Israel Medical Association Journal

Objectives: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation.

Methods: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4–6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women.

Results: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of the "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women.

Conclusions: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a promising alternative for short-term estrogen-progesterone therapy.

Objective: To describe the prevalence of overweight and obesity in the Israeli population, based on findings of the first national health and nutrition survey (MABAT).

Methods: This cross-sectional survey was carried out during 1999–2000. MABAT is based on a representative sample (n=3,246) of the general Israeli population aged 25–64 years. The current study population comprised those with complete data on measured weight and height (n=2,781). Participants were interviewed in person and had their weight and height measured by the interviewer.

Results: Over 50% of the study participants were women (n=1,410); 76% were Jews and 24% Arabs. Most participants had an education of at least 12 years (72%). Body mass index ≥30.0 was more prevalent in women compared to men (P < 0.001) in both population groups (Jews and Arabs). Obesity rates increased with age and reached 22.4% for men and 40.4% for women aged 55–64 years. Lower education was associated with higher obesity rates, with lowest rates observed for Jewish women with an academic education (13.6%) and highest rates observed for Arab women with a basic education (57.3%). Multiple logistic regression analyses showed age to be a significant risk factor in men. Age, education and origin (Arab, and the former Soviet Union for Jews) were significant risk factors for obesity in women.

Conclusions: Obesity rates in Israel are high and comparable to those in the United States. Of special concern is the subgroup of older Arab women (55–64 years), whose obesity rates reached 70%.

Objective: To investigate hemodynamic variables, including small and large artery compliance, in cirrhotic patients during total paracentesis.

Methods: The study included 15 cirrhotic patients admitted for an episode of tense diuretic-resistant ascites. Hemodynamic variables including vascular compliance were measured using an HDI pulse wave cardiovascular profiling instrument CR-2000. The variables were measured in these patients before, immediately after and 24 hours following large volume (mean 5.6 L) paracentesis.

Results: Cardiac output increased immediately after paracentesis due to increment in stroke volume, with no change in heart rate. However, 24 hours later the cardiac output decreased to below the basal level. The fluctuation was statistically significant (P < 0.05). There was no change in large artery compliance, but small artery compliance increased after paracentesis (P < 0.05) and partially returned to the basal level after 24 hours. Systemic vascular resistance measurement showed the same pattern of change: vasodilatation occurred during paracentesis and was attenuated 24 hours later.

Conclusions: Large volume paracentesis with albumin replacement caused an accentuation of the vasodilatation (small but not large artery) already present in these patients. This may be the first sign of enhanced vasodilatation due to large volume paracentesis before the clinical expression of impaired hemodynamics and deterioration of renal function.

Objectives: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA[1] isolates recovered from hospitalized patients.

Methods: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin), and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method.

Results: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC₉₀ was 2.0 mg/ml for vancomycin and teicoplanin (range 0.5–2.0 mg/ml and 0.125–2.0 mg/ml, respectively), and 0.5 mg/ml for pristinamycin and linezolid (range 0.125–0.75 mg/ml and 0.125–0.5 mg/m, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ[2] (P < 0.01) and an apparent increase in resistance to other antibiotics.

Conclusion: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.

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[1] MRSA = methicillin-resistant Staphylococcus aureus

[2] TMP-SMX = trimethoprim/sulfamethoxazole

Objectives: To evaluate the diagnostic accuracy and outcome of coccygectomy.

Methods: We retrospectively reviewed the operative results in nine patients (seven females and two males) who underwent coccygectomy for coccygodynia in the last 5 years following conservative treatment failure.

Results: The outcome of the procedure was excellent in five patients, good in one patient and poor in two patients.

Conclusions: It is mandatory to perform bone scanning in every patient with coccygodynia and before coccygectomy in order to rule out the presence of malignancy. Coccygectomy is recommended for patients with isolated coccygodynia.

Objective: To present our algorithm of urgent and elective donor selection.

Methods: Urgent selection is expeditious and protocol‑based. Elective selection permits a comprehensive process. Both include medical, psychosocial and surgical-anatomic evaluations. Liver volumes and vascular anatomy are evaluated with computerized tomographic angiography. Informed consent is obtained after painstaking explanations. Independent institutional committees review and approve all cases.

Results: Between July 2003 and June 2004 we evaluated 43 potential live donors for 12 potential recipients (fulminant hepatic failure, n=5; chronic end-stage liver disease, n=6); primary graft non-function, n=1). Thirty-three candidates (76%) were excluded due to blood type incompatibility (n=14, 42%), incompatible anatomy (n=8, 24%) – including problematic volume distribution (n=2) or vascular anatomy (n=6) – psychosocial issues (n=4, 12%), or medical co-morbidity (n=7, 22%). Five recipients (FHF[1], n=4; chronic ESLD[2], n=1) were successfully transplanted from living donors. In the acute setting, two patients (FHF, PGNF[3]) died in the absence of an appropriate donor (cadaveric or living donor). In the elective group, one patient died of unexpected variceal bleeding and one received a cadaveric graft just before the planned living donor transplantation was performed. One candidate was transplanted overseas and two cases are scheduled. The ratio of compatibility for donation was 34% (10/29) for blood type-compatible candidates.

Conclusions: Donor selection for living donor liver transplantation is a complex, labor-intensive multidisciplinary process. Most exclusions are due to blood type incompatibility or anatomic details. Psychosocial aspects of these donations warrant special attention.

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[1] FHF = fulminant hepatic failure

[2] ESLD = chronic end-stage liver disease

[3] PGNF = primary graft non-function

Background: Device replacement or revision may constitute 25% of pacemaker procedures. In patients needing pacemaker system replacement the usual approach is from the ipsilateral side of the previous system. In cases where the contralateral side is used the previous pulse generator is removed.

Objective: To test the feasibility of implanting a new system in the contralateral side without the removal of the old system.

Methods: We present 10 patients, age range 30–88 (median 73), with clinical indication of pacemaker replacement where the contralateral side was used. In eight patients the replacement was lead-related, and in the remaining two was due to other clinical indications. In all cases the ipsilateral approach was felt to be contraindicated because of local vein and/or pocket complications. Following the new pacemaker implantation the old system was reprogrammed at the lowest rate, lowest output and highest sensitivity.

Results: All patients underwent uneventful implantation. Post-surgery monitoring and Holter recordings failed to show any interference of the old system.

Conclusions: In clinically indicated cases it is feasible to implant a new device in the contralateral side without removing the old pulse generator, thereby avoiding an additional surgical procedure and reducing periprocedural complications.

Background: Bladder exstrophy is a severe congenital defect that requires a multidisciplinary treatment approach. Soft tissue repair may be successful during the first few days after birth but a combination of pelvic osteotomies and bladder reconstruction is necessary later in life. The combination of externally fixed anterior and posterior osteotomies has biomechanical advantages over previous techniques for achieving primary bladder closure.

Objectives: To describe our experience with a combined vertical and horizontal pelvic osteotomy approach for the repair of bladder exstrophy.

Methods: Four children underwent bladder exstrophy closure; the mean age at surgery was 19 months (range 9–33 months)... We stabilized the osteotomies with a small Synthes AO external fixator, 4.0 mm rod diameter.

Results: All four patients had successful bladder repair with no dehiscence; two of them achieved partial continence, and bladder neck reconstruction is planned for the other two. Three of the four patients sustained neurologic injury; two completely recovered, and the third continues to suffer from right drop foot. The average follow-up was 39 months (range 10–60 months).

Conclusions: Vertical and horizontal pelvic osteotomies stabilized by external fixator and bladder repair is an effective treatment for bladder exstrophy.

The world now faces the dreadful possibility of biological weapons attacks by terrorists. Healthcare systems would have to cope with such emergencies should all preemptive measures fail. Information gained from the Global Mercury exercise and the SARS outbreak has shown that containing an outbreak at the start is more effective than reacting to it once it has spread and that containment should be treated both nationally and internationally. On the national level this entails developing rapid and effective methods to detect and identify infected cases, and implementing isolation and control measures to lower the risk of further transmission of the disease while assuring the safety of medical teams and laboratory workers. Strategic contingency plans should incorporate well-defined procedures for hospitalization and isolation of patients, providing regional backup of medical personnel and equipment and maintaining close cooperation between the various bodies in the healthcare system. Quarantine is an effective containment measure, especially if voluntarily imposed. Modern communication systems can help by sending professional teams timely instructions and providing the public with information to reduce panic and stress during quarantine procedures. Informing the public poses a dilemma: finding a balance between giving advance warning of an imminent epidemic outbreak and ascertaining the likelihood of its occurrence. Containment of international bioterrorist attacks depends entirely on close international cooperation to implement national and international strategic contingency plans with free exchange of information and recognition of procedures.

Background: Laron Syndrome, first described in Israel, is a form of dwarfism similar to isolated growth hormone deficiency caused by molecular defects in the GH[1] receptor gene.

Objective: To characterize the molecular defects of the GH-R[2] in Laron syndrome patients followed in our clinic.

Methods: Of the 63 patients in the cohort, we investigated 31 patients and 32 relatives belonging to several ethnic origins. Molecular analysis of the GH-R gene was performed using the single strand conformation polymorphism and DNA sequencing techniques.

Results: Eleven molecular defects including a novel mutation were found. Twenty-two patients carried mutations in the extracellular domain, one in the transmembrane domain, and 3 siblings with typical Laron syndrome presented a normal GH-R. Of interest are, on one hand, different mutations within the same ethnic groups: W-15X and 5, 6 exon deletion in Jewish-Iraqis, and E180 splice and 5, 6 exon deletion in Jewish-Moroccans; and on the other hand, identical findings in patients from distinct regions: the 785-1 G to T mutation in an Israeli-Druze and a Peruvian patient. A polymorphism in exon 6, Gly168Gly, was found in 15 probands. One typical Laron patient from Greece was heterozygous for R43X in exon 4 and heterozygous for Gly168Gly. In addition, a novel mutation in exon 5: substitution of T to G replacing tyrosine 86 for aspartic acid (Y86D) is described.

Conclusions: This study demonstrates: a) an increased focal incidence of Laron syndrome in different ethnic groups from our area with a high incidence of consanguinity; and b) a relationship between molecular defects of the GH-R, ethnic group and geographic area.

Background: Pulmonary disease is the most frequent cause of morbidity and mortality in cystc fibrosis patients. New techniques such as non-invasive positive pressure ventilation have resulted in prolongation of life expectancy in CF[1] patients with end-stage lung disease.

Objectives: To determine the role of NIPPV[2] in CF patients awaiting lung transplantation.

Methods: Between 1996 and 2001 nine CF patients (5 females) with end-stage lung disease were treated with bi-level positive airway pressure ventilation in the "spontaneous" mode.

Results: The patients' mean age at initiation of BiPAP[3] was 15 years (range 13–40 years) and the mean duration of BiPAP usage was 8 months (range 3–16 months). Four patients underwent successful lung transplantation, three patients died while awaiting transplantation, and the remaining two are still on NIPPV while waiting for transplantation. Patients' body mass index increased significantly (P < 0.05) during BiPAP therapy (from 16.1 to 17.2 kg/m²). Blood pH, p_aCO₂, and bicarbonate improved significantly (from 7.31 to 7.38, 90.8 to 67.2 mmHg, and 48.9 to 40.3 mEq/L, respectively). Pulmonary function tests were not affected by BiPAP usage. The patients experienced a significant alleviation in morning headaches and improvement in quality of sleep (P < 0.003). There were no major complications during BiPAP usage.

Conclusions: We demonstrated that long-term NIPPV can stabilize and improve physiologic parameters such as ventilation, arterial blood gases and body mass index, as well as subjective symptoms such as sleep pattern, daily activity level, and morning headaches in CF patients with end-stage lung disease. Further prospectively controlled studies are needed to evaluate the potential of BiPAP therapy and its influence on morbidity and mortality in the post-lung transplantation period.