Biomedical subjects

Nira Koren-Morag

Publications and source records attributed to Nira Koren-Morag.

16 recordsLinked to original sources

PubMed2006

Renal dysfunction and risk of ischemic stroke or TIA in patients with cardiovascular disease.

BACKGROUND: Mild renal insufficiency is increasingly recognized as an independent risk factor for cardiovascular disease. However, few data exist regarding its relation to risk of ischemic stroke. METHODS: Patients with chronic coronary heart disease and measured serum creatinine levels (n = 6,685) were followed up for incident ischemic stroke or TIA over 4.8 to 8.1 years. Glomerular filtration rate was estimated by the Cockroft-Gault equation and by the four-component Modification of Diet in Renal Disease (MDRD) equation and a rate < or =60 mL/minute/1.73 m2 defined chronic kidney disease (CKD). RESULTS: Among 6,685 patients, a quarter of patients had CKD. Adjusting for conventional risk factors and related medications, patients with CKD exhibited 1.54-fold hazard ratios (95% CI 1.13 to 2.09) of incident ischemic stroke or TIA by the Cockroft-Gault equation (1.53; 95% CI 1.16 to 2.01 by the MDRD equation). The corresponding adjusted hazard ratio associated with an increment of 1 SD in GFR was 0.71 (95% CI 0.57 to 0.88) when estimated by the Cockroft-Gault equation (0.84; 95% CI 0.75 to 0.95 estimated by the MDRD equation). CONCLUSIONS: Mild degrees of renal dysfunction are associated with increased risk of incident ischemic stroke or TIA in patients with pre-existing atherothrombotic disease. These findings expand the recommendation that patients with renal dysfunction should be considered as a high-risk group for cardiovascular disease and for ischemic stroke.

Age Distribution↗

PubMed2006

Impact of methionine synthase gene and methylenetetrahydrofolate reductase gene polymorphisms on the risk of sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss (SSNHL) represents a frequently encountered otological disease of unknown etiology. In recent years, several inherited risk factors have been found in the pathogenesis of vascular diseases. In the present study, we determined whether specific polymorphism or the combination of polymorphisms in folate-dependent homocysteine metabolism genes can act as predisposing inherited vascular risk factors in the development of SSNHL. We conducted a prospective case-control study using DNA samples extracted from 81 patients diagnosed as suffering from SSNHL and 264 healthy control subjects. Three functional polymorphisms were analyzed by polymerase chain reaction amplification, restriction enzyme digestion, and DNA fragment separation by electrophoresis: methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C, and methionine synthase (MTR) A2756G polymorphisms. The prevalence of the homozygous genotype of MTR 2756GG in the SSNHL patients (9%) was significantly higher than in the control group (4%) (p = 0.011). The allelic frequency of the G allele of the MTR A2756G polymorphism among SSNHL patients (12.5%) was also significantly higher than in the control group (5%) (p = 0.033). The prevalence of patients possessing two polymorphisms (31%) and three polymorphisms (17%) in the SSNHL group was significantly higher than in the control group (23 and 9%, respectively; p = 0.019). The frequency of patients with a very high rank risk (double homozygous) was significantly higher in the SSNHL group, MTHFR 677TT/MTR 2675GG--7%, than the frequency of patients in the control group, MTHFR 677TT/MTR 2675GG--3% (p = 0.030). Certain polymorphisms in genes encoding enzymes in the folate-dependent homocysteine metabolism are associated with SSNHL. In our case-control study, a significant association between MTR 2756GG genotype and SSNHL was found which may represent an inherited vascular risk factor in the pathogenesis of SSNHL.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2006

TH1/TH2 cytokine balance in patients with both type 1 diabetes mellitus and asthma.

BACKGROUND AND OBJECTIVE: T1DM and asthma are mediated by opposite arms of the cellular immune system namely T helper (Th)1 and Th2 CD4(+) cells, respectively. Our aim was to characterize the Th1/Th2 cytokine balance in patients with both T1DM and asthma. METHODS: Forty-four patients, mean age 19 years were matched by gender and age, to 4 paired groups: T1DM and asthma, asthma only, T1DM only and healthy controls. Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with disease-specific recombinant antigens; glutamic acid decarboxylase and house dust mite (Der p1 antigen) for T1DM and asthma, respectively, and non-specific mitogens; phytohemaglutinin (PHA), tetanus toxin and anti-CD3 mAb. ELISPOT and ELISA technique were used to determine INF-gamma, IL-2, IL-4, IL-13 and IL-10 expression. RESULTS: Patients with T1DM and asthma demonstrated a similar cytokine pattern but lower Th1/Th2 ratio compared to patients with T1DM only. The Th2 cytokines response to Der p1 was enhanced in patients with both diseases compared to controls. The IL-10 overall secretion was higher in patients with both diseases compared to one disease only. CONCLUSION: The Th1 and Th2 secretory pattern of patients with T1DM and asthma combines features of both diseases suggesting a unique Th1/Th2 balance.

Adolescent↗

PubMed2006

Long-term versus intermediate-term supervised exercise training in advanced heart failure: effects on exercise tolerance and mortality.

AIM: To date there have been no studies exploring the effects of long-term versus intermediate-term and short-term supervised exercise training program in patients with severe chronic heart failure (CHF) on optimal medical therapy. We assessed exercise tolerance and mortality in CHF patients undergoing long- versus intermediate-term exercise training (ET). METHODS: Forty-two consecutive severe CHF patients (New York Heart Association functional class III) were referred for a supervised exercise and cardiac rehabilitation program and were followed-up for 3 years: 20/42 (48%) patients discontinued ET after intermediate-term period of 1.6+/-0.8 years (Group A, intermediate-term ET), and 22/42 (52%) remained on the ET program for 3.0+/-0.3 years (Group B, long-term ET). Exercise duration, 6-min walked distance and metabolic equivalents (METs) assessed by modified Bruce protocol were recorded before, 4.5 months after, and 3 years after initiation of ET. RESULTS: Both groups were comparable regarding age, gender, prevalence of ischemic etiology, mean ejection fraction and medications. Risk factors for ischemic heart disease were similar, except for the prevalence of diabetes, which was higher in Group A compared to Group B (11/20 versus 5/22, p=0.03). Significantly more Group A patients died after ET discontinuation (4/20 versus 0/22, p=0.01). At the end of follow-up a significant improvement could be seen in Group B patients compared to A in exercise duration, 6-min walked distance and metabolic equivalents (p<0.01 for all). CONCLUSIONS: Higher survival rate was observed in severe CHF patients undergoing long-term versus intermediate-term exercise training. Long-term supervised exercise training is safe and improves exercise tolerance in these patients.

Exercise Therapy↗

PubMed2006

A national survey of acute cerebrovascular disease in Israel: burden, management, outcome and adherence to guidelines.

BACKGROUND: There are no national data on the burden and management of acute cerebrovascular disease in Israel. OBJECTIVES: To delineate the burden, characteristics, management and outcomes of hospitalized patients with acute cerebrovascular disease in Israel, and to examine adherence to current guidelines. METHODS: We prospectively performed a national survey in all 28 hospitals in Israel admitting patients with acute cerebrovascular events (stroke or transient ischemic attacks) during February and March 2004. RESULTS: During the survey period 2174 patients were admitted with acute cerebrovascular disease (mean age 71 +/- 13 years, 47% women; 89% ischemic stroke or TIA, 7% intracerebral hemorrhage and 4% undetermined stroke). Sixty-two percent of patients were admitted to departments of medicine and a third to neurology, of which only 7% were admitted to departments with a designated stroke unit. Head computed tomography was performed during hospitalization in 93% of patients. The overall rate of urgent thrombolytic therapy for acute ischemic stroke was 0.5%. Among patients with ischemic stroke or TIA, 94% were prescribed an antithrombotic medication at hospital discharge, and among those with atrial fibrillation about half were prescribed warfarin. Carotid duplex was performed in 30% and any vascular imaging study in 36% of patients with ischemic events. The mean (+/-SD) length of hospital stay was 12 +/- 27 days for ICH and 8 +/- 11 days for ischemic stroke. Among patients with ICH, 28% died during hospitalization and 66% died or remained with severe disability while for ischemic stroke the corresponding rates were 7% and 41% respectively. Mortality rates within 3 months were 34% for ICH and 14% for ischemic stroke. CONCLUSIONS: This national survey demonstrates the high burden of acute stroke in Israel and reveals discordance between existing guidelines and current practice. The findings highlight important areas for which reorganization is imperative for patients afflicted with acute stroke.

Acute Disease↗

PubMed2005

Family history, plasma homocysteine, and age at onset of symptoms of myocardial ischemia in patients with different methylenetetrahydrofolate reductase genotypes.

A high plasma homocysteine level is associated with early onset of coronary artery disease (CAD), particularly in homozygotes for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. Family history is a predictor of increased plasma homocysteine and may be involved in early-onset CAD. This study examined the relations among family history, plasma homocysteine, and age at onset of CAD, and the role of the MTHFR genotype in this context. We screened 284 patients who developed first symptoms of CAD at < or =65 years of age for fasting plasma homocysteine and the C677T mutation. On multiple regression analysis, homocysteine, family history, male gender, and smoking were independently associated with age at onset of CAD. However, separate analysis of patients who had the MTHFR 677 T/T genotype (n = 57) and those who did not (n = 209) showed that plasma homocysteine and family history were associated with earlier onset of CAD only in T/T homozygotes and that family history in patients who had this genotype was also associated with higher plasma homocysteine levels and a stronger association between plasma homocysteine and age at onset of CAD. In patients who had other genotypes, these associations were not observed, and earlier onset of CAD was associated only with male gender and smoking. Thus, the MTHFR genotype modifies the effects of family history and other risk factors on age at onset of CAD. In T/T homozygotes, family history is associated with earlier onset of CAD, higher plasma homocysteine levels, and a stronger association between plasma homocysteine and age at onset of CAD.

Age of Onset↗

PubMed2005

Pretreatment with corticosteroids attenuates the efficacy of colchicine in preventing recurrent pericarditis: a multi-centre all-case analysis.

AIMS: Effective prevention of recurrent pericarditis remains an important yet elusive goal. Corticosteroid therapy often needs to be continued for a prolonged period and causes severe side effects. We performed a multi-centre all-case analysis to investigate the efficacy of colchicine in preventing subsequent relapses of pericarditis, and addressed the hypothesis that pretreatment with corticosteroids may attenuate the beneficial effect of colchicine. METHODS AND RESULTS: One hundred and forty published and unpublished cases of patients treated with colchicine after at least two relapses of pericarditis were aggregated from European centres. Of those, 119 were included in the study group. Only 18% of the patients had relapses under colchicine therapy, and 30% after its discontinuation. There were significantly more relapses among male patients after colchicine treatment (36 vs. 17%, P=0.046), and those with previous corticosteroid treatment (43 vs. 13%, P=0.02). Multivariate logistic regression analysis identified previous corticosteroid therapy (OR 6.68, 95% CI: 1.65-27.02) and male gender (OR 4.20, 95% CI: 1.16-15.21) as independent risk factors for recurrence following colchicine therapy. CONCLUSION: Treatment with colchicine is highly effective in preventing recurrent pericarditis, while pretreatment with corticosteroids exacerbates and extends the course of recurrent pericarditis.

Adolescent↗

PubMed2005

White blood cell count and the incidence of ischemic stroke in coronary heart disease patients.

PURPOSE: White blood cell (WBC) count is a marker of inflammation and has been associated with the development of cardiovascular disease. We investigated the relationship between WBC counts and the incidence of ischemic cerebrovascular disease in a large cohort of patients with pre-existing atherothrombotic disease and defined blood lipid boundaries. SUBJECTS AND METHODS: We followed up patients with documented coronary heart disease for 4.8 to 8.1 years. An extensive medical evaluation, conducted at baseline, included assessment of vascular risk factors and measures of blood lipids. Among 5435 patients with WBC counts, free of stroke, 295 developed an ischemic cerebrovascular disease (fatal and nonfatal). After review of available medical records, 186 of these cases had ischemic stroke or TIA. RESULTS: Higher WBC counts were associated with increased risk for ischemic cerebrovascular disease. Age-adjusted hazard ratio (HR) was 1.55 with 95% confidence interval (CI) 1.16-2.07, upper WBC tertile compared with the lowest. Adjusting for clinical covariates, WBC count remained an independent predictor for ischemic cerebrovascular disease (HR = 1.39; 95% CI 1.03-1.87, upper WBC tertile compared with the lowest). A similar trend appeared for the endpoint of ischemic stroke/transient ischemic attack (TIA). Further adjustment for plasma fibrinogen did not change the association materially (HR = 1.32; 95% CI 1.01-1.80; upper tertile of WBC compared with lowest). CONCLUSIONS: These findings support the role of WBC count as a simple inexpensive and readily available marker for risk stratification of ischemic cerebrovascular disease among patients with pre-existing atherothrombotic disease and defined blood lipid boundaries.

Aged↗

PubMed2005

Poor nutritional habits are predictors of poor outcome in very old hospitalized patients.

BACKGROUND: Malnutrition is prevalent in elderly populations. Recommended methods of nutritional screening are often too complicated and time-consuming for routine application in frail, very old, hospitalized patients. OBJECTIVE: Our aims were to identify risk factors for development of malnutrition in very old hospitalized patients and to evaluate the total Mini Nutritional Assessment (MNA) score and MNA subscores as predictors of in-hospital and long-term mortality. DESIGN: A prospective cohort study of patients aged > or =75 y was conducted in a geriatric hospital. Assessment included demographic, clinical, and laboratory data and cognitive, functional, and nutritional status. Follow-up was conducted for < or =2.7 y. RESULTS: Of the 414 patients studied, only 73 (17.6%) were well-nourished. Low serum albumin and phosphorus concentrations, dementia, and cerebrovascular accident (CVA) were significant risk factors for malnutrition. Survival was significantly lower in malnourished patients and patients at risk of malnutrition than in well-nourished patients (P < 0.0001). Low MNA-3 subscores (dietary habits) were significantly correlated with laboratory indexes of malnutrition and were significantly lower in patients with infections, malignancy, pressure ulcers, dementia, recent orthopedic surgery, and CVA. Multivariate analysis showed that a low MNA-3 score was an independent predictor of mortality; scores <7.5 increased the risk of death 2.05-fold. CONCLUSIONS: The prevalence of malnutrition was high in elderly hospitalized patients. Dietary habits were significant predictors of poor hospitalization outcome. A questionnaire on dietary habits can serve as a useful tool in assessing nutritional status and prognosis in elderly patients.

Aged↗

PubMed2005

Coronary artery calcium measurement with multi-detector row CT and low radiation dose: comparison between 55 and 165 mAs.

PURPOSE: To prospectively compare the results of coronary artery calcium (CAC) measurements obtained with 55- and 165-mAs electrocardiographically gated multi-detector row computed tomography (CT). MATERIALS AND METHODS: Institutional clinical study review board approval and written informed consent were obtained. Fifty-one consecutive subjects (mean age, 59 years +/- 10) were scanned consecutively by using 165 and 55 mAs. For each examination, the number of lesions, total calcium score (TCS) calculated with Agatston algorithm (130-HU threshold), and calcium mass (in milligrams) were measured. Noise was measured by averaging 1 standard deviation of the CT attenuation values in five consecutive transverse sections of the ascending aorta. Paired t test and Pearson correlation were used to compare measurements between the examinations. RESULTS: By using 55 mAs, CAC was detected (TCS > 0) in all 33 subjects in whom CAC was initially detected with 165 mAs. The mean values of CAC measures with 165 and 55 mAs, respectively, were as follows: number of lesions, 6.2 +/- 9.6 and 6.1 +/- 9.4; TCS, 123 +/- 223 and 126 +/- 225; and calcium mass, 23.25 mg +/- 43 and 24.25 mg +/- 44 (P value was not significant for all parameters). Significant high correlation was found between the two methods for all measures (r > 0.90, P < .01). Similar results were obtained with analysis by coronary vessel. Image noise was 9.3 HU +/- 2.1 with 165 mAs and 14.7 HU +/- 3.9 with 55 mAs (P < .001), with a parallel decrease in the volume CT dose index from 12 to 4 mGy. CONCLUSION: Radiation dose can be reduced (eg, 55 mAs) for CAC detection and measurement at multi-detector row CT and provides results comparable to those obtained with 165 mAs.

Adult↗

PubMed2004

Resumption and maintenance of employment after a first acute myocardial infarction: sociodemographic, vocational and medical predictors.

In a community cohort of 833 women and men aged <60 years, employed at the time of a first acute myocardial infarction (AMI), the relation of sociodemographic, vocational, and medical variables to the following three aspects of employment was investigated longitudinally: resumption of employment anytime within 5 years after AMI, resumption of employment within 3 months of the AMI, and maintenance of employment 5 years after AMI. Different sets of characteristics of persons with a first AMI were related to the different criteria of employment. Only sociodemographic and vocational variables were related to early resumption of employment, whereas maintenance of employment 5 years after AMI was influenced by both medical and nonmedical variables. These results support the importance of examining different aspects of resumption and maintenance of employment after AMI. They also suggest that early resumption of employment after AMI and employment anytime 5 years after AMI are more a function of the sociodemographic and vocational characteristics of the person with the AMI than of that person's medical condition, whereas long-term maintenance of employment after an AMI is also related to the person's medical condition.

Age Factors↗

PubMed2004

Accelerated progression of coronary calcification: four-year follow-up in patients with stable coronary artery disease.

PURPOSE: To prospectively assess the 4-year progression rate of coronary artery calcium (CAC) in patients with clinically stable coronary artery disease (CAD) with multi-detector row computed tomography (CT). MATERIALS AND METHODS: The study group consisted of 382 consecutive patients. All underwent baseline dual-sector spiral CT, and CT was repeated at 2 and 4 years later. Progression of CAC was assessed with measurement of the increase in total calcium score (TCS) and with repeated-measures analysis and multivariate linear regression models. Logistic regression model was used to predict incidence of new lesions. RESULTS: Eighty-seven percent (333 of 382) of the study group were men, with mean age of 65 years +/- 11, and 13% (49 of 382) were women, with mean age of 68 years +/- 11. The average TCS increased after 4 years by sixfold from baseline in the 1st quartile, and by four-, two- and 1.5-fold in the 2nd, 3rd, and 4th quartiles of baseline TCS (P <.01), respectively. Multiple linear regression analysis included age; sex; natural logarithm of baseline TCS; history of hypertension, diabetes mellitus, current smoking, hypercholesterolemia, and lipid-lowering therapy with cholesterol synthesis enzyme inhibitor (statin); and family history of premature CAD. Results demonstrated that natural logarithm of baseline TCS and history of current smoking were independent predictors of the 4th-year natural logarithm of TCS levels (R(2) = 0.85, P <.001). New lesions were diagnosed in 56 (15%) patients. History of statin therapy (odds ratio = 0.35; 95% confidence interval [CI]: 0.16, 0.77; P <.01), age with an increment of 5 years (odds ratio = 0.76; 95% CI: 0.64, 0.90; P =.01), and natural logarithm of baseline TCS (odds ratio = 0.73; 95% CI: 0.62, 0.86; P <.01) were independent predictors for new calcific lesions during 4 years. CONCLUSION: Accelerated progression of CAC during 4 years was found in clinically stable patients with CAD.

Aged↗

PubMed2004

Fasting plasma glucose and risk of incident ischemic stroke or transient ischemic attacks: a prospective cohort study.

BACKGROUND AND PURPOSE: Diabetes and impaired fasting glucose are diagnosed based on an elevated plasma glucose level after an overnight fast. The diagnostic cutpoint of diabetes arises from the threshold for development of microvascular complications. Our aim was to examine the associations between clinical relevant categories of fasting glucose levels and the risk of incident ischemic stroke. METHODS: Patients with documented coronary heart disease who were screened for inclusion in a secondary prevention clinical trial (n=13,999) were followed-up. At baseline, medical histories were obtained and plasma glucose and lipids assessed at a central study laboratory. During a 6- to 8-year follow-up period 1037 cases were identified with ischemic cerebrovascular disease, of which, after reviewing hospital records with diagnoses of cerebrovascular disease, 576 cases were verified to have had ischemic stroke or transient ischemic attacks. RESULTS: Increasing fasting glucose level categories were positively associated with increasing age, male gender, body mass index, hypertension, total cholesterol, and triglycerides, and were inversely associated with high-density lipoprotein cholesterol and percent high-density lipoprotein of total cholesterol. In comparison with patients with fasting glucose levels of 90 to 99 mg/dL (n=3706) who constitute the largest category, the odds ratios of ischemic cerebrovascular disease, adjusting for potential confounders, were 1.47 (95% CI, 1.07 to 2.02) for fasting glucose <80, 1.22 (0.98 to 1.52) for 80 to 89, 1.27 (1.02 to 1.60) for 100 to 109, 1.60 (1.26 to 2.03) for 110 to 125, 1.82 (1.33 to 2.49) for 126 to 140, and 2.82 (2.32 to 3.43) for >140 mg/dL. Similar J-shaped associations were observed in analysis excluding patients with known diagnosis of diabetes mellitus. CONCLUSIONS: The association between fasting plasma glucose and incident ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease is J-shaped. Rates increase for fasting plasma glucose levels >100 mg/dL and also for those with low fasting glucose levels. These findings may carry important implications for prevention strategies.

Aged↗

PubMed2002

Low- and high-density lipoprotein cholesterol and ischemic cerebrovascular disease: the bezafibrate infarction prevention registry.

BACKGROUND: Despite increasing evidence that beta-hydroxy-beta-methyglutaryl coenzyme A reductase inhibitors reduce the incidence of stroke in patients with coronary heart disease (CHD), the associations between blood lipid levels and cerebrovascular disease (CVD) are not clear. OBJECTIVE: To evaluate whether blood cholesterol level and its fractions are risk factors for stroke in a large group of patients with CHD. METHODS: We followed up 11 177 patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study, a secondary prevention randomized clinical trial of lipid modification, and had no history of stroke for subsequent CVD. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic CVD, of whom 487 had verified ischemic stroke or transient ischemic attack (TIA). RESULTS: Increases in age-adjusted rates of both nonhemorrhagic CVD and verified ischemic stroke or TIA were identified with increasing cholesterol and low-density lipoprotein cholesterol levels, decreasing high-density lipoprotein cholesterol levels, and decreasing percentage of total serum cholesterol contained in the HDL moiety. In logistic regression models, adjusting for clinical covariates, the following odds ratios (95% confidence intervals) were identified for lipid values in the upper vs lower tertile for the end point of nonhemorrhagic CVD: total cholesterol, 1.43 (1.20-1.70); low-density lipoprotein cholesterol, 1.52 (1.27-1.81), high-density lipoprotein cholesterol, 0.84 (0.70-1.00); and percentage of serum cholesterol contained in HDL, 0.69 (0.58-0.83). Similar trends appeared for the end point of verified ischemic stroke or TIA. CONCLUSION: These findings clearly support the role of total cholesterol and its fractions in prediction of ischemic CVD among patients with established CHD.

Adult↗

PubMed2002

Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice: the Multicenter rt-PA Stroke Survey.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (rtPA) is an effective therapy for acute ischemic stroke, but it is associated with risk of intracerebral hemorrhage (ICH). Our aim was to identify, in a large cohort of patients, readily available baseline factors that are associated with thrombolysis-related ICH. METHODS AND RESULTS: In a multicenter retrospective and prospective investigation of individual data from 1205 patients treated in routine clinical practice with intravenous rtPA within 3 hours of stroke symptom onset, 72 patients (6%) developed symptomatic ICH and 86 additional patients (7%) had asymptomatic ICH identified on a routine follow-up CT. In analyses based on clinical variables alone, the main attributes associated with ICH were a history of diabetes mellitus and cardiac disease, increasing stroke severity, advancing age, use of antiplatelet agents other than aspirin before stroke onset, and elevated pretreatment mean blood pressure. In additional analyses that incorporated baseline CT and laboratory findings (in a subset of patients), the main associations were early ischemic CT changes, in particular if exceeding one third of middle cerebral artery territory; increasing stroke severity; diabetes mellitus or elevated serum glucose; and lower platelet counts. Final independent attributes associated with parenchymatous hematoma, defined by purely radiologically based criteria, were similar to those of symptomatic ICH. CONCLUSIONS: Readily available factors can identify acute ischemic stroke patients at high and low risk for rtPA-related ICH. These factors require confirmation in a prospective cohort before clinical implementation.

Acute Disease↗

PubMed2002

Vitamin D and calcium-sensing receptor genotypes in men and premenopausal women with low bone mineral density.

BACKGROUND: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes involved in osteoporosis have been proposed, but the precise genes and their relative contribution remain unknown. OBJECTIVES: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986S in the calcium-sensing receptor gene. METHODS: We analyzed 86 Jewish Israeli patients with LBMD: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986S polymorphism in the CaSR gene was performed using the denaturing gradient gel electrophoresis technique. RESULTS: In LBMD women the distributions of VDR alleles in Apal polymorphism were AA = 7/28, Aa = 16/28 and aa = 5/28; in Taql polymorphism TT = 10/31, Tt = 16/31 and tt = 5/31; and in Bsml polymorphism BB = 7/32, Bb = 14/32 and 11/32. In LBMD men the distributions were AA = 17/39, Aa = 21/39 and aa = 1/39; in Taql polymorphism TT = 12/42, Tt = 23/42 and tt = 7/42; and in Bsml polymorphism BB = 12/41 Bb = 18/41 and bb = 11/32. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986S polymorphism, compared with 40 of 203 controls (19.7%) (P = 0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD between homozygotes and heterozygotes (p = 0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD. CONCLUSIONS: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well as between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

Adolescent↗