Prognostic significance of p16 protein levels in oropharyngeal squamous cell cancer.

PURPOSE: Functional inactivation of p16 is an early and frequent event in head and neck squamous cell cancers. In this study, we sought to determine whether p16 expression is of prognostic importance in oropharyngeal squamous cell carcinoma. EXPERIMENTAL DESIGN: p16 protein expression was evaluated by immunohistochemistry in a tissue microarray composed of 123 oropharyngeal squamous cell cancers with a mean patient follow-up time of 33 months. RESULTS: p16 overexpression was associated with more advanced Tumor-Node-Metastasis stage and higher histologic grade. Despite this association with unfavorable features, p16 overexpression was associated with decreased 5-year local recurrence rates (11 versus 53%) and increased 5-year disease-free survival (62 versus 19%) and overall survival (60 versus 21%). In multivariate analysis, p16 expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. CONCLUSIONS: In patients with oropharyngeal squamous cell carcinoma, overexpression of p16 as determined by immunohistochemistry is associated with significantly improved prognosis and lower local recurrence rates.     

Therapy of heart failure

The incidence and prevalence of heart failure is on the rise. It has become the single most expensive health care item in the United States and the number one discharge diagnosis in the elderly. The goals of therapy include both prevention and treatment of heart failure. In recent years research studies and randomized clinical trials have revolutionized the understanding of the pathophysiology and treatment of this disease. This article focuses on the medical management of chronic systolic heart failure based on the pathophysiology of the disease. Systolic heart failure is characterized by a decrease in left ventricular function and cardiac output, which results in activation of several neurohormonal compensatory systems. The long term effects of this neurohormonal activation leads to further deterioration of cardiac function. The use of hydralazine and nitrates to reduce the systemic vascular resistance was the first to show an improvement in mortality and morbidity. Then angiotensin converting enzyme inhibitors, by inhibiting the renin angiotensin system, demonstrated a greater improvement in mortality and morbidity. More recently the inhibition of the sympathetic stimulation with beta-blockers has been shown to have an additive effect on morbidity and mortality in combination with angiotensin-converting enzyme inhibitors. Digoxin and diuretics remain important for improving symptoms and decreasing hospitalizations but have not been shown to decrease mortality. The most recent advance in the treatment of cardiac failure is the demonstration that the aldosterone antagonists, spironolactone decreases morbidity and mortality.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.     

Cyclin d1 is a valuable prognostic marker in oropharyngeal squamous cell carcinoma.

BACKGROUND: The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC). EXPERIMENTAL DESIGN: We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue. RESULTS: The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years. CONCLUSIONS: Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.     

氯地滴眼液的含量测定

目的：采用ＨＰＬＣ法测定氯地滴眼液中氯霉素和地塞米松磷酸钠的含量。方法：色谱分析条件：ＯＤＳ柱作分析柱,流动相为甲醇／水体系,０￣８ｍｉｎ使用４０％甲醇,８￣１６ｍｉｎ使用６０％甲醇,流速１ｍｌ／ｍｉｎ,０￣９ｍｉｎ２４０ｎｍ紫外检测,：二组分分离良好。各组各组性关系良好,平均回收率氯霉素９９．８％（ＲＳＤ＝１．２％,ｎ＝５）,地塞米松磷酸钠９９．４％（ＲＳＤ＝０．７％,ｎ＝５）,结论：该法用于氯     

Assessing social support in elderly adults

We examined the relationship among stress, social support and health status in patients with symptomatic osteoarthritis. Further, we compared three approaches to measuring social support (i.e. objective measures, subjective indicators, and satisfaction). Generally, subjective, rather than objective, indicators of support were more strongly associated with satisfaction with the amount of support received. Regardless of how social support was assessed, we failed to find evidence that support buffers individuals from negative health-related consequences of exposure to stressors. Univariate analyses also demonstrated that being black, married, better educated, and having a higher income were positively associated with social support. Social support continues to be a complex concept in terms of its operational definition and identification of the mechanism by which it influences health outcomes.     

Effects of histamine-receptor antagonists on histamine-stimulated renin secretion

The effects of histamine H1- and H2-receptor antagonists on histamine-stimulated renin secretion were examined in anesthetized dogs. Tripelennamine (H1 blocker) further enhanced renin secretion in the presence of exogenous histamine. Moreover, tripelennamine alone increased renin secretion. These effects are probably due to non-specific properties of the drug and not to interaction of tripelennamine with H1 receptors. Conversely, cimetidine (H2 blocker) significantly inhibited histamine-induced increases in renin secretion, renal blood flow, and sodium excretion without any changes in mean arterial blood pressure or glomerular filtration rate. Cimetidine alone had no effect. We conclude that H2 receptors mediate the effect of histamine on renin secretion in dogs with innervated, intact kidneys.