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: Although the comprehensive evaluation of the fetal heart includes echocardiography by an experienced pediatric cardiologist, economic constraints sometimes dictate the need to select patients.

Objectives: To analyze the usefulness of fetal echocardiography in the detection of congenital heart disease according to the referral indication.

Methods: This retrospective survey relates to all 3965 FE studies performed in our center from January 2000 to December 2004. The diagnosed cardiac anomalies were classified as significant and non-significant malformations. All FE[1] studies were done by a single operator (A.L.) at Meir Medical Center, a referral center for a population of about 400,000. The 3965 FE studies were performed for the following indications: abnormal obstetric ultrasound scans, maternal and family history of cardiac malformations, medication use during the pregnancy, and maternal request. The relative risk of detecting CHD[2] was calculated according to the various referral indications.

Results: Overall, 228 (5.8%) cases of CHD were found. The most common indication for referral was suspicion of CHD during a four-chamber view scan in a basic system survey or during a level II ultrasound survey. No correlation was found between maternal age and gestational age at the time of scanning and the likelihood of finding CHD.

Conclusions: Our data suggest that a suspicious level-II ultrasound or the presence of polyhydramnios is an important indication for FE in the detection of significant CHD.

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.
 

Background: Anti-ribosomal-P antibodies have been associated with central nervous manifestations of systemic lupus erythematosus. However, inconsistencies in their prevalence and clinical correlations have become an obstacle to their use as a diagnostic marker of the disease. This lack of consistency might stem from several factors, such as the lag period between clinical manifestations and the time blood was drawn, or the different methods used for antibodies detection.

Objectives: To evaluate three different enzyme-linked immunosorbent assay tests for the detection of anti-Rib-P Abs[1] in patients with SLE[2] and normal controls.

Methods: Sera from 50 SLE outpatients and 50 healthy subjects were tested with three ELISA[3] kits: Kit-1, which uses synthetic peptide comprising the 22 C-terminal amino-acids; Kit-2, which uses native human ribosomal proteins (P0, P1, P2); and Kit-3, which is coated with affinity-purified human ribosomal proteins. ELISA studies were performed according to the manufacturers' instructions.

Results: The prevalence of anti-Rib-P Abs in SLE patients and controls was 30% vs. 0%, 17% vs. 21%, and 30% vs. 14% in kits 1-3 respectively. Anti-Rib-P Abs detected by Kit-1 correlated with the SLEDAI score (SLE Disease Activity Index). No correlation between prior CNS[4] manifestations and anti-Rib-P Abs was observed.

Conclusions: A significant difference was documented between the ELISA kits used for the detection of anti-Rib-P Abs. A correlation was found between these antibodies (evaluated by Kit-1) and concurrent SLEDAI scores, in contrast to the lack of correlation with previous CNS manifestations. This supports the notion of "active serology" that is evaluated at the same time manifestations are present, as well as the need for standardization of laboratory assays in the future that enable a better assessment of anti-Rib-P Abs presence and clinical correlation. 

Background: Magnetic resonance imaging of the breast has emerged as a valuable imaging tool in addition to conventional imaging modalities. It has high sensitivity for malignant lesions, and can detect mammographically, sonographically and clinically occult cancers. “MR only” lesions are best biopsied under MR guidance; however, this may be a challenging task.

Objectives:  To evaluate our initial clinical experience with MR-guided core needle breast biopsy and MR-guided needle localization.

Methods: We retrospectively evaluated 81 women with 97 lesions, who were scheduled for guided core needle biopsy or MR-guided needle localization followed by surgery. Lesions were categorized as malignant, high risk, or benign according to the BI- RADS MR classification system. MR findings were compared with final histopathology or with follow-up imaging findings.

Results: Fifteen (16%) lesions were malignant (9 invasive ductal carcinoma, 2 invasive lobular carcinoma, 4 ductal carcinoma in situ); 7 (7%) lesions were high risk (4 atypical ductal hyperplasia, 3 radial scars); 75 (77%) lesions were benign, mainly fibrocystic changes. Other benign findings were sclerosing adenosis, pseudoangiomatous stromal hyperplasia, fat necrosis, intraductal papilloma, fibroadenoma, capillary hemangioma, and florid ductal hyperplasia. No major complications were encountered.
Conclusions: MR-guided interventional procedures of the breast are accurate, safe and feasible methods for sampling breast lesions detected only by MR and have become a significant tool in the management of certain patients.

Background: Sickle cell anemia is a hemolytic anemia caused by a single mutation in position 6 of the β globin molecule. About 80 patients with SCA[1] in northern Israel are currently receiving treatment.

Objectives: To assess a screening program in northern Israel aimed at detecting couples at risk for having offspring with SCA.

Methods: Since 1987, screening for β thalassemia in pregnant women in northern Israel has been conducted, and from 1999 all the samples were also tested for hemoglobin S, Hgb C, Hgb D, Hgb O Arab and others.

Results: During the 20 year period 1987–2006 a total of 69,340 women were screened; 114 couples who carried Hgb S were detected and 187 prenatal diagnoses were performed in couples at risk for having an offspring with Hgb S. The mean gestational age was 13 ± 4 weeks. Fifty-four of those diagnoses revealed affected fetuses and in 4 cases the couple declined to perform therapeutic abortion.

Conclusions: The economic burden to the health services for treating SCA patients is about U.S.$ 7000 per year, and the institution of prevention programs has proven cost-effective in populations with a high frequency of carriers. Since our program is aimed to also detect β thalassemia, a disease that is more frequent in this area (> 2.5%), the added cost for the prevention of SCA is less significant in spite a low incidence of the S gene in our population, namely < 1%.

Background: Although unprotected left main coronary artery disease is considered by contemporary guidelines to be an indication for surgery, percutaneous coronary intervention may be necessary in patients at high surgical risk.

Objectives: To assess the outcome of angioplasty in the treatment of unprotected LMCA[1] disease.

Methods: Angiographic and clinical data were collected prospectively for all patients who underwent emergent or non-emergent (planned) therapeutic PCI[2] for unprotected LMCA disease at our center from 2003 to 2007. Baseline values were compared with findings at 1, 6 and 12 months after the procedure.

Results: The study group comprised 71 consecutive patients with a mean age of 74 ± 12 years; 63% were men, and 31% had diabetes. Forty-three patients had a planned procedure and 28 an emergent procedure. Mean EuroScore was 7.3 ± 3.6 (range 5–12). Forty-nine percent of the procedures were performed with bare metal stents and 51% with drug-eluting stents. Procedural success was achieved in 100% of cases. The overall mortality rate was 11.3% at 1 month, 18.3% at 6 months and 19.7% at 12 months. Elective PCI was associated with significantly lower mortality (2.3% vs. 25% at 1 month, 4.6% vs. 39% at 6 months and 6.9% vs. 39% at 12 months), and the use of drug-eluting stents was associated with lower rates of target vessel revascularization and major adverse cardiac events than use of bare metal stents (2.8% vs. 14% at 1 month, 8.3% vs. 43% at 6 and 12 months). Variables that correlated with increased mortality or MACE[3] at 6 and 12 months were cardiogenic shock, emergent PCI, ejection fraction < 35%, renal failure, distal left main stenosis location, and reference diameter < 3 mm.

Conclusions: PCI is a feasible and relatively safe therapeutic option for unprotected LMCA. The less favorable outcome of emergent compared to planned PCI is probably attributable to the overwhelming acute myocardial ischemic injury in emergent cases. The use of drug-eluting stents may improve the intermediate-term restenosis rate.

[1] LMCA = left main coronary artery

[2] PCI = percutaneous coronary intervention

Background: The role of endoscopic ultrasound in evaluating the response of esophageal cancer to neoadjuvant chemotherapy is controversial.

Objectives: To evaluate the accuracy of EUS[1] in restaging patients who underwent NAC[2].

Methods: The disease stage of patients with esophageal cancer was established by means of the TNM classification system. The initial staging was determined by chest and abdominal computed tomography and EUS. Patients who needed NAC underwent a preoperative regimen consisting of cisplatin and fluouracil. Upon completion of the chemotherapy, patients were restaged and then underwent esophagectomy. The results of the EUS staging were compared with the results of the surgical pathology staging. This comparison was done in two groups of patients: the study group (all patients who received NAC) and the control group (all patients who underwent primary esophagectomy without NAC).

Results: NAC was conducted in 20 patients with initial stage IIB and III carcinoma of the esophagus (study group). Post-chemotherapy EUS accurately predicted the surgical pathology stage in 6 patients (30%). Pathological down-staging was noted in 8 patients (40%). However, the EUS was able to observe it in only 2 patients (25%). The accuracy of EUS in determining the T status alone was 80%. The accuracy for N status alone was 35%. In 65% of examinations the EUS either overestimated (35%) or underestimated (30%) the N status. Thirteen patients with initial stage I-IIA underwent primary esophagectomy after the initial staging (control group). EUS accurately predicted the surgical pathology disease stage in 11 patients (85%).

Conclusions: EUS is an accurate modality for initial staging of esophageal carcinoma. However, it is not a reliable tool for restaging esophageal cancer after NAC and it cannot predict response to chemotherapy.

Background: High levels of plasma homocysteine constitute a risk for cardiovascular disease. Physical activity, known to reduce CVD[1] risk, has been related to levels of Hcy[2]. Recently, higher Hcy was shown to be associated with lower cardiovascular fitness in women but not in men.

Objectives: To further explore the relationship between cardiorespiratory fitness and plasma total homocysteine levels in a large cohort of adult males and females.

Methods: This cross-sectional study included 2576 fitness and Hcy examinations in adults (62% males) aged 30–59 years, randomly drawn from a population undergoing a periodic health examination in the Sheba Medical Center's Executive Screening Survey. Blood tests were collected for tHcy[3] and a sub-maximal exercise test was performed to estimate cardiorespiratory fitness. Information on CVD/CVD risk factors (coronary heart disease, cerebrovascular accident, diabetes, hypertension or dyslipidemia) was self-reported.

Results: Mean tHcy plasma levels were 14.4 ± 7.7 and 10.2 ± 3.0 µmol/ml, and mean maximal oxygen uptake 36.5 ± 11.7 and 29 2 ± 9.5 ml/kg/min for males and females, respectively. A multiple regression analysis, adjusting for age, body mass index and CVD/CVD risk factors, showed no association between cardiorespiratory fitness and level of tHcy in males (P = 0.09) or in females (P = 0.62).

Conclusions: In this sample no relationship was found between level of cardiorespiratory fitness and plasma tHcy in men or women. The inconsistency of findings and the small number of studies warrant further research of the association between cardiorespiratory fitness and tHcy, an association that may have clinical implications for the modifications of cardiovascular risk factors.