Israel Medical Association Journal

Background: Acarbose has become an important adjuvant therapy for diabetic patients. Many of these patients are also treated with digoxin for congestive heart failure or chronic atrial fibrillation

Objective: To evaluate a possible drug interaction between acarbose and digoxin.

Methods: An open-label, analyst-blind, randomized, crossover, two-period study was conducted in 11 healthy subjects. In period I, each subject received one single oral dose of 0.75 mg digoxin. In period ll, they were given acarbose tablets., 60 mg-3 times a day for 12 days. On day 8, one hour after acarbose administration, a single oral dose of 0.75 mg digoxin was administered. The study periods were separated by a 3 week washout interval: Serum. digoxin levels., over. time, in the two periods were compared by standard techniques;

Results: There were no differences in the pharmacokinetic parameters of digoxin in the two periods, apart from a significant increase in the mean maximum serum concentration (Cmax) when digoxin was given with acarbose (5.97 compared to 4.67 g/L, P = 0.02). Simulated steady-state peak levels of digoxin (Cmax,ss) achieved with a daily dose of 0.25 mg digoxin, in the presence.and absence of acarbose, were 2.89 and 2.40 g/L respectively (P =0.05); Simulated steady-state trough (Cmin,ss) and average (Cave,ss) concentrations were similar and within the therapeutic window.

Conclusion: There was no significant pharmacokinetic interaction between digoxin and acarbose at current therapeutic doses in the healthy volunteers. This interaction should be further studied with higher doses of acarbose and at steady-state conditions.
 

Background: While most allelic pairs of DNA replicate synchronously during the S phase of the cell cycle, some genes normally replicate asynchronously, i.e., genes on the X chromosome and imprinted genes. The replication control mechanism is unknown but was shown to be impaired in malignancies and chromosomal trisomies where replication pattern becomes asynchronous.

Objectives: To determine the level of asynchronization in replication timing of cells from patients with microdeleted genomes.

Methods: We applied monocolor fluorescent in situ hybridization with different probes on leukocytes from microdeleted genomes.

Results: All samples derived from the microdeleted genomes showed significantly higher levels of an asynchronized pattern compared to normal individuals.

Conclusions: Even a “small” genetic imbalance (microdeletion) can interfere with gene replication and cell cycle progression, as previously shown in full trisomies.
 

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: 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.

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.