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עמוד בית
Sun, 24.11.24

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March 2002
Moshe Wald, MD, Sarel Halachmi, MD, Gilad Amiel, MD, Shahar Madjar, MD, Michael Mullerad, MD, Ines Miselevitz, MD, Boaz Moskovitz, MD and Ofer Nativ, MD

Background: The bladder tumor antigen stat is a simple and fast one-step immunochromatographic assay for the detection of bladder tumor-associated antigen in urine.

Objectives: To evaluate the BTA[1] stat in non-bladder cancer patients in order to identify the categories contributing to its low specificity.

Methods: A single voided urine sample was collected from 45 patients treated in the urology clinic for conditions not related to bladder cancer. Each urine sample was examined by BTA stat test and cytology.

Results: The overall specificity of the BTA stat test was 44%, which was significantly lower than that of urine cytology, 90%. The false positive rates for BTA stat test vary among the different clinical categories, being highest in cases of urinary tract calculi (90%), and benign prostatic hypertrophy (73%). Exclusion of these categories from data analysis improved BTA stat specificity to 66%.

Conclusions: Clinical categories contributing to low BTA stat specificity can be identified, and their exclusion improves the specificity of this test.






[1] BTA = bladder tumor antigen


Konstantin Lavrenkov, MD, PhD, Sofia Man, MD, David B. Geffen, MD and Yoram Cohen, MD

Background: Recent years have brought significant progress to the development of hormonal therapies for the treatment of breast cancer. Several new agents have been approved for the treatment of breast cancer in the metastatic setting, among which is the new non-steroidal aromatase inhibitor, anastrozole, introduced for clinical use in Israel in March 1997.

Objectives: To evaluate the response rate and survival duration of patients treated with anastrozole for metastatic breast cancer, who had previously received at least one line of hormonal therapy.

Methods: Anastrozole was administered to 37 patients with metastatic breast cancer. The median age was 64 years. Estrogen receptor was positive in 20 patients, negative in 10 and unknown in 7. All patients were previously treated with tamoxifen in the adjuvant setting or as first-line hormonal therapy for metastatic disease. Anastrozole was given orally, 1 mg/day. Response was evaluated 2 months after the initiation of treatment and reevaluated every 2 months. Therapy was given until disease progression. Ten ER[1]-negative patients were excluded from the final analysis.

Results: Twenty-seven patients were eligible for response and toxicity analysis. The median follow-up was 20 months. One patient (3.7%) achieved complete response and remains free of disease 28 months after start of therapy. No partial responses were seen. Twenty patients (74%) had stable disease. Two year actuarial survival was 57%. Median survival was 26.5 months after starting therapy and median progression free survival was 11 months. The toxicity was mild: one patient (3.7%) complained of weight gain and one patient (3.7%) had mild fatigue.

Conclusion: Although the response rate was low, hormonal therapy with anastrozole seems to be beneficial in terms of disease stabilization, freedom from progression, and overall survival without serious toxicity.  






[1] ER = estrogen receptor


Eliyahu H. Mizrahi, MD, Donald W. Jacobsen, PhD and Robert P. Friedland, MD
Alexander Kagan, MD, Nurit Haran, PhD, Ludmila Leschinsky, MD, PhD, Ruty Sarafian, RN, BA, Dan Aravot, MD, Jaffa Dolberg, RN, Ziv Ben-Ary, MD and Jason Rapoport, MB, BS, MRCP

Background: Leptin is a 16 kDa hormone synthesized by adipocytes and involved in body weight regulation.

Objectives: To determine serum leptin concentrations in heart, liver and kidney transplant recipients.

Methods: We investigated 57 patients: 18 male heart transplant recipients (age 25-69 years) at 1-66 months after transplantation, 6 female and 8 male liver transplant recipients (age 33-70) at 11-73 months after transplantation, and 10 female and 15 male kidney transplant recipients (age 20-61) at 3-138 months after transplantation. All recipients were receiving immunosuppressive therapy, including prednisone 0-20 mg/day, azathioprine 75-125 mg/day, cyclosporin 100-250 mg/day or tacrolimus 2-10 mg/day. The results were compared to those of 10 female and 10 male healthy controls. Morning serum concentrations of leptin were measured with a commercial radioimmunoassay (Linco Research Inc., USA), and serum insulin and cortisol levels were measured by radioimmunoassay.

Results: Patients (both men and women) after heart, liver and kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/body mass index ratios than controls. Serum leptin concentrations were significantly higher in women than in men and correlated very significantly with BMI[1] in all cases. The multivariate stepwise analyses showed that among parameters including BMI, gender, age, time after transplantation, prednisone dose, hematocrit, serum concentrations of glucose, albumin, creatinine, cortisol and insulin, only BMI, gender, cortisol and insulin were significant independent determinants of serum leptin levels in these patients.

Conclusions: This is the first report showing that, in addition to body mass index and gender, basal cortisol and insulin levels affect the hyperleptinemia in transplant patients. The clinical relevance of hyperleptinemia in these patients will require further investigation.






[1] BMI = body mass index



 
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
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.
 

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.

______________________________________

[1] FACC = Fanconi anemia complementation group C


[2] BS = Bloom syndrome

Freda DeKeyser, RN, PhD, Malka Avitzour, MPH, Dorraine Day Watts, PhD, RN, Arthur L. Trask, MD and Michael Muggia-Sullam, MD

Background: Trauma is viewed by many as a global problem. The phenomenon of similar outcomes within differing healthcare delivery systems can illuminate the strengths and weaknesses of various trauma systems as well as the effects of these characteristics on patient outcome.

Objectives: To compare and contrast demographic and injury characteristics as well as patient outcomes of two urban/suburban trauma centers, one in Israel and the other in the United States.

Methods: Study data were obtained from the trauma registries of two trauma centers. Demographic variables, injury characteristics and outcomes were compared statistically between registries.

Results: Significant differences between the registries were found in demographic variables (age), injury characteristics (Injury Severity Score and mechanism of injury), and outcome (mortality and length of stay). Age and Injury Severity Score were found to be significant predictors of outcome in both registries. The Glasgow Coma Score was found to contribute to patient outcomes more than the ISS[1]. Differences were found in the relative impact of injury and demographic factors on outcomes between the registries. After including the influence of these factors on patient outcomes, significant differences still remained between the outcomes of the trauma centers.

Conclusions: Despite possible explanations for these differences, true comparisons between centers are problematic.

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[1] ISS = Injury Severity Score


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