Israel Medical Association Journal

Background: Burnout is a professional occupational disease that puts both physicians and patients at risk. Triggered by the increase in burnout levels among physicians, the European Forum of Medical Associations and the World Health Organization issued a statement in March 2003 expressing serious concerns about the situation, urging all national medical associations to increase awareness of the problem, monitor it and study its causes in order to develop preventive strategies.

Objectives: To compare burnout levels in two separate samples of primary care physicians measured in the mid-1990s, with burnout levels in a similar but small and independent sample, assessed in 2001; and to outline the theoretical bases of burnout.

Methods: Altogether, 508 primary care physicians employed by Clalit Health Services responded anonymously to a self-report questionnaire. The samples were not representative and included family physicians, pediatricians and clinic directors.

Results: Burnout levels were significantly higher in the 2001 sample than in the mid-1990s samples, especially among clinic directors.

Conclusions: Despite methodologic limitations of the study, the findings suggest that burnout levels may be increasing among primary care physicians in Israel. This may be due to substantial increases in workload and role conflicts, following implementation of the Health Insurance Law and Patients’ Rights Act. Because these findings are consistent with the trend in Europe, this situation cannot be ignored, and systematic studies of burnout among all medical specialties should be carried out to uncover current sources of the syndrome and to devise measures of prevention and treatment.
 

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: Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients.

Objectives: To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment.

Methods: In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B₆ daily and one monthly injection of 200 µg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 µg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy[1] levels were determined after at least 4 weeks washout from all folic acid and B-vitamins that were given. MFTHR[2] alleles were analyzed, as were activated protein C resistance, von Willebrand factor and lupus anticoagulant.

Results: Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects (33.8 ± 4.3 vs. 4.5 to 14.0 mmol/L). Following treatment, Hcy levels were significantly reduced to 21.2 ± 1.6 in group A and 18.6 ± 1.4 mmol/L in group B (P < 0.01). There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study. There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients. Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR (n = 5) was associated with higher Hcy levels and better response to treatment (Hcy levels decreased by 58%, from 46.2 ± 14.6 to 19.48 ± 4.1 mmol/L following treatment). In patients with heterozygous thermolabile MTHFR (n = 25), Hcy levels decreased by 34%, from 31.2 ± 3.7 to 18.1 ± 1.1 mmol/L following treatment. The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable.

Conclusions: Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients, independently of the tested doses. In addition, mutations in MTHFR were associated with elevated plasma levels of Hcy. Neither vascular access nor.

Background: Since the early 1970s testicular scintigraphy has been used to diagnose the cause of acute scrotal pain. The advent of Doppler sonography further enhances diagnosis by  providing simultaneous real-time scrotal imaging with superimposed testicular blood flow information.

Objectives: To assess the diagnostic value of Doppler sonography in patients with acute scrotal pain and scintigraphic findings suggestive of testicular torsion.

Methods: Seventy-five patients with acute scrotal pain underwent testicular scintigraphy and Doppler sonography. All patients who had scintigraphic findings suggestive of testicular torsion were included in the study and their files were retrospectively reviewed.

Results: Twenty-seven patients had scintigraphic findings suggestive of testicular torsion. Radionuclide scintigraphy accurately detected all cases of testicular torsion. However, abscess, hematoma, hydrocele and other conditions simulated testicular torsion on scintigraphy, lowering the test specificity. These pathologies were clarified by Doppler sonography that was 95% specific and 86% sensitive for testicular torsion.

Conclusions: Doppler sonography should be used as the first-line modality in the evaluation of patients with suspected testicular torsion. Scintigraphy should be performed only in certain settings of equivocal sonographic findings to prevent false negative sonographic diagnosis.
 

Background: Increased levels of high density lipoprotein (over 60 mg/dl) are considered to be a risk factor for ischemic heart disease. However, some patients with high HDL[1] still develop cardiovascular diseases.

Objective: To find out why patients with very high HDL still suffer from cardiovascular diseases.

Methods: We analyzed several risk factors, such as increased lipid peroxidation, hyperhomeocysteinemia and increased release of inflammatory molecules that could be related to the development of vascular disease in patients with high serum HDL levels. Patients with HDL cholesterol levels above 75 mg/dl were selected for this study and were separated into two groups based on the presence of atherosclerotic vascular disease, i.e., those with vascular disease (patients) and those without (controls).

Results: Plasma isolated from the patient group exhibited significantly increased lipid peroxidation by 21% and decreased total antioxidant status by 17%, but there were no differences regarding their serum or their paraoxonase activity. Moreover, both groups exhibited similar levels of serum C-reactive protein, fibrinogen and homocysteine, enabling us to eliminate these risk factors in the etiology of cardiovascular disease in the patient group.

Conclusion: Increased oxidative stress could be one of the factors leading to cardiovascular diseases in patients with high serum HDL levels.

Background: Dizziness and vertigo can be a complaint in various psychiatric conditions, where it usually constitutes only one of the features of the syndrome. Lately, a somatoform disorder characterized by almost mono-symptomatic dizziness and unsteadiness has been described. Since phobic postural vertigo usually presents without anxiety or other psychological symptomatology, patients with this condition seek help at neurologic and otolaryngologic clinics where they are often misdiagnosed as suffering from organic vertigo.

Objectives: To present the clinical features of 55 consecutive patients diagnosed with phobic postural vertigo at our clinic during 1998–2002.

Methods: We conducted a retrospective review of patients’ medical records and report two typical cases as illustration.

Results: The patients presented with complaints of unsteadiness with or without dizziness, and attacks of sudden veering that caused them to grasp for support. Accompanying anxiety was admitted by only 5% and vegetative symptoms were reported in 18%. In 16% the symptoms resulted in avoidance behavior. A stressful life event or an unrelated somatic disease triggered the onset of PPV[1] in 35% of patients, whereas a vestibular insult preceded the symptoms in 13%. The mean duration of symptoms was 26.7 ± 39.1 months (range 0.5–20 years). In 72% of patients the symptoms resolved after the psychological mechanism of their symptoms were explained to them; 24% improved with antidepressant treatment (selective serotonin reuptake inhibitors or tricyclic antidepressants), and only in 4% did the symptoms persist.

Conclusions: Since PPV is a frequently encountered diagnosis at some specialized dizziness clinics, familiarity with this entity resulting in early diagnosis can avoid unnecessary examinations and lead to effective treatment.

Progressive neurodegenerative disorders share common mechanisms of cell death, and in all likelihood multiple factors are involved in every disease. Therefore, several neuroprotective agents are being investigated with the purpose of slowing or preventing further deterioration of cell loss. These include experimental animal and clinical studies on the neuroprotective effects of caspase inhibitors, antioxitands, glutamate antagonists, anti-inflammatory agents and trophic factors in several neurodegenerative diseases. At present there is limited clinical evidence for direct neuroprotective effects against these diseases, but much effort is being invested in research on novel technologies and compounds.

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: Genetic factors have been shown to play a major role in the development of peak bone mass, with hereditability accounting for about 50-85% of the variance in bone mass. Numerous candidate genes were proposed to be involved in osteoporosis, but the precise genes and their relative contribution remain unknown.

Objectives: To gain insight into the genetic basis of idiopathic low bone mineral density in Israeli patients by analyzing the impact of two candidate genes: polymorphism of the vitamin D receptor gene and polymorphism A986s in the calcium-sensing receptor gene.

Methods: We analyzed 86 Jewish Israeli patients with LBMD[1]: 38 premenopausal women and 48 men, and compared the allelic pattern distribution with that of the general population (126 men and 112 women). Genotyping of the VDR[2] gene was performed in three polymorphic sites using restriction enzymes, and allelic analysis of A986s polymorphism in the CaSR[3] gene was performed using the denaturing gradient gel electrophoresis technique.  

Reaults: In LBMD women the distributions of VDR alleres in Apal polymorphism were AA=7/28, Aa=16/28 and aa=5/28; in TaqI polymorphism TT=10/31, Tt=16/31 and tt=5/31; and in BsmI polymorphism BB=7/32, Bb=14/32 and 11/32. In LBMD men the distributions were AA=17/39, Aa=21/39 and aa=1/39; in TaqI polymorphism TT=12/42, Tt=23/42 and tt=7/42; and in BsmI polymorphism BB=12/41 Bb=18/41 and bb=11/41. The distributions of all these polymorphisms in the control groups were not significantly different. Adjusting for the independent age and gender parameters confirmed that these three polymorphisms of the VDR gene did not have a significant effect on bone mineral density. Thirty percent (24/79) of LBMD patients of either sex displayed heterozygosity of the CaSR A986s polymorphism, compared with 40 of 203 controls (19.7%) (P=0.059). Adjusting for age and gender in these patients revealed a significant difference in the femoral neck BMD[4] between homozygotes and heterozygotes (P=0.002). The age at menarche of the LBMD women was found to predict 61% of the variance of femoral neck BMD.

Conclusions: In Israeli Jewish men and premenopausal women VDR gene alleles do not seem to be associated with lower lumbar spine or femoral neck BMD. A trend towards heterozygosity for a CaSR polymorphism missense mutation was noted in the LBMD patients. Age at menarche in the LBMD women was found to be an important predictor of BMD. A significant difference was found between LBMD women and healthy control women towards heterozygosity for a CaSR polymorphism, as well between homozygotes and heterozygotes for a CaSR polymorphism in BMD. The significance of these findings and their applicability to a larger population awaits further studies.

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Background: Primary idiopathic pulmonary hypertension is a rapidly progressive disease with a median survival of less than 3 years. Recently its prognosis was shown to dramatically improve with the use of epoprostenol, an arachidonic acid metabolite produced by the vascular endothelium, which increases the cardiac output and decreases the pulmonary vascular resistance and pulmonary arterial pressure. This drug enhances the quality of life, increases survival and delays or eliminates the need for transplantation.

Objective: To review the experience of Israel hospitals with the use of epoprostenol.

Methods: The study group comprised 13 patients, 5 men and 8 women, with an age range of 3–53 years. All patients suffered from arterial pulmonary hypertension. Epoprostenol was administered through a central line in an increased dose during the first 3 months, after which the dose was adjusted according to the clinical syndrome and the hemodynamic parameters.

Results: After 3 months the mean dose was 10 ng/kg/min and the pulmonary artery pressure decreased from 7 to 38%. After one year, the PAP decreased at a slower rate. Two cases required transplantation, three patients died, and seven continued taking the drug (one of whom discontinued). Four episodes of septicemia were observed. Today 10 patients are alive and well and 7 continue to take epoprostenol.

Conclusion: We found that epoprostenol improves survival, quality of life and hemodynamic parameters, with minimum side effects.

Background: Previous studies have demonstrated myocardial salvage by basic fibroblast growth factor administration following chronic myocardial ischemia or acute myocardial infarction.

Objectives: To study the effect of bFGF[1] on left ventricular morphometry following coronary occlusion and reperfusion episode in rats.

Methods: bFGF (0.5 mg) or placebo was continuously administered for a period of one week using an implanted osmotic pump. Animals were sacrificed 6 weeks after surgery and myocardial cross-sections were stained with Masson-trichrome and with anti-proliferating cell nuclear antigen antibody.

Results: LV[2] area, LV cavity diameter, LV cavity/wall thickness ratio, and injury size were unchanged compared with control animals. Proliferating endothelial cells were significantly more abundant in injured compared with normal myocardium, but with no differences between animals treated or not treated with bFGF.

Conclusions: One week of systemic bFGF administration following coronary occlusion and reperfusion had no additional effect on LV geometry or cellular proliferation in rats.

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[1] bFGF = basic fibroblast growth factor

[2] LV = left ventricular