Israel Medical Association Journal

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: The 5 year survival rate in patients with advanced epithelial ovarian cancer is 25–40% and treatment is mainly palliative once the disease recurs.

Objectives: To determine the time to progression, overall survival and toxicity of 1 year maintenance treatment with carboplatin in women with advanced EOC[1] after achieving complete remission with platinum‑based combination chemotherapy.

Methods: Twenty-two women with epithelial ovarian cancer stage III-IV previously treated with platinum‑based combinations who had achieved complete remission evidenced by symptoms, pelvic examination, computerized tomography and serum CA-125, were assigned to the study protocol consisting of: carboplatin of AUC=6, three cycles every 2 months, followed by two cycles once every 3 months for a total of five courses over 1 year.

Results: Median follow‑up in the 22 patients was 83 months (range 18–133 months), median disease‑free survival was 36 months (range 2.5–126.4, 95% confidence interval 16.39–56.34). The 5 year survival was 59.7% with a mean overall survival of 83 months (range 18–133, 95% CI[2] 39.11-127.29). Eleven patients have relapsed and died, 11 are alive, 6 are still in complete remission, and 5 are alive with recurrent disease. Grade III-IV toxicity was shown in some of the patients, anemia in 9%, thrombocytopenia in 9%, fatigue in 4.5%, and hypersensitivity in 4.5%.

Conclusions: A 1 year extension of treatment with a single‑agent carboplatin, administered to women with advanced EOC who had achieved complete recovery on platinum‑based chemotherapy as their first‑line therapy, has an acceptable toxicity. The disease-free survival and overall survival values noted in this study are encouraging and warrant further investigation.

Background: Lipoid pneumonia is a pneumonitis resulting from the aspiration of lipids, and is commonly associated with the use of mineral oil as a laxative. LP[1] is relatively unfamiliar to clinicians and is probably underdiagnosed.

Objectives: To increase physicians' awareness of LP, its diagnosis and prevention.

Methods: We present two illustrative cases of LP and review the literature.

Results: Two cases of LP were diagnosed within half a year in an internal medicine ward. Both cases were elderly patients, and LP was associated with the use of mineral oil as a laxative agent. Computerized tomography revealed bilateral low attenuation infiltrates, associated with a "crazy paving" pattern in one case. Sudan Black staining was diagnostic in both cases – in one on a transbronchial biopsy specimen, and in the other on sputum cytologic examination. Both patients suffered from neurologic diseases and were at risk of aspiration. In both cases clinical symptoms and signs continued for several months prior to diagnosis but resolved after the mineral oil was discontinued.

Conclusions: LP often occurs in elderly patients who are at risk of aspiration. The condition may be underdiagnosed. Since in most cases mineral oil cathartics are the causative agent, an effort at primary prevention is indicated. It is suggested that the licensing of mineral oil for internal use be changed.

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. 

Background: Sentinel lymph node mapping is the standard of care for patients with malignant melanoma and breast cancer. Recently, SLN[1] mapping was introduced to the field of gastric cancer.

Objectives: To evaluate SLN mapping in patients with gastric cancer.

Methods: In 43 patients with gastric cancer, open intraoperative subserosal dye injection in four opposing peritumoral points was used. Ten minutes following dye injection, stained LNs were located, marked and examined postoperatively from the surgical specimen.

Results: SLN mapping was performed in 43 with gastric cancer; 782 lymph nodes were harvested and evaluated. SLNs were stained in 34 of the patients (79.1%) with a mean of 2.85 SLNs per patient. The false negative rate was 20.9%, the positive predictive value 100%, the negative predictive value 78.6% and the sensitivity 86.9%.

Conclusions: SLN mapping in patients with gastric cancer is feasible and easy to perform. SLN mapping may mainly affect the extent of lymph node dissection, and to a lesser degree gastric resection. However, more data are needed.

In this issue of IMAJ, two articles discuss and review the roles of chronic airway infection (1) and inflammation (2) respectively in cystic fibrosis lung disease.

Stem cell research offers great hope to patients suffering from neuronal damage. Stem cell-based regenerative medicine holds huge potential to provide a true cure for patients affected by a neurodegenerative disease or who have suffered a stroke.

Orbital dog bites, although uncommon, occur mostly in children and are reported to be associated with severe ocular adnexal injury without globe involvement.

Amyloidosis is characterized by the extra-cellular deposition of abnormal insoluble fibrillar proteins in organs and tissues.

Twenty years ago the Israeli Association of Allergy and Clinical Immunology was established, unifying these two fields into one speciality.

Intravenous immunoglobulins have been used as therapeutic proteins since the early 1980s.

Although the airway granulomata in Wegener's granulomatosis were stressed initially by Friedrich Wegener himself, in the last few decades systemic lesions mainly caused by acute vasculitis have received the most attention. However, recently, the implication of granulomatous manifestations in WG[1] has raised much interest. The present data suggest that an aberrant Th1-type response might play a role in the initiation of WG, clinico-pathologically characterized by granulomatous inflammation rather than vasculitis. Disease progression to generalized WG with the predominance of vasculitic manifestations is associated with a “switch” or further complexity of the collective T cell response with the appearance of another subset of Th2-type cells and a less prominent Th1-type cytokine production in the granulomatous lesions of the upper respiratory tract. However, the clinical significance of the granulomatous inflammation is not yet completely understood. Further research will also have to focus on the role of the granulomata during relapsing disease. We review present knowledge of granulomatous inflammation in WG. Morphologic aspects, the scale of cytokine alterations as well as the variety of clinical manifestations are discussed.

Background: Dyspnea may be a presenting symptom of type I food hypersensitivity, and bronchial hyper-reactivity, without known asthma, can coexist in patients with food allergy.

Objective: To evaluate airway involvement in young adult patients with food allergy and no asthma and compare the findings to those of patients with food allergy and asthma, with food allergy and allergic rhinitis, with asthma and no food allergy, and of apparently healthy controls.

Methods: The evaluation involved prick skin test to food (65 allergens) and inhalants (24 allergens), spirometry, methacholine inhalation challenge, and induced sputum for cell analysis. The five groups consisted of 18 patients with food allergy alone, 11 with food allergy and asthma, 13 with food allergy and allergic rhinitis, 10 with asthma alone, and 10 controls.

Results: Patients with food allergy alone were mainly (86%) skin sensitive to pollens. Those with either asthma or allergic rhinitis were mainly (95%) sensitive to mites. BHR was detected in 40% of the patients with food allergy alone, 55% of the patients with allergic rhinitis, and 100% of the patients with asthma. Cell counts in the sputum of patients with asthma and in those with food allergy and asthma showed higher eosinophil counts compared to those with food allergy and allergic rhinitis. Patients with food allergy and no asthma, regardless of BHR status, had mainly neutrophils in the sputum.

Conclusions: Patients with food allergy are highly likely to have concomitant asymptomatic BHR. Mite sensitivity in patients with food allergy predicts respiratory allergy (either asthma or allergic rhinitis). High eosinophil levels in the sputum of food allergy patients predict respiratory involvement.

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

Objective: To assess the effect of establishing a new dedicated acute stroke unit within a department of neurology on indicators of process of care and outcome of acute stroke in a routine clinical setting in Israel.

Methods: Stroke patients admitted to the Sheba Medical Center during the period March 2001 to June 2002 were included in a prospective study according to selection criteria. Data on demographics, risk factors, co-morbidities and stroke severity were collected. Indicators of process of care and outcome were assessed at hospital discharge and 30 days follow-up. Comparison between outcome variables by hospitalization ward was conducted using logistic regression analysis adjusting for confounders.

Results: Of 616 acute stroke patients (mean age 70 years, 61% men, 84% ischemic stroke), 353 (57%) were admitted to general wards and 263 (43%) to the stroke unit. Diagnostic procedures were performed more often, and infection rate was lower in the setting of the stroke unit. Poor outcome (modified Rankin scale ≥3 or death) was present less often in patients managed in the stroke unit both at hospital discharge (adjusted odds ratio 0.5, 95% confidence interval 0.3–0.8) and at 30 day follow-up (adjusted OR[1] 0.6, 95%CI[2] 0.3–0.9). A Functional Independence Measure score ≤90 or death at 30 day follow-up was less frequent among patients managed in the stroke unit than in general wards (adjusted OR 0.5, 95%CI 0.2–0.8).

Conclusions: Improved outcomes and higher adherence to guidelines were observed in patients treated in a stroke unit within a department of neurology. The results suggest that patients with acute stroke should have access to treatment in a dedicated stroke unit.