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עמוד בית
Mon, 20.05.24

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September 2011
E. Lahat, E. Heyman, A. Livne, M. Goldman, M. Berkovitch and D. Zachor

Background: Several studies have suggested that iron deficiency may be related to the pathophysiology of attention deficit hyperactivity disorder (ADHD) due to the role of iron in the production of dopamine and noradrenaline.

Objectives: To evaluate the status of iron deficiency in ADHD children, using ferritin levels, a reliable measure of iron storage in body tissue, as an iron status marker, and to investigate a possible correlation between ferritin levels and the diagnosis of ADHD.

Methods: The study group included 113 newly referred ADHD children aged 5–15 years (mean age 8.8 ± 2.7).

Results: Ferritin levels were below 20 ng/ml in 67 children (59%) and above 20 ng/ml in 45 (41%). There was a very low inverse statistical correlation between scores on Conners’ Rating Scale and ferritin levels, probably without clinical significance. 

Conclusions: Our findings suggest that low iron stores may be related to ADHD pathophysiology; therefore, ferritin should be included in the overall evaluation of children with ADHD.

 
 

April 2011
A. Naimushin, M. Lidar, I. Ben Zvi and A. Livneh

Background: Familial Mediterranean fever (FMF) is a recessively inherited disease with a variety of clinical presentations. The disease is associated with mutations in the FMF gene (MEFV), which encodes for the pyrin protein. The role of the E148Q pyrin mutation in the FMF phenotype remains inconclusive, and some authors even view it as a disease-insignificant polymorphism. The calculated change, imposed by this mutation on pyrin structure, may help to understand the role of this mutation

Objectives: To calculate the relative electrochemical effect of the E148Q mutation on the structure of pyrin protein.

Methods: The electronic properties of the wild-type pyrin molecule and its common mutated forms were computed for the full-length molecule and its segments, encoded by exons 2 and 10, using the HyperChem 7.5 program with one of the molecular mechanical methods (MM+). The change in the structure of the molecule, expressed as a change in energy gain, conferred by the mutations was determined.

Results: The E148Q mutation caused deviation from the wild-type pyrin segment encoded by exon 2 by 1.15% and from the whole pyrin molecule by 0.75%, comparable to the R202Q mutation and less than the M694V mutation which caused a deviation from the wild-type structure of the whole pyrin molecule by 1.5%.

Conclusions: A quantum-chemistry based model suggests that the structural effect of the E148Q mutation is indeed low, but not zero. 
 

S. Kivity, I. Danilesko, I. Ben-Zvi, B. Gilburd, O.L. Kukuy, R. Rahamimov and A. Livneh

Background: Amyloidosis of familial Mediterranean fever (FMF) may lead to end-stage renal failure, culminating in kidney transplantation. Since amyloidosis is prompted by high serum amyloid A (SAA) levels, increased SAA is expected to persist after transplantation. However, no data are available to confirm such an assumption.

 Objectives: To determine SAA levels in kidney-transplanted FMF-amyloidosis patients and evaluate risk factors for the expected high SAA levels in this patient group.

Methods: SAA, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were obtained from 16 kidney-transplanted FMF-amyloidosis patients, 18 FMF patients without amyloidosis and 20 kidney-transplanted patients with non-inflammatory underlying disease. Demographic, clinical and genetic risk factors evaluation was based on data extracted from files, interviews and examination of the patients.

Results: SAA level in FMF patients who underwent kidney transplantation due to amyloidosis was elevated with a mean of 21.1 ± 11.8 mg/L (normal ≤ 10 mg/L). It was comparable to that of transplanted patients with non-inflammatory disorders, but tended to be higher than in FMF patients without amyloidosis (7.38 ± 6.36, P = 0.08). Possible risk factors for the elevated SAA levels in kidney transplant patients that were excluded were ethnic origin, MEFV mutations, gender, age and disease duration.

Conclusions: Kidney-transplanted patients with FMF-amyloidosis and with other non-FMF causes displayed mildly elevated SAA levels, possibly resulting from exposure to foreign tissue rather than from various FMF-related factors. 

 

March 2010
July 2006
A. Leibovitz, M. Lidar, Y,. Baumoehl, A. Livneh and R. Segal

Backgound: Colchicine is widely used for treating gout and familial Mediterranean fever. However, studies in animal models have reported ill effects of colchicine on the central nervous system, including cognitive function.

Objectives: To evaluate the cognitive status of elderly FMF[1] patients on long-term colchicine treatment.

Methods: The study group consisted of 55 FMF patients aged 74 ± 5, attending an FMF outpatient clinic and receiving colchicine treatment for 25.1 ± 8.9 years. The Mini-Mental State Examination was used for cognitive evaluation. Patients' scores were compared with accepted age- and education-adjusted cutoff scores, population-based norms, and scores of a matched control group of 56 subjects.

Results: Individually, all colchicine-treated FMF patients scored well above the age- and education-corrected cutoff scores. Overall, there was a large difference, 5.0 ± 1.6, from the expected cutoff points, in favor of the study group scores (P < 0.001). The individual scores of the control group were also above the cutoff points, however with a lower but still statistically significant difference (3.71 ± 1.15 points, P < 0.001). Compared to population-based norms adjusted by age and education, the study group had significantly higher mean MMSE[2] scores (27.2 ± 2.2 vs. 25.5 ± 2.4, P < 0.001). The control group’s scores were also somewhat higher than expected, but not significantly so.

Conclusions: Our results do not support the view that prolonged colchicine treatment may be associated with cognitive impairment. On the contrary, it is possible that long-term colchicine treatment may even confer protection against cognitive decline in patients with FMF.


 





[1] FMF = familial Mediterranean fever

[2] MMSE = Mini-Mental State Examination


September 2005
N. Tweezer-Zaks, I. Marai, A. Livneh, I. Bank and P. Langevitz
 Background: Benign prostatic hypertrophy is the most common benign tumor in males, resulting in prostatectomy in 20–30% of men who live to the age of 80. There are no data on the association of prostatectomy with autoimmune phenomena in the English-language medical literature.

Objectives: To report our experience with three patients who developed autoimmune disease following prostatectomy.

Patients: Three patients presented with autoimmune phenomenon soon after a prostectomy for BPH[1] or prostatic carcinoma: one had clinically diagnosed temporal arteritis, one had leukocytoclastic vasculitis, and the third patient developed sensory Guillian-Barré syndrome following prostatectomy.

Conclusions: In view of the temporal association between the removal of the prostate gland and the autoimmune process, combined with previously known immunohistologic features of BPH, a cause-effect relationship probably exists.

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[1] BPH = benign prostatic hypertrophy

June 2005
J. Ben Chaim, P.M. Livne, J. Binyamini, B. Hardak, D. Ben-Meir and Y. Mor
 Background: In Israel, virtually all children undergo circumcision in the neonatal period. Traditionally, it is commonly performed by a “Mohel” (ritual circumciser) but lately there is an increasing tendency among the educated secular population to prefer a medical procedure performed by a physician and with local anesthetic injection.

Objectives: To evaluate the outcome of this procedure and to compare the complication rate following circumcisions performed by ritual circumcisers and by physicians.

Methods: In 2001, of the 19,478 males born in four major medical centers in Israel 66 had circumcision-related complications. All the children were circumcised in non‑medical settings within the community. The patients were medically evaluated either urgently due to immediate complications or electively in outpatient clinics later on. Upon the initial assessment a detailed questionnaire was filled to obtain data regarding the procedure, the performer and the subsequent complications.

Results: All the circumcisions were performed during the early neonatal life, usually on day 8 of life (according to Jewish law). In 55 cases (83%) it was part of a ritual ceremony conducted by a ritual circumciser (Mohel), while in 11 babies (17%) physicians were involved. Acute bleeding after circumcision was encountered in 16 cases (24%), which required suturing in 8. In addition, we found two cases of wound infection and one case of partial amputation of glans penis in which the circumcision was performed by a ritual circumciser. Among the late complications, the most common was excess of skin in 38 cases (57%); 5 children (7.5%) had penile torsion and 4 children (6%) had shortages of skin, phimosis and inclusion cyst. The overall estimated complication rate of circumcision was 0.34%.

Conclusions: Complications of circumcision are rare in Israel and in most cases are mild and correctable. There appears to be no significant difference in the type of complications between medical and ritual circumcisions.

May 2005
J. Bishara, G. Livne, S. Ashkenazi, I. Levy, S. Pitlik, O. Ofir, B. Lev and Z. Samra

Background: The prevalence of extended-spectrum β-lactamase-producing organisms and their antimicrobial resistance patterns may vary between geographic areas.

Objectives: To evaluate the prevalence and susceptibility of ESBL[1]-producing organisms among Klebsiella pneumoniae and Escherichia coli isolated from adult and pediatric patients in two Israeli hospitals.

Methods: ESBL production was tested according to recommendations of the Clinical and Laboratory Standards Institute, using ceftazidime (30 μg) and a combination of ceftazidime/clavulanate (30/10 μg) disks with a ≥5 mm difference indicating positivity. Antibiotic susceptibilities were determined by the disk diffusion method according to CLSI[2] standards. Minimum inhibitory concentrations were determined by the E-test.

Results: The prevalence of ESBL-producing organisms was significantly higher among K. pneumoniae than E. coli isolates – 32% (241/765) vs. 10% (57/547) respectively (P < 0.001), and more frequently isolated from adults than children (odds ratio 2.27 for K. pneumoniae and 12.94 for E. coli). Resistance rates for amoxicillin/clavulanate, piperacillin-tazobactam, amikacin, and ciprofloxacin among the ESBL-producing K. pneumoniae and E. coli isolates were 95%, 82%, 49% and 77% for K. pneumoniae, and 77%, 35%, 25% and 100% for E. coli. Two (0.8%) ESBL-producing and 4 (0.7%) ESBL-negative K. pneumoniae isolates showed intermediate susceptibility (MIC[3] 6 μg/ml) to meropenem. All isolates were sensitive to ertapenem and colistin.  

Conclusion: ESBL production among K. pneumoniae and E. coli is more prevalent in the adult population than the pediatric population and is associated with multidrug resistance.







[1] ESBL = extended spectrum β-lactamase

[2] CLSI = Clinical and Laboratory Standards Institute (formerly the NCCLS)

[3] MIC = minimum inhibitory concentration





 

January 2005
I. Dudkiewicz, I. Cohen, S. Horowitz, S. Regev, M. Perelman, A. Chechik, P. Langevitz, S. Strasburg, A. Livneh and M. Salai

Background: Heterotopic ossification is a common complication of hip surgery and musculoskeletal or brain traumas.

Objectives: To confirm by in vivo study that colchicine inhibits osteoblast cell proliferation with marked decrease in tissue mineralization.

Methods: Heterotopic ossification was induced in three groups of New Zealand white rabbits (females, 6 months old, weight 3–3.5 kg) by injecting 2 ml bone marrow drawn from the iliac crest into their right thigh muscle. To prevent heterotopic ossification, colchicine (0.25 mg/day) was administered orally for 4 weeks to two groups of adult rabbits: group A (preload group) – 1 week preceding bone marrow injection; group B – on day of injection; and group C – control group.

Results: After 4 weeks the rabbits were evaluated by radiographs and ultrasound for evidence of heterotopic ossification. At the end of the study histologic samples were taken from all the thighs. Imaging and histologic studies showed, with statistical significance, almost complete prevention of heterotopic ossification formation in group A (preload) and a marked decrease in group B, when compared with the controls in whom large new bone had formed at the injection site. These results indicated the inhibitory effects of colchicine on a bone-forming process in soft tissue such as heterotopic ossification.

Conclusions: The role of colchicine in preventing heterotopic ossification in other bone-forming conditions, such as hip arthroplasty or pelvic trauma, and after brain trauma, remains to be evaluated in a clinical setting.

 
 

October 2004
E. Gnessin, P.M. Livneh, J. Baniel and G. Gillon
Background: Sphincter-related incontinence after radical prostatectomy, benign prostatectomy or due to neurogenic disease has a considerable negative impact on quality of life. Artificial urinary sphincter implantation is a mainstay therapeutic option for these patients.

Objectives: To assess patient satisfaction, subjective long-term continence and complications after AMS 800 artificial urinary sphincter implantation.

Methods: The medical records of 34 patients who underwent artificial urinary sphincter implantation for radical prostatectomy (n=23), simple prostatectomy (n=9) or neurogenic disease (n=2) between 1995 and 2003 were studied retrospectively. Median follow-up was 49 months (range 3–102 months). Records were analyzed for urinary sphincter survival and complications. Quality of life and continence assessment was done by mailing an impact questionnaire.

Results: In 4 of the 34 patients (11.7%) the device was removed due to infection. One of the four had surgical revision elsewhere, and the other three were not interested in re-implantation of the device. Two patients (5.9%) underwent revisions due to mechanical failure. One patient died and three patients were not located. Twenty-seven out of a possible 30 patients (88%) completed the questionnaire; 22 (85%) achieved social continence (0–2 pads daily), and one patient had subjective difficulty activating the device. Subjective improvement and patient satisfaction was rated as 4.22 and 4.11, respectively (scale 0 to 5).
Conclusions: Artificial urinary sphincter implantation is an efficacious option for sphincter-related incontinence. This study documents the positive impact of artificial urinary sphincter implantation on quality of life with acceptable complications; these results are comparable to other published studies.

February 2004
August 2003
N. Zaks, Y. Shinar, S. Padeh, M. Lidar, A. Mor, I. Tokov, M. Pras, P. Langevitz, E. Pras and A. Livneh

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by recurrent attacks of fever and serositis. The disease is caused by mutations in the MEFV gene, presumed to act as a down-regulator of inflammation within the polymorphonuclear cells.

Objectives: To present the results of 412 FMF patients genotyped for three MEFV mutations, M694V, V726A and E148Q.

Results: The most frequent mutation, M694V, was detected in 47% of the carrier chromosomes. This mutation, especially common among North African Jewish FMF[1] patients, was not found in any of the Ashkenazi (East European origin) patients. Overall, one of the three mutations was detected in 70% of the carrier chromosomes. M694V/M694V was the most common genotype (27%), followed by M694V/V726A (16%). The full genotype could be assessed in 57% of the patients, and one disease-causing mutation in an additional 26%. Only one patient with the E148Q/E148Q genotype was detected despite a high carrier rate for this mutation in the Jewish population, a finding consistent with a low penetrance of this genotype. The M694V/M694V genotype was observed in 15 patients with amyloidosis compared to 4 amyloidosis patients with other genotypes (P < 0.0001).

Conclusions: Because of low penetrance and as yet other undetermined reasons, mutation analysis of the most common MEFV mutations supports a clinical diagnosis in only about 60% of patients with definite FMF.

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[1] FMF = familial Mediterranean fever


July 2003
H. Blau, M. Livne and H. Mussaffi

Background: Cystic fibrosis is no longer a terminal illness of childhood and mean survival is now over 30 years. Adult patients with atypical CF[1] are increasingly being diagnosed. In Israel, all patients are still followed in pediatric centers.

Objectives: To describe our experience with adult CF, stressing the importance of adult-related health and psychosocial issues.

Methods: Twenty-five CF patients aged 20–50 years, constituting 44% of the 57 patients followed at our center, were analyzed for pulmonary and extrapulmonary features and management.

Results: Nineteen were diagnosed as children and 6 as adults. Nineteen were pancreatic-insufficient and 6 were pancreatic-sufficient, including 5 diagnosed as adults. Pulmonary status was usually stable, with forced expiratory volume in 1 second 66.3 ± 21% (mean ± SD) and no difference between pancreatic-sufficient and insufficent patients. The latter had more hemoptysis, Pseudomonas infection, intestinal obstruction, liver disease and diabetes. Two patients died of malignancy and two of advanced lung disease. A majority received continuous inhaled and oral antibiotics, bronchodilators, Dnase, physiotherapy and periodic home intravenous antibiotics. Psychosocial functioning was excellent: 60% were employed, 36% were married and 40% had children (none with CF). Patients diagnosed as adults had mild multisystem disease or isolated severe lung disease.

Conclusions: CF adults generally have a good quality of life. Advances in understanding the CF defect and a plethora of new treatment modalities bode well for the future. Patients must be maintained in optimal condition to reap the benefits, and there is an urgent necessity for adult physicians to develop expertise in CF.

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[1] CF = cystic fibrosis

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