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: 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: Gastrointestinal stromal tumors are the most common mesenchymal neoplasms of the human gastrointestinal tract.

Objectives: To review our accumulated experience using surgery to treat gastrointestinal stromal tumors.

Methods: We reviewed all patient charts and histological diagnoses of leiomyomas, leiomyosarcomas, leiomyoblastomas and schwannomas. Only tumors that displayed c-kit (CD117) immunopositivity were defined as GISTs[1].

Results: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.9% of the tumors were classified as malignant, 39.8% as benign, and 19.4% as of uncertain malignancy. Fifty-six GISTs were located in the stomach (60.2%), 29 in the small bowel (31.2%), 4 in the duodenum (4.3%), 2 in the colon (2.1%) and 2 in the rectum (2.1%). Incidental GISTs were found in 23.7% of our patients. Mean overall survival time for malignant gastric GISTs was 102.6 months (95% confidence interval 74.2–131.1) as compared to 61.4 months mean overall survival for malignant small bowel GISTs (95% CI[2] 35.7–87) (P = 0.262). The mean disease-free survival period for patients with malignant gastric GISTs was 97.5 months (95% CI 69.7–125.2) as compared to only 49.6 months (95% CI 27.4–71.7) for patients with small bowel malignant GISTs (P = 0.041).

Conclusions: We found a high percentage of incidental GISTs. Gastric GISTs are more common than small bowel GISTs. Patients with malignant gastric GISTs have a significantly better prognosis than patients with malignant small bowel GISTs. A statistically significant correlation was found between age and malignant potential of the GIST.

Background: Multiple drug allergy syndrome is a rarely reported clinical condition characterized by an adverse reaction to more than one different class of pharmacologically and structurally unrelated drugs. The pathogenesis may involve immediate-type or delayed-type hypersensitivity.

Objectives: To further characterize patients with MDA[1] in terms of the type of CADR, drug intake and clinical drug suspicion.

Methods: The study group comprised 12 patients (6 males, 6 females) with CADRs[2] showing in vitro drug-induced IFNγ[3] release for multiple drugs, suggesting the presence of MDA. The diagnostic role of in vitro IFNγ release in identifying the culprit drugs was evaluated in terms of clinical data and the results of in vivo tests (withdrawal and/or challenge tests) with the offending drugs.

Results: Clinical relevance was attributed to in vitro drug-induced IFNγ release towards multiple drugs in this series of 12 patients with a variety of CADRs, implying MDA. The results of in vivo tests for the offending drugs confirmed the diagnosis. The main causative agents responsible were antibiotics and non-steroidal anti-inflammatory drugs.

Conclusions: The study further supports the role of a T cell-mediated mechanism in the pathogenesis of MDA. The in vitro drug-induced IFNγ release test may serve as a laboratory tool to identify the culprit drugs associated with this allergy.  

Background: Women frequently suffer perineal trauma while giving birth. Interventions to increase the possibility for an intact perineum are needed.

Objectives: To evaluate the effectiveness of antenatal perineal massage in increasing the likelihood of delivering with an intact perineum.

Methods: This single blinded prospective controlled trial included 234 nulliparous women with a singleton fetus. Women allocated to the study group were instructed to practice a 10 minute perineal massage daily from the 34th week of gestation until delivery. Primary outcome measures included the episiotomy rate; first, second, third and fourth-degree perineal tear rates; and intact perineum. Secondary outcomes were related to specific tear locations and the amount of suture material required for repair.

Results: Episiotomy rates, overall spontaneous tears and intact perineum rates were similar in the study and control groups. Women in the massage group had slightly lower rates of first-degree tears (73.3% νs. 78.9%, P = 0.39) and slightly higher rates of second-degree tears (26.7% νs. 19.3%, P = 0.39), although both of these outcomes did not reach statistical significance. The rates of anterior perineal tears were significantly higher in the massage group (9.5% vs. 3%, P = 0.05), whereas internal lateral tears rates were slightly lower but without statistical significance (11.5% νs.13.1%, P = 0.44).

Conclusions: The practice of antenatal perineal massage showed neither a protective nor a detrimental significant effect on the occurrence of perineal trauma.
 

Background: Acute generalized exanthematous pustulosis is a rare pustular severe cutaneous adverse reaction characterized by a rapid clinical course and unique histological findings. It is usually attributed to drugs, although other factors have also been implicated.

Objectives: To analyze demographic, clinical and laboratory data of AGEP[1] cases in Israel, based on the RegisCAR study, a multinational European study.

Methods: Patients included in the present study were actively recruited by the Israeli RegiSCAR network, which comprised 10 dermatology departments and units. The cases were validated by a multinational expert committee of dermatologists based on a standardized scoring system.

Results: Overall, 11 potential cases of AGEP were collected in Israel: 9 (81.8%) definite and 2 (19.2%) possible. The adjusted annual incidence of AGEP in Israel was 0.35/million/year. The nine definite cases that entered the analyses showed a male/female ratio of 0.28 with an age range of 10–60 years. Most cases were reported during the summer months. The clinical course and laboratory findings in most of our patients were in accordance with previous reports. A drug etiology was suspected in the majority of cases and consisted of analgesics (66.7%), antibiotics (22.2%) and non-steroidal anti-inflammatory drugs (11.1%) as the main culprit drugs.

Conclusions: Whereas the clinical and laboratory findings of AGEP in Israel corresponded to the reported features of AGEP in the literature, unique findings consisting of marked female predominance, seasonality and a profile of culprit drugs were noted.

7.4.10.6.04

Background: Occult breast cancer without clinically or mammographically detectable breast tumor is an uncommon presentation.

Objectives: To assess the role of breast MRI in women with metastatic carcinoma and an occult primary, and to define the MRI characteristics of the primary breast tumor.

Methods: This retrospective study evaluated 20 women with metastatic carcinoma of unknown origin who underwent breast MRI between 2000 and 2006. Four women were excluded, leaving 16 in the study group. Probability of malignancy was assessed according to BIRADS classification. MRI performance in detecting lesions and evaluating disease extent was assessed, with the gold standard being surgical or biopsy pathology.

Results: MRI detected suspicious lesions in 15 patients. Lesion size ranged from 0.4 to 7 cm (median 1.5 cm). MRI detected a single lesion in 6 patients (40%), multifocal disease in 3 (20%), multicentric disease in 4 (27%), and bilateral breast lesions in 2 (13%). In 13 patients MRI depicted the primary breast cancer. Initial treatment was surgical in nine; MRI correctly estimated disease extent in 6 (67%), underestimated disease extent in 1 (11%), and overestimated it in 2 (22%). Four patients had biopsy followed by chemotherapy; one had multicentric disease and one had multifocal disease. MR findings were false positive in two patients and false negative in one.

Conclusions: MRI is sensitive in detecting the primary tumor and beneficial in assessing tumor extent. Small size and multiple foci are common features. We suggest that bilateral breast MRI be part of the evaluation of women with metastatic carcinoma and an occult primary.
 

Background: Iron deficiency is the most common single cause of anemia worldwide. Treatment consists of improved nutrition along with oral, intramuscular or intravenous iron administration.

Objectives: To describe the efficacy and adverse effects of intravenous iron sucrose therapy in a group of children with iron deficiency anemia who did not respond to oral iron therapy.

Methods: We conducted a prospective investigation of 45 children, aged 11 months to 16 years, whose oral iron therapy had failed. The children attended the Pediatric Ambulatory Care Unit where they received intravenous iron sucrose infusion.

Results: Forty-four of the 45 patients were non-compliant. Nine had Helicobacter pylori gastritis and 16 patients suffered from intestinal malabsorption from different causes. Before treatment, the blood mean hemoglobin concentration was 7.43 g/dl (range 5–10.1 g/dl). Fourteen days after treatment the mean hemoglobin concentration increased to 9.27 g/dl (SD 1.23) and 6 months later to 12.40 g/dl (SD 1.28). One patient demonstrated a severe side effect with temporary and reversible reduced blood pressure during treatment.

Conclusions: These preliminary data suggest that administration of intravenous iron in pediatric patients is well tolerated and has a good clinical result, with minimal adverse reactions.

Background: In contrast to the relative scarcity of donor kidneys and hearts, the potential supply of deceased donor pancreata is exceeding the demand. However, this potential organ surplus is not being fully realized because in current transplantation practice the duration of pancreas storage before transplantation is limited and many organs with established or anticipated cold ischemia time exceeding 8–10 hours are discarded owing to the extreme vulnerability of pancreatic tissue to anaerobic damage caused by preservation.

Objectives: To reduce cold ischemic injury in order to increase the utilization of donor pancreases in Israel for whole-organ and cell transplantation.

Methods: We evaluated a novel two-layer preservation oxygenated cold storage method that uses perfluorocarbon to continuously supply oxygen to the pancreas during preservation in conventional University of Wisconsin solution.

Results: Pancreatic tissue morphology, viability and adenosine-triphosphate content were serially examined during preservation of the pig pancreas for 24 hours either by a two-layer or by conventional simple cold storage. Already after 12 hours of storage, the superiority of the two-layer method over the University of Wisconsin method was apparent. Starting at this time point and continuing throughout the 24 hours of preservation, the tissue architecture, mitochondrial integrity, cellular viability and ATP[1] tissue concentration were improved in samples preserved in oxygenated UW[2]/PFC[3] as compared to controls stored in conventional UW solution alone.

Conclusions: The UW/PFC two-layer preservation method allowed tissue ATP synthesis and amelioration of cold ischemic tissue damage during extended 24 hour pancreas preservation. This method could be implemented in clinical practice to maximize utilization of pancreata for whole-organ and islet transplantation as well as for pancreas sharing with remote centers.

Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE[1], but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.

Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.

Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg[2] (approximately 0.5 g/kg body weight).

Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.

Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.

Background: Germline mutations in BRCA1 and BRCA2 genes account for only 20–40% of familial breast cancer cases. The CHEK2 gene encodes a checkpoint kinase, involved in response to DNA damage, and hence is a candidate gene for breast cancer susceptibility. Indeed, the CHEK2*1100delC truncating mutation was reported in a subset of mostly North European breast cancer families. The rate of the CHEK2*1100delC variant in the Ashkenazi* Jewish population was reported to be 0.3%.

Objectives: To evaluate whether CHEK2 germline mutations contribute to a breast cancer predisposition in Ashkenazi-Jewish high risk families.

Methods: High risk Ashkenazi Jewish women, none of whom was a carrier of the predominant Jewish mutations in BRCA1/BRCA2, were genotyped for germline mutations in the CHEK2 gene by exon-specific polymerase chain reaction followed by denaturing gradient gel electrophoresis and sequencing of abnormally migrating fragments.

Results: Overall, 172 high risk women were genotyped: 75 (43.6%) with breast cancer (average age at diagnosis 49.6 ± 9.6 years, mean ± SD) and 97 asymptomatic individuals (age at counseling 48.3 ± 8.2 years). No truncating mutations were noted and four previously described missense mutations were detected (R3W 1.2%, I157T 1.2%, R180C 0.6% and S428F 5%), one silent polymorphism (E84E 20.5%) and one novel missense mutation (Y424H 1.2%). Segregation analysis of the I157T and S428F mutations (shown to affect protein function) with the cancer phenotype showed concordance for the CHK2*I157T mutation, as did two of three families with the CHK2*S428F mutation.

Conclusions: CHEK2 missense mutations may contribute to breast cancer susceptibility in Ashkenazi Jews.