Israel Medical Association Journal

Background: The association between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) has been suggested previously, but prior studies provided contradicting findings. 

Objectives: To characterize the expression profile of eight classic and non-classic aPL in patients diagnosed with MS.

Methods: Using the BioPlex™ 2200 immunoassay, we measured the levels of serum immunoglobulin (Ig)M and IgG isotypes of three classic aPL and five non-classic aPL in 98 subjects with MS and 237 healthy controls. 

Results: Three non-classic aPL were significantly more prevalent among MS patients in comparison to the control group. These antibodies included IgM and IgG against phosphatidylserine-β2GPI (PS-B2), IgG prothrombin complex (PT-PT) and IgM prothrombin (PT). The positive results according to Bonferroni correction are PS-B2 IgG and PT-PT IgG. The remaining aPL profiles did not differ significantly between the two groups.

Conclusions: An association between certain non-classic aPL and MS has been established. The specific role of these autoantibodies in the pathogenesis of the condition remains uncertain.  

 

Background: The efficacy of video-assisted thoracoscopic surgery lobectomy in patients with previous coronary artery bypass grafting (CABG) surgery is controversial.

Objectives: To investigate whether skeletonized left internal mammary artery (LIMA) mobilization contributes to the development of severe adhesions, which will affect what type of lung surgery (open or closed procedure) will be required in the future.

Methods: Eight patients (mean age 73.9 years) with previous CABG surgery using a LIMA to left anterior descending (LAD) graft underwent left-sided lobectomy for operable non-small cell lung carcinoma. 

Results: The lobectomy by thoracotomy rate was 62.5% (5 patients), generally in patients with tumors in the left upper lobe or in patients post-neoadjuvant chemotherapy, while the video-assisted thoracic surgery lobectomy rate was 37.5% (3 patients). Mean hospital stay was 8.3 days. There was no mortality or major morbidity, apart from six minor complications in four patients (50%) (air leak, atrial fibrillation, atelectasis, pneumonia). 

Conclusions: Patients with operable non-small cell lung carcinoma following CABG surgery who need left upper lobe resection do not benefit from the video-assisted thoracoscopic surgery technique due to significant adhesions between the LIMA to LAD graft and the lung. The method of preserving a small portion of the lung on the LIMA to LAD graft may help during left upper lobe resections. Adhesions in the left pleural space after LIMA mobilization appear to generally minimally affect left lower lobe video-assisted thoracoscopic surgery.

 

Abstract

Background: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.

Objectives: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.

Methods: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.

Results: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 mM among TT homozygotes as compared to 12.3 ± 5.6 mM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal (£ 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).

Conclusions: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency should be tested for MTHFR polymorphism to identify potential vascular abnormalities and increased cardiovascular risk. 

Abstract:

Background: Waterpipe tobacco smoking (WTS) is common in some populations and may add increased risk for tobaccorelated diseases.

Objectives: To assess the rates of WTS and risk practices associated with WTS in three distinct populations in Israel: long-term Jewish residents (LTJR), immigrants from the former Soviet Union (fSU), and Arabs.

Methods: We conducted a cross-sectional survey of 899 randomly selected participants, age 30–65 years, using face-toface interviews with subjects from the three population groups in Israel. Respondents reported WTS, cigarette smoking, alcohol consumption, and socioeconomic characteristics.

Results: Among men, WTS at least once a week was reported by 4.8% of LTJR, 3.2% of fSU immigrants and 20.3% of Arabs. Lower rates were reported among women of all groups. The younger, less educated men and the younger unmarried women had higher odds of WTS. LTJR who smoked cigarettes and drank alcohol had higher odds of WTS [odds ratio (OR) 32.6, confidence interval (CI) 9.36–113.6; OR = 3.57, CI =1.48–8.63, respectively], compared to non-smokers and non-drinkers. fSU immigrants who smoked cigarettes had higher odds of WTS (OR = 3.40, CI = 0.99–11.7) compared to non-smokers. Among Arabs, cigarette smoking and alcohol consumption were not associated with WTS.

Conclusions: Arabs are more likely than other Israeli populations to engage in WTS. This behavior may add to increased inequalities in rates of tobacco-induced diseases between Arabs and Jews in Israel. Including WTS in the policies for smoke-free public places is called for.

Background: QT segment prolongation is a high risk factor for fatal arrhythmias. Several studies have indicated a possible relation between low testosterone levels and QT interval prolongation. 

Objectives: To compare the QT interval length in elderly patients with prostate carcinoma who were on anti-testosterone treatment and those who were not.

Methods: We screened the electrocardiograms (ECGs) of 100 prostate cancer patients divided into two groups: 50 patients on anti-testosterone drug treatment and 50 patients not. QT interval length was measured according to the accepted methods.

Results: The mean QTc 12 leads in the entire group was 0.45 ± 0.04 sec, which is close to the upper limit. Mean QTc was actually longer in the control group and there was no QTc difference between the groups after adjustment for possible confounders. Prolonged QTc 12-lead ECG (48% in treated and 54% in non-treated) and lead L2 QT interval (50% in treated and 56% in non-treated) did not differ significantly between the groups. The analysis of QTc 12-lead ECG indicated no significant effects of anti-testosterone drug treatment. Only the use of furosemide was associated with QT prolongation. 

Conclusions: The results of this preliminary study do not support our initial concern of an alarmingly prolonged QT interval in the anti-testosterone treated group. However, further prospectively designed studies are needed. In the meanwhile we call for a close follow-up of the QT interval length in patients receiving anti-testosterone treatment. 

 

Background: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood.

Objectives: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression.

Methods: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1β, IL-18, IL-33, TGF-β, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1β were also determined by immunohistochemistry. Clinical characteristics were evaluated.

Results: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ±1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1β, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-β (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1β, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1β cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls.

Conclusions: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

Background: New animal models provide insights into the pathogenesis of different types of inflammatory bowel disease as well as novel pathways for new therapeutic options. However, the scarcity of large animal models hinders the research and development of new surgical procedures and technological devices in inflammatory bowel disease surgery. Common small animal inducible models involve chemical agents that result in the development of acute intestinal inflammation.

Objectives: To assess a novel method for the induction of Crohn’s-like colitis using intramural injection of sclerosants in a porcine model.

Methods: Seven domestic pigs underwent several experimental protocols to assess the efficacy of intramural colonic injections of two different compounds (lauromacrogol, and phenol in almond oil). Twenty-five different large bowel segments were treated with intramural injections of the compounds. The animals were followed for 6 weeks, and treated colonic segments were resected for histopathological examination.

Results: Intramural injection of lauromacrogol resulted in non-specific, mild reactive foreign body changes only. Injection of various dosages of 5% phenol in almond oil caused a range of histopathological changes varying from focal fibrosis to Crohn’s-like reactions comprising acute and chronic infiltrates, mucosal ulceration and focal necrosis with enteric and lymphoid non-caseating granulomas.

Conclusions: Intramural colonic phenol in almond oil injection in pigs induces inflammatory reactions that histologically resemble Crohn's disease in humans. 

Background: Congenital hepatic hilar cysts are rare. Some are simple and do not require intervention, but some biliary cystic malformations impose the risk of morbidity and mortality. Objectives: To assess a series of five patients presenting with congenital hepatic hilar cysts. 

Methods: We retrospectively reviewed all cases presenting to our pediatric surgical service between January 2010 and December 2012 and found to have a congenital hepatic hilar cyst. Data regarding clinical, radiological, operative and pathological features were analyzed.

Results: Five children with congenital cyst of the hepatic hilum were identified; four of them were diagnosed prenatally. Four children had undergone surgical intervention: one with intrahepatic choledochal cyst, one with epidermoid cyst, and two with biliary atresia and an associated cyst of the common bile duct. In another case of choledochal cyst the treatment was conservative. All children except one had a good prognosis; one child with biliary atresia required liver transplantation.

Conclusions: The differential diagnosis of congenital hepatic hilar cyst includes a broad spectrum of pathologies. It is essential to diagnose biliary atresia as early as possible. Signs such as smaller cysts in association with a hypoplastic gallbladder and direct hyperbilirubinemia may be suggestive of biliary atresia.