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עמוד בית
Mon, 25.11.24

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July 2001
Michael D. Lockshin, MD
Autoimmune diseases are said to have high female/male (F/M) ratios, but these ratios are imprecise. Published definitions and classifications of autoimmune diseases differ substantially, as do the F/M ratios themselves. Imputed causality of auto-immune diseases requires better precision. Some thyroid, rheumatic and hepatic diseases consistently have high F/M ratios, but marked differences exist in the reported quantity of the ratios. Other autoimmune diseases have low F/M ratios. Because F/M ratios reflect incidence and not severity of disease, gonadal hormones, if they play a role, must do so through a threshold or permissive mechanism. Sex differences related to environmental exposure, X-inactivation, imprinting, X or Y chromosome genetic modulators, and intrauterine influences remain as alternate, theoretical, explanations for sex differences of incidence. The epidemiology of the sex­discrepant autoimmune diseases - young, female - suggests that an explanation for sex discrepancy lies in differential exposure, vulnerable periods, or thresholds, rather than in quantitative aspects of immunomodulation.

Mehrdad Herbert, MD, Michael Segal, MD, Gratiana Hermann, MD and Judith Sandbank, MD
June 2001
Elisheva Simchen, MD, MPH, Irit Naveh, RN, MSc, Yana Zitser-Gurevich, MD, MPH, Dalit Brown, MSc and Noya Galai, PhD

Objective: To explore the putative effect of cardiac rehabilitation programs on the health-related quality of life’ and ‘return to work’ in pre-retirement patients one year after coronary artery bypass grafting.

Methods: Of the 2085 patients aged 45-4 who survived one year after CABG and were Israeli residents, 145 (6.9%) had participated in rehabilitation programs. Of these, 124 (83%) who answered QOL questionnaires were individually matched with 248 controls by gender, age within 5 years. and the time the questionnaire was answered. All patients had full clinical follow-up including a pre-operative interview. The Short Form-36 QOL questionnaire as well  as a specific questionnaire were mailed to surviving patients one year after surgery. Study outcomes included the scores on eight scales and two summary components of the SF-36, as well as return to work’ and ‘satisfaction with medical services’ from the specific questionnaire. Analysis was done for matched samples.

Results: Cardiac rehabilitation participants had signifi­cantly higher SF-36 scores in general health, physical functioning, and social functioning. They had borderline significant higher scores in the physical summary component of the SF-36. The specific questionnaire revealed significantly better overall functioning, higher satisfaction with medical care. and higher rate of return to work. While participants in cardiac rehabilitation and their controls were similar in their socio­-demographic and clinical profiles, participating patients tended to be more physically active and more fully employed than their controls.

Conclusions: Rehabilitation participants had a self-per­ception of better HRQOL, most significantly in social function­ing. Our findings of more frequent return to work and higher satisfaction with medical care should induce a policy to encourage participation in cardiac rehabilitation programs after CABG.
 

Alex Kessler, MD, Ephraim Eviatar, MD, Judith Lapinsky, MD, Tifha Horne, MD, Nathan Shlamkovitch, MD and Shmuel Segal, MD
Alexander Blankstein, MD, Ilan Cohen, MD, Zehava Heiman, MD, Moshe Salai, MD, Lydia Diamant, RT, Michael Heim, MD and Aharon Chechick, MD

Background: Foreign bodies are sometimes overlooked in the initial evaluation of soft tissue wounds in the emergency room setting. The physical examination identifies foreign bodies that are superficial enough to be seen or palpated, while radiographs reveal those that are radio-opaque. If these two criteria are not met, however, the foreign body may remain undetected. These patients present later with long-standing pain in the area of penetration sometimes associated with localized tenderness.

Objectives: To assess the role of ultrasonography in the diagnosis and management of patients with a suspected retained foreign body.

Methods: Ultrasound was used in 21 patients with suspected retained foreign bodies and the diagnosis was positive in 19. Fifteen underwent a surgical exploration in which the ultrasound was used as an adjunctive modality either pre- or intraoperatively to assist in the localization of the foreign body.

Results: All procedures were successful. No postoperative complications were recorded at an average follow-up of 2 years. Three patients gradually became asymptomatic and were left untreated. One patient was lost to follow-up.

Conclusion: Sonography is an extremely effective tool for the late diagnosis of retained foreign bodies in the soft tissues. We suggest that its availability in the emergency room may decrease the rate of misdiagnosis and avoid these unfortunate cases, although this remains tc be proven.
 

Hanna J. Garzozi, MD, Nur Shoham, MD, Hak Sung Chung, MD, PhD, Larry Kagemann, MS and Alon Harris, PhD
May 2001
Aaron Ciechanover, MD, DSc

Between the 1960s and 1980s, the main focus of biological research was nucleic acids and the translation of the coded information into proteins. Protein degradation was a neglected area and regarded by many as a scavenger, non-specific and end process. While it was known that proteins are turning over, the large extent and high specificity of the process - where distinct proteins have half-lives that range from a few minutes to several days - have not been appreciated. The discovery of the lysosome by Dr. Christian de Duve did not change this view significantly, as this organelle is involved mostly in the degradation of extra- and not intracellular proteins, and it was clear that lysosomal proteases, similar to those of the gastrointestinal tract, cannot be substrate specific. The discovery of the complex cascade of the ubiquitin pathway has changed this view dramatically. It is now clear that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a broad array of basic pathways during cell life and death. With the multitude of substrates targeted and processes involved, it is not surprising that aberrations in the pathway have been recently implicated in the pathogenesis of many diseases, certain malignancies and neurodegeneration among them. Degradation of a protein via the ubiquitin pathway involves two successive steps: a) conjugation of multiple ubiquitin moieties to the substrate, and b) degradation of the tagged protein by the downstream 263 proteasome complex with release of free and re-utilizable ubiquitin. Despite intensive research, the unknown still exceeds what we currently know on intracellular protein degradation and major key problems remain unsolved. Among these are the modes of specific and timed recognition of the myriad substrates of the system and the nature of the mechanisms that underlie aberrations in the system and pathogenesis of diseases.

Dov Estlein, MD, Gil Ohana, MD, Ruven Weil, MD, Lea Rath-Wolfson, MD and Yaakov Wolloch, MD
April 2001
Dror Harats, MD, Offer Yodfat, MD, Ram Doolman, MSc, Slava Gavendo, MSc, Daniella Marko, BSc, Aviv Shaish, PhD and Ben-Ami Sela, PhD

Background: Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.

Objectives: To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.

Methods and Results: We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n=26), a 17% reduction n homocysteine was detected in the group treated with bezafibrate (n=12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.

Conclusions: These results indicate that an increase In plasma homocysteine levels following administration of flbrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
 

Ofer N. Gorfit, MD and Khalil Abu-Dalu, MD

Background: Despite years of research and clinical experience with acute appendicitis, the rate of complications in the pediatric age group continues to be high.

Objective: To characterize the profile of the child with appendicitis complicared by perforation or intraabdominal abscess.

Methods: Between 1 January 1985 and 31 December 1997 in our department, 581 children under the age of 14 years were clinically diagnosed as suffering from "acute appendici­tis". The final diagnoses were: white appendix in 28 cases (4.8%), acute non-complicated appendicitis in 472 (81%), and complicated appendicitis in 81 (13.9%), including 51 cases of free perforation (8.7%) and 30 cases of intraabdominal abscess (5.2%). We retrospectively reviewed the charts of all children with complicated appendicitis and those of 70 randomly selected children with non-complicated appendicitis, and compared patient age, gender, weight percentile, past medical history, and course of the illness.

Results: The children with complicated appendicitis were significantly younger (R~4.8*10~7), they had higher oral and rectal temperatures (P=7.9*10-8), higher platelet count (P=0.0008) and lower hemoglobin level (P=0.004). No difference was found in white blood count (P=0.41). Total delay from symptom onset to surgery was 33 hours (SD 23) in the non-complicated group, 60 hours (SD 38) in the perforated appendicitis group, and 176 hours (SD 107) in the intra­abdominal abscess group (P=4.6*10-8). No difference in intra­hospital delay was found.

Conclusions: Children with complicated appendicitis are characterized by younger age, longer delay from symptom onset to correct diagnosis, and typical laboratory findings. Delays in diagnosis can be avoided by first considering the diagnosis of acute appendicitis in the differential diagnosis when examining any child with abdominal pain.

Allan Wilk

Anti-neutrophil cytoplasm antibodies are important markers of certain small vessel necrotizing vasculitides, but the optimal use of laboratory results in daily clinical practice necessitates collaboration between clinicians and laboratory specialists. Physicians must familiarize themselves with ANCA tests in ANCA-related vasculitides as well as in differential diagnostic patient populations in order to define cutoff values. Indirect immunofluorescence with a consensus-agreed technique combined with standardized enzyme immunoassays is the modality for detecting the main SSV-associated ANCA specificities using cutoff values that can sufficiently distinguish SVV from non-SVV patients. The combined use of IF and direct EIA to demonstrate proteinase 3-ANCA and myeloper­oxidase-ANCA at significant levels leads to a very high diagnostic specificity towards SVV conditions such as Wegen­er’s granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome, and limited forms of these such as renal-limited focal necrotizing glomerulonephritis. A strong reactivity of ANCA against several azurophil granule components indicates a drug-induced syndrome. ANCA-related SVV and drug­induced vasculitis or lupus syndromes have characteristic ANCA profiles that can help distinguish these conditions from other inflammatory diseases.

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