Radiological findings of early invasive pulmonary aspergillosis in immune-compromised patients.

Data on the radiological features of invasive pulmonary aspergillosis (IPA) in early stages is scanty. Detection of Aspergillus (ASP) species in broncho-alveolar (BAL) fluid by polymerase chain reaction (PCR) enables early diagnosis of IPA. This study describes the radiological features of early stages of IPA. Chest computerized tomography (CT) films of 22 consecutive immune-compromised patients with IPA diagnosed with the aid of ASP PCR testing from BAL fluid were characterized and compared to that of 18 similar patients diagnosed with traditional bacteriological methods and to data from the literature. It was found that patients diagnosed with the aid of ASP PCR testing tended to have focal disease as manifested by more 11-30 mm nodules with halo (68% vs. 33%, p = 0.04), more focal ground glass (single area 32% vs. 6%, p = 0.05, patchy 32% vs. 0%, p = 0.01) and less diffuse ground glass (0% vs. 22%, p = 0.03), less cavitations (5% vs. 28%, p = 0.05) and less consolidations (segmental 14% vs. 50%, p = 0.02 and diffuse 14% vs. 67%, p = 0.001). It was concluded that the radiological appearance of early IPA diagnosed with the aid of PCR testing included mainly discrete small nodules with halo and focal ground glass, representing the early stage of the disease.

Impact of PCR-based diagnosis of invasive pulmonary aspergillosis on clinical outcome.

The mortality rate of 60-90% in invasive pulmonary aspergillosis (IPA) is partly explained by diagnostic delay due to the limitation of current diagnostic tests. We assessed the influence of Aspergillus species (ASP) DNA detection by PCR from bronchoalveolar lavage (BAL) fluid, a new tool for diagnosing IPA, on the outcome of this disease in immune-compromised patients. The study population comprised 107 consecutive patients with hematological malignancies from a single medical center with IPA diagnosed between 1998 and 2005. Clinical variables and mortality rates were compared between two groups diagnosed according to traditional criteria without and with PCR-based ASP DNA detection in BAL fluid. The overall mortality rate during the study period was 38.3%. The addition of PCR to the diagnostic criteria shifted 31 patients from possible to probable IPA. Patients diagnosed with probable IPA according to traditional microbiological methods had significantly higher mortality rates compared to their counterparts who had in addition a PCR-based diagnosis (80 vs 35.6%, P=0.003). This study demonstrates that PCR-based ASP DNA detection for a diagnosis of IPA from BAL fluid has a significant effect on the outcome of patients with IPA, probably related to earlier diagnosis.

Nosocomial outbreak of Legionella pneumophila serogroup 3 pneumonia in a new bone marrow transplant unit: evaluation, treatment and control.

A nosocomial outbreak of pneumonia caused by Legionella pneumophila serogroup 3 occurred in four patients following hematopoietic stem cell transplantation (HSCT) in a new bone marrow transplantation (BMT) unit during a 2 week period. The causative organism was recovered from the water supply system to the same unit just before the outbreak. Nineteen other BMT patients were hospitalized in the same unit at the same time, giving a frequency of proven infection of 4/23 = 17%. Immediately after recognition of the outbreak, use of tap water was forbidden, humidifiers were disconnected, and ciprofloxacin prophylaxis was started for all patients in the unit, until decontamination of the water was achieved. No other cases were detected. In conclusion, contamination of the hospital water supply system with legionella carries a high risk for legionella pneumonia among BMT patients. Early recognition of the outbreak, immediate restrictions of water use, antibiotic prophylaxis for all non-infected patients, and water decontamination, successfully terminated the outbreak.

The problem of empyematous pleural effusion in rheumatoid arthritis: report of two cases and review of the literature.

Two patients with rheumatoid arthritis and empyematous pleural effusion were treated with repeated drainage and intrapleural corticosteroids. One patient with active joint disease improved within 3 months without sequelae, probably because of the systemic therapy. The other patient, with non-active joint disease, had persistent pleural effusion which resulted in pleural thickening and symptomatic restrictive disturbance. It appears that early intervention intended to prevent the accumulation of empyematous pleural effusion could also prevent pleural thickening and fibrosis. Therapeutic options are discussed.

High-dose-rate endobronchial brachytherapy in endobronchial metastatic malignant chondroid syringoma.

A 65-year-old man with malignant chondroid syringoma (MCS) was found to have pulmonary metastases in the form of multiple pulmonary nodules 4 years after wide excision and adjuvant radiotherapy of a primary abdominal wall tumor. Atelectasis of the lingula due to obstructive endobronchial metastasis, resistant to combination chemotherapy, led us to perform high-dose rate (HDR) endobronchial brachytherapy for the first time in this rare tumor with a favorable response. This case emphasizes the role of HDR brachytherapy as a palliative procedure in endobronchial tumors not responding to other treatment modalities, even those considered to be radioresistant.

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.

Background diseases in 671 patients with moderate to severe pulmonary hypertension.

BACKGROUND: Data regarding the epidemiology of secondary pulmonary hypertension are scanty. OBJECTIVES: To describe the spectrum and relative incidence of background diseases in patients with significant secondary PHT. METHODS: We identified 671 patients with systolic pulmonary artery pressure of 45 mm Hg or more from the database of the echocardiographic laboratory. Their background diseases were recorded and classified into three subgroups: cardiac, pulmonary and pulmonary vascular disease without pulmonary parenchymal disease. Age at the first echocardiographic study, gender and systolic PAP values were recorded. Data between the three subgroups were compared. RESULTS: The mean age of the patients was 65 +/- 15 years, mean systolic PAP 61 +/- 14 mm Hg and female:male ratio 1.21:1. At the time of diagnosis 85% of the patients were older than 50. PHT was secondary to cardiac disease in 579 patients (86.3%), to PVD without PPD in 54 patients (8%) and to PPD in only 38 patients (5.7%). Mean age and mean systolic PAP did not differ significantly among the three subgroups. There was a significantly higher female:male ratio in patients with PVD without PPD compared with cardiac or pulmonary diseases (1.7:1 vs. 1.2:1 and 1.7 vs. 0.8:1 respectively, P < 0.05). CONCLUSIONS: The majority of patients with significant PHT are elderly with heart disease. PVD without PPD and chronic PPD are a relatively uncommon cause of significant PHT. Since the diagnosis of PHT is of clinical significance and sometimes merits different therapeutic interventions, we recommend screening by Doppler echocardiography for patients with high risk background diseases.

Clinical efficacy and safety of fluticasone propionate 1 mg per day administered via a HFA 134a pressurized metered dose inhaler to patients with moderate to severe asthma. International study group.

This multi-national, double-blind, randomized, parallel-group study compared the efficacy and tolerability of fluticasone propionate 500 microg twice daily propelled either by the non-chlorofluorocarbon (CFC) propellant, hydrofluoroalkane (HFA) 134a, or the CFC propellants 11 and 12 used in the established pressurized metered dose inhaler (pMDI). The study period was 12 months and involved 412 subjects with moderate to severe asthma (HFA 134a pMDI: n = 203; CFC pMDI: n = 209). For the first 3 months, subjects kept a daily record card and attended the clinic every 4 weeks. Thereafter, they kept daily diaries for 2 weeks before each clinic assessment, which were performed at the end of 6, 9 and 12 months. Mean morning peak expiratory flow (PEF) increased during the first week in both treatment groups. By the end of week 12 the adjusted mean increase from baseline in morning PEF was 21 and 23 l min(-1) in the HFA 134a and CFC pMDI groups, respectively, and this increase was maintained throughout the 12-month study period. Similar improvements were detected in other diary card parameters and in clinic lung function measurements. The two groups were shown to be clinically equivalent in terms of all efficacy variables and there were no differences in tolerability. There were few reports of low serum cortisol levels during the 12-month study period, and serum cortisol levels were similar at baseline and after 12 weeks and 12 months of treatment in the two groups. In conclusion, the new HFA 134a fluticasone propionate pMDI is as effective and safe as the established CFC fluticasone propionate pMDI when used at a dosage of 1 mg day(-1).

Diffuse alveolar hemorrhage following thrombolytic therapy for acute myocardial infarction.

We describe a 66-year-old patient with hemoptysis, a drop in hematocrit, hypoxemia and new bilateral alveolar infiltrates after receiving streptokinase for acute myocardial infarction. Markedly increased carbon monoxide diffusion capacity suggested a diagnosis of alveolar hemorrhage. Underlying conditions included congestive heart failure. The patient recovered uneventfully within 7 days of conservative treatment. Alveolar hemorrhage is a rare and often unrecognized life-threatening complication of thrombolytic therapy. Particular attention should be paid to the pulmonary status of patients with congestive heart failure scheduled to receive thrombolytic therapy.

Recurrent, self-limited, menstrual-associated bronchiolitis obliterans organizing pneumonia.

A 39-year-old woman presented with recurrent acute illness, characterized by high-grade fever, pleuritic chest pain, and unilateral nodular infiltrate on chest radiograph. During the follow-up period, there were six similar episodes, each starting 2 to 3 days prior to her menstrual period and resolving within 5 to 10 days. Persistent symptoms in the seventh episode led us to perform an open lung biopsy; the specimen showed histologic changes compatible with the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). To the best of our knowledge, this is the first report describing BOOP in association with a menstrual period. This exceptional case emphasizes the wide and unexpected spectrum of this disease.

Laryngotracheobronchial involvement in a patient with nonendemic rhinoscleroma.

We report the first case of rhinoscleroma in an Israeli citizen, a former sailor with a transatlantic shipping company. Characteristic histologic changes from a tracheal biopsy and isolation of Klebsiella rhinoscleromatis from a blood culture after diagnostic bronchoscopy confirmed the diagnosis. Extreme delay in the diagnosis, a not uncommon feature in nonendemic areas, was associated with severe advanced laryngotracheobronchial disease. Treatment with quinolones was followed by significant improvement, but the patient died 1 month after presentation, apparently from upper airway obstruction.

Incidence of bacteraemia following fibreoptic bronchoscopy.

Guidelines for antibiotic prophylaxis of infective endocarditis prior to fibreoptic bronchoscopy, are based on only five studies, which showed a bacteraemia rate of <1% among 291 patients studied. T his study was designed to expand the current data regarding the frequency of bacteraemia following fibreoptic bronchoscopy. Aerobic and anaerobic cultures of venous blood and of lavage fluid were drawn from 200 consecutive patients undergoing fibreoptic bronchoscopy without respiratory infection or antibiotic treatment prior to the procedure. The true bacteraemia rate was calculated after excluding probable "contaminated" blood cultures. A possible correlation between type of procedure performed during the bronchoscopy and occurrence of bacteraemia was investigated. Positive blood cultures were noted following 26 bronchoscopy examinations. Coagulase negative Staphylococcus was found in the cultures of 18 patients, coagulase positive Staphylococcus in 3 patients, nonhaemolytic streptococci and a Klebsiella species in 2 patients each, and beta haemolytic streptococcus in one patient. After exclusion of 13 "contaminated" specimens the bacteraemia rate was 6.5% (13/200 patients). This study showed a bacteraemia rate of 6.5%, significantly higher than previously recognized in a cohort of patients undergoing fibreoptic bronchoscopy without either pulmonary infection or an unusually high rate of invasive procedures. These findings should be taken into account in future evaluations of recommendations for antibiotic prophylaxis of endocarditis.

Pleural empyema: An unusual presentation of esophageal perforation.

A 67-year-old patient presented with pleural empyema as the sole manifestation of thoracic esophageal perforation, 2 weeks after accidental fish bone ingestion. Nonspecific chest pain and general deterioration, unusual presenting symptoms in themselves, accounted for the extreme delay in the diagnosis. The empyema was treated surgically, and the esophageal perforation conservatively. Despite the poor prognostic factors, the patient recovered completely after 50 days in hospital.

Severe humoral hypercalcemia in primary isolated non-Hodgkin's lymphoma of the heart.

The etiology of hypercalcemia was investigated in a patient with primary isolated non-Hodgkin's lymphoma of the heart. There was no evidence of bone involvement, and parathyroid hormone and calciterol levels were suppressed. Plasma parathyroid-hormone-related protein (PTHrP 1-86) detected by immunoradiometric assay was increased (15 pmol/l compared with < 0.3 pmol/l in a control). We demonstrated that PTHrP was the humoral mediator of severe hypercalcemia in our patient.

Pulmonary lymphangioleiomyomatosis: prolonged survival despite multiple pregnancies and no hormonal intervention.

Pulmonary lymphangioleiomyomatosis (PLAM) is rare progressive, fatal interstitial lung disease, considered to be sex hormones related. We report a follow-up, after 19 years, in a patient with PLAM without intervention. Despite excessive oestrogen production during four pregnancies there was only mild deterioration of her respiratory disease. Patients with good functional reserve should be followed-up closely before deciding on hormonal ablative treatment.

Epidemiology and clinical spectrum of pneumococcal infections: an Israeli viewpoint.

We performed a prospective study of consecutive pneumococcal infections documented during a six-month period in our clinical microbiology laboratory. A total of 59 cultures obtained from clinically significant specimens of 58 patients were positive for Streptococcus pneumoniae. Relative penicillin resistance occurred in 14 strains (24%) and only one (1.7%) was highly resistant to penicillin (minimum inhibitory concentration = 2.0 micrograms ml-1). Resistance to common alternative drugs was not found. Serotypes were of a wide variety, however types 1, 7 and 14 predominated (60% of all blood culture isolates). Twenty-three patients with community-acquired infection required hospitalization. Nosocomial pneumonia developed in three additional cases (14%). Invasive disease was diagnosed in 24 patients with pneumonia representing the most common infection (22 patients). Pneumonia was characterized by a high incidence of serious underlying diseases (82%) and associated bacteraemia (68%). Compared with controls, patients with penicillin-resistant pneumococcal pneumonia had a significantly higher incidence of previous hospitalizations and use of antibiotics (57 vs. 7%, P = 0.02). The overall case fatality rate was high (36%) and did not differ significantly between patients with pneumonia due to resistant and susceptible strains. The epidemiology and clinical spectrum of serious pneumococcal infections in Israel is similar to those described in many parts of the world, but high level resistance to penicillin and to other alternative drugs is still rare.

Spontaneous renal subcapsular hematoma. An unusual presentation.

We report a 76-year-old patient with an unusual presentation of spontaneous renal subcapsular hematoma. The etiology of the bleeding remains unexplained after extensive workup including laparotomy and follow-up of 12 months.

Toxic multinodular goiter: a variant of autoimmune hyperthyroidism.

The aim of this study was to examine whether at least a subgroup of patients with toxic multinodular goiter may have autoimmune thyroid disease. Thyroid-stimulating immunoglobulin (TSI) activity, measured by a sensitive bioassay employing cultured human thyroid cells, was determined in patients with toxic multinodular goiter and other thyroid disorders. All patients with active Graves' disease (n = 47) had detectable serum TSI activity, whereas TSI was undetectable in patients with thyroid disease not believed to be of autoimmune origin: toxic adenoma (n = 13), cold nodule (n = 5), and nontoxic goiter (n = 19), with a single exception in the latter group. Toxic multinodular goiter (n = 26) was diagnosed based on clinical and laboratory evidence of hyperthyroidism associated with a multinodular goiter on palpation and scintiscan. The toxic multinodular goiter group was then subclassified according to scintiscan pattern (type A, diffuse but uneven distribution of technetium uptake; type B, multiple discrete nodules of varying size and function). All but 1 of the 11 TSI-positive toxic multinodular goiter patients had a type A scintiscan pattern. The patients with the type A scintiscan pattern were younger and more often had elevated antithyroid antibody titers, ophthalmopathy, and concurrent development of goiter and hyperthyroidism (rather than long-standing goiter preceding hyperthyroidism) compared to the type B patients. Thus, a subgroup of patients with clinically defined toxic multinodular goiter (type A) probably have autoimmune hyperthyroidism (a variant of Graves' disease), while in another subgroup (type B) hyperthyroidism is not related to an autoimmune etiology (a variant of toxic adenoma).