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עמוד בית Mon, 26.08.19

July 2008


Perspective
Z. Laron

The question of who discovered insulin is controversial. One of the scientists working on pancreas extracts was Nicolae Paulescu, the so-called Forgotten Man. In addition to his scientific research he was also active in politics. He was the father of the virulent antisemitic fascist movement “Garda de Fer” in Romania; he raved against the “Jewish Peril,” claimed in his writings that the Jews are a genetically degenerate people trying to cheat and poison the Rumanian people by alcoholism, and more. His name came up in 2003 when Romanian diabetologists initiated a move to honor him. But voices rose in protest, claiming that persons who incite hatred, support persecution and genocide and distort science as their political tools cannot be accepted or rewarded. The protesters won.

Original Articles
I. Gotsman, A. Stabholz, D. Planer, T. Pugatsch, L. Lapidus, Y. Novikov, S. Masrawa, A. Soskolne and C. Lotan

Background: Atherosclerosis is a chronic inflammatory process resulting in coronary artery disease.

Objectives: To determine the relationship between inflammatory markers and the angiographic severity of CAD[1].

Methods: We measured inflammatory markers in sequential patients undergoing coronary angiography. This included C-reactive protein, fibrinogen, serum cytokines (interleukin-1 beta, IL-1[2] receptor antagonist, IL-6, IL-8, IL-10) and tumor necrosis factor-alpha), all measured by high sensitivity enzyme-linked immunoabsorbent assay.

Results: There was a significant correlation between TNFα[3] and the severity of CAD as assessed by the number of obstructed coronary vessels and the Gensini severity score, which is based on the proximity and severity of the lesions. Patients had more coronary vessel disease (> 70% stenosis) with increasing tertiles of serum TNFα; the mean number of vessels affected was 1.15, 1.33, and 2.00 respectively (P < 0.001). IL-6 correlated with the Gensini severity score and coronary vessel disease (> 70% stenosis). A weaker correlation was present with IL-1 receptor antagonist. A significant correlation was not found with the other inflammatory markers. After adjustment for major risk factors, multivariate analyses showed that significant independent predictors of CAD vessel disease were TNFα (P < 0.05) and combined levels of TNFα and IL-6 (P < 0.05). IL-6 levels were independently predictive of Gensini coronary score (P < 0.05).

Conclusion: TNFa and IL-6 are significant predictors of the severity of coronary artery disease. This association is likely an indicator of the chronic inflammatory burden and an important marker of increased atherosclerosis risk.






[1] CAD = coronary artery disease



[2] IL = interleukin



[3] TNFa = tumor necrosis factor-alpha


E. Mei-dan, A. Walfisch, I. Raz, A. Levy and M. Hallak

Background: Women frequently suffer perineal trauma while giving birth. Interventions to increase the possibility for an intact perineum are needed.

Objectives: To evaluate the effectiveness of antenatal perineal massage in increasing the likelihood of delivering with an intact perineum.

Methods: This single blinded prospective controlled trial included 234 nulliparous women with a singleton fetus. Women allocated to the study group were instructed to practice a 10 minute perineal massage daily from the 34th week of gestation until delivery. Primary outcome measures included the episiotomy rate; first, second, third and fourth-degree perineal tear rates; and intact perineum. Secondary outcomes were related to specific tear locations and the amount of suture material required for repair.

Results: Episiotomy rates, overall spontaneous tears and intact perineum rates were similar in the study and control groups. Women in the massage group had slightly lower rates of first-degree tears (73.3% νs. 78.9%, P = 0.39) and slightly higher rates of second-degree tears (26.7% νs. 19.3%, P = 0.39), although both of these outcomes did not reach statistical significance. The rates of anterior perineal tears were significantly higher in the massage group (9.5% vs. 3%, P = 0.05), whereas internal lateral tears rates were slightly lower but without statistical significance (11.5% νs.13.1%, P = 0.44).

Conclusions: The practice of antenatal perineal massage showed neither a protective nor a detrimental significant effect on the occurrence of perineal trauma.
 

C. Hartman, D. Berkowitz, B. Weiss, R. Shaoul, A. Levine, O. Eshach Adiv, R. Shapira, A. Fradkin, M. Wilschanski, A. Tamir and R. Shamir

Background: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease.

Objectives: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFβ2[1]-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease.

Methods: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD™ as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus®) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet.

Results: The Modulen-treated children showed a significant decrease in PCDAI[2] from 34.3 to 15.7 (P < 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P = 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P = 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group.

Conclusions: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI[3], suggesting an additional advantage of nutritional therapy in children with this disease.






[1] TGF-β2 = transforming growth factor-β2

[2] PCDAI = Pediatric Crohn's Disease Activity Index

[3] BMI = body mass index


A. Malkiel, P. Mor, H. Aloni, E. Gdansky and S. Grisaru-Granovsky

Background: Intrapartum risk is based mainly on obstetric history, which is lacking in primiparous women.

Objectives: To ascertain whether the traditional known risk of primiparity is an independent variable for both maternal and neonatal outcome.

Methods: All women admitted to labor during March-April 2002 were canvassed for eligibility for participation in the study based on an obstetric risk scoring system developed and validated for our population. During the study period, 1473 women presented for delivery. Of these, 298 women (20%) were eligible according to the exclusion criteria as "low risk" parturients: 135 (45%) were primiparous and 163 (55%) were multiparous (2–5 births).

Results: After correction for significant confounding factors, primiparity was revealed as an independent significant risk factor for instrumental delivery (odds ratio 15.5, 95%confidence interval 1.88–125) and for early postpartum hemorrhage (OR[1] 5.6, 95%CI[2] 1.9–16.6).

Conclusions:
This study highlights early postpartum hemorrhage as a significant risk for primiparous women, independent of mode of delivery, and also confirms previous reports of maternal complications requiring transfer from birth centers/home deliveries to tertiary centers.






[1] OR = odds ratio

[2] CI = confidence interval


D. Dicker, Y. Belnic, R. Goldsmith, D. Nitzan Kaluski

Background: It has been suggested that increased calcium intake plays a role in preventing obesity and promoting weight loss.

Objectives: To assess the association between calcium intake, body mass index and waist circumference in Israel.

Methods: MABAT is a cross-sectional survey based on a random sample of 3246 Israelis aged 25 to 64. Of the 3246 survey participants, height and weight measurements were recorded for 2782 (1371 men and 1411 women). These were divided into three groups according to their BMI[1] (group A ≤ 24.9, group B 25–29.9, and group C ≥ 30) and given a 24 hour food consumption recall questionnaire. Waist circumference was measured in 2601 participants (1760 men and 841 women) and was considered to be excessive if ≥102 cm for men or 88 cm for women.

Results: The mean calcium intake was 511.5 ± 301.8 mg for group A, 499.4 ± 283.7 mg for group B, and 464.7 ± 280.1 mg for group C (group A significantly differed from group C, P < 0.002). The mean daily milk consumption in group A was higher than in groups B and C (103.4 ± 147.5, 85.7 ± 122.25, and 84.5 ± 135.1 g, respectively; P < 0.01). There was no correlation between daily dietary calcium intake and waist circumference for men but women with a waist circumference below 88 cm consumed significantly more dietary calcium than those with a waist circumference ≥ 88 cm (P < 0.03).

Conclusions: The study confirms the inverse relationship between daily dietary calcium intake and obesity. This linkage relates to the intake of milk, but not to other dairy products.






[1] BMI = body mass index


A. Mager, N. Koren-Morag, M. Shohat, A. Dadashev, R. Kornowski, A. Battler and D. Hasdai

Background: The C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with early onset of coronary artery disease in some populations with certain ethnic backgrounds. However, data on its effect on CAD[1] development in women are limited and conflicting.

Objectives: To investigate the effects of the MTHFR C677T mutation and ethnicity on the development and age at onset of CAD in women in Israel.

Methods: The sample included 135 Jewish women with well-documented CAD (62 Ashkenazi, 44 Oriental and 29 of other origins) in whom CAD symptoms first developed at age ≤ 65 years. DNA samples from 235 women served as the control.

Results: CAD symptoms developed later in Ashkenazi than in Oriental women or women of other origins (51.0 ± 7.0 years vs. 48.3 ± 7.5 and 46.3 ± 7.7 years, respectively, P = 0.024). Among Ashkenazi women, the T/T genotype was less common in patients in whom CAD symptoms appeared after age 50 (6.4%) than in patients with earlier CAD symptoms (25.8%, P = 0.037) and Ashkenazi control subjects (23.3%, P = 0.045). Among women from other origins, these differences were not significant. On logistic regression analysis, the T/T genotype was associated with a nearly fourfold increase in the risk of early onset (age < 50 years) of CAD (odds ratio 3.87, 95% confidence interval 1.12–13.45, adjusted for risk factors and origin) and a trend towards an influence of ethnicity (P = 0.08). Compared to Ashkenazi women, the risk of early development of CAD associated with the T/T genotype among Oriental ones was 0.46 (95%CI[2] 0.189–1.114) and in women of other origins, 5.84 (95%CI 1.76–19.34). Each additional risk factor increased the risk of earlier onset of CAD by 42% (OR[3] 1.42, 95%CI 1.06–1.89).

Conclusions: The age at onset of CAD in Israeli women is influenced by the MTHFR genotype, ethnic origin and coronary risk factors.






[1] CAD = coronary artery disease

[2] CI = confidence interval

[3] OR = odds ratio


S. Badarny, Z. Susel and S. Honigman

Background: Long-term therapy with botulinum toxin is sometimes associated with therapy failure following repeated injections of the neurotoxin, presumably due to specific antibody production. Primary therapy failure with botulinum toxin is less common and poorly understood.

Objectives: To examine the effectiveness of the botulinum neurotoxin Dysport® in patients with blepharospasm and hemifacial spasm after primary or secondary failure with Botox® treatments. .

Methods: In this case series study, eight patients with blepharospasm and hemifacial spasm who experienced primary or secondary therapy failure with Botox were treated with Dysport. In order to render an equivalent Dysport dose, a conversion ratio of 1:3 to 1:4 Botox /Dysport was used.

Results: Two patients, one with blepharospasm and the other with hemifacial spasm, who showed primary therapeutic failure with Botox showed good response to Dysport treatments. One patient with tardive blepharospasm did not respond to either drug. Two patients with blepharospasm and three patients with hemifacial spasm who experienced Botox secondary therapy failure responded well to Dysport treatments.

Conclusions: Botox and Dysport are both serotype A botulinum toxins but carry different characteristics of biological activity. These differences possibly account for the favorable therapeutic response to Dysport in patients with hemifacial spasm or blepharospasm following failure with Botox treatments.
 

Reviews
Issues In Rheumatology and Autoimmunity
V. K. Shanmugam, V. D. Steen and T. R. Cupps

Lower extremity ulcers are a late complication of connective tissue diseases and occur more commonly in patients with this disease than in the general population. Although these lesions have historically been attributed to vasculitis, it is now recognized that inflammatory vessel injury accounts for fewer than 20% of ulcers in connective tissue disease. The pathogenesis of these lesions is complex, and often several processes act synergistically to initiate and perpetuate tissue injury. We review the evidence for antiphospholipid antibodies and prothrombotic states contributing to a vasculopathy in patients with connective tissue disease, precipitating ulceration and impairing healing.

Toxic Chemical Compounds
I. Makarovsky, G. Markel, T. Dushnitsky and A. Eisenkraft
Medical Education
R. Baumal and J. Benbassat

Research in the acquisition of patient interviewing skills by medical students has dealt mostly with the evaluation of the effectiveness of various teaching programs and techniques. The educational approaches (i.e., the tutor-learner relationship and learning atmosphere) have rarely been discussed. These approaches may be grouped into: a) "teacher-centered" (didactic), in which the students are passive recipients of instruction; b) "learner-centered," in which the tutor functions as a facilitator of small group learning, whose task is not to teach but rather to ensure that all students participate in the discussions and share knowledge with other students; and c) "integrated learner-and teacher-centered" or "experiential learning," which consists of an ongoing dialogue between the tutor and the students. In this paper, we review the strengths and weaknesses of these educational approaches and attempt to identify the current trends in their use in the teaching of interviewing skills. It would appear to us that, until the 1960s, medical students acquired interviewing skills without any expert guidance. On the other hand, since the 1970s, there has been a tendency to offer and upgrade undergraduate programs aimed at imparting communication skills to medical students. Initially, these programs were didactic; however, during the last decade, there has been an increasing shift to teaching interviewing skills by promoting experiential learning.

ECG of the Month
A. Unterman and S. D. Moscavitch
הבהרה משפטית: כל נושא המופיע באתר זה נועד להשכלה בלבד ואין לראות בו ייעוץ רפואי או משפטי. אין הר"י אחראית לתוכן המתפרסם באתר זה ולכל נזק שעלול להיגרם. כל הזכויות על המידע באתר שייכות להסתדרות הרפואית בישראל. מדיניות פרטיות
ז'בוטינסקי 35 רמת גן, בניין התאומים 2 קומות 10-11, ת.ד. 3566, מיקוד 5213604. טלפון: 03-6100444, פקס: 03-5753303