Israel Medical Association Journal

Background: The prevalence of morbid obesity is increasing rapidly. Weight reduction is very difficult using diet restriction and physical activity alone. Sibutramine has been shown to be effective and safe as an adjuvant therapy to diet restrictions.

Objectives: To describe our experience using sibutramine in weight reduction treatment of adolescents suffering from morbid obesity.

Methods: The study group comprised 20 young persons (13 females, mean age 15 years 4 months, range 13–18 years) with morbid obesity (body mass index over the 95th percentile for age and/or ≥ 30 kg/m²) were treated with sibutramine 10 mg once a day for 1 year.

Results: Mean BMI[1] was 40 ± 5.6 kg/m² (range 30.1–49.5 kg/m²) at the beginning of treatment. Most patients showed an early weight reduction to mean BMI 39.3 ± 4.9 and 35.9 ± 5.7 at 3 and 6 months respectively, but stopped losing weight over the next 6 months. During the follow-up period 17 patients discontinued the treatment. The main reason for dropout was the slow rate of weight reduction after 6 months. Patients suffering from concomitant disorders (severe asthma, hypertension, sleep obstructive apnea) showed improvement after weight reduction. Adverse reactions from the treatment were transient, mild and well tolerated.

Conclusions: Sibutramine may help in achieving weight reduction for a short period and in improving concomitant health problems, however its long-term effect is limited.

Regenerative medicine concerns the development of cells, tissues and organs for the purpose of restoring function through transplantation.

Stem cell research offers great hope to patients suffering from neuronal damage. Stem cell-based regenerative medicine holds huge potential to provide a true cure for patients affected by a neurodegenerative disease or who have suffered a stroke.

Intravenous immunoglobulins have been used as therapeutic proteins since the early 1980s.

Objectives: To examine the effect of postoperative loco-regional radiotherapy on local and regional recurrence and survival in breast cancer patients with four or more involved lymph nodes or extracapsular tumor extension.

Methods: This controlled clinical trial included 258 breast cancer patients with four or more involved nodes or ECE[1]. Eighty-nine patients in the control group had modified radical mastectomy and received adjuvant chemotherapy with melphalan and 5FU, but no radiation therapy. The 169 patients in the study group (87 with MRM[2] and 82 with lumpectomy and axillary dissection) received various adjuvant chemotherapy regimes and radiation therapy to the chest wall/breast, supraclavicular region and full axilla.

Results: With an average follow-up of more than 5 years, loco-regional radiation significantly reduced local and regional disease recurrence. The median disease-free survival was significantly longer in radiated patients (59.2 months and 63.3 months in the MRM and L+AXLND[3] groups, respectively, vs. 28.4 months in the control group; P < 0.01). There was no difference in the rate of systemic recurrence and overall survival. The median overall survival was 71.2 and 67.5 months in the study groups (MRM and L+AXLND, respectively) and 70.5 months in the control group (P = 0.856).

Conclusions: Radiotherapy to the breast/chest wall and to the draining lymphatics, in addition to surgery and adjuvant therapy, significantly reduced the risk of local and regional recurrence in high risk breast cancer patients with four or more involved lymph nodes or ECE.

Objective: To study the efficacy of balneotherapy and climatic therapy (climatotherapy) at the Dead Sea area in patients with ankylosing spondylitis.

Methods: In a single-blind randomized controlled study, 28 patients suffering from ankylosing spondylitis were allocated into two groups of 14 patients each. The first group (the combined treatment group) received balneotherapy (mud packs and sulfur pool) and exposure to the unique climatic conditions of the Dead Sea. The second group (the climatotherapy group) used the fresh water pool and experienced the same climatic conditions. The duration of treatment was 2 weeks and the follow-up period 3 months.

Results: For both patient groups a significant improvement was found in the outcome measures: Bath AS[1] Disease Activity Index (P = 0.002), Visual Analog Scale for pain (P = 0.002) and VAS[2] for spinal movement (P = 0.011). The variability was explained by the effect of time (within group effect) rather than the type of treatment (within group effect). Quality of life, assessed by the SF-36 questionnaire, was very low prior to the study, but improved in terms of pain amelioration in the combined treatment group.

Conclusions: Climatotherapy at the Dead Sea area can improve the condition of patients suffering from long-standing ankylosing spondylitis.

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.

Background: Repaglinide, a new insulin secretagogue, is purported to be as effective as sulphonylurea but is less hypoglycemic-prone.

Objectives: To assess the efficacy of repaglinide and its proclivity for hypoglycemia in a post-marketing study.

Methods: The study group comprised 688 patients, aged 26–95 years, clinically diagnosed with non-insulin-dependent type 2 diabetes. The patients were divided into three groups based on previous therapy: a) sulphonylurea-treated (group 1, n=132); b) metformin with or without sulphonylurea where sulphonylurea was replaced with repaglinide. (group 2, n=302); and c) lifestyle modification alone (drug-naïve) (group 3, n=254). At initiation of the study, all patients were transferred from their current treatment to repaglinide. Only patients in group 2, with combined sulphonylurea plus metformin, continued with metformin plus repaglinide. Fasting blood sugar, hemoglobin A1c and weight were measured at study entry and 4–8 weeks following repaglinide therapy. A questionnaire documented the number of meals daily and the presence of eating from fear of hypoglycemia.

Results: The fasting blood sugar level of the entire cohort dropped from 191 ± 2.4 to 155 ± 2.0 mg/dl (P < 0.0001); HbA1c from 8.8 ± 0.1 to 7.7 ± 0.1% (P < 0.0001). The drop of HbA1c in groups 1, 2 and 3 respectively were: 1.04 ± 0.22% (P < 0.0001), 1.14 ± 0.24% (P < 0.0001), and 1.51 ± 0.31% (P = 0.0137). Weight dropped from 81 ± 0.7 to 80.2 ± 0.7 kg (P < 0.0001), and eating from fear of hypoglycemia from 157 to 97 (P < 0.001). The daily number of meals decreased from 2.9 ± 0.4 to 2.4 ± 0.4 (P < 0.001). No serious adverse reactions occurred during the study.

Conclusions: Repaglinide is an effective oral hypoglycemic agent taken either as monotherapy or combination therapy. There is less eating to avoid hypoglycemia, fewer meals consumed, and weight loss.
 

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.
 

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.

Classic anticoagulant drugs, such as heparin and warfarin, are very effective. Although in use for more than 50 years, they have some clinical drawbacks. Heparin, now better termed unfractionated heparin, can only be used intravenously and its laboratory control is complicated. Warfarin is orally administered, but its therapeutic window is very narrow and patients need repeated laboratory tests. Moreover, both drugs are non-specific, as they inhibit the coagulation cascade at several steps. Pharmaceutic research has developed new drugs, some of which are already on the market, such as fondaparinux, a pentasaccharide that can interact with antithrombin, thus inhibiting factor Xa. This pentasaccharide is part of the parent heparin molecule and can be chemically synthesized, with the advantage of avoiding extractive compounds. Fondaparinux has a half-life compatible with once-a-day administration; modification of its structure (idraparinux) has led to more stable binding with antithrombin and to an increase in its half-life to allow once-a-week administration. Alternatives to oral anticoagulants have been developed following the study of some compounds like hirudin, which directly binds thrombin and blocks its catalytic site. One of these molecules, ximelagatran, is in advanced clinical development. Ximelagatran is converted into its active form, melagatran, in the circulation, and thrombin activity can be blocked by oral administration twice daily. There is no need for laboratory control and phase II and phase III studies are encouraging. The next few years should bring great changes in the treatment of patients with thromboembolic disorders.