Israel Medical Association Journal

Background: Fat tissue mediates the production of inflammatory cytokines and oxidative products, which are key steps in the development of type 2 diabetes and atherosclerosis. Antioxidant-rich diets protect against chronic diseases, but antioxidants may interfere with pro-inflammatory signals.

Objectives: To investigate the effect of the potent tomato-derived antioxidant carotenoid, lycopene, on plasma antioxidants (carotenoids and vitamin E), inflammatory markers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha), and oxidation products (conjugated dienes).

Methods: Eight obese patients (body mass index 37.5 ± 2.5 kg/m²) were compared with a control group of eight lean, age and gender-matched subjects (BMI[1] 21.6 ±  0.6 kg/m²), before and after 4 weeks of lycopene supplementation (tomato-derived Lyc-O-Mato) (30 mg daily).

Results: Plasma carotenoids were significantly reduced in the obese compared to control subjects (0.54 ± 0.06 vs. 0.87 ± 0.08 mg/ml, P < 0.01). CRP[2] levels were significantly higher (6.5 vs. 1.1 mg/L, P = 0.04) in obese vs. controls, as were IL-6[3] and conjugated dienes (3.6 and 7.9-fold, respectively). CRP, IL-6 and conjugated dienes correlated with BMI, while IL-6 and conjugated dienes correlated inversely with carotenoids (P < 0.05). Following lycopene treatment, a significant elevation of plasma carotenoids (1.79 vs. 0.54 ug/ml) and specifically lycopene (1.15 vs 0.23 ug/ml) (P < 0.001) occurred in the treatment vs. placebo group, respectively. Markers of inflammation and oxidation products were not altered by lycopene.
Conclusions: Obese patients showed abnormally higher markers of inflammation and oxidation products and lower plasma carotenoids. The lack of reduction of pro-inflammatory markers could be attributed to the short period of the study and the small number of participants. More studies are needed on the protective qualities of natural antioxidant-rich diets against obesity-related co-morbidities.

Background: High sensitivity C-reactive protein, a marker of inflammation, has been proposed to stratify coronary artery disease risk and is lowered by HMG-CoA reductase (statin) therapy. However, the reproducibility of persistently elevated hs-CRP[1] levels and association with other markers of inflammation in patients with stable CAD[2] on aggressive statin therapy is unknown.

Objectives: To determine the reproducibility of hs-CRP levels measured within 2 weeks in patients with documented CAD with stable symptoms and to identify associations with other markers of inflammation.

Methods: Levels of hs-CRP were measured twice within 14 days (7 ± 4) in 23 patients (22 males and 1 female, average age 66 ± 10 years) with stable CAD and hs-CRP ≥ 2.0 mg/L but ≤ 10 mg/L at visit 1. All patients had received statins for cholesterol management (low density lipoprotein-cholesterol 84 ± 25 mg/dl) with no dose change for > 3 months. None had a history or evidence of malignancy, chronic infection or inflammation, or recent trauma. There was no change in medications between visits 1 and 2, and no patient reported a change in symptoms or general health during this interval. White blood cell count and pro- and anti-inflammatory cytokines were measured at both visits.

Results: hs-CRP levels tended to be lower at visit 2 (median 2.4 mg/L, range 0.8–11 mg/L) than at visit 1 (median 3.3 mg/L, range 2.0–9.7 mg/L; P = 0.1793). However, between the two visits hs-CRP levels decreased by more than 1.0 mg/L in 10 patients and increased by more than 1.0 mg/L in 4 patients. Changes in hs-CRP levels were unrelated to changes in levels of white blood cells (P = 0.4353). Of the cytokines tested, only the anti-inflammatory cytokine interleukin-1 receptor antagonist and the pro-inflammatory cytokine interleukin-8 were above lower limits of detection, but there were no correlations between changes in these values and changes in hs-CRP (both P > 0.5).

Conclusions: In stable CAD patients on aggressive statin therapy, hs-CRP levels may fluctuate over brief periods in the absence of changes in health, cardiac symptom status and medications, and without corroboration with other measures of inflammation. Accordingly, elevated hs-CRP levels should be interpreted with caution in this setting.

Background: Patients with hypertrophic cardiomyopathy are prone to ventricular arrhythmias and sudden death. Identifying patients at risk of sudden death is difficult.

Objectives: To determine whether microvolt T-wave alternans detected during exercise or rapid atrial pacing can identify patients with HCM[1] who are at risk of ventricular arrhythmias and sudden death.

Methods: This prospective observational study included 21 patients with HCM: 11 with hypertrophic obstructive cardiomyopathy, 9 with non-obstructive hypertrophic cardiomyopathy, and 1 with apical hypertrophic cardiomyopathy. TWA[2] was measured while the patients were on anti-arrhythmic medication.

Results: TWA was positive in 9 patients (43%) and negative in 12 (57%). Three patients were resuscitated after sudden death before their enrolment in the study and two patients developed ventricular tachycardia and fibrillation respectively during the study period. After combining the endpoint of sudden death from a ventricular arrhythmia and the presence of ventricular arrhythmias on a Holter monitor, there was no significant correlation between the presence of a positive TWA and the presence of ventricular arrhythmias on the Holter monitor or a history of sudden death.  

Conclusion: TWA cannot be used as a non-invasive test for detecting patients with HCM and electrical instability. TWA is not useful for predicting sudden death in patients with HCM.

Approximately 1 in 31 people suffers from an autoimmune disease. The clinical care of patients with autoimmunity crosses multiple disciplines within pediatrics and internal medicine, including, for example, allergy-clinical immunology, rheumatology, nephrology, hematology, pulmonology and neurology. There are two major areas that are considered in the analysis of autoimmunity in human patients. The first of course is etiology and the second, and of even greater importance, is therapy. Towards that end, considerable attention has focused on the role of hematopoietic stem cell transplantation to either reverse or modulate autoimmune disease. Indeed, it is a field that has far more promise than premise based on a variety of issues, including economics, health care delivery, and obviously efficacy and safety. To put this in perspective, we have attempted to review some of the issues that pertain to this novel approach to the management of autoimmunity. Finally, we emphasize the need to incorporate basic research into therapeutic trials, a vacuum all too often present in clinical intervention.

Background: The predictive value of electrophysiologic studies depends on the aggressiveness of the programmed ventricular stimulation protocol.

Objectives: To assess if non-inducibility with an "aggressive" protocol of PVS[1] identifies post-infarction patients with low ejection fraction (EF[2] ≤ 30%) who may safely be treated without implantable cardioverter defibrillator.

Methods: We studied 154 patients during a 9 year period. Our aggressive PVS protocol included: a) stimulus current five times the diastolic threshold (≤ 3 mA) and b) repetition of double and triple extrastimulation at the shortest coupling intervals that capture the ventricle.

Results: Sustained ventricular tachyarrhythmias were induced in 116 patients (75.4%) and 112 (97%) of them received an ICD[3] (EPS[4]+/ICD+ group). Of the 38 non-inducible patients, 34 (89.5%) did not receive an ICD (EPS-/ICD- group). In comparison to the EPS+/ICD+ group, EPS-/ICD- group patients were older (69 ± 10 vs. 65 ± 10 years, P < 0.05), had a lower EF (23 ± 5% vs. 25 ± 5%,  P < 0.05) and a higher prevalence of left bundle branch block (45.5% vs. 20.2%, P < 0.005). Follow-up was longer for EPS+/ICD+ patients (40 ± 26 months) than for EPS-/ICD- patients (27 ± 22 months) (P = 0.011). Twelve EPS+/ICD+ patients (10.7%) and 5 EPS-/ICD- patients (14.7%) died during follow-up (P = 0.525). Kaplan-Meier survival curves did not show a significant difference between the two groups (P = 0.18).
Conclusions: The mortality rate in patients without inducible VTAs[5] using an aggressive PVS protocol and who did not undergo subsequent ICD implantation is not different from that of patients with inducible arrhythmias who received an ICD. Using this protocol, as many as one-fourth of primary prevention ICD implants could be spared without compromising patient prognosis

Background: Stent thrombosis is a rare but devastating complication of coronary stent implantation. The incidence and potential predictors were assessed in a "real world” single center.

 Objectives: To examine whether socioeconomic status indeed affects the occurrence of stent thrombosis.

Methods: We searched our database for cases of "definite" stent thrombosis (according to the ARC Dublin definitions). Each case was matched by procedure date, age and gender; three cases of stenting did not result in stent thrombosis. Demographic and clinical parameters were compared and socioeconomic status was determined according to a standardized polling and market survey database.

Results: A total of 3401 patients underwent stent implantation in our hospital during the period 2004–2006. Their mean age was 63 ± 11 years, and 80% were males. Twenty-nine cases (0.85%) of “definite” sub-acute/late stent thrombosis were recorded. Mortality at 30 days was recorded in 1 patient (3.5%). Thrombosis occurred 2 days to 3 years after stent implantation. All patients presented with acute myocardial infarction. Premature clopidogrel discontinuation was reported in 60%. Patients with stent thrombosis had significantly higher rates of AMI[1] at the time of the initial procedure (76 vs. 32%, P < 0.001) and were cigarette smokers (60 vs. 28%, P < 0.001). Drug-eluting stents were used less in the stent thrombosis group. There was no difference in stent diameter or length between the two groups. Socioeconomic status was significantly lower at the stent thrombosis group, 3.4 ± 2.4 vs. 5.4 ± 2.6 (mean ± SD, scale 1–10, P < 0.01).

Conclusions: The incidence rate of stent thrombosis is at least 0.85% in our population. It appears in patients with significantly lower socioeconomic status and with certain clinical predictors. These results warrant stricter follow-up and support the policy of healthcare providers regarding patients at risk for stent thrombosis.

Background: Respiratory syncytial virus bronchiolitis is the single leading cause of pediatric admissions for infants in the first year of life, presenting regularly in epidemic proportions in the winter months and impacting in a major way on pediatric inpatient services.

Objective: To quantitate the burden of RSV[1] disease on a pediatric service with the purpose of providing a database for proper health planning and resource allocation.

Methods: We conducted a prospective 5 year study of documented RSV infections in a single pediatric service. RSV disease was confirmed by direct immunofluorescence testing of nasal swabs from all hospitalized cases of bronchiolitis.

Results: On average, 147 ± 17 cases of RSV bronchiolitis were admitted annually in the November–March RSV season, representing 7%–9% of admissions and 10%–14% of hospital days. There was a consistent male preponderance of admissions (55–64%) and 15–23% of admissions were patients less than 1 month old. In peak months RSV cases accounted for as many of 40% of the hospitalized infants and was the leading cause of over-occupancy (up to 126%) in the pediatric ward during the winter,

Conclusions: RSV infection is a major burden for pediatric inpatient services during the winter season. This recurrent and predictable “epidemic,” which regularly leads to over-occupancy, requires increased manpower (nursing) and resources (beds, pulse oximeters) to facilitate proper care. Since this annual event is not a surprise nor an unexpected peak, but rather a cyclical predictable epidemiological phenomenon, proper planning and allocation of services are crucial.

Background: Gunshot wounds impose a continuous burden on community and hospital resources. Gunshot injuries to the extremities might involve complex soft tissue, bone, vascular, musculotendinous, and nerve injuries. A precise knowledge of anatomy is needed to evaluate and treat those injuries.

Objectives: To review our experience with gunshot wounds to the extremities.

Methods: We retrospectively reviewed all cases of gunshot wounds to the limbs in a civilian setting treated in our institution during 2003–2005. Altogether, we evaluated 60 patients with 77 injuries.

Results: Of the 60 patients 36 had fractures, 75% of them in the lower extremity and 81% in long bones. The most common fixation modality used was external fixation (33%), followed by intramedullary nailing (25%). This relatively high percentage of fracture treated with external fixation may be attributed to the comminuted pattern of the fractures, the general status of the patient, or the local soft tissue problems encountered in gunshot wounds. About one-fifth of the fractures were treated by debridement only without hardware fixation. We treated 10 vascular injuries in 8 patients; 6 of them were injuries to the popliteal vessels. Fractures around the knee comprised the highest risk factor for vascular injuries, since 5 of the 12 fractures around the knee were associated with vascular injury requiring repair or reconstruction. There were 13 nerve injuries (16.8%), most of them of the deep peroneal nerve (38%). Only three patients had concomitant nerve and vascular injuries. The overall direct complication rate in our series was 20%.

Conclusions: Treating complex gunshot injuries requires a team approach, necessary for a favorable outcome. This team should be led by an orthopedic surgeon knowledgeable in the functional anatomy of the limbs.