Tuberculous epididymo-orchitis and prostatitis: a case report.

The worldwide prevalence of tuberculosis (TB) is still high, remaining almost unchanged over the past century. The genitourinary tract belongs to one of the most common sites of extrapulmonary TB. Although rare, epididymal TB may be the only clinically evident location of infection. We present an unusual case of tuberculous epididymitis and prostatitis, demonstrating the need for insistent diagnostic procedures to confirm diagnosis. The treatment of choice is primarily medical, consisting of a combination of three or four anti-TB drugs, sometimes combined with surgery.

Fuzzy logic-based tumor marker profiles improved sensitivity of the detection of progression in small-cell lung cancer patients.

Tumor markers were used for disease monitoring in small-cell lung cancer patients. The aim of this study was to improve diagnostic efficiency in the detection of tumor progression in small-cell lung cancer patients by using fuzzy logic modeling in combination with a tumor marker panel (NSE, ProGRP, Tumor M2-PK, CYFRA 21-1, and CEA). Thirty-three consecutive small-cell lung cancer patients were included in a prospective study. The changes in blood levels of tumor markers and their analysis by fuzzy logic modeling were compared with the clinical evaluation of response versus non-response to therapy. Clinical monitoring was performed according to the standard criteria of the WHO. Tumor M2-PK was measured in plasma with an ELISA, all other markers were measured in sera. At 90% specificity, clinically detected tumor progression was found by the best single marker, NSE, in 32% of all cases. A fuzzy logic rule-based system employing a tumor marker panel increased the sensitivity significantly (P>0.0001) in small-cell carcinomas to 67% with the threemarker combination NSE/ProGRP/Tumor M2-PK and to 56% with the best two-marker combination ProGRP/Tumor M2-PK, respectively. An improvement of sensitivity was also observed using the two-marker combination of ProGRP/NSE (sensitivity 49%) or NSE/Tumor M2-PK (sensitivity 52%). The fuzzy classifier was able to detect a higher rate of progression in small-cell lung cancer patients compared with the multiple logistic regression analysis using the marker combination NSE/ProGRP/Tumor M2-PK (sensitivity 44%; AUC=0.76). With the fuzzy logic method and different tumor marker panels (NSE, ProGRP and Tumor M2-PK), a new diagnostic tool for the detection of progression in patients with small-cell lung cancer is available.

Altered fatty acid composition of lung surfactant phospholipids in interstitial lung disease.

Deterioration of pulmonary surfactant function has been reported in interstitial lung disease; however, the molecular basis is presently unclear. We analyzed fatty acid (FA) profiles of several surfactant phospholipid classes isolated from large-surfactant aggregates of patients with idiopathic pulmonary fibrosis (IPF; n = 12), hypersensitivity pneumonitis (n = 5), and sarcoidosis (n = 12). Eight healthy individuals served as controls. The relative content of palmitic acid in phosphatidylcholine was significantly reduced in IPF (66.8 +/- 2.5%; means +/- SE; P < 0.01) but not in hypersensitivity pneumonitis (78.5 +/- 1.8%) and sarcoidosis (78.2 +/- 3.1%; control 80.1 +/- 0.7%). In addition, the phosphatidylglycerol FA profile was significantly altered in the IPF patients, with a lower relative content of its major FA, oleic acid, at the expense of saturated FA. In the phosphatidylcholine class, a significant correlation between the impairment of biophysical surfactant function and decreased percentages of palmitic acid was noted. We conclude that significant alterations in the FA profile of pulmonary surfactant phospholipids occur predominantly in IPF and may contribute to the disturbances of alveolar surface activity in this disease.

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Quantitative detection of tumor M2-pyruvate kinase in plasma of patients with lung cancer in comparison to other lung diseases.

Lung cancer is one of the predominant causes of cancer death. The aim of this project is the development of a screening method in persons with high risk for developing lung cancer, based on the measurement of Tumor M2-pyruvate kinase (Tumor M2-PK). Tumor M2-PK is quantitatively detectable in ethylenediaminetetraacetic acid-plasma with a sensitive enzyme-linked immunosorbent assay. So far, 60 patients with newly diagnosed lung cancer were included. These were compared to 24 patients with acute inflammatory lung diseases, 56 patients with pneumoconiosis, 22 patients with obstructive airway diseases, and 28 healthy persons. Tumor patients and some individuals suffering from severe inflammatory lung diseases had significantly higher Tumor M2-PK concentrations in ethylenediaminetetraacetic acid-plasma than all the other groups. The histologic tumor type had no influence on the plasma levels of Tumor M2-PK. Tumor M2-PK concentrations correlate strongly with the tumor stage, showing significantly increasing concentrations with progressive tumor stages. The present data indicate that Tumor M2-PK could be a valuable tumor marker for the detection of lung cancer.

Comparison of the tumor markers tumor M2-PK, CEA, CYFRA 21-1, NSE and SCC in the diagnosis of lung cancer.

The study presents data comparing the new tumor marker Tumor M2-PK with CEA, CYFRA 21-1, NSE and SCC in the diagnosis of lung cancer. Tumor M2-PK is quantitatively detectable in EDTA-plasma with a sensitive ELISA. The results of the tumor marker test were compared with respect to the different histological tumor types and with the tumor staging. So far 144 newly diagnosed lung cancer patients were included. Significantly elevated tumor marker concentrations were found with progressive tumor stages. The best correlation with the tumor stage was observed for Tumor M2-PK and CYFRA 21-1. Comparison of the sensitivities in the detection of lung cancer indicated that the Tumor M2-PK-test (sensitivity: 58%) is more efficient than the CEA-Test (sensitivity: 39%) or CYFRA 21-1 (sensitivity: 48%). Generally higher sensitivity for non-small cell lung cancer only was shown for Tumor M2-PK (sensitivity: 65%), CEA (sensitivity: 42%) and CYFRA 21-1 (sensitivity: 58%). For small-cell lung cancer the marker NSE was more sensitive than all other markers. Initial follow-up studies indicate that Tumor M2-PK and CYFRA 21-1 can be used to monitor disease with tumor progression or regression during chemotherapy. The present data indicated that Tumor M2-PK could be a valuable tumor marker for the detection of lung cancer.

Surfactant abnormalities in idiopathic pulmonary fibrosis, hypersensitivity pneumonitis and sarcoidosis.

Bronchoalveolar lavage fluids (BALF) from patients with idiopathic pulmonary fibrosis (IPF; n=36), hypersensitivity pneumonitis (HP; n=32) and sarcoidosis (n=44) were investigated for their surfactant properties and compared to healthy control subjects (n=29). The phospholipid (PL) and protein concentration, the PL:protein ratio, PL subclasses, and the surfactant apoproteins (SP)A and SP-B were quantified in BALF. Large surfactant aggregates (LSA) were measured by means of ultracentrifugation and assayed for surface activity using the pulsating bubble surfactometer. As compared to controls, SP-A concentrations, LSA content and PL:protein ratios were significantly decreased in all groups, whereas PL and SP-B concentrations remained unchanged. Changes in the phospholipid profile, with reduced percentages of phosphatidylcholine (not significant) and phosphatidylglycerol and increased fractions of phosphatidylinositol and sphingomyelin (p<0.05), occurred more in IPF than in HP, and not in sarcoidosis. Surface activity was found to be severely impaired in IPF (minimum surface tension (gamma min) approximately 15-20 mN x m(-1)), but only modestly affected in HP and sarcoidosis (gamma min approximately 5 mN x m(-1)) compared to controls (gamma min approximately 0 mN x m(-1)). Reconstitution of pelleted surfactant material with soluble BALF proteins further increased gamma min values. In conclusion, moderate changes in biochemical and physical surfactant properties are encountered in hypersensitivity pneumonitis and sarcoidosis, but pronounced disturbances occur in idiopathic pulmonary fibrosis.

Expression of mucosa-related integrin alphaEbeta7 on alveolar T cells in interstitial lung diseases.

The expression of alphaEbeta7 integrin has been related to the selective retention of lymphocytes in mucosal tissues of gut, urogenital tract and lung. To identify potential disease-associated alphaEbeta7 expression patterns on cells accounting for lymphocytic alveolitis in interstitial lung disease (ILD), alphaE expression on CD4+ and CD8+ T cell subsets was evaluated by dual-colour flow cytometry in peripheral blood and bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF; n = 18), hypersensitivity pneumonitis (HP; n = 20) and sarcoidosis (n = 44) in comparison with healthy controls (n = 15). In both healthy individuals and all patient groups the proportion of alphaE-bearing T cells in peripheral blood was < 2%, whereas the vast majority of alveolar CD8+ T cells consistently co-expressed alphaE. Absolute alveolar CD8+alphaE+ cell numbers/ml were up to 30-fold increased in HP patients. Proportions of alphaE-bearing CD4+ cells in BALF were significantly elevated in IPF (74.0 +/- 2.7%) and HP (70.0 +/- 2.4%) compared with normals (30.0 +/- 1.8%) (mean +/- s.e.m.; P < 0.01). In sarcoidosis, the alphaE expression on BALF CD4+ cells displayed subgroup dependency: proportions significantly lower than normal were noted in chest radiographic stage I (14.3 +/- 1.5%), but increased proportions in stages II (50.0 +/- 3.8%) and III (64.0 +/- 4.8%). Correlations between common markers of T cell activation or BALF transforming growth factor-beta (TGF-beta ) bioactivity and alphaE expression were not noted. We conclude that the vast majority of alveolar CD8+ T cells consistently express alphaEbeta7 and that distinct patterns of alphaEbeta7 expression on alveolar CD4+ lymphocytes in sarcoidosis are related to the diverse manifestations of the sarcoid inflammatory process in the lung.

[Effect of microbial aerosols on the human]. / Wirkung von mikrobiellen Aerosolen auf den Menschen.

Based on numerous publications dealing with the effects of microbial emissions on workers in waste processing plants and on few papers concerning the assessment of the environmental health relevance of microbial aerosols on people living in the vicinity of composting facilities, the current state of the art in this field is presented. With regard to occupational exposure the possible health effects like infections, toxicity and allergies are specified. Since to date only few studies have been made of populations exposed to microbial aerosols in ambient air, the environmental health aspects are reviewed in the context of a study of three compost plants in Hesse, where ambient air measurements as well as epidemiological investigations were carried out. Final recommendations are given and the research needs regarding the environmental health significance of microbial aerosols are formulated.

[Detection of mycobacterial DNA from paraffin-embedded tissue in lung and lymphoid epithelial granulomas]. / Nachweis mykobakterieller DNA aus Paraffin-eingebettetem Lungen- und Lymphknotengewebe mit Epitheloidzell-Granulomen.

Standard techniques for the detection of mycobacteria in granulomatous diseases can be inadequate. We analysed 71 formalin fixed and paraffin-embedded tissue blocks from 68 non-immunocompromised patients with caseating, non-caseating, scarred, and miliary granulomas of lung and lymph nodes. A reamplification PCR protocol was established to detect a 123 bp product of the repetitive insertion sequence IS986/IS6110. After exclusion of 6 PCR-negative cases with clinical sarcoidosis 97% of lung tissue blocks with more than 10% caseating and non-caseating granulomas contained mycobacterial DNA. By routine microbiology mycobacteria could be detected in 78% of the patients. Scarred granulomas were PCR-negative. All miliary granulomas were PCR-positive. Lymph nodes showed comparable results. We think that this method facilitates aetiologic analysis of granulomatous diseases especially when the suspicous tissue is fixed and microbiology is not available.

[Delayed hypersensitivity to protamine and immediate hypersensitivity to insulin]. / Protaminallergie vom Spättyp und Insulinallergie vom Soforttyp.

A 63-year-old female, with type II diabetes mellitus, diagnosed in 1967, was started on combination therapy with sulphonylureas and human depot insulin in May 1989, because of inadequate blood sugar control with sulphonylureas alone. Within 3 months she began to develop nodular skin reactions at the site of injection, 12-24 hours after insulin injections. Intradermal testing demonstrated delayed (Gell and Coombs type IV) hypersensitivity to protamine. No specific IgE or IgG antibodies were demonstrable. She was changed to protamine-free human delayed action insulin. After an initial reaction-free period, red urticarial lesions, attributable to immediate (Gell and Coombs type I) hypersensitivity to human insulin, appeared at the injection sites. There were no other complications with continued insulin therapy, and after about 6 weeks no further local reactions were detectable. When an allergic reaction to an insulin preparation is suspected, careful immunological investigation should be performed, to ensure adequate treatment without risk to the patient.

[Recurrent hypoglycemia in the insulin autoimmune syndrome]. / Rezidivierende Hypoglykämien bei Insulin-Autoimmunsyndrom.

A 72-year-old man with recurrent hypoglycaemia was suspected of having an insulinoma. But several diagnostic methods (computed tomography; mesenteric and coeliac angiography; sella imaging) did not reveal any tumour. 72-hour hunger test did not precipitate any spontaneous hypoglycaemia. A falling insulin-glucose ratio spoke against an insulin-producing tumour. Reactive symptomatic hypoglycaemia occurred 4.5 hours after an oral glucose test. Measurement of insulin concentration demonstrated a slow but pronounced increase (3500 microU) over an already raised initial value (816 microU/ml), typical of prediabetic metabolic regulation. Demonstration of insulin autoantibodies confirmed the diagnosis of an insulin autoimmune syndrome, which has a good prognosis. The patient became free of symptoms on a regimen of frequent small, carbohydrate-poor but fat and bulk-rich meals. Hypoglycaemia recurred when the diet was not observed.

[Insulin and immunology--a correlation]. / Insulin und Immunologie--eine Wechselbeziehung.

In comparison to former decenniums the relations between insulin and immunology have changed and continued to develop. Still up to 20 years ago the immunological side effects of an insulin therapy stood well to the fore concerning the clinical interest, nowadays, however, they are the autoantibodies against insulin and it is the role of insulin for a functioning immune system, which is not in the least exactly recognized.

[Onset of Wegener's granulomatosis with skin and joint symptoms]. / Beginn einer Wegenerschen Granulomatose mit Haut- und Gelenksymptomatik.

A 54-year-old female presenting with arthralgias, weight loss, and anemia developed Raynaud's phenomenon and subcutaneous nodules at her hands. Granulomatous inflammation was observed in biopsies taken from her hands and sinuses, and later on the patient suffered from glomerulonephritis. The diagnosis Wegener's granulomatosis was further supported by detection of anticytoplasmic antibodies.

[Characteristics of lung function in patients with type I diabetes mellitus]. / Lungenfunktionscharakteristika bei Patienten mit Diabetes mellitus Typ I.

Employing routine clinical methods, the pulmonary function of 21 type 1 diabetics prior to and after exercise, was examined. In type 1 diabetics, at the time of the manifestation of the disorder, a reversible, seemingly metabolism-related emphysematous expansion was to be seen. In comparison with a control group and diabetics with no late complications, type 1 diabetics with secondary complications proved to have a significantly reduced vital and total capacity with relative hyperexpansion; an obstructive ventilation disorder was not demonstrable. These results are confirmed by those reported in the literature, and suggest the existence of a diabetic pneumopathy.

[Hemodynamic and lung function analytic findings in so-called collagen diseases]. / Hämodynamische und lungenfunktionsanalytische Befunde bei sogenannten Kollagenosen.

Twenty-four patients with connective tissue disease as defined by ARA criteria were submitted to a thorough cardiological and pulmonary diagnostic evaluation. Mean pulmonary arterial pressure was elevated in 54 per cent of the patients, a left-ventricular functional disorder taking the form of elevated pulmonary capillary occlusive pressure was almost equally as frequent. Interindividual comparisons suggest only a low progressivity of the cardiac involvement, while pulmonary involvement progresses rapidly, to become the prognostically predominating factor. This suspicion must be checked by performing follow-up examinations with repeated cath. examinations of the right heart in individual patients. In common with ACE determinations, haemodynamically effective pericardial disorders are of no significance in connective tissue diseases. Patients with "collagenosis" should be submitted to right-heart catheterisation early on. Attempts at therapy taking the form of aggressive treatment of the underlying disease or administration of nitrates or calcium antagonists, would appear meaningful.

[Churg-Strauss syndrome]. / Churg-Strauss-Syndrom.

The Churg-Strauss syndrome, or allergic angiitis and granulomatosis of the lungs, is one of the systemic vasculitides with predominantly involvement and an unclear genesis. The clinical picture is characterized by a combination of intrinsic bronchial asthma, eosinophila with elevated IgE, and systemic vasculitis of the small blood vessels. Apart from the lungs, other organ systems may also be involved. We report, here, on a case, observed for a period of eight months, that showed complete remission under treatment with corticosteroids.

[Effect of histamine on bronchial hyperreactivity in sarcoidosis and other lung diseases]. / Einfluss des Histamins auf die bronchiale Hyperreaktibilität bei Sarkoidosen und anderen pulmonalen Erkrankungen.

Bronchial hyperreactivity is the central symptom of bronchial asthma which, however, can also be observed in various other diseases affecting the lungs and bronchi, such as, for example, sarcoidosis. In response to unspecific inhalative provocation, obstruction of the bronchi occurs; a genetic predisposition is thought to be involved. During this reaction, histamine is released by various cells, predominantly mast cells. In comparison with normal subjects, patients with bronchial asthma, sarcoidosis or a hyperreactive bronchial system are found to have significantly higher basal plasma levels if histamine. In response to unspecific provocation with acetylcholine and Carbachol, significantly higher histamine levels are observed in bronchial asthma and sarcoidosis. Although an increase is also observed in normal subjects and hyperreactives, it is appreciably lower than in the other two groups of patients. In contrast to asthmatics and patients with sarcoidosis, in particular in patients with hyperreactivity, a significant increase in plasma histamine is found following ergometer exercise. These results show that endogenous histamine is liberated by provocation challenges in various diseases, and may have a possible influence on bronchial obstruction.