Effect of etilefrine in preventing syncopal recurrence in patients with vasovagal syncope: a double-blind, randomized, placebo-controlled trial. The Vasovagal Syncope International Study.
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BACKGROUND: Etilefrine is an alpha-agonist agent with a potent vasoconstrictor effect, which is potentially useful in preventing vasovagal syncope by reducing venous pooling and/or by counteracting reflex arteriolar vasodilatation. The present multicenter, randomized, placebo-controlled study was designed to evaluate the efficacy of this drug for the long-term management of patients with recurrent vasovagal syncope. METHODS AND RESULTS: In the 20 participating centers, 126 patients with recurrent vasovagal syncope (at least 3 episodes in the last 2 years) and a positive baseline head-up tilt response were randomly assigned to placebo (63 patients) or etilefrine at a dosage of 75 mg/d (63 patients) and were followed up for 1 year or until syncope recurred. The primary end-point of the study was the first recurrence of syncope. There were no differences between the 2 study groups in the patients' baseline characteristics. During follow-up, the group treated with etilefrine had a similar incidence of first syncopal recurrence to that of placebo group both in the intention-to-treat analysis (24% versus 24%) and in on- treatment analysis (26% versus 24%). Moreover, the median time to the first syncopal recurrence did not significantly differ between the 2 study groups (106 days in the etilefrine arm and 112 days in the placebo arm). CONCLUSIONS: Oral etilefrine is not superior to placebo in preventing spontaneous episodes of vasovagal syncope. Randomized controlled studies are essential to assess the real usefulness of any proposed therapy for patients with vasovagal syncope. (+info)
Relation of weight and rate of increase in weight during childhood and adolescence to body size, blood pressure, fasting insulin, and lipids in young adults. The Minneapolis Children's Blood Pressure Study.
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BACKGROUND: Weight gain is of concern during early development because adult obesity and its cardiovascular consequences appear to have their origins during childhood. Insulin resistance is known to be related to obesity. Thus, weight gain beginning in childhood may influence the development of insulin-induced cardiovascular risk during adulthood. METHODS AND RESULTS: We monitored 679 individuals from 7.7+/-0.1 years of age with repeated measures of height, weight, and systolic blood pressure (SBP) until 23.6+/-0.2 years of age, when blood samples were obtained for measurements of insulin and lipids. Initial childhood weight, body mass index (BMI), and height were significantly correlated with young adult weight, BMI, and height and with fasting insulin, lipids, and SBP. The increases in weight and BMI but not height during childhood were significantly related to the young adult levels of insulin, lipids, and SBP. CONCLUSIONS: These data suggest that weight gain in excess of normal growth during childhood is a determinant of adult cardiovascular risk. The finding in multiple linear regression analysis that weight gain during childhood rather than the childhood weight at 7.7 years of age is significantly related to young adult risk factors suggests that a reduction in weight gain could reduce subsequent levels of cardiovascular risk. (+info)
The epidemiology of rheumatoid arthritis in Rochester, Minnesota, 1955-1985.
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OBJECTIVE: To describe trends in the epidemiology of rheumatoid arthritis (RA) over a period of 30 years in a population-based cohort. METHODS: An inception cohort of Rochester, Minnesota residents who were > or =35 years of age and had RA (as defined by the 1987 American College of Rheumatology criteria for RA) first diagnosed between January 1, 1955 and January 1, 1985 was assembled and followed up until January 1, 1995. Incidence rates were age- and sex-adjusted to the 1970 US white population. Prevalence of RA in this cohort was estimated on January 1, 1985. A birth-cohort analysis was performed by calculating and comparing incidence rates in each of 16 birth cohorts. RESULTS: Of the 425 Rochester residents who fulfilled the inclusion criteria, there were 113 men (26.6%) and 312 women (73.4%), with a mean age at diagnosis of 60.2 years. The mean followup time was 15.1 years. The overall age- and sex-adjusted annual incidence of RA among Rochester, Minnesota residents > or =35 years of age (1955-1985) was 75.3 per 100,000 population (95% confidence interval 68.0-82.5). This incidence was approximately double in women compared with that in men and increased steadily with age, until age 85, after which the incidence of RA decreased. Secular trends in the incidence of RA over the entire study period were demonstrated. The overall prevalence of RA on January 1, 1985 was approximately 1%. The birth-cohort analysis showed peak incidence rates in the 1880-1895 birth cohorts. CONCLUSION: The epidemiology of RA is dynamic. The findings in this study lend further support to the hypothesis of a host-environment interaction in the pathogenesis of RA. (+info)
Microscopic polyangiitis: clinical and laboratory findings in eighty-five patients.
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OBJECTIVE: To retrospectively analyze the clinical symptoms, laboratory findings, and outcomes in patients with microscopic polyangiitis (MPA) who were enrolled in various clinical trials conducted by the French Vasculitis Study Group. METHODS: A cohort of 85 patients meeting the Chapel Hill criteria for MPA participated in the study. Seventy-one of them were included in prospective therapeutic trials. Eighty-one diagnoses were biopsy proven. In the other patients, diagnosis was based on clinical findings. RESULTS: Forty-seven men and 38 women, with a mean +/- SD age of 56.8 +/- 14.6 years, met the criteria for MPA. Their main clinical symptoms were renal manifestations (78.8%), weight loss (72.9%), skin involvement (62.4%), fever (55.3%), mononeuritis multiplex (57.6%), arthralgias (50.6%), myalgias (48.2%), hypertension (34.1%), lung involvement (24.7%; alveolar hemorrhage 11.8%), and cardiac failure (17.6%). The mean +/- SD serum creatinine level before treatment was 2.59 +/- 2.96 mg/dl; 47 patients had renal insufficiency (serum creatinine > 1.36 mg/dl). Eight patients underwent dialysis at the time of diagnosis, and long-term dialysis was necessary for 10 patients. Antineutrophil cytoplasmic antibodies (ANCA) were present in 38 of 51 patients (74.5%), of whom 33 had a perinuclear staining pattern (pANCA) and 5 had a cytoplasmic pattern. Antibodies to proteinase 3 were present in 4 patients and antibodies to myeloperoxidase were detected in 31, as determined by enzyme-linked immunosorbent assay. Of the 30 patients who underwent renal and celiac angiography, 4 had microaneurysms. Of the 29 patients (34.1%) who had relapses, 8 died during or after the relapse. During followup, 28 of the 85 patients (32.9%) died. The mean +/- SD duration of followup of the group was 69.9 +/- 60.6 months. Deaths were less frequent when patients had been treated with steroids and immunosuppressive drugs (13 patients [24.1%]) than with steroids alone (15 patients [48.4%]) (P < 0.01). The 5-year survival rate was 74%. CONCLUSION: This study demonstrated that MPA is a multisystemic disease in which renal symptoms are frequent, but the disease is also associated with general symptoms, arthritis, mononeuritis multiplex, and other manifestations that are also seen in various vasculitides. The rarity of abnormal angiogram findings and the high frequency of pANCA are characteristic of MPA. In most cases, the outcome is comparable with those of other systemic vasculitides, but relapses are frequent. (+info)
Epidemiological analysis of site relationships of synchronous and metachronous multiple primary cancers in the National Cancer Center, Japan, 1962-1996.
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BACKGROUND: Multiple primary cancer (MPC) has been recognized as a problem commonly encountered in routine medical practice. A study of MPC is necessary not only to provide insights into the etiology of cancer, but also to provide information for effective medical care by clinical oncologists. METHODS: A cohort of 49,751 cancer patients who were admitted to the National Cancer Center Hospital between 1962 and 1996 was used to study the site relationship of MPC. Logistic and Poisson regression analyses using an internal reference group within the cohort were applied for the calculation of the prevalence odds ratio (POR) for site relationships of synchronous MPC and the incidence rate ratio (IRR) for those of metachronous MPC. RESULTS: Three site combinations with elevated risks for both synchronous and metachronous MPCs, eight with elevated risk for synchronous MPC, five with elevated risk for metachronous MPC and six with decreased risk for synchronous MPC were identified with statistical significance. Among them, the increased risk of metachronous stomach cancer following lymphoma and myeoloma (POR = 1.0 and 1.1, P > 0.05; IRR = 2.5, P < 0.05) and the inverse site-correlation of synchronous MPC between [trachea, bronchus and lung] and other sites of the upper aerodigestive tract [lip, oral cavity and pharynx] (POR = 0.5 and 0.3, P < 0.05) and esophagus (POR = 0.7 and 0.3, P < 0.05) have not been reported previously. CONCLUSIONS: Our results suggest that interventions for lymphoma and myeloma might affect the development of subsequent stomach cancer and additional etiological factors other than tobacco smoking are associated with the development of cancer in the upper aerodigestive tract. (+info)
A prospective study on folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer.
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To investigate the incidence of breast cancer and prediagnostic serum levels of folate, B12, and pyridoxal 5'-phosphate (B6), we conducted a nested case-control study using resources from the Washington County (Maryland) serum bank. In 1974, 12,450 serum specimens were donated, and in 1989, 14,625 plasma specimens were donated by female residents of Washington County. One hundred ninety-five incident breast cancer cases and 195 controls were matched by age, race, menopausal status at donation, and cohort participation as well as by date of blood donation. In both cohorts and all menopausal subgroups, median B12 concentrations were lower among cases than controls. Differences reached statistical significance only among women who were postmenopausal at donation (1974 cohort, 413 versus 482 pg/ml, P = 0.03; 1989 cohort, 406 versus 452 pg/ml, P = 0.02). Among women postmenopausal at blood donation, observed associations of B12 suggested a threshold effect with increased risk of breast cancer in the lowest one-fifth compared to the higher four-fifths of the control distribution [lowest versus highest fifth: 1974 cohort, matched odds ratio = 4.00 (95% confidence interval = 1.05-15.20); 1989 cohort, matched odds ratio = 2.25 (95% confidence interval = 0.86-5.91)]. We found no evidence for an association between folate, B6, and homocysteine and breast cancer. Findings suggested a threshold effect for serum B12 with an increased risk of breast cancer among postmenopausal women in the lowest one-fifth compared to the higher four-fifths of the control distribution. These results should stimulate further investigations of potentially modifiable risk factors, such as these B-vitamins, for prevention of breast cancer. (+info)
N-acetyltransferase 1 genetic polymorphism, cigarette smoking, well-done meat intake, and breast cancer risk.
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N-Acetyltransferase 1 (NAT1), encoded by the polymorphic NAT1 gene, has been shown to be one of the major enzymes in human breast tissue that activates aromatic and heterocyclic amines. Humans are mainly exposed to these carcinogens through cigarette smoking and consumption of well-done meat. To test the hypothesis that variations in the NAT1 gene are related to breast cancer risk, particularly among women who smoke or consume high levels of well-done meat, a nested case-control study was conducted in a prospective cohort study of 41,837 postmenopausal Iowa women. Information on cigarette smoking and other breast cancer risk factors was obtained at the baseline survey conducted in 1986. DNA samples and information on the consumption of well-done meat were obtained, in the case-control study, from breast cancer cases diagnosed from 1992 to 1994 and a random sample of cancer-free cohort members. Genomic DNA samples obtained from 154 cases and 330 controls were assayed for 11 NAT1 alleles (NAT1*3, *4, *5, *10, *11, *14, *15, *16, *17, *19, and *22). The NAT1*4 allele was the predominant allele observed in this study population, accounting for 73.2% (72.4% in cases versus 73.8% in controls) of the total alleles analyzed. Compared to controls, breast cancer cases had a slightly higher frequency of the NAT1*10 allele (18.8% in cases versus 17.3% in controls) and a substantially higher frequency of the NAT1*11 allele (3.6% versus 1.2%). In multivariate analyses, we found a 30% [95% confidence interval (CI) = 0.8-1.9] elevated risk of breast cancer associated with the NAT1*10 allele and a nearly 4-fold (95% CI = 1.5-10.5) elevated risk associated with the NAT1*11 allele. The positive association of breast cancer with the NAT1*11 allele was more evident among smokers [odds ratio (OR) = 13.2, 95% CI = 1.5-116.0] and those who consumed a high level of red meat (OR = 6.1, 95% CI = 1.1-33.2) or consistently consumed their red meat well done (OR = 5.6, 95% CI = 0.5-62.7). The association of the NAT1*10 allele with breast cancer was mainly confined to former smokers (OR = 3.3, 95% CI = 1.2-9.5). These findings are consistent with a role for the NAT1 gene in the etiology of human breast cancer. (+info)
Soluble interleukin 2 receptor levels and cervical neoplasia: results from a population-based case-control study in Costa Rica.
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Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner. In a previous study (A. Hildesheim et al., Cancer Epidemiol. Biomark. Prev., 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia. We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica. We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37). Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women <30 years of age (P = 0.008). When women with cervical disease (LSIL+) were compared with controls, women in the upper quartile of the sIL-2R distribution had an age-adjusted odds ratio (OR) of 2.1 [95% confidence interval (CI), 1.1-4.1]. Comparing each advancing state of neoplasia with its precursor, we found that women with LSIL had higher sIL-2R levels than controls (OR for upper quartile of sIL-2R, 2.3; 95% CI, 1.1-5.2; comparing LSIL cases with controls); women diagnosed with HSIL were similar to the LSIL group (OR for upper quartile of sIL-2R, 1.1; 95% CI, 0.5-2.4; comparing HSIL cases with LSIL cases); and those with cancer had higher sIL-2R levels than subjects with an HSIL diagnosis (OR for upper quartile of sIL-2R = 1.8; 95% CI, 0.5-7.1; comparing cancer cases with HSIL cases). These data suggest that among our study subjects, sIL-2R levels most likely rise as a response to the events of infection and cancerous invasion, but that sIL-2R levels are unlikely to be predictive of disease progression among women with LSIL. (+info)