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Hyperglycemia and nocturnal systolic blood pressure are associated with left ventricular hypertrophy and diastolic dysfunction in hypertensive diabetic patients.

BACKGROUND: The aim of this study was to determine if hypertensive type 2 diabetic patients, when compared to patients with essential hypertension have an increased left ventricular mass index (LVMI) and a worse diastolic function, and if this fact would be related to 24-h pressoric levels changes. METHODS: Ninety-one hypertensive patients with type 2 diabetes mellitus (DM) (group-1 [G1]), 59 essential hypertensive patients (group-2 [G2]) and 26 healthy controls (group-3 [G3]) were submitted to 24-h Ambulatory Blood Pressure Monitoring (ABPM) and echocardiography (ECHO) with Doppler. We calculated an average of fasting blood glucose (AFBG) values of G1 from the previous 4.2 years and a glycemic control index (GCI) (percentual of FBG above 200 mg/dl). RESULTS: G1 and G2 did not differ on average of diurnal systolic and diastolic BP. However, G1 presented worse diastolic function and a higher average of nocturnal systolic BP (NSBP) and LVMI (NSBP = 132 +/- 18 vs 124 +/- 14 mmHg; P < 0.05 and LVMI = 103 +/- 27 vs 89 +/- 17 g/m2; P < 0.05, respectively). In G1, LVMI correlated with NSBP (r = 0.37; P < 0.001) and GCI (r = 0.29; P < 0.05) while NSBP correlated with GCI (r = 0.27; P < 0.05) and AFBG (r = 0.30; P < 0.01). When G1 was divided in tertiles according to NSBP, the subgroup with NSBP> or =140 mmHg showed a higher risk of LVH. Diabetics with NSBP> or =140 mmHg and AFBG>165 mg/dl showed an additional risk of LVH (P < 0.05; odds ratio = 11). In multivariate regression, both GCI and NSBP were independent predictors of LVMI in G1. CONCLUSION: This study suggests that hyperglycemia and higher NSBP levels should be responsible for an increased prevalence of LVH in hypertensive patients with Type 2 DM.

Adult↗

Mobility impairments and use of screening and preventive services.

OBJECTIVES: Primary care for people with disabilities often concentrates on underlying debilitating disorders to the exclusion of preventive health concerns. This study examined use of screening and preventive services among adults with mobility problems (difficulty walking, climbing stairs, or standing for extended periods). METHODS: The responses of non-institutionalized adults to the 1994 National Health Interview Survey, including the disability and Healthy People 2000 supplements, were analyzed. Multivariable logistic regressions predicted service use on the basis of mobility level, demographic characteristics, and indicators of health care access. RESULTS: Ten percent of the sample reported some mobility impairment; 3% experienced major problems. People with mobility problems were as likely as others to receive pneumonia and influenza immunizations but were less likely to receive other services. Adjusted odds ratios for women with major mobility difficulties were 0.6 (95% confidence interval [CI] = 0.4, 0.9) for the Papanicolaou test and 0.7 (95% CI = 0.5, 0.9) for mammography. CONCLUSIONS: More attention should be paid to screening and preventive services for people with mobility difficulties. Shortened appointment times, physically inaccessible care sites, and inadequate equipment could further compromise preventive care for this population.

Adult↗

Physicians' choice in using Internet and fax for patient recruitment and follow-up in a randomized controlled trial.

OBJECTIVE: To examine the physicians' preference between Web and fax-based remote data entry (RDE) system for an ongoing randomized controlled trial (RCT) in Japan. METHODS: We conducted a survey among all the collaborating physicians (n = 512) of the CASE-J (Candesartan Antihypertensive Survival Evaluation in Japan) trial, who have been recruiting patients and sending follow-up data using the Web or a fax-based RDE system. The survey instrument assessed physicians' choice between Web and fax-based RDE systems, their practice pattern, and attitudes towards these two modalities. RESULTS: A total of 448 (87.5%) responses were received. The proportions of physicians who used Web, fax, and the combination of these two were 45.9%, 33.3% and 20.8%, respectively. Multivariate logistic regression analyses revealed that physicians 55 years or younger [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.1-3.3] and regular users of computers (OR = 4.2, 95% CI = 2.1-8.2) were more likely to use the Web-based RDE system. CONCLUSIONS: This information would be useful in designing an RCT with a Web-based RDE system in Japan and abroad.

Adult↗

The influence of microvessel density on ovarian carcinogenesis.

OBJECTIVE: Tumor microvessel density, measured by CD31 immunohistochemistry, correlates with survival in patients with ovarian cancer. CA 125 is secreted by most ovarian cancers, and we have previously shown that the rate of decline of CA 125 is also predictive of ovarian cancer survival. Because increased tumor vascularity may allow metastases on one hand, while facilitating the delivery of chemotherapy on the other, we investigated the relationship of tumor microvessel density to preoperative CA 125, residual disease, and the initial response to treatment. METHODS: FIGO stage, grade, age, residual disease, and CD31 microvessel density count were correlated with consecutive patients (n = 202) diagnosed with epithelial ovarian cancer who met entry criteria. The relationship of CD31 staining to preoperative CA 125, and the rate of decline in CA 125 (slope) as a measure of initial response to therapy, was also evaluated based on complete CA 125 data. Spearman correlation and the Wilcoxon rank sum test were used for bivariate analyses. Linear and logistic regression was used for multivariate analysis. RESULTS: There were 21 stage I, 14 stage II, 125 stage III, and 42 stage IV patients diagnosed with epithelial ovarian cancer included in the study. More than half (N = 126) of the patients were optimally cytoreduced. Elevated microvessel density was associated with advanced stage of disease (P = 0.0453), grade (P = 0.0002), and an increased amount of residual disease (P = 0.0144). CA 125 values were higher in patients with residual disease versus patients without residual disease (P = 0.0357), and the decline in the CA 125 (slope) was less steep in patients without residual disease versus patients with residual disease (P = 0.0003). However, the initial response to chemotherapy was unrelated to the microvessel density count as measured by CD31 antibody staining (P = 0.7911). In multivariate analyses, CD31 counts remained significant in relationship to grade. Nonideal slopes, indicating decreased response, were associated with increasing age (P = 0.0008) and residual disease (P = 0.0035). CONCLUSION: Elevated ovarian cancer microvessel density count is related to advanced stage and grade of disease, and compromised potential for cytoreduction. Residual disease is associated with higher CA 125 levels and faster CA 125 decline rates. The rate of decline of CA 125 during the initial response to treatment cannot be predicted based on CD31 counts, confirming a complex relationship between tumor vascularity, metastasis, and response to treatment.

CA-125 Antigen↗

Blocked arteries and multivariate regression.

Ultrasound blood flow waveforms may be used in the diagnosis of arterial occlusive disease in human legs. We develop a statistical model to predict disease severity, conditional on the ultrasound data and some training data. It belongs to the class of models known as seemingly unrelated regressions, for which the Bayesian predictive density function cannot be evaluated analytically. Allowing for missing components of response vectors in the training data, we describe a first-order approximation to the predictive density, based on a Bayes estimate of the precision matrix. This approximation is then used to generate cross-validated predictions of disease severity in a set of 31 patients. We conclude with a discussion of the results.

Arterial Occlusive Diseases↗

Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy.

OBJECTIVE: To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset. METHODS: Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery. RESULTS: 27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses. CONCLUSION: Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.

Adult↗

Altered composition of high density lipoproteins in women with the polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) appear at increased cardiovascular risk due in part to a dyslipidemia characterized by increased plasma triglyceride and reduced high density lipoprotein (HDL) cholesterol levels. This is a detailed exploratory study of HDL composition in 35 obese [body mass index (BMI), > 27] and 22 nonobese subjects with PCOS and in 14 healthy obese and 18 nonobese women. Although we found reduced levels of total and HDL2 cholesterol in obese women with PCOS, HDL composition was modified by depletion of lipid relative to protein, with reduced ratios of HDL total cholesterol and HDL phospholipids to apolipoprotein A-I (apoA-I) compared to those in obese controls (P = 0.008 and P = 0.012, respectively). This was explained by reduced cholesterol (P = 0.004) and phospholipid (although not significant, P = 0.07) in HDL with no change in the content of apoA-I, its major protein. Obesity, insulin resistance, and hyperandrogenemia are features of PCOS and potentially affect lipid metabolism. Insulin sensitivity was assessed by the reduction in endogenous glucose concentration after exogenous insulin; the insulin, glucose, and fatty acid responses to oral glucose; and the fasting insulin concentration. When age, BMI, free androgen index, insulin sensitivity determined by all methods, and the presence of PCOS were subjected to stepwise multivariate regression analysis, the presence of PCOS was the most consistent predictor of lipid-depleted HDL (HDL total cholesterol/apoA-I and HDL phospholipids/apoA-I). We speculate that altered activity of hepatic lipase or lipid transfer protein could explain this aspect of the dyslipidemia. Obesity has an important influence on the lipid profile. Obese PCOS and control subjects had higher levels of cholesterol, triglyceride, apoB, and fatty acids than their lean counterparts, and BMI proved the best predictor of blood levels on multiple regression analysis. In contrast, lean PCOS patients had normal sensitivity to insulin and lipid profiles similar to those of the lean controls and did not manifest the HDL abnormalities. Although in PCOS, correlations were obtained between the free androgen index and cholesterol, triglyceride, and apoB levels and between the integrated glucose and insulin responses after oral glucose and fasting fatty acid and triglyceride levels, when age and adiposity were included as covariates only fatty acids and the integrated glucose response remained significantly correlated. Among the controls, total, low density lipoprotein cholesterol, triglycerides, and apoB were related to aspects of insulin sensitivity independent of age and BMI. Lipid metabolism in PCOS is dependent on several related factors, but subjects with PCOS who are obese show a specific reduction in HDL lipid, suggesting a reduced capacity for cholesterol removal from tissues with diminished antiatherogenic potential. Efforts should be directed toward reducing obesity in PCOS to improve the metabolic disturbance in addition to ameliorating the presenting symptoms.

Adipose Tissue↗

Alcohol consumption is associated with an increased risk of distal colon and rectal cancer in Japanese men: the Miyagi Cohort Study.

The association between alcohol consumption and the risk of cancer of the proximal or distal colon or rectum remains controversial. We examined this association in a large population-based cohort of Japanese men. In 1990, a self-administered questionnaire on alcohol drinking and other health habits was delivered to 25,279 Japanese men aged 40 to 64 years of age. After exclusion of subjects who gave incomplete responses on alcohol drinking or prevalent cancer cases at the baseline, a total of 21,199 men remained. Of these, 307 men were diagnosed as having colorectal cancer after 11 years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustments made for potential confounders. Compared with never drinkers, past and current drinkers had multivariate HRs of 1.1 (95% CI, 0.6-1.9) and 1.6 (95% CI, 1.1-2.2) for colorectal cancer, respectively. A dose-response relationship with current volume of alcohol drinkers was observed for cancer of the distal colon and rectum, but not for proximal colon. The multivariate HRs for distal colon and rectal cancer among current heavy drinkers (45.6 g or more ethanol per day) as compared with never drinkers were 4.2 (1.6-10.7; p for trend=0.0002) and 1.8 (1.1-3.2; p for trend=0.04), respectively. In contrast, no significant linear association was found for proximal colon cancer (p for trend=0.2). These data indicate that alcohol consumption in Japanese men is associated with a statistically significant increased risk of cancer of the distal colon and rectum, but not cancer of the proximal colon.

Adult↗

Dose-response relationship between ischemic heart disease mortality and long-term arsenic exposure.

The cardiovascular effects of inorganic arsenic have been documented, but the dose-response relationship between ischemic heart disease (ISHD) and long-term arsenic exposure remains to be elucidated. Mortality rates from ISHD among residents in 60 villages of the area in Taiwan with endemic arseniasis from 1973 through 1986 were analyzed to examine their association with arsenic concentration in drinking water. Based on 1 355 915 person-years and 217 ISHD deaths, the cumulative ISHD mortalities from birth to age 79 years were 3.4%, 3.5%, 4.7%, and 6.6%, respectively, for residents who lived in villages in which the median arsenic concentrations in drinking water were <0.1, 0.1 to 0.34, 0.35 to 0.59, and > or = 0.6 mg/L. A cohort of 263 patients affected with blackfoot disease (BFD), a unique arsenic-related peripheral vascular disease, and 2293 non-BFD residents in the endemic area of arseniasis were recruited and followed up for an average period of 5.0 years. There was a monotonous biological gradient relationship between cumulative arsenic exposure through drinking artesian well water and ISHD mortality. The relative risks were 2.5, 4.0 and 6.5, respectively, for those who had a cumulative arsenic exposure of 0.1 to 9.9, 10.0 to 19.9, and > or = 20.0 mg/L-years compared with those without the arsenic exposure after adjustment for age, sex, cigarette smoking, body mass index, serum cholesterol and triglyceride levels, and disease status for hypertension and diabetes through proportional-hazards regression analysis. BFD patients were found to have a significantly higher ISHD mortality that non-BFD residents, showing a multivariate-adjusted relative risk of 2.5 (95% CI, 1.1 to 5.4).

Adolescent↗

Clinical outcome after 4 years follow-up of HIV-seropositive subjects with incomplete virologic or immunologic response to HAART.

The duration of the clinical, virologic, and immunologic response to HAART, is not well defined. In this observational multi-center study 2,143 patients were enrolled classified according to virologic suppression (<500 cp/ml) and immune recovery (>100 CD4+ cells/mul from baseline) at month 12 of HAART as complete responders, virologic only responders, immunologic only responders and non-responders. Kaplan Meyer curves, multivariate and politomous regression analysis were used. Complete responders patients were 781 (36.4%), immunologic only responders 441 (20.6%), virologic only responders 336 (15.7%), and non-responders 585 (27.3%). Using multivariate analysis, being antiretroviral-naive increased the probability of having both a virologic only or a complete response and reduced the probability of an immunologic only response (P < 0.001 for all tests). Older age was associated directly with a virologic only response and inversely associated with an immunologic only response (P = 0.027 and P = 0.035, respectively). Using politomous analysis, patients baseline HIV-RNA level more than 5 log cp/ml had a 1.9-fold higher probability of an immunologic response than of a complete response (P = 0.001). After 4 years, the clinical progression rate was six times greater in non-responders, 1.9 times greater in virologic only responders, and 2.3 times greater in immunologic only responders than for responders. However, patients with virologic only response or with immunologic only response had a significantly reduced risk for clinical progression than non-responders (P < 0.001). After 4 years of HAART, the risk of clinical progression in patients with immunologic only or virologic only response is low but still higher than in complete responder patients.

Adult↗

Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndrome.

Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N = 40) and another of non-asthmatic controls (N = 42), matched for age and sex. Prevalence of sensitization (>or=1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management.

Asthma↗

The emergency contraceptive pill: a survey of knowledge and attitudes among students at Princeton University.

OBJECTIVE: Our purpose was to measure and analyze knowledge and attitudes about emergency contraceptive pills. The hypothesis we tested was that more accurate knowledge about the regimen would be associated with favorable attitudes towards its use. STUDY DESIGN: We conducted a random sample telephone survey and a series of focus group discussions at Princeton University (results for 11 focus groups are presented elsewhere) A total of 550 undergraduate and graduate students were selected randomly for participation in the survey, and the response rate was 82%. The study's primary outcome measure was attitudes toward the emergency contraceptive pill as a method of fertility control. We used multivariate regression analysis with ordered logit models to test the hypothesized association between knowledge and attitudes. RESULTS: Basic awareness and approval of the emergency contraceptive pill were widespread, yet students lacked detailed knowledge, which did contribute to health and ethical misgivings about the regimen. Students with accurate information, especially those students who knew that the therapy is a large dose of regular oral contraceptives and that side effects are generally minor, were significantly more likely than others to report favorable attitudes. Many students confused the pills dispensed by the university health services (Oral, Wyeth-Ayerst, Philadelphia) with the abortifacient RU 486. Students noted discussion of the method is rare, and many wanted to know more about it. Statistical results are reported with a 95% confidence level. CONCLUSIONS: Educational efforts should offer specific information about the composition of emergency contraceptive pills, the side effects, and how the regimen works.

Abortifacient Agents, Steroidal↗

Interferon and amantadine in naive chronic hepatitis C: a double-blind, randomized, placebo-controlled trial.

Recent controlled trials on the efficacy of an amantadine/interferon combination in treatment-naive patients with chronic hepatitis C yielded contradictory results. We therefore conducted a large, double-blind, placebo-controlled, multicenter trial in naive patients with chronic hepatitis C: 246 patients were randomized to receive interferon alfa-2a (6 MIU sc thrice weekly for 20 weeks, then 3 MIU sc thrice weekly) and either amantadine sulphate (2 x 100 mg p.o. QD) or placebo. Treatment continued for a total of 52 weeks, if HCV-RNA in serum polymerase chain reaction (PCR) had fallen below detection limit (1,000 copies/mL) at treatment week 10, and stopped otherwise. All patients were followed for 24 weeks off therapy. After 10 weeks of treatment, 66/121 patients treated with amantadine (55%) and 78/125 treated with placebo (62%) had lost HCV-RNA (n.s.). After 24 weeks of follow-up, 25 patients in the amantadine (21%) and 17 (14%) in the placebo group remained HCV-RNA negative (n.s.). During therapy, virologic breakthroughs occurred less often in the amantadine than in the placebo group [14 (12%) vs. 27 (22%) patients; P =.04]. Multivariate logistic regression analysis revealed genotype, viremia level, age, and amantadine therapy [risk ratio 0.4 (95%CI 0.2-1.0), P =.05] as predictors of sustained virologic response. Adverse events and impact of therapy on quality of life were similar in amantadine and placebo treated patients. Compared with current standard treatment (interferon/ribavirin), the interferon/amantadine combination was not cost-effective. In conclusion, amantadine does not add to a clinically relevant extent to the treatment of naive patients with chronic hepatitis C.

Adult↗

Incidence and associated factors of neutralizing anti-interferon antibodies among chronic hepatitis C patients treated with interferon in Taiwan.

BACKGROUND: The administration of interferon (IFN) could be complicated by the development of neutralizing anti-interferon antibodies (NA). This study evaluates the frequency and associated factors of NA among chronic hepatitis C patients treated with different IFNs. METHODS: Ninety-five chronic hepatitis C patients were randomized to be treated with recombinant IFN-alpha2a (n = 28), IFN-alpha2b (n = 39) or lymphoblastoid IFN-alpha1 (n = 28) given intramuscularly, 3-6 million units, thrice weekly for 24 weeks. Serum samples collected before, during and after the cessation of treatment were checked for NA. RESULTS: Three patients were withdrawn from treatment. All patients were negative for NA before treatment and 13 (14%) patients developed neutralizing antibodies. Of the 26 patients treated with IFN-alpha2a, 6 (23.1%) developed NA. whereas NA were detected in only 6 (15.4%) of 39 and 1 (3.7%) of 27 patients treated with IFN-alpha2b and IFN-alphanl, respectively. Age, gender, HCV genotype, ALT level, IFN total dose and liver histology were not associated with the development of NA. By using multivariate logistic regression it was shown that pretreatment HCV RNA level and IFN preparation were the two major factors related to the production of NA. The response of treatment was related to pretreatment viremia but not to the presence of NA. CONCLUSIONS: The frequency of development of NA among Taiwanese patients with chronic hepatitis C might be related to different IFN preparations and pretreatment HCV RNA level. The response of treatment was related to pretreatment HCV RNA level but not to the presence of NA.

Adult↗

Anxiety disorders associated with suicidal ideation and suicide attempts in the National Comorbidity Survey.

This study examined the relationship between anxiety disorders and suicidal ideation or suicide attempts in a nationally representative sample (N = 5877; age, 15-54; response rate, 82.4%). A modified version of the Composite International Diagnostic Interview was used to make DSM-III-R mental disorder diagnoses. Two multivariate logistic regression analyses were performed with suicidal ideation (N = 754) and suicide attempts (N = 259) as dependent variables. In each regression, the independent variables entered were lifetime social phobia, panic disorder, agoraphobia, generalized anxiety disorder, simple phobia, and posttraumatic stress disorder (PTSD). Covariates in the analyses were sociodemographics, lifetime mood disorders, substance use disorders, nonaffective psychosis, antisocial personality disorder, and presence of three or more lifetime DSM-III-R diagnoses. PTSD was significantly associated with suicidal ideation (adjusted odds ratio = 2.79; p < 0.01) and suicide attempts (adjusted odds ratio = 2.67; p < 0.01). None of the other anxiety disorders were significantly associated with suicidal ideation or attempts. The robust association between PTSD and suicide attempts has important implications for psychiatric assessment of suicidal behavior. Future research is required to investigate the mechanisms underlying the relationship between PTSD and suicidal behavior.

Adolescent↗

Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.

Antiviral Agents↗

Preliminary evaluation of whole-blood gamma interferon release for clinical assessment of cellular immunity in patients with active coccidioidomycosis.

Assessment of the cellular immune response in coccidioidomycosis has epidemiologic and prognostic importance. Measurement of delayed-type hypersensitivity to skin testing has been used in the past to determine cellular immunity in coccidioidomycosis. However, no skin tests are currently available in the United States. Assay of gamma interferon (IFN-gamma) release in whole blood in response to incubation with antigen has been used to assess cellular immunity in tuberculosis. We used a similar assay using the coccidioidal antigen preparation T27K to measure the in vitro cellular immune responses among a cohort of 69 subjects with active coccidioidomycosis. IFN-gamma release was bimodal, with concentrations above and below 5 IU/ml. Using multivariate logistic regression, underlying disease and disseminated or chronic pulmonary coccidioidomycosis was significantly associated with the release of IFN-gamma at a concentration of <5 IU/ml (P = 0.02 or 0.05, respectively). In addition, the release IFN-gamma concentration was <5 IU/ml in all subjects with a clinical severity score of > or =6 (P = 0.02). The release IFN-gamma concentration correlated with expression of CD69 on T lymphocytes in an in vitro assay using T27K as the antigen (Spearman's rho = 0.59; P < 0.01). These results suggest that the IFN-gamma release assay with T27K as the antigen may be a useful clinical test for assessing cellular immunity in patients with active coccidioidomycosis.

Antigens, CD↗

Aging and severity of hypertension attenuate endothelium-dependent renal vascular relaxation in humans.

Endothelial dysfunction may be related to cardiovascular risk factors, such as aging, hypertension, and atherosclerosis. We investigated whether aging and hypertension independently alter endothelial function in the renal circulation in humans in the absence of abnormalities in lipid and glucose metabolism. L-Arginine (500 mg/kg over 30 minutes) was intravenously administered to 33 patients with essential hypertension and 35 normotensive subjects. The L-arginine-induced increases in renal plasma flow (10.1+/-0.8% versus 15.8+/-0.9%, P<.05) and plasma cGMP (53+/-4% versus 82+/-5%, P<.05) were significantly smaller in patients with essential hypertension than in the normotensive subjects. Multivariate stepwise regression analysis showed that age (P<.0002) and the mean blood pressure (P<.0001) were independently and negatively correlated with the renal plasma flow response to L-arginine. Age (P<.002), mean blood pressure (P<.0001), and male sex (P<.05) were independently correlated with the L-arginine-induced increase in plasma cGMP. The peak change in plasma cGMP was significantly correlated with the L-arginine-induced increase in renal plasma flow (r=.63, P<.001). These findings suggest that aging and hypertension may independently impair endothelium-dependent renovascular dilation and that this effect may be caused at least in part by a decrease in nitric oxide production.

Adult↗