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Insulin resistance is an early predictor of development of noninsulin-dependent diabetes mellitus (NIDDM) in Pima Indians, a population with the highest reported prevalence of NIDDM. The insulin receptor plays a central role in mediating insulin action, and previous studies have demonstrated that mutations in the insulin receptor gene may cause insulin resistance. Therefore, we have cloned the insulin receptor cDNA from an insulin-resistant Pima Indian to determine if there is a mutation in the patient's insulin receptor gene. We obtained nine cDNA clones spanning exons 4-10 and 12-22 of the patient's insulin receptor gene. Polymorphisms in the nucleotide sequences for codons 523 (Ala), 1058 (His), and 1062 (Leu) provided useful markers to differentiate the patient's two alleles of the insulin receptor gene. These substitutions were silent, in that they did not alter the predicted amino acid sequence. The sequence of exons 1-3 and 11 was determined directly from genomic DNA that had been amplified using the polymerase chain reaction catalyzed by Taq DNA polymerase. Other investigators have reported defects in insulin binding and insulin receptor tyrosine kinase activity in diabetic Pima Indians. However, we did not detect any mutations in this patient's insulin receptor gene. Thus, these observations are consistent with the interpretation that the defects in insulin receptor function are acquired rather than derived from defects in the primary structure of the receptor.

polC, the gene specifying the structure of the replication-specific DNA polymerase III of B. subtilis, was mapped by exploiting azp-12, a mutation conferring resistance to azopyrimidine which determines a mutant, azopyrimidine-resistant enzyme. azp-12 was located in the area of the pyrA locus and is between spcB1 and recA1. azp-12 was linked by transformation to four other mutations which influence the in vitro behaviour of DNA polymerase III--polC25, polC26, mut-1(ts), and DNAF133; the close linkage of these five mutations strongly suggests that they are alleles of the same gene.

A new localizer system and a stereotactic frame based on cylindrical coordinates are described and discussed. Preliminary neurosurgical experience.

The Authors report three cases of non tumoral aqueductal stenosis associated with von Recklinghausen disease in children. Moreover, 16 similar cases collected from the literature are illustrated. The clinical features are evaluated in light of literature's data. Among all 19 cases, the median age was 19 years (range 6-46 years) and 9 patients were under the age of 13 years. In this latter group, the most represented clinical symptoms were headache and gait disturbances. As regards the neuroradiological procedures, CT scan represented the best tool in the evaluation of the ventricular size. Our own three cases underwent to ventriculo-atrial shunt procedures, followed by clinical recovery (follow-up: 3 months-5 years). In conclusion it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, aqueductal stenosis seems to belong to the natural history of this disease.

The authors reviewed 460 patients with intermittent claudication. With primarily conservative management, these patients were followed for an average of 4.1 years (one to ten years). The mean age was 71.7 years, ranging from thirty-six to eighty-four years; 55.9% were males. The subsequent follow-up study revealed that the status of 44.1% of the patients with underlying arterial insufficiency deteriorated. Eventually, they underwent vascular surgery for limb-threatening ischemia. From this study, the analysis of the parameters could predict the clinical outcome of intermittent claudication at the time of initial and follow-up evaluation. During initial evaluation, when the ankle brachial index (ABI) was higher than 0.7 or when follow-up evaluation did not show a decrease of ABI by 0.15, the chance of favorable outcome was increased by 2.4 and 1.6 times respectively. When the ABI was less than 0.5 at the initial evaluation and decreased 0.15 or more during follow-up studies, the risk of requiring vascular surgery for limb salvage increased by 3.8 and 1.9 times, respectively. The onset of major vascular events in other areas appeared to influence the time of significant deterioration in the lower limb arterial disease, indicating multifactorial and systemic contribution in the natural history of intermittent claudication. In this homogeneous patient population with arterial insufficiency referred to the vascular surgeon, conservative management with strong supervision for smoking cessation, exercise, diet control, body weight reduction, and medical regimen can modify the natural course of intermittent claudication and associated vascular problems.

The authors report three cases of primary nontumoral aqueductal stenosis associated with von Recklinghausen's disease in children. Moreover, 16 similar cases collected from the literature are presented. The clinical features are evaluated in light of data from the literature. Among all 19 cases, the median age was 19 years (range 6-46 years), and nine patients were under the age of 13 years. Our own patients underwent ventriculoatrial shunt procedures, followed by clinical recovery (follow-up 2-5 years). In one patient, computed tomography scanning performed 20 months after the operation showed a chronic calcified subdural hematoma in the right frontoparietal area. In conclusion, it is felt that, among all the pathological events usually described in patients affected by neurofibromatosis, primary aqueductal stenosis seems to be part of the natural history of this neurological syndrome.