Minimal dataset for post-registration surveillance of new drugs in hemophilia: communication from the SSC of the ISTH

Clinical epidemiolog

Higher blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations correlate with lower olfactory scores in essential tremor

Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease

Induction of Myocarditis and Valvuluitis in Lewis Rats by Different Epitopes of Cardiac Myosin and its Implications in Rheumatic Carditis

Immune responses against cardiac myosin and group A streptococcal M protein have been implicated in the pathogenesis of rheumatic heart disease. Although cardiac myosin is known to produce myocarditis in susceptible animals, it has never been investigated for its role in production of valvular heart disease, the most serious sequelae of group A streptococcal infection in acute rheumatic fever. In our study, cardiac myosin induced valvulitis in the Lewis rat, and epitopes responsible for production of valvulitis were located in the rod region. Human and rat cardiac myosins induced severe myocarditis in the Lewis rats as expected. A purified S2 fragment (amino acid sequences 842 to 1295) produced the most severe myocarditis as well as valvulitis. Different regions of light meromyosin produced valvulitis (residues 1685 to 1936) or myocarditis (residues 1529 to 1611). Because streptococcal M proteins produced valvular heart disease in Lewis rats and have been linked to anti-cardiac myosin responses, we reacted myosin-sensitized lymphocytes isolated from the hearts of Lewis rats with peptides of streptococcal M5 protein in tritiated thymidine assays. Infiltrating lymphocytes responded most strongly to peptides within the B repeat region of streptococcal M protein. These data show direct evidence that immune responses against cardiac myosin lead to valvular heart disease and the infiltration of the heart by streptococcal M protein reactive T lymphocytes

Dietary epidemiology of essential tremor: meat consumption and meat cooking pactices

Background/Aim: Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods: Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results: Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion: This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation

Cancer and blood concentrations of the comutagen harmane in essential tremor

Blood concentrations of harmane, a tremor-producing neurotoxin, are elevated in essential tremor (ET). Harmane is also a comutagen. Using a case-control design, we compared the prevalence of cancer in ET cases vs. controls, and determined whether blood harmane concentrations are elevated among ET cases with cancer. 66/267 (24.7%) ET cases vs. 55/331 (16.6%) controls had cancer (adjusted OR 1.52, 95% CI 1.01 — 2.30, P = 0.04). Among specific cancer types, colon cancer was more prevalent in ET cases than controls (2.6% vs. 0.6%, P = 0.04). Log blood harmane concentration was higher in ET cases vs. controls (P = 0.02) and in participants with vs. without cancer (P = 0.02). Log blood harmane concentration was highest in ET cases with cancer when compared with other groups (P = 0.009). These links between cancer and ET and between high blood harmane and cancer in ET deserve further study

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g−10/ml vs. 0.35 ± 0.62 g−10/ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (ORadjusted 1.56, 95% CI 1.01–2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07–3.39, p = 0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g−10/ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g−10/ml) and lowest in controls (0.35 ± 0.62 g−10/ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors

Temporal Variability and Predictors of Urinary Bisphenol A Concentrations in Men and Women

Background: Bisphenol A (BPA) is used to manufacture polymeric materials, such as polycarbonate plastics, and is found in a variety of consumer products. Recent data show widespread BPA exposure among the U.S. population.Objective Our goal in the present study was to determine the temporal variability and predictors of BPA exposure. Methods: We measured urinary concentrations of BPA among male and female patients from the Massachusetts General Hospital Fertility Center. Results: Between 2004 and 2006, 217 urine samples were collected from 82 subjects: 45 women (145 samples) and 37 men (72 samples). Of these, 24 women and men were partners and contributed 42 pairs of samples collected on the same day. Ten women became pregnant during the follow-up period. Among the 217 urine samples, the median BPA concentration was 1.20 μg/L, ranging from below the limit of detection (0.4 μg/L) to 42.6 μg/L. Age, body mass index, and sex were not significant predictors of urinary BPA concentrations. BPA urinary concentrations among pregnant women were 26% higher (–26%, +115%) than those among the same women when not pregnant (p > 0.05). The urinary BPA concentrations of the female and male partner on the same day were correlated (r = 0.36; p = 0.02). The sensitivity of classifying a subject in the highest tertile using a single urine sample was 0.64. Conclusion: We found a nonsignificant increase in urinary BPA concentrations in women while pregnant compared with nonpregnant samples from the same women. Samples collected from partners on the same day were correlated, suggesting shared sources of exposure. Finally, a single urine sample showed moderate sensitivity for predicting a subject’s tertile categorization