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Biomedical subjects

Edna Schechtman

Publications and source records attributed to Edna Schechtman.

At least 19 recordsLinked to original sources
PubMed2007

Cloprostenol, a prostaglandin F(2alpha) analog, induces hypoxia in rat placenta: BOLD contrast MRI.

Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F(2alpha) (PGF(2alpha)) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprostenol (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by BOLD contrast MRI, in correlation with induction of vascular endothelial growth factor (VEGF) gene (Vegfa) expression in the corresponding placenta (r = 0.56, p = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was also observed at early gestation (day 9) in the forming placenta (p = 0.04) and uterus (p = 0.03). Cloprostenol increased the expression levels of endothelin-1 (ET-1) gene (Edn1) (p = 0.03) and its corresponding peptide (p = 0.02) in the forming placenta, as well as the expression of the endothelin receptor type A (ETA) gene (Ednra) in both the forming placenta (p = 0.009) and the uterus (p = 0.01). The levels of the endothelin receptor type B (ETB) gene (Ednrb) were not affected in response to cloprostenol, but a significant elevation in the expression level of this receptor was observed in the uterus at mid- and late gestation (day 22) (p = 0.04 and 0.01 respectively), suggesting a role for ETB in the vasodilatory status of the pregnant uterus. It is suggested that PGF(2alpha) induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part in mediating this effect, probably via activation of ETA receptor. The uteroplacental vasoconstriction induces hypoxia, as manifested by significant changes in BOLD MRI and by upregulation of VEGF.

Animals↗
PubMed2006

Reduced repair of the oxidative 8-oxoguanine DNA damage and risk of head and neck cancer.

An increasing number of studies indicate that reduced DNA-repair capacity is associated with increased cancer risk. Using a functional assay for the removal of the oxidative DNA lesion 8-oxoguanine by the DNA-repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), we have previously shown that reduced OGG activity is a risk factor in lung cancer. Here, we report that OGG activity in peripheral blood mononuclear cells from 37 cases with squamous cell carcinoma of the head and neck (SCCHN) was significantly lower than in 93 control subjects, frequency matched for age and gender. Retesting of OGG activity 3 to 4 years after diagnosis and successful treatment of 18 individuals who recovered from the disease showed that OGG activity values were similar to those determined at diagnosis, suggesting that reduced OGG activity in case patients was not caused by the disease. Logistic regression analysis indicated that the adjusted odds ratio (OR) associated with a unit decrease in OGG activity was statistically significantly increased [OR, 2.3; 95% confidence interval (95% CI), 1.5-3.4]. Individuals in the lowest tertile of OGG activity exhibited an increased risk of SCCHN with an OR of 7.0 (95% CI, 2.0-24.5). The combination of smoking and low OGG was associated with a highly increased estimated relative risk for SCCHN. These results suggest that low OGG is associated with the risk of SCCHN, and if confirmed by additional epidemiologic studies, screening of smokers for low OGG activity might be used as a strategy for the prevention of lung cancer and SCCHN.

Adult↗
PubMed2006

Education effects on cognitive function in a healthy aged Arab population.

BACKGROUND: The Mini-mental State Examination (MMSE) has not been validated in Arabic speaking populations. The Brookdale Cognitive Screening Test (BCST) has been developed for use in low schooling populations. We investigated the influence of gender, education and occupation in a cognitively normal community sample which was assessed using an Arabic translation of the MMSE and the BCST. METHODS: Cognitively normal subjects (n=266, 59.4% males, mean age (SD): 72.4 (5.5) years) from an Arab community in northern Israel (Wadi Ara) were evaluated. Education was categorized into levels: 1=0-4 years, 2=5-8 years, 3=9-12 years. Effects of gender, education and occupation on MMSE and BCST were analyzed by ANOVA, taking age as a covariate. RESULTS: The mean MMSE score of males [26.3 (4.1)] was higher than that of females [23.6 (4.2) points]. Two-way ANOVA showed a significant interaction between gender and education on MMSE (p=0.0017) and BCST scores (p=0.0002). The effect of gender on MMSE and BCST was significant in education level 1 (p<0.0001, both tests) and level 2 (p<0.05, both tests). For education level 1, MMSE and BCST scores were higher for males, while both scores were higher for females in education level 2. The effect of occupation was not significant for both genders. CONCLUSION: Education and gender influence performance when using the Arabic translation of the MMSE and BCST in cognitively normal elderly. Cognitively normal females with 0-4 years of education scored lower than males. These results should be taken into consideration in the daily use of these instruments in Arabic.

Aged↗
PubMed2006

Development of an enzymatic DNA repair assay for molecular epidemiology studies: distribution of OGG activity in healthy individuals.

While the role of reduced DNA repair in susceptibility to hereditary cancers is well established, its role in sporadic cancer is less understood. One of the reasons is the lack of specific DNA repair assays that are suitable for epidemiology studies. Here we describe the development of the OGG test, an epidemiology-grade enzymatic assay for the activity of the base excision repair enzyme 8-oxoguanine DNA glycosylase, in protein extracts prepared from human blood cells. The assay is robust and reproducible, with a coefficient of variation of 10%. Using the OGG test we determined OGG activity in 120 healthy individuals. Our results show an inter-individual variation of 2.8-fold in OGG activity, from 3.6 up to 10.1units/microg protein, with a mean value of 7.2units/microg protein. There was no significant difference in OGG activity between males and females, or between smokers and non-smokers. Interestingly, there was a gender-specific effect of age: OGG activity was slightly but significantly lower in males older than the age of 55 years compared to younger males, but not in females at the same age groups. Analysis of OGG1 mRNA by quantitative real-time RT-PCR showed a group trend of an increase in OGG enzymatic activity with increasing mRNA expression, but the correlation between activity and mRNA in individuals was poor, indicating the importance of factors other than mRNA expression. The OGG test described is expected to be useful in studying the role of 8-oxoguanine repair in cancer, as recently demonstrated for non-small cell lung cancer [T. Paz-Elizur, M. Krupsky, S. Blumenstein, D. Elinger, E. Schechtman, Z. Livneh, J. Natl. Cancer Inst. 95 (2003) 1312-1319]. In addition, it may serve as a paradigm for the development of additional functional DNA repair tests, which are needed in order to gain further insight into the role of DNA repair in cancer risk and pathology.

Biological Assay↗
PubMed2006

On the similarities between the perception and production of elliptical trajectories.

In an earlier study, Viviani and Stucchi (J Exp Psychol Hum Percept Perform 18:603-623, 1992) have introduced a visual illusion, whereby it was shown that when subjects are asked to determine what movement of a light spot, when tracing an elliptical trajectory, appears to be most uniform, they tend to choose movements that are close to obeying the 2/3 power law (Lacquaniti et al. Acta Psychol 54:115-130, 1983) rather than constant speed movements, even though the actual changes in velocity could exceed 200%. Here we have extended the study of this illusion by directly testing the effect of the shape (eccentricity) and size (perimeter) of the elliptical trajectory, the duration of the tracing of the ellipse and the effect of fixation on the subjects' decision regarding movement uniformity. We found that the ellipse's eccentricity and tracing out speed of the elliptical trajectory significantly affect the subjects' decisions, although the effect of eccentricity seems to be stronger than that of speed. Our findings also indicated that fixation significantly affects the subject's decision for ellipses that are more eccentric. Surprisingly, the ellipse's perimeter had a much smaller effect on the subjects' decisions, although changes in the ellipse's perimeter should have the same effect on the average velocity as changes in the time it takes to trace out the ellipse. This suggested the possibility that the subjects based their decision regarding movement uniformity on other velocity variables in addition to tangential velocity. Computer simulations we have performed have led us to conclude that the subjects' perception of movement uniformity may also be based on assessing the variations in angular velocity and possibly also in affine velocity. Our behavioral and simulation studies thus suggest that the motion perception system is quite responsive to variations in the velocity along an elliptical trajectory but in a way that depends on the path's curvature. Furthermore, the movement is judged to be more uniform when there are minimal differences in angular, tangential and perhaps also in affine velocities, along the trajectory. Our results suggest the existence of similar underlying constraints that affect both the motion perception and production systems when the movements are associated with very large velocities or large changes in velocity along more curved portions of the trajectory. Our observations therefore provide further insight into the possibility that these constraints are either imposed by the underlying neuronal dynamics, the internal architecture of the cortical neural populations or the variables used in the coding of both sensory and motor information regarding movement.

Adolescent↗
PubMed2006

Association between amantadine and the onset of dementia in Parkinson's disease.

The objective of this study is to compare the occurrence of dementia among Parkinson's disease (PD) patients treated with amantadine (AM group) with those never exposed to it (NoAM group). PD dementia shares neuroanatomical and biochemical similarities with Alzheimer's disease (AD). Memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist has been shown to be beneficial in AD. Memantine is a dimethyl derivative of amantadine, which also possesses NMDA receptor blocking properties. We hypothesized that amantadine could have a beneficial effect on the occurrence of PD dementia. PD patients attending the Movement Disorders Clinics in Hillel Yaffe, Asaf Harofe Medical Centers (Israel) and Pisa (Italy) were included. Taking the onset of dementia as the endpoint, survival curves for AM and NoAM patients were estimated by the Kaplan-Meier method. The study population consisted of 593 patients (age, 69.5 +/- 9.9 years; PD duration, 9.2 +/- 6.0 years; 263 patients (44%) amantadine treated). The endpoint of dementia was reached by 116 patients (20%). PD duration until dementia was significantly longer for AM patients (9.1 +/- 5.7 years) than for NoAM patients (5.9 +/- 4.6 years, P = 0.006). The duration of amantadine exposure positively correlated with PD duration until dementia (P = 0.0001). Survival analysis, taking dementia onset as endpoint, showed slower mental decline in AM patients (Log rank P = 0.0049, Wilcoxon P = 0.0024). Mini-Mental State Examination scores were significantly higher for AM patients than for the NoAM group (P = 0.01). Age of PD onset also significantly influenced the duration of PD until dementia. Amantadine use may delay the onset of dementia in PD patients and may attenuate its severity.

Aged↗
PubMed2005

Magnetic resonance imaging reveals functional diversity of the vasculature in benign and malignant breast lesions.

BACKGROUND: Tumor perfusion through the microvascular network can be imaged noninvasively by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The objective of the current study was to quantify the microvascular perfusion parameters in various human breast lesions and to determine whether they varied between benign lesions and malignancy and whether they were altered with increased invasiveness. METHODS: Perfusion parameters in 22 benign fibrocystic changes, 15 ductal carcinomas in situ (DCIS), 30 infiltrating ductal carcinomas (IDC), and 22 fibroadenomas were measured using high-resolution DCE-MRI. Pixel-by-pixel image analysis yielded parametric images of two perfusion indicators: the influx transcapillary transfer constant (k(trans)) and the efflux transcapillary rate constant (k(ep)). Correlations of lesion type and perfusion parameters were calculated using Spearman correlation. Logistic regression analysis evaluated the best predictors of the kinetic parameters that differentiate between IDC and benign lesions. RESULTS: The perfusion parameters exhibited a progressive increase from benign fibrocystic changes to DCIS and IDC, with a significant correlation between lesion type and the parameters' values (range of correlation coefficients, 0.56-0.76; P < 0.0001). In addition, k(trans) increased from low-grade DCIS to high-grade DCIS. Fibroadenomas were characterized uniquely by high k(trans) but low k(ep). Stepwise logistic regression selected k(trans) as the best predictor for distinguishing benign fibrocystic changes from IDC, yielding 93% sensitivity and 96% specificity. CONCLUSIONS: The microvascular perfusion parameters in breast lesions were elevated with invasiveness. Quantification of these parameters using high-resolution DCE-MRI was helpful for differentiating between breast lesions and should improve breast carcinoma diagnosis.

Breast Neoplasms↗
PubMed2005

Association between family history of dementia and hallucinations in Parkinson disease.

OBJECTIVE: To identify familial risk factors for hallucinations in patients with Parkinson disease (PD). METHODS: Two hundred seventy-six outpatients with PD participated in the study. The presence of hallucinations was determined using a validated questionnaire, including items regarding the occurrence of visual, auditory, or other types of hallucinations. Family history of PD and dementia was determined by a structured interview and examination of medical records and affected family members. Patients with young-onset PD (<50 years) who reported another PD patient among their siblings were tested for parkin mutations. Stepwise logistic regression was applied for the detection of risk factors. The regression model included a set of family history-related variables (family history of PD and of dementia) and a set of disease-related variables (age, age at onset of PD, stage, duration of PD and of l-dopa therapy, l-dopa dose, and number of antiparkinsonian drugs). RESULTS: Hallucinations were present in 32% of the 276 patients. Risk factors for hallucinations included Mini-Mental State Examination score (p < 0.0001) and positive family history of dementia (p = 0.0005). CONCLUSION: Family history of dementia and lower Mini-Mental State Examination scores are risk factors for hallucinations in Parkinson disease.

Age Factors↗
PubMed2005

The effect of Center High Mounted Stop Lamp (CHMSL) on rear-end accidents in Israel.

This paper examines the effect of the use of Center High Mounted Stop Lamp (CHMSL) on rear-end accidents, as reflected in Israeli police records from calendar years 1991-2002. The basic analysis, similar to that used in previous CHMSL studies, compares the involvement in accidents of passenger cars of model years 1994-1996 that are equipped with CHMSL with passenger cars of model years 1991-1993 that are not equipped with CHMSL. The number of involvements as the struck vehicle in a rear-end accident was used as the relevant measurement and the number of involvements as the striking vehicle in a rear-end accident was used as the reference measurement. The results yielded an odds ratio of 0.93. The explanation that the CHMSL is responsible for the 7% decrease is intuitively appealing and is consistent with previous findings. However, the strength of this evidence is marginal (p = 0.07). Additional analyses evaluated the model year effect in greater detail, in order to determine whether there exists a change point between 1993 and 1994 as would be expected from a CHMSL effect, or whether the effect is spurious. Detailed analyses were performed on the ratio of struck to striking involvements as well as the rates of involvement of both types. These analyses showed that (1) the chosen reference measurement is an appropriate one, but (2) the 0.93 odds ratio is quite possibly due to other reasons unrelated to the CHMSL, thus further limiting the confidence in CHMSL effectiveness.

Accidents, Traffic↗
PubMed2005

Drug identification performance on the basis of observable signs and symptoms.

A double blind study was performed to evaluate the ability of trained police officers to detect drug impairments and to identify the type of drug responsible for the impairment, on the basis of observed symptoms and psychophysical measurements of performance alone. The officers were not allowed to interview the subjects, and their conclusions were based solely on observable signs and symptoms on systematically measured vital signs, and on standardized sobriety tests of motor coordination. Results showed that with this partial information, the officers are able to detect drug impairment at better-than-chance levels with a sensitivity (correct detection of impairments) of 72%, but with a specificity of 43% (false alarm rate of 57%). Furthermore, the association between drug ingestion and identification of the specific impairing drug category was not very high, with sensitivities ranging from a low of 10% for amphetamine to a high of 49% for cannabis. Based on both sensitivity and specificity, drug identification was best for alprazolam impairment, noticeably poorer for cannabis and codeine impairment, and no better than chance for amphetamine impairment. Performance could have been improved if the officers were to list the two most probable impairing drugs (rather than limit their decision to only one), and if they were more consistent in their interpretation of observable signs and symptoms.

Accidents, Traffic↗
PubMed2005

Modeling drug detection and diagnosis with the 'drug evaluation and classification program'.

In this study, we propose formal models and algorithms to detect drug impairment and identify the impairing drug type, on the basis of data obtained by a Drug Evaluation and Classification (DEC) investigation. The DEC program relies on measurements of vital signs and observable signs and symptoms. A formal model, based on data collected by police officers trained to detect and identify drug impairments, yielded sensitivity levels greater than 60% and specificity levels greater than 90% for impairments caused by cannabis, alprazolam, and amphetamine. For codeine, with a specificity of nearly 90% the sensitivity was only 20%. Using logistic regression, the formal model was much more accurate than the trained officers in identifying impairments from cannabis, alprazolam, and amphetamine. Both the formal model and the officers were quite poor in identifying codeine impairment. In conclusion, the joint application of the DECP procedures with the formal model is useful for drug detection and identification.

Accidents, Traffic↗
PubMed2005

Repair of the oxidative DNA damage 8-oxoguanine as a biomarker for lung cancer risk.

DNA repair has a major role in suppressing the rate of accumulation of mutations. Therefore, variations in DNA repair are likely to play an important role in determining cancer risk. While there is compelling evidence that defects in DNA repair cause high predisposition to several hereditary cancers, there is a paucity of data on the role of DNA repair in sporadic cancers. We present our approach of using functional DNA repair tests, rather than gene polymorphism, to study the potential of DNA repair enzymes to serve as biomarkers for lung cancer risk. We have previously developed a functional DNA repair blood test for the enzymatic repair of the oxidative DNA lesion 8-oxoguanine, and found that reduced OGG activity is a risk factor in non-small cell lung cancer. Moreover the combination of smoking and low OGG activity was associated with a greatly increased lung cancer risk (Paz-Elizur et al, JNCI 95 (2003) 1312-1319). The use of OGG activity as a potential biomarker for lung cancer risk is validated in collaboration with the M. D. Anderson Cancer Center, under the sponsorship of the Associate Members Program of the Early Detection Research Network (EDRN, NCI, NIH).

Biomarkers, Tumor↗
PubMed2005

[Diabetic retinopathy following cataract surgery].

BACKGROUND: Approximately 20% of patients undergoing cataract surgery have diabetes mellitus. AIM: To evaluate the course of diabetic retinopathy after cataract surgery. METHODS: Diabetic patients with no or mild to moderate preoperative diabetic retinopathy were included and classified into 4 groups (A-D): A--The course of retinopathy, B--macular edema, C--the effect of voltaren ophtha eye drops and D--systemic glycemic control. Group E included eyes with previous laser treatment for proliferative retinopathy. Clinical and angiographic retinal findings were scored before and after surgery. Progression was defined as an increase in the retinal score. In groups A, C, D and E the non-operated eye served as a control. In group B, the eyes of nondiabetic patients who had undergone cataract surgery served as a control. RESULTS: Retinopathy was stable in 66% and progressed in 34% (p < 0.005). Progression occurred during the first 6 postoperative months in 84%. Preoperative retinopathy was a risk factor for progression. Good visual acuity was achieved in 67% and was correlated with: preoperative retinopathy and postoperative deterioration. Macular edema was found in 50% of eyes compared to 8% of the controls (p < 0.005). Its development was correlated with preoperative retinal status. Twenty six eyes were treated with voltaren eye drops and 24 with placebo. Progression of macular edema was seen less often in eyes treated with voltaren (p < 0.001). Deterioration of retinopathy was less common in cases when HbA1C was equal to or lower than 7.5 mg%. CONCLUSIONS: Close retinal follow-up after cataract surgery is recommended, especially in patients with preoperative diabetic retinopathy. Systemic control of diabetes and antiinflammatory eye drops may improve surgical results.

Cataract Extraction↗
PubMed2003

DNA repair activity for oxidative damage and risk of lung cancer.

BACKGROUND: Although smoking is a major cause of lung cancer, only a proportion of smokers develop lung cancer, suggesting a genetic predisposition in some individuals. Because tobacco smoking is associated with the increased formation of DNA lesions, including those induced from oxidative damage, we investigated whether the activity of the DNA repair enzyme 8-oxoguanine DNA N-glycosylase (OGG), which repairs the oxidative DNA lesion 8-oxoguanine, is associated with lung cancer. METHODS: We conducted a molecular epidemiologic case-control study that included 68 case patients with non-small-cell lung cancer and 68 healthy control subjects, frequency matched for age and sex. Enzymatic OGG activity was determined in protein extracts prepared from peripheral blood mononuclear cells or lung tissue by assaying the cleavage product of a radiolabeled synthetic DNA oligonucleotide containing an 8-oxoguanine residue. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined by conditional logistic regression. All statistical tests were two-sided. RESULTS: OGG activity was lower in peripheral blood mononuclear cells from case patients than in those from control subjects. After adjustment for age and smoking status, individuals in the lowest tertile of OGG activity had an increased risk of non-small-cell lung cancer compared with individuals in the highest tertile (OR = 4.8, 95% CI = 1.5 to 15.9). The adjusted OR associated with a unit decrease in OGG activity was statistically significantly increased (OR = 1.9, 95% CI = 1.3 to 2.8). There was no interaction between OGG activity and smoking status. The estimated relative risk of lung cancer for smokers with low OGG activity was 34- or 124-fold higher for smokers with a low OGG activity of 6.0 or 4.0 U/ micro g protein, respectively, than for nonsmokers with a normal OGG activity of 7.0 U/ micro g protein, illustrating the cumulative effect of low OGG activity and smoking. CONCLUSIONS: Low OGG activity is associated with an increased risk of lung cancer. Although prospective studies are needed to validate the results, they suggest that smoking cessation in individuals with reduced OGG activity might be an effective strategy in lung cancer prevention.

Adult↗
PubMed2003

Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization.

OBJECTIVE: Exploration of the possibility that local injury of the endometrium increases the incidence of implantation. DESIGN: Prospective study. SETTING: Clinical IVF unit. PATIENT(S): A group of 134 patients, defined as good responders to hormonal stimulation, who failed to conceive during one or more cycles of IVF and embryo transfer (ET). INTERVENTION(S): The IVF treatment and ET were preceded by repeated endometrial biopsies, in a randomly selected 45 of a total of 134 patients. MAIN OUTCOME MEASURES: Outcome of IVF-ET treatments. RESULT(S): Transfer of a similar number of embryos (3.4 +/- 1.0 and 3.1 +/- 0.9 in the experimental and control patients, respectively) resulted in rates of implantation (27.7% vs. 14.2%, P =.00011), clinical pregnancy (66.7% vs. 30.3%, P =.00009), and live births per ET (48.9% vs. 22.5%, P =.016) that were more than twofold higher in the experimental group as compared to controls. CONCLUSION(S): These results suggest that IVF treatment that is preceded by endometrial biopsy doubles the chance for a take-home baby.

Adult↗
PubMed2003

Cabergoline, pramipexole and ropinirole used as monotherapy in early Parkinson's disease: an evidence-based comparison.

Dopamine agonists have been widely used as add-on to levodopa in the treatment of Parkinson's disease with motor fluctuations. However, the use of dopamine agonists in early Parkinson's disease and levodopa-naive patients is controversial. Although dopamine agonists have been compared with levodopa, no studies exist which directly compare one dopamine agonist with another. This evidence-based review compares the results of large published studies of early treatment of Parkinson's disease with dopamine agonists (cabergoline, ropinirole or pramipexole) with similar studies using levodopa. Because of their design, the common variables analysed in all studies were the proportion of patients who developed dyskinesia, those withdrawn from the trial and the mean change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III scores. Cabergoline, pramipexole and ropinirole were similarly effective in reducing the risk for dyskinesia relative to levodopa (p < 0.01 for all three). The reduction in risk for dyskinesia was slightly more evident for pramipexole and ropinirole (p < 0.0001) than cabergoline (p = 0.0074). Odds ratios (95% confidence intervals [CI]) relative to levodopa were 0.38 (0.19-0.78) for cabergoline, 0.25 (0.13-0.47) for pramipexole and 0.31 (0.18-0.53) for ropinirole. The absolute risk reductions (95% CI) were, respectively, 8% (2.2-13.7), 20% (11.7-29.8) and 25% (13.6-36.7), ropinirole reducing the risk significantly more than cabergoline. The mean change from baseline UPDRS was similar for pramipexole and ropinirole (not evaluated for cabergoline). The proportion of withdrawn patients and the adverse effect profiles of the three agonists were similar to each other, with the exception of oedema, which was less prominent for ropinirole than for the other two agonists. Cabergoline, pramipexole and ropinirole are comparable choices for the delay of dyskinesia. Their adverse effect profiles are also similar, but they are less well tolerated than levodopa. The motor antiparkinsonian benefit of dopamine agonists is somewhat smaller than that of levodopa.

Age of Onset↗