Showing papers in "Israel Medical Association Journal in 2009"

The long-term consequences of exposure to lead.

Abstract: More than 90% of body lead is stored in bone. The technique of K-X-Ray fluorescence developed in the 1990s has enabled the quantitative measurement of decades of cumulative lead in bone, whereas blood lead levels reflect only recent exposure to lead. Bone lead is mobilized into the blood like bone calcium, as in osteoporosis, and exposes the patient to increased lead load. Many studies have assessed the toxic effect of chronic exposure from childhood to old age in present or former workers in industrial lead, as well as in non-occupational citizens in whom social and environmental circumstances might have induced higher exposure levels. This review points to the effects of elevated levels of bone lead and the associated cognitive decline among the elderly, with lead toxicity being one of the possible causes of degenerative dementia. There is evidence of an association between increased bone lead levels and renal disease, degenerative diseases like cataract, and suggestive but not causal association with blood pressure and hypertension. Community surveys show increased mortality associated with exposure to lead. Removal of sources of lead exposure, for example the use of non-leaded petrol, has reduced lead levels in the population, and there are currently strong recommendations to further lower the present allowed blood lead level to minimize chronic cumulative lead toxicity.

Contemporary management of head and neck cancers.

Abstract: Head and neck cancer is the sixth most common cancer worldwide. HNCs can originate in the skin or soft tissue, in the upper aerodigestive tracts (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, salivary glands), or in the thyroid. In each of these sites, tumors vary not only by the primary site but also by pathophysiology, biological behavior, and sensitivity to radiotherapy or chemotherapy. Management should be planned according to the tumor's characteristics, patient factors and expertise of the medical team. The main goals of therapy are ablation of the cancer while minimizing morbidity and preserving function and cosmesis. A multidisciplinary team is needed to achieve these goals. Early-stage HNC (stage I and II) should be managed with a single modality, and advanced tumors (stage III and IV) with multimodality therapy. Treatment should be directed to the primary tumor and the area of its lymphatic drainage -the neck lymph nodes. Evidence of metastases in the neck necessitates comprehensive clearance of regional lymphatic basins. However, even if there is no evidence of lymph nodes metastases, when the risk for positive neck lymph nodes exceeds 15―20% elective neck dissection is indicated. Advances in minimally invasive techniques now enable reliable microscopic and endoscopic procedures that mimic the open approaches. Development of contemporary surgical techniques and reconstructive means will help improve the quality of life of patients and prolong survival.

The role of infection in inflammatory bowel disease: initiation, exacerbation and protection.

Abstract: Inflammatory bowel disease, a collective term for ulcerative colitis and Crohn's disease, is a chronic, immune-mediated disease of the gastrointestinal tract that develops in genetically susceptible individuals. The role of infection in the development of inflammatory bowel disease is underscored by various clinical observations, such as the delayed age of onset, suggesting that childhood exposure to pathogens is essential, and the clinical improvement that follows decreasing bacterial intestinal load. Over the years, many a pathogen has been linked to the development and exacerbation of inflammatory bowel disease, notably; Mycobacterium paratuberculosis, Escherichia coli, Listeria monocytogenes and Chlamydia as well as viruses such as measles, mumps, rubella, Epstein-Barr virus and cytomegalovirus. Presently, leading theories of disease pathogenesis suggest loss of immune tolerance to normal commensal bacteria coupled with excessive exposure to bacterial antigenic products. This review describes the most commonly implicated pathogens in the causation of IBD and presents the evidence supporting their pathogenic role as well as data that offset their importance.

The Effect of Tomato-Derived Lycopene on Low Carotenoids and Enhanced Systemic Inflammation and Oxidation in Severe Obesity

Abstract: 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. 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 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 microg/ml, P < 0.01). CRP levels were significantly higher (6.5 vs. 1.1 mg/L, P = 0.04) in obese vs. controls, as were IL-6 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 microg/ml) and specifically lycopene (1.15 vs 0.23 microg/ml) (P < 0.001) occurred in the treatment vs. the 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.

18F- FDG-PET/CT for the diagnosis of tumor thrombosis.

Abstract: Background Venous thromboembolism is a well-recognized and relatively frequent complication of malignancy, whereas tumor thrombosis is a rare complication of solid cancers. The correct diagnosis of tumor thrombosis and its differentiation from VTE can alter patient management and prevent unnecessary long-term anticoagulation treatment. Objectives To evaluate the contribution of 18F-fluorodeoxyglucose positron emission tomography/computed tomography to the diagnosis of tumor thrombosis and its differentiation from VTE. Methods PET/CT scans from 11 patients with suspected tumor thrombosis were retrospectively evaluated. Suspicion arose from positive PET/CT in eight cases, or from findings on contrast-enhanced CT in three patients. Criteria for positivity of PET/CT included increased focal or linear uptake of 18F-FDG in the involved vessel. Findings were categorized as PET/CT positive, or PET/CT negative and compared to contrast-enhanced or ultrasound Doppler, pathology where available, and clinical follow-up. Results Eight occult tumor thromboses were identified by PET/CT-positive scans. Underlying pathologies included pancreatic, colorectal, renal cell, and head-neck squamous cell carcinoma, as well as lymphoma (4 patients). Three thrombotic lesions on contrast-enhanced CT were PET/ CT negative, due to VTE (2 patients) and leiomyomatosis. Accuracy of PET/CT to differentiate between tumor thrombosis and benign VTE was 100% in this small study. Conclusions Contrast-enhanced CT defines the extent of thrombotic lesions, while the functional information from PET/CT characterizes the lesions. It appears that PET/CT may be helpful in the diagnosis of occult tumor thrombosis and its differentiation from VTE.

Serum 25-OH vitamin D levels in patients with fibromyalgia.

Abstract: BACKGROUND The association between low levels of 25-hydroxyvitamin D and non-specific musculoskeletal pain, including fibromyalgia syndrome, is controversial Several studies have reported a "positive association" and two others found "no association" OBJECTIVES To test levels of 25OHD in patients with fibromyalgia syndrome and in matched controls METHODS The study population comprised 68 premenopausal women with a diagnosis offibromyalgia and 82 age-matched premenopausal women without The former were identified from the computerized medical databases of five primary care urban clinics in the south of Israel, and the control subjects were attending the participating clinics for regular periodic blood tests For each patient, the matched control interview and blood test were performed within a week or two from the patient's interview and blood test, thus controlling for expected seasonal variations RESULTS Serum 25OHD was measured using different cutoff levels and compared between the groups (< 30 ng/ml, < 20 ng/ml and <15 ng/ml) No statistically significant differences were found between the groups regardless of the cutoff level used A logistic regression model for predicting women with 25OHD levels 20 ng/ml showed that all the variables examined in both groups (age, country of birth, education) were not statistically significant We found the expected seasonal variations of 25OHD levels, though these were not statistically significant CONCLUSIONS We found no association between fibromyalgia and low 25OHD levels as previously suggested in other studies

Cytokines as the major mechanism of mesenchymal stem cell clinical activity: expanding the spectrum of cell therapy.

Abstract: Mesenchymal stem cells, or mesenchymal stromal cells, have emerged as a major new cell technology with a diverse spectrum of potential clinical applications. MSCs were originally conceived as stem/progenitor cells to rebuild diseased or damaged tissues. Over the last 14 years, since the first report of MSC infusions in patients, the cells have been shown to suppress graft vs. host disease, stimulate linear growth in a genetic disorder of bone, and foster engraftment of haplo-identical hematopoietic stem cells. In all cases, few, if any, MSCs were identified at the site of clinical activity. This experience suggests a remarkable clinical potential, but a different general mechanism of action. Systemically infused MSCs seem to exert a therapeutic effect through the release of cytokines that act on local, or perhaps distant, target tissues. Rather than serving as stem cells to repair tissues, they serve as cellular factories that secrete mediators to stimulate the repair of tissues or elicit other beneficial effects. Since both the tissue source of MSCs and the ex vivo expansion system may significantly impact the cytokine expression profile, these parameters may be critically important determinants of clinical activity. Furthermore, cell processing protocols may be developed to optimize the cell product for a specific clinical indication. For example, MSC-like cells isolated from placenta and expanded in a three-dimensional bioreactor have recently been shown to increase blood flow in critical limb ischemia. Future efforts to understand the cytokine expression profile will undoubtedly expand the range of MSC clinical applications.

Gastrointestinal stromal tumors: a 19 year experience.

Abstract: 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. r esults: The study group comprised 40 female and 53 male patients (age 26–89 years); 40.8% 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 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.

Adult neurotrophic factor-secreting stem cells: a potential novel therapy for neurodegenerative diseases.

Abstract: background: Stem cell-based therapy is a promising approach for the treatment of neurodegenerative disease. In our laboratory, a novel protocol has been developed to induce bone marrow-derived mesenchymal stem cells into neurotrophic factor-secreting cells. These cells produce and secrete factors such as BDNF (brain-derived neurotrophic factor) and GDNF (glial-derived neurotrophic factor). Objectives: To evaluate the migratory capacity and efficacy of NTF-SC in animal models of Parkinson’s disease and Huntington’s disease. methods: MSCs underwent two-phase medium-based induction. An efficacy study was conducted on the 6-hydroxydopamine-induced lesion, a rat model for Parkinson’s disease. Cells were transplanted on the day of 6OHDA administration, and amphetamine-induced rotations were measured as a primary behavioral index. In a second experiment, migratory behavior was examined by transplanting cells a distance from a quinolinic acidinduced striatal lesion, a rat model for Huntington’s disease. Migration, in vivo, was monitored using longitudinal magnetic resonance imaging scans followed by histology. r esults : NTF-SCs attenuated amphetamine-induced rotations by 45%. HPLC analysis demonstrated a marked decrease in dopamine depletion, post-cellular treatment. Moreover, histological assessments revealed that the engrafted cells migrated and acted to regenerate the damaged striatal dopaminergic nerve terminal network. In a preliminary work on an animal model for Huntington’s disease, we demonstrated by high resolution MR images and correlating histology that induced cells migrated along the internal capsule towards the QA-induced lesion. conclusions: The induced MSCs are a potential therapy for neurodegenerative diseases, due both to their NTF secretion and their ability to migrate towards the diseased tissue. IMAJ 2009;11:201–204 mesenchymal stem cells, neurotrophic factors, Parkinson’s disease, Huntington’s disease, magnetic resonance imaging, migration, 6-hydroxydopamine, quinolinic acid, R6/2

Current status and perspectives of the immunotherapy of leishmaniasis.

Abstract: There is still a need for innovative and alternative therapies against leishmaniasis. Despite recent advances in immunology, effective immunotherapy against the disease has not yet been proven. Live, attenuated and dead parasites, purified and recombinant specific antigens, DNA vaccines as well as DC-based immunization that have been employed in the development of protective vaccine have not yet been adopted as immunotherapeutic agents. Recently, a commercially prophylactic vaccine (Leish-110f) was developed by BioPharm International, by constructing a recombinant fusion protein consisting of TSA (thiol-specific antioxidant), LmSTI1 (L. major stress-inducible protein 1) and LeIF (Leishmania elongation initiation factor). This vaccine, when administered together with the adjuvant monophosphoryl lipid A (MPL), either alone or plus squalene (MPL-SE) or AdjuPrime, protected mice against L. major and L. infantum infections. Also, Leishvacin (Leishvacin, Biobrs, Montes Carlos, State of Minas Gerais, Brazil), a commercial non-living promastigote polyvalent Leishmania vaccine administered either alone or combined with BCG, was found to be highly immunogenic against American CL in humans. Leishvacin alone was also found to be effective as a prophylactic vaccine, sensitizing lymphocytes from normal uninfected humans, which was further accelerated by recombinant GM-CSF. Standardization and additional carefully controlled studies in animals and humans, using these new vaccines and other immunomodulators in conjunction with various chemotherapeutic agents, are still required to determine the optimal conditions for the development of a potent anti-leishmanial immunotherapy and immunochemotherapy.

The hemophagocytic syndrome/macrophage activation syndrome: a final common pathway of a cytokine storm.

Abstract: agents. Malignancies and especially lymphomas can be associated with reactive HPS. The prevalence of HPS is difficult to estimate due to its rarity. A special form of HPS develops in association with autoimmune diseases and is termed macrophage-activation syndrome. MAS occurs most commonly in the setting of systemic juvenile rheumatoid arthritis, systemic lupus erythematosus, adult Still's disease and Sjogren syndrome, but occurrence with other autoimmune diseases such as systemic sclerosis and vasculitis has been reported [1]. The prevalence of MAS in one report was 3% [1]. Mortality due to MAS or HPS associated with autoimmune diseases is significantly high, 38.5%, according to a recent French multicenter study [2]. Clinically, HPS is characterized by persistent fever, lymphadenopathy, hepatosplenomegaly and pancytopenia. Typical laboratory abnormalities include elevated levels of liver transminases, bilirubin, lactate dehydrogenase, ferritin and triglycerides, but low levels of fibrinogen. The active phase of the disease is characterized by increased levels of the α-chain of the soluble interleukin-2R (sCD25), which makes it a valuable marker for diagnosis [3] as well as for prognosis since increased levels correlate with increased mortality [4]. Impairment or absence of NK and cytotoxic T cell activity has also been demonstrated [5]. The clinical picture and laboratory manifestations result from increased levels of inflammatory cytokines secreted

Treating civilian gunshot wounds to the extremities in a level 1 trauma center: our experience and recommendations.

Abstract: 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 civilian cases of gunshot wounds to the limbs 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 (168%), 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 To successfully treat complex gunshot injuries a team approach is necessary This team should be led by an orthopedic surgeon knowledgeable in the functional anatomy of the limbs

Osteoporosis in patients with systemic lupus erythematosus.

Abstract: In recent years the survival of patients with systemic lupus erythematosus has increased markedly. Consequently, long-term complications, such as osteoporosis, are currently of paramount importance. SLE is known to increase the risk of bone fractures, and numerous studies have found that SLE patients have osteoporosis. Of the various risk factors associated with osteoporosis in SLE, disease duration, the use of corticosteroids and chronic disease-related damage are consistently reported, with differences between studies probably due to the different populations studied. The role of chronic inflammation in osteoporosis is also important. On the other hand, little attention has been paid to osteoporotic fractures, especially of the vertebra, which are associated with reduced quality of life, increased mortality rates and increased risk of new vertebral and non-vertebral fractures in the general population.

Heart failure--new insights.

Abstract: Ten years ago we published a review updating current knowledge on heart failure. We summarized that heart failure is a neuro-humoral and inflammatory syndrome, and that proinflammatory cytokines are involved in cardiac depression and in the complex syndrome of heart failure. We suggested that understanding the role of these cytokines may enable us to reverse cardiac depression and heart failure. Now we know that there are several mechanisms involved in this syndrome, including inflammation, nitric oxide-dependent pathways, apoptosis, reactive oxygen species, and mitochondrial energy metabolism. This review will focus on the up-to-date mechanistic aspects of heart failure, including clinical trials that have contributed to our better understanding of this entity. IMAJ 2009;11:105–111

Hyperimmune gammaglobulin for the treatment of West Nile virus encephalitis.

Abstract: Background West Nile virus, the etiologic agent of West Nile fever, is an emerging mosquito-borne disease. WNV was recognized as a cause of severe human meningoencephalitis in elderly patients during outbreaks in various parts of the world. Objectives To analyze WNV encephalitis therapy and its outcome after prescribing hyperimmune gammaglobulin therapy. Methods Eight subjects with WNV encephalitis were treated with supportive therapy and 5 days of IVIG 0.4 g/kg/day containing high WNV antibodies obtained from healthy blood donors. Results Patients who were treated with IVIG as soon as possible exhibited an improvement in their symptoms. All subjects presented with high fever, progressive confusion and headaches, nausea and vomiting. The Glasgow Coma Screen for six patients ranged between 8 and 13 and all were discharged with a score of 15. The remaining two subjects died during their hospitalization. Conclusions In severe WNV infection, where the disease affects the central and/or peripheral nervous system, early intervention with IVIG together with supportive treatment is recommended.

Coagulation and anticoagulation in pulmonary arterial hypertension.

Abstract: Pulmonary arterial hypertension is a complex pulmonary vascular disease with a broad range of abnormal vascular abnormalities Vasoconstriction, remodeling and thrombosis contribute to some extent to increased pulmonary vascular resistance and pressure This review presents current knowledge on the role of the thrombotic process in the pathogenesis of PAH and evaluates the rationale for anticoagulation therapy

MRI, not CT, to rule out recurrent cholesteatoma and avoid unnecessary second-look mastoidectomy.

Abstract: Background Aural cholesteatoma is an epidermal cyst of the middle ear or mastoid that can be eradicated only by surgical resection. It is usually managed with radical or modified radical mastoidectomy. Clinical diagnosis of recurrent cholesteatoma in a closed postoperative cavity is difficult. Thus, the accepted protocol in most otologic centers for suspected recurrence consists of second-look procedures performed approximately 1 year after the initial surgery. Brain herniation into a post-mastoidectomy cavity is not rare and can be radiologically confused with cholesteatoma on the high resolution computed tomographic images of temporal bones that are carried out before second-look surgery. Objectives To present our experience with meningoceles that were confused with recurrent disease in patients who had undergone primary mastoidectomy for cholesteatoma and to support the use of magnetic resonance imaging as more suitable than CT in postoperative follow-up protocols for cholesteatoma. Methods We conducted a retrospective chart review of four patients. Results Axial CT sections demonstrated a soft tissue mass in the middle ear and mastoid in all four patients. Coronal reconstructions of CT scans showed a tympanic tegmen defect in two patients. CT failed to exclude cholesteatoma in any patient. Each underwent a second-look mastoidectomy and the only finding at surgery was meningocele in all four patients. Conclusions Echo-planar diffusion-weighted MRI can differentiate between brain tissue and cholesteatoma more accurately than CT. We recommend that otolaryngologists avoid unnecessary revision procedures by using the newest imaging modalities for more precise diagnosis of patients who had undergone mastoidectomy for cholesteatoma in the past.

Computerized community cholesterol control (4C): meeting the challenge of secondary prevention.

Abstract: Background: Dyslipidemia remains underdiagnosed and under-treated in patients with coronary artery disease. The Computer-based Clinical Decision Support System provides an opportunity to close these gaps. Objectives: To study the impact of computerized intervention on secondary prevention of CAD. Methods: The CDSS was programmed to automatically detect patients with CAD and to evaluate the availability of an updated lipoprotein profile and treatment with lipid-lowering drugs. The program produced automatic computer-generated monitoring and treatment recommendations. Adjusted primary clinics were randomly assigned to intervention (n=56) or standard care arms (n=56). Reminders were mailed to the primary medical teams in the intervention arm every 4 months updating them with current lipid levels and recommendations for further treatment. Compliance and lipid levels were monitored. The study group comprised all patients with CAD who were alive at least 3 months after hospitalization. Results: Follow-up was available for 7448 patients (median 19.8 months, range 6-36 months). Overall, 51.7% of patients were adequately screened, and 55.7% of patients were compliant with treatment to lower lipid level. In patients with initial low density lipoprotein > 120 mg/dl, a significant decrease in LDL levels was observed in both arms, but was more pronounced in the intervention arm: 121.9 ± 34.2 vs. 124.3 ± 34.6 mg/dl (P< 0.02). A significantly lower rate of cardiac rehospitalizations was documented in patients who were adequately treated with lipid-lowering drugs, 37% vs. 40.9% (P< 0.001). Conclusions: This initial assessment of our data represent a real-world snapshot where physicians and CAD patients often do not adhere to clinical guidelines, presenting a major obstacle to implementing effective secondary prevention. Our automatic computerized reminders system substantially facilitates adherence to guide-Lines and supports wide-range implementation.

Intermittent balneotherapy at the Dead Sea area for patients with knee osteoarthritis.

Abstract: Background Balneotherapy, traditionally administered during a continuous stay at the Dead Sea area, has been shown to be effective for patients suffering from knee osteoarthritis Objectives To evaluate the effectiveness of an intermittent regimen of balneotherapy at the Dead Sea for patients with knee osteoarthritis Methods Forty-four patients with knee osteoarthritis were included in a prospective randomized single-blind controlled study The patients were divided into two groups: a treatment group (n=24), which were treated twice weekly for 6 consecutive weeks in a sulfur pool heated to 35-36 degrees C, and a control group (n=20) treated in a Jacuzzi filled with tap water heated to 35-36 degrees C Participants were assessed by the Lequesne index of osteoarthritis severity, the WOMAC index, the SF-36 quality of health questionnaire, VAS scales for pain (completed by patients and physicians), and physical examination Results A statistically significant improvement, lasting up to 6 months, was observed in the treatment group for most of the clinical parameters In the control group the only improvements were in the SF-36 bodily pain scale at 6 months, the Lequesne index at 1 month and the WOMAC pain score at the end of the treatment period Although the patients in the control group had milder disease, the difference between the two groups was not statistically significant Conclusions Intermittent balneotherapy appears to be effective for patients with knee osteoarthritis

Conservative treatment for acute cholecystitis: clinical and radiographic predictors of failure.

Abstract: Background Current treatment options for acute calculous cholecystitis include either early cholecystectomy, or conservative treatment consisting of intravenous antibiotics and an interval cholecystectomy several weeks later. Percutaneous drainage is reserved for patients in whom conservative therapy failed or as a salvage procedure for high risk patients. Objective To identify clinical and radiographic factors leading to failure of conservative treatment. Methods We prospectively collected data on consecutive patients admitted with the diagnosis of acute cholecystitis. Parameters were compared between patients who were successfully treated conservatively and those who required percutaneous cholecystostomy. Logistic regression analysis was performed to identify predictors for failure of conservative treatment. Results The study population comprised 103 patients with a median age of 60 who were treated for acute cholecystitis. Twenty-seven patients (26.2%) required PC. On univariate analysis, age above 70 years, diabetes, elevated white blood cell count, tachycardia (> 100 beats/min) at admission, and a distended gallbladder (> 5 cm transverse diameter) were found to be significantly more common in the PC group (P Conclusions Age above 70, diabetes, and a distended gallbladder are predictors for failure of conservative treatment and such patients should be considered for early cholecystostomy. Persistently elevated WBC (> 15,000) suggests refractory disease and should play a central role in the clinical follow-up and decision-making process for elderly patients with acute cholecystitis.

Surgery for sporadic abdominal desmoid tumor: is low/no recurrence an achievable goal?

Abstract: Background Sporadic abdominal desmoid tumors are rare and data on these tumors as a distinct disease entity are lacking. Previous abdominal surgery, trauma, pregnancy and estrogen intake are considered risk factors. Although desmoids are benign, invasion and a high recurrence rate are common. Objectives To evaluate outcomes of surgery for this rare disease. Methods Since 1995, 16 patients with pathologically confirmed desmoid tumor were operated on in our center. All familial adenomatous polyposis patients were excluded. A retrospective analysis of data was performed. Results Of the 16 patients 12 (75%) were females. Mean age was 40.5 years (range 24-70). Thirteen patients were symptomatic and 3 were incidentally diagnosed. All patients presented with an isolated mass; 7 (50%) originated in the abdominal wall, 6 (37.5%) were retroperitoneal and 3 were (18.8%) mesenteric. All tumors except one were completely excised. Morbidity was low with no mortality. One patient was reoperated due to involved margins. None of the patients had recurrence within a median follow-up of 64 months (range 5-143). Conclusions The perception of sporadic abdominal desmoids as tumors with a high recurrence rate (20-70%) is probably incorrect. Adequate surgery with wide margins leads to a very low recurrence rate; cure is a legitimate goal.

The e-Patient: A Survey of Israeli Primary Care Physicians' Responses to Patients' Use of Online Information during the Consultation

Abstract: Background : The internet has transformed the patientphysician relationship by empowering patients with information. Because physicians are no longer the primary gatekeepers of medical information, shared decision making is now emerging as the hallmark of the patient-physician relationship. Objectives: To assess the reactions of primary care physicians to encounters in which patients present information obtained from the internet (e-patients) and to examine the influence of the physicians' personal and demographic characteristics on their degree of satisfaction with e-patients. methods: A questionnaire was developed to assess physicians' attitudes to e-patients, their knowledge and utilization of the internet, and their personal and professional characteristics. Family physicians in central Israel were interviewed by telephone and in person at a continuing medical education course. r esults: Of the 100 physicians contacted by phone, 93 responded to the telephone interviews and 50 physicians responded to the questionnaire in person. There was an 85% response rate. The mean age of respondents was 49 years. Most physicians were born in Israel, with a mean seniority of 22 years. Most had graduated in Eastern Europe, were not board certified and were employees of one of the four health management organizations in Israel. Most physicians responded positively when data from the internet were presented to them by patients (81%). A number of respondents expressed discomfort in such situations (23%). No association was found between physicians' satisfaction in relationships with patients and comfort with data from the internet presented by patients. conclusions: Physicians in this sample responded favorably to patients bringing information obtained online to the consultation. Though it may be difficult to generalize findings from a convenience sample, Israeli family physicians appear to have accepted internet use by patients.

Uveal melanoma in Israel in the last two decades: characterization, treatment and prognosis.

Abstract: BACKGROUND Uveal melanoma is the most common primary intraocular tumor in adults. In the last two decades the Hadassah-Hebrew University Medical Center ocular oncology clinic has become a referral center for uveal melanoma patients. OBJECTIVES To describe the characteristics of uveal melanoma patients in Israel, their treatment modalities and outcomes during the years 1988-2007. METHODS Data were collected from the files of uveal melanoma patients in the departments of ophthalmology and oncology in our facility. Statistical analysis was performed using JMP statistical software. RESULTS Data were available for 558 patients. The annual incidence of uveal melanoma in the last 5 years was 47.2 +/- 7.1 new cases per year (mean +/- standard error). There were 309 women (55.4%). The age at diagnosis was 60.8 +/- 16.5 years (range 5-95). Overall, 6.6%, 16.8% and 86.9% involved the iris, ciliary-body and choroid, respectively. Tumors were classified as small, medium and large (9.0%, 64.5% and 17.9%, respectively) according to the COMS grouping criteria. The most common primary treatment was brachytherapy (74%), followed by enucleation (17.9%). Local recurrence was noted in 11.1% of patients, while metastases developed in 13.3%. The 5, 10 and 15 year melanoma-related mortality rate was 11.4%, 17.0% and 23.3%, respectively. Of the overall study population 9.3% died of metastatic uveal melanoma. CONCLUSIONS Uveal melanoma patients in Israel have tumors with characteristics similar to those in other countries. Brachytherapy is the predominant treatment, the local recurrence rate is low, and survival is comparable to that reported in the medical literature.

Influenza vaccine and autoimmunity

Abstract: i nfluenza, commonly known as the flu, is an infectious disease caused by RNA viruses of the Orthomyxoviridae family. The first influenza pandemic was documented in 1580 and ever since has remained a viral disease of global dimension, presenting with annual epidemics and infrequent pandemics [1]. During the Spanish flu pandemic in 1918 the only efficient therapy was transfusing blood from recovered patients to new victims of the virus. Following this observation and the ability to grow the virus in embryonated hen eggs discovered in 1931, the United States military developed the first inactivated influenza vaccine in the 1940s [1]. Currently the advanced-type vaccine, composed of two inactivated viruses – influenza A and influenza B – are used worldwide for the prevention of influenza and its serious complications [2]. Unlike other viral vaccines, the influenza vaccine must be administered every year, and its antigenic profile differs yearly [2]. Current human vaccines are considered safe and effective by the medical community, for the general population as well as for patients with autoimmune rheumatic diseases [3,4]. Nevertheless, post-vaccination adverse events especially those of an autoimmune nature, although rare, have been described. In the current issue of IMAJ, a case report by Vainer-Mossel et al. [5] describes a 55 year old woman who presented 4 days after receiving an influenza vaccine, with acute confusional state and a middle cerebral artery occlusion detected by magnetic resonance imaging. The patient was concomitantly diagnosed with systemic lupus erythematosus and secondary antiphospholipid syndrome. Thus, an intriguing link between influenza vaccine and SLE/APS-associated diffuse neurological symptoms (i.e., stroke and possible lupus cerebritis) was suggested. Systemic and neurological autoimmune phenomena have been documented following influenza vaccine. Post-vaccination production of autoantibodies, which had become one of the safety criteria of vaccines, was reported in several studies following inoculation. Abu-Shakra and colleagues [6] evaluated 24 women with SLE who received an influenza vaccine. Antibodies reacting with Sm, Sm/RNP, Ro and La antigens were observed 6–12 weeks following vaccination, and six and three patients developed immunoglobulin G and M anticardiolipin antibodies, respectively. Recently, autoantibody production (i.e., antinuclear antibody, aCL and anti-beta-2 glycoprotein 1) was studied in 92 healthy medical workers after influenza vaccination. For subjects with autoantibodies before vaccination, increased titers were documented 1 and 6 months post-vaccination in 11% and 13% of them respectively. Moreover, four participants developed de novo autoantibodies 6 months after vaccination, one of them with very high titers, alluding to a possible long-lasting effect of the vaccine [7]. In addition to the appearance of autoantibodies, clinical presentations or

Contrast-induced nephropathy among Israeli hospitalized patients: incidence, risk factors, length of stay and mortality.

Abstract: Background Radiological procedures utilizing intravascular contrast media are being widely applied for both diagnostic and therapeutic purposes. This has resulted in the increasing incidence of procedure-related contrast-induced nephropathy. In Israel, data on the incidence of CIN and its consequences are lacking. Objectives To describe the epidemiology of CIN among hospitalized patients in the Western Galilee Hospital, Nahariya (northern Israel), and to explore the impact of CIN on mortality and length of stay. Methods The study group was a historical cohort of 1111 patients hospitalized during the year 2006 who underwent contrast procedure and whose serum creatinine level was measured before and after the procedure. Data were electronically extracted from different computerized medical databases and merged into a uniform platform using visual basic application. Results The occurrence of CIN among hospitalized patients was 4.6%. Different CIN rates were noticed among various high risk subgroups such as patients with renal insufficiency and diabetes mellitus (14.1%-44%). Average in-hospital length of stay was almost twice as long among patients with CIN compared to subjects without this condition. Furthermore, the in-hospital death rate among CIN patients was 10 times higher. A direct association was observed between severity of CIN based on the RIFLE classification and risk of mortality. Conclusions Low CIN occurrence was demonstrated in general hospitalized patients (4.6%), and high rates (44%) in selected high risk subgroups of patients (with renal insufficiency or diabetes mellitus). Furthermore, prolonged length of stay and high in-hospital mortality were directly related to CIN severity.

Fetal alcohol spectrum disorder in Israel.

Abstract: BACKGROUND Fetal alcohol spectrum disorder is a range of disabilities caused by gestational exposure to alcohol. FASD is the leading cause of preventable mental retardation and developmental disability in the United States, with an incidence of 1-10 per 1000 live births. FASD in Israel has yet to be examined systematically. OBJECTIVES To evaluate professionals' experience, awareness and knowledge of FASD in Israel and their awareness of maternal consumption of alcohol, and to collect epidemiological data on the syndrome in Israel. METHODS A short questionnaire was sent to all 43 program directors of genetic institutes (n = 14) and child developmental centers in Israel (n = 29). Four questions related to their experience and knowledge of FASD. The epidemiological survey included data from all 17 hospitals in Israel and from the two main health management organizations within the public health care system. RESULTS The response rate was 98% (n = 42). A total of 38.1% of respondents reported having diagnosed at least one case of FASD and fewer than 10% of respondents stated that the knowledge regarding FASD among physicians in Israel was adequate. Developmental pediatricians were more likely to have diagnosed at least one case as compared to geneticists. During the period 1998-2007 the diagnosis of FASD appeared in the records of only 4 patients from the total number of 17 hospitals in Israel. During the same period only six patients were diagnosed at the HMO within the public health care system. CONCLUSIONS Despite the accumulated knowledge on FASD in many countries and the increase in alcohol consumption in Israel, professionals' awareness of its potential damage is limited. Educational programs to increase physician awareness should accompany publicity campaigns warning the public of the dangers associated with alcohol consumption during pregnancy.

Hyperbaric oxygen therapy for non-healing wounds.

Abstract: c hronic wounds are a significant challenge to the health care system and its professionals. It has been estimated that 1–2% of the population in the industrial world will suffer from leg wounds that might need professional treatment during their lifetime. In 2001, McGuckin et al. [1] estimated that 3 billion dollars a year are expended for the treatment of leg ulcers in the United States. Moreover, this figure does not include the loss of 2 million working days. In 1994 Lazarus and colleagues [2] defined chronic wound as a wound that fails to proceed through an orderly and timely process to produce anatomic and functional integrity, or proceed through the repair process and stages without establishing a sustained anatomic and functional result. Another way to define a chronic wound is by the healing time, i.e., a wound that does not demonstrate a tendency towards healing after 8 weeks of standard wound care. Other terminologies that are used in the literature for the treatment of difficult wounds include: "non-healing wound," "hard to heal wound," "problem wound" and "chronic cutaneous ulcer." The treatment approach to non-healing wounds is based on three principles: a) treating the main etiology, b) locating and removing the delaying factors, and c) providing the optimal environment for wound healing. Local wound treatment includes: cleansing and debridement, modern wound dressing, and innovative treatments for wound healing – such as negative pressure wound treatment, topical growth factors, cultured skin, and macrophages. Oxygen is an essential component of wound healing, and the rate of healing can be directly linked to the level of tissue oxygenation. According to Mogford and Mustoe [3], wound ischemia is, arguably, the most common cause of wound-healing failure. Hyperbaric oxygen therapy is a treatment for hypoxic wounds. It utilizes oxygen as a drug and the hyperbaric chamber as the mechanical tool for elevating its concentration at the target area. During the treatment, the patient breathes 100% of oxygen, while the surrounding atmospheric pressure is higher than at sea level. This review article elaborates on the history of HBOT, the rationale of the physiological treatment, clinical indication and contraindications, patient selection, treatment protocols and side effects.

Elevated cardiac troponins: the ultimate marker for myocardial necrosis, but not without a differential diagnosis.

Abstract: Cardiac troponins are released from myocytes following myocardial damage and loss of membrane integrity. Their significance when diagnosing acute myocardial infarction is immense, e.g., their high sensitivity and specificity for myocardial tissue, the prognostic information they bear, and their role in risk stratification and therapeutic decisions. However, one cannot fully and blindly rely on cTn testing in diagnosing acute MI since many other conditions are associated with elevation of troponin. A review of the literature demonstrates a myriad of such examples including non-thrombotic cardiac injury, systemic diseases and laboratory interferences. Failure to acknowledge the differential diagnosis of elevated troponin may lead to over-diagnosis of MI and, accordingly, misdiagnosis of the real cause. It is of utmost importance that all physicians who measure troponin recognize the possibility of falsely diagnosing Ml and are familiar with the main alternative causes for cardiac troponin elevation.

Pediatric tissue expansion: our experience with 103 expanded flap reconstructive procedures in 41 children.

Abstract: Background Tissue expansion is a well-recognized technique for reconstructing a wide variety of skin and soft tissue defects. Its application in the pediatric population has enabled the plastic surgeon to achieve functional and aesthetic goals that were previously unobtainable. Objectives To review the use of tissue expansion in the pediatric population, with particular emphasis on indication, operative technique, regional considerations and how to avoid complications. Methods We retrospectively reviewed data on 103 expanded flap reconstructions performed in 41 pediatric patients during the period 2003-2006. Tissue expanders were placed on a subcutaneous plane above the fascia and inflated weekly. The expanded skin was used as a transposition flap or a full thickness skin graft for the reconstruction of the involved area. Forty-three tissue expanders were inserted to the head and neck in 21 patients, 45 were inserted to the trunk in 13 patients and 15 were inserted to the groin and lower extremity in 8 patients. Twenty-eight patients had one round of tissue expansion, while 13 patients had two to six rounds. A plastic surgeon, medical student and a lawyer reviewed the patients' photographs and evaluated their aesthetic outcome: Results Eighty-six percent of the head and neck reconstructions and 40% of the trunk and extremity reconstructions were graded as having excellent aesthetic outcome, and 11% of the head and neck reconstructions and 37% of the trunk and extremity reconstructions were graded with good aesthetic outcome. The remaining patients were graded with moderate outcome. None of our patients was graded as poor aesthetic outcome. Complications included infection in 6 patients (6%), extrusion in 3 (3%), hematoma in 2 (2%), flap ischemia in one patient (1%), and expander perforation after percutaneous stabbing in one patient (1%). Conclusions Tissue expansion is an efficient and valuable technique for reconstruction of large skin lesions and scars.

Olfaction--a window to the mind.

Abstract: Although our knowledge of the brain, the olfactory sense and autoimmunity continues to evolve, examining the olfaction ability is not yet routinely applied by clinicians in the process of diagnosis and treatment. Moreover, assessment of the sense of smell and olfactory impairments is usually overlooked by patients and their clinicians. Given the clinical data reviewed here, clinicians should be encouraged to screen for olfactory impairments, which can help in the early diagnosis of CNS diseases such as Parkinson, dementia and schizophrenia, as well as CNS-autoimmune diseases such as neuropsychiatric lupus.