A novel substitution I381V in the sterol 14alpha-demethylase (CYP51) of Mycosphaerella graminicola is differentially selected by azole fungicides.

SUMMARY The recent reduction in the efficacy of azole fungicides in controlling Septoria leaf blotch of wheat, caused by Mycosphaerella graminicola, has prompted concerns over possible development of resistance, particularly in light of the recent emergence of widespread resistance to quinone outside inhibitors (QoIs). We have recently implicated alterations in the target-encoding sterol 14alpha-demethylase protein (CYP51), and over-expression of genes encoding efflux pumps, in reducing sensitivity to the azole class of sterol demethylation inhibitors (DMIs) in M. graminicola. Here we report on the prevalence and selection of two CYP51 alterations, substitution I381V and deletion of codons 459 and 460 (DeltaY459/G460), in populations of M. graminicola. Neither alteration has previously been identified in human or plant pathogenic fungi resistant to azoles. The presence of DeltaY459/G460 showed a continuous distribution of EC(50) values across isolates with either I381 or V381, and had no measurable effect on azole sensitivity. Data linking fungicide sensitivity with the presence of I381V in M. graminicola show for the first time that a particular CYP51 alteration is differentially selected by different azoles in field populations of a plant pathogen. Substitution I381V although not an absolute requirement for reduced azole sensitivity, is selected by tebuconazole and difenoconazole treatment, suggesting an adaptive advantage in the presence of these two compounds. Prochloraz treatments appeared to select negatively for I381V, whereas other azole treatments did not or only weakly impacted on the prevalence of this substitution. These findings suggest treatments with different members of the azole class of fungicides could offer a resistance management strategy.

Image cytometric bcl-2:bax and bcl-2:bcl-x ratios in invasive breast carcinoma: correlation with prognosis.

BACKGROUND: The bcl-2 family of proteins are important regulators of apoptosis. Some of the members, such as bcl-2 and bcl-x(L), inhibit cell death, whereas others, such as bax and bcl-x(S), promote cell death. We evaluated the ratios of bcl-2:bax and bcl-2:bcl-x expression by image cytometry in invasive breast carcinoma to determine prognostic significance. DESIGN: Five-micron sections of formalin-fixed, paraffin-embedded tissue from 88 invasive breast carcinomas were immunostained using steam antigen retrieval, an avidin biotin-complex technique with automated stainer and primary antibodies against bcl-2 (1/160; Dako, Carpenteria, CA), bax (1/1,500; PharMingen, San Diego, CA), and bcl-x (1/1,500; PharMingen). Positive controls were tonsil (bcl-2) and normal breast (bax and bcl-x) tissue samples. Immunostain was measured in 15 high power fields as percentage positive area (PPA) in nuclei and cytoplasm using the CAS 200 image analyzer (Becton Dickinson, San Jose, CA). RESULTS: Median follow-up was 105 months (range 11-130). Significantly improved disease-free survival was found in patients with a bcl-2:bcl-x ratio > or = 1 by univariate and multivariate analyses. The bcl-2:bax ratio was not predictive of overall or disease-free survival. A significant difference in overall and disease-free survival was found between carcinomas with positive and negative bcl-2 expression by univariate analysis; by multivariate analysis, bcl-2 expression was an independent prognostic factor for disease-free survival. The 5-year survival rates were 77% and 50% in patients with bcl-2-positive and bcl-2-negative carcinomas, respectively. CONCLUSION: A bcl-2:bcl-x ratio > or = 1, assessed by image cytometry, is significantly associated with improved disease-free survival in patients with invasive breast carcinoma. Significantly increased overall and disease-free survival is associated with positive bcl-2 expression.

Long-term efficacy of olanzapine in the control of psychotic and behavioral symptoms in nursing home patients with Alzheimer's dementia.

BACKGROUND: Psychotic symptoms and behavioral disturbances are a leading cause of institutionalization in elderly patients with Alzheimer's disease (AD). OBJECTIVES: Elderly nursing home patients (n=105) with possible or probable AD were entered into a multicenter study to determine the long-term efficacy and safety of olanzapine in treatment of psychotic symptoms and behavioral disturbances due to AD. METHODS: Following a double-blind, 6-week exposure to fixed-dose olanzapine (5, 10, or 15 mg/d), patients entered an additional 18-week, open-label, flexible-dose treatment. Baseline was defined from the start of the extension phase. RESULTS: Patients improved significantly on the primary efficacy measure, defined a priori, which consisted of the sum of the Agitation/Aggression, Delusions, and Hallucinations items ('Core':) of the NPI/NH. Olanzapine also significantly improved scores for the NPI/NH total and the Core item-associated Occupational Disruptiveness of the NPI/NH, as well as the BPRS total and CGI Severity-of-Alzheimer's scores. Barnes Akathasia scores improved significantly from baseline, while Simpson-Angus and AIMS scores were not significantly changed. Treatment-emergent symptoms included somnolence, accidental injury, and rash. No significant changes were seen in ECGs, including QT(c) interval, nor in weight or vital signs, including orthostasis. CONCLUSIONS: Low-dose olanzapine appears to be effective and well tolerated for treatment of behavioral disturbances and psychotic symptoms due to AD in elderly patients.

Experience with routine voluntary perinatal human immunodeficiency virus testing in an inner city hospital.

Women enrolled in prenatal care at Grady Health System, Atlanta, GA, have routinely been offered HIV counseling and voluntary testing since 1987. Consistently >90% have accepted testing. With implementation of US Public Health Service guidelines for perinatal zidovudine prophylaxis in 1994, the mother-to-child HIV transmission rate rapidly decreased from 18% to 8% during the subsequent 2 years.

Accounting for dropout bias using mixed-effects models.

Treatment effects are often evaluated by comparing change over time in outcome measures. However, valid analyses of longitudinal data can be problematic when subjects discontinue (dropout) prior to completing the study. This study assessed the merits of likelihood-based repeated measures analyses (MMRM) compared with fixed-effects analysis of variance where missing values were imputed using the last observation carried forward approach (LOCF) in accounting for dropout bias. Comparisons were made in simulated data and in data from a randomized clinical trial. Subject dropout was introduced in the simulated data to generate ignorable and nonignorable missingness. Estimates of treatment group differences in mean change from baseline to endpoint from MMRM were, on average, markedly closer to the true value than estimates from LOCF in every scenario simulated. Standard errors and confidence intervals from MMRM accurately reflected the uncertainty of the estimates, whereas standard errors and confidence intervals from LOCF underestimated uncertainty.

The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease.

BACKGROUND: Elderly patients with Alzheimer's disease (AD) commonly exhibit psychotic symptoms, prompting clinicians to administer antipsychotics. This article compares the effects of olanzapine and placebo in the emergence of hallucinations or delusions in AD patients with symptoms of agitation/aggression but little or no psychotic symptomatology at baseline. METHOD: A multicenter, double-blind, placebo-controlled study was conducted in nursing home patients with AD according to DSM-IV criteria and symptoms of agitation/aggression and/or psychosis. Patients (N = 206) were randomly assigned to receive either placebo or fixed-dose olanzapine (5, 10, or 15 mg/day) for up to 6 weeks. This article analyzes data from a subgroup of patients (N = 165) with no or minimal delusions and/or hallucinations at baseline as measured by the Neuropsychiatric Inventory-Nursing Home Version (NPI/NH). Three subsets of patients were identified on the basis of their symptoms at baseline: those with no clinically significant hallucinations, those with no clinically significant delusions, and those with no clinically significant delusions or hallucinations. RESULTS: Of the patients without hallucinations or delusions at baseline (N = 75), the placebo-treated patients showed significantly greater development of these symptoms compared with olanzapine-treated patients overall (NPI/NH hallucinations + delusions mean change score, +2.73 vs. +0.27, p = .006). Similarly, of the patients without baseline hallucinations (N = 153), the placebo-treated patients showed greater hallucinations score increases than did olanzapine-treated patients overall (+1.25 vs. +0.33, p = .026), whereas patients without baseline delusions (N = 87) showed no significant treatment effects. Olanzapine had a favorable safety profile in each patient subset. CONCLUSION: These results suggest that, overall, olanzapine effectively attenuated emergence of psychosis in a short-term trial of patients with Alzheimer's disease.

Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: a double-blind, randomized, placebo-controlled trial. The HGEU Study Group.

BACKGROUND: Patients with Alzheimer disease (AD) commonly exhibit psychosis and behavioral disturbances that impair patient functioning, create caregiver distress, and lead to institutionalization. This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and/or agitation/aggression in patients with AD. METHODS: A multicenter, double-blind, placebo-controlled, 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and/or behavioral symptoms. Patients were randomly assigned to placebo or a fixed dose of 5, 10, or 15 mg/d of olanzapine. The primary efficacy measure was the sum of the Agitation/Aggression, Hallucinations, and Delusions items (Core Total) of the Neuropsychiatric Inventory-Nursing Home version. RESULTS: Low-dose olanzapine (5 and 10 mg/d) produced significant improvement compared with placebo on the Core Total (-7.6 vs -3.7 [P<.001] and -6.1 vs -3. 7 [P =.006], respectively). Core Total improvement with olanzapine, 15 mg/d, was not significantly greater than placebo. The Occupational Disruptiveness score, reflecting the impact of patients' psychosis and behavioral disturbances on the caregiver, was significantly reduced in the 5-mg/d olanzapine group compared with placebo (-2.7 vs -1.5; P =.008). Somnolence was significantly more common among patients receiving olanzapine (25.0%-35.8%), and gait disturbance occurred in those receiving 5 or 15 mg/d (19.6% and 17.0%, respectively). No significant cognitive impairment, increase in extrapyramidal symptoms, or central anticholinergic effects were found at any olanzapine dose relative to placebo. CONCLUSION: Low-dose olanzapine (5 and 10 mg/d) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD.

Bcl-2: bax and bcl-2: Bcl-x ratios by image cytometric quantitation of immunohistochemical expression in ovarian carcinoma: correlation with prognosis.

Bcl-2 is a proto-oncogene which is involved in prolonging cell survival by inhibiting programmed cell death. Bax and bcl-x are members of the bcl-2 family; when overexpressed, they can counteract the ability of bcl-2 to inhibit apoptosis. This suggests a model in which the ratios of bcl-2 to bax and bcl-x can be used to determine response to therapy and prognosis. The expression of bcl-2, bax and bcl-x was studied in 50 ovarian carcinomas. The percentage of positive area immunostained (PPA) in the nucleus and cytoplasm of each ovarian carcinoma was quantitated in 15 high power fields by image cytometry. The ratios were obtained by dividing the PPA of bcl-2 by the PPA of bax and bcl-x. 17 of 50 ovarian carcinomas (34%) stained positively for bcl-2, 39 for bax (78%) and 47 for bcl-x (94%). Although there is no significant statistical correlation between expression of bcl-2, bax or bcl-x and grade (P = 0.15; P = 0. 47; P = 0.56), stage (P = 0.71; P = 0.6; P = 0.42), and overall or disease-free survival (P = 0.26; P = 0.55; P = 0.16), increased bcl-2 expression was demonstrated in patients with shortened overall and disease-free survival. Also, increased expression of bax and bcl-x was associated with increased overall and disease-free survival. Bcl-2:bax and bcl-2:bcl-x ratios less than 1 are associated with survival advantage, although not statistically significant (P = 0.83; P = 0.93). Image cytometric measurement of bcl-2, bax, and bcl-x expression is feasible. There is a tendency for their expression to correlate with prognosis in ovarian carcinomas.

Determinants of mortality in patients with advanced cirrhosis after transjugular intrahepatic portosystemic shunting.

BACKGROUND & AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) placement is effective in the treatment of complications of portal hypertension. This study evaluated the predictors of mortality in a group of cirrhotic patients with advanced liver disease after placement of TIPS. METHODS: A retrospective analysis of all patients undergoing TIPS placement over a 21/2-year period was undertaken. RESULTS: Fifty-six patients had TIPS placement for variceal hemorrhage, 49 for refractory ascites, and 24 for hepatic hydrothorax (total, 129). Of 21 variables available before TIPS placement, variceal hemorrhage requiring emergent TIPS placement (relative risk [RR], 37.5; 95% confidence interval [CI], 5.4-259) and bilirubin concentration > 3.0 mg/dL (RR, 5.4; 95% CI, 1.4-10.2) were independent predictors of 30-day mortality. Variceal hemorrhage requiring emergent TIPS placement (hazard ratio [HR], 5.1, 95% CI, 2. 2-9.1), alanine aminotransferase level > 100 IU/L (HR, 2.5; 95% CI, 1.2-5.5), bilirubin level > 3.0 mg/dL (HR, 2.6; 95% CI, 1.1-4.6), and pre-TIPS encephalopathy unrelated to bleeding (HR, 2.2; 95% CI, 1.2-4.8) independently predicted death during the follow-up period. A model was developed that separated the patients into 3 groups with significantly different survival rates. CONCLUSIONS: A clinical index consisting of 4 pre-TIPS variables can reliably predict outcome after TIPS.

Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis.

OBJECTIVE: When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers. RESEARCH DESIGN AND METHODS: This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia. RESULTS: The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups. CONCLUSIONS: Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.

Causes and outcome of upper and lower gastrointestinal bleeding: the Grady Hospital experience.

BACKGROUND: Gastrointestinal (GI) bleeding remains a common medical condition, with a mortality rate believed to have remained unchanged over the past five decades. METHODS: Over a 50-month period, the gastroenterology consultative service at a large inner-city hospital prospectively evaluated acute upper GI (UGI) bleeding or lower GI (LGI) bleeding in consecutive patients. A number of clinical variables were recorded at admission on a standardized data collection form. The cause of bleeding was determined in most patients by endoscopic examination. RESULTS: Of the 796 patients assessed for UGI bleeding, 727 (91%) had upper endoscopy. The most common causes of UGI bleeding were gastric ulcer (32%), duodenal ulcer (28%), esophageal varices (9%), and Mallory-Weiss tear (6%). The rebleeding rate was 14% and 20% of patients had endoscopic therapy. Surgical therapy for bleeding was required in 7% of patients. Of the 165 patients assessed for LGI bleeding, 150 (91%) had colonoscopy. Colonic diverticulosis was considered etiologic in 56% of patients, followed by colonic ulcers in 10%, carcinoma in 7%, and vascular ectasias in 5%. The rebleeding rate in these patients was 20%, and surgical therapy for bleeding was required in 10%. The overall mortality for patients with UGI bleeding was 9% and was independently associated with portal hypertension and rebleeding. In contrast, the mortality rate for LGI bleeding was 4%, and there was little power to determine significant factors associated with death. CONCLUSIONS: The causes of gastrointestinal bleeding remain little changed over the past several decades, though in our large series the need for surgical therapy and the mortality from both upper and lower GI bleeding were low.

Health literacy and the risk of hospital admission.

OBJECTIVE: To determine the association between patient literacy and hospitalization. DESIGN: Prospective cohort study. SETTING: Urban public hospital. PATIENTS: A total of 979 emergency department patients who participated in the Literacy in Health Care study and had completed an intake interview and literacy testing with the Test of Functional Health Literacy in Adults were eligible for this study. Of these, 958 (97.8%) had an electronic medical record available for 1994 and 1995. MEASUREMENTS AND MAIN RESULTS: Hospital admissions to Grady Memorial Hospital during 1994 and 1995 were determined by the hospital information system. We used multivariate logistic regression to determine the independent association between inadequate functional health literacy and hospital admission. Patients with inadequate literacy were twice as likely as patients with adequate literacy to be hospitalized during 1994 and 1995 (31. 5% vs 14.9%, p <.001). After adjusting for age, gender, race, self-reported health, socioeconomic status, and health insurance, patients with inadequate literacy were more likely to be hospitalized than patients with adequate literacy (adjusted odds ratio [OR] 1.69; 95% confidence interval [CI] 1.13, 2.53). The association between inadequate literacy and hospital admission was strongest among patients who had been hospitalized in the year before study entry (OR 3.15; 95% CI 1.45, 6.85). CONCLUSIONS: In this study population, patients with inadequate functional health literacy had an increased risk of hospital admission.

Modifying risk for extracorporeal circulation: trial of four antiinflammatory strategies.

BACKGROUND: Despite recent rediscovery of beating heart cardiac surgical techniques, extracorporeal circulation remains appropriate for most heart operations. To minimize deleterious effects of cardiopulmonary bypass, antiinflammatory strategies have evolved. METHODS: Four state-of-the-art strategies were studied in a prospective, randomized, preoperatively risk stratified, 400-patient study comprising primary (n = 358), reoperative (n = 42), coronary (n = 307), valve (n = 27), ascending aortic (n = 9), and combined operations (n = 23). Groups were as follows: standard, roller pump, membrane oxygenator, methylprednisolone (n = 112); aprotinin, standard plus aprotinin (n = 109); leukocyte depletion, standard plus a leukocyte filtration strategy (n = 112); and heparin-bonded circuitry, centrifugal pumping with surface modification (n = 67). RESULTS: Analysis of variance, linear and logistic regression, and Pearson correlation were applied. Actual mortality (2.3%) was less than half the risk stratification predicted mortality (5.7%). The treatment strategies effectively attenuated markers of the inflammatory response to extracorporeal circulation. Compared with the other groups the heparin-bonded circuit had highly significantly decreased complement activation (p = 0.00001), leukocyte filtration blunted postpump leukocytosis (p = 0.043), and the aprotinin group had less fibrinolysis (p = 0.011). Primary end points, length of stay, and hospital charges, were positively correlated with operation type, age, pump time, body surface area, stroke, pulmonary sequelae, predicted risk for stroke, predicted risk for mortality, and risk strata/treatment group interaction (p = 0.0001). In low-risk patients, leukocyte filtration reduced length of stay by 1 day (p = 0.02) and mean charges by $2,000 to $6,000 (p = 0.05). For high-risk patients, aprotinin reduced mean length of stay up to 10 fewer days (p = 0.02) and mean charges by $6,000 to $48,000 (p = 0.0007). CONCLUSIONS: These pharmacologic and mechanical strategies significantly attenuated the inflammatory response to extracorporeal circulation. This translated variably into improved patient outcomes. The increased cost of treatment was offset for selected strategies through the added value of significantly reduced risk.

Thymic dysfunction and time of infection predict mortality in human immunodeficiency virus-infected infants. CDC Perinatal AIDS Collaborative Transmission Study Group.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

Euthanasia and doctor-assisted suicide: responses by oncologists and non-oncologists.

PURPOSE: Public interest concerning euthanasia and doctor-assisted suicide is creating ethical dilemmas in the health care profession. We surveyed the views of oncologists and non-oncologists in Florida. METHODS: Physicians responded to an attitudinal questionnaire. The data collected were compared with standard statistical methods. RESULTS: Both oncologists and non-oncologists had similar opposition to euthanasia on philosophic or general grounds, with more opposition on general grounds expressed by oncologists. Both groups preferred better pain control and improved quality of life rather than euthanasia, but more oncologists than non-oncologists favored this alternative. Both groups admitted to participation in passive euthanasia, with little support for active euthanasia and doctor-assisted suicide. However, should the acts of euthanasia and doctor-assisted suicide become legalized, more non-oncologists than oncologists would agree to participate. CONCLUSION: In Florida, more opposition to aspects of the termination of life was expressed by oncologists than by non-oncologists.

The prevalence and significance of leukocytosis in upper gastrointestinal bleeding.

Although leukocytosis has long been recognized to occur in patients with hemorrhage, there are no data regarding leukocytosis in patients with upper gastrointestinal bleeding. We evaluated the prevalence and significance of the admission white blood cell count in consecutive patients admitted to Grady Memorial Hospital with upper gastrointestinal bleeding seen prospectively over a 50-month period. Any white count greater than 8.5 x 10(3)/mm3 was considered abnormal. Of the 731 patients eligible for the study, leukocytosis was seen in 463 (63%). When compared to patients with a normal white count, patients with leukocytosis on admission were more likely to be tachycardic (31.4% versus 24.3%, P = 0.04) and hypotensive (10.9% versus 5.7%, P = 0.018), required more units of blood (4.6+/-5.9 versus 3.5+/-6.0, P = 0.01), had a longer hospital stay (7.3+/-9.7 versus 5.9+/-6.2 days, P = 0.01), and required more frequent surgical intervention for bleeding (8.0% versus 4.2%, P = 0.04). No significant difference in mortality was seen between patients with leukocytosis and those with a normal white count (8.7% versus 6.4%, P = 0.27). Leukocytosis is common in patients with upper gastrointestinal bleeding, appears to reflect the severity of the bleeding episode, and is associated with a more complicated course.

Clinical comparison of an enhanced-sensitivity branched-DNA assay and reverse transcription-PCR for quantitation of human immunodeficiency virus type 1 RNA in plasma.

The performance characteristics of an enhanced-sensitivity branched-DNA assay (bDNA) (Quantiplex HIV-1 version 2.0; Chiron Corp., Emeryville, Calif.) and a reverse transcription (RT)-PCR assay (AMPLICOR HIV-1 Monitor; Roche Diagnostic Systems, Inc., Branchburg, N.J.) were compared in a molecular diagnostic laboratory. Samples used in this evaluation included linearity and reproducibility panels made by dilution of a human immunodeficiency virus type 1 (HIV-1) stock culture of known virus particle count in HIV-1-negative plasma, a subtype panel consisting of HIV-1 subtypes A through F at a standardized level, and 64 baseline plasma specimens from HIV-1-infected individuals. Plots of log10 HIV RNA copies per milliliter versus log10 nominal virus particles per milliliter demonstrated that both assays were linear over the stated dynamic ranges (bDNA, r = 0.98; RT-PCR, r = 0.99), but comparison of the slopes of the regression lines (bDNA, m = 0.96; RT-PCR, m = 0.83) suggested that RT-PCR had greater proportional systematic error. The between-run coefficients of variation for bDNA and RT-PCR were 24.3 and 34.3%, respectively, for a sample containing 1,650 nominal virus particles/ml and 44.0 and 42.7%, respectively, for a sample containing 165 nominal virus particles/ml. Subtypes B, C, and D were quantitated with similar efficiencies by bDNA and RT-PCR; however, RT-PCR was less efficient in quantitating subtypes A, E, and F. One non-B subtype was recognized in our clinical specimens based on the ratio of values obtained with the two methods. HIV-1 RNA was quantitated in 53 (83%) baseline plasma specimens by bDNA and in 55 (86%) specimens by RT-PCR. RT-PCR values were consistently greater than bDNA values, with population means of 142,419 and 67,580 copies/ml, respectively (P < 0.01). The results were highly correlated (r = 0.91), but the agreement was poor (mean difference in log10 copies per milliliter +/- 2 standard deviations, 0.45 +/- 0.61) for the 50 clinical specimens that gave discrete values with both methods.

Smoking cessation among inner-city African Americans using the nicotine transdermal patch.

OBJECTIVE: To determine the efficacy of the transdermal nicotine patch for smoking cessation in inner-city African Americans. DESIGN: Double-blind, placebo-controlled, randomized trial. SETTING: Outpatient in an inner-city hospital. PATIENTS AND PARTICIPANTS: A computer-generated random numbers table with a block size set at 20 was used to randomize 410 patients to one of two study arms. INTERVENTIONS: The transdermal nicotine patch for 10 weeks as an adjunct to brief counseling. MEASUREMENTS AND MAIN RESULTS: Of the 410 patients randomized, mean age was 48 years, 65% were female, 41% had less than a high school education, 51% had an annual household income of less than $8,000, and the average number of cigarettes smoked per day was 20. Quit rates at 10 weeks were 21.5% (44/205) with the nicotine patch, and 13.7% (28/205) with the placebo patch (p = .03). At 6 months, quit rates were 17.1% (35/205) with the nicotine patch, and 11.7% (24/205) with the placebo patch (p = .08). After adjusting for baseline differences in age and educational attainment, differences remained significant at 10 weeks (p = .04), but were not significant at 6 months (p = .14). Compliance rates for return visits were 83%, 78%, 55%, and 52%, at 1, 2, 6, and 10 weeks, respectively. CONCLUSIONS: The nicotine patch significantly improves short-term quit rates in inner-city African Americans who are interested in trying to quit smoking. Efforts should be made to reach underserved populations through smoking cessation programs, and to assist in maintaining abstinence.

Knowledge about smoking, reasons for smoking, and reasons for wishing to quit in inner-city African Americans.

OBJECTIVE: To determine knowledge about smoking, reasons for smoking, and reasons for wishing to quit and the association of these variables with abstinence at ten weeks and six months. DESIGN: Descriptive study and longitudinal intervention. SETTING: Inner-city public hospital clinics. PARTICIPANTS: 410 African-American cigarette smokers interested in quitting were surveyed at baseline and subsequently enrolled into a double-blind, placebo-controlled, randomized trial of the transdermal nicotine patch. MAIN OUTCOME MEASURES: Descriptive information about smoking knowledge, reasons for smoking, and reasons for wishing to quit, and association of these variables with abstinence at 10 weeks and 6 months. RESULTS: Among the 410 patients randomized, mean age was 48 years, 61% were female, 41% had less than a high school education, 51% had an annual household income less than $8,000, and the average number of cigarettes smoked a day was twenty. The average number of questions answered correctly was nine out of eleven (84%). The most cited reason for smoking was relaxation/tension reduction and the least cited were stimulation and handling of the cigarette. Ninety-nine percent of patients stated they wished to quit for health reasons. Knowledge, reasons for smoking, and reasons for wishing to quit were not significantly associated with 10-week or 6-month abstinence. CONCLUSIONS: In this group of inner-city African-American smokers, knowledge about cigarette smoking was high. Reasons for smoking were related to relaxation, craving, and pleasure, and reasons for wishing to quit were largely health-related. Knowledge, reasons for smoking, and reasons for wishing to quit were not associated with 10 week or 6 month abstinence. Since knowledge about smoking is already high, future efforts should be directed at promoting cessation through proven behavioral and pharmacological approaches, rather than didactic patient education.

Prospective evaluation of the gastrointestinal tract in patients with iron deficiency and no systemic or gastrointestinal symptoms or signs.

BACKGROUND: Although endoscopic evaluation of the gastrointestinal tract is commonly performed to evaluate iron deficiency, little data is available regarding the underlying causes, yield of evaluation, and long-term outcome for those in whom gastrointestinal and systemic symptoms and signs are absent. METHODS: In- or out-patients seen by the gastroenterology consultative service at a large inner-city hospital over a 56-month period were considered eligible for the study when iron deficiency (serum ferritin <50 ng/mL) was documented. Exclusion criteria included: any gastrointestinal or systemic symptoms/signs, radiographic or endoscopic examinations of the gastrointestinal tract within 3 and 5 years, respectively, or obvious source of blood loss. Patients underwent colonoscopy and if no lesions other than carcinoma were found, upper endoscopy was then performed with a pediatric colonoscope. RESULTS: Fifty-two patients were evaluated (mean age, 66 +/- 13 years; range, 20 to 89 years; 32 men/20 women). At the time of evaluation, the mean (+/-SD) hematocrit was 25% +/- 7% (range, 14% to 42%). Overall, 23 patients (44%; 95% CI 30% to 59%) had an identifiable gastrointestinal lesion considered the cause of iron deficiency, including: colonic carcinoma, 11 (21%); colonic and/or esophagogastric/duodenal vascular ectasias, 9 (17%); and gastric carcinoma, colonic polyposis, and colonic ulcers in 1 patient each. Long-term follow-up (median 24 months, range 2 to 63 months) identified only 1 patient with a cause found (colonic carcinoma), and in this patient, complete colonoscopy was not technically possible at the time of initial evaluation. There were no clinical or laboratory features that distinguished patients with an etiology for iron deficiency to the idiopathic group. CONCLUSIONS: Approximately half of patients with iron deficiency in whom gastrointestinal or systemic signs or symptoms are absent have an underlying gastrointestinal lesion. Nevertheless, despite a thorough endoscopic evaluation, some patients will have no etiology found; the prognosis for these patients is excellent.