Israel Medical Association Journal

Background: Hypertension is considered resistant if blood pressure cannot be reduced to <140/90 mmHg with an appropriate triple-drug regimen, including an oral diuretic, with all agents administered at maximal dosages. This definition has evolved with the development of new therapies and evidence-based data supporting treatment to lower BP[1] goals.

Objective: To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia.

Methods: Forty-eight hyperlipidemic subjects with RH[2] (office systolic BP >140 mmHg and/or office diastolic BP >90 mm/Hg notwithstanding antihypertensive treatment with three medications in maximal doses) were randomized into three groups to receive additional medication for 8 weeks. Group VTC (n = 17) – mean 24 hour SBP[3] 150.6 ± 5.2 mmHg, DBP[4] 86.1 ± 3.3 mmHg, low density lipoprotein 158.1 ± 24.5 mg/dl) – received vitamin C 500 mg per day; Group ATR (n = 15) – mean 24 hour SBP 153.1 ± 4.8 mmHg, DBP 87.1 ± 6.7 mmHg, LDL[5] 162.6 ± 13.6 mg/dl) – received atorvastatin 20 mg/day; and Group PLA (n = 16) – mean 24 hour SBP 151.1 ± 7.4 mmHg, DBP 84.8 ± 5.9 mmHg, LDL 156.7 ± 26.1 mg/dl – received a placebo. High resolution ultrasound was used to calculate brachial artery flow-mediated dilation, and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks.

Results: In the ATR group there were significant reductions of SBP (DSBP1-2: 13.7 ± 5.6 mmHg, P < 0.001), DBP (DDBP1-2: 7.8 ± 5.7 mmHg, P < 0.01), LDL (DLDL1-2: 67.7 ± 28.3 mg/dl, P < 0.001) and improvement of brachial artery FMD[6] (DFMD2-1: 4.2 ± 2.6%). No significant changes in BP, LDL and FMD were observed in the other two groups.

Conclusions: In subjects with RH and dyslipidemia, atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period. A larger trial is needed to assess the drug's efficacy in this population for longer periods.

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.

Obstructive sleep apnea syndrome is a major public health hazard affecting 2–4% of the adult population; only 10% of these patients are recognized by healthcare providers. In the last decade the number of referrals for polysomnography increased threefold in Israel, compared to 12-fold worldwide, and is expected to increase even more in the coming years. This constant demand for PSG[1] studies is beyond the current capacity of sleep laboratories, thus preventing diagnosis for most patients with suspected OSAS[2]. In the current review, we examine problems facing decision-makers on how to treat the increasing flood of patients presenting with symptoms suggestive of sleep-disordered breathing. We evaluate the cost-effectiveness of current technologies for OSA diagnosis, i.e., laboratory versus at-home technologies. We conclude that no current alternative exists to the use of PSG for OSA diagnosis. When at-home technologies are suggested for OSAS diagnosis, data should be provided on factors influencing its cost-effectiveness, e.g., accuracy rates of diagnosis, relative cost of human resources, and case-mix of patients tested. Since PSG remains the gold standard for diagnosis of OSAS, in Israel resources should be allocated to increasing the volume of beds for PSG studies in order to increase access to diagnosis and treatment, which in turn provides better quality of life, saves scarce resources of the healthcare system, prevents unnecessary accidents and increases workers’ productivity.

Background: Follow-up examinations in a rehabilitation center clinic after stroke are essential for coordinating post-acute services and monitoring patient progress. Of first-stroke patients discharged from our rehabilitation ward to the community 92% are invited for ambulatory check-up once every 6 months.

Objectives: To review patient complaints at follow-up and the recommendations issued by the attending physical medicine and rehabilitation specialist at the outpatient clinic.

Methods: We extracted relevant data from the records, and assessed the relationship between functional status on admission and discharge (measured by FIM[1]), length of stay, and number of complaints. Patients were divided according to the side of neurologic damage, etiology, whether the stroke was a first or recurrent event, and main clinical syndrome (neglect or aphasia).

Results: Patients' complaints included: decreased hand function (40%), general functional deterioration (20%), difficulty walking (11%), speech dysfunction (10%), various pains (especially in plegic shoulder) (8%), urine control (2%), sexual dysfunction (3%), swallowing difficulties (2%), and cognitive disturbances (2%). Patients received the following recommendations: physiotherapy (52.5%), occupational therapy (37.5%), speech therapy (12.5%), different bracing techniques (22.5%), pain clinic treatment (12.5%), changing medication prescriptions (7.5%), psychological treatment (10%), sexual rehabilitation (5%), vocational counseling (2.5%), counseling by social workers (2.5%), and recurrent neuropsychological diagnosis (2.5%). A reverse correlation was found between the number of complaints and FIM at admission (P = 0.0001) and discharge (P = 0.0003), and between LOS[2] and FIM at admission (P = 0.0001) and discharge (P = 0.004). A direct correlation was found between the number of complaints and LOS (P = 0.029). No relation was found between age, type of stroke, first and recurrent event, and clinical syndromes and patient complaints in the outpatient rehabilitation. Community rehabilitation services met 58% of all recommendations in 62% of patients, mainly physiotherapy and occupational therapy, with 34% of patients waiting for implementation of the recommendations and 4% not available for follow-up.

Conclusions: Follow-up examinations should be an integral part of post-stroke rehabilitation. Rehabilitation treatment in the community must be strengthened.

Background: Prone sleeping has been recognized as a risk factor for sudden infant death syndrome. Ten years ago, non-prone sleeping was recommended in many countries around the world including Israel. The rate of infants sleeping prone and the rate of parents' adherence with the recommendations have not been studied.

Objectives: To study infants' sleep position and parents’ adherence to recommendations, and to identify risk factors for prone sleeping following the campaign to prevent prone sleeping in the Israeli population.

Methods: We conducted a longitudinal telephone survey with the parents of 608 randomly selected 2 month old infants, repeated at 4 and 6 months.

Results: Non-prone sleeping decreased from 75% to 67% and 63% at 2, 4 and 6 months respectively. There was a significant relationship between prone positioning and the use of a home apnea monitor at 2 months (P = 0.038, odds ratio 1.37, 95% confidence interval 0.94–2.15). Other risk factors for prone sleeping were the level of religious practice, with ultra-Orthodox Jews having the highest prevalence (2 months: OR[1] 2.78, 95% CI[2] 1.75–4.55) and higher parity – especially in families with more than five children (P = 0.041).

Conclusions: The prone sleeping position is relatively high in Israel. Groups at high risk were closely associated with the level of religiousness and parity. Efforts to promote supine sleeping should be directed towards identifiable groups.

Background: Gallium scintigraphy is frequently used in the evaluation of fever of unknown origin, although its utility has been addressed in only a few studies.

Objectives: To evaluate the utility of gallium scintigraphy in the evaluation of patients with FUO[1] in our department.

Methods: We reviewed the charts of all patients from our department who had undergone gallium scintigraphy during the years 1995–2002 for the evaluation of FUO and who met the criteria for the definition of FUO. Demographic, clinical and laboratory data in addition to the results of gallium scintigraphy were documented. The patients were divided into two groups: those with a normal gallium study (group 1) and those with an abnormal gallium study (group 2). The second group was further divided into two groups: those whose gallium study results contributed to the diagnosis of the cause of FUO (group 2A) and those whose gallium study results did not (group 2B).

Results: A total of 102 patients met the study criteria. The male: female ratio was 54:48 and the mean age ± SD was 62.4 ± 20 years. A final diagnosis had been reached in 63 patients (62%), among whom the etiology was infectious in 54%, neoplastic in 19% and immunologic/rheumatic in 16%. Forty-one patients (40% of all the patients) (Group 2) had an abnormal gallium scintigraphy, and in only 21 patients (21% of all the patients) (Group 2A) did the gallium study results contribute to the diagnosis of the cause of FUO. However, in only two patients from Group 2A (2% of all the patients in our study) was the contribution of gallium study considered significant or crucial to the diagnosis of the cause of FUO.

Conclusions: The utility of gallium scintigraphy in the evaluation of FUO is very limited.

Background: The prognosis of patients with fulminant hepatic failure without timely liver transplantation is dismal. Given the limited availability of cadaveric organs for urgent transplantation in Israel, adult-to-adult living-donor segmental liver transplantation may be the only alternative.

Objectives: To report our initial experience with urgent lifesaving LDLT[1] in this unique scenario.

Methods: Three adult patients with FHF[2] (two of unknown etiology, one with paracetamol intoxication) were transferred from other institutions and admitted to our intensive care unit. Initial treatment and monitoring included intracranial pressure monitoring and hepatic dialysis using the Molecular Adsorbent Recirculating System. Expeditious potential donor selection included medical, psychosocial and surgical evaluation. Liver volume and vascular anatomic compatibility were assessed with computed tomography angiography.

Results: Between July and October 2003 we performed three procedures of urgent adult-to-adult LDLT. The donors (two uncles, one sister) underwent hepatic resection (two right lobes, one left lateral segment) and recovered well. The recipients underwent total hepatectomy with caval preservation, followed by lobar grafting. All recipients recovered and are alive with good liver function and without any neurologic complications.

Conclusions: Urgent adult-to-adult living-donor segmental liver transplantation can be performed safely and timely as a lifesaving procedure in the setting of comatose patients with FHF.

Background: Leukotriene antagonist therapy in asthmatic patients alleviates symptoms and improves exercise tolerance, however the effect of these drugs on bronchial provocation tests and exhaled nitric oxide levels are less clearly established.

Objective: To determine the effect of montelukast treatment on airway hyperresponsiveness to exercise, methacholine and adenosine-5’-monophosphate and on exhaled nitric oxide levels in steroid-naive asthmatics.

Methods: Following a 2 week run-in period, 20 mild to moderate asthmatics were enrolled in an open label 6 week trial of oral montelukast-sodium therapy. Bronchial hyperreactivity (exercise, methacholine and adenosine-5’-monophosphate challenges) and exhaled nitric oxide levels were measured before and after the 6 week period.

Results: Montelukast treatment resulted in a significant improvement in exercise tolerance: median DFEV₁ 20.0% (range 0–50) prior to treatment vs. 15.0% (range 0–50) post-treatment (P = 0.029). A significant difference was also observed for exhaled NO[1] following therapy: median NO 16.0 ppb (range 7–41) vs. 13.0 (range 4.8–26) (P = 0.016). No change was seen in baseline lung function tests (FEV₁, MEF₅₀) or in the bronchial responsiveness (PC₂₀) for methacholine and adenosine-5’-monophosphate.

Conclusions: This study demonstrates that the leukotriene antagonist, montelukast-sodium, reduces bronchial hyperreactivity in response to exercise and reduces exhaled nitric oxide levels but has little effect on bronchial responsiveness to methacholine and adenosine challenges.

Background: The Israeli Blood Pressure Control program was initiated to enhance the control of modifiable risk factors among high risk hypertensive patients followed by general practitioners in Israel.

Objective: To report the baseline results of the state of the treatment regarding blood pressure management, lipid and glucose control as well as obesity and smoking cessation among the patients.

Methods: Hypertensive patients were screened in 30 general practice clinics supervised by family medicine specialists seeing 1,000–5,000 patients each. Between 50 and 250 hypertensive patients were diagnosed at each participating clinic. Blood pressure levels, body mass index, lipid and glucose levels, as well as target organ damage and medications were recorded for all patients.

Results: Of the 4,948 patients registered, 2,079 were males (42%). Mean age was 64.8 ± 12. Blood pressure control was achieved in only 33.1% of total hypertensive patients. Low density lipoprotein control was achieved in 31.1% of all patients, and glucose control in only 28.5%% of diabetic patients (glucose < 126 mg/dl); 20.7% of the diabetics had glucose levels above 200 mg/dl. In this group of patients 38.9% were obese (BMI[1] >30 kg/m²). While there were more obese females than males (48.0% vs. 35.6%), no difference was found in blood pressure, lipid or glucose control between the genders.

Conclusion: Risk factor management of hypertensive patients attending general practice clinics in Israel is not optimal, especially among those with diabetes or in need of secondary prevention measures. A long-term intervention program for high risk patients in the community is needed to improve the current situation.

Background: An organ sharing system should achieve fairness and optimal graft longevity. Balancing between social and utilitarian considerations is a sensitive ethical, public and medical issue that requires a means to examine the consequences of any allocation policy or planned changes thereof.

Objective: To evaluate the performance and applicability of a computerized simulation model by examining the impact of two opposing organ allocation policies (social or utilitarian) on predicted organ distribution regarding age, waiting time, recipient sensitization measured by panel reactive antibody level and overall donor-recipient tissue matching (measured by the number of HLA antigen mismatches).

Methods: Using a computerized simulation model, virtual donors and recipients were emulated and organs were allocated according to either social algorithms or utilitarian policies. The resulting number of HLA mismatches, PRA[1], age, and waiting time distributions were compared between allocation strategies.

Results: Simulating allocation of 7,000 organs to 17,000 candidate recipients and implementing social policies yielded donor-recipient compatibility comparable to utilitarian policies (0–1 mm: 19.4% vs. 28%) while allocating 66.7% of organs to long waiters (>48 months).

Conclusion: This computerized simulation model is a valuable tool for decision-makers establishing or modifying organ allocation policies.

Background: Acute myocardial infarction is rare in people under the age of 30.

Objective: To determine the clinical features and outcome in young patients presenting with AMI.

Methods: All patients aged 30 years and younger hospitalized with AMI during a period of 8 years (1993–2000) were evaluated for clinical features and outcome.

Results: Of the 3,758 patients with AMI, 15 were 30 years old or younger (0.4%). The mean age was 28 (range 21–30 years) and all were male. Eight had normal coronary arteries on angiogram; seven had obstructive coronary artery disease. Patients with OCA[1] had more classical risk factors for coronary disease. A complete diagnostic work-up was abnormal in four patients with NCA[2]: thrombophilia in two patients, spasm due to alcohol withdrawal and hyperthyroidism in one patient each. All patients presented with typical new-onset chest pain. None had a previous history of angina. All patients with OCA received reperfusion therapy as compared to one patient with NCA. Peak creatine phosphokinase in NCA and OCA was 504 ± 547 and 1,328 ± 440 respectively (P < 0.01). All patients with NCA had good left ventricular function on follow-up echocardiography, compared to only three in the OCA group (P = 0.02). There was one death due to cardiogenic shock in a patient with OCA. Follow-up of 4 ± 2 years demonstrated recurrent acute coronary syndromes in four of seven patients with OCA versus none in the NCA patients (P = 0.02).

Conclusions: AMI is rare in very young patients, and more than half have NCA. A thrombophilic tendency or spasm should be considered. Young patients with NCA have an excellent prognosis.

Background: In southern Israel, a discrepancy between a relatively high prevalence of Group B streptococcus maternal carriage (12.3%) and a very low incidence of neonatal disease (0.1/1,000 live births) has been found despite the fact that no preventive strategy has been implemented.

Objectives: To determine the risk factors for maternal carriage in order to clarify this discrepancy and further examine the different aspects of GBS[1] in southern Israel.

Methods: Cultures for GBS were obtained from 681 healthy pregnant women and relevant demographic and obstetric data were collected. The medical records of 86 neonates born to carrier women were retrospectively examined. Statistical analysis was performed using the Pearson chi-square test.

Results: Women who were not born in Israel, particularly immigrants from the former USSR, were significantly prone to carry the pathogen compared to native Israeli women (Bedouin Arabs and Jews) (P = 0.03).

Conclusions: A high GBS transmission rate is expected among immigrants who came from areas with a high prevalence of maternal carriage to one with a low incidence of neonatal disease environment and were not subject to any preventive strategy. Clinical attention should be directed to this issue throughout Israel.

The relevance of central neurotransmission to aggressive and impulsive behavior has become more evident due to extensive research in humans and in animals. Among other findings, there are abundant data relating low serotonergic activity – as measured by low cerebrospinal fluid 5-hydroxyindolacetic acid, and a blunted response of prolactin to fenfluramine – to impulsive behavior. Many studies on testosterone activity show a relation between high plasma levels and a tendency towards aggression. It is hypothesized that the interaction between low serotonin and high testosterone levels in the central nervous system has a significant effect on the neural mechanisms involved in the expression of aggressive behavior. It seems that testosterone modulates serotonergic receptors activity in a way that directly affects aggression, fear and anxiety. Our survey reviews the main findings on serotonin, testosterone and the possible interaction between them with regard to these behavioral phenomena.