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עמוד בית
Sat, 23.11.24

Search results


October 2002
Eytan Cohen, MD, Shlomo Almog, PhD, Daniel Staruvin, MD and Moshe Garty, MD, MSc

Background: Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation

Objective: To evaluate a possible drug interaction between acarbose and digoxin.

Methods: An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period ll, they were given acarbose tablets., 60 mg-3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval: Serum. digoxin levels., over. time, in the two periods were compared by standard techniques;

Results: There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence.and absence of acarbose, were 2.89 and 2.40 g/L respectively (P =0.05); Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window.

Conclusion: There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.
 

Kosta Y. Mumcuoglu, PhD, Jacqueline Miller, PhD, Chen Zamir, MD, MPH, Gary Zentner, FRACP, Valery Helbin, MD and Arieh Ingber, MD

Background: Head louse infestations are prevalent worldwide. Over the past 20-25 years, 15-20% of all children in Israel between 4 and 13 years of age have been infested with head lice; This is mainly due to the existence of ineffective pediculicides on the market.

Objective: To examine the pediculicidal efficacy and safety of a natural remedy (”Chick-Chack") and to compare it in an open clinical study with a known pesticide spray.

Methods: The natural remedy, which contains coconut oil, anise ail and ylang ylang oil:, was applied to the hair of infested.children three times at 5 day intervals. Each treatment lasted for 15 minutes. The control pediculicide was a spray, formulation containing permethrin, malathion, piperonyl butoxide, isododecane and propellant gas, which was applied twice for 10 minutes with a 10 day interva1 between applications.

Results: Of 940 Children, aged 6-14 years, from six schools in Jerusalem who were examined for head louse infestastion,199 (21:.2÷/) were infested with lice and eggs, while 164 (17.4% ) were infested only  with nits. Altogether, 119 children were randomly treated with either the natural remedy or the control product. Treatment was successful with the natural remedy  in 60 children (92.3%) and with the control pediculicide in 59 children (92.2%). There were no significant side effects associated with either formulation.

Conclusions: The natural remedy was very effective in controlling  louse infestations under clinical conditions and caused no serious side effects.
 

Veronica Silva Vilela, MD, Nilson Ramirez de Jesus, MD and Roger Abramino Levy, MD, PhD
Arie Bitterman, MD, Richard I. Bleicher, MD, Myles C. Cabot, PhD, Yong Y. Liu, MD, PhD and Armando E. Giuliano, MD
Hannah Tamary, MD, Raanan Bar-Yam, BSc, Michal Zemach, MD, Orly Dgany, PhD, Lea Shalmon, MSc and Isaac Yaniv, MD

Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Aharon Klar, MD, Ariel Halamish, MD, David Shoseyov, MD, Pascal Cassinotti, PhD, Gunter Siegl, Chaim Springer, MD, Gila Shazberg, MD and Haggit Hurvitz, MD
Ashraf Hamdan, MD, Dania Hirsch, MD, Pnina Green, MD, PhD, Avivit Neumann, Tamara Drozd and Yair Molad, MD
Arie Shifman, DMD, Shmuel Orenbuch, MA and Mel Rosenberg, PhD
September 2002
Dafna Merom, MPH, Anneke Ifrah, MA, MPH, Irit Cohen-Manheim, MSc, Ayelet Chinich, MA and Manfred S. Green, MD, PhD

Background: Despite the controversy regarding the risks and benefits of hormone replacement therapy, studies in various countries indicate a two- to threefold increase in the use of HRT[1] during the last decade.

Objectives: To estimate the prevalence of HRT use among post-menopausal Jewish women in Israel and to determine the variables predicting current HRT use.

Methods: A cross-sectional telephone survey was conducted in 1998 on a random sample of Jewish women aged 45–74. Of 935 women who were located and eligible, 704 (75%) were interviewed by means of a structured questionnaire.

Results: A total of 589 women (85%) were peri-menopausal or post-menopausal.  Ninety-nine of them (16.8%) were currently using HRT and 78 (13.2%) were past users. Higher rates of current use were found among women who had undergone hysterectomy and/or oophorectomy (38%) than among all other women (13.5%).  Among naturally menopausal women the highest rate of current use (25.6%) was found in those aged 55–59.  A multiple logistic regression showed that the variables associated with current HRT use among naturally menopausal women  were: having a regular gynecologist (odds ratio 3.6, 95% confidence interval 1.7–7.5), visiting a gynecologist during the past year (OR[2] 2.9, 95% CI[3] 1.4–6.0), experiencing symptoms of menopause (OR 2.0, 95% CI 1.01–3.8), having more than a high-school education (OR 1.9, 95% CI 1.04–3.6), and a lower body mass index (OR 0.91, 95% CI 0.85–0.99).

Conclusions: The factors associated with HRT use may be markers for other socioeconomic or psychological characteristics. The disparities noted between population subgroups may be indicative of differences in awareness or in the delivery of preventive healthcare services to women in Israel, and as such need to be addressed by the health system.

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[1] HRT = hormone replacement therapy

[2] OR = odds ratio

[3] CI = confidence interval

Yaacov Ori, MD, Haim Neuman, MD, Avry Chagnac, MD, Annette Siegal, MD, Ana Tobar, MD, Maxim Itkin, MD, Uzi Gafter, MD, PhD and Asher Korzets, MB, BS

Background: The use of an automated biopsy system for renal biopsy has recently gained popularity, but its safety in single functioning kidneys is unclear.

Objective: To report our experience with the automated system for closed renal biopsy during a 5 year period.

Methods: Eighty-five patients underwent percutaneous native renal biopsy with the automated biopsy gun (16G needle) under real-time ultrasound. They were chronologically divided into two groups: 41 patients (group A), using an older ultrasound machine; and 44 patients (group B), using a newer ultrasound machine. Nine patients biopsied with a manual 14G Tru-cut needle served as the control (group C).

Results: The number of "attempted" passes at the kidney was 4.0 ± 0.1 in group B, 4.7 ± 0.3 in group A (P < 0.05 vs. group B), and 5.8 ± 0.5 in group C (P < 0.01 vs. group B). The number of successful passes did not differ (3.3 ± 0.1, 3.3 ± 0.1, 3.1 ± 0.2). The ratio of "attempted/successful" was 1.28 ± 0.07 in group B, 1.95 ± 0.38 in A, and 1.90 ± 0.21 in C (P < 0.01 vs. B). The number of glomeruli obtained was similar in the three groups. Adequate tissue was obtained in 95%, 98%, and 100%, respectively. Hemoglobin decreased by 4.3 ± 1.1% in group B, 6.9 ± 1.3% in group A, and 11.3 ± 1.8% in group C (P < 0.05 vs. B). Perinephric/subcapsular hematoma occurred in 5 patients (11.4%) in group A (2 taking aspirin), in 2 patients (4.9%) in group B, and in none in group C. The necessity for blood transfusion post-biopsy was similar in all groups. Four of five patients with single functioning kidneys (one in group A and four in group B) had uneventful biopsies, and adequate tissue was obtained in three.

Conclusions: The use of the automated biopsy gun is effective, safe and has a low rate of major complications. It may be used safely in single functioning kidneys.

Aliza Amiel, PhD, Orit Reish, MD, Elena Gaber, PhD, Ronit Masterman, MD, Tally Tohami, MSc and Moshe D. Fejgin, MD

Background: While most allelic pairs of DNA replicate synchronously during the S phase of the cell cycle, some genes normally replicate asynchronously, i.e., genes on the X chromosome and imprinted genes. The replication control mechanism is unknown but was shown to be impaired in malignancies and chromosomal trisomies where replication pattern becomes asynchronous.

Objectives: To determine the level of asynchronization in replication timing of cells from patients with microdeleted genomes.

Methods: We applied monocolor fluorescent in situ hybridization with different probes on leukocytes from microdeleted genomes.

Results: All samples derived from the microdeleted genomes showed significantly higher levels of an asynchronized pattern compared to normal individuals.

Conclusions: Even a “small” genetic imbalance (microdeletion) can interfere with gene replication and cell cycle progression, as previously shown in full trisomies.
 

Kelen C.R. Malmegrim, BSc2, Ger J.M. Pruijn, PhD and Walther J. van Venrooij, PhD

Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that may initiate and drive systemic autoimmunity in susceptible hosts. The uridine-rich small nuclear ribonucleoprotein complex is a common target for autoantibodies present in the serum of patients with systemic lupus erythematosus and SLE[1]-overlap syndromes. Four modifications occurring in this complex during apoptosis have been described to date: the caspase-mediated cleavage of the U1-70K protein, the U1 RNA and the Sm-F protein, and the association with hyperphosphorylated SR proteins. In addition, the U1 snRNP[2] complex has been shown to translocate from its normal subcellular localization to apoptotic bodies near the surface of cells undergoing apoptosis. This redistribution might facilitate exposure of the modified components of the U1 snRNP complex to the immune system when the clearance of apoptotic cell remnants is somehow disturbed. The modifications in the U1 snRNP components during apoptosis might represent the initial epitopes to which an immune response is generated and may be the trigger for the production of autoantibodies to this complex in patients with SLE or SLE-overlap syndromes. Therefore, it can be hypothesized that the exposure of elevated levels of apoptotically modified U1 snRNP to the immune system of a genetically susceptible individual might lead to the breaking of immunologic tolerance towards the U1 snRNP complex.

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[1] SLE = systemic lupus erythematosus

[2] U snRNP = uridine-rich small nuclear ribonucleoprotein

Zvi Fireman, MD, Arkady Glukhovsky, PhD, Harold Jacob, MD, FACG, Alexandra Lavy, MD, Shlomo Lewkowicz, DSc and Eitan Scapa, MD
Mogher Khamaisi, PhD and Itamar Raz, MD
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