Biochemopreventive therapy for patients with premalignant lesions of the head and neck and p53 gene expression.
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Anticarcinogenic Agents↗
Biomedical subjects
J Myers
Publications and source records attributed to J Myers.
Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis.
BACKGROUND: Women who report childhood sexual abuse (CSA) are at increased risk for developing psychiatric disorders in adulthood. What is the diagnostic specificity and cause of this association? METHODS: In a population-based sample of 1411 female adult twins, 3 levels of CSA were assessed by self-report and cotwin report: nongenital, genital, and intercourse. Interviews with twins and parents assessed family background and diagnoses of psychiatric and substance dependence disorders. Odds ratios (ORs) were calculated by logistic regression. RESULTS: By self-report, 30.4% reported any CSA and 8.4% reported intercourse. Self-reported CSA was positively associated with all disorders, the highest ORs being seen with bulimia and alcohol and other drug dependence. The ORs were modest and often nonsignificant with nongenital CSA and increased with genital CSA and especially intercourse, where most ORs exceeded 3.0. A similar pattern of findings was seen with CSA as reported by the cotwin, although many ORs were smaller. Controlling for family background factors and parental psychopathology produced a small to modest reduction in ORs. In twin pairs discordant for CSA, the exposed twin was at consistently higher risk of illness. CONCLUSIONS: Women with CSA have a substantially increased risk for developing a wide range of psychopathology. Most of this association is due to more severe forms of CSA and cannot be explained by background familial factors. Although other biases cannot be ruled out, these results are consistent with the hypothesis that CSA is causally related to an increased risk for psychiatric and substance abuse disorders.
Adult↗
Cardiopulmonary exercise testing and prognosis in severe heart failure: 14 mL/kg/min revisited.
BACKGROUND: Accurately establishing prognosis in severe heart failure has become increasingly important in assessing the efficacy of treatment modalities and in appropriately allocating scarce resources for transplantation. Peak exercise oxygen uptake appears to have an important role in risk stratification of patients with heart failure, but the optimal cutpoint value to separate survivors from nonsurvivors is not clear. METHODS: Six hundred forty-four patients referred for heart failure evaluation over a 10-year period participated in the study. After pharmacologic stabilization at entrance into the study, all participants underwent cardiopulmonary exercise testing. Survival analysis was performed with death as the end point. Transplantation was considered a censored event. Four-year survival was determined for patients who achieved peak oxygen uptake values greater than and less than 10, 11, 12, 13, 14, 15, 16, and 17 mL/kg/min. RESULTS: Follow-up information was complete for 98.3% of the cohort. During a mean follow-up period of 4 years, 187 patients (29%) died and 101 underwent transplantation. Actuarial 1- and 5-year survival rates were 90.5% and 73.4%, respectively. Peak ventilatory oxygen uptake (VO(2)) was an independent predictor of survival and was a stronger predictor than work rate achieved and other exercise and clinical variables. A difference in survival of approximately 20% was achieved by dichotomizing patients above versus below each peak VO(2) value ranging between 10 and 17 mL/kg/min. Survival rate was significantly higher among patients achieving a peak VO (2) above than among those achieving a peak VO (2) below each of these values (P <.01), but each cutpoint was similar in its ability to separate survivors from nonsurvivors. CONCLUSION: Peak VO (2) is an important measurement in predicting survival from heart failure, but whether an optimal cutpoint exists is not clear. Peak VO(2) may be more appropriately used as a continuous variable in multivariate models to predict prognosis in severe chronic heart failure.
Breath Tests↗
The influence of esophageal length on outcomes after laparoscopic fundoplication.
BACKGROUND: It has been suggested that laparoscopic antireflux surgery has been associated with an increased incidence of postoperative paraesophageal hiatus herniation, and that this comes (at least in part) from not performing an esophageal lengthening procedure in patients with preoperative esophageal shortening. This study was undertaken to determine whether patients with esophageal shortening have an increased risk of reoperation after laparoscopic antireflux surgery. STUDY DESIGN: All patients who underwent a laparoscopic fundoplication between December 1991 and March 1999, and who had undergone preoperative esophageal manometry in our department were included in this study. Preoperative, operative, and followup data were collected prospectively, and original manometry recordings were reviewed to determine the length of the esophagus (the distance between the midpoints of the upper and lower esophageal sphincters). An index of esophageal length versus height was also calculated by dividing esophageal length by height. Esophageal length and the index were then compared with clinical outcomes. In addition, outcomes for the 50 patients with the shortest index was compared with outcomes of the 50 patients with the longest index. RESULTS: This study included 484 patients from an overall experience of 774 laparoscopic antireflux procedures. Postoperative followup ranged from 3 months to 5 years (median 2 years). Mean esophageal length was 23 cm (range 14 to 30 cm). There was a significant correlation between height and esophageal length (r = 0.44, p < 0.0001). Although patients with large hiatus hernias tended to have a shorter esophagus, preoperative endoscopic esophagitis grading did not influence length. Esophageal length did not influence the overall requirement for further surgical reintervention, although an analysis of esophageal length in patients who developed specific complications demonstrated that postoperative paraesophageal herniation was more likely in patients with a shorter esophagus, and reoperation for a tight esophageal hiatus was less likely in patients with a short esophagus. The incidence of paraesophageal hernia in the 50 patients with the shortest index was 8% versus 2% in the 50 patients with the longest index (p = 0.36). CONCLUSIONS: Although the overall reoperation rate after laparoscopic fundoplication was not influenced by esophageal length, this study did demonstrate an association between esophageal shortening and postoperative paraesophageal herniation. But the increased risk of this problem is small, and for this reason a case cannot be made for patients with a manometrically short esophagus to routinely undergo an esophageal lengthening procedure.
Adolescent↗
Parenting and adult mood, anxiety and substance use disorders in female twins: an epidemiological, multi-informant, retrospective study.
BACKGROUND: Although parenting has long been considered an important risk factor for subsequent psychopathology, most investigations of this question have studied a single informant, clinical populations, one or a few disorders and did not consider relevant covariates. METHODS: Three dimensions of parenting (coldness, protectiveness and authoritarianism) were measured by combining the retrospective reports from adult female twins, their co-twins, and their mothers and fathers. We assessed by personal interview, lifetime history in the twins of eight common psychiatric and substance abuse disorders and a range of predictors of parenting. Analyses were performed using logistic regression. RESULTS: Examined individually, high levels of coldness and authoritarianism were modestly but significantly associated with increased risk for nearly all disorders, while the impact of protectiveness was more variable. These associations declined modestly when putative predictors of parenting were added as covariates. Maternal and paternal parenting were equally associated with outcomes in adult daughters. When coldness, protectiveness and authoritarianism were examined together, nearly all significant associations were seen solely with coldness. Few significant interactions were found between maternal and paternal parenting or between coldness, protectiveness and authoritarianism. The shared experience of these three dimensions of parenting predicts a quite small correlation in liability to these disorders in dizygotic twin pairs (e.g. r < 0.04). CONCLUSION: In women, parenting behaviour, especially levels of coldness, is probably causally related to risk for a broad range of adult psychiatric disorders. The impact of parenting on substance use disorders may be largely mediated through their co-morbidity with major depression, phobias and generalized anxiety disorder. In general population samples, the association of poor parenting with psychiatric illness is modest, largely non-specific and explains little of the observed aggregation of these disorders in families.
Adolescent↗
Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype.
Inhibitory neurotransmission in the brain is largely mediated by GABA(A) receptors. Potentiation of GABA receptor activation through an allosteric benzodiazepine (BZ) site produces the sedative, anxiolytic, muscle relaxant, anticonvulsant and cognition-impairing effects of clinically used BZs such as diazepam. We created genetically modified mice (alpha1 H101R) with a diazepam-insensitive alpha1 subtype and a selective BZ site ligand, L-838,417, to explore GABA(A) receptor subtypes mediating specific physiological effects. These two complimentary approaches revealed that the alpha1 subtype mediated the sedative, but not the anxiolytic effects of benzodiazepines. This finding suggests ways to improve anxiolytics and to develop drugs for other neurological disorders based on their specificity for GABA(A) receptor subtypes in distinct neuronal circuits.
Allosteric Site↗
Exercise training and myocardial remodeling in patients with reduced ventricular function: one-year follow-up with magnetic resonance imaging.
BACKGROUND: Exercise training is now an accepted therapeutic intervention in patients with reduced ventricular function after a myocardial infarction. However, there are conflicting reports on the effects of training on the remodeling process of the heart, and previous studies have only assessed short-term effects of training. METHODS AND RESULTS: Twenty-five patients with reduced ventricular function after myocardial infarction were randomly assigned to an intensive 2-month exercise training program or to a control group (control group: n = 13, aged 55 +/- 7 years, ejection fraction 33.3% +/- 6%; exercise group: n = 12, aged 56 +/- 5 years, ejection fraction 31.5% +/- 7%) and followed up for 1 year. Measures of left ventricular size, function, and wall thickness in the infarct and noninfarct areas were made by magnetic resonance imaging at baseline, after the 2-month training period, and 1 year later. Maximal oxygen uptake increased in the trained group, from 19.7 +/- 3 mL/kg per minute at baseline to 25.1 +/- 5 and 24.2 +/- 5 mL/kg per minute after 2 months and 1 year, respectively (P <.05 vs baseline for both), whereas the control group did not change significantly. Ejection fraction, end-diastolic volumes, and end-systolic volumes did not change at any measurement point throughout the study period in either the trained or control groups. Myocardial wall thickness measurements at end-diastole and end-systole and their differences determined by magnetic resonance imaging yielded no significant interactions between groups. When myocardial wall thickness measurements were classified by infarct or noninfarct areas, no differences were observed between groups over the study period. CONCLUSIONS: Intensive exercise training in patients with reduced ventricular function resulted in a significant improvement in exercise capacity after 2 months, and this improvement was sustained over 1 year. In contrast to some recent reports, training had no deleterious effects on left ventricular volume, function, or wall thickness regardless of infarct area.
Exercise Test↗
Effect of exercise training on heart rate variability in patients with new-onset left ventricular dysfunction after myocardial infarction.
BACKGROUND: Cardiac rehabilitation with exercise training alters sympathovagal control of heart rate variability (HRV) toward parasympathetic dominance in patients after acute myocardial infarction (MI). However, its effects on HRV in patients after MI with new-onset left ventricular dysfunction are yet unknown. We aimed to investigate the effects of 8 weeks of supervised, high-intensity exercise training on time- and frequency-domain measures of HRV in this selected patient population. METHODS AND RESULTS: Twenty-five men with an acute MI and a low ejection fraction were randomly assigned to enter or not to enter a training program in a regional rehabilitation center. HRV was evaluated before and after 1 and 2 months of training and at 12 months. Maximal exercise testing with respiratory gas exchange was performed at baseline and after training. Resting heart rate decreased (P <. 01) and the percentage of R-R intervals differing >50 ms from the preceding one (pNN50) increased (P <.05) after training. The standard deviation of R-R intervals (SDRR) tended to increase, but frequency-domain indexes remained unchanged. There was a significant decrease in SDRR (P <.05) and high-frequency power (P <.01) at 12 months in untrained patients. Exercise time increased by 38% and maximal oxygen uptake increased by 29% in the training group (P <. 01). CONCLUSIONS: Despite beneficial effects on clinical variables, exercise training did not markedly alter HRV indexes. A significant decrease in SDRR and high-frequency power in the control group suggests an ongoing process of sympathovagal imbalance in favor of sympathetic dominance in untrained patients after MI with new-onset left ventricular dysfunction.
Aged↗
Ramp exercise protocols for clinical and cardiopulmonary exercise testing.
Historically, the protocol used for exercise testing has been based on tradition, convenience or both. In the 1990s, a considerable amount of research has focused on the effect of the exercise protocol on test performance, including exercise tolerance, diagnostic accuracy, gas exchange patterns and the accuracy with which oxygen uptake (VO2) is predicted from the work rate. Studies have suggested that protocols which contain large and/or unequal increments in work cause a disruption in the normal linear relation between VO2 and work rate, leading to an overprediction of metabolic equivalents. Other studies have demonstrated that such protocols can mask the salutary effects of an intervention, and some have suggested that the protocol design can influence the diagnostic performance of the test. Guidelines published by major organisations have therefore suggested that the protocol be individualised based on the patient being tested and the purpose of the test. The ramp approach to exercise testing has recently been advocated because it facilitates recommendations made in these guidelines. This article reviews these issues and discusses the evolution of ramp testing which has occurred in the 1990s.
Energy Metabolism↗
Initial report of a cutaneous T-cell lymphoma appearing on the auricular helix.
We report a case of cutaneous T-cell lymphoma in which the first sign of disease was involvement of the superior auricular helix. A review of the literature reveals that T-cell lymphoma often presents cutaneously, but it usually does not involve the ear, and an auricular lesion is rarely the first sign. The uncommon nature of this presentation, in addition to the potential need for multiple biopsies for a tissue diagnosis, can lead to a delay in diagnosis. When evaluating skin lesions in the head and neck, a high index of suspicion for cutaneous T-cell lymphoma is a key factor in its early diagnosis.
Aged↗
Identification and distribution of Parkin in rat brain.
Mutations within the amino acid sequence of Parkin, the encoded protein of the parkin gene, appear to trigger the degeneration of dopaminergic neurons in the substantia nigra. Here, the presence and anatomical distribution of Parkin within the rat was examined. Immunoblot analysis of tissue homogenates showed two major bands at 50 and 44kDa. Within the brain, Parkin-containing neurons were identified in the basal ganglia, including the substantia nigra and caudate-putamen. Parkin was visualized in the raphe nucleus, which as in the substantia nigra, was closely localized to monoaminergic-encoding neurons. In addition, Parkin was detected in laminar structures such as the cortex and hippocampus; a substantial number of Parkin-immunoreactive neurons was seen in the cerebellum as well. Parkin therefore is widely distributed in brain pathways implicated in the pathology of Parkinson's disease.
Animals↗
Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison.
BACKGROUND: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication. METHODS: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months. FINDINGS: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001). INTERPRETATION: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options.
Aged↗
HIV testing after implementation of name-based reporting.
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AIDS Serodiagnosis↗
Young workers at risk when working in agricultural production.
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Accidents, Occupational↗
Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications.
Cyclin D1, p16, and Rb genes play a critical role in the regulation of the G1-S transition of the cell cycle and are frequently altered in several neoplastic entities. Analysis of the protein products of these genes by molecular and immunohistochemical methods provides information on their functional status and allows for the phenotypic evaluation of tumor cells. We performed Western blotting and immunohistochemical analysis on tissues from 35 primary oral and laryngeal squamous carcinoma specimens with previous molecular analysis of the p16 gene and correlated the results with relevant clinicopathologic factors. Our study shows significant concordance between Western blotting and immunostaining results for cyclin D1 (P = .01), p16 proteins (P = .01), and Rb (P = .04). Heterogeneous staining of tumor cells and the positivity of non-neoplastic host elements for Rb by immunohistochemistry contributed to the discrepancy noted in some tumors by Western blotting. Significant reciprocal relationship between p16 and Rb proteins was observed (P < .001); in most tumors, absence of p16 (89%) and detectable Rb (94%) proteins were found. Two tumors had negative cyclin D1 expression, and one third overexpressed this protein. There was a lack of correlation between cyclin D1 overexpression and the clinicopathologic factors studied. Our results indicate that the absence of p16 in most of these tumors may constitute an early tumorigenic event and that the loss of the Rb function plays a minor role in HNSC.
Adult↗
Genetic alterations in oral squamous cell carcinoma of young adults.
The underlying molecular abnormalities associated with head and neck squamous cell carcinoma in young adults (< 40 years) are unknown. We analyzed DNA extracted from paired microdissected samples of normal squamous epithelia and invasive oral squamous cell carcinomas from 36 young adults at microsatellite loci commonly found in older patients and correlated the results with clinicopathologic parameters and outcome. Our results showed that 30 of the 36 (83%) tumors manifest loss of heterozygosity (LOH) in at least one marker. Microsatellite instability was manifested in only six tumors (< 17%). The highest incidences of alterations were noted at markers D9S168 (9p23-22), TP53 (17p13), and D17S799 (17p11) on the short arms of chromosomes 9 and 17. In general, the incidences of LOH at 3, 9 and 17p regions in young adults were similar to those found in older patients. No correlation between LOH at chromosomes 3, 9, and 17p and clinicopathologic parameters was found. Our study indicates that chromosomal regions with frequent genetic alterations involved in young adult squamous tumorigenesis are similar to those reported in older patients. Further studies of other chromosomes in this population are underway to define the novel molecular features of these tumors.
Adult↗
Influence of high-intensity exercise training on the ventilatory response to exercise in patients with reduced ventricular function.
BACKGROUND: Exercise training increases exercise capacity in patients with reduced ventricular function in part through improved skeletal muscle metabolism, but the effect training might have on abnormal ventilatory and gas exchange responses to exercise has not been clearly defined. METHODS: Twenty-five male patients with reduced ventricular function after a myocardial infarction were randomized to either a 2-month high-intensity residential exercise training program or to a control group. Before and after the study period, upright exercise testing was performed with measurements of ventilatory gas exchange, lactate, arterial blood gases, cardiac output, and pulmonary artery and wedge pressures. RESULTS: In the exercise group, peak VO2 and VO2 at the lactate threshold increased 29 and 39%, respectively, whereas no increases were observed among controls. Maximal cardiac output increased only in the exercise group (1.7 L x min(-1), P < 0.05), and no changes in rest or peak exercise pulmonary pressures were observed in either group. At baseline, modest inverse relationships were observed between pulmonary wedge pressure and peak VO2 both at rest (r = -0.56, P < 0.05) and peak exercise (r = -0.43, P < 0.05). Maximal VE/VCO2 was inversely related to maximal cardiac output (r = -0.72, P < 0.001). Training did not have a significant effect on these relationships. Training lowered VE/VO2, heart rate, and blood lactate levels at matched work rates throughout exercise and tended to lower maximal Vd/Vt. The slope of the relationship between VE and VCO2 was reduced after training in the exercise group (0.33 pre vs 0.27 post, P < 0.01), whereas control patients did not differ. CONCLUSIONS: Exercise training among patients with reduced left ventricular function results in a systematic improvement in the ventilatory response to exercise. Training increased maximal cardiac output, tended to lower Vd/Vt, and markedly improved the efficiency of ventilation. Peak VO2 and ventilatory responses to exercise were only modestly related to pulmonary vascular pressures, and training had no effect on the relationships between exercise capacity, ventilatory responses, and pulmonary pressures.
Anaerobic Threshold↗
Effect of betaxolol on the hemodynamic, gas exchange, and cardiac output response to exercise in chronic atrial fibrillation.
BACKGROUND: beta-blockade controls the ventricular response to exercise in chronic atrial fibrillation (AF), but the effects of beta-blockers on exercise capacity in AF have been debated. METHODS: Twelve men with AF (65+/-8 years) participated in a randomized, double-blind, placebo-controlled study of betaxolol (20 mg daily). Patients underwent maximal exercise testing with ventilatory gas exchange analysis, and a separate, submaximal test (50% of maximum) during which cardiac output was measured by a CO2 rebreathing technique. RESULTS: After betaxolol therapy, heart rate was reduced both at rest (92+/-27 vs 62+/-12 beats/min; p < 0.001) and at peak exercise (173+/-22 vs 116+/-24 beats/min; p < 0.001). Maximal oxygen uptake (VO2) was reduced by 19% after betaxolol (21.8+/-5.3 with placebo vs 17.6+/-5.1 mL/kg/min with betaxolol; p < 0.05), with similar reductions observed for maximal exercise time, minute ventilation, and CO2 production. VO2 was reduced by a similar extent (19%) at the ventilatory threshold. Submaximal cardiac output was reduced by 15% during betaxolol therapy (12.9+/-2.3 vs 10.9+/-1.3 L/min; p < 0.05), and stroke volume was higher (88.0+/-21 vs 105.6+/-19 mL/beat; p < 0.05). CONCLUSION: Betaxolol therapy in patients with AF effectively controlled the ventricular rate at rest and during exercise, but also caused considerable reductions in maximal VO2 and cardiac output during exercise. The observed increase in stroke volume could not adequately compensate for reduced heart rate to maintain VO2 during exercise.
Adrenergic beta-Antagonists↗