Israel Medical Association Journal

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: Open reduction and internal fixation are the current trends of treatment for comminuted calcaneal fractures. Assessing treatment results is often difficult due to discrepancy between objective parameters such as range of movement, and subjective results such as pain.

Objectives: To test the reliability of footprint analysis as an adjuvant method of postoperative assessment of patients who sustained calcaneal fractures.

Methods: Dynamic and static footprint analysis was used as an adjuvant method to objectively assess operative results. This method is simple and is independent of the patient’s initiatives. This modality was used in 22 patients followed-up 9–90 months postoperatively.

Results: We found a good correlation between footprint analysis and objective and subjective parameters of results expressed by the American Orthopedic Foot and Ankle Society hind foot score. In certain cases, this method can be used to distinguish between uncorrelated parameter results, such as malingering, and workmens’ compensation claims.

Conclusion: We recommend the use of this simple, non-invasive objective test as an additional method to assess the results of ankle and foot surgery treatment.
 

Background: Matrix metalloproteinases are proteolytic enzymes that degrade extracellular matrix components. Numerous studies have demonstrated that individual MMPs[1] play a crucial role in tumor invasion and metastasis.

Objective: To examine the expression of MMPs and their inhibitor TIMP-2 in neoplastic and normal thyroid tissues.

Methods: We examined 33 cases of thyroid tumor (papillary, follicular and medullary carcinoma, follicular adenoma and multinodular goiter). MMP protein content and activity were measured by enzyme-linked immunosorbent assay and gel zymography. Immunohistochemistry was also performed.

Results: The thyroid tissues examined secreted MMP-2 and 9 as well as TIMP-2, but only MMP-2 was significantly higher in papillary carcinoma cases compared to the adjacent normal tissue or to the other tumor entities. Increased MMP-2 immunohistochemical staining was demonstrated in the neoplastic papillary epithelial component. No significant difference was seen between papillary carcinomas with lymph node metastases and those without.

Conclusions: Increased MMP-2 expression may be useful as a diagnostic marker to differentiate papillary carcinoma from other thyroid neoplasms, but it cannot serve as a useful prognostic marker.

Background: Primary idiopathic pulmonary hypertension is a rapidly progressive disease with a median survival of less than 3 years. Recently its prognosis was shown to dramatically improve with the use of epoprostenol, an arachidonic acid metabolite produced by the vascular endothelium, which increases the cardiac output and decreases the pulmonary vascular resistance and pulmonary arterial pressure. This drug enhances the quality of life, increases survival and delays or eliminates the need for transplantation.

Objective: To review the experience of Israel hospitals with the use of epoprostenol.

Methods: The study group comprised 13 patients, 5 men and 8 women, with an age range of 3–53 years. All patients suffered from arterial pulmonary hypertension. Epoprostenol was administered through a central line in an increased dose during the first 3 months, after which the dose was adjusted according to the clinical syndrome and the hemodynamic parameters.

Results: After 3 months the mean dose was 10 ng/kg/min and the pulmonary artery pressure decreased from 7 to 38%. After one year, the PAP decreased at a slower rate. Two cases required transplantation, three patients died, and seven continued taking the drug (one of whom discontinued). Four episodes of septicemia were observed. Today 10 patients are alive and well and 7 continue to take epoprostenol.

Conclusion: We found that epoprostenol improves survival, quality of life and hemodynamic parameters, with minimum side effects.

Intractable forms of autoimmune diseases follow a rapid course, with a significantly shortened life expectancy sometimes comparable to that of malignant diseases. Immunoablative therapy, including high dose cytotoxic agents and hematopoietic autologous stem cell rescue, was recently introduced as an aggressive approach to treat autoimmune diseases that have a rapid course and are resistant to conventional therapy. The most frequent indication for this type of treatment is multiple sclerosis, seconded by systemic sclerosis. The results of immunoablative treatment with documented responses in both diseases are encouraging. The data are mature enough to begin comparative randomized studies of immunoablative versus conventional treatment to validate the benefit of the aggressive approach. A randomized trial involving SSc[1] was recently launched (ASTIS) and a trial involving MS[2] is under preparation. Considerably less experience with immunoablative treatment has been gained in systemic lupus erythematosus, rheumatoid arthritis, and other disorders with an autoimmune pathophysiology. Autologous hematopoietic stem cell transplantation in humans offers more long-lasting immunosuppression than reeducation of lymphocytes. In fact, allogeneic transplantation may replace the whole immune system. However, this attractive approach is still associated with considerable morbidity and mortality and is not yet justified for treatment of automimmune diseases. Non-myeloablative allogeneic transplantation and sub-myeloblative high dose cyclophosphamide without stem cell support are alternative approaches that could be explored in pilot studies.

_______________________________

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.

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.

______________________________________

[1] FACC = Fanconi anemia complementation group C

Background: Familial Mediterranean fever is an autosomal recessive disease characterized by sporadic attacks of inflammation affecting the serosal spaces. The gene associated with FMF[1] (MEFV), mainly expressed in neutrophils, was recently found to be expressed also in primary cultures of serosal origin (peritoneal and synovial fibroblasts). A C5a inhibitor, previously detected in normal serosal fluids, was recently identified in serosal cultures as well, and was found to be deficient in serosal fluids and cultures obtained from FMF patients.

Objective: To investigate the effect of colchicine (the main therapeutic agent for FMF patients) and certain inflammatory cytokines (IL-1b, TNF-a, IFN-a, IFN-g) on MEFV expression and C5a inhibitor activity in neutrophils and primary peritoneal fibroblast cultures.

Methods: Human primary peritoneal fibroblast cultures and neutrophils were studied for MEFV expression and C5a inhibitor activity, using reverse transcription-polymerase chain reaction and C5a-induced myeloperoxidase assay, respectively, in the presence and absence of colchicine and cytokines.

Results: MEFV expression in neutrophils was high and could not be induced further. Its expression in the peritoneal fibroblasts was lower than in neutrophils and could be induced using colchicine and cytokines parallel with induction of C5a inhibitor activity. Semi-quantitative RT-PCR[2] assays enabled estimation of MEFV induction by the cytokines at 10–100-fold and could not be further increased by concomitant addition of colchicine.

Conclusion: Serosal tissues, which are afflicted in FMF, express colchicine and cytokine-inducible MEFV and contain inducible C5a inhibitor activity. The relation between colchicine ability to induce MEFV and C5a inhibitor activity, and its efficacy in FMF treatment, require further investigation.

______________

[1] RT-PCR = reverse transcription-polymerase chain reaction

[2] FMF = familial Mediterranean fever