Israel Medical Association Journal

Background: Oral anticoagulation with warfarin can lead to life-threatening events as a result of either over-anticoagulation or undertreatment. One of the main contributors to an undesirable warfarin effect is the need to adjust its daily dose for a specific patient. The dose is adjusted empirically based on the experience of the clinician, a method that is often imprecise. There is currently no other well-accepted method for predicting the maintenance dose of warfarin.

Objective: To describe the application of an artificial neural network to the problem of warfarin maintenance dose prediction.

Methods: We designed a neural network that predicts the maintenance dose of warfarin. Data on 148 patients attending a large anticoagulant clinic were collected by file review. Using correlational analysis of the patients' data we selected the best input variables. The network was trained by using the back-propagation algorithm on a subset of our data and the results were validated against the rest of the data. We used a multivariate linear regression to create a comparable model.

Results: The neural network generated reasonable predictions of the maintenance dose (r = 0.823). The results of the linear regression model were similar (r = 0.800).

Conclusion: Neural networks can be applied successfully for warfarin maintenance dose prediction. The results are promising, but further investigation is needed.
 

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: 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.

Background: Head lice move easily from head to head. The lack of safe, effective repellents leads to reinfestation.

Objectives: To test the efficacy of a slow-release citronella formulation as a repellent against the head louse.

Methods: During 4 months in 2003 a randomized, placebo-controlled double-blind clinical study was conducted in four elementary schools; 103 children were treated with the test formulation and 95 with a placebo.

Results: A significant difference was observed during the second examination 2 months later, when 12.0% of the children treated with the test repellent and 50.5% of those treated with placebo were infested with lice. A significant difference was also observed at the third examination 2 months later, when 12.4% of the children treated with the test repellent and 33.7% treated with placebo were infested. Overall, there were significant differences between those treated with the repellent and those treated with the placebo (15.4% and 55.1% respectively, P < 0.0001). Side effects were observed in 4.4% of children who disliked the odor of the formulation, and an additional 1.0% who complained of a slight itching and burning sensation.

Conclusions: Use of an effective repellent could significantly lower the incidence of reinfestations, which would lower expenditure on lice control, including pediculicides, combs and products for nit removal, and the time spent on treatment and removal of the nits.

The prevalence of obesity worldwide has risen sharply during the last four decades. The etiology of obesity is complex and includes a host of genetic influences in addition to the overconsumption of energy coupled with a sedentary lifestyle. Obesity is known to cause or exacerbate many co-morbid conditions such as diabetes, hypertension, dyslipidemia, coronary heart disease, stroke, certain cancers, arthritis and obstructive sleep apnea. Modest weight losses of 5–10% of actual weight are related to significant improvements in co-morbid conditions, but unfortunately the rate of recidivism with short-term therapy for obesity is high. The recent recognition of obesity as a chronic disease that should be treated with long-term programs and possibly with polypharmacy, and the alarming increase in its prevalence, have prompted extensive research and the development of new pharmacotherapy.

Melanoma is the leading cause of death from skin tumors worldwide, with an annual increase in incidence over the past decade. The molecular mechanisms involved in melanoma pathogenesis are beginning to be unraveled. While a family history of melanoma and exposure to ultraviolet irradiation have been known for years as risk factors in melanoma development, the precise genes involved in inherited predisposition were defined only in the past decade. Germline mutations in two genes that play a pivotal role in controlling cell cycle and division – CDKN2A and cyclin-dependent kinase 4 (CDK4) – have been detected in autosomal, dominant, high penetrance familial melanoma cases. In addition to these two highly penetrant genes, germline mutations and polymorphisms in a few low penetrance genes have been reported in familial melanoma cases: melanocortin-1 receptor, epidermal growth factor, glutathione s-transferase M1, cytochrome p450 debrisoquine hydroxylase locus (CYP2D6) and vitamin D receptor.

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: Advances in surgical techniques and retractor-stabilizer devices allowing access to all coronary segments have resulted in increased interest in off-pump coronary artery bypass. The residual motion in the anastomotic site and potential hemodynamic derangements, however, render this operation technically more demanding.

Objectives: To evaluate the OPCAB[1] experience in a single Israeli center.

Methods: Between 2000 and 2003 in our institution, 1,000 patients underwent off-pump operations. Patients were grouped by the type of procedure, i.e., minimally invasive direct coronary artery bypass or mid-sternotomy OPCAB.

Results: One hundred MIDCAB[2] operations were performed. Of the 900 OPCAB, 767 patients received multiple grafts with an average of 2.6 ± 0.6 grafts per patient (range 2–4) and the remaining patients underwent single grafting during hybrid or emergency procedures. In the multiple-graft OPCAB group, complete revascularization was achieved in 96%. Multiple arterial conduits were used in 76% of the patients, and total arterial revascularization without aortic manipulation, using T-graft (35%) or in situ configurations, was performed in 61%. The respective rates for early mortality, myocardial infarction and stroke in the MIDCAB were 1%, 0% and 2%, and 2%, 1.3% and 0.9% in the multiple-vessel OPCAB groups. Multivariate analysis identified renal dysfunction (odds ratio 11.5, confidence interval 3.02–43.8; P < 0.0001) and emergency operation (OR[3] 8.74, CL[4] 1.99–38.3; P = 0.004) as predictors of mortality. The proportion of off-pump procedures increased from 9% prior to the study period to 59%.

Conclusions: The use of OPCAB does not compromise the ability to achieve complete myocardial revascularization. Our procedure of choice is OPCAB using arterial conduits, preferably the 'no-touch' aorta technique.