Israel Medical Association Journal

Background: Long QT syndrome is an inherited cardiac disease, associated with malignant arrhythmias and sudden cardiac death.

Objectives: To map and identify the gene responsible for LQTS[1] in an Israeli family.

Methods: A large family was screened for LQTS after one of them was successfully resuscitated from ventricular fibrillation. The DNA was examined for suspicious loci by whole genome screening and the coding region of the LQT2 gene was sequenced.

Results: Nine family members, 6 males and 3 females, age (median and interquartile range) 26 years (13, 46), who were characterized by a unique T wave pattern were diagnosed as carrying the mutant gene. The LQTS-causing gene was mapped to chromosome 7 with the A614V mutation. All of the affected members in the family were correctly identified by electrocardiogram. Corrected QT duration was inversely associated with age in the affected family members and decreased with age.
Conclusions: Careful inspection of the ECG can correctly identify LQTS in some families. Genetic analysis is needed to confirm the diagnosis and enable the correct therapy in this disease

Background: Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.

Objectives: To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM[1] in a transfer model of NOD mice.

Methods: Our vaccination technique involved the insertion of CD44s[2] or CD44v[3] cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN[4] were implanted 20 days before and 3 days after cell transfer.

Results: In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.

Conclusions: These findings may open new opportunities for IDDM therapy in the future.

Background: In recent years there has been an increase in endovascular repair of thoracic aortic aneurysms. In cases of insufficient neck length, occlusion of left subclavian artery achieves proper sealing and is usually well tolerated. Selected cases require revascularization of the left subclavian artery, including patients after coronary bypass surgery (left internal mammary to left anterior descending) and those with arm claudication or subclavian steal syndrome.

Objectives: To evaluate the tolerability of left subclavian artery occlusion by stent graft without revascularization.

Methods: Thirty patients with thoracic aortic aneurysms underwent endovascular repair between July 2000 and November 2004. Eleven of them had occlusion of the left subclavian artery that required revascularization in two. Follow-up (average 3 years) included a) blood pressure measurements of both arms at rest, after effort and pulse palpation, and b) vertebral blood flow by duplex scan.

Results: Of nine patients with no revascularization, 8 (89%) tolerated left subclavian artery occlusion with no claudication or steal syndrome; one (11%) suffered mild claudication only after effort and required no intervention. No left radial pulses were palpated in the nine patients. Blood pressure measurements in the left arm showed an average decrease of 40%, which remained constant after induced effort in all patients and was clinically insignificant. Duplex scan demonstrated reverse flow in the left vertebral artery in 8 of 9 patients (89%) and occlusion in 1 (originating in the arch and covered by the stent graft) with no clinical symptoms.

Conclusions: Left subclavian artery occlusion by stent graft is a tolerable procedure in the long term. In most cases, the constant decrease in blood pressure remained unchanged during follow-up and had no significant adverse affects. Most patients do not require revascularization prior to the endovascular procedure.
 

Background: The etiology of chest pain with normal epicardial coronary arteries (cardiac syndrome X) seems to be related to endothelial cell dysfunction. Multiple factors are implicated in the pathophysiology, including evelated levels of homocysteine in the blood. Mutations in the MTHFR gene are associated with evelated levels of homocysteine.

Objectives: To test whether abnormal homocysteine metabolism is associated with syndrome X.

Methods: Forty-two women with chest pain, positive stress test and normal coronary arteries (syndrome X) and 100 asymptomatic women (controls) were studied for the C677T mutation. Vitamin B12, folic acid, and plasma levels of homocysteine were also measured. Endothelial cell function was studied in 10 patients with syndrome X and homozygosity for C677T mutation, and in 10 matched healthy controls. Folic acid (5 mg daily) was prescribed to syndrome X patients after initial measurements of ECF[1]. Following 13 weeks of treatment, ECF and blood tests were repeated and compared to baseline measurements.

Results: Homozygosity for C677T mutation was doubled in syndrome X vs. control (33%, 14/42 vs. 16%, 16/100, P < 0.02), and homocysteine levels were increased (9.16 ± 2.4 vs. 8.06 ± 2.6 μmol/L, P = 0.02). In the 10 homozygous patients, homocysteine levels decreased significantly after treatment with 5 mg/day folic acid (10 ± 3.3 vs. 5.4 ± 1.1 µmol/L, P = 0.004). Abnormal baseline ECF improved after treatment with folic acid: flow-mediated dilatation was greater (11.3 ± 7.9% vs. 0.7 ± 4.5%, P < 0.002), as was nitroglycerin-mediated dilatation (15.2 ± 9.0% vs. 5.6 ± 6.4%, P < 0.003). Frequency of chest pain episodes was significantly reduced after 13 weeks of folic acid treatment.

Conclusion: Our findings establish the association between the C677T mutation, endothelial cell dysfunction and cardiac syndrome X, and provide a novel and simple therapy for a subset of patients with syndrome X and homozygosity for the C677T mutation.

Objectives: To determine whether there is an association between the presence and severity of adult calcific aortic stenosis and Chlamydia pneumoniae seropositivity

Methods: Forty adult patients (23 women, 17 men) were divided into three groups according to echocardiographic aortic valve area: Group A – 7 symptomatic subjects (age 67 ± 7 years) with normal aortic valve and normal coronary angiogram, Group B – 16 patients (age 73 ± 6) with moderate ACAS[1] (AVA[2]> 0.8 £ 1.5 cm²), and Group C – 17 patients (age 76 ± 7) with severe ACAS (AVA £ 0.8 cm²). We tested for immunoglobulins M, G and A as retrospective evidence of C. pneumoniae infection using the micro-immunofluorescence method. Past C. pneumoniae infection was defined by IgG titer > 16 £ 512.

Results: No patients in Group A showed positive Ig[3] for C. pneumoniae. IgM was not detected in any of the patients with ACAS (groups B and C) while 2 of 17 patients (12%) in group C showed IgA for the pathogen. High titers of IgG were found in 14 of 33 (42%) of the patients with moderate or severe ACAS: 5 of 16 (31%) in group B and 9 of 17 (53%) in group C (P = 0.2). Both groups had the same prevalence of coronary artery disease (66%). AVA was lower in IgG-seropositive patients than in the seronegative group (0.88 ± 0.3 cm² vs. 1.22 ± 0.4 cm², respectively, P = 0.02).

Conclusions: Past C. pneumoniae infection may be associated with a higher prevalence and greater severity of ACAS.

Objectives: To identify patients with PPD and to describe their consultation patterns with primary care physicians for themselves and their babies.

Methods: Using a telephone survey and the Edinburgh Postnatal Depression Scale questionnaire we identified PPD in a sample of women who gave birth in HaEmek Medical Center. We also assessed the extent to which the women consulted with family physicians, gynecologists and/or pediatricians.

Results: The survey included 574 women, of whom 9.9% were diagnosed with PPD. There was a higher rate of PPD among Arab compared to Jewish women, among women with a prior history of depression, among women whose pregnancy was unplanned, among those who described the course of pregnancy as “difficult,” and among women who described their general health as “not good.” Women with PPD consulted more with family physicians and pediatricians. The reasons for the consultations are physical and emotional. There were cases of somatization manifested directly by the mother or indirectly through the baby.

Conclusions: Women with PPD have higher consultation rates than those without. By asking a few simple questions it is possible to identify a significant proportion of women with PPD.

Background: Ultrasound is useful in detecting acromioclavicular pathologies in cases of trauma, inflammations and degenerative changes.

Objectives: To describe the sonographic findings of the acromioclavicular joint pathology in patients with anterior shoulder pain.

Methods: Sonographic examination of the ACJ[1] was used to examine 30 adults with anterior shoulder pain. As a control group we studied 30 asymptomatic patients and compared the findings to plain radiographs of the symptomatic group.

Results: The pathologic findings consisted of swelling of the joints, bone irregularities, widening and/or narrowing of the ACJ, soft tissue cyst formation, excessive fluid collection, and calcification. All these signs represent degenerative changes compatible with early osteoarthritis. We encountered one case of septic arthritis that required joint aspiration and antibiotic treatment.

Conclusions: It is our belief that ultrasonography should be used routinely in cases of anterior shoulder pain since it demonstrates various pathologies undetected by plain radiographs.

Ghrelin, a 28 amino acid acylated peptide predominantly produced by the stomach, displays strong growth hormone-releasing activity mediated by the hypothalamus-pituitary GH[1] secretagogue receptors that were found to be specific for a family of synthetic, orally active GH secretagogues. The discovery of ghrelin brings us to a new understanding of the regulation of GH secretion. However, ghrelin is much more than simply a natural GH secretagogue. It also acts on other central and peripheral receptors and exhibits other actions, including stimulation of lactotroph and corticotroph secretion, orexigenia, influences gastroenteropancreatic functions, and has metabolic, cardiovascular and anti-proliferative effects. Knowledge of the whole spectrum of biologic activities of this new hormone will provide new understanding of some critical aspects of neuroscience, metabolism and internal medicine. In fact, GHS[2] were born more than 20 years ago as synthetic molecules, eliciting the hope that orally active GHS could be used to treat GH deficiency as an alternative to recombinant human GH. However, the dream did not become reality and the usefulness of GHS as an anabolic anti-aging intervention restoring the GH/IGF-I[3] axis in somatopause is still unclear. Instead, we now face the theoretic possibility that GHS analogues acting as agonists or antagonists could become candidate drugs for the treatment of pathophysiologic conditions in internal medicine totally unrelated to disorders of GH secretion. 

Background: The emergency department is one of the hospital’s busiest facilities and is frequently described as a bottleneck. Management by constraint is a managerial methodology that helps to focus on the most critical issues by identifying such bottlenecks. Based on this theory, the benefit of adding medical staff may depend on whether or not physician availability is the bottleneck in the system.

Objective: To formulate a dynamic statistical model to forecast the need for allocating additional medical staff to improve the efficacy of work in the emergency department, taking into account patient volume.

Methods: The daily number of non-trauma admissions to the general ED[1] was assessed for the period 1 January 1992 to 1 December 1995 using the hospital computerized database. The marginal benefit to shortening patient length of stay in the ED by adding a physician during the evening shift was examined for different patient volumes. Data were analyzed with the SAS software package using a Gross Linear Model.

Results: The addition of a physician to the ED staff from noon to midnight significantly shortened patient LOS[2]: an average decrease of 6.61 minutes for 80–119 admissions (P<0.001). However, for less than 80 or more than 120 admissions, adding a physician did not have a significant effect on LOS in the ED.

Conclusions: The dynamic model formulated in this study shows that patient volume determines the effectiveness of investing manpower in the ED. Identifying bottleneck critical factors, as suggested by the theory of constraints, may be useful for planning and coordinating emergency services that operate under stressful and unpredictable conditions. Consideration of patient volume may also provide ED managers with a logical basis for staffing and resource allocation.