Israel Medical Association Journal

Objectives: To study the necessity of bone marrow examination for the diagnosis and clinical course of MGUS[1].

Methods: We retrospectively screened the medical records of all patients in whom monoclonal protein was found in the serum during 2001–2002 in the medical laboratories of Sapir Medical Center. Asymptomatic patients who had serum monoclonal immunoglobulin G < 3.0 g/dl or IgA[2] < 2.0 g/dl or IgM < 1.0 g/dl without anemia, renal failure, hypercalcemia or any bone lesions on skeletal survey were eligible. Full records of patients who were evaluated in the hematology clinic were available (group 1). The remaining patients were followed by their family physicians; thus we had access only to their electronic files including laboratory results and new diagnoses (group 2). Demographic and clinical parameters as well as clinical course were evaluated.

Results: Both groups (57 and 255 patients, respectively) had similar demographic, laboratory and clinical characteristics. Bone marrow examination was performed in 30 of 57 patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6 had excess of pathologic plasma cells. However, only in two of the latter six could a diagnosis of multiple myeloma be established. All group 1 patients were followed for 22 ± 11 months and only two developed overt multiple myeloma. During the same period, 6 of 255 patients (group 2) were diagnosed as multiple myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no change in their laboratory values.

Conclusions: Our findings suggest that bone marrow examination should not be performed routinely in patients who fulfill strict clinical and laboratory criteria of MGUS.

Objectives: To assess the risk of microvascular complications associated with the metabolic syndrome in diabetes subjects.

Methods: The study group comprised 415 diabetic subjects attending a primary care clinic. The prevalence of microvascular complications was compared between 270 diabetic subjects with metabolic syndrome (NCEP-III criteria) and 145 diabetic patients without.

Results: We found that as a group, diabetic subjects with metabolic syndrome had significantly higher frequency of microvascular-related complications than diabetic subjects without the syndrome (46.6% and 26.8% respectively, P = 0.0005). These include microalbuminuria (41.5% vs. 23.9%, P = 0.013), neuropathy (10.4% vs. 7.5%, P = 0.38), retinopathy (9.6% vs. 4.1%, P = 0.046) and leg ulcers (7.9% vs. 2.8%, P = 0.044). After adjustment for age, gender, glycemic control, disease duration, lipid profile and blood pressure, metabolic syndrome was associated with a significantly higher risk of microvascular complications: odds ratio (95% confidence interval) for nephropathy 2.27 (1.53–3.34), neuropathy 1.77 (0.79–4.0), retinopathy 3.42 (1.2–9.87), and leg ulcers 3.57 (1.08–11.95).

Conclusions: In addition to hyperglycemia and disease duration, the metabolic syndrome is a significant risk factor for the development of microvascular complications in diabetic subjects.

Background: Metastatic melanoma is an aggressive and highly malignant cancer. The 5 year survival rate of patients with metastatic disease is less than 5% with a median survival of only 6–10 months. Drugs like dacarbazin (DTIC) as a single agent or in combination with other chemotherapy agents have a response rate of 15–30%, but the duration of response is usually short with no impact on survival. Interleukin-2-based immunotherapy has shown more promising results. The National Institutes of Health recently reported that lymphodepleting chemotherapy, followed by an adoptive transfer of large numbers of anti-tumor specific tumor-infiltrating lymphocytes, resulted in an objective regression in 51% of patients.

Objectives: To introduce the TIL[1] technology to advanced metastatic melanoma patients in Israel.

Methods: We generated TIL cultures from tumor tissue, choosing those with specific activity against melanoma and expanding them to large numbers.

Results: TIL cultures from nine patients were established and examined for their specific activity against the patients' autologous tumor cells. Twelve TIL cultures derived from 5 different patients showed the desired anti-tumor activity, making those 5 patients potential candidates for the therapy.

Conclusions: Pre-clinical studies of the TIL technology in a clinical laboratory set-up were performed successfully and this modality is ready for treating metastatic melanoma patients at the Sheba Medical Center's Ella Institute.

Background: Elevated fibrinogen levels are considered a risk factor for the development of atherosclerosis and might be used as a predictor of risk for the development of atherothrombotic events. Several studies have reached equivocal conclusions regarding the effect of statins on fibrinogen.

Objectives: To evaluate the effect of atorvastatin on plasma fibrinogen levels in patients with severe hypercholesterolemia and no other risk factors.

Methods: Twenty-two patients with low density lipoprotein-cholesterol levels above 170 mg/dl (4.40 mmol/L) and with no other risk factors were included in the study. None of the patients had ever received hypolipidemic medication. Patients were followed for 24 weeks (6 office visits 4 weeks apart). During office visits, lipid profile, complete blood count, fibrinogen and C-reactive protein levels were measured.

Results: After 24 weeks of follow-up, total cholesterol decreased by 33% (287 ± 10 to 192 ± 8 mg/dl, P < 0.001), LDL-C[1] by 45% (198 ± 8 to 111 ± 7 mg/dl, P < 0.001) and triglycerides by 21% (189 ± 26 to 138 ± 15 mg/dl, P <0.001). Fibrinogen levels dropped by 18% (355 ± 26 to 275 ± 7 mg/dl, P = 0.01). CRP[2] levels decreased from 0.51 ± 0.15 to 0.28 ± 0.10 mg/dl, but the difference was not statistically significant (P = 0.09). High density lipoprotein, hemoglobin, white blood cell and platelet counts did not change.

Conclusions: We found that atorvastatin reduces plasma fibrinogen in patients with hypercholesterolemia.

Background: The indication for aortic valve replacement in patients with significant aortic stenosis is symptomatology. Aortic stenosis may be associated with bleeding from colonic angiodysplasia, resulting in anemia. Persistent anemia in such patients, despite lack of an identifiable source of bleeding, is not considered an indication for valve replacement.

Objectives: To report our experience with two elderly female patients who suffered from severe asymptomatic aortic stenosis, low levels of large von Willebrand factor multimer (10% and 5% respectively) and persistent anemia requiring multiple blood transfusions.

Methods: Both patients underwent an intensive work-up, but a source of bleeding could not be identified. Aortic valve replacement was performed in both patients.

Results: Aortic valve replacement abolished the need for further blood transfusions during a follow-up period of 20 months with normalization of the vWF[1] multimer level (20% and 30% respectively).

Conclusion: We suggest that aortic valve replacement be considered in selected patients with severe, otherwise asymptomatic aortic stenosis, who suffer from persistent anemia requiring multiple blood transfusions, lack an identifiable source of bleeding and have low levels of large vWF multimers.

Background: Leptospirosis is a zoonotic disease that occurs worldwide, found predominantly in agricultural workers, port workers and dairy workers.

Objective: To investigate the risk of disease transmission to dairy workers following an outbreak in 1999 of Leptospirosis hardjo in the dairy herds of two kibbutzim in southern Israel.

Methods:  A seroepidemiologic survey of all the dairy workers from these two kibbutzim was conducted, including individual interview and examination. Data were collected on the presence of clinical symptoms of leptospirosis during the previous month. One month later the medical personnel on the two kibbutzim were contacted in order to determine if any worker had subsequently developed clinical signs or symptoms of leptospirosis. All dairy workers had blood drawn for serology. Those workers whose initial serology had been borderline for leptospirosis had a repeated serology test between 2 and 4 weeks later. Doxycycline was given prophylactically to all dairy workers on one kibbutz only.

Results:  Either with or without chemoprophylaxis, no dairy workers exposed to herds infected with Leptospira hardjo showed evidence of seroconversion or disease. This indicated a low risk of transmission of this serovar from cows to dairy workers.

Conclusion: Since human illness with leptospirae can cause illness associated with significant morbidity we recommend that dairy workers exposed to an infected herd receive doxycycline prophylaxis.