Serum hypercholesterolemia may be an early risk factor for the development of AD amyloid pathology.

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Increased levels of a 40-42 amino-acid peptide called the amyloid b protein (Ab) and evidence of oxidative damage are early neuropathological markers of Alzheimer's disease (AD). Previous investigations have demonstrated that melatonin is decreased during the aging process and that patients with AD have more profound reductions of this hormone. It has also been recently shown that melatonin protects neuronal cells from Ab-mediated oxidative damage and inhibits the formation of amyloid fibrils in vitro. However, a direct relationship between melatonin and the biochemical pathology of AD had not been demonstrated. We used a transgenic mouse model of Alzheimer's amyloidosis and monitored over time the effects of administering melatonin on brain levels of Ab, abnormal protein nitration, and survival of the mice. We report here that administration of melatonin partially inhibited the expected time-dependent elevation of b-amyloid, reduced abnormal nitration of proteins, and increased survival in the treated transgenic mice. These findings may bear relevance to the pathogenesis and therapy of AD.

Rabbits and rats are becoming popular models for in vitro as well as in situ studies of myocardial infarction. In the present analysis we evaluated the results of several of our completed investigations and tested whether blood-free perfusate, anesthesia, or risk zone size affects infarction in these species. In addition, the influence of the method used for determining infarct size (histology or histochemistry) was examined in rabbits. All hearts experienced 30 min of regional ischemia followed by either 2-3 h of reperfusion in animals in which infarct size was assessed by staining with triphenyltetrazolium chloride or 72 h in those in which histological methods were used to measure infarct size. Eighteen rabbit and seven rat hearts perfused with Krebs buffer, seventeen open-chest rabbits, eight rats anesthetized with pentobarbital, and ten conscious rabbits were studied. Risk zone size measured with fluorescent particles was plotted against infarct size. Infarct size was linearly correlated with risk zone size and did not differ among models for each species. In rat hearts the regression line passed through the origin so that zero infarction occurred with zero risk zone size. However, in the rabbit heart there was no apparent infarction for risk zone sizes < 0.3 cm3. Although the relationship between risk zone and infarction was found to be remarkably independent of the model chosen, the nonzero intercept for the rabbit heart can be an important, previously unrecognized source of experimental variability when infarct size is expressed as a percentage of the risk zone.

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I Many physicians believe that patients with sickle cell disease (SCD) are more likely to become addicted to pain medication than are other patient populations. This study hypothesizes that physicians' attitudes towards addiction in patients with SCD affects pain management practices. The Physician Attitudes Survey was sent to 286 physicians at seven National Institutes of Health-funded university-based comprehensive sickle cell centres. The survey assessed demographic information; and physician's attitudes toward and knowledqe of pain, pain treatment, and drug addiction and abuse. Significant Pearson product-moment correlations were found between attitudes towards pain and beliefs regarding addiction to prescribed opioids. Physicians reported varied pain management strategies, however, many believe that attitudes toward addiction and to patients in pain crises may result in undertreatment of pain. These results indicate that physicians might benefit from additional education regarding sickle cell disease, addiction to pain medication, the pharmacology of opioids, and the assessment and treatment of pain. Resume I La plupart des rnedeclns sont d'opinion que les patients atteints d'anemla falciforme sont plus susceptibles de developper une accoutumance aux medicaments contre la douleur que ne Ie sont d'autres groupes de patients. Cette etude emst I'hypothese que I'attitude des msdectns visA -vis de la dependance aux medicaments de ces patients affecte la demarche therapeutique des medecins dans Ie traitement de la douleur. Afin de verifier cette hypothese, on a envoys un questionnaire A 286 rnedecins rattaohes a 7 centres universitaires specialises dans Ie traitement de l'anemie falciforme et subventlonnes par les Instituts nationaux de la sante. Cette enquete avait pour objectif d'svaluer "information dsrnoqraphlque de rnerne que I'attitude et les connaissances des medecins en ce qui a trait a la douleur, au soulagement de la douleur, ala dependance aux medicaments et a I'abus de ces derniers. Selon Ie coefficient de correlation de Pearson, il existe des liens significatifs entre les attitudes visA -vis de la douleur et les croyances au sujet de J'accoutumance aux opio'ides delivres sur ordonnance. Les medecins ont repondu qU'i1s avaient recours a plusieurs strategies pour contr61er la douleur. Cependant un nombre important d'entre eux sont d'avis que les attitudes aI'egard de la dependance face a des patients en crise de douleur peut conduire a un traitement insuffisant de la douleur. Ces rssultats indiquent que les medeclns auront besoin de plus de formation sur l'anernle falciforme, sur I'accoutumance aux medicaments delivres pour soulager la douleur, sur la pharmacologie des opio'ides et les facons d'evaluer et de traiter la douleur.

Radiographic studies to discriminate benign from malignant pulmonary masses have previously focused on the morphologic and, more recently, the computed tomographic (CT) attenuation characteristics of the lung mass. Experience with the use of an intravenously administered iodinated contrast medium in examining the enhancement properties of lung masses was reviewed. Distinctive differences in the vascularity, pathophysiologic features, and pharmacodynamics of malignant versus benign pulmonary masses were identified. Forty-five patients with peripheral pulmonary masses were examined. Enhancement was evaluated by means of optical density values measured on trispiral tomograms of the lung masses before and after bolus injection of contrast medium. Results suggest that contrast enhancement of pulmonary masses can be measured on sectional images and that this may become a feasible diagnostic method in the detection of lung cancer. CT offers a simplified technique that is now being explored by the authors.