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: In Japan, helicopters have rarely been used for emergency medical services. The use of helicopters not only ensures rapid evacuation but may also serve to provide emergency management to patients with life-threatening injuries in the prehospital setting.

Objectives: To evaluate a Japanese helicopter-based emergency medical system including an onboard physician, particularly in terms of probability of survival.

Methods: We conducted a retrospective review of trauma victims, and calculated two estimates of PS[1] – at the scene and on arrival at the emergency department – based on patient age, Injury Severity Score, and Revised Trauma Score.

Results: We identified trauma victims who had an ISS[2] above 15 and were transported from the scene by helicopter. Excluding cardiopulmonary arrest at the scene, 151 cases were studied. Thirty-two patients had hemodynamic instability with systolic blood pressures below 90 mmHg, caused by hemorrhagic shock (29 cases) or obstructive shock (3 cases). Their PS values were 0.56 ± 0.38 in the prehospital setting and 0.65 ± 0.38 on arrival at the ED[3], representing a significant difference (P = 0.0003). Twenty-four of these patients survived, reflecting successful resuscitation during prehospital and ED management.

Conclusions: A doctor-helicopter system was shown to improve probability of survival for life-threatening trauma in the Japanese emergency medical system.

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.

Background: Advanced glycation end products, formed by the non-enzymatic glycation of proteins with reducing sugars, are thought to play a pathogenetic role in the vascular complications of diabetes, uremia and atherosclerosis. β2-microglobulin is a major constituent of amyloid fibrils in dialysis-related amyloidosis. AGE[1]-modified β2m[2] has been found in amyloid deposits of long-term hemodialysis patients. AGE-modified β2m has also been shown to enhance chemotaxis and increase tumor necrosis factor-alpha and interleukin-1 beta secretion by circulating and tissue monocytes/macrophages.

Objectives: To investigate the effect of AGE-modified β2m and AGE-human serum albumin on TNF-α[3] and IL-1β[4] secretion by human peritoneal macrophages derived from patients on continuous ambulatory peritoneal dialysis.

Methods: Human PMØ[5] were isolated from peritoneal dialysis effluent of stable CAPD[6] patients and were incubated for 24 hours with AGE-modified β2m, β2m, AGE-HSA[7], HSA or lipopolysaccharide. TNF-α or IL-1β secretion was measured by enzyme-linked immunosorbent assay in cell-free culture supernatants.

Results: Both AGE-modified β2m and AGE-HSA significantly increased TNF-α and IL-1β secretion by human PMØ in a dose-dependent manner (50–200 μg/ml). In contrast, β2m or HSA had no such stimulatory effect on TNF-α secretion but had a small significant increase in IL-1β secretion.

Conclusions: AGE-modified β2m promotes in vitro TNF-α and IL-1β secretion by human PMØ of CAPD patients. Activation of these macrophages by AGE-modified β2m may be a contributory factor to the morphologic changes and altered permeability of the peritoneal membrane in long-term CAPD. 

Non-steroidal anti-inflammatory drugs, mainly ibuprofen, are extensively used in children as analgesics and antipyretics.

Objectives: To evaluate the extent and characteristics of CAM[1] use among cancer patients in northern Israel.

Methods: Telephone interviews were conducted with 2,176 newly registered cancer patients or their family members, at least 1 year following referral.

Results: The rates of CAM use varied significantly according to demographic characteristics and chemotherapy treatment, from 3% in the basically educated elderly group up to 69% of educated Israeli-born Jews younger than 70 years receiving chemotherapy. The overall rate of CAM use was 17%. The most influential factors determining CAM use were academic or high school education, chemotherapy treatment, Israel as country of birth, and age 41–50 years. All patients used CAM in addition to conventional therapies. Less than half of them reported it to their physicians. The most frequently used treatments were various chemical, biological, botanic and homeopathy remedies. Friends and relatives were the main recommenders of CAM. Most CAM users reported that they used CAM because they believed it “strengthens the immune system,” alleviates side effects of chemotherapy, improves quality of life and helps to overcome pain and stress, and 62% of them reported subjective beneficial effects.

Conclusions: A predicting module of CAM user patients was built, which may help physicians initiate conversations with their patients on CAM use. Expanding physicians' knowledge on CAM methods will encourage them to provide additional advice, promote the use of beneficial therapies, and inform patients about potentially harmful methods.

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[1] CAM = complementary and alternative medicine

Objectives: To assess the prevalence of metabolic syndrome and different glucose intolerance states in healthy, overweight Arab individuals attending a primary healthcare clinic in Israel.

Methods: We randomly recruited 95 subjects attending a primary healthcare clinic who were healthy, overweight (body mass index >27) and above the age of 40. Medical and family history was obtained and anthropometric parameters measured. Blood chemistry and oral glucose tolerance test were performed after overnight fasting.

Results: Twenty-seven percent of the subjects tested had undiagnosed type 2 diabetes according to WHO criteria, 42% had impaired fasting glucose and/or impaired glucose tolerance and only 31% had a normal OGTT[1]. Metabolic syndrome was found in 48% according to criteria of the U.S. National Cholesterol Education Program, with direct correlation of this condition with BMI[2] and insulin resistance calculated by homeostasis model assessment. Subjects with metabolic syndrome had a higher risk for abnormality in glucose metabolism, and the more metabolic syndrome components the subject had the higher was the risk for abnormal glucose metabolism. Metabolic syndrome predicted the result of OGTT with 0.67 sensitivity and 0.78 specificity. When combined with IFG[3], sensitivity was 0.83 and specificity 0.86 for predicting the OGTT result.

Conclusions: According to our initial evaluation approximately 70% of the overweight Arab population in Israel has either metabolic syndrome or abnormal glucose metabolism, indicating that they are at high risk to develop type 2 diabetes and cardiovascular morbidity and mortality. This population is likely to benefit from an intervention program.

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[1] OGTT = oral glucose tolerance test

[2] BMI = body mass index

[3] IFG = impaired fasting glucose
 

Background: Continuous positive airway pressure is the treatment of choice for patients with obstructive sleep apnea syndrome.

Objective: To determine the factors influencing treatment initiation with a CPAP[1] device in a healthcare system in which co-payment is required.

Methods: A total of 400 adult patients with OSAS[2] who required CPAP therapy completed questionnaires at three different stages of the diagnostic and therapeutic process: CPAP titration study (stage 1), patient adaptation trial (stage 2), and purchase of a CPAP device (stage 3). Logistic regression was used to analyze the variables influencing CPAP use at the different stages of the diagnostic and therapeutic processes.

Results: Only 32% of the patients who underwent CPAP titration study purchased a CPAP device. The number of subjects who purchased a CPAP device increased gradually as monthly income increased, 28% vs. 62% in the “very low” and “very high” income levels respectively. Reporting for the titration increased in patients with excessive daytime sleepiness and an Epworth Sleepiness Scale score above 9 (odds ratio = 1.9, P = 0.015). Higher socioeconomic status increased reporting to stage 2 (OR[3] = 1.23, P = 0.03) and CPAP purchase (stage 3, OR = 1.35, P = 0.002). Excessive daytime sleepiness increased reporting to stage 2 (OR = 2.28, P = 0.006). Respiratory disturbance index above 35 increased CPAP purchasing (OR = 2.01, P = 0.022). Support from the bed partner, referring physician and sleep laboratory team increased CPAP purchasing.

Conclusions: A supportive environment for a patient with OSAS requiring CPAP is crucial to increase initiation of CPAP treatment. Minimizing cost sharing for the CPAP device will reduce inequality and may increase CPAP treatment initiation.