Polymorphisms at the Werner locus: II. 1074Leu/Phe, 1367Cys/Arg, longevity, and atherosclerosis

Werner syndrome (WS) is a progeroid syndrome caused by autosomal recessive null mutations at the WRN locus. The WRN gene encodes a nuclear protein of 180 kD that contains both exonuclease and helicase domains. WS patients develop various forms of arteriosclerosis, particularly atherosclerosis, and medial calcinosis. The most common cause of death in Caucasian subjects with WS is myocardial infarction. Previous studies have identified specific polymorphisms within WRN that may modulate the risk of atherosclerosis. Population studies of the 1074Leu/Phe and 1367Cys/Arg polymorphisms were undertaken to evaluate the role of WRN in atherogenesis. Frequencies of the 1074Leu/Phe polymorphisms in Finnish and Mexican populations revealed an age-dependent decline of 1074Phe/Phe genotype. In Mexican newborns, but not in Finnish newborns, the 1074Leu/Phe and 1367Cys/ Arg polymorphisms were in linkage disequilibrium. Among coronary artery disease subjects, there was a tendency for the 1074Phe allele to be associated with coronary stenosis in a gene dose-dependent manner. Furthermore, the 1367Arg/Arg genotype predicted a lower degree of coronary artery occlusion, as measured by NV50, when compared to the 1367Cys/Cys or 1367Cys/Arg genotypes. However, these tendencies did not achieve statistical significance. Samples from Mexican patients with ischemic stroke showed a trend of haplotype frequencies different from that in a control group of Mexican adults. These data support the hypothesis that WRN may mediate not only WS, but may also modulate more common age-related disorders and, perhaps, a basic aging process.     

Effect of lidocaine on harmaline-induced tremors in the rat

The present study was undertaken to investigate the effect of lidocaine on harmaline-induced tremors in the rat. Four groups of Wistar rats weighing 45-50 g were injected with harmaline (50 mg/kg i.p.) for inducing experimental tremors. The rats in group 1 served as control, whereas the animals in groups 2, 3, and 4 were also given lidocaine i.p. at doses of 12.5, 25, and 50 mg/kg, respectively, 10 min after the onset of tremors (therapeutic study). In a separate four groups of animals intraperitoneal lidocaine injection was given 10 min before harmaline (prophylactic study) in the same dose regimen as mentioned above. The latency of onset, intensity, and duration of tremor and electromyographic responses were recorded. Lidocaine dose dependently attenuated harmaline-induced tremors in rats. The latency period was increased, and duration and intensity of harmaline-induced tremors was reduced by lidocaine. Our electromyography (EMG) study also revealed a decrease in the amplitude of harmaline-induced tremors in lidocaine-treated rats. In conclusion, the results of this study clearly suggest beneficial effects of lidocaine in harmaline-induced tremors.     

Diagnosis of sacral perineural cysts by computed tomography

Three cases of sacral perineural cysts associated with chronic low-back pain are described with their myelography, computed tomography, and plain film findings. Significant findings include multiple cystic dilatations of lumbosacral nerve root sheaths, enlargement of the sacral foramina by masses isodense with cerebrospinal fluid, and asymmetric epidural fat distribution. Recognition of these findings on unenhanced computed tomography scans should preclude further evaluation by myelography and intrathecal metrizamide (Amipaque) computed tomography. These cysts are usually not the primary cause of back and leg pain.     

Facial augmentation with Proplast and nonporous hydroxylapatite in rhesus monkeys

Using an extra-oral approach, subperiosteal pockets were created bilaterally over zygomatic and mandibular areas in six Rhesus monkeys. One side of each anatomic site received a Proplast I implant and the contralateral a nonporous hydroxylapatite (NPHA) block. Two animals were killed postoperatively at 3, 6, and 12 months, and the implants retrieved en bloc for histologic evaluation. Clinical evaluation showed the Proplast implants more stable than NPHA implants. Histologic evaluation for Proplast implants demonstrated complete encapsulation, fibrous tissue infiltration, fragmentation of implants, and some giant cell reaction. The NPHA implants were completely encapsulated with fibrous tissues, and no giant cell response, fragmentation, biodegradation, or bone formation was observed. We concluded that the Proplast was more stable than NPHA implants, but the NPHA produced less inflammatory cell and giant cell reaction.     

Unusual manifestation of an ampullary tumor presenting with severe upper gastrointestinal bleeding.

Ampullary tumors can occasionally ulcerate and present as frank gastrointestinal bleeding. The most common clinical presentation is jaundice like in other tumors of the biliary tree. We report on a 68-year-old man who presented with severe upper gastrointestinal hemorrhage secondary to an asymptomatic mass of the ampulla of Vater. An endoscopic biopsy specimen revealed a villous adenoma with moderate dysplasia. A curative resection was performed, and pathological work-up revealed the presence of an infiltrating, moderately differentiated ampullary adenocarcinoma.     

Altering physicians' practice patterns--a nationwide educational experiment: evaluation of the Clinical Education Program of the American Diabetes Association

A comprehensive evaluation of the Clinical Education Program (CEP) of the American Diabetes Association on type II diabetes was undertaken in a cohort of 5640 primary-care physicians to determine whether practice patterns are affected by such continuing medical education programs. The educational and behavioral objectives were defined and the extent to which these objectives were met was evaluated by use of questionnaires completed by conference attendees both before and after they participated in the program and by in-office interviews 2 mo later with 288 of the primary-care physicians who had attended the conference. Prior to participation, approximately half of the primary-care physicians described diabetes practice patterns consistent with excellent care. The proportion who stated that they intended to improve their practice patterns increased significantly after the conference. Similarly, the majority of these same physicians knew the basic educational objectives before the conference, with a significant increase in the proportion of physicians knowing these objectives after the conference. The office interviews indicated that the changes noted in the proportion of physicians intending to carry out a practice at the end of the conference were sustained or actually increased in this cohort. Exceptions to this trend occurred in the area of use of glucosylated hemoglobin and perhaps in the area of periodic assessment of macrovascular circulation. Two interesting additional findings from the in-office interviews were that physicians prefer the conference format for learning and that distribution of printed material alone is not very effective in influencing knowledge and behavior in primary-care physicians. The CEP met its educational and behavioral objectives.(ABSTRACT TRUNCATED AT 250 WORDS)