Israel Medical Association Journal

Ventricular remodeling and heart failure are the inevitable consequences of myocardial infarction. Current options to cure myocardial infarction and subsequent heart failure suffer from specific limitations. Thus, alternative, additional long-term therapeutic strategies are needed to cure this costly and deadly disease. Cardiac regeneration is a promising new therapeutic option. Through cellular and molecular therapies, the concept of in situ "growing" heart muscle, vascular tissue and manipulating the extracellular matrix environment promises to revolutionize the approach of treating heart disease. Recent studies have suggested that stem cells resident within the bone marrow or peripheral blood can be recruited to the injured heart. The regeneration of damaged heart tissue may include the mobilization of progenitor or stem cells to the damaged area or stimulation of a regenerative program within the organ. There is now evidence accumulating that the heart contains resident stem cells that can be induced to develop into cardiac muscle and vascular tissue. The present review aims to describe the potential, the current status and the future challenges of myocardial regeneration by adult stem cells.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

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: 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: 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: During the last decade, Israel, a country with low tuberculosis rates, absorbed some 900,000 new immigrants from TB[1]-endemic countries.

Objectives: To analyze the specific impact of our screening procedures on active TB among children in Israel.

Methods: We conducted a retrospective analysis of epidemiologic and clinical data of all children (aged 0–17) with TB notified to the Ministry of Health between 1990 and 1999.

Results: There were 479 children with TB (male/female ratio 1.36). Most cases (81.8%) were foreign born, predominantly (88.2%) immigrants from Ethiopia and, therefore, huge differences existed in TB incidence rates according to countries of origin. Some 80% were diagnosed within 3 years of arrival, mainly due to active case-finding. Pulmonary TB, with infiltrates on chest X-ray, was found in 49.5%. Extra-pulmonary TB sites were: intra-thoracic lymphadenitis (31.1%), extra-thoracic lymphadenitis (12.5%), bones (3.6%), pleura (1.3%), meninges (1%), and others (1%). Seventy percent had a tuberculin skin test reaction ≥10 mm in size. Two (non-immigrant) children died of TB meningitis.

Conclusions: Most of the pediatric TB cases occurred in recent immigrants and were diagnosed within 3 years of immigration. These data support our policy of active case-finding among new immigrants from Ethiopia and extensive contact evaluation for all TB cases.

Background: Lipoid pneumonia is a pneumonitis resulting from the aspiration of lipids, and is commonly associated with the use of mineral oil as a laxative. LP[1] is relatively unfamiliar to clinicians and is probably underdiagnosed.

Objectives: To increase physicians' awareness of LP, its diagnosis and prevention.

Methods: We present two illustrative cases of LP and review the literature.

Results: Two cases of LP were diagnosed within half a year in an internal medicine ward. Both cases were elderly patients, and LP was associated with the use of mineral oil as a laxative agent. Computerized tomography revealed bilateral low attenuation infiltrates, associated with a "crazy paving" pattern in one case. Sudan Black staining was diagnostic in both cases – in one on a transbronchial biopsy specimen, and in the other on sputum cytologic examination. Both patients suffered from neurologic diseases and were at risk of aspiration. In both cases clinical symptoms and signs continued for several months prior to diagnosis but resolved after the mineral oil was discontinued.

Conclusions: LP often occurs in elderly patients who are at risk of aspiration. The condition may be underdiagnosed. Since in most cases mineral oil cathartics are the causative agent, an effort at primary prevention is indicated. It is suggested that the licensing of mineral oil for internal use be changed.

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.

Orbital dog bites, although uncommon, occur mostly in children and are reported to be associated with severe ocular adnexal injury without globe involvement.

The autoimmune lymphoproliferative syndrome is a recently described human disorder that affects lymphocyte programmed cell death (apoptosis).