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Micha T Maeder,1 Otto D Schoch,2 Hans Rickli1 1Department of Cardiology, 2Department of Respiratory Medicine, Kantonsspital St Gallen, St Gallen, Switzerland Abstract: Obstructive sleep apnea (OSA) is associated with cardiovascular risk factors, cardiovascular diseases, and increased mortality. Epidemiological studies have established these associations, and there are now numerous experimental and clinical studies which have provided information on the possible underlying mechanisms. Mechanistic proof-of-concept studies with surrogate endpoints have been performed to demonstrate that treatment of OSA by continuous positive airway pressure (CPAP) has the potential to reverse or at least to attenuate not only OSA but also the adverse cardiovascular effects associated with OSA. However, no randomized studies have been performed to demonstrate that treatment of OSA by CPAP improves clinical outcomes in patients with cardiovascular risk factors and/or established cardiovascular disease and concomitant OSA. In the present review, we summarize the current knowledge on the role of OSA as a potential cardiovascular risk factor, the impact of OSA on cardiac function, the role of OSA as a modifier of the course of cardiovascular diseases such as coronary artery disease, atrial fibrillation, and heart failure, and the insights from studies evaluating the impact of CPAP therapy on the cardiovascular features associated with OSA. Keywords: obstructive sleep apnea, cardiovascular, risk, heart failure, atrial fibrillation, hypertension

In December 2022, based on the assessment of new evidence, the World Health Organization (WHO) updated its guidelines for the treatment of drug-resistant tuberculosis (TB). The evaluation of both, these recommendations, and the latest study data, makes it necessary to update the existing guidelines on the treatment of at least rifampicin-resistant tuberculosis for the German-speaking region, hereby replacing the respective chapters. A shortened MDR-TB treatment of at least 6 month using the fixed and non-modifiable drug combination of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) is now also recommended for Germany, Austria, and Switzerland under certain conditions. This recommendation applies to TB cases with proven rifampicin resistance, including rifampicin monoresistance. For treatment of pre-extensively drug resistant TB (pre-XDR-TB), an individualized treatment for 18 months adjusted to resistance data continues to be the primary recommendation. The non-modifiable drug combination of bedaquiline, pretomanid, and linezolid (BPaL) may be used alternatively in pre-XDR TB if all prerequisites are met. The necessary prerequisites for the use of BPaLM and BPaL are presented in this amendment to the S2k guideline for 'Tuberculosis in adulthood'., Competing Interests: Informationen zu Interessenkonflikten finden Sie auf den Seiten der AWMF (http://www.awmf.org/leitlinien/awmf-regelwerk.html)., (Thieme. All rights reserved.)

In Germany tuberculosis is a rare disease and usually well treatable. Worldwide it is one of the most common infectious diseases with approximately 10 million new cases every year. Even with low incidences in Germany, tuberculosis is an important differential diagnosis especially due to international developments and migration movements. With a decreasing experience there's a continuous demand on accurate and up-to-date information. This guideline covers all aspects of microbiological diagnostics, basic principles of standard therapy, treatment of extrapulmonary tuberculosis, management of side effects, special features of diagnosis and treatment of resistant tuberculosis, and treatment in TB-HIV coinfection. Also, it explains when treatment in specialized centers is required, aspects of care and legal regulations and the diagnosis and preventive therapy of latent tuberculosis infection. The update of the S2k guideline "Tuberculosis in Adults" is intended to serve as a guideline for prevention, diagnosis, and treatment of tuberculosis for all those involved in tuberculosis care and to help meet the current challenges in dealing with tuberculosis in Germany., Competing Interests: Eine Übersicht der Interessenkonflikte findet sich im Internet unter http://awmf.org; AWMF-Registriernummer 020-019, (Thieme. All rights reserved.)

History: We report on a 35-year-old male patient who presented to the emergency department a day after celebrations. The night before, the alcoholized patient tried to spit fire with an oily fuel paste. A fever, dyspnea and chest pain were present., Findings and Diagnosis: The patient is febrile, but in reduced general conditions. In laboratory chemistry shows elevated inflammatory parameters. Due to the conventional radiology findings we completed the diagnostic with a CT-scan, which shows confirmed streaky opacities, especially in the middle lobe., Diagnosis: Based on the very suggestive history and diagnostic findings, a fire eater's lung was diagnosed., Therapy and Course: Under treatmen with CoAmoxicillin, oxygen, inhalation with Ipratropiumbromid/Salbutamol and symptomatic treatment, we could reach a clinical improvement and discharged within three days., Conclusion: Aspiration of oily fuel paste led to lipoid pneumonia. Few such cases have been described so far, but the medical history, symptoms and radiological imaging are very characteristic. Antibiotic therapy is not primarily necessary, however, depending on the clinical condition may help to prevent bacterial superinfection. The administration of systemic steroids is controversial in this situation., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups., Objective: To provide long-term data of the Swiss PH registry of 1998-2012., Methods: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012., Results: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy., Conclusion: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications., (© 2015 S. Karger AG, Basel.)

High altitude periodic breathing (PB) shares some common pathophysiologic aspects with sleep apnea, Cheyne-Stokes respiration and PB in heart failure patients. Methods that allow quantifying instabilities of respiratory control provide valuable insights in physiologic mechanisms and help to identify therapeutic targets. Under the hypothesis that high altitude PB appears even during physical activity and can be identified in comparison to visual analysis in conditions of low SNR, this study aims to identify PB by characterizing the respiratory pattern through the respiratory volume signal. A number of spectral parameters are extracted from the power spectral density (PSD) of the volume signal, derived from respiratory inductive plethysmography and evaluated through a linear discriminant analysis. A dataset of 34 healthy mountaineers ascending to Mt. Muztagh Ata, China (7,546 m) visually labeled as PB and non periodic breathing (nPB) is analyzed. All climbing periods within all the ascents are considered (total climbing periods: 371 nPB and 40 PB). The best crossvalidated result classifying PB and nPB is obtained with Pm (power of the modulation frequency band) and R (ratio between modulation and respiration power) with an accuracy of 80.3% and area under the receiver operating characteristic curve of 84.5%. Comparing the subjects from 1(st) and 2(nd) ascents (at the same altitudes but the latter more acclimatized) the effect of acclimatization is evaluated. SaO(2) and periodic breathing cycles significantly increased with acclimatization (p-value < 0.05). Higher Pm and higher respiratory frequencies are observed at lower SaO(2), through a significant negative correlation (p-value < 0.01). Higher Pm is observed at climbing periods visually labeled as PB with > 5 periodic breathing cycles through a significant positive correlation (p-value < 0.01). Our data demonstrate that quantification of the respiratory volume signal using spectral analysis is suitable to identify effects of hypobaric hypoxia on control of breathing.

Tuberculosis control activities focus on identification and treatment of sputum smear positive tuberculosis patients. As soon as these patients can be treated, they not only have an optimal chance for cure, they also no longer spread Mycobacterium tuberculosis (M.tb) in the community. Screening is a systematic search for tuberculosis disease, often performed by radiological or by sputum smear examinations. On the other hand, Screening for Infection with M.tb is with immunological tests. Persons infected with M.tb have an increased risk to develop active tuberculosis in the future. Screening for infection is recommended in tuberculosis contact tracing and in several risk groups for the progression to tuberculosis disease, specifically before the start of immunosuppressive therapy with tumor necrosis factor antagonists or in transplant recipients. Several immunological tests are available. If compared to the traditional in vivo Mantoux tuberculin skin test, in vitro blood tests called Interferon Gamma Release Assays (IGRA) are more specific because the cell wall antigens used for the tests are not present in the wall of Bacille Calmitte Guerin BCG and most atypical mycobacteria. Another advantage of IGRA is the mitogen positive control, which detects unreliable tests in immunodeficiency. Persons found to be infected with M.tb are treated with prophylactic isoniacid for 9 months.

Principles: Data on changes of haemostatic parameters at altitudes above 5000 m are very limited. So far it is unknown, whether altered coagulation could contribute to the development of acute mountain sickness., Methods: Thirty four healthy mountaineers were randomised to two acclimatisation protocols and undertook an expedition on Muztagh Ata (7549 m) in China. Tests were performed at five altitudes up to 6865 m. Haemostatic parameters, such as PT, aPTT, D-Dimer, APC-Resistance (APCR), von Willebrand Factor activity (RCo), ADAMTS-13 & C-Natriuretic Peptide (CNP) were assessed together with Lake Louise AMS score., Results: D-Dimer significantly increased with increasing altitude (median 0.62 to 0.81 mcg/L, p <0.0001). During ascent, PT increased (83% to >100%) and APCR decreased significantly from 0.95 to 0.8 (p <0.01). Furthermore, a significant increase of aPTT (38 to 43 sec) was paralleled by significant changes of RCo (102% to 62%) (both p <0.001). There were no significant changes in ADAMTS-13 and CNP. No significant relationship between investigated parameters and AMS scores could be detected. When comparing the participants of the two acclimatisation protocols, there was an overall higher RCo in patients with a faster ascent protocol (p = 0.04). This was accompanied by lower ADAMTS-13 of the coagulation system in these patients (p = 0.04)., Conclusions: Coagulation parameters change significantly during hypobaric hypoxia. Whereas we could detect no association between AMS scores and coagulation parameters, our results do show some parameters to be associated with an acclimatisation protocol and a successful ascent to the summit.

Setting: Treatment of tuberculosis (TB) is critically dependent on adherence. Directly observed treatment (DOT) has been shown to be effective., Objective: To determine operational treatment outcome using administrative treatment monitoring (ATM) to assess the need for more vigorous promotion of DOT., Design: Cohort study in eastern Switzerland, where ATM was started in 2002. Bi-monthly progress forms and a treatment outcome form (after 6 months) were sent to the treating doctors. Forms not returned within 6 weeks were followed up with phone calls., Results: Between 2002 and 2004, 98 (87.5%) of 112 new TB patients completed a 6-month treatment course. Eight elderly patients died of causes other than TB while on treatment, four travelled out of the region and two were lost to follow-up. Treating doctors opted for DOT in only seven cases., Conclusion: Given the high success rate of 87.5% in our cohort, more vigorous promotion of DOT is not a priority for TB case management in eastern Switzerland. In our setting, ATM in collaboration with the family doctors offers a valuable alternative to the more time-consuming universal DOT.

Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised histologically by an intra-alveolar accumulation of fine granular eosinophilic and periodic acid-Schiff positive material. In a retrospective study, the composition of the intra-alveolarly accumulated material of adult patients with PAP was analysed by means of immunohistochemistry and Western blotting. In patients with PAP, the current authors found an intra-alveolar accumulation of surfactant protein (SP)-A, precursors of SP-B, SP-B, variable amounts of mono-, di-, and oligomeric SP-C forms, as well as SP-D. Only in one patient was a precursor of SP-C detected. By means of immuno-electron microscopy, the current authors identified not only transport vesicles labelled for precursors of SP-B and SP-C, but also transport vesicles containing either precursors of SP-B or SP-C in type-II pneumocytes in normal human lungs. It is concluded that pulmonary alveolar proteinosis in adults is characterised by an intra-alveolar accumulation of surfactant protein A, precursors of surfactant protein B, and surfactant proteins B, C and D. The current data provide evidence that not only an impairment of surfactant clearance by alveolar macrophages, but also an abnormal secretion of transport vesicles containing precursors of surfactant protein B (but not surfactant protein C) and an insufficient palmitoylation of surfactant protein C, which may lead to the formation of di- and oligomeric surfactant protein C forms, play a role in the pathogenesis of pulmonary alveolar proteinosis.

Background: The microbiological analysis of respiratory specimens is the most reliable approach to diagnose active pulmonary tuberculosis., Patient and Methods: We report a 60-year-old female patient (index patient) who underwent diagnostic bronchoscopy for chronic cough. No acid-fast bacilli were detected in bronchial washings. Although cough subsided with symptomatic treatment, Mycobacterium tuberculosis grew on egg-based media after 12 weeks. A false-positive culture result was suspected. Chart review and DNA fingerprinting were carried out., Results: The bronchoscope used to examine the index patient was previously used for a 30-year-old patient (source patient) with smear- and culture-positive pulmonary tuberculosis. Restriction fragment length polymorphism (RFLP) analysis based on the IS 6110 element confirmed that the two strains were identical., Conclusion: Cross-contamination is a reason for false-positive cultures with M. tuberculosis and should be suspected in patients with a low clinical probability for active tuberculosis.

Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM-CSF in patients with idiopathic AP. Fourteen patients received 5 microg/kg/d GM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]DO2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 microg/kg/d GM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 microg/kg/d GM- CSF, and one of four patients responded after dose escalation (20 microg/kg/d). The overall response rate was 43% (mean improvement in [A-a]DO2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM- CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

Previously, we reported the specific occurrence of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid from 11 Japanese patients with idiopathic pulmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence of the autoantibody is not limited to the Japanese patients, we examined sera from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detection of the autoantibody in sera can be used for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis of I-PAP, we developed a novel latex agglutination test using latex beads coupled with recombinant human GM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determined by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 40 normal subjects. These results establish that the latex agglutination test is a reliable method for serological diagnosis of I-PAP with high sensitivity (100%) and specificity (98%).

Background: Osteonecrosis is a known complication after transplantation of solid organs. The incidence of osteonecrosis after lung transplantation is not well documented., Methods: We investigated the incidence of symptomatic osteonecrosis in lung transplant recipients, transplanted between November 1992 and June 1998 at our institution. For the detection of osteonecrosis, all patients complaining of musculoskeletal pain underwent magnetic resonance imaging. Demographic characteristics, time after transplantation, etiology of underlying lung disease, and the number of steroid pulses for rejection episodes were compared for patients with and without osteonecrosis., Results: Of 63 transplant recipients, all 49 with a follow-up of >3 months were included for analysis. Of seven symptomatic transplant recipients, five cases of osteonecrosis (10%) were detected at a median duration of 216 days (range 44-600) after transplantation. Patients with osteonecrosis have been treated with the same immunosuppressive regimen and with an equal number of steroid pulses for acute rejection episodes (1.4+/-1.1 vs. 1.4+/-1.5, P=0.69), but were younger (26+/-8 vs. 40+/-11 years, P<0.01) than other transplant recipients. Symptomatic osteonecrosis was detected in four of 14 patients (29%) with cystic fibrosis (CF), compared with one osteonecrosis among 35 patients (3%) with other underlying diseases (P<0.02). Within the group of CF patients, specific clinical and demographic characteristics correlating with the risk for subsequent osteonecrosis could not be found., Conclusion: In lung transplant recipients, CF may be a risk factor for the development of symptomatic osteonecrosis.

Guidelines for the control and prevention of nosocomial tuberculosis include recommendations for surveillance of hospital employees with tuberculin skin tests (TST). We analysed a 2 1/2-year period of tuberculin skin testing at Kantonsspital St. Gallen, an 850-bed hospital in eastern Switzerland with 2000 employees and 21,000 admissions yearly. Tuberculosis cases among employees are reported for a 10-year period. TST were performed on engagement, if no recent positive result was available. A new TST was read in 717 (58%) of 1241 persons starting employment during the study period. In 261 workers in contact with 23 sputum smear positive tuberculosis patients, 180 (69%) follow-up TST were performed. Of a total of 37 increases in TST, 20 (54%) were retrospectively attributed to other causes than a recent infection with M. tuberculosis (vaccination with BCG, booster phenomenon, doubts concerning the previous test result). Of the remaining 17 TST converters, 5 finally completed a full course of preventive chemotherapy. With a total workload of 547 hours for this result, half a year's working hours were necessary to prevent one case of active tuberculosis. Over a 10-year period, 4 out of 9 active tuberculosis cases in employees were likely to be nosocomially acquired, but none was diagnosed thanks to TST surveillance. We conclude that surveillance with TST is time consuming, but has little impact on the tuberculosis situation in hospital employees. Alternative strategies to this unsatisfactory system are discussed.

Background: The Epworth Sleepiness Scale (ESS) is a questionnaire widely used in English speaking countries for assessment of subjective daytime sleepiness., Objective: Our purpose was to translate and validate the ESS for use in German-speaking countries., Methods: A German translation of the ESS was administered to 159 healthy German-speaking Swiss and to 174 patients with various sleep disorders., Results: The mean +/- SD of ESS scores in normals was 5.7+/-3.0, in patients it was 13.0+/-5.1 (p<0.001). Scores were not correlated with age or gender but with the percentage of time spent at an oxygen saturation <90% (R = 0.35, p<0.001), and the respiratory disturbance index (R = 0.26, p<0.001) in primary snorers and sleep apnea patients. Item analysis confirmed internal consistency of the scale (Cronbach alpha = 0.60 in normals, and 0.83 in patients). Follow-up scores in 25 sleep apnea patients on treatment showed a reduction by 7+/-5 points (p<0.05)., Conclusions: Our data validate the ESS for application in German-speaking populations. The simplicity, reliability and the apparent lack of relevant influences of language and cultural background on performance of the ESS makes it a valuable tool for clinical management and research.

The pathogenesis of acquired pulmonary alveolar proteinosis (PAP), a rare lung disease characterized by excessive surfactant accumulation within the alveolar space, remains obscure. Gene-targeted mice lacking the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) or the signal-transducing beta-common chain of the GM-CSF receptor have impaired surfactant clearance and pulmonary pathology resembling human PAP. We therefore investigated the hematopoietic effects of GM-CSF in patients with PAP. The hematologic response of 5 infants with congenital PAP to 5 microgram/kg/d was of normal magnitude. By contrast, despite normal expression of GM-CSF receptor alpha- and beta-common chains on peripheral blood myelomonocytic cells (n = 6) and normal binding affinity of bone marrow mononuclear cells for GM-CSF (n = 3), each of the 12 patients with acquired PAP treated displayed impaired responses to GM-CSF; 5 microgram/kg/d produced only minor eosinophilia, and doses of 7.5 to 20 microgram/kg were required to induce >/=1.5-fold neutrophil increments in the 3 patients who underwent dose-escalation. However, neutrophilic responses to 5 microgram/kg granulocyte colony-stimulating factor (G-CSF) were normal (n = 4). In vitro, the proportion of hematopoietic progenitors responsive to GM-CSF (16.1% +/- 8.9%; P = .042) or interleukin-3 (IL-3; 19.3% +/- 7.7%; P = .063), both of which utilize the beta-common chain of the GM-CSF receptor complex, were reduced among patients with acquired PAP (n = 4) compared with normal bone marrow donor controls (47.2% +/- 25.9% and 40.9% +/- 18.6%, respectively). In the one individual who had complete resolution of lung disease during the period of study, this was temporally associated with correction of this defective in vitro response to GM-CSF and IL-3 on serial assessment. These data establish that patients with acquired PAP have an associated impaired responsiveness to GM-CSF that is potentially pathogenic in the development of their lung disease. Based on these observations, we propose a model of the pathogenesis of acquired PAP that suggests the disease arises as a consequence of an acquired clonal disorder within the hematopoietic progenitor cell compartment., (Copyright 1998 by The American Society of Hematology.)

Five patients with adverse reactions to peak flow monitoring are presented: 2 patients had herniation of abdominal content, while the others presented with vasovagal syncope, minor depression and neurotic preoccupation with peak flow values, respectively. As a result, 3 of the 5 patients became noncompliant. For nonpsychological somatic adverse reactions, we calculated an incidence of 1.1 cases/1,000 patients started on peak flow monitoring. Adverse reactions with a psychological background may be more frequent. Clinicians should bear in mind that patients noncompliant with peak flow monitoring may have discontinued because of adverse reactions.

Interstitial lung disease (ILD) is a complication of polymyositis (PM) and dermatomyositis (DM). It often manifests itself in association with myositis-specific antisynthetase autoantibodies, among which anti-Jo-1 antibodies are the most commonly encountered. In contrast, ILD associated with anti-Jo-1 antibodies without muscle involvement is rare and not well characterized. We report four patients presenting with ILD associated with anti-Jo-1 antibodies. Histological findings of transbronchial biopsies disclosed a pattern consistent with nonspecific interstitial pneumonitis, a CD8+ lymphocytosis was found in bronchoalveolar lavage. Only one of these patients developed an "antisynthetase syndrome" with PM, after nearly 2 yrs of severe ILD. The clinical conditions of all four cases showed stabilization or improvement when cyclosporine was added to their immunosuppressive treatment. These cases confirm that a CD8+ lymphocytic interstitial lung disease may be the first, and sole manifestation of autoimmune disease associated with anti-Jo-1 antibodies. Furthermore, they suggest that this form of interstitial lung disease apparently has a poor response to steroids and cytotoxic drugs, but may respond to moderate doses of cyclosporine and azathioprine in addition to low doses of steroids.

In Africa, a rapid increase of human immunodeficiency virus (HIV)-associated tuberculosis cases has been observed; 80% of a worldwide 6 million dually infected persons live in this part of the world. The annual risk of progression to clinically overt tuberculosis in dually infected persons approaches the lifetime risk in persons with tuberculosis but no HIV infection. Zimbabwe is an example which illustrates the rapid increase in notified tuberculosis cases since 1985, accounted for primarily by HIV-associated tuberculosis cases. In sputum-smear positive HIV-associated tuberculosis, classical symptoms are reported with the same frequency as in HIV negative cases. Thus, case-finding activities need not be altered. In sputum-smear negative patients, reliable diagnostic tests are not available. Therapeutic trials are widely used and this causes overdiagnosis of tuberculosis. Extrapulmonary manifestations are common in HIV-associated tuberculosis. A majority of lymph node enlargements, pleurisy and pericarditis in Africa are now due to tuberculosis. If compliance is ensured, response to chemotherapy is excellent, but overall case fatality and relapse rates are increased. The cost-effectiveness of tuberculosis control programmes using directly observed therapy for at least the first 2 months of treatment is well established. With the prominent global significance of tuberculosis and the possibility of cost-effective interventions, a commitment to the fight against the worldwide epidemic is more important than ever before.

Treating chronic Pseudomonas infection of the bronchial tree is a very important part of the treatment strategy in patients with cystic fibrosis. There are only a few antibiotics which are effective against pseudomonas. Many of them soon lead to bacterial resistance (e.g. fluoro-quinolones). Inhaling antibiotics produces high sputum concentrations and low systemic toxicity. Tolerance is good and resistance rare. Several clinical studies, some of them doubleblind placebo controlled, have shown a positive effect of inhaled antibiotics on symptoms, on frequency of necessary i.v. therapies and also on pulmonary function. Most commonly aminoglycosides (tobramycin) and colistin, which is not yet registered in Switzerland, are used. The main indication is chronic therapy of Pseudomonas infection.

Human immunodeficiency virus (HIV) infection has a large impact on tuberculosis in Africa. In this study, the prevalence of HIV infection in a population of hospitalized tuberculosis patients in Zimbabwe was determined and demographic characteristics, clinical signs and symptoms, as well as radiographic appearance were compared in tuberculosis patients with and without HIV infection. During a 5 month observation period, information on tuberculosis patients referred to Driefontein Tuberculosis Sanatorium, Mvuma, Zimbabwe was collected, computerized and analysed with commercially available software. Of 467 patients admitted, 255 were sputum smear positive for acid-fast bacilli. Of 196 patients with complete information, 127 (65%) were HIV-seropositive. When compared to the 69 HIV-seronegative patients, HIV-infected patients were not different in age, gender, the period of delay between the onset of symptoms and diagnosis, radiographic appearance, history of previous antituberculosis treatment and symptoms and signs reported, with the exception of herpes zoster and other sexually-transmitted disease. The prevalence of HIV infection in our population of tuberculosis patients was large. However, since demographic and clinical characteristics are remarkably similar in tuberculosis patients with and without HIV infection, case-finding activities need not be altered in the wake of the HIV epidemic.

Together with three of our own observations of intramural rupture (IRO) or hematoma (IHO) of the esophagus, we have analyzed 91 case reports from the literature. Precipitating factors were identified in 63% of all patients. Most frequently potentially traumatic events such as vomiting (22%) or instrumentation (17%) preceded IRO/IHO. In 21% there were disturbances of hemostasis, either alone (15%) or in addition to a traumatic event (6%). 37% of IRO/IHO were spontaneous. In 35% the typical clinical triad of acute retrosternal pain, odynophagia or dysphagia and hematemesis was complete; in 46% only two out of three symptoms were present. IRO/IHO was managed conservatively in 84% of the patients, whereas 9% required surgery for complications. 7% were operated on without a precise indication. One patient died following surgery for endoscopic perforation. The rare syndrome of IRO/IHO must be considered in patients with acute retrosternal pain. Treatment is primarily conservative and the prognosis is excellent.

In a sample of 4358 male joggers (= 76.1% of the participants in a popular 16 km race in Berne 1984) 45.8% of joggers sustained running-related injuries during a one year period. 14.2% sought medical help and 2.3% missed work because of jogging injuries. The most important factor in running-related injuries is (average) weekly mileage. Joggers see the doctor less often than the reference population, although this difference cannot be attributed directly to jogging. Increasing mileage is associated with more frequent visits to the doctor, and this increased frequency of medical consultations is due entirely to jogging-related injuries.