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עמוד בית
Sat, 23.11.24

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March 2002
Amir Halkin, MD and Gad Keren, MD
Anna Villa, MD, Christina Sobacchi, PhD and Paulo Vezzoni, MD, PhD

Severe combined immunodeficiencies represent a heterogeneous group of hereditary defects of the immune system that affect both T and B cells and whose etiology has only recently begun to be understood. A portion of these SCID patients bear a defect in either of the two recombination-activating genes, Rag-1 or Rag-2, while others have mutations in a newly identified gene, Artemis. Omenn syndrome is an unusual severe immunodeficiency with T cells but no B cells, and peculiar features also due to a defect in Rag-1 or Rag-2 genes. All these three forms are characterized by an impairment of the VDJ recombination, the process that insures the somatic diversification of immunoglobulin and T cell receptor-encoding genes. Recent findings have enabled us to better understand the pathophysiology of these three immunodeficiencies, which affect the V(D)J recombination process to a different extent and in different ways.

Dov Gefel, MD, Maria Doncheva, MD, Eli Ben-Valid, MD, Abed El Wahab-Daraushe, MD, Gil Lugassy, MD and Ben-Ami Sela, PhD
Kobi Stav, MD, Dan Leibovici, MD, Yoram I. Siegel, MD and Arie Lindner, MD, MPH
Ben-Zion Garty, MD, Itamar Ofer, MD and Yaron Finkelstein, MD
Menachem Gross, MD, Abraham Goldfarb, MD and Ron Eliashar, MD
Giselle Zandman-Goddard, MD and Sigal Tal, MD
February 2002
Diab Mutlak, MD, Luis Gruberg, MD, Shimon Reisner, MD and Walter Markiewicz, MD, FACC

Background: Percutaneous transluminal septal ablation was recently introduced as an alternative to surgical treatment of hypertrophic obstructive cardiomyopathy. In this procedure, alcohol is injected into a proximal septal artery to create a localized myocardial infarction.

Objectives: To characterize the immediate and mediumterm results following PTSMA.

Methods: Of 13 patients referred for PTSMA, 8 were found suitable for the procedure. Hemodynamic parameters were evaluated prior to and following the procedure, and clinical and echo-Doppler parameters at 2 weeks and 9 months later.

Results: The procedure was technically successful in all patients. Resting left ventricular outflow gradient at rest (by Doppler) fell from 82 + 37 to 15 + 8 mmHg (P<0.001) 9 months later. Late post-procedural gradient after the Valsalva maneuver was 2 + 24 mmHg. The degree of mitral regurgitation fell from 2.0 + 0 to 1.5 + 0.5 (P<0.05). New York Heart Association class for dyspnea improved from 2.8 + 0.5 to 1.8 + (P<0.01) and Canadian Cardiovascular Society class for angina from 2.0 + 1.3 to 1.3 + 1.2 (P=0.08). Complete right bundle branch block developed in six patients, temporary complete atrioventricular block in three, and persistent block requiring permanent pacing in one. No flow in the distal left anterior descending coronary artery (presumably due to spilling of alcohol) was seen in one (with development of a small antero-apical infraction) and ventricular fibrillation 2 hours post-procedure in one. None of the patients died.

Conclusion: PTSMA provided a substantial reduction in left ventricular outflow gradient associated with an improvement in symptomatology. Serious complications are not uncommon. Long-term follow-up is unknown.
 

Jochanan G. Peiser, MD, MPH and Dan Greenberg, MSc

Background: Acute appendicitis is one of the most common conditions requiring surgical intervention. Open appendectomy has been a safe and effective operation for acute appendicitis for more than a century. Recently, several authors proposed that the new technique of laparoscopic appendectomy should be the preferred treatment for acute appendicitis. However, unlike laparoscopic cholecystectomy, LA[1] has not yet gained popularity.

Objectives: To compare open with laparoscopic appendectomy for length of operation, complications, postoperative pain control, length of hospitalization, and hospital costs.

Methods: A sample of 194 patients who underwent OA[2] and LA during 1995 was randomly selected for the study. Patients' demographic data, preoperative laboratory and physical values, histopathologic diagnosis of removed appendix, mean operating time, length of hospitalization, and postoperative pain control and complications were reviewed.

Results: Acute appendicitis was confirmed in 66% of patients. The groups were similar demographically (gender and mean age). We could not find any statistical differences in intraoperative and postoperative complications and use of antibiotics. The operative time was longer in the OA group (62.4 vs. 57.3 minutes), but the difference was not statistically significant (P=0.075). The hospital stay was 2.5 days in the LA group and 2.7 days in the OA group. Higher operative costs were observed in the LA group.

Conclusion: Laparoscopic appendectomy is comparable to open appendectomy with regard to complications, length of operation, hospital stay, but it is more costly. Laparoscopic appendectomy does not offer any significant benefit over the open approach.






[1] LA = laparoscopic appendectomy



[2] OA = open appendectomy


Leah Peleg, PhD, Rachel Pesso, PhD, Boleslaw Goldman, MD, Keren Dotan, Merav Omer, Eitan Friedman, MD, PhD, Michal Berkenstadt, PhD, Haike Reznik-Wolf, PhD and Gad Barkai, MD

Background: The Bloom syndrome gene, BLM, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase. The Fanconi anemia complementation group C gene was mapped to chromosome 9q22.3, but its product function is not sufficiently clear. Both are recessive disorders associated with an elevated predisposition to cancer due to genomic instability. A single predominant mutation of each disorder was reported in Ashkenazi Jews: 2281delATCTGAinsTAGATTC for Bloom syndrome (BLM-ASH) and IVS4+4A®T for Fanconi anemia complementation group C.

Objectives: To provide additional verification of the mutation rate of BLM and FACC[1] in unselected Ashkenazi and non-Ashkenazi populations analyzed at the Sheba Medical Center, and to trace the origin of each mutation.

Methods: We used polymerase chain reaction to identify mutations of the relevant genomic fragments, restriction analysis and gel electrophoresis. We then applied the ProntoTM kit to verify the results in 244 samples and there was an excellent match.

Results: A heterozygote frequency of 1:111 for BLM-ASH and 1:92 for FACC was detected in more than 4,000 participants, none of whom reported a family history of the disorders. The ProntoTM kit confirmed all heterozygotes. Neither of the mutations was detected in 950 anonymous non-Ashkenazi Jews. The distribution pattern of parental origin differed significantly between the two carrier groups, as well as between each one and the general population.

Conclusions: These findings as well as the absence of the mutations in non-Ashkenazi Jews suggest that: a) the mutations originated in the Israelite population that was exiled from Palestine by the Roman Empire in 70 AD and settled in Europe (Ashkenazi), in contrast to those who remained; and b) the difference in origin distribution of the BS[2] and FACC mutations can be explained by either a secondary migration of a subgroup with a subsequent genetic drift, or a separate geographic region of introduction for each mutation.

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[1] FACC = Fanconi anemia complementation group C


[2] BS = Bloom syndrome

Mickey Scheinowitz, PhD, Arkady-Avi Kotlyar, PhD, Shachar Zimand, MD, Ilan Leibovitz, MD, Nira Varda-Bloom, Dan Ohad, Iris Goldberg, PhD, Santiego Engelberg, MD, Nafthali Savion, PhD and Michael Eldar, MD

Background: Previous studies have demonstrated myocardial salvage by basic fibroblast growth factor administration following chronic myocardial ischemia or acute myocardial infarction.

Objectives: To study the effect of bFGF[1] on left ventricular morphometry following coronary occlusion and reperfusion episode in rats.

Methods: bFGF (0.5 mg) or placebo was continuously administered for a period of one week using an implanted osmotic pump. Animals were sacrificed 6 weeks after surgery and myocardial cross-sections were stained with Masson-trichrome and with anti-proliferating cell nuclear antigen antibody.

Results: LV[2] area, LV cavity diameter, LV cavity/wall thickness ratio, and injury size were unchanged compared with control animals. Proliferating endothelial cells were significantly more abundant in injured compared with normal myocardium, but with no differences between animals treated or not treated with bFGF.

Conclusions: One week of systemic bFGF administration following coronary occlusion and reperfusion had no additional effect on LV geometry or cellular proliferation in rats.

________________________

[1]
bFGF = basic fibroblast growth factor

[2] LV = left ventricular

Shomron Ben Horin, MD, David Luria, MD, Michael Glikson, MD and Avi Livneh, MD
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