Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

Identifying incident cases of parkinsonism among veterans using a tertiary medical center.

To better understand the impact of incident Parkinson's disease (PD) on the Veteran's Health Administration (VHA) and to develop methods applicable to future epidemiological research, we performed a medical record review study at a tertiary referral VHA medical center. Searching the local data base, we identified 782 veterans with diagnostic codes for PD or secondary parkinsonism (SP) between 1998 and 2000. Based on structured medical record review, a movement disorders specialist confirmed diagnoses for incident parkinsonism cases. Among the 782, 191 incident parkinsonism cases were identified (100 PD, 75 SP, and 16 Parkinson's Plus). Incident PD cases were older at diagnosis (74.5 vs. 70.4 yr; P < 0.05) and more likely to be white (81% vs. 62; P < 0.07) than incident SP cases. Diagnostic codes were insufficient to distinguish between incident PD and SP (positive predictive value, 57% and 39%, respectively), and VHA sources failed to identify 21% of confirmed deaths among the incident PD cohort by November 2004. Although the large number of incident cases identified suggests PD is an important cause of disability among elderly VHA users, observed limitations of VHA sources for identifying incident PD cases and determining their vital status should be considered when designing future studies.     

Development of a "leak-proof," knitted Dacron vascular prosthesis

We have developed a technique to render knitted Dacron prostheses totally impervious to blood leak by impregnating the cloth with collagen. These grafts were prepared by the manufacturer, sterilized, and have an indefinite shelf life. The objective of this study was to determine whether collagen impregnation has a deleterious effect on surface thrombogenicity and graft healing. The infrarenal aortas of 30 mongrel dogs were replaced with 6 cm X 6 mm Dacron grafts (15 collagen-impregnated and 15 control). The collagen-impregnated prostheses were visibly indistinguishable from the control. After blood flow was restored, no interstitial bleeding occurred in the collagen grafts, in contrast to the control grafts that initially leaked profusely. When they recovered, the dogs were divided into three groups: group I (five collagen, five control), group II (five collagen, four control), and group III (five collagen, three control). The grafts were harvested at 3, 6, and 9 months, respectively. Retroperitoneal healing response, capsular thickness and adherence, completeness of neointimal healing, surface fibrinolytic activator activity, and sections taken for light and scanning electron microscopy were studied and compared in a blinded fashion. In a separate set of experiments, experimental and control grafts were compared for in vivo surface thrombogenicity. The healing data were identical in the experimental and control prostheses in all parameters. Of particular interest was that initial capsule adherence was better and surface thrombogenicity less in the collagen-impregnated prosthesis. We conclude that collagen impregnation of a knitted Dacron prosthesis has no deleterious effect for the term of observation of this experiment.     

Post-carotid endarterectomy hypertension: association with elevated cranial norepinephrine

The cause and mechanism of post-carotid endarterectomy hypertension remains unknown. To determine the influence of the sympathetic and renin-angiotensin system, we measured cranial and peripheral plasma levels of catecholamine and renin in patients undergoing carotid endarterectomy. Baseline samples were drawn just before carotid clamping (sample I) and compared with study samples drawn immediately after clamp release (sample II), 2 to 6 hours after surgery (sample III), and then 18 to 24 hours after surgery (sample IV). The patients with post-carotid endarterectomy hypertension had an associated increase of cranial and peripheral norepinephrine levels in the postoperative hypertensive period whereas the patients without post-carotid endarterectomy hypertension did not. This association was most pronounced and statistically significant in cranial samples II (p = 0.032) and III (p = 0.005). Epinephrine and dopamine values did not correlate with post-carotid endarterectomy hypertension. Renin values were higher in cranial than in peripheral samples at time period 2 (p = 0.011), suggestive of a central nervous system Goldblatt phenomenon. However, the renin values did not correlate with post-carotid endarterectomy hypertension. We conclude that post-carotid endarterectomy hypertension is associated with elevated cranial norepinephrine levels, suggestive of a central nervous system sympathomimetic mechanism. Optimal prevention and treatment of this brief but frequently occurring hypertension should include a central-acting sympatholytic agent.     

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.     

New South Wales Nurse Education Project

Abstract: The development of a teaching package for nurse educators on drug and alcohol problems is described and the contents of its 16 modules outlined.     

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.