Preconception and prenatal cystic fibrosis carrier screening of African Americans reveals unanticipated frequencies for specific mutations.

PURPOSE: It is recommended that cystic fibrosis (CF) carrier screening be made available to African Americans who are either pregnant or planning a pregnancy. We analyzed the carrier and mutant allele frequencies for African Americans undergoing CF carrier screening in our laboratories. METHODS: Between December 2001 and September 2003, we performed carrier screening for 2189 African Americans, testing for at least the 25 recommended mutations. RESULTS: A total of 33 CF carriers were identified. The most common mutations detected were deltaF508, G622D, R117H/7T, and G551D. The G622D allele frequency among African Americans was 0.18%. We did not detect any 3120 + 1G --> A carriers, although 4 were expected (P < 0.05). CONCLUSIONS: When considering only the 25 recommended CF mutations, 1 in 75 African Americans screened in our laboratories were carriers (within the expected range, given a 69% mutation detection rate). The addition of 2 mutations, G622D and Q98R (incidentally identified while screening for ACOG/ACMG mutations), increased the observed carrier frequency to 1 in 66, which is not significantly different from the known African American carrier frequency of 1 in 65. The frequencies of several specific mutations detected were unanticipated, as was the absence of 3120 + 1G --> A carriers. Further studies on African American patients with classic CF are needed to examine the incidence of CF mutations that are not part of the current panel, such as G622D.     

High blood pressure in children and adolescents

High blood pressure in children and adolescents is a growing health problem that is often overlooked by physicians. Normal blood pressure values for children and adolescents are based on age, sex, and height, and are available in standardized tables. Prehypertension is defined as a blood pressure in at least the 90th percentile, but less than the 95th percentile, for age, sex, and height, or a measurement of 120/80 mm Hg or greater. Hypertension is defined as blood pressure in the 95th percentile or greater. A secondary etiology of hypertension is much more likely in children than in adults, with renal parenchymal disease and renovascular disease being the most common. Overweight and obesity are strongly correlated with primary hypertension in children. A history and physical examination are needed for all children with newly diagnosed hypertension to help rule out underlying medical disorders. Children with hypertension should also be screened for other risk factors for cardiovascular disease, including diabetes mellitus and hyperlipidemia, and should be evaluated for target organ damage with a retinal examination and echocardiography. Hypertension in children is treated with lifestyle changes, including weight loss for those who are overweight or obese; a healthy, low-sodium diet; regular physical activity; and avoidance of tobacco and alcohol. Children with symptomatic hypertension, secondary hypertension, target organ damage, diabetes, or persistent hypertension despite nonpharmacologic measures should be treated with antihypertensive medications. Thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, and calcium channel blockers are safe, effective, and well tolerated in children.     

Vergiftungen. (Gewerbliche auch unter Gewerbehygiene)

Ohne Zusammenfassung     

Effects of smoking on benzo(α)pyrene- and glutathione-metabolizing enzymes in human lung tissue

Summary The influence of smoking on the metabolism of benzo()pyrene and glutathione was investigated in 190 patients with primary bronchial carcinoma and 20 patients with benign lung diseases. There were no significant differences in the activities of drug-metabolizing enzymes in the lung tissue of smokers, regardless of whether they smoked low- or high-tar and -nicotine cigarettes; former smokers; or nonsmokers; nor were there such differences between female and male patients. No significant differences existed between patients with squamous cell carcinoma and those with adenocarcinoma. Impaired detoxification due to decreased activity of glutathione S-transferases, rather induction of benzo()pyrene-metabolizing enzymes, may disturb the delicate balance between the generation and detoxification of reactive metabolites. This impairment may lead to the accumulation of these compounds in the cell.Abbreviations BP benzo()pyrene - ECDE 7-ethoxycoumarin O-deethylase - EH epoxide hydrolase - ERDE 7-ethoxyresorufin O-deethylase - GST glutathione S-transferases - LAK lymphokine-activated killer cells - PAH polycyclic aromatic hydrocarbon - SCC squamous cell carcinoma - T/N tar/nicotine This paper is dedicated to the memory of Prof. E.E. Ohnhaus     

Overexpression of sarcoplasmic reticulum Ca(2+)-ATPase improves cardiac contractile function in hypothyroid mice.

OBJECTIVE: Prolonged cardiac contraction and relaxation in hypothyroidism are in part related to diminished expression of the gene coding for the calcium pump of the sarcoplasmic reticulum (SERCA2a). Therefore, we examined whether or not transgenic SERCA2a gene expression in mice may compensate for the cardiac effects of hypothyroidism. METHODS: SERCA2a mRNA and protein were analyzed from hearts of euthyroid and hypothyroid mice of wild-type or SERCA2a transgene status. Contractile function was studied in isolated left ventricular papillary muscles. RESULTS: We found significant decreases of SERCA2a mRNA and protein levels in hearts of hypothyroid wild-type mice in comparison with euthyroid wild-type mice (controls). Papillary muscles from hypothyroid wild-type mice showed significant increases in time to peak contraction and relaxation times compared with controls. In contrast, SERCA2a mRNA and protein levels were significantly higher in hypothyroid SERCA2a transgenic mice than in hypothyroid wild-type mice. The transgene led to a functional improvement by compensating for the prolonged contraction and relaxation of papillary muscles. CONCLUSIONS: Our murine model of hypothyroidism revealed decreases in SERCA2a gene expression accompanied by prolonged contraction and relaxation of papillary muscles, and an improvement of the contractile phenotype due to compensated SERCA2a gene expression in SERCA2a transgenic mice.     

Hypertension and exposure to noise near airports: the HYENA study

BACKGROUND: An increasing number of people are exposed to aircraft and road traffic noise. Hypertension is an important risk factor for cardiovascular disease, and even a small contribution in risk from environmental factors may have a major impact on public health. OBJECTIVES: The HYENA (Hypertension and Exposure to Noise near Airports) study aimed to assess the relations between noise from aircraft or road traffic near airports and the risk of hypertension. METHODS: We measured blood pressure and collected data on health, socioeconomic, and lifestyle factors, including diet and physical activity, via questionnaire at home visits for 4,861 persons 45-70 years of age, who had lived at least 5 years near any of six major European airports. We assessed noise exposure using detailed models with a resolution of 1 dB (5 dB for United Kingdom road traffic noise), and a spatial resolution of 250 x 250 m for aircraft and 10 x 10 m for road traffic noise. RESULTS: We found significant exposure-response relationships between night-time aircraft as well as average daily road traffic noise exposure and risk of hypertension after adjustment for major confounders. For night-time aircraft noise, a 10-dB increase in exposure was associated with an odds ratio (OR) of 1.14 [95% confidence interval (CI), 1.01-1.29]. The exposure-response relationships were similar for road traffic noise and stronger for men with an OR of 1.54 (95% CI, 0.99-2.40) in the highest exposure category (> 65 dB; p(trend) = 0.008). CONCLUSIONS: Our results indicate excess risks of hypertension related to long-term noise exposure, primarily for night-time aircraft noise and daily average road traffic noise.     

The impact of smoking-cessation intervention by multiple health professionals

BACKGROUND: Smokers have contact with many different types of health professionals. The impact of tobacco intervention by multiple types of heath professionals is not known. METHODS AND MATERIALS: As part of the 2003 Minnesota Adult Tobacco Survey, smokers (n=1723) reported on tobacco treatment by medical doctors, nurses, dentists, pharmacists, or other health professionals. This analysis examined: (1) smokers' report of tobacco intervention by different types of healthcare providers, (2) the proportion of smokers who report intervention by multiple provider types, and (3) the relationship between smokers' report of intervention by multiple provider types and readiness to quit, quit attempts, and recent quitting. RESULTS: Among past-year smokers, 65% had visits with two or more types of health professionals. Among smokers who visited health professionals (n=1523), only 34% reported being asked about smoking by two or more types of professionals. Among current smokers (n=1324), advice or assistance from more than one type of professional was uncommon (26% and 7%, respectively). Being asked about smoking by two or more types of professionals substantially increased the odds of recent quitting (OR=2.37; 95% CI=1.15-4.88). Among current smokers, being advised to quit by two or more types of professionals increased the odds of having made a quit attempt in the past year (OR=2.92; 95% CI=1.56-5.45) or intending to quit in the next 6 months (OR=2.17; 95% CI=1.10-4.29). CONCLUSIONS: Smoking-cessation interventions by more than one type of health professional have the potential to substantially increase quitting and readiness to quit in the population.