labelling indices and cell cycle distribution in cells that underwent combined treatment is essentially like that seen for single-agent treatment: for LY-S cells like that for radiation, for LY-R cells like that for CPT. We found no direct relation between the patterns of cell cycle distributions and the enhancement of the lethal effect of X-irradiation by CPT post-treatment. The sublines are not markedly differentially sensitive to beta-lapachone, which modifies topoisomerase I activity, and not sensitized to X-rays by post-irradiation treatment with the drug.     

Acute effects of estradiol infusion and naloxone on luteinizing hormone secretion in pubertal boys

We have shown previously in pubertal boys that testosterone (T) suppresses the nocturnal augmentation of luteinizing hormone (LH) secretion principally by decreasing LH pulse frequency. As T can be aromatised to estradiol (E2), and E2 effects on LH secretory dynamics may be separate from those of T, we examined the effects of acute E2 infusion on LH secretion in pubertal boys. Opioid receptor blockade has been reported to increase LH secretion after estradiol suppression in adult men, so we also examined whether naloxone might augment LH secretion during E2 treatment in pubertal boys. Starting at 1000 h, eight pubertal boys were given a 33 h saline infusion, followed 1 week later by an E2 infusion at 4.6 nmol/m2/h. During both infusions, four iv boluses of saline were given hourly beginning at 1200 h on the first day, and four naloxone iv boluses, 0.1 mg/kg each, were given hourly beginning at 1200 h on the second day. Blood was obtained every 15 min for LH, and every 60 min for T and E2, from 1200 h until the end of the infusion. Pituitary responsiveness to gonadotropin-releasing hormone (GnRH) was assessed after both infusions by iv administration of 250 ng/kg synthetic GnRH. Estradiol infusion increased the mean plasma E2 concentration from 23 +/- 4 to 46 +/- 6 pmol/L (P < 0.01) and suppressed mean plasma T from 4.9 +/- 1.4 to 3.0 +/- 3.5 nmol/L (saline vs. E2 infusion, P < 0.05). The overall mean LH was suppressed by E2 infusion from 3.7 +/- 0.5 to 2.2 +/- 0.4 IU/L (saline vs. E2 infusion, P < 0.01). LH pulse frequency was suppressed by 50%, whereas mean LH pulse amplitude was not different between saline and E2 infusions. Administration of naloxone did not alter the mean LH, LH pulse frequency, or amplitude during either saline or E2 infusions. Pituitary responsiveness to exogenous GnRH was similar during both infusions. These studies indicate that E2 produces its negative feedback in pubertal boys principally by suppression of LH pulse frequency, and naloxone does not reverse these suppressive effects. Thus E2 suppression of LH secretion is mediated by a decrease of hypothalamic GnRH secretion that is independent of endogenous opioid pathways.     

Formation of unilamellar liposomes from total polar lipid extracts of methanogens

Unilamellar liposomes were formed by controlled detergent dialysis of mixed micelles consisting of acetone-insoluble total polar lipids extracted from various methanogens and the detergent n-octyl-beta-D-glucopyranoside. The final liposome populations were studied by dynamic light scattering and electron microscopy. Unilamellar liposomes with mean diameters smaller than 100 nm were obtained with lipid extracts of Methanococcus voltae, Methanosarcina mazei, Methanosaeta concilii, and Methanococcus jannaschii (grown at 50 degrees C), whereas larger (greater than 100-nm) unilamellar liposomes were obtained with lipid extracts of M. jannaschii grown at 65 degrees C. These liposomes were shown to be closed intact vesicles capable of retaining entrapped [14C]sucrose for extended periods of time. With the exception of Methanospirillum hungatei liposomes, all size distributions of the different liposome populations were fairly homogeneous.