Frequency of cytokine polymorphisms in populations from western Europe,Africa, Asia,the Middle East and South America

PCR-SSOP identification procedures for IL-2, IL-6, IL-10, TNF-alpha and TNF-beta cytokine polymorphisms have been developed. Application of the procedures to a range of diverse geographically distributed populations has identified ethnic differences within the groups studied. Five populations were investigated, Northern Ireland, South African Zulu, Omani, Singapore Chinese and Mexican Mestizos.     

Using the literature in developing McGill's guidelines for interactions between residents and the pharmaceutical industry.

Evidence suggests that the pharmaceutical industry exerts a large influence on residents' education and practice. Yet existing guidelines by professional bodies do not cover the specifics of residents' interactions with the pharmaceutical industry. At the psychiatry residency program of the McGill University Health Center, the authors set out to systematically evaluate areas of concern for residents and to develop guidelines for use by residents during and outside their training. Areas of concern included educational activities, training, fundraising, and other specific resident-industry interactions. In 1998, a committee of residents and faculty systematically evaluated areas of concern and, based on a review of the literature and discussions with experts, in 2000 developed guidelines for use by McGill's psychiatry program residents. The process for guideline development and methods for their implementation in 2001 are described. Education and training of residents on resident-industry interactions were included early in the curriculum. Guidelines were developed to address limitations on fundraising activities; restriction of direct gifts to residents; the appropriateness and awarding of industry fellowships; and the handling of drug samples, meals, and other presentations to residents. While guidelines for residents are useful adjuncts for guiding residents' interactions with the pharmaceutical industry, the authors conclude that they need to be reinforced with education and sensitization by faculty.     

CD39 activity correlates with stage and inhibits platelet reactivity in chronic lymphocytic leukemia

Background  

Chronic lymphocytic leukemia (CLL) is characterized by accumulation of mature appearing lymphocytes and is rarely complicated by thrombosis. One possible explanation for the paucity of thrombotic events in these patients may be the presence of the ecto-nucleotidase CD39/NTDPase-1 on the surface of the malignant cells in CLL. CD39 is the major promoter of platelet inhibition in vivo via its metabolism of ADP to AMP. We hypothesize that if CD39 is observed on CLL cells, then patients with CLL may be relatively protected against platelet aggregation and recruitment and that CD39 may have other effects on CLL, including modulation of the disease, via its metabolism of ATP.     

Relationship among pulmonary function, bronchial reactivity, and exhaled nitric oxide in a large group of asthmatic patients.

BACKGROUND: Bronchial reactivity and exhaled nitric oxide (eNO) are not often used to monitor control and severity of asthma in clinical practice. OBJECTIVE: To evaluate the relationship among different physiologic measures (pulmonary function, nonspecific bronchial reactivity, and eNO) in asthmatic patients. METHODS: Cross-sectional, hospital-based study conducted in patients with varied asthma severity. RESULTS: A total of 392 patients participated in the study. There was no difference in eNO levels between patients taking inhaled corticosteroids (ICS group) and patients not receiving inhaled corticosteroids (NICS group). However, the percentage of predicted forced expiratory volume in 1 second (FEV1) and the provocative dose of methacholine causing a 20% decrease in FEV1 were significantly lower in the ICS group compared with the NICS group (mean, 83.2%; 95% confidence interval [CI], 80.4%-86.0%; vs mean, 94.1%; 95% CI, 91.1%-97.1%; P = .001; and geometric mean, 0.32 mg; 95% CI, 0.23-0.45 mg; vs geometric mean, 0.58 mg; 95% CI, 0.42-0.81 mg; P = .01; respectively). Patients with more severe bronchial hyperresponsiveness had a lower percentage of predicted FEV1 values (P < .001) and levels of eNO were significantly increased with increasing bronchial hyperresponsiveness (P < .001). There was no relationship between the percentage of predicted FEV1 and eNO. Atopic patients had significantly higher eNO levels than nonatopic patients (geometric mean, 11.21 ppb; 95% CI, 10.07-12.49 ppb; vs geometric mean, 7.76 ppb; 95% CI, 6.11-9.85 ppb; P = .006; respectively). CONCLUSIONS: eNO values are not related to the degree of airway obstruction but are related to airway reactivity and atopic status independent of inhaled corticosteroid use. Higher values of eNO are seen with increased airway reactivity.     

Underdiagnosis of genital herpes by current clinical and viral-isolation procedures.

BACKGROUND. The current clinical strategy for diagnosing genital herpes simplex virus (HSV) infection in women relies on clinical findings plus the selective use of viral culture. The effectiveness of this approach for identifying women with genital herpes is unknown. METHODS. We performed physical examinations, colposcopy, Pap smears, viral cultures, and HSV type-specific serologic assays of 779 randomly selected women attending a sexually transmitted disease clinic. RESULTS. Evidence of HSV type 2 infection was detected in 363 women (47 percent), and 9 others (1 percent) had positive cultures indicative of urogenital or anal infection with HSV type 1. Of these 372 women, only 82 (22 percent) had symptoms. Fourteen women (4 percent) had viral shedding without symptoms, 60 (16 percent) had formerly had symptomatic episodes, and 216 (58 percent) had antibodies to HSV-2 with neither viral shedding nor a history of clinical episodes. Characteristic ulcerations of the external genitalia were present in only two thirds of the 66 women with positive HSV cultures; the others had atypical genital lesions or asymptomatic viral shedding. Isolation of HSV from a genitourinary tract specimen was the most sensitive (77 percent) test for confirming a first episode of infection. The detection of HSV-2-specific antibodies was the most sensitive (97 percent) way to confirm symptomatic reactivations of HSV-2 infection. HSV-2 serologic testing also identified the 290 women with asymptomatic HSV-2 infections (37 percent), including 14 (5 percent) who were shedding virus asymptomatically on the day of the examination. CONCLUSIONS. The current strategy for diagnosing genital HSV infection in women misses many cases. Newly developed type-specific serologic methods can identify women with recurrent genital HSV-2 infection, as well as those with unrecognized or subclinical infection.     

Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons

BACKGROUND: Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. METHODS: We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. RESULTS: HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0 percent vs. 2.7 percent). Of the 53 subjects who had no reported history of genital herpes, 33 (62 percent) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days vs. five days; P<0.001) and the frequency lower (median, 3.0 per year vs. 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only 1 of these 53 subjects had no clinical or virologic evidence of HSV infection. CONCLUSIONS: Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.     

Clinical correlates of index values in the focus HerpeSelect ELISA for antibodies to herpes simplex virus type 2 (HSV-2).

BACKGROUND: Clinical correlates of HerpeSelect ELISA index values are poorly understood. OBJECTIVES: This study was designed to determine the effects of time of infection, test variability, and antibody avidity on index values. STUDY DESIGN: Sera (N=313) from 81 patients with new HSV-2 infections and 236 sera from 32 patients with long-standing (median 11.3 years) HSV-2 were tested by HerpeSelect HSV-2 ELISA. High positive, low positive and negative controls were run on 42 test plates to establish test variability. RESULTS: Index values tended to rise after infection, peaking a median of 9-10 weeks post-infection (range 8-323 days). Of 32 patients with established HSV-2 infections, 7 (22%) had at least one low index value (>1.1 to < or =3.5), and one had a transient seroreversion event. Test variability of index values was substantially lower than inter- or intra-patient variability. Median antibody avidity was higher in sera with high versus low index values in established infections, but unrelated to index value in patients with early infections. CONCLUSIONS: Index values or index value changes are not absolute indicators of early versus established HSV-2 infection or solely a function of test variability. Low antibody avidity may contribute to low index values once infection is established.