Israel Medical Association Journal

Fanconi anemia is a rare autosomal recessive disorder characterized clinically by congenital abnormalities, progressive bone marrow failure, and a predisposition to malignancy. FA cells are sensitive to DNA cross-linking agents. Complementation analysis of FA cells using somatic cell fusion has facilitated the identification of eight complementation groups, suggesting that FA is a genetically heterogeneous disorder. Six genes (FANCA, FANCC, FANCD2, FANCE, FANGF, FANCG) have been cloned so far. The majority of affected patients belong to FA group A. Of the 32 unrelated Israeli patients with FA that we studied, 6 carried the FANCC mutations and 15 the FANCA mutations. Among the Jewish patients, ethnic-related mutations were common. Recent cumulative evidence suggests that the FA proteins are repair proteins. FANCC, FANCA and FANCG bind and interact in a protein complex found in the cytoplasm and nucleus of normal cells. FANCD2 exists in two isoforms; the long active form, FANCD2-L, is absent from FA cells of all complementation groups. FANCD2 co-localized with BRCA1 in unclear foci, probably as part of a large genomic surveillance complex. Studies using FANCA and FANCC knockout mice suggest that bone marrow precursors express interferon-g hypersensitivity and show progressive apoptosis. The definition of the molecular basis of FA in many affected families now enables prenatal diagnosis.

Background: The use of an automated biopsy system for renal biopsy has recently gained popularity, but its safety in single functioning kidneys is unclear.

Objective: To report our experience with the automated system for closed renal biopsy during a 5 year period.

Methods: Eighty-five patients underwent percutaneous native renal biopsy with the automated biopsy gun (16G needle) under real-time ultrasound. They were chronologically divided into two groups: 41 patients (group A), using an older ultrasound machine; and 44 patients (group B), using a newer ultrasound machine. Nine patients biopsied with a manual 14G Tru-cut needle served as the control (group C).

Results: The number of "attempted" passes at the kidney was 4.0 ± 0.1 in group B, 4.7 ± 0.3 in group A (P < 0.05 vs. group B), and 5.8 ± 0.5 in group C (P < 0.01 vs. group B). The number of successful passes did not differ (3.3 ± 0.1, 3.3 ± 0.1, 3.1 ± 0.2). The ratio of "attempted/successful" was 1.28 ± 0.07 in group B, 1.95 ± 0.38 in A, and 1.90 ± 0.21 in C (P < 0.01 vs. B). The number of glomeruli obtained was similar in the three groups. Adequate tissue was obtained in 95%, 98%, and 100%, respectively. Hemoglobin decreased by 4.3 ± 1.1% in group B, 6.9 ± 1.3% in group A, and 11.3 ± 1.8% in group C (P < 0.05 vs. B). Perinephric/subcapsular hematoma occurred in 5 patients (11.4%) in group A (2 taking aspirin), in 2 patients (4.9%) in group B, and in none in group C. The necessity for blood transfusion post-biopsy was similar in all groups. Four of five patients with single functioning kidneys (one in group A and four in group B) had uneventful biopsies, and adequate tissue was obtained in three.

Conclusions: The use of the automated biopsy gun is effective, safe and has a low rate of major complications. It may be used safely in single functioning kidneys.

Background: Ventilator-dependent patients represent an increasing clinical, logistic and economic burden.  An alternative solution might be monitored home care with high-tech ventilatory support systems. 

Objectives: To explore the implications of such home-care management, such as its impact on quality of life and its cost-effectiveness, and to assess the practical feasibility of this mode of home care in Israel.

Methods: We surveyed 25 partly or fully home-ventilated patients (17 males and 8 females), average age 37.6 years (range 1–72), who were treated through a home-care provider during a 2 year period.

Results: Most patients (n=18) had a neuromuscular respiratory disorder.  The average hospital stay of these patients prior to entry into the home-care program was 181.2 days/per patient.  The average home-care duration was 404.9 days/per patient (range 60–971) with a low hospitalization rate of 3.3 ± 6.5 days/per patient.  The monthly expenditure for home care of these patients was one-third that of the hospital stay cost ($3,546.9 vs. $11,000, per patient respectively).  The patients reported better quality of life in the home-care environment, as assessed by the Sickness Impact Profile questionnaire. 

Conclusions: Home ventilation of patients in Israel by home-care providers is a practical and attractive treatment modality in terms of economic benefits and quality of life.
 

Background: The progressive increase in the number of elderly patients with hip fractures and the particular multidisciplinary needs of this population call for the investigation of other models of orthogeriatric care.

Objectives: To describe the nature and assess the feasibility of a comprehensive orthogeriatric unit attending to patients' surgical, medical and rehabilitation needs in a single setting.

Methods: This retrospective chart review describes consecutive older patients with hip fractures admitted directly from the emergency ward to an orthogeriatric ward.

Results: The mean age of the 116 patients evaluated was 82.4 years. Delay to surgery was 3.6±3.1 days and total length of stay 23.9±11.0 days. No patient was transferred to other acute medical wards of the hospital and 66.4% were able to return to their previous living place. Rates of major complications and mortality were extremely low.

Conclusion: The present model of a comprehensive orthogeriatric ward is a practical, applicable and feasible service for elderly hip fracture patients and can cover the various needs of these patients. The deployment arrangements needed to establish and operate the ward were minimal and there were only a few management and organizational problems. The cost-effectiveness and other comparative benefits of this type of service have yet to be clarified.
 

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