Stability of risk factors for cardiovascular diseases in Portuguese children and adolescents from the Porto area.

An important aspect of preventive medicine is to identify subjects at risk as soon as possible, so preventive strategies can be introduced at early ages. The justification for this strategy is twofold: firstly, the assumption that children maintain a particular high value of a risk factor for disease throughout life; and secondly, the assumption that lowering the level of the risk factor in early life will have a greater impact on the disease than will risk factor changes in later life. In epidemiology the analysis of such factors over time is referred to as tracking. Tracking analysis has been applied to risk factors for cardiovascular diseases (CVD) in pediatric years. The aims of this study were: I) to analyze the stability of biological risk factors [high blood pressure (BP), high percentage of fat mass (%FM) and high total cholesterol (TC)] and lifestyle risk factors [low physical activity index (PAI)] in isolation; and II) to analyze the stability of zero, one, two or three biological risk factors. There were two evaluations in 692 children and adolescents (325 boys and 367 girls), aged between 8 and 15 years. The quartiles, adjusted for age and gender, were the criterion used to identify subjects with biological risk factors (fourth quartile) and with lifestyle risk factors (first quartile) for CVD. The stability was calculated through the relative frequency of subjects who maintained or changed quartile between the two evaluations. There is stability for biological risk factors as well as for behavioral and/or lifestyle risk factors. However, the highest stability is seen in biological risk factors.     

Wrist ratio correlation with carpal tunnel syndrome in industry

Employees from a large midwestern automobile manufacturing plant completed a preemployment evaluation which included a personal and family history, physical examination, and wrist ratio determinations obtained by dividing the anteroposterior diameter by the mediolateral diameter of the wrist. Over a 3-year period, 80 of these employees who developed symptoms compatible with carpal tunnel syndrome within 4-12 months of employment were entered into the study and were evaluated with standard electrodiagnostic techniques. The symptoms included nocturnal hand pain, paresthesia and weak grasp. Thirty-nine of the 80 employees had wrist ratios equal to or greater than 0.70. Twenty-four percent of the employees with wrist ratios less than 0.70 had abnormal electrodiagnostic studies compared with 74% of employees with wrist ratios greater than or equal to 0.70. Regression analysis performed on the data revealed a significant positive correlation between distal median motor latency and wrist ratio (P = 0.001). The study suggests the practical value of wrist ratio determination in job placement.     

Eales' disease presenting as stroke in the young adult

Eales' disease is an uncommon idiopathic disorder characterized by retinal perivasculitis and recurrent vitreous hemorrhages in young males. Associated neurological involvement is rare. We report a 38-year-old man who presented with stroke attributed to Eales' disease.     

ADP plays a key role in thrombogenesis in rats

The relative importance of ADP, arachidonic acid metabolites and serotonin as thrombogenic factors was evaluated in rats by comparing, after oral administration, the effects of two inhibitors of ADP-induced platelet aggregation (ticlopidine and PCR 4099), three cyclo-oxygenase inhibitors (aspirin, triflusal and indobufen) and a selective serotonin 5HT2 receptor antagonist (ketanserin) on platelet aggregation, in four platelet-dependent thrombosis models and on bleeding time. Platelet aggregation induced by ADP and collagen was completely inhibited by ticlopidine and PCR 4099 whereas only the collagen aggregation was reduced by the cyclo-oxygenase inhibitors. Ketanserin or a depletion of platelet serotonin by reserpine did not affect platelet aggregation. Ticlopidine and PCR 4099 greatly prolonged rat tail transection bleeding time. This is probably related to their known ability to inhibit ADP-mediated platelet aggregation. In contrast, the cyclooxygenase inhibitors did not affect bleeding time at all. Reserpine and ketanserin prolonged bleeding time by interfering with the action of serotonin on the vascular wall. Ticlopidine and PCR 4099 were very potent antithrombotics in all the models. Aspirin, only at a high dose, inhibited poorly thrombus formation on a silk thread in an arterio-venous shunt, suggesting that the inhibition of cyclo-oxygenase was not responsible. Triflusal was inactive in all models while indobufen slightly reduced thrombus formation in the silk thread and metallic coil models. Ketanserin and reserpine reduced thrombus only in the metallic coil model. Thrombus formation was greatly reduced in fawn-hooded rats, which lack ADP in their platelet dense granules because of a genetic storage pool deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temazepam impairs effortful but not automatic processing of stimulus elements

The experiment investigated the effects in healthy volunteers of a single dose of temazepam (30 mg, oral) on effortful and automatic processing, by measuring memory for information and its context. Effortful processing was impaired, as shown by significant impairments in free recall of an 18-item list, but automatic processing was spared, as evidenced by no impairments in recall of the frequency of presentation, the colour, size or form of the items. In a second task, temazepam significantly impaired both recognition and recency memory of 30 items, although these scores were not correlated. Temazepam caused significant sedation, measured by an objective test and by subjective ratings, but this did not correlate with the memory impairments. The pattern of results is discussed with reference to the hypothesis that the memory impairments resulting from benzodiazepines are due to a reduction in information processing resources and thus affect effortful processing more than automatic processing.     

Hepatoprotective effects of diethylcarbamazine in acute liver damage induced by carbon tetrachloride in rats

This research was carried out to determine a potential role of leukotrienes in the acute hepatotoxicity induced by CC14 in rats. An inhibitor of leukotrienes biosynthesis, diethylcarbamazine (DEC, 25 and 50 mg ·kg-1 ip) exerted hepatoprotective effects, decreasing the activity of alanine aminotransfer-ase in serum and the concentration of liver triglycerides. DEC reduced histological damage of liver evidenced by electron microscopy. The hepatoprotective effects of DEC were dose-dependent. The results favor the role of leukotrienes in CC14 hepatotoxicity.     

Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study.

To determine whether pulsatile hypothermic perfusion with University of Wisconsin preservation solution is superior to topical cooling as a method for the preservation of amputated limbs, six pairs of amputated canine limbs were preserved for twelve to fifteen hours. One limb of each pair was subjected to topical cooling and the other, to pulsatile hypothermic perfusion with University of Wisconsin solution. The bioenergetic status of the limbs was monitored by 31phosphorus magnetic-resonance spectroscopy, and histological evaluation was performed to assess ischemic changes in the preserved tissue. The pH and tissue levels of adenosine triphosphate declined three times more slowly in the limbs that were preserved by pulsatile hypothermic perfusion than in the topically cooled limbs. Consistent with these findings, the perfused limbs also had less histological evidence of ischemic injury. The data from this in vitro study show that pulsatile hypothermic perfusion with University of Wisconsin solution, in combination with an optimum degree of topical cooling, is superior to topical cooling alone as a method of preserving the bioenergetic status of amputated limbs.     

Activation of muscle fibers in individual motor units revealed by 2-deoxyglucose-6-phosphate

Motor units of the cat tibialis posterior muscle were selectively activated by prolonged electrical stimulation of functionally isolated motor axons in situ. During the activation, the glucose analog 2-deoxyglucose (DG) was administered systemically. Single muscle fibers were subsequently examined for accumulation of the metabolite 2-deoxyglucose-6-phosphate (DG6P) by an analytical assay and for depletion of glycogen by a PAS glycogen-specific staining reaction (periodic acid Schiff; PAS). In general, levels of DG6P were 20 times greater in unstained (PAS-negative) fibers compared with stained (PAS-positive) fibers. However, some glycogen-depleted fibers, particularly in putative ischemic fascicles of the muscle, did not have elevated DG6P, suggesting that depletion of glycogen is not always a reliable indicator of fiber activation. Furthermore, the PAS-staining reaction was not necessarily indicative of quantitative glycogen levels in single fibers. Thus, this report shows that DG6P accumulation enhances the identification of motor-unit fibers selectively activated via their common motor-nerve axon. Evidence is also presented for differential glucose uptake in muscle fibers of different phenotype, thereby indicating that the DG6P measurement in muscle has broad applicability to the investigation of cellular glucose utilization.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.