Outcome of hospitalized MDR-TB patients: Israel 2000-2005.

MDR-TB has emerged in Israel following an immigrations wave from the Former Soviet Union (FSU) and Ethiopia. The purpose of this study was to outline characteristics and outcome of hospitalized MDR-TB patients. We retrospectively summarized charts of MDR-TB patients hospitalized in the national referral tuberculosis centers from January 2000 to December 2005, and followed them for 2 years. One hundred thirty-two patients were identified with a median age of 40 years and male predominance (77%). The majority of the patients were immigrants from FSU (83%) and Ethiopia (7.6%). They were characterized by alcohol (25.8%) and IV drug abuse (23.5%), presented with advanced disease manifested by hypoalbuminemia (50.8%) and smear positivity (70.5%). Cure was achieved in 50.3% and 30.4% died. Factors independently associated with death were patients' age (OR = 1.036 for each year, 95%CI 1.0-1.1, p = 0.014), hypoalbuminemia (OR = 2.95, 95%CI 1.1-7.6, p = 0.025), smear positivity at diagnosis (OR = 3.7, 95%CI 1.2-11.4, p = 0.023), alcohol abuse (OR = 4.8, 95%CI 1.7-13.7, p = 0.004) and XDR-TB resistance pattern (OR 8.3, 95%CI 1.5-44.6, p = 0.014). This study brings out the poor prognosis of a highly vulnerable immigration population. Efforts should be focused on earlier diagnosis and treatment in a well controlled hospital environment and to professional support groups to attend to this population's special needs.

Liver tuberculosis in an HIV patient: diagnosis and management.

Hepatic involvement is common in miliary and extra-pulmonary tuberculosis but is usually clinically silent. Therefore, it is rarely diagnosed. We report the case of a patient that presented with prolonged fever and hepatomegaly. Liver biopsy revealed non-necrotizing granulomas that led in turn to the diagnosis of generalized tuberculosis and HIV infection. The patient reported an old untreated tuberculosis and depression of the immune system provoked the reactivation of this old tuberculosis focus. We describe the clinical course of the disease and the challenges associated with the complexity of the treatment. Diagnosis of hepatic tuberculosis requires a high degree of suspicion especially in AIDS patients who show atypical presentations. However, it is a potential curable disease and good results have been obtained with the four drug regimen.

Absence of human herpesvirus 8 DNA sequences in lung biopsies from Israeli patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary hypertension is a severe pulmonary vascular disease leading to rapid deterioration and death. Histological and clinical evidence suggests that smooth muscle proliferation is part of the pathogenesis of the disease. Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus that is implicated in malignancies and in Kaposi's sarcoma. Recently, the association of HHV-8 with idiopathic pulmonary arterial hypertension (PAH) has been found. OBJECTIVE: The aim of this study was to investigate the presence of HHV-8 in the lung tissue of Israeli patients with PAH. METHOD: The presence of HHV-8 sequences was investigated by polymerase chain reaction examination in 6 biopsies of patients with pulmonary hypertension. Three patients had idiopathic pulmonary hypertension, 2 patients pulmonary venoocclusive disease, and 1 patient pulmonary hypertension associated with mixed connective tissue disease. RESULT: We did not find any association between HHV-8 and PAH in these Israeli patients, as all the samples were negative for polymerase chain reaction. CONCLUSION: Our findings, together with the epidemiological data of HHV-8 prevalence and incidence rates of Kaposi's sarcoma and PAH in Israel, provide further evidence which argues against an association between HHV-8 infection and PAH.

Multidrug resistant tuberculosis following lung transplantation: treatment with pulmonary resection.

Recipients of organ transplants are at increased risk for infection owing to their immunosuppressed state and the possibility of contamination of the donor organ. We report a case of multidrug resistant tuberculosis (MDR) transmission via a donor lung. After medical treatment with four drugs had failed, the patient underwent right upper lobectomy. There were no signs of disease on follow up more than 2 years later. To our knowledge, this is the first report of MDR tuberculosis in a lung transplant recipient. The need for a non-conservative approach, including pulmonary resection, to eradicate the infection is emphasised.

Hyperuricemia as a prognostic factor in pulmonary arterial hypertension.

Pulmonary arterial hypertension is a malignant disease with a median survival of 3 years. Uric acid levels are elevated in severe heart failure and in states of hypoxemia. Early data suggest a correlation between hyperuricemia and severe pulmonary arterial hypertension. We studied 29 patients with pulmonary arterial hypertension diagnosed and treated between 1998 and 2001. Clinical characteristics (6 min walk test and New York Heart Association class) and hemodynamic parameters (pulmonary artery pressure, pulmonary vascular resistance and cardiac output) were evaluated and correlated to uric acid level in a retrospective study. Uric acid levels correlated positively with New York Heart Association class (r=0.66, P<0.001) and negatively with 6 min walk test (r=-0.35, P=0.03). Uric acid levels were higher in patients who died than in patients who survived at the end ofthe follow-up period (8.8 vs. 5.7 mg/dl, P=0.001). This study shows that uric acid levels are elevated in severe pulmonary arterial hypertension and can be used as a prognostic marker of disease severity.

Elevation of ELISA d-dimer levels in patients with primary pulmonary hypertension.

BACKGROUND: Vasoconstriction, vascular wall remodeling and thrombosis are considered as possible etiologies of primary pulmonary hypertension (PPH). D-dimer, a degradation product of fibrin, has been increasingly used as a marker and prognostic factor in various diseases. OBJECTIVE: To assess elevated ELISA D-dimer levels as a marker of endogenous fibrinolysis in patients with PPH. PATIENTS AND METHODS: Comparison of ELISA D-dimer levels of 12 PPH patients (11 female, 1 male) aged 27-73 years (median 51 years) with those of sex- and age-matched healthy controls. RESULTS: Eleven patients had New York Heart Association (NYHA) class III or IV symptoms, and one patient had NYHA class II symptoms. All patients with PPH were treated with anticoagulants and vasodilators: 5 patients were treated with continuous intravenous prostacyclin, 4 patients with continuous UT-15 and 2 patients with intermittent intravenous iloprost. Mean ELISA D-dimer levels +/- SD were significantly higher in the PPH group than in the matched control group (473 +/- 109 vs. 182 +/- 103 ng/ml; mean difference: 291 +/- 79, 95% CI: 240-341, p < 0.0001). CONCLUSION: These results suggest the possible involvement of endogenous fibrinolysis in the pathophysiology of PPH.

[Latent tuberculosis infection: diagnosis and treatment].

The essential component of tuberculosis elimination strategy is to identify and treat persons with latent tuberculosis infection (LTBI) who are at high risk for developing active tuberculosis. The tuberculin skin test is the only proven method for identifying LTBI. Although the specificity and the sensitivity are decreased by cross reaction with BCG vaccination and by non tuberculous mycobacteria, there is no better diagnostic tool. The test's positive predictive value is poor in populations with low risk for tuberculosis. Identification of persons with LTBI is focused on groups at high risk who would benefit from therapy (targeted tuberculin testing). The interpretation of the tuberculin skin test reaction is dependent on the risk factors and the immune status of the patient. For the past 30 years, Isoniazid has been the drug of choice for treating patients with LTBI, but its application has been limited by poor compliance and toxicity. Therefore, there has been interest in the development of shorter course treatments such as rifampin (4 months) or rifampin and pyrazinamide (2 months). We describe the new guidelines for targeted tuberculin testing and different treatment regimens for LTBI as recommend by the American Thoracic Society.

Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature.

OBJECTIVE: To determine the characteristic features and outcome of pulmonary carcinoid tumors in Israel. METHODS: Retrospective analysis of the clinicopathologic data and outcome of patients from four major hospitals in Israel in the last 20 years. RESULTS: There were 142 cases of pulmonary carcinoid tumors: typical (n = 128) and atypical (n = 14). We calculated an annual incidence of about 2.3 to 2.8 cases per 1 million population. The ratio of female to male patients was 1.6:1. The prevalence of smoking was similar to the general population in patients with typical carcinoids and twice as high in the atypical group. Bronchial obstruction was the cause of most of the presenting symptoms and signs and included obstructive pneumonitis, pleuritic pain, atelectasis, and dyspnea (41%). Carcinoid syndrome was extremely rare and occurred in only one patient with metastatic disease. Most of the tumors (68%) arose in the major bronchi. Diagnosis was made using fiberoptic bronchoscopy in 52% of patients without evidence of endobronchial hemorrhage. Nodal involvement and distant metastases occurred in 57% and 21%, respectively, in the atypical group, and 10% and 3%, respectively, in the typical group. The treatment of choice was surgical: lobectomy (56%) or pneumonectomy (16%). The respective 5-year survival rates for patients with typical and atypical tumors were 89% and 75% (not significant), and the 10-year survival rates were 82% and 56% (p < 0.05). A review of large series from the literature is presented. CONCLUSION: Pulmonary carcinoid is an uncommon tumor in the Israeli population. With early diagnosis and aggressive surgical therapy, long-term prognosis is excellent.

Primary pulmonary hypertension in Israel: a national survey.

OBJECTIVES: To characterize the incidence of patients with primary pulmonary hypertension (PPH) in Israel and their outcomes. METHODS: We have evaluated retrospectively all the patients in Israel in whom PPH was diagnosed between the years 1988 and 1997. We looked at medical history, hemodynamic data, pulmonary function and gas exchange, and demographic variables. Patients were followed up for survival until November 1997. Life table analysis and Kaplan-Meier statistics were used to estimate the overall survival distribution. Regression analysis was used to examine the relations between survival and selected variables. RESULTS: Overall, we found 44 patients with PPH. The estimated incidence of PPH in Israel is 1.4 new cases per year per million population. The mean (+/- SD) age at diagnosis was 43 +/- 13 years. In the Jewish population, PPH was more frequent among immigrants from Europe and the United States. The mean interval from the onset of symptoms to diagnosis was 3 years (median, 2 years). The median survival time was 4 years. The 1-year, 3-year, and 5-year survival rates were 82%, 57%, and 43%, respectively. The major variables influencing the survival rate were the following: interval from symptom onset to diagnosis; and hemodynamic measurements (ie, mean pulmonary artery pressure, mean right atrial pressure, and cardiac index). In comparison to rates discerned from the National Institutes of Health registry data, the survival rate in Israel is somewhat better and prognosis is influenced by similar hemodynamic variables. CONCLUSION: PPH is a rare and fatal disease in Israel. New therapeutic modalities such as prostacyclin therapy and lung transplantation may improve survival among patients with this malignant disease.

[High dose endobronchial brachytherapy for malignant airway obstruction: first study of 30 patients].

Brachytherapy is especially suitable for palliative treatment of endobronchial tumors adjacent to internal organs that might be damaged by intensive external beam radiation, but are easily accessed with a flexible bronchoscope. This treatment is mostly palliative. 30 patients underwent such palliative high-dose endobronchial brachytherapy to alleviate malignant airway obstruction. With the aid of a flexible fiberoptic bronchoscope an endobronchial catheter was inserted adjacent to the tumor and treatment delivered using a 192Ir remote afterloader for 5-10 min, in 2 or 3 sessions. There was symptomatic improvement in 26 (86%) and objective improvement in 27 (90%). 1 patient died of hemoptysis.

Pulmonary calcifications: a review.

Pulmonary calcification is a common asymptomatic finding, usually discovered on routine chest X-ray or at autopsy. Pulmonary calcifications are caused mainly by two mechanisms: the dystrophic form and the metastatic form (1). Despite the different aetiologies, the pulmonary function and clinical manifestations are quite similar in both forms. We present a review of the clinical and radiology findings of the different aspects of pulmonary calcifications according to its pathogenesis and its anatomic distribution: parenchymal, lymphe node and pleural.

Splenic lymphoma presenting as warm autoimmune hemolytic anemia associated with pure red cell aplasia.

BACKGROUND AND OBJECTIVE: Warm autoimmune hemolytic anemia (AIHA) is a condition in which peripheral red blood cell (RBC) destruction is induced by the presence of an autoantibody. Pure red cell aplasia (PRCA) represents an isolated process of decreased erythropoiesis. The combination of both is quite rare, with a very poor prognosis. We describe a patient with isolated splenic lymphoma whose presentation was a combination of AIHA and PRCA. The patient was resistant to all treatment. MATERIALS AND METHODS: Erythroid colony assays were performed, in order to compare the effect of the patient's serum on colonies with that of a normal control. RESULTS: The patient's serum significantly suppressed normal erythroid colony growth. A red cell eluate revealed the presence of a warm autoantibody. CONCLUSIONS: The patient's serum contained warm autoantibody responsible for peripheral RBC destruction and a humoral factor, perhaps the warm autoantibody, which suppressed bone marrow erythropoiesis. Establishing an early diagnosis, and treatment of the underlying disease might result in a better prognosis.

Splenectomy for haematological diseases--a single institution experience.

OBJECTIVES: To evaluate our experience with splenectomy for haematological disease over 15 years, focusing on the diseases and indications requiring surgery, the complications and the haematological results. DESIGN: A single institution retrospective analysis. SETTING: Departments of Surgery, Internal Medicine and Haematology, Rabin Medical Center, Hasharon Hospital, Petah-Tikva, Israel. PATIENTS: Sixty-nine patients undergoing splenectomy for haematological diseases between 1980 and 1994. PARAMETERS STUDIED: (1) the patient characteristics; (2) the haematological disorders and the indications for splenectomy; (3) the splenic size; (4) perioperative complications; (5) the haematological and other results of surgery. RESULTS: The common disease requiring splenectomy in our patient population was immune thrombocytopenic purpura (ITP). Eighteen patients (26%) suffered from ITP, 12 (17.4%) had lymphoproliferative (LP) disorders, including 11 patients with non-Hodgkin's lymphoma (NHL), 9 (13%) immune haemolytic anaemia (IHA), 8 (11.6%) Hodgkin's disease (HD), and 8 patients with myeloproliferative diseases (MPD). Fifty-two patients (75.4%) underwent surgery for therapeutic purposes while 25 patients (36.2%) underwent diagnostic surgery. Eight patients were operated on for both indications. Patients with HD and ITP were younger (mean age in the 30th year) as opposed to patients with congestive splenomegaly and LP (mean age in the 60th year). Most patients with ITP, NHL and IHA were female. Patients with HD and ITP had a small spleen (< 300 g), in contrast with HCL and MPD (> 2400 g). No perioperative mortality was observed. Twenty-one patients (30.4%) experienced perioperative complications, including bleeding in 9 patients (13%) and infection in 10 patients (14.5%). Of the 34 patients evaluable for platelet response to splenectomy, 26 (76.5%) achieved complete response (CR), including 15 of 18 patients with ITP. Eleven of the 17 (64.7%) anaemic patients evaluable for haemoglobin (Hb) response achieved CR. Eight of the 9 leucopenic patients obtained CR. In 15 patients, splenectomy established the diagnosis, including 8 patients with NHL. In 2 others, surgery confirmed the tentative diagnosis. In 2 of the 8 HD patients the spleen was found to be involved. CONCLUSIONS: From both therapeutic and diagnostic standpoints splenectomy is a relatively safe and effective procedure. However, no long-term follow-up data are provided to allow conclusions regarding the long-term prognosis of diseases such as myelo- or lymphoproliferative disorders.

[Bleeding due to platelet dysfunction as a presenting symptom of systemic lupus erythematosus].

A 32-year-old woman was admitted for evaluation of fever, blurred vision in the left eye, nasal and gingival bleeding and arthralgia. There was a macular hemorrhage, a tender mass in the left lower abdomen and edema of both legs. She also had anemia, mild thrombocytopenia, platelet function abnormalities, kidney dysfunction, and albuminuria. Serology was positive for antinuclear antibodies and double-stranded DNA; complement level was low, and circulating anticoagulants were present. Kidney biopsy established the diagnosis of systemic lupus erythematosus (SLE). Abdominal sonography demonstrated perisplenic and pelvic bleeding. A pulse therapy of corticosteroids with low-dose oral cyclophosphamide, along with platelet transfusions and infusions of deamino-d-arginine vasopressin resulted in symptomatic and laboratory improvement. Bleeding stopped, platelet function became normal, kidney function tests returned to normal and she became seronegative. It is emphasized that platelet function abnormalities are rare in SLE. The thrombocytopenia was too mild to cause spontaneous bleeding, and lupus anticoagulant is usually associated with thromboembolic complications and not with spontaneous bleeding. It is therefore conceivable that in this case platelet function abnormalities were responsible for the spontaneous bleeding, the presenting sign which led to establishing the diagnosis.

Extensive nuclear lobulation in the cells of a patient with acute myelomonocytic leukemia. The role of electron microscopy for establishment of a correct diagnosis.

Extensive nuclear convolution and lobulation was found in the peripheral blood cells of a patient with acute leukemia. While the morphology of the cells, such as observed with the light microscope, was compatible with the diagnosis of acute myeloid leukemia, the finding of Sezary-like cells with the electron microscope helped to establish the diagnosis of acute myelomonocytic leukemia. This report emphasizes the importance of the electron microscope for the correct diagnosis of leukemias.