Kallmann syndrome represents the association of hypogonadotropic hypogonadism with anosmia. Three modes of transmission, X chromosome-linked, autosomal recessive and autosomal dominant, have been described. The KAL gene, responsible for the X-linked form of the disease, has been isolated and its intron-exon organization recently determined. We have searched for mutations of the KAL gene in 21 unrelated males affected by familial Kallmann syndrome. In these families, segregation of the disease was suggestive of the X-linked mode of transmission. In 2 families, large Xp22.3 deletions, both including the entire KAL gene, have been detected by Southern blot analysis. Here we report the sequence analysis of the entire coding region of the KAL gene in the 19 remaining patients. The approach consisted of sequencing each of the 14 coding exons and splice site junctions. Each exon was amplified by PCR on the genomic DNA, using oligonucleotides from the flanking intronic sequences as specific primers. Nine point mutations were identified at separate locations in four exons and one splice site, providing strong evidence for heterogeneity in mutations responsible for the X-linked Kallmann syndrome. In addition, the high frequency of unilateral renal aplasia in X-linked Kallmann patients (6 out of 11 males with identified alterations of the KAL gene) should be emphasized.

OBJECTIVE -The aim of this study was to determine the predictive value of silent myocardial ischemia (SMI) and cardiac autonomic neuropathy (CAN) in asymptomatic diabetic patients.RESEARCH DESIGN AND METHODS -We recruited 120 diabetic patients with no history of myocardial infarction or angina, a normal 12-lead electrocardiogram (ECG), and two or more additional risk factors. SMI assessment was carried out by means of an ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole, and 48-h ECG monitoring. CAN was searched for by standardized tests evaluating heart rate variations. Accurate follow-up information for 3-7 years (mean 4.5) was obtained in 107 patients.RESULTS -There was evidence of SMI in 33 patients (30.7%). CAN was detected in 33 of the 75 patients (38.9%) who were tested, and a major cardiac event occurred in 11 of them. Among these 75 patients, the proportion of major cardiac events in the SMI ϩ patients was not significantly higher than that in the SMI Ϫ patients (6 of 25 vs. 5 of 50 patients), whereas it was significantly higher in the CAN ϩ patients than in the CAN Ϫ patients (8 of 33 vs. 3 of 42 patients; P = 0.04), with a relative risk of 4.16 (95% CI 1.01-17.19) and was the highest in the patients with both SMI and CAN (5 of 10 patients). After adjusting for SMI, there was a significant association between CAN and major cardiac events (P = 0.04).CONCLUSIONS -In asymptomatic diabetic patients, CAN appears to be a better predictor of major cardiac events than SMI. The risk linked to CAN appears to be independent of SMI and is the highest when CAN is associated with SMI.

OBJECTIVE: To get accurate measurements of visceral adipose tissue (VAT) using dual energy X-ray absorptiometry (DXA). DESIGN: DXA and anthropometric data and their combinations were compared to the VAT area calculated from a computed tomography (CT) single scan. SUBJECTS: 71 overweight subjects (44 women, 27 men), age: 16 ± 70 y, BMI: 27 ± 52 kgam 2 . MEASUREMENTS: Total body and segmental tissue composition, and new parameters obtained from DXA, in addition to waist and hip cicumferences and abdominal sagittal diameter measurements. RESULTS: The ratio measured at the umbilical level (sagittal diameter À À subcutaneous fat width) Â (transverse internal diameter)a(height) was closely related to VAT (r 0.94 for women and 0.88 for men). It gave the most predictive equation for VAT: y 79.6x (s.e. 3.9) À À 149 cm 2 for the whole population (r 2 0.86, P`0.0001, root mean square error 38.2 cm 2 . An independent relationship between lean mass or its index (r 0.52 and 0.72, P`0.001) and VAT was also found in women. CONCLUSION: This study demonstrates the potential usefulness of DXA to supply accurate measurements of VAT in addition to total body composition determination in obese subjects.

PCOS was associated with a significant decrease of insulin sensitivity, independent of obesity. The correlation between LH and insulin sensitivity suggests a complementary action in PCOS.