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Biomedical subjects

M R Kramer

Publications and source records attributed to M R Kramer.

At least 19 recordsLinked to original sources

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.

Adolescent↗

Use of noninvasive tools in primary pulmonary hypertension to assess the correlation of right ventricular function with functional capacity and to predict outcome.

UNLABELLED: Most patients with Primary Pulmonary Hypertension (PPH) have severe exertional limitation which ultimately leads to right heart failure and death. The purpose of the study was to assess the correlation between right ventricular (RV) systolic and diastolic noninvasive variables and exercise tolerance, as well as the predictors of adverse outcome in treated patients. METHODS: We prospectively studied 29 patients, 17 with PPH and 12 with PPH due to collagen disease. RV parameters were assessed by echocardiography and Radionuclide ventriculography. Pulmonary function and clinical profile were assessed by 6 min walk test and NYHA class. The patients were followed-up during 2 years for cardiac death and cardiac deterioration. RESULTS: Mean age was 51 +/- 15 years, 22 (78%) women. NYHA class1 in 2 pts, class 2 in 17, class 3 in 8 and class 4 in 2 pts. Pulmonary function (DLCO) was low in 25 (86%) pts, mean 22 +/- 48%. Six minutes walk distance was 358 +/- 132 m, RVEF was 34 +/- 11% (range 16-51%). Among RV variables, RVEF, RA area and TR were independently correlated to 6 min walk. Within follow up of 2 years, there were 10 patients with adverse outcome (4 deaths and 6 deteriorated to NYHA class 3 and 4). Among all clinical and noninvasive variables, RVEF only was correlated to adverse outcome. CONCLUSION: The noninvasive tests of RVEF, RA size and TR were closely correlated to exercise tolerance. However, among the various clinical, functional and RV variables, RVEF was the only variable correlated with adverse outcome in pts with PPH.

Adult↗

Normal D-dimer levels in patients with latent tuberculosis infection.

Studies have demonstrated a link between acute pulmonary tuberculosis and a hypercoagulable state, but there are no data on the coagulation state of patients with latent tuberculosis infection (LTI). The present prospective observational study was designed to help fill this gap. The sample included 84 patients (high school students and adults) with suspected LTI referred for the purified protein derivative (PPD) test. Results were read according to the criteria of the American Thoracic Society. Blood samples were collected at admission and assayed for D-dimer, the marker of the coagulation state, with the quantitative Miniquant test. D-dimer values were correlated with the PPD status and clinical parameters. Fifty-seven patients tested positive for LTI and 27 tested negative. There was no significant difference in D-dimer level between these groups (341 +/- 106 and 360 +/- 60 microg/ml, respectively). No significant correlation was found between D-dimer level and PPD status, patient age or occupation (health care worker or not), or clinical indication for the tuberculin test. The normal D-dimer levels in this series suggest that low-level inflammations such as LTI do not lead to a hypercoagulable state.

Adolescent↗

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.

Adolescent↗

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.

Adolescent↗

Successful lung transplantation following lung volume reduction surgery.

BACKGROUND: Lung volume reduction surgery (LVRS) is an accepted treatment modality for patients with advanced emphysema. Recently, successful lung transplantation (LTX) has been reported following LVRS. We assess the pulmonary functions in lung transplant recipients after LVRS. METHODS: 8 patients - 5 males and 3 women--aged 53-66 years with advanced emphysema underwent LVRS. Following clinical deterioration and decline of pulmonary function, patients underwent single LTX. Post transplantation follow-up included pulmonary function, 6 minute walk distance (6 MWD) and recording perioperative complications. RESULTS: Median forced expiratory in one second (FEV 1) before and after LVRS were 24 % with 31 % predicted, respectively. All but one showed improvement in lung function and 6 MWD following LVRS. Median maximal 6 MWD before and after LVRS was 222 and 316 meters, respectively. Median time from LVRS to LTX was 46 months (range 10-83). All patients survived and were discharged after LTX. Median FEV1 before and after LTX was 23 % with 57 % predicted, respectively. Median 6MWD before and after LTX was 240 and 462 meters, respectively. NYHA classes improved from 3-4 to 1-2 in 7 surviving patients. At transplantation, bleeding due to pleural adhesions was observed in 4 patients; two required blood transfusions. One patient developed acute respiratory distress syndrome and one had unilateral vocal cord paralysis. At nine-month follow-up, 7 patients are doing remarkably well, while one patient died 6 months after LTX due to bronchiolitis obliterans syndrome (BOS). CONCLUSIONS: LVRS is a therapeutic option in patients with end-stage emphysema. When emphysema deteriorates, LTX can be successfully performed with significant improvement of quality of life without significant additional risk.

Aged↗

Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile virus encephalitis.

During the summer of 2000, a countrywide epidemic of West Nile fever (WNF) occurred in Israel, with 417 confirmed cases and 35 deaths. Immunosuppressed patients had a 31% case-fatality rate, which was significantly higher compared to non-immunosuppressed patients (13%). We describe a 42-year-old male lung-transplant recipient with serologically confirmed West Nile virus (WNV) encephalitis and deteriorating level of consciousness. He was treated with 0.4 g/kg intravenous immunoglobulin preparation from Israeli donors that contained a high titer of anti-WNV antibodies (1 : 1600). The patient showed rapid improvement within 24 h and complete disappearance of signs and symptoms within 48 h. This is the second case of an immunosuppressed patient responding to the same preparation of intravenous immunoglobulins. Larger studies are required in order to establish the therapeutic role of immunoglobulins in patients with WNF.

Adult↗

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.

Adult↗

[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.

Antitubercular Agents↗

Successful use of high dose rate brachytherapy for non-malignant bronchial obstruction.

High dose rate (HDR) endobronchial brachytherapy is a palliative treatment for symptomatic airway obstruction by malignant tumours. We report a novel use of HDR brachytherapy for treating non-malignant bronchial obstruction. The patient had a metal stent placed in a reconstructed airway after a bronchial tear to ensure patency. Granulation tissue formation in and around the stent caused symptomatic occlusion of the airway, necessitating multiple laser applications. A single treatment of HDR brachytherapy (1000 cGy) was delivered following laser therapy. The patient remains well 15 months after treatment with no evidence of recurrent granulation tissue formation on bronchoscopy. HDR brachytherapy is an effective treatment for non-malignant airway obstruction.

Adult↗

Nasal potential difference measurements in patients with atypical cystic fibrosis.

The diagnosis of cystic fibrosis (CF) is based on characteristic clinical and laboratory findings. However, a subgroup of patients present with an atypical phenotype that comprises partial CF phenotype, borderline sweat tests and one or even no common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The aim of this study was to evaluate the role of nasal potential difference (PD) measurements in the diagnosis of CF patients with an atypical presentation and in a population of patients suspected to have CF. Nasal PD was measured in 162 patients from four different groups: patients with classical CF (n = 31), atypical phenotype (n = 11), controls (n = 50), and patients with questionable CF (n = 70). The parameter, or combination of nasal PD parameters was calculated in order to best discriminate all CF patients (including atypical CF) from the non-CF group. The patients with atypical CF disease had intermediate values of PD measurements between the CF and non-CF groups. The best discriminate model that assigned all atypical CF patients as CF used: e(response to chloride-free and isoproterenol/response to amiloride) with a cut-off >0.70 to predict a CF diagnosis. When this model was applied to the group of 70 patients with questionable CF, 24 patients had abnormal PD similar to the atypical CF group. These patients had higher levels of sweat chloride concentration and increased rate of CFTR mutations. Nasal potential difference is useful in diagnosis of patients with atypical cystic fibrosis. Taking into account both the sodium and chloride transport elements of the potential difference allows for better differentiation between atypical cystic fibrosis and noncystic fibrosis patients. This calculation may assist in the diagnostic work-up of patients whose diagnosis is questionable.

Adolescent↗

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.

Adolescent↗

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.

Adolescent↗

Relationship between pulmonary function and unsupported arm exercise in patients with COPD.

UNLABELLED: In patients with chronic obstructive pulmonary disease (COPD) the limitation on unsupported arm exercise (UAE) is predominantly respiratory muscle function-dependent. It is characterized by neuromechanical dysfunction (thoracoabdominal dyssynchrony) of the inspiratory muscles (diaphragm, accessory), superimposed by lung mechanics dysfunction. The undergoing mechanism is probably multifactorial. To study the relationship of resting pulmonary function and UAE performance in patients with COPD. Twenty-one patients, mean age 63 +/- 7 years, with COPD [forced expiratory volume in the first second (FEV1) 42 +/- 12% of predicted] underwent assessment of resting lung function (inspiratory capacity 57 +/- 17%; functional residual capacity 204 +/- 38% of predicted), maximal inspiratory pressure (67 +/- 14 cmH2O), upper arm circumference (30 +/- 2 cm), and symptom-limited cardiopulmonary UAE assessments. UAE consisted of bilateral anterior arm elevation to shoulder level at a rate of 40 arm strokes.minute-1. A series of stepwise multiple regression models were fitted to the data to predict exercise time from resting pulmonary function indices. RESULTS: Statistically significant correlations (r) were found between exercise time and inspiratory capacity (% of predicted) (r = 0.67, p = 0.0008), maximal inspiratory pressure (cmH2O) (r = 0.47, p = 0.03), upper arm circumference (r = 0.74, p = 0.0001), FEV1 (% of predicted) (r = 0.62, p = 0.0026), oxygen uptake (r = 0.56, p = 0.0085) and functional residual capacity (% of predicted) (r = -0.41, p = 0.06, borderline). Inspiratory capacity (% of predicted), functional residual capacity (% of predicted), upper arm circumference (cm) and FEV1 (% of predicted) explained 77% of the variance in exercise time. Therapeutic strategies that aim to increase inspiratory capacity or decrease functional residual capacity, or increase inspiratory muscle strength and upper arm/torso muscle endurance are likely to alleviate symptoms and improve UAE performance in patients with COPD.

Aged↗