Coronary thrombosis in myocardial infarction: Report of a workshop on the role of coronary thrombosis in the pathogenesis of acute myocardial infarction

In recent years the widely held concept that coronary thrombi cause myocardial infarcts has been seriously questioned. On the basis of pathologic studies, several reports have suggested that coronary thrombi do not cause infarcts but instead are the result of infarction. Should these findings become generally substantiated, the antithrombotic approach to the prevention and therapy of ischemic heart disease must be revised. This workshop was organized to examine more closely this issue and to sort out reasons for such divergent views of the role of thrombosis in the pathogenesis of myocardial infarction.     

The dose-response relationship for ultraviolet-light-induced mutations at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster ovary cells

Exposure of Chinese hamster ovary (CHO) cells clone K ₁BE₄ to ultraviolet (UV) light at doses up to 86 ergs/mm² did not significantly reduce cell survival, but UV doses of 86–648 ergs/mm² produced an exponential cell killing. Observed mutation frequency to 6-thioguannine resistance induced by UV increases approximately in proportion to increasing doses up to 260 ergs/mm² in a range of 5–648 ergs/mm² examined. The pooled data of mutation frequency f(X) as a function of dose X from 0–260 ergs/mm² is adequately described by f(X)=10^?6 (13.6+2.04 X). That the UVinduced mutations to 6-thioguanine resistance affects the hypoxanthineguanine phosphoribosyltransferase (HGPRT) locus is supported by the observation that all randomly isolated drugresistant colonies contained highly reduced or undetectable HGPRT activity.     

Comparison of radial forearm with fibula and scapula osteocutaneous free flaps for oromandibular reconstruction

OBJECTIVE: To compare our experience with the osteocutaneous radial forearm free flap (group 1) (n = 108) with other commonly used osteocutaneous free flaps (group 2) (n = 56) such as the fibula and scapula in single-stage oromandibular reconstruction. DESIGN: Retrospective case review. SETTING: Tertiary-care academic medical center. PATIENTS: One hundred sixty-three consecutive patients who underwent 164 mandibular reconstructions with osteocutaneous free flaps. MAIN OUTCOME MEASURES: Assessment of preoperative and intraoperative variables for both groups. We compared recipient-site complication rate, intensive care unit stay, total hospital stay, and postoperative function. RESULTS: The most common donor site used was the radius (n = 108 [66%]), followed by the fibula (n = 36 [22%]) and scapula (n = 20 [12%]). Mean follow-up was 29 months (range, 1-116 months). Group 2 patients had larger soft tissue and/or bony defects. Surgical and medical complication rates and major donor site morbidity in group 1 were similar or better when compared with those in group 2. The lengths of the intensive care unit (4 vs 7 days; P = .009) and hospital stays (13 vs 15 days; P = .06) were shorter in group 1. Although the microvascular success rate was similar in both groups, the local wound complication rate was significantly better for group 1. The difference for the length of intensive care unit stay was statistically significant and potentially amounts to more than 6000 dollars of savings. Functional outcomes, including the ability to tolerate oral diet, tracheostomy presence, and dental rehabilitation, were similar between the groups. CONCLUSIONS: The primary site long-term morbidity, donor site morbidity, and postoperative function of osteocutaneous radial forearm free flaps are comparable to those of other commonly used osteocutaneous free flaps such as the fibula and scapula when used in single-stage oromandibular reconstruction.     

Approach to the treatment of cutaneous malignancy in HIV-infected patients

Patients infected with human immunodeficiency virus (HIV) have an increased risk of developing skin cancers. These at-risk patients may have atypical presentations and/or altered clinical courses. This article will review and discuss management issues for the following malignancies: lymphomas, malignant melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi's sarcoma.     

Role of paraoxonase (PON1) status in pesticide sensitivity: genetic and temporal determinants

Individual differences in detoxication capacities for specific organophosphorous (OP) compounds are due largely to differences in catalytic efficiency or abundance of the HDL-associated enzyme, paraoxonase (PON1). First, we provide evidence that children less than 2 years of age represent a particularly susceptible population for OP exposure due to low abundance of PON1 and variable onset of plasma PON1 activity. Second, we describe studies examining the neurotoxic effects of chronic, low-level OP pesticide exposure in mice. PON1 knockout (PON1(-/-)) and wild-type mice were exposed chronically (PN4 to PN21) to low levels of chlorpyrifos oxon (CPO). Endpoints included cholinesterase activity, histopathology, gene expression, and behavior. Even at PN4, when PON1 levels were low in wild-type mice, PON1(-/-) mice were more sensitive to inhibition of brain cholinesterase by CPO. At PN22, and persisting as long as 4 months, chronic developmental exposure to 0.18 mg/kg/d or 0.25 mg/kg/d CPO resulted in perinuclear vacuolization of cells in a discrete area of the neocortex and irregular distribution of neurons in the cortical plate, with an increase in the number of affected cells at 0.25mg/kg/d. Third, we describe a transgenic mouse model in which human transgenes encoding either hPON1Q192 or hPON1R192 were expressed at equal levels in place of mouse PON1. The developmental onset of expression followed the mouse time course and was identical for the two transgenes, allowing these mice to be used to assess the importance of the Q192R polymorphism during development. Adult mice expressing hPON1R192 were significantly more resistant than hPON1Q192 mice to CPO toxicity. Our studies indicate that children less than 2 years old, especially those homozygous for PON1Q192, would be predicted to be particularly susceptible to CPO toxicity.