Israel Medical Association Journal

Background: We recently published preliminary evidence on the effectiveness of hypertonic saline in infants with viral bronchiolitis.

Objective: To further establish the efficacy of nebulized hypertonic saline in these infants

Methods: In a continuing, second-year randomized, double-blind controlled trial, an additional 41 infants (age 2.6 ± 1 months) hospitalized with viral bronchiolitis were recruited during the winter of 2001–2002. The infants received inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was repeated three times daily until discharge. Pooling our 2 years of experience (2000–2002), a total of 93 hospitalized infants with viral bronchiolitis were recruited; 45 were assigned to Group I and 48 to Group II.

Results: The clinical scores at baseline were 7.6 ± 0.7 for Group I vs. 7.4 ± 1.3 for Group II (P = NS). However, the clinical scores at days 1 and 2 after inhalation differed significantly between the two groups, invariably favoring Group II: 7 ± 1 vs. 6.25 ± 1.1 (P < 0.05), 6.45 ± 1 vs. 5.35 ± 1.35 (P < 0.05), respectively. Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization stay from 3.5 ± 1.7 days in Group I to 2.6 ± 1.4 in Group II (P < 0.05). The pooled data of both years revealed that adding 3% saline to the inhalation mixture decreased hospitalization stay from 3.6 ± 1.6 to 2.8 ± 1.3 days (P < 0.05).
Conclusions: This second-year experience and our 2 year pooled data analysis strengthen the evidence that the combination of 3% saline/1.5 mg epinephrine benefits hospitalized infants with viral bronchiolitis

The adult human heart has limited regenerative capacity and, therefore, functional restoration of the damaged heart presents a great challenge. Despite the progress achieved in the pharmacological and surgical treatment of degenerative myocardial diseases, they are still considered a major cause of morbidity and mortality in the western world. Repopulation of the damaged heart with cardiomyocytes represents a novel conceptual therapeutic paradigm but is hampered by the lack of sources for human cardiomyocytes. The recent derivation of pluripotent human embryonic stem cell lines may provide a solution for this cell sourcing problem. This review will focus on the derivation of the hESC[1] lines, their mechanism of self-renewal, and their differentiation to cardiomyocytes. The possible signals and cues involved in the commitment and early differentiation of cardiomyocytes in this model will be discussed as well as the molecular, structural and electrophysiologic characteristics of the generated hESC-derived cardiomyocytes. Finally, the hurdles and challenges toward fully harnessing the potential clinical applications of these unique cells will be described.

Background: Men and postmenopausal women with iron deficiency anemia are routinely evaluated to exclude a gastrointestinal source of suspected internal bleeding. Iron deficiency anemia in premenopausal women is often treated with simple iron replacement, under the assumption that the condition is due to excessive menstrual blood loss.

Objectives: To determine the yield of endoscopy evaluations in premenopausal women with iron deficiency anemia.

Methods: Upper and lower gastrointestinal endoscopic examinations were conducted in 45 premenopausal women with iron deficiency anemia not related to gynecologic or nutritional causes.

Results: Forty-three of the 45 women fulfilled the entry criteria and were enrolled. Their mean age was 35 ± 15 years and their mean hemoglobin level 9.3 ± 2.3 g/dl. Twenty‑eight upper gastrointestinal lesions were demonstrated in 24 of the 43 patients (55.8%): erosive gastritis in 12 (27.9%), erosive duodenitis in 4 (9.3%), erosive esophagitis in 3 (7.0%), hiatus hernia (with Cameron lesions) in 3 (7.0%), active duodenal ulcer in 1 (2.3%) and hyperplastic polyp (10 mm) in 1 (2.3%). Five lower gastrointestinal lesions were detected in 5 patients (16.3%): 2 (4.6%) had adenocarcinoma of the right colon, 2 (4.6%) had pedunculate adenomatous polyp > 10 mm, and 1 (2.3%) had segmental colitis (Crohn's disease). One patient (2.3%) had pathologic findings in both the upper and lower gastrointestinal tracts.

Conclusions: Our findings of a gastrointestinal source of chronic blood loss in 28 of 43 premenopausal women with iron deficiency anemia (65.1%) suggest that this population will benefit from bi‑directional endoscopic evaluations of the gastrointestinal tract.

Background: Magnetic resonance imaging is a diagnostic tool of growing importance. Since its introduction, certain medical implants, e.g., pacemakers, were considered an absolute contraindication, mainly due to the presence of ferromagnetic components and the potential for electromagnetic interference. Patients with such implants were therefore prevented from entering MRI systems and not studied by this modality. These devices are now smaller and have improved electromechanical interference protection. Recently in vitro and in vivo data showed that these devices may be scanned safely in the MRI.

Objectives: To report our initial experience with three patients with pacemakers who underwent cerebral MRI studies.

Methods: The study included patients with clear clinical indications for MRI examination and who had implanted devices shown to be safe by in vitro and in vivo animal testing. In each patient the pacemaker was programmed to pacing-off. During the scan, continuous electrocardiographic telemetry, breathing rate, pulse oximetry and symptoms were monitored. Specific absorption rate was limited to 4.0 W/kg for all sequences. Device parameters were assessed before, immediately after MRI, and 1 week later.

Results: None of the patients was pacemaker dependent. During the MRI study, no device movement was felt by the patients and no episodes of inappropriate inhibition or rapid activation of pacing were observed during the scan. At device interrogation here were no significant differences in device parameters pre-, post-, and 1 week after MRI. Image quality was unremarkable in all imaging sequences used and was not influenced by the presence of the pacemaker.

Conclusion: Given appropriate precautions, MRI can be safely performed in patients with a selected permanent pacemaker. This may have significant implications for current MRI contraindications.  

Background: Intramural duodenal hematoma generates partial or complete obstruction that develops slowly and progressively with a consequent delay in diagnosis. Many diagnostic and therapeutic measures remain debatable and justify a review of current management policy.

Objectives: To highlight the diagnostic and therapeutic steps in pediatric IDH[1].

Methods: The records of 12 children with post-traumatic IDH who were treated in the Hillel Yaffe Medical Center between 1986 and 2000 were retrospectively reviewed. Three of them had clotting disorders and were excluded. The interval between their admission and diagnosis as well as the therapeutic decisions were evaluated and analyzed.

Results: Nine children were treated for IDH. The interval between admission and diagnosis ranged from 24 hours to 6 days. Five children had associated traumatic pancreatitis. Initially, all the children were conservatively treated. In seven the hematoma resolved after 9–20 days. Two children were operated upon because the obstruction failed to resolve. All nine children recovered without permanent complications.

Conclusions: Intramural duodenal hematoma has many clinical and therapeutic puzzling aspects. Bicycle handlebar, road accidents and sports trauma are the main etiologic factors in children, but child abuse should be kept in mind. Associated traumatic pancreatitis is common. Gastroduodenal endoscopy may be useful to clarify doubtful cases. Pediatric surgeons should increase awareness regarding IDH in order to reduce delay in diagnosis and the need for surgical decompression.

Background: The contribution of drugs and alcohol to current trauma‑related morbidity and mortality in Israel is not known. Identification of these factors in the fast-changing demographics of the Israeli population might lead to better care and, no less importantly, to targeted prevention measures.

Objectives: To determine the incidence of alcohol‑related trauma, and to specify the time of day, the cause of trauma, and the morbidity and mortality rates as compared to non-alcohol‑associated trauma in the tertiary trauma unit of a large medical center in Tel Aviv.

Methods: Data were obtained from the Israel National Trauma Registry, based on patient records in our institution (Tel Aviv Sourasky Medical Center) from January 2001 to December 2003.

Results: Of the 5,529 patients who were enrolled in the study, 170 had high alcohol blood levels (> 50 mg/dl). Patients intoxicated with alcohol had higher rates of road accident injuries (35% versus 24% non‑intoxicated) and stab wounds (29% vs. 7%). The Injury Severity Score of the alcohol‑intoxicated patients was higher (32% ³ 16 vs. 12% ³ 16). The alcohol‑intoxicated patients were more likely to be non-Jewish (34% vs. 9%), young (82% aged 15–44 years) and males (91%). Most of the alcohol‑related injuries occurred during the weekend (47%) and during evening‑late night hours (from 7 a.m. to 11 p.m.; 55%).

Conclusions: Alcohol‑associated trauma differs from non-alcohol‑associated trauma in many ways. Since the population at risk can be identified, it is important that legislative, social, enforcement and educational measures be adopted to reduce the extent of alcohol abuse and thereby improve the level of public safety.
 

Background: Cardiovascular disease is now well established as a multifactorial disease. In a given individual, the level of cardiovascular risk is due to the interaction between genetic and environmental components. The BIP cohort comprised 3000 patients with cardiovascular disease who were tested for the benefits of bezafibrate treatment. This cohort has the data for the lipid profile of each individual, fibrinogen, Insulin, as well as clinical, demographic and lifestyle parameters

Objectives: To genotype up to 64 variable sites in 36 genes in the BIP cohort. The genes tested in this assay are involved in pathways implicated in the development and progression of atherosclerotic plaques, lipid and homocystein metabolism, blood pressure regulation, thrombosis, rennin-angiotensin system, platelet aggregation, and leukocyte adhesion.

Methods:  DNA was extracted from 1000 Israeli patients from the BIP cohort. A multilocus assay, developed by the Roche Molecular System, was used for genotyping. Allele frequencies for some of the markers were compared to the published frequencies in a healthy population (the French Stanislas cohort, n=1480).

Results: Among the 26 comparable alleles checked in the two cohorts, 16 allele frequencies were significantly different from the healthy French population: ApoE (E3, E2, E4), ApoB (71ile), ApoC (3482T, 455C, 1100T, 3175G, 3206G), CETP (405val), ACE (Del), AGT (235thr), ELAM (128arg); p<0001 and LPL (93G, 291Ser, 447ter); p < 005.

Conclusions: Although a comparable healthy Israeli population study is needed for more precise interpretation of these results, frequency differences in these polymorphic alleles, associated with lipid metabolism, renin-angiotensin system and leukocyte adhesion mechanism, between CVD patients and healthy individuals nevertheless implicate these candidate genes as predisposing for CVD.lic safety.
 

Background: Persistent creatine kinase elevation is occasionally encountered in subjects without any clinical manifestation of a neuromuscular disorder or any condition known to be associated with increased serum CK[1] levels. It is still unresolved whether extensive investigations and specifically a muscle biopsy should be performed in clinically normal individuals with elevated CK levels.

Objective: To study the muscle pathology of patients with asymptomatic or minimally symptomatic hyperCKemia.

Methods: The clinical and laboratory data of patients with persistent hyperCKemia and normal neurologic examination were reviewed and their muscle biopsies evaluated.

Results: The study group included 40 patients aged 7–67 years; the male to female ratio was 3:1. Nineteen patients were completely asymptomatic, 20 had mild non-specific myalgia, and 1 had muscle cramps. Electromyography was performed in 27 patients and showed myopathic changes in 7 (26%). Abnormal muscle biopsy findings (e.g., increased variation in fiber size, increased number of central nuclei and occasional degenerating fibers) were detected in 22 of the 40 patients (55%). No fat or glycogen accumulation was detected. Immunohistochemistry demonstrated abnormal dystrophin staining in 3 patients (8%), resembling the pathologic changes of Becker muscular dystrophy. No abnormal findings were detected on immunohistochemical staining for merosin, dysferlin, caveolin 3, or alpha and gamma sarcoglycans. The EMG[2] findings did not correlate with the pathologic findings.

Conclusions: Abnormal muscle biopsies were found in 55% of patients with asymptomatic or minimally symptomatic hyperCKemia. Specific diagnosis of muscular dystrophy, however, was possible in only 8% of the patients.

Evidence that crystalline silica is associated with an increased rate of lung cancer led the International Agency for Research on Cancer to conclude in 1997 that crystalline silica is a known human carcinogen. In Israel too, crystalline silica is considered as such. The decision raised a debate in the scientific arena, and a few scientists have questioned the basis upon which causality was determined. We review the literature regarding the level of evidence of crystalline silica carcinogenicity.

Human embryonic stem cells may serve as a potentially endeless source of  transplantable cells to treat various neurologic disorders. Accumulating data have shown the therapeutic value of various neural precursor cell types in experimental models of neurologic diseases. Tailoring cell therapy for specific disorders requires the generation of cells that are committed to specific neural lineages. To this end, protocols have been developed recently for the derivation of dopaminergic neurons, spinal motor neurons and oligodendrocytes from hESC[1]. These protocols recapitulate normal development in culture conditions. However, a novel concept emerging from these studies is that the beneficial effect of transplanted stem cells is not only via cell replacement in damaged host tissue, but also by trophic and protective effects, as well as by an immunomodulatory effect that down-regulates detrimental brain inflammation.

Three decades have elapsed since the inception of Level I trauma centers as the final link in the trauma system "chain of survival".

Background: Phototherapy is considered the standard of care for neonatal jaundice. However, its short term cardiorespiratory effects have not been studied thoroughly.

Objectives: To assess the cardiorespiratory effect of phototherapy during sleep in term infants with physiologic jaundice.

Methods: We performed two polysomnography studies during 3 hours sleep in 10 healthy term infants with physiologic jaundice; each infant served as his/her own control. The first study was performed just prior to phototherapy and the second study during phototherapy 24 hours later. Heart and respiratory rates, type and duration of apneas, and arterial oxygen saturation were analyzed during active and quiet sleep.

Results: Term infants (gestational age 38.6 ± 1.4 weeks, birth weight 3.2 ± 0.5 kg) underwent the two polysomnography studies within a short time interval and had a comparable bilrubin level (3.6 ± 0.8 and 4.5 ± 0.8 days; 14.5 ± 1.4 and 13.8 ± 2.1 mg/dl, P = NS, respectively). There was no difference in sleeping time or the fraction of active and quiet sleep before or during phototherapy. During active sleep under phototherapy there was a significant decrease in respiratory rate and increase in heart rate (54.3 ± 10.3 vs. 49.1 ± 10.8 breaths/minute, and 125.9 ± 11.7 vs. 129.7 ± 15.3 beats/minute, respectively, P < 0.05), as well as a decrease in respiratory effort in response to apnea. These effects were not found during quiet sleep. Phototherapy had no significant effect on oxygen saturation, apnea rate or periodic breathing in either sleep state. No clinical significant apnea or bradycardia occurred.

Conclusions: Phototherapy affected the cardiorespiratory activity during active sleep but not during quiet sleep in term infants with physiologic jaundice. These effects do not seem to have clinical significance in "real-life" conditions.

Background: Ischemic mitral regurgitation is associated with reduced survival after coronary artery bypass surgery.

Objectives: To compare long-term survival among patients undergoing coronary surgery for reduced left ventricular function and severe ischemic MR[1] in whom the valve was either repaired, replaced, or no intervention was performed.

Methods: Eighty patients with severe left ventricular dysfunction and severe MR underwent coronary bypass surgery. The mean age of the patients was 65 years (range 42–82), and 63 (79%) were male. Sixty-three (79%) were in preoperative NYHA functional class III-IV (mean NYHA 3.3), and 26 (32%) were operated on an urgent/emergent basis. Coronary artery bypass surgery was performed in all patients. The mitral valve was repaired in 38 and replaced in 14, and in 28 there was no intervention. The clinical profile was similar in the three groups, although patients undergoing repair were slightly younger.

Results: Operative mortality was 15% (8%, 14%, and 25% for the repair, replacement and no intervention respectively; not significant). Long-term follow up was 100% complete, for a mean of 38 months (range 2–92). Twenty-nine patients (57%) were in NYHA I-II (mean NYHA 2.3). Among the surgery survivors, late survival was improved in the repair group compared to the other groups (P < 0.05). Predictors for late mortality were non-repair of the mitral valve, residual MR, and stroke (P = 0.005).

Conclusions: Patients with severe ischemic cardiomyopathy and severe MR undergoing coronary bypass surgery should have a mitral procedure at the time of surgery. Mitral valve repair offers a survival advantage as compared to replacement or no intervention on the valve. Patients with residual MR had the worst results.