Israel Medical Association Journal

Objectives: To test whether an early change in neurohormonal and inflammatory markers after implantation can predict the clinical response to CRT.

Methods: The study group included 32 patients with advanced symptomatic systolic heart failure and a prolonged QRS complex and who were assigned to undergo CRT. Baseline plasma levels of B-type natriuretic peptide and high sensitivity C-reactive protein were determined in the peripheral venous blood and coronary sinus. Post-implantation levels were determined 2 weeks post-procedure in the PVB[2]. Baseline levels and their change in 2 weeks were correlated with all-cause mortality and hospitalization for congestive heart failure.

Results: At baseline, coronary sinus levels of BNP[3] but not hsCRP[4] were significanly elevated compared to the PVB. Compared to baseline levels, BNP and hsCRP decreased significantly within 2 weeks after the implantation (BNP mean difference 229.1 ± 102.5 pg/ml, 95% confidence interval 24.2–434, P < 0.0001; hsCRP mean difference 5.2 ± 2.4 mg/dl, 95% CI[5] 0.3–10.1, P = 0.001). During a mean follow-up of 17.7 ± 8.2 months 6 patients died (18.7%) and 12 (37.5%) were hospitalized due to exacerbation of CHF[6]. Baseline New York Heart Association and CS[7] BNP levels predicted CHF-related hospitalizations. HsCRP levels or their change over 2 weeks did not predict all-cause mortality or hospitalizations.

Conclusions: BNP levels in the CS and peripheral venous blood during biventricular implantation and 2 weeks afterwards predict cilinical response and may guide patient management.

We describe a unique E3, the F-box protein, Ufo1, of yeast. Ufo1 recruits the mating switch endonuclease, Ho, to the SCF complex for ubiquitylation. In addition to the F-box and WD40 protein-protein interaction domains found in all F-box proteins, Ufo1 has a unique domain comprising multiple copies of the ubiquitin-interacting motif. Ufo1 interacts with the UbL-UbA protein, Ddi1, via its UIMs[1], and this is required for turnover of SCF ^Ufo1 complexes. This is a novel function for an UbL-UbA protein. Deletion of the genomic UFO1 UIMs is lethal and our data indicate that Ufo1ΔUIM acts as a dominant negative leading to inhibition of the SCF pathway of substrate degradation and to cell cycle arrest. Furthermore, we found that Ddi1 is required for the final stages of degradation of Ho endonuclease. In the absence of Ddi1, Ho does not form a complex with the 19S RP and is stabilized. Stabilization of Ho leads to perturbation of the cell cycle and to the formation of multi-budded cells. Our experiments uncover a novel role for the ubiquitin-proteasome system in maintenance of genome stability.

Background: The relationship between the amount of rehabilitation therapy and functional outcome in stroke patients has not been established.

Objectives: To evaluate the effectiveness of inpatient rehabilitation for post-acute stroke, and examine the relationship between intensity of therapies and functional status at discharge.

Methods: We evaluated 50 first-stroke patients, average age 63 years, in a prospective, descriptive study. The impairment and Functional Independence Measurement were assessed both at admission to rehabilitation and at discharge. Patients were monitored weekly during their stay by means of discipline-specific measures of activity level. Predictor variables included intensity of physical, occupational and speech therapies; demographic characteristics; length of stay; and time since the stroke.

Results: A significant reduction in impairment was observed at discharge. The predictors of gains and activity level at discharge as well as motor vs. cognitive components of the FIM[1] were neither consistent nor did they occur in the same trend of functional improvement. Greater FIM motor level at discharge was associated with younger age, higher admission motor and cognitive level, and receipt of any speech therapy, while greater FIM cognitive level was associated with higher cognitive level at admission, shorter interval from onset to admission, and more intense occupational therapy. More intense OT[2] was associated with greater and more cognitive improvement during the hospitalization.   

Conclusion: Since the sample was relatively small and heterogeneous in terms of the patients’ functional abilities, the findings cannot be generalized to the whole population of stroke patients. Further efforts to identify the best timing, modalities, intensity and frequency of the various treatments are needed to improve the cost-benefit equation of rehabilitation in stroke patients.

Background: Reports from Europe and North America indicate that significant changes have occurred in the practice of cardiac surgery in the last two decades.

Objectives: To examine the trends and case-mix in cardiac surgery in Israel and their relationship with changes in invasive cardiology.

Methods: We analysed data collected by the Ministry of Health from all cardiac centers in Israel from 1985 to 2002.

Results: Three periods were identified: the 1980s, when a relatively small number of operations were performed; 1990–1994, characterized by a dramatic rise in the number of operations; and 1994–present, characterized by a small decline and stabilization in the rate of operations. The percentage of valve procedures increased significantly from 15% of all cardiac surgeries in 1991 to 21% in 2002 (P = 0.002). In addition, the chance of a diagnostic coronary angiography being followed, in the same patient, by an interventional procedure such as percutaneous transluminal coronary angioplasty or by a coronary artery bypass graft increased dramatically from 42% in 1991 to 69% in 2002. At Rabin Medical Center, there was a constant decline in the percent of repeated CABGs[1] out of the total CABGs performed, from 6.7% in 1996 to 1.3% in 2002.

Conclusions: Despite the rise in the rate of percutaneous coronary interventions since 1991, there has been no significant decline in the rate of CABGs performed. However, there is a significant shift to more complex operations. The number of repeated CABG operations has significantly decreased and, in view of the growing use of arterial grafts and further improvements in invasive cardiology techniques, we expect this decline to continue.

Background: Congestive heart failure is extremely common in octogenarians and is associated with severe fatigue, shortness of breath, recurrent hospitalizations, and death. These patients, many of whom are anemic, are often resistant to standard CHF[1] therapy including angiotensin-converting enzyme inhibitors, beta-blockers and diuretics.

Objectives: To examine whether correction of the anemia (hemoglobin <12 g/dl) in CHF patients lowers their resistance to therapy.

Methods: Forty octogenarians with anemia and severe resistant CHF were administered a combination of subcutaneous erythropoietin and intravenous iron sucrose.

Results: This combination therapy led to a marked improvement in cardiac function, shortness of breath and fatigue, a marked reduction in the rate of hospitalization and a stabilizing of renal function.

Conclusion: Anemia appears to be an important but ignored contributor to the progression of CHF, and its correction may improve cardiac and renal status as well as the quality of life in elderly patients.

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 Pronto^TM 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 Pronto^TM 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