Risk factors for prehypertension in the community: a prospective analysis from the Western New York Health Study.

BACKGROUND AND AIM: Prehypertension is an increasingly highly prevalent condition in the general population, and is associated with an increased risk for coronary heart disease and stroke. However, evidence from population-based studies of the risk factors for prehypertension is scant. We sought to examine the predictors of progression from normotension to prehypertension in a community-based population from Western New York. METHODS AND RESULTS: A longitudinal analysis, over 6 years of follow-up, among 569 men and women (mean age 51.8 years) who were free of prehypertension, hypertension, cardiovascular disease and diabetes at the baseline examination, in the Western New York Health Study (WNYHS). Incident prehypertension at follow-up was defined as systolic blood pressure of 120-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg. The cumulative six year incidence of prehypertension was 33.5% (189/564). In bivariate analyses, there were several correlates of incident prehypertension, including age, BMI and waist circumference, impaired fasting glucose (IFG), uric acid, and baseline blood pressure levels. After multivariate adjustment, IFG at baseline [odds ratio (OR): 1.70, 95% CI: 1.07-2.69) and weight gain since age 25 (OR: 1.12, 1.04-1.21 per 10 lb increase)] were the strongest significant predictors of prehypertension at follow-up. Neither baseline waist circumference nor change in BMI were predictor variables in models when they were substituted for weight gain. CONCLUSIONS: Results from this study suggest early dysregulation of glucose metabolism and weight gain over the lifespan may represent important risk factors for prehypertension in the general population.

Differential expression and cellular localization of novel isoforms of the tendon biomarker tenomodulin.

Tenomodulin (Tnmd, also called Tendin) is classified as a type II transmembrane glycoprotein and is highly expressed in developing as well as in mature tendons. Along with scleraxis (scx), Tnmd is a candidate marker gene for tenocytes. Its function is unknown, but it has been reported to have anti-angiogenic properties. Results in a knockout mouse model did not substantiate that claim. It has homology to chondromodulin-I. Single nucleotide polymorphisms of TNMD have been associated with obesity, macular degeneration, and Alzheimer's disease in patients. In the present study, three Tnmd isoforms with deduced molecular weights of 20.3 (isoform II), 25.4 (isoform III), and 37.1 (isoform I) kDa were proposed and verified by Western blot from cells with green fluorescent protein-linked, overexpressed constructs, tissue, and by qPCR of isoforms from human tissues and cultured cells. Overexpression of each Tnmd isoform followed by immunofluorescence imaging showed that isoforms I and II had perinuclear localization while isoform III was cytoplasmic. Results of qPCR demonstrated differential expression of each Tnmd isoform in patient's specimens taken from flexor carpi radialis, biceps brachii, and flexor digitorum profundus tendons. Knockdown of Tnmd increased the expression of both scleraxis (scx) and myostatin, indicating a potential negative feedback loop between Tnmd and its regulators. Knockdown of all Tnmd isoforms simultaneously also reduced tenocyte proliferation. I-TASSER protein three-dimensional conformation modeling predictions indicated each Tnmd isoform had different structures and potential functions: isoform 1, modeled as a cytosine methyltransferase; isoform 2, a SUMO-1-like SENP-1 protease; and isoform 3, an α-syntrophin, plextrin homology domain scaffolding protein. Further functional studies with each Tnmd isoform may help us to better understand regulation of tenocyte proliferation, tendon development, response to injury and strain, as well as mechanisms in tendinoses. These results may indicate novel therapeutic targets in specific tenomodulin isoforms as well as treatments for tendon diseases.

Polychlorinated biphenyl serum concentrations, lifestyle and time-to-pregnancy.

BACKGROUND: Consumption of fish contaminated with polychlorinated biphenyls (PCBs) and prenatal PCB serum concentrations have been associated with a longer time-to-pregnancy (TTP). However, the relationship between preconception serum PCBs concentrations and TTP has not been previously studied. METHODS: Eighty-three women (contributing 442 menstrual cycles) planning pregnancies completed daily diaries regarding menstruation, intercourse, home pregnancy test results, and reported use of alcohol and cigarettes. TTP denoted the number of observed menstrual cycles required for pregnancy. Preconception blood specimens underwent toxicologic analysis for 76 PCB congeners via gas chromatography with electron capture; serum lipids were quantified with enzymatic methods. A priori, PCB congeners were summed into a total and three groupings-estrogenic, anti-estrogenic and other-and entered into discrete analogs of Cox models with time-varying covariates to estimate fecundability odds ratios (FOR) and corresponding 95% confidence intervals (CIs). RESULTS: Estrogenic and anti-estrogenic PCB concentrations (ng/g serum) conferred reduced FORs in fully adjusted models (0.32; 95% CI 0.03, 3.90 and 0.01: 95% CI < 0.00, 1.99, respectively). Reduced FORs (0.96) were observed for alcohol consumption standardized to a 28-day menstrual cycle in the same adjusted model (FOR = 0.96; 95% CI 0.93, 1.00). CONCLUSIONS: These data suggest that environmental exposures including those amenable to change, such as alcohol consumption, may impact female fecundity. The findings are sensitive to model specification and PCB groupings, underscoring the need to further assess the impact of chemical mixtures on sensitive reproductive outcomes, such as TTP, especially in the context of lifestyle factors which are amenable to change, thereby improving reproductive health.

The utility of neural network in the diagnosis of Cheyne-Stokes respiration.

The aim of this study was to design a diagnostic model to identify patients with Cheyne-Stokes respiration (CSR-CSA) based on indices of oximetric spectral analysis. A retrospective analysis of oximetric recordings of 213 sleep studies conducted over a one-year period at a Veterans Affairs medical facility was performed. A probabilistic neural network (PNN) was developed from salient features of the oximetric spectral analysis, desaturation events and the delta index. A fivefold cross-validation was used to assess the accuracy of the neural network in identifying CSR-CSA. When compared to overnight polysomnography, the PNN achieved a sensitivity of 100% (95% confidence interval [CI] 85%-100%) and a specificity of 99% (95% 97%-100%) with a corresponding area under the curve of 99% (95% CI 99%-100%). When combined with overnight pulse oximetry, PNN offers an accurate and easily applicable tool to detect CSR-CSA.

Early computed tomography hypodensity predicts hemorrhage after intravenous tissue plasminogen activator in acute ischemic stroke.

Parenchymal hypodensity is a proposed risk factor for hemorrhage after recombinant tissue plasminogen activator (TPA) thrombolysis for ischemic stroke. In Buffalo, NY, and Houston, TX, the authors reviewed 70 patients who were treated with intravenous TPA for acute middle cerebral artery (MCA) stroke. Two observers blinded to clinical outcome analyzed initial noncontrast head computed tomography (CT) scans. Basal ganglia CT hypodensity was quantitated in Hounsfield units (HUs). Contralateral-ipsilateral difference in density was calculated using the asymptomatic side as a control. Ictus time to TPA averaged 2.5 hours. Six patients developed symptomatic intraparenchymal hematomas (2 fatal). The hemorrhage group had more severe basal ganglia hypodensity (mean 7.5 +/- 1.4, range 6-10 HU) than the nonhemorrhage group (2.2 +/- 1.4, range 0-9 HU) (P < .0001). The hemorrhage group had hypodensity of > 5 HU; the nonhemorrhage group had hypodensity of < or = 4 HU, except 1 patient with hypodensity of 9 HU. In predicting hemorrhage, the positive predictive value of hypodensity > 5 HU was 86%; the negative predictive value was 100%. Prethrombolysis NIH Stroke Scale (NIHSS) deficit (P = .0007) and blood glucose (P = .005) were also higher in the hemorrhage group. Age, gender, smoking, hypertension, and ictus time to TPA infusion did not differ between the 2 groups. Logistic regression indicated that basal ganglia hypodensity was the best single predictor of hemorrhage. Hypodensity and NIHSS score together predicted all cases of hemorrhage. The authors conclude that basal ganglia hypodensity quantified by CT may be a useful method of risk stratification to select acute MCA stroke patients for thrombolytic therapy.

Gray matter T2 hypointensity is related to plaques and atrophy in the brains of multiple sclerosis patients.

Cortical and subcortical gray matter hypointensities on T2-weighted MR images (T2WI) occur commonly in MS brains and have been related to disease duration, clinical course, and the level of neurologic disability. These hypointensities have been reported to occur in the thalamus, basal ganglia, and rolandic cortex. We assessed whether T2 hypointensity is associated with the severity of white matter plaques and atrophy of MS brains. In 114 MS patients, hypointensity of the thalamus, putamen, caudate, and sensorimotor cortex was ordinally rated against age- and gender-matched normal controls on 1.5-T MRI fast spin-echo axial T2WI. Regional and global T2 hyperintense and T1 hypointense parenchymal lesion loads were ordinally rated. Enlargement of subarachnoid and ventricular spaces (atrophy) was ordinally rated vs. age- and gender-matched normal controls. T2 hypointensity was highly, positively correlated with many other MRI variables. Regression modeling showed that T2 hypointensity was related to total atrophy, total T2 lesion load, third ventricular enlargement, parietal atrophy, and to a lesser extent, frontal T1 lesions and cerebellar T2 lesions, but not related to gadolinium enhancement. Ordinal ratings of T2 lesions and central atrophy showed high correlations with quantitative computerized assessments. We conclude that gray matter hypointensity on T2WI may reflect pathologic iron deposition and brain degeneration in MS. This T2 hypointensity is associated with brain atrophy and other MR markers of tissue damage. Further study is warranted to determine if T2 hypointensity is predictive of disease course in MS and is a useful surrogate outcome measure in therapeutic trials.

Parental consumption of contaminated sport fish from Lake Ontario and predicted fecundability.

Wildlife studies suggest that consumption of contaminated fish from the Great Lakes may expose humans to polychlorinated biphenyls and persistent chlorinated pesticides. To assess whether time to pregnancy or fecundability is affected, we conducted a telephone survey in 1993 with female members of the New York State Angler Cohort Study who were considering pregnancy between 1991 and 1994 (N = 2,445). Among the 1,234 (50%) women who became pregnant, 895 (73%) had a known time to pregnancy. Upon enrollment into the cohort in 1991, both partners reported duration and frequency of Lake Ontario sport fish consumption. We estimated lifetime exposure to polychlorinated biphenyls from recent consumption and used a discrete-time analog of Cox proportional hazards analysis to estimate conditional fecundability ratios and 95% confidence intervals (CIs) for fish consumption among couples with complete exposure data who discontinued birth control to become pregnant (N = 575). Maternal consumption of fish for 3-6 years was associated with reduced fecundability (fecundability ratio = 0.75; 95% CI = 0.59-0.91), as was more than a monthly fish meal in 1991 (fecundability ratio = 0.73; 95% CI = 0.54-0.98). Our findings suggest that maternal but not paternal consumption of contaminated fish may reduce fecundability among couples attempting pregnancy.

Fatigue in multiple sclerosis and its relationship to depression and neurologic disability.

We studied multiple sclerosis fatigue (MSF) and its relationship to depression and disability. Seventy-one patients [50 relapsing-remitting, 21 secondary progressive] were grouped by Fatigue Severity Scale (FSS) into MS-fatigue (MSF) (FSS>/=5; n=46) or MS-nonfatigue (MSNF) (FSS

Double-stranded hamstring tendons for anterior cruciate ligament reconstruction.

Bone-patellar tendon-bone autograft is the most commonly used tissue for ACL reconstruction; however, the harvesting of patellar tendon as a free graft can lead to significant morbidity. Alternate grafts may lower morbidity, yet the most commonly used alternate grafts including the double-stranded semi-tendinosus or gracilis have not been studied biomechanically. This study investigated the morphometric and biomechanical properties of double-stranded semi-tendinosus and gracilis tendons separately along with the patellar and quadriceps tendons obtained bilaterally from six fresh, 77-year-old cadaveric specimens. The quadriceps tendon was the thickest and therefore had the largest cross-sectional area, whereas double-stranded semitendinosus had the highest mean peak load to failure (1029+/-158.4 N), 11.5% and 10.3% stronger than patellar tendon and quadriceps tendons, respectively. Midsubstance rupture occurred in the hamstring tendons, whereas the patellar and quadriceps tendons failed at the bone-tendon junctions. Semitendinosus tendons with higher cross-sectional area had higher peak loads to failure. This linear relationship between cross-sectional area and the peak load to rupture also was observed in the other tendon groups (except gracilis). These results indicate that despite a lower cross-sectional area of the double-stranded semitendinosus, this tendon demonstrated a comparable mean peak load to rupture and stress compared with patellar and quadriceps tendons. It also was demonstrated that combined double-stranded semitendinosus and gracilis tendons produce a stronger graft with initial strength twice that of the patellar tendon, but requires further testing.

Influence of family history on clinical expression of Tourette's syndrome.

OBJECTIVE: To determine the influence of family history on clinical expression of Tourette's syndrome (TS). BACKGROUND: Recent studies have suggested that clinical expression of TS is similar among sporadic (SP) and familial patients but may be influenced by bilineal (BIL) transmission of tics or obsessive-compulsive behavior (OCB) in high-density pedigrees. METHODS: The authors used family history methodology, supported by direct examination of affected relatives in 73% of familial patients, to determine the frequency of SP TS, and of unilineal (UNL) and BIL transmission of tics or OCB in 111 consecutively ascertained juvenile TS patients. For individuals in each group, severity of tics, attention deficit hyperactivity disorder (ADHD), and OCB were assessed at presentation and after a mean follow-up interval of 2.6 years, using the Tourette's Syndrome Global Scale and the Clinical Global Impression scales. The phenomenology of OCB was evaluated using the symptom checklist of the Children's Yale-Brown Obsessive Compulsive Scale. RESULTS: The authors documented BIL transmission of tics in seven patients (6%). Patient age and sex were similar for the SP (n = 21; 19%), UNL (n = 66; 59%), and BIL (n = 24; 22%) groups, as was ADHD and tic severity at presentation and follow-up. Severity of OCB differed significantly between groups, with moderate to severe OCB affecting 5% of SP, 12% of UNL, and 37% of BIL patients at presentation (p = 0.007), and 5% of SP, 17% of UNL, and 54% of BIL patients at follow-up (p = 0.0001). Relative to UNL or SP patients, BIL patients were more likely to exhibit self-injurious behaviors (p = 0.0005). CONCLUSIONS: OCB is less prominent in SP than in familial TS, perhaps reflecting a more restricted pathophysiology in this subgroup. Although BIL transmission of tics is relatively infrequent in consecutive TS pedigrees, cotransmission of OCB from an otherwise unaffected parent is common and significantly influences development of OCB and self-injurious behaviors, but not tics, in offspring. Genetic heterogeneity, epigenetic factors, and gene-environment interactions may play a more important role than genetic dosage effects in determining tic severity in TS.

Mechanism controlling sleep organization of the obese Zucker rats.

We tested the hypothesis that the obese (fa/fa) Zucker rat has a sleep organization that differs from that of lean Zucker rats. We used the polygraphic technique to identify and to quantify the distribution of the three main states of the rat: wakefulness (W), non-rapid-eye-movement (NREM), and rapid-eye movement (REM) sleep states. Assessment of states was made with light present (1000-1600), at the rats thermoneutral temperature of 29 degrees C. Obese rats, compared with lean ones, did not show significant differences in the total time spent in the three main states. Whereas the mean durations of W and REM states did not differ statistically, that of NREM did (P = 0.046). However, in the obese rats, the frequencies of switching from NREM sleep to W, which increased, and from NREM to REM sleep, which decreased, were statistically significantly different (P = 0.019). Frequency of switching from either REM or W state was not significantly different. We conclude that sleep organization differs between lean and obese Zucker rats and that it is due to a disparity in switching from NREM sleep to either W or REM sleep and the mean duration of NREM sleep.

Fatty acid composition of the subcutaneous adipose tissue and risk of proliferative benign breast disease and breast cancer.

BACKGROUND: Studies in animals and geographic correlations across populations suggest that fatty acid intake may have a positive relationship with breast cancer risk, but analytic epidemiologic studies of fat intake have been less supportive. Adipose tissue analysis provides a more objective assessment of intakes of fatty acids that are not endogenously synthesized than do the questionnaire survey methods used in many epidemiologic studies. PURPOSE: This case-control study of postmenopausal women was designed to examine the relationship between fatty acid composition of subcutaneous adipose tissue and risk of breast cancer and proliferative benign breast disease. In addition, we examined specific hypotheses that breast cancer risk is negatively associated with long-chain N-3 fatty acid intake, positively associated with trans fatty acid intake, and positively associated with increased intake of polyunsaturated fat together with low intake of antioxidants. METHODS: Aspirates of subcutaneous fat from the buttocks were obtained from 380 women with newly diagnosed stage I or II breast cancer and 176 with proliferative benign breast disease. A total of 397 women who were evaluated for breast abnormalities at the same institutions but did not require breast biopsy or whose biopsy revealed nonproliferative benign breast disease served as the control group. We examined associations between saturated, monounsaturated, polyunsaturated, trans, or long-chain N-3 fatty acids and breast cancer, atypical hyperplasia, or proliferative benign breast disease without atypia. RESULTS: We observed no consistent patterns of association between breast cancer risk and any of the categories of fatty acids or the individual constituent fatty acids in the adipose tissue. Saturated fatty acids were inversely associated with risk of proliferative benign breast disease without atypia but not with atypical hyperplasia or breast cancer. This association was not observed, however, when total fat intake was taken into account. Women with high levels of polyunsaturated fatty acids in adipose tissue and low serum or dietary levels of antioxidants were not observed to be at higher risk of breast cancer. CONCLUSIONS: Using an objective measure of intake, we observed no major associations between polyunsaturated fatty acids, including long-chain N-3 fatty acids and trans fatty acids, and risk of breast cancer or proliferative benign breast disease. IMPLICATIONS: These data do not support the hypothesis that intake of specific fatty acids, particularly polyunsaturated and trans fatty acids, is an important risk factor for malignant or benign breast disease.

Carotenoids, retinol, and vitamin E and risk of proliferative benign breast disease and breast cancer.

We investigated the relationship between serum levels of retinol, beta-carotene, alpha-carotene, lycopene, alpha-tocopherol, and gamma-tocopherol as well as intakes of retinol, carotene, and vitamin E and the risks of breast cancer and proliferative benign breast disease (BBD) in a case-control study of postmenopausal women in the Boston, MA (United States) area. Serum nutrient data were available for 377 women with newly diagnosed stage I or II breast cancer and 173 women with proliferative BBD. Controls were 403 women who were evaluated at the same institutions but did not require a breast biopsy or whose biopsy revealed nonproliferative BBD. We observed no significant associations between serum levels of these micronutrients and risk of proliferative BBD or breast cancer. The risk of breast cancer was decreased among women in the highest quintile of intake of vitamin E from food sources only (odds ratio [OR] for the highest quintile = 0.4, 95 percent confidence interval [CI] = 0.2-0.9; P, trend across quintiles = 0.02) but less so for total vitamin E intake including supplements (OR = 0.7, CI = 0.4-1.3; P, trend = 0.07).

Cerebral surface pH changes during asphyxia, hypotension, and circulatory arrest in the dog.

A technic is described for the measurement of cerebral surface pH in acute experiments in anesthetized dogs. During asphyxia and circulatory arrest, cerebral surface pH fell promptly and more profoundly than arterial blood or muscle surface pH; during hypovolemic hypotension (30 to 50 torr) cerebral surface pH declined later and less than muscle surface pH. The cerebral surface pH reflects the pH of the cortical interstitial fluid. Since the blood brain barrier is effectively impermeable to lactate, the changes recorded in the cerebral surface pH are a useful index of cortical intracellular metabolism.

The relationship between muscle surface pH and oxygen transport.

The relationship between muscle surface pH (pHM) and the arterial-venous oxygen content difference (AVO2D) was studied in 4 patients undergoing reconstructive arterial surgery and in 6 patients undergoing acute normovolemic hemodilution. There was a consistent inverse relation between pHM in the ischemic lower extremity and the femoral AVO2D before, during and after aortic clamping. There was also an inverse relation between AVO2D and pHM during hemodilution. These data confirm that pHM is a reliable indicator of tissue perfusion and correlates with the AVO2D.