Israel Medical Association Journal

Background: The beneficial effect of 3-hydroxy-3-methylglutyaryl co-enzyme A reductase inhibitors on cardiovascular risk reduction has been clearly established. Concerns have been raised that lowering blood cholesterol by other hypolipidemic drugs or by a non-pharmacologic approach may have deleterious effects on psychopathologic parameters. Garlic is one of the most commonly used herbal remedies and is considered to have hypocholesterolemic as well as other cardio-protective properties. Its effect on psychopathologic parameters has never been reported.

Objectives: To evaluate the effect of garlic on lipid parameters and depression, impulsivity, hostility and temperament in patients with primary type 2 hyperlipidemia.

Methods: In a 16 week prospective double-blind placebo-controlled study, 33 patients with primary hypercholesterolemia and no evidence of cardiovascular disease were randomly assigned to receive either garlic or placebo. Garlic in the form of alliin 22.4 mg/day was given to 13 patients, and placebo to 20. Both groups received individual dietary counseling. The changes in lipid profile and the various psychopathologic parameters were determined at the beginning and end of the trial. The differences in lipid parameters were evaluated by Student’s t-test. The psychological data were analyzed by one-way analysis of variance (ANOVA) with repeated measures and Neuman-Keuls test.

Results: No significant changes were observed in levels of total cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol and triglycerides, or in the psychopathologic parameters evaluated.

Conclusion: Short-term garlic therapy in adults with mild to moderate hypercholesterolemia does not affect either lipid levels or various psychopathologic parameters.

Background: Decreased elasticity of the aorta is associated with aging and several risk factors of atherosclerosis. The data regarding this phenomenon in patients with familial hypercholesterolemia are rather sparse.

Objectives: To evaluate non-invasively the elasticity of the proximal ascending aorta of 51 heterozygous FH[1] patients compared to 42 normal age and gender-matched controls.

Methods: Aortic elasticity was estimated by transthoracic echocardiography using the “pressure-strain” elastic modulus and aortic strain formulas.

Results: The elastic modulus score was higher in the FH group than in the controls (1.12 ± 0.91 10⁶ dynes/cm² vs. 0.65 ± 0.46 10⁶ dynes/cm² respectively, P = 0.01). This was consistent in both the pediatric (0.5 ± 0.2 10⁶ dynes/cm² vs. 0.4 ± 0.1 10⁶ dynes/cm² respectively, P = 0.009) and adult subgroups (1.3 ± 1.0 10⁶ dynes/cm² vs. 0.8 ± 0.5 10⁶ dynes/cm² respectively, P = 0.0004). Aortic strain was significantly lower in patients with FH than in controls (6 ± 4% vs. 9 ± 5% respectively, P = 0.0002). These findings reflected decreased elasticity of the proximal ascending aorta in the FH patients. In multivariate analysis, age, serum cholesterol level and serum triglycerides level were the independent predictors of the elastic modulus score, whereas age was the predictor of aortic strain.

Conclusions: The elasticity of the proximal ascending aorta is decreased in heterozygous FH patients.

Background: Cystinuria is an autosomal recessive disease that is manifested by the development of kidney stones. Mutations in SLC3A1 cause type I disease, while mutations in SLC7A9 are associated with non-type I disease. In Israel cystinuria is especially common among Libyan Jews who suffer from non-type I disease.

Objectives: To compare clinical manifestations of patients with mutations in SLC3A1 to those with mutations in SLC7A9, and to assess the carrier rate among unaffected Libyan Jewish controls.

Methods: Clinical manifestations were evaluated in patients with mutations in SLC3A1 and in patients with mutations in SLC7A9. Carrier rates for two SLC7A9 mutations were assessed in 287 unaffected Libyan Jewish controls.

Results: Twelve patients with mutations in SLC3A1 were compared to 15 patients with mutations in SLC7A9. No differences were detected between the patients with mutations in SLC3A1 and those with mutations in SLC7A9 in relation to the age of disease onset, the estimated number of stones, the number of invasive procedures, the number of patients receiving drug therapy, or the patients’ urinary pH. Eleven of the unaffected Libyan Jewish controls were found heterozygotes for the V170M mutation, establishing a carrier rate of 1:25. The 1584+3 del AAGT mutation was not found in any of the Libyan Jewish controls.

Conclusion: Mutations in SLC3A1 and SLC7A9 cystinuria patients result in indistinguishable disease manifestations. The high carrier rate among Libyan Jews is a result of a single missense mutation, V170M.
 

Background: Concomitant mitral valve regurgitation is often present in patients with aortic stenosis. The additional MV[1] replacement is associated with high operative risk. Previous studies have shown an amelioration of MV regurgitation after aortic valve replacement but most of the patient groups were heterogenous.

Objectives: To determine whether AV[2] replacement for aortic stenosis has any effect on MV regurgitation.

Methods: We reviewed two-dimensional echocardiography and color flow Doppler assessment of both aortic stenosis and MV regurgitation severity in 30 patients. Patients with previous MV surgery, organic MV disease, occlusive carotid artery disease, ejection fraction < 50%, and coexisting significant AV regurgitation were excluded. Preoperatively, MV regurgitation was mild in 23 patients (77%) and moderate in 7 (23%); in no patient was the condition severe. All patients had severe atrial stenosis (peak average aortic gradient was 86  ± 22 mmHg in the mild MV regurgitation group, and 83 ± 26 mmHg in the moderate group). The patients were divided into two groups according to the severity of MV regurgitation (associated mild, and moderate). Group 2, with moderate MV regurgitation, was the most problematic in terms of decision making for concomitant MV surgery. Therefore, additional assessment of several parameters was required.

Results: There was a significant decrease in MV regurgitation area (7.6 ± 1.9 vs. 3.0 ± 1.2 cm², P £ 0.012) and percent (28 ± 5% vs. 12 ± 6%, P £ 0.001) between pre- and postoperative evaluation. Thus, the severity of the condition in all patients with moderate MV regurgitation decreased after AV replacement; in the mild group it remained unchanged in 53% or improved in 47%. There was no association between the preoperative gradient on the aortic valve and the degree of MV regurgitation.

Conclusions: In our population of patients with severe atrial stenosis there were no patients with coexisting severe MV regurgitation. The decision to repair or replace a severely leaking mitral valve is an easy one, as in mild MV regurgitation. The clinical problem often presents in patients with severe aortic stenosis and moderate MV regurgitation. We believe that additional MV surgery is not necessary, at least in patients with preserved left ventricular function and without organic MV disease.

Background: The implementation of treatment guidelines is lacking worldwide.

Objectives: To examine whether follow-up in a specialized lipid clinic improves the achievement rate of the treatment guidelines, as formulated by the National Cholesterol Education Program and the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.

Methods: The study group included patients who were referred to the lipid clinic because of hyperlipidemia. At each of five visits over a 12 month period, lipid levels, liver and creatine kinase levels, body mass index, and adherence to diet and medications were measured, and achievement of the NCEP[1] target level was assessed.

Results: A total of 1,133 patients (mean age 61.3 years, 60% males) were studied. Additional risk factors for atherosclerosis included hypertension (41%), type II diabetes mellitus (21%), smoking (17%), and a positive family history of coronary artery disease (32%). All patients had evidence of atherosclerotic vascular disease (coronary, cerebrovascular or peripheral vascular diseases). The low density lipoprotein target of <100 mg was present in only 22% of patients before enrollment, with improvement of up to 57% after the follow-up period. During follow-up, blood pressure control was improved (from 38% at the time of referral to 88% after 12 months, P < 0.001), as was glycemic control in diabetic patients (HgA₁C improved from 8.2% to 7.1% after 12 months, P < 0.001). Improved risk factor control was due to increased compliance to medication treatment (from 66% at enrollment to more than 90% after 12 months), as well as careful attention to risk factor management that translated into a change in the treatment profile during the follow-up. There was an increase in the use of the following medications: aspirin from 68% to 96%, statins from 42% to 88%, beta blockers from 20% to 40%, and angiotensin-converting enzyme inhibitors from 28% to 42%; while calcium channel blocker use decreased from 40% to 30% in patients during follow-up.

Conclusion: Follow-up of patients in a specialized clinic enhances the achievement of LDL[2]-cholesterol treatment goals as well as other risk factor treatment goals, due to increased patient compliance and increased use of medications.

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Southern Sinai, a mountainous desolated arid area, is inhabited by Bedouin nomad tribes composed of Arabic-speaking Moslems. Until the Six Day War between Egypt and Israel in 1967, healthcare services in the region were based on traditional medicine performed by the Darvish, a local healer. Over the course of Israeli rule (1967-1982) an elaborate healthcare service was established and maintained, providing modern, up to date, comprehensive medical services that were available to all free of charge.

Background: The modest clothing that Orthodox Jewish women wear exposes very little of their skin to sunlight. Under these conditions they may develop vitamin D deficiency, even in sunny Israel.

Objectives: To determine and compare the vitamin D nutritional status in Jewish orthodox mothers to that of non-orthodox mothers who live in the same metropolitan area in Israel.

Methods: 25-Hydroxyvitamin D was measured by compe­titive protein-binding radioassay in the sera of 341 Jewish Israeli mothers (156 orthodox and 185 non-orthodox). The sera were obtained 48-72 hours after childbirth during the late summer of 1998 and the spring of 1999.

Results: The mean (SD) serum concentration of 25-OHD was significantly (P<0.002) lower (13.5 ± 7.5 ng/ml) in the orthodox than in the non-orthodox mothers (18.6 + 9.6 ng/ml). Vitamin D deficiency (<5 ng/ml) and insufficiency (<10 ng/ml) were more common in the orthodox mothers (5.1% and 32.7% respectively) than in the non-orthodox mothers (2.7% and 13%, respectively). In subgroups of mothers supplemented with 400 units of vitamin D daily during pregnancy, vitamin D deficiency and insufficiency were less common (2.2% and 13%, respectively) in orthodox and non-orthodox mothers (0% and 8.1%, respectively). Vitamin D insufficiency was more common in the winter than in the summer only among non­orthodox mothers.

Conclusions: The high prevalence of vitamin D deficiency and insufficiency in Israeli mothers raises the question whether vitamin D supplements should be given to pregnant women in Israel, at least to orthodox mothers.
 

Background: Routine prenatal ultrasound has increased the frequency of prenatal diagnosis of congenital cystic lung malformation, such as cystic adenomatoid malformation, pulmonary sequestration, congenital lobar emphysema, and bronchogenic cyst.

Objectives: To evaluate the methods of postnatal diag­nosis, the optimal age for operation since surgery is always required, and the optimal extent of lung resection.

Methods: The clinical courses of 11 patients with congenital lung cysts who underwent surgical lung resection (8 lobectomies and 3 segmentectomies) were reviewed.

Results: The diagnosis was confirmed by computed tomography scan in all. In nine patients the diagnosis was made prenatally. Chest X-ray was normal postnatally in all patients except for two who had recurrent pneumonia. Post­operative follow-up showed excellent recovery in all operated children. One patient who underwent surgery for CCAM following episodes of severe pneumonia died from another cause 5 months later. Postoperative chest CT scan showed no residual disease in eight patients. In two who had undergone limited resection, tomography showed a small segment of residual disease in one and a suspected residual lesion in the other.

Conclusion: With prenatal ultrasound the true frequency of congenital cystic lung anomaly appears to be higher than previously reported. Postnatal CT is mandatory to confirm or to rule out the diagnosis. The mere presence of cystic lung malformation is an indication for surgery. Complete removal of the affected lung lobe is recommended. Segmental resection may be inadequate. Early operation is tolerated well by infants and small children and we recommend that surgery be performed in children between 6 and 12 months of age.

Background: High dose interleukin-2 therapy, adminis­tered in bolus, is considered to be a reasonable treatment option in a selected group of patients with metastatic malignant melanoma.

Objectives: To present our experience using this mode of therapy in 21 patients with metastatic melanoma.

Materials and Methods: The 21 patients in our study group comprised 13 men and 8 women with a mean age of 46 years (range 29-63). Their metastatic disease was present in all extracranial sites, dermal and sub-dermal metastases being the most common (15 patients had at least one site, in addition to other locations of metastases). Patients with intracranial disease were excluded due to the poor effectivity of IL-2 at this site. Treatment comprised a course of 2 weeks of therapy with a 1 week rest interval between. Radiological and physical evaluation was performed 6-8 weeks after the first course. If a response was achieved a second course of therapy was given. Patients received up to 14 planned doses of IL-2 in each week, 720,000 lU/kg of IL-2 per dose iv. in 15 minutes. All treatments were given in the surgical ward, and only one patient was hospitalized in the intensive care unit.

Results: Of the 21 patients, one had a complete response that has lasted for 17 months and 5 patients had a partial response (range 3 months to 3 years). One patient died during treatment, and one patient who refused further treatment because of no response died a few days after completion of treatment. Prior to therapy three of the responders had received autologous vaccines with good immunological response (P=0.115). Toxic side effects were significant, but they were treated successfully with no residual damage.

Conclusions: High dose IL-2 can be administered safely in a surgical department. The response rates achieved in this series justify the use of high dose IL-2 in a selected group of patients. To improve response rates, a combination of auto­logous vaccines prior to high dose IL-2 may be recommended.