Endocrinology Institute

Ramat Gan, Israel

Endocrinology Institute

Ramat Gan, Israel

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Ratzon R.,Tel Aviv University | Reshef A.,Allergy and Immunology Unit | Efrati O.,Tel Aviv University | Efrati O.,Safra Childrens Hospital | And 9 more authors.
Annals of Allergy, Asthma and Immunology | Year: 2016

Background Drug provocation tests (DPTs) are the gold standard in the diagnosis of β-lactam hypersensitivity. However, no consensus exists on the need for extended provocation tests, even though the effectiveness of the short DPT is relatively low and there has been an increase in the relative incidence of nonimmediate hypersensitivity reactions. Objective To evaluate the effectiveness of a 7-day (extended) DPT compared with a 1-day-only (short) DPT in the management of hypersensitivity reactions to β-lactam antibiotics. Methods Patients referred to the allergy clinic of the Sheba Medical Center for suspected β-lactam hypersensitivity from January 2008 to December 2012 underwent in vivo skin tests and an immediate short DPT with the culprit drug. Unless an immediate reaction was clearly documented, patients were offered a 7-day, extended DPT. Long-term effectiveness, calculated as the subsequent use of the tested antibiotic, and satisfaction levels were assessed with a telephone questionnaire. Results Of 49 negative DPT results, 26 (53%) were long and 23 (47%) were short. A total of 78% of the patients who underwent the long DPT reported that they used the drug compared with 61% of those who underwent only the short DPT (P =.049). Most patients were very satisfied with the drug allergy evaluation process. Conclusions An extended DPT protocol increased the effectiveness of the allergy workup in our center without compromising patient satisfaction and safety, and it should be recommended to patients with a history of nonimmediate reaction to β-lactam. © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.


Cukierman-Yaffe T.,Endocrinology Institute | Cukierman-Yaffe T.,Tel Aviv University | Cukierman-Yaffe T.,Hamilton Health Sciences | Anderson C.,Royal Prince Alfred Hospital | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2015

Context: Avoidance of death, disability, dementia, and cognitive dysfunction (DDCD) are high priorities for people in aging societies. Evidence is mounting that these conditions are associated with impaired glycemic control. Objective: The aim of this study was to assess the strength of relationship between the degree of glucose elevation and the development of the composite elements of DDCD that impede successful/ healthy aging in a population at high risk for cardiovascular disease. Design, Setting, Participants, and Main Outcome Measure: The relationship between baseline fasting plasma glucose values and DDCD was determined among 31 227 participants of the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE intolerant Subjects With Cardiovascular Disease studies followed up for a median of 4.7 years. Several statistical models were used for the entire cohort and for those with and without normal fasting plasma glucose (ie, 5.6 mmol/L) or a history of diabetes mellitus. Results: After adjusting for age and sex, a diagnosis of diabetes mellitus was associated with an approximately 1.6 greater odds of DDCD; every 1 mmol/L higher baseline fasting plasma glucose value was associated with a 1.09 (95% confidence interval 1.07, 1.10) greater odds. These associations persisted in the multivariate models (a 1.08 95% confidence interval 1.07, 1.1 greater odds after adjustment for age, sex, education, and depression). Conclusion: In individuals with high cardiovascular risk, a direct relationship exists between levels of dysglycemia and the risk of DDCD. Further research is needed to understand the mechanisms underlying such an association and whether benefits can be derived from preventative strategies. (J Clin Endocrinol Metab 100: Copyright © 2015 by the Endocrine Society.


Kalich-Philosoph L.,Fertility Preservation Research Laboratory | Kalich-Philosoph L.,Bar - Ilan University | Roness H.,Fertility Preservation Research Laboratory | Carmely A.,Fertility Preservation Research Laboratory | And 12 more authors.
Science Translational Medicine | Year: 2013

Premature ovarian failure and infertility are major side effects of chemotherapy treatments in young cancer patients. A more thorough understanding of the mechanism behind chemotherapy-induced follicle loss is necessary to develop new methods to preserve fertility in these patients. We show that the alkylating agent cyclophosphamide (Cy) activates the growth of the quiescent primordial follicle population in mice, resulting in loss of ovarian reserve. Despite the initial massive apoptosis observed in growing, though not in resting, follicles of Cy-treated mice, differential follicle counts demonstrated both a decrease in primordial follicles and an increase in early growing follicles. Immunohistochemistry showed that granulosa cells were undergoing proliferation. Analysis of the phosphatidylinositol 3-kinase signaling pathway demonstrated that Cy increased phosphorylation of proteins that stimulate follicle activation in the oocytes and granulosa cells. Coadministration of an immunomodulator, AS101, reduced follicle activation, thereby increasing follicle reserve and rescuing fertility after Cy, and also increased the efficacy of Cy against breast cancer cell lines. These findings suggest that the mechanism in Cy-induced loss of ovarian reserve is accelerated primordial follicle activation, which results in a "burnout" effect and follicle depletion. By preventing this activation, AS101 shows potential as an ovarian-protective agent, which may be able to preserve fertility in female cancer patients.


Fried M.,OB Klinika A.s. | Fried M.,Charles University | Dolezalova K.,OB Klinika A.s. | Sramkova P.,OB Klinika A.s. | Sramkova P.,Endocrinology Institute
Surgery for Obesity and Related Diseases | Year: 2011

Background The intended purpose of gastrogastric imbrication sutures in laparoscopic adjustable gastric banding is to reduce band-related complications; however, evidence demonstrating imbrication suture utility has been lacking. A 3-year randomized controlled trial on the safety and efficacy of laparoscopic adjustable gastric banding with and without imbrication sutures was undertaken. We performed a prospective investigation of the outcomes using the Swedish adjustable gastric band (SAGB) with and without imbrication sutures. Methods From January to September 2006, 100 patients undergoing SAGB placement were randomized to group 1 (n = 50, <2 imbrication sutures) or group 2 (n = 50, no imbrication sutures). The SAGB was implanted in both groups using a standardized pars flaccida technique. The mean operative time, hospitalization time, percentage of excess weight loss, body mass index, band fill volume, and complications were recorded. The Fisher exact test for categorical data, the independent samples t test for continuous data, and the paired t test to assess the body mass index reduction were performed. All tests were 2-tailed, and statistical significance was set at P <.05. Results The mean operative time was 75 ± 7 minutes (range 5092) and 48 ± 4 minutes (range 3275) for groups 1 and 2, respectively (P <.001). The mean hospitalization time was 26 ± 12 hours (range 2096) and 23 ± 9 hours (range 2048) for groups 1 and 2, respectively (P <.17). The 3-year percentage of excess weight loss was 55.7% ± 3.4% and 58.1% ± 4.1% for groups 1 and 2, respectively (95% confidence interval -4.0% to -.8%, P <.01). The body mass index at 3 years was 34.0 ± 5.8 kg/m2 and 30.3 ± 6.4 kg/m2 (range 1.26.2) for groups 1 and 2, respectively (P <.01). The fill volume at 3 years was 3.6 ± 1.2 mL (range 1.05.5) and 4.5 ± 0.5 mL (range .05.0) for groups 1 and 2, respectively (P <.01). Finally, slippage occurred in 1 patient (2.2%) and 1 patient (2.0%) and migration in 1 patient (2.2%) and 1 patient (2.0%) in groups 1 and 2, respectively (P = NS). No patient died in either group. Conclusion The results of our randomized controlled trial have demonstrated that SAGB combined with a conservative approach to band adjustments and limited retrogastric dissection is effective and safe with and without imbrication sutures. Not using imbrication sutures results in significant benefits in operative speed with comparable clinical weight loss and intermediate term safety. These randomized controlled trial data suggest that imbrication sutures are not indispensable to laparoscopic adjustable gastric banding and their use can be left to the surgeon's discretion. © 2011 American Society for Metabolic and Bariatric Surgery. All rights reserved.


Natovich R.,Ben - Gurion University of the Negev | Natovich R.,Endocrinology Institute | Kushnir T.,Ben - Gurion University of the Negev | Kushnir T.,Ariel University | And 15 more authors.
Diabetes Care | Year: 2016

Objective The presence of a foot ulcer increases the self-treatment burden imposed on the individual with diabetes. Additionally, this condition increases the cognitive demands needed for adherence tomedical recommendations. A potential gap could exist between medical recommendations and the individual's ability to implement them. Hence, the goal of this study was to examine whether the cognitive profile of peoplewith diabetic foot ulcers differs fromthat of peoplewith diabetes without this complication. RESEARCH DESIGN AND METHODS This was a case-control study. Ninety-nine individuals with diabetic foot ulcers (case patients) and 95 individuals with type 2 diabetes (control subjects) (age range 45-75 years), who werematched for diabetes duration and sex, underwent extensive neuropsychological evaluation using a NeuroTrax computerized battery, digit symbol, and verbal fluency tests. A global cognitive score after standardization for age and education was computed as well as scores in the following six cognitive domains: memory, executive function, reaction time, attention, psychomotor abilities, and estimated premorbid cognition. RESULTS Individuals with diabetic foot ulcers had significantly (P < 0.001) lower cognitive scores than individuals with diabetes without this complication, in all tested cognitive domains, excluding estimated premorbid cognition. Individuals with diabetic foot ulcers demonstrated a significant difference between precognitive and current cognitive abilities, as opposed to the nonsignificant difference among control subjects. The differences persisted inmultivariable analysis after adjusting for depression and smoking. CONCLUSIONS Individuals with diabetic foot ulcers were found to possess fewer cognitive resources than individuals with diabetes without this complication. Thus, they appear to face more self-treatment challenges, while possessing significantly fewer cognitive resources. © 2016 by the American Diabetes Association.


Shemesh E.,Ben - Gurion University of the Negev | Rudich A.,Ben - Gurion University of the Negev | Harman-Boehm I.,Soroka Medical Center | Cukierman-Yaffe T.,Gertner Institute for Epidemiology and Health Policy Research | Cukierman-Yaffe T.,Endocrinology Institute
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Aim: Epidemiological and mechanistic studies raised the possibility that cognitive function may be affected by brain responses to insulin. We systematically reviewed and analyzed existing clinical trials thatassessedthepotential beneficial effectsofintranasal insulinadministrationoncognitive functions. Methods: Interventional studies measuring changes in cognitive functions in response to intranasal insulin were retrieved and included if they were in English and assessed cognitive functions before and after treatment. Cohen's effect size was calculated to allow comparison between studies. Results: Eight studies (328 participants) were analyzed. No significant side effects of intranasal insulin administration were reported. Seven studies included healthy subjects' response to intranasal insulin, and three evaluated the cognitive effect among patients with minimal cognitive impairment or overt Alzheimer's disease. In healthy people, Cohen's effect size calculations suggest that only 160 IU/d intranasal insulin induced potential beneficial effects. Although females, when compared head-to-head, exhibited greater improvements in cognitive tests than men, the composite analysis of all included studies did not support this trend. Among cognitively impaired patients, only lower doses of insulin were assessed, and 20 IU revealed potential beneficial effects on cognitive functions. This was significant in a single study assessing long-term intranasal insulin administration, whereas acute administration of 20 IU intranasal insulin tended to show a beneficial effect on immediate recall in Apo ε4(-), but not Apo ε4(+), patients. Conclusions: The current limited clinical experience suggests potential beneficial cognitive effects of intranasal insulin. Analyses provide clinical considerations for future research aimed at elucidating whether intranasal insulin may be used to improve cognitive functions. Copyright © 2012 by The Endocrine Society.


Elhayany A.,Meir Medical Center | Elhayany A.,Central District Clalit Health Services | Elhayany A.,Tel Aviv University | Lustman A.,Central District Clalit Health Services | And 6 more authors.
Diabetes, Obesity and Metabolism | Year: 2010

Background: The appropriate dietary intervention for overweight persons with type 2 diabetes mellitus (DM2) is unclear. Trials comparing the effectiveness of diets are frequently limited by short follow-up times and high dropout rates.Aim: The effects of a low carbohydrate Mediterranean (LCM), a traditional Mediterranean (TM), and the 2003 American Diabetic Association (ADA) diet were compared, on health parameters during a 12-month period.Methods: In this 12-month trial, 259 overweight diabetic patients (mean age 55 years, mean body mass index 31.4 kg/m2) were randomly assigned to one of the three diets. The primary end-points were reduction of fasting plasma glucose, HbA1c and triglyceride (TG) levels.Results: 194 patients out of 259 (74.9%) completed follow-up. After 12 months, the mean weight loss for all patients was 8.3 kg: 7.7 kg for ADA, 7.4 kg for TM and 10.1 kg for LCM diets. The reduction in HbA1c was significantly greater in the LCM diet than in the ADA diet (-2.0 and -1.6%, respectively, p < 0.022). HDL cholesterol increased (0.1 mmol/l ± 0.02) only on the LCM (p < 0.002). The reduction in serum TG was greater in the LCM (-1.3 mmol/l) and TM (-1.5 mmol/l) than in the ADA (-0.7 mmol/l), p = 0.001.Conclusions: An intensive 12-month dietary intervention in a community-based setting was effective in improving most modifiable cardiovascular risk factors in all the dietary groups. Only the LCM improved HDL levels and was superior to both the ADA and TM in improving glycaemic control. © 2010 Blackwell Publishing Ltd.


Singer P.,Intensive Care Unit | Anbar R.,Nutrition Unit | Cohen J.,Intensive Care Unit | Silva V.,Intensive Care Unit | Singer J.,Endocrinology Institute
Nutritional Therapy and Metabolism | Year: 2014

Introduction: Altered levels of adipokines, which may be influenced by energy availability, have been demonstrated in critically ill patients. These patients frequently undergo fasting and underfeeding. This study investigated the effect of continuous nutritional support on adipokine levels in critically ill patients. Materials and Methods: Patients admitted to the intensive care unit were randomized to receive nutritional support with an energy target determined either by (i) repeated indirect calorimetry measurements (study group), or (ii) a weight-based formula (25 Kcal/kg/day; control group). Adipokine levels (serum leptin, resistin, ghrelin, and adiponectin) were measured on days 1 and 7. Both cumulative energy balance (energy balance at discharge from intensive care unit or after 7 days) and maximal negative energy balance (most negative energy balance observed during the study) were assessed. Results: The daily energy balance (p=0.001), cumulative energy balance (p=0.01), and maximal negative energy balance (p=0.01) were significantly positive for the study group and negative for the control group. There were no significant between-group differences in adipokine levels on day 1 or day 7. In the control group, serum ghrelin increased significantly over time (p<0.05) and a trend for an increase in resistin (p<0.065) was noted. For the whole group, a more positive cumulative energy balance and a lower maximal negative energy balance were associated with a significantly smaller increase in serum ghrelin levels (p=0.008 and p=0.035, respectively) and a smaller increase in resistin levels (p=0.061 and p=0.027, respectively). Conclusions: A positive cumulative energy balance in critically ill patients appears to influence the levels of ghrelin and, to a lesser extent, resistin. The clinical significance of this finding requires further investigation. © 2014 SINPE-GASAPE.


Cukierman-Yaffe T.,Endocrinology Institute | Cukierman-Yaffe T.,Gertner Institute for Epidemiology and Health Policy Research | Cukierman-Yaffe T.,Tel Aviv University | Konvalina N.,Endocrinology Institute | And 2 more authors.
Diabetes Research and Clinical Practice | Year: 2011

Objective: Clinical trials have demonstrated that in individuals with type 1 diabetes the use of CSII pump resulted in better glucose control. Advantages of pumps therapy include many features such as the bolus calculators (wizard). These features are optional and therefore it is important to determine whether their use is associated with better glucose control. Thus, the aim of this analysis was to assess which features and parameters of insulin pump use are associated with better glucose control. Methods: Data regarding consecutive patients with type 1 diabetes treated with an insulin pump and attending a tertiary referral for intensive glucose control was included in this analysis. The relationship between glycemic indices and treatment parameters (number of insulin units, number of glucose readings, bolus calculator use etc.) was assessed. Results: A statistically significant relationship was found between glycemic indices and wizard use. Thus, individuals that used the wizard function in 50% of their boluses had an A1C, mean blood glucose values that were 0.6% (p = 0.008) and 25. mg/dL (p = 0.000) lower respectively. Conclusion: The use of the bolus calculator feature was associated with better glucose control. Larger prospective clinical trials are needed in order to further validate this finding. © 2011 Elsevier Ireland Ltd.


PubMed | Endocrinology Institute
Type: Journal Article | Journal: Diabetes research and clinical practice | Year: 2011

Clinical trials have demonstrated that in individuals with type 1 diabetes the use of CSII pump resulted in better glucose control. Advantages of pumps therapy include many features such as the bolus calculators (wizard). These features are optional and therefore it is important to determine whether their use is associated with better glucose control. Thus, the aim of this analysis was to assess which features and parameters of insulin pump use are associated with better glucose control.Data regarding consecutive patients with type 1 diabetes treated with an insulin pump and attending a tertiary referral for intensive glucose control was included in this analysis. The relationship between glycemic indices and treatment parameters (number of insulin units, number of glucose readings, bolus calculator use etc.) was assessed.A statistically significant relationship was found between glycemic indices and wizard use. Thus, individuals that used the wizard function in 50% of their boluses had an A1C, mean blood glucose values that were 0.6% (p=0.008) and 25mg/dL (p=0.000) lower respectively.The use of the bolus calculator feature was associated with better glucose control. Larger prospective clinical trials are needed in order to further validate this finding.

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