Israel Medical Association Journal

Background: Pregnant diabetic women are often subjected to frequent and prolonged hospitalizations to assure tight glycemic control, but in recent years attempts have been made at ambulatory control. The financial and social advantages of ambulatory management are obvious, but no report to date has prospectively compared its efficacy with that of hospitalization.

Objectives: To evaluate the efficacy and cost of ambulatory care as compared to repeated hospitalizations for management of diabetes in pregnancy.

Methods: We conducted an 8 year prospective controlled study that included 681 diabetic women, experiencing 801 singleton pregnancies, with commencement of therapy prior to 34 gestational weeks. During 1986–1989, 394 pregnancies (60 pre-gestational diabetes mellitus and 334 gestational diabetes mellitus) were managed by hospitalization, and for the period 1990–1993, 407 pregnancies (61 PGDM and 346 GDM) were managed ambulatorily. Glycemic control, maternal complications, perinatal mortality, neonatal morbidity and hospital cost were analyzed.

Results: There was no difference in metabolic control and pregnancy outcome in women with PGDM between the hospitalized and the ambulatory groups. Patients with GDM who were managed ambulatorily had significantly lower mean capillary glucose levels, later delivery and higher gestational age at induction of labor as compared to their hospitalized counterparts. In this group there were also lower rates of neonatal hyperbilirubinemia, phototherapy and intensive care unit admissions and stay. The saved hospital cost (in Israeli prices) in the ambulatory group was $6,000 and $15,000 per GDM and PGDM pregnancy, respectively.

Conclusions: Ambulatory care is as effective as hospitalization among PGDM patients and more effective among GDM patients with regard to glycemic control and neonatal morbidity. This is not only more convenient for the pregnant diabetic patient, but significantly reduces treatment costs.
 

Background: The recent influx of Ethiopian immigrants to Israel has created challenges for healthcare workers. Qualitative research methods have proven to be of value in providing useful data in cross-cultural medical settings.

Objective: To learn about parents' perception of the health of their children among a group of Ethiopian immigrants in Israel.

Methods: Ethiopian parents of children under age 3 registered with a family medicine clinic in Jerusalem were invited to participate in two focus groups. Transcripts of the group discussions were analyzed to reveal themes relating to children's health.

Results: Analysis of the transcripts revealed five themes relating to the health of children in two domains: the intra-familial and the extra-familial. Specific themes that emerged in the intra-familial domain were: the role of traditional medicine, gender-specific roles in child care, and decision-making in seeking extra-familial medical help. Themes in the extra-familial domain were recognition of illness and the meaning of symptoms, and notions of prevention and resistance to illness. The collected data found application in the daily clinical work of the researchers and enriched understanding of their patients.

Conclusions: Ethiopian immigrants to Israel share special perceptions of their children’s health that differ from prevailing beliefs in Israel. Focus groups provide health workers with a wealth of data on these beliefs that will enable them to offer more culturally sensitive care.
 

Background: Fibroadema, one of the most common benign breast lesions, has a characteristic age-specific incidence and is associated with other pathological entities in 50% of cases. The clinical or imaging diagnosis of fibroadenoma may be erroneous, and in some cases is found to be invasive cancer. The clustering of such entities, their correlation with age, and the risk of synchronous breast malignancy are uncertain.

Objective: To explore the possibility of any sigficant clustering of fibroadenoma-associated benign breast disease and to assess the possible risk of concomitant breast cancer.

Method: We analyzed the pathological results of 147 women undergoing excisional biopsies for fibroadenoma diagnosed pre-operatively either by clinical examination and imaging (n=117) or by radiology alone (n=30). The inter-relationships among all entities associated with fibroadenoma were studies by hierarchial cluster analysis. The correlation of the various pathologies with the risk of invasive breast cancer in relation to the patient’s age was also evaluated.

Results: Fibroadema-associated pathologies were found in 48% of the cases: sclerosing adenosis (23%), duct ectasia (17/7%), apocrine metaplasia (15.6%), florid fibrocystic disease (12.9%), duct papillomatosis (11.6%), infiltrating duct carcinoma (5.4%), duct carcinoma in situ (3.4%), and 1 case of lobular carcinoma in situ (0.6%). An orderly internal hierarchy and three significant clusters emerged: a) epithelial apocrine metaplasia, duct ectasia and sclerosing adenosis (similarity coefficients 16.0, 11.0 and 8.0 respectively); b) papillomatosis, florid fibrocystic disease and calcifications (similarity coefficients of 6.0, 4.0 and 2.0 respectively); and c) infiltrating duct carcinoma in situ (similarity coefficients of 1.8 and 1.6 respectively). Seven of the eight patients with breast cancer were older than 40 years.

Conclusions: In about half of the cases fibroadema was associated with other pathological entities clustered in an orderly hierarchy. The rarity of synchronous breast cancer in the younger age group and its more common association with fibroadema in the older age groups dictate a different approach to each. The finding of fibroadema in women older than 40 indicates the need for surgical excision.
 

Fibromyalgia syndrome is a chronic, painful musculoske­letal disorder of unknown etiology and/or pathophysiology. During the last decade many studies have suggested autonomic nervous system involvement in this syndrome, although contradictory results have been reported. This review focuses on studies of the autonomic nervous system in fibromyalgia syndrome and related disorders, such as chronic fatigue syndrome and irritable bowel syndrome on the one hand and anxiety disorder on the other, and highlights techniques of dynamic assessment of heart rate variability, It raises the potentially important prognostic implications of protracted autonomic dysfunction in patient populations with fibromyalgia and related disorders, especially for cardiovas­cular morbidity and mortality.

Background: The neurosteroids dehydroepiandrosterone (DHEA) and its sulfated metabolite (DHEAS) have been reported to possess neuroprotective as well as anti-tumoral activity in vitro and in vivo.

Objectives: To compare the effect of the two neurohor­mones on cell viability in primary whole-brain fetal mouse culture and isolated neuronal culture, as well as in a human neuroblastoma cell line (SK-N-SH).

Methods: Cell viability and cell proliferation were deter­mined with the neutral red and ³H-thymidine uptake methods, Apoptosis in propidium iodide-stained neuroblastoma cells was determined using flow cytometry.

Results: DHEA (1 nM-10 ìM) decreased the viability of selected primary neuronal cells (33-95% after 24 and 72 hours) but not of whole-brain cultured cells (neuron+glia). DHEAS did not significantly modify cell viability in either primary culture. In a human neuroblastoma cell line, DHEA (1 nM- 1 ìM) decreased ³H-thymidine uptake (30-60%) and cell viability (23-52%) after 24 hours. DHEAS did not significantly modify, or only slightly stimulated, cell viability and uptake of  ³H-thymidine (132% of controls). The combination of DHEA and DHEAS neutralized the toxic effect of DHEA in both primary neuronal culture and neuroblastoma cell line. Flow cytometric analysis of DNA fragmentation in neuroblastoma cells treated with 100 nM DHEA/DHEAS for 24 hours showed an increase in apoptotic events (31.9% and 26.3%. respec­tively, vs. control 2.54%).

Conclusions: Our results do not confirm a neuroprotective role for DHEA and suggest that DHEA and DHEAS have a differential role: DHEA possesses a neurotoxic (expressed only in isolated neurons) and anti-proliferative effect DHEAS demonstrates only a slight neuroprotective effect.
 

Background: Fixed dose combination therapy varies among countries.

Objective: To compare the list of fixed-dose combination therapies used in the USA, UK and Israel.

Methods: The total list of drugs and FDC drugs were counted manually from a list of generic names. We also counted the number of drugs in four characteristic subgroups:

cardiovascular, anti-infective, gastrointestinal, and dermatolo­gical. Data for drugs in the USA, UK and Israel were taken from the Physician’s Desk Reference (PDR 1997), the British National Formulary (BNF March 1997) and the Monthly Ethical Drug Indexed Compilation (MEDIC July 1997) respectively.

Results: The global percentage of FDC drugs in the USA and UK was higher than in Israel (20%, 25% and 15% respectively). A similar trend was found in all subclasses of FDC drugs except for the anti-infective category in which the percentage of FDC drugs was low and similar in all countries.

Conclusion: The list of FDC drugs varies greatly between the USA, UK and Israel. reflecting the differences in the outcome of debate between the pharmaceutical companies and the regulatory authorities.

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.
 

Background: The transfer of therapeutic genes into malignant brain tumors has been the subject of intense pre­clinical and clinical research in recent years. Most approaches have used direct intratumoral placement of a variety of vectors and genes, such as retroviruses or adenoviruses carrying drug-susceptibility genes, modified replication-competent herpes virus, and several vectors carrying tumor suppressor genes such as the p53 gene. However, clinical results have so far been disappointing, mainly due to the limited ability to effectively distribute the genetic material into the target cell population. Accordingly, alternative delivery approaches into the central nervous system, e.g., intravascular, are under investigation. Genetic vectors administered intravascularly are unlikely to penetrate the blood-brain barrier and transfer a gene into brain or tumor parenchyma. However, intravascular delivery of vectors may target endothelial cells lining the blood vessels of the brain. Since endothetial cells participate in a variety of physiological and pathological processes in the brain, their modulation by gene transfer may be used for a variety of therapeutic purposes. Angiogenically stimulated endothelial cells within tumors replicate rapidly and hence may become targets for retroviral-mediated gene transfer.

Objective: To assess the anti-tumor effect of transferring a drug-susceptibility gene into endothelial cells of the tumor vasculature.

Methods: As a model for this approach we delivered concentrated retroviral vectors carrying a drug-susceptibility gene via the internal carotid artery of rats with malignant brain tumors. The safety and efficacy of this approach, without and with subsequent treatment with a pro-drug (ganciclovir). was evaluated.

Results: No acute or long-term toxicity was observed after intraarterial infusion of the vector. Treatment with ganciclovir resulted in variable hemorrhagic necrosis of tumors, indicating preferential transduction of the angiogenically stimulated tumor vasculature. This was accompanied by severe toxicity caused by subarachnoid hemorrhage and intracerebral hemorrhage in vascular territories shared by the tumor and adjacent brain.

Conclusion: The data indicate that endothelial cells can be targeted by intraarterial delivery of retroviral vectors and can be used for devising new gene therapy strategies for the treatment of brain tumors.

Background: The free-to-total prostate-specificantigen ratio is the best marker for optimizing prostate cancer detection. The main problem with studies of percent free PSA is the variability of reported cutoff values.

Objectives: To evaluate the influence of prostate size on the ratio of free to total PSA.

Methods: The study group included 58 patients (mean age 66.4 years) with clinically localized prostate cancer treated surgically at our institution. Total PSA and free PSA levels were measured by a solid phase enzyme immunoassay test (Hoffman-La Roche, Basel, Switzerland). The percent free PSA was compared with prostate size as determined from the surgical specimen.

Results: A direct relation was noted between prostate size and the percent free PSA value (r=0.49, P=0.0001). Mean percentage free PSA was 9%0.004 in men with normal-sized gland while in men with large prostate (60 g) the average percent free PSA was 15.90.09 (P=0.001).

Conclusions: In patients with prostate cancer the percent free PSA level is influenced by the gland size. The larger the prostate the higher the proportion of the free PSA. Such information may have influence on the recommendation for prostate biopsy in screening programs for early detection of prostate cancer.