Quantitation of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene binding to nuclear macromolecules in human and rat mammary epithelial cells

Our laboratory has developed virtually identical techniques for the isolation and culture of mammary epithelial cells (MEC) from rats and humans. In a cell-mediated mutagenesis assay, rat MEC activated 7,12-dimethylbenz(a)anthracene (DMBA) but not benzo(a)pyrene [B(a)P] to mutagenic forms, and the opposite pattern was found with human MEC. These species-specific patterns were not readily explained by either qualitative or quantitative differences in Phase I metabolism of these compounds. In contrast, relative levels of covalent binding of these compounds to DNA in the human and rat cells under identical assay conditions generally parallel the pattern of the mutagenesis results, while not reflecting the absolute levels of metabolism in each system. The ability of the rat MEC to bind relatively higher levels of DMBA than B(a)P to nuclear DNA, and the reversed pattern in human MEC, was found at all incubation times tested between 6 and 48 h. Culture density was found to exert a greater effect on the levels of PAH-DNA binding in rat than in human cells, but in neither case did it affect the ratio of DMBA to B(a)P binding within a species. C2SO4 gradient separation of nuclear macromolecules from PAH-treated MEC revealed that the relative DNA binding levels of DMBA and B(a)P did not correlate with relative levels of nuclear protein binding. For both species, nuclear (DNA + protein) binding levels of B(a)P were approximately 2-fold higher than DMBA. However, these binding levels were 4 to 5-fold higher for both carcinogens in the human than in the rat MEC. The species-specific patterns of PAH activation shown by these cells suggest that caution should be used in extrapolating rodent carcinogenesis data to humans, for either quantitative or qualitative purposes.     

Rhabdomyosarcoma of the alveolar ridge in an adult

Rhabdomyosarcoma of the head and neck is rare in adults, and past reports indicate that it is a more aggressive disease than that which is found in children. We report the case of a 63-year-old woman with an alveolar type of rhabdomyosarcoma located on the mandibular alveolar ridge. Rhabdomyosarcoma of the oral cavity appears to carry a particularly poor prognosis, especially when bone is involved. Multimodal treatment with surgery, radiation therapy, and chemotherapy is indicated in all patients.     

Computer-assisted instruction in mixed dentition analysis

A computer-assisted instruction (CAI) tutorial in the basics of mixed dentition analysis was developed and evaluated as a substitute for a one-hour lecture segment on the same topic. The instructional effectiveness of the program was evaluated using an experimental CAI-lecture group design. A posttest included in the final examination for the course served to compare learning outcomes of 24 students instructed via the computer with 28 students instructed by the traditional lecture method. The results of this investigation revealed that: the CAI group performed significantly better on the posttest than did the lecture group, there was no significant correlation between posttest scores and the time used to view the program for students in the computer groups, and student attitude toward the use of this CAI program was favorable.     

Thoracoscopic excision of mediastinal parathyroid adenomas: a report of two cases and review of the literature

Background:Most abnormal parathyroid glands can be removed through a standard cervical incision; even those in the superior mediastinum. Those located in certain areas of the mediastinum, for example posteriorly or in the aortopulmonic window, historically have required excision through a median sternotomy or thoracotomy. Angioablation is a nonsurgical alternative to management of these lesions.Study Design:We present two case reports of mediastinal parathyroid adenomas that were excised thoracoscopically, and review the literature regarding the management of mediastinal parathyroid adenomas.Results:Both patients who underwent precise localization and thoracoscopic excision of their mediastinal parathyroid adenomas had resolution of their hypercalcemia with minimal associated morbidity and shortened recovery periods.Conclusions:We suggest that thoracoscopic excision of mediastinal parathyroid adenomas is the better means of controlling hypercalcemia secondary to parathyroid adenoma in those patients considered for either median sternotomy, thoracotomy or angiographic ablation where the exact location of the lesion can be established preoperatively.     

Intravenous Phenylephrine Preconditioning of Cardiac Grafts From Non–Heart-Beating Donors

Background. Hypoxia and warm ischemia produce severe injury to cardiac grafts harvested from non–heart-beating donors. To potentially improve recovery of such grafts, we studied the effects of intravenous phenylephrine preconditioning.Methods. Thirty-seven blood-perfused rabbit hearts were studied. Three groups of non–heart-beating donors underwent intravenous treatment with phenylephrine at 12.5 (n = 8), 25 (n = 7), or 50 μg/kg (n = 7) before initiation of apnea. Non–heart-beating controls (n = 8) received saline vehicle. Hypoxic cardiac arrest occurred after 6 to 12 minutes of apnea, followed by 20 minutes of warm in vivo ischemia. A 45-minute period of ex vivo reperfusion ensued. Nonischemic controls (n = 7) were perfused without antecedent hypoxia or ischemia.Results. Phenylephrine 25 μg/kg significantly delayed the onset of hypoxic cardiac arrest compared with saline controls (9.6 ± 0.5 versus 7.7 ± 0.4 minutes; p = 0.00001), yet improved recovery of left ventricular developed pressure compared with saline controls (57.1 ± 5.3 versus 41.0 ± 3.4 mm Hg; p = 0.04). Phenylephrine 25 μg/kg also yielded a trend toward less myocardial edema than saline vehicle (p = 0.09).Conclusions. Functional recovery of nonbeating cardiac grafts is improved by preconditioning. We provide evidence that the myocardium can be preconditioned with phenylephrine against hypoxic cardiac arrest.(Ann Thorac Surg 1997;63:1664–8)     

Correlates of cognitive dysfunction in an ambulatory elderly population

Mini-Mental State Examination (MMSE) scores were studied in an ambulatory elderly population to identify correlates with self-reported signs, symptoms, diseases, drugs and laboratory values. A total of 1,264 subjects were studied including 844 women and 420 men. In this study, 5.0% of men and 5.3% of women scored less than 24 on the MMSE. A linear-regression model revealed eleven factors of significance in predicting scores on the MMSE. The most important predictors were age (p less than 0.0001), self-reported memory loss (p less than 0.0001), complaints of swollen feet or ankles (p less than 0.0010), the total number of diseases reported (0.0006) and the serum lactate dehydrogenase concentration (p less than 0.0098). Results suggest that cognitive function in the elderly is not related to the general level of health or consistently affected by specific disease states.     

The case of the disappearing generalist: does it need to be solved?

The proportion of generalist physicians in the United States has declined steadily over 50 years, bringing it to the lowest percentage of trained primary care physicians of any developed country; the trend toward subspecialization is accelerating. Many analysts believe this imbalance between generalists and subspecialists to be a major cause of America's high health care costs, heavy dependence on biotechnology, and consumer dissatisfaction. Others argue that sub-specialists can provide excellent primary care services, and the decrease in the number of generalists is not a problem. Three contrasting views on the implications of this trend state that today's generalists are an important and scarce resource that must be bolstered; that subspecialists can replace generalists as providers of primary care; and that the free market will determine the best manpower mix. A final view, on the marketplace option, posits that generalism will not recover until it creates a vital, and unique, role in handling the primary care challenges of the twenty-first century. These competing viewpoints are used to clarify assumptions underlying our major policy options in the arena of health manpower.     

Multiplex PCR analysis of in vivo-arising deletion mutations in the hprt gene of human T-lymphocytes

A multiplex polymerase chain reaction (PCR) procedure was adapted for the rapid and efficient evaluation of deletions of the hypoxanthine guanine phosphoribosyltransferase (hprt) gene in human T-lymphocytes. The hprt clonal assay was used to isolate in vivo-arising hprt-deficient T-cells from six healthy males. Mutant frequencies ranged from 9-27 × 10^?6. Simple crude cellular extracts from 223 mutants were analyzed for hprt gene deletion. Sixteen (7.2%) were found to be due to total gene deletion and 22 (9.9%) were due to partial gene deletion. The relatively high frequency of total gene deletions was caused by replicate isolates of a single mutational event as shown by single-strand conformation polymorphism (SSCP) analysis of rearranged T-cell receptor (TCR)-γ genes. Eighteen of the 22 partial hprt gene deletion mutants were determined to be of independent origin based on a unique hprt mutation or SSCP-TCR-γ pattern. One-half (9/18) of the partial deletion mutants involved all or part of exon 4 alone, suggesting that this region of the hprt gene is prone to deletion. The small deletions effecting exon 1 (1 mutant), exon 2 (2 mutants), and exon 4 (6 mutants) would not have been detected by conventional Southern blot analysis and may represent a new, previously unrecognized class of mutations. The ready isolation of such intragenic deletions will allow the characterization of breakpoint junctions and may provide insights into the important processes of DNA breakage and rejoining. © 1994 Wiley-Liss, Inc.     

Biopterin in Parkinson''s disease.

Tetrahydrobiopterin is an essential co-factor in the natural synthesis of dopamine. Oral tetrahydrobiopterin was given in small doses to four patients with early Parkinson's disease but had no discernible effect.