Vacuum-assisted closure therapy of paradoxical reaction in tuberculous lymphadenopathy caused by Mycobacterium africanum.

A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli with a positive PCR for Mycobacterium tuberculosis complex. After debridement, vacuum-assisted closure therapy was performed for 6 weeks. Five months after the beginning of antituberculous therapy, a second paradoxical reaction occurred, with painful swelling of two contralateral supraclavicular lymph nodes. Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the culture was negative. Antituberculous treatment was continued, and additional treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks was introduced, resulting in a decrease in lymphadenopathy. Antituberculous treatment was continued for a total of 9 months. The outcome was favorable, no further lymphadenopathy occurred over the following 6 months.

[Travel-associated pneumonias]. / Pneumonien mit Reiseanamnese.

Respiratory infections are responsible for up to 11% of febrile infections in travellers or immigrants from tropical and subtropical regions. The main pathogens are the same as in temperate climate zones: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, influenza viruses, Legionella pneumophila. However, some pulmonary diseases can be attributed to bacterial, parasitic, viral or fungal pathogens that are endemic in tropical and subtropical regions. The most commonly imported infections are malaria, dengue, and tuberculosis. Pulmonary symptoms and eosinophilia in returning travellers and migrants may be caused by several parasitic infections such as Katayama syndrome, Loeffler syndrome, tropical pulmonary eosinophilia, amebiasis, paragonimiasis, echinococcosis, and toxocariasis. In Asia, Tsutsugamushi fever is transmitted by chiggers, spotted fever rickettsiae are transmitted by ticks. Transmission of zoonotic diseases occurs mainly via contact with infected animals or their excretions, human-to-human transmission is generally rare: MERS-CoA (dromedary camels), pulmonary hantavirus infection (rodents), tularemia (rabbits and hares), leptospirosis (rats), Q-fever (sheep and goats), very rarely anthrax (hides of ruminants) and pest (infected rats and wildlife). Inhalation of contaminated dust can cause infections with dimorphic fungi: histoplasmosis (bat guano) and coccidioidomycosis in America and parts of Africa, blastomycosis in America. Some infections can cause symptoms years after a stay in tropical or subtropical regions (melioidosis, tuberculosis, histoplasmosis, schistosomiasis-associated pulmonary hypertension). Noninfectious respiratory diseases caused by inhalation of high amounts of air pollution or toxic dusts may also be considered.

Ciprofloxacin reduces the risk of hemolytic uremic syndrome in patients with Escherichia coli O104:H4-associated diarrhea.

BACKGROUND: Whether antibiotic treatment in patients with enterohemorrhagic Escherichia coli (EHEC)-associated diarrhea influences the risk of hemolytic uremic syndrome (HUS) has still to be elucidated. PATIENTS AND METHODS: During the EHEC epidemic which occurred in northern Germany in spring 2011, 24 patients with E. coli O104:H4 infection were treated at our hospitals, 19 of whom developed HUS. The use of antibiotics before and after the onset of HUS was documented, and the outcome in patients with and without antibiotic treatment was evaluated. RESULTS: Of the 24 patients with EHEC-associated diarrhea, seven received antibiotics before any signs of HUS were present (ciprofloxacin, cefotaxime, amoxicillin and/or metronidazole). Four of these seven patients (57 %) and 15 of the 17 patients (88 %) who were treated without antibiotics developed HUS (p = 0.12). Microbiological testing showed all E. coli O104:H4 to be extended-spectrum beta lactamase producers and thus susceptible only to fluoroquinolones, aminoglycosides and carbapenems. Two of the five patients (40 %) treated with ciprofloxacin and 17 of the 19 patients (89 %) treated without ciprofloxacin developed HUS (p = 0.043). CONCLUSION: In our E. coli O104:H4-infected patients, treatment of diarrhea with antibiotics did not increase the risk of HUS. Significantly fewer patients treated with ciprofloxacin developed HUS than patients who did not receive ciprofloxacin.

[Tuberculosis in 22 Au-pairs in Germany and Austria - rapid diagnosis reduces risk of infection for host families]. / Tuberkulose bei 22 Au-pairs in Deutschland und Österreich - rasche Diagnose verringert Infektionsrisiko für Gastfamilien.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate tuberculosis (TB) in au-pairs in Germany and Austria and to assess the risk of infection for the host families. METHODS: Reports from local health authorities were obtained between 2002 and 2010 (Bavaria, 12 cases) and from 2006 to 2010 (Baden-Wuerttemberg 6, North Rhine-Westphalia and Hesse, 1 each, additionally 2 from Austria). RESULTS: 22 cases of tuberculosis were reported to the local health authorities, all of them concerning young female au-pairs, age 19 - 27 years. Countries of origin were: Kenya (9), Georgia (4), Mongolia (3), Indonesia (2), Nepal, Russia, Romania, and Peru (1 each). In 17 au-pairs, sputum-smear positive pulmonary tuberculosis was diagnosed. Three au-pairs presented with extrapulmonary tuberculosis without or only with minor pulmonary involvement. In two asymptomatic cases, sputum-smear negative tuberculosis was diagnosed by screening. The time between entry and the beginning of symptoms was 7.5 ± 5.8 months (0 - 19.3). 10.0 ± 6.1 weeks (range 3 - 20 weeks) elapsed between the first symptoms and the diagnosis. No infection of the host families was caused by 5 au-pairs who had no or only minor pulmonary involvement. In 17 au-pairs with high mycobacterial burden, the infection rate increased with the duration of time between symptoms and diagnosis (1 - 11 infections per au-pair). A total of 46 contacts (21 children, 25 adults) were infected. 17 children received chemoprophylaxis with isoniazid (INH); none of them developed active disease. One child out of four who did not get INH was diagnosed with pulmonary TB. In addition, 5 out of 24 adults without chemoprevention developed active TB. 4 TB-strains were drug-resistant strains, one of them multidrug-resistant. CONCLUSIONS: In au-pairs from countries with high burden of tuberculosis, long lasting cough and weariness should prompt diagnostics for tuberculosis. By screening, the disease can be detected before it gets infectious. If infection has occurred, chemoprevention with INH for nine months can prevent overt tuberculosis.

[New recommendations for contact tracing in tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose*1.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

[New recommendations for contact tracing in tuberculosis. German Central Committee against Tuberculosis]. / Neue Empfehlungen für die Umgebungsuntersuchungen bei Tuberkulose. Deutsches Zentralkomitee zur Bekämpfung der Tuberkulose.

In 2007, the German Central Committee against Tuberculosis (DZK) published recommendations for contact tracing that introduced the new interferon gamma release assays (IGRAs). Meanwhile, substantial progress has been made in documenting the utility of IGRAs. Because IGRAs are usually superior to the tuberculin skin test (TST) in detecting latent TB infection (LTBI) with respect to sensitivity and specificity in adult contact populations that are at least partially BCG vaccinated, it is now recommended that instead of two-step testing only IGRAs be used.[nl]As the literature does not yet provide sufficient data on the accuracy of IGRAs in children younger than 5 years, the TST remains the method of choice in that age group. To date, also, no clear body of data exists to substantiate better performance for IGRAs than for the TST in older children, thus in this age group using of either test is recommended. The new recommendations also underscore the importance of a diligent preselection of close contacts in order to achieve a high probability that positive test results represent recent infection and to thus increase the benefit of chemopreventive treatment for those identified as requiring it. In a third point of update, it is noted that re-testing of contacts individuals found positive for LTBI may produce a considerable number of false-negative results and should thus be avoided in case of documented exposure.

Mutational spectrum in the cardiac transcription factor gene NKX2.5 (CSX) associated with congenital heart disease.

Heterozygous mutations in the human transcription factor gene NKX2.5 are associated with either isolated or combined congenital heart disease (CHD), primarily secundum atrial septal defect-II (ASD-II), ventricular septal defect (VSD) or tetralogy of Fallot (TOF). Thus, NKX2.5 has an important role at different stages of cardiac development. The frequency of NKX2.5 mutations in a broader phenotypic spectrum of CHD is not completely determined. Here, we report the identification of two novel mutations in the NKX2.5 gene in a screening of 121 patients with a broad spectrum of CHDs. However, mutations were only associated with familial ASD-II and in both, patients also showed atrioventricular (AV) block. We found one missense mutation (R190L) in two siblings with ASD-II and a frame-shift mutation (A255fsX38) at the C-terminus in a mother and daughter. In addition, a single patient with hypoplastic left heart syndrome (HLHS) had the reported sequence variant R25C. Importantly, sporadic cases of CHD that share phenotypic aspects of NKX2.5 mutation carriers were negative for genetic analysis. Thus, even important for cardiac development, germline mutations in NKX2.5 are rare in patients with sporadic CHD and genetic and/or pathophysiologic heterogeneity is likely for sporadic forms of CHD.

[The impact of viruses in lower respiratory tract infections of the adult. Part III: therapy and prevention]. / Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen. Teil 3: Therapie und Prävention.

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations to prove the presence of respiratory viruses their impact in the pathogenesis of lower respiratory tract infection has probably been underestimated for a long time. Therefore, there might have been many cases of unnecessary antibiotic treatment, especially in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological cause. With the introduction of more sensitive investigational procedures, such as polymerase chain reaction, it is possible to sufficiently prove respiratory viruses and therefore illuminate their role in the pathogenesis of lower respiratory tract infections of the adult. We have reviewed the current literature on the impact of viruses in lower respiratory tract infections to elucidate the role of viruses in the pathogenesis of lower respiratory tract infections. The preceding parts of this series provided an introduction to the frequently found viruses, pathogenesis, and diagnostic procedures (part I) as well as common viral infections of the lower respiratory tract (part II). The present 3 (rd) part deals with therapy for and prevention of viral LRTI.

[The impact of viruses in lower respiratory tract infections of the adult. Part II: acute bronchitis, acute exacerbated COPD, pneumonia, and influenza]. / Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen. Teil 2: Akute Bronchitis, exazerbierte COPD, Pneumonie und Influenza.

In industrialized countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections affect the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series described frequent viral pathogens, pathogenesis of viral LRTI, and diagnostic procedures. In this 2 (nd) part the aetiological role of viruses in the most frequent forms of LRTI will be highlighted, and the third and last part will provide an overview of therapeutic and preventive options.

[The impact of viruses in lower respiratory tract infections of the adult. Part I: Pathogenesis, viruses, and diagnostics]. / Die Rolle von Viren bei tiefen Atemwegsinfektionen des Erwachsenen. Teil 1: Erreger, Pathogenese und Diagnostik.

In industrialised countries respiratory tract infections are one of the most common reasons for medical consultations. It is assumed that almost one third of these infections include the lower respiratory tract (LRTI), e. g. acute bronchitis, acute exacerbation of chronic obstructive pulmonary disease (COPD), community- or hospital-acquired pneumonia and influenza. Due to a lack of sufficient and valid investigations on the epidemiology of respiratory viruses, their impact on the pathogenesis of LRTI has probably been underestimated for a long time. Therefore, there might have been many cases of needless antibiotic treatment, particularly in cases of acute bronchitis or acute exacerbations of COPD, because of an assumed bacteriological aetiology. Following the introduction of diagnostic procedures with increased sensitivity, such as polymerase chain reaction, it is possible to reliably detect respiratory viruses and to illuminate their role in the pathogenesis of LRTI of the adult. We have reviewed the current literature to elucidate the role of viruses in the pathogenesis of LRTI. The first part of this series deals with the relevant pathogens, pathogenesis, and diagnostic procedures. In the subsequent 2 parts of this series a review will be given on the most common variants of viral LRTI (part II), and therapeutic and preventive options (part III).

A decade of staged Norwood palliation in hypoplastic left heart syndrome in a midsized cardiosurgical center.

Hypoplastic left heart syndrome (HLHS) is a challenge for the pediatric cardiologist and the surgeon. It is generally assumed that the postoperative outcome after surgery for congenital heart disease is influenced by the institutional size. We present the results of 43 patients with true HLHS (situs solitus and atrioventricular and ventriculoarterial concordance) referred for operation between 1992 and 2002 in our center. Two children had atrioseptostomy: one died soon after the operation, and the other one was transplanted successfully but died at the age of 6 months following acute rejection. The remaining 41 underwent Norwood I palliation, 21 stage II palliation, and 10 stage III palliation. Early mortality was 29% after stage I operation, 4.7% after stage II palliation, and 0% after stage III operation. Overall mortality was 39% after stage I, 9.5% after stage II, and 10% after stage III operation. Low birth weight was associated with a higher mortality (p < 0.05). Mortality declined with increasing experience, comparable to the results of very large cardiosurgical centers with many more patients. The quality of surgery and perioperative management in smaller pediatric cardiosurgical centers can reach the level of very large centers.

Long QT syndrome and life threatening arrhythmia in a newborn: molecular diagnosis and treatment response.

Intrauterine and neonatal manifestations of congenital long QT syndrome are associated with a high cardiac risk, particularly when atrioventricular block and excessive QT prolongation (> 600 ms(1/2)) are present. In a female newborn with these features, treatment with propranolol and mexiletine led to complete reduction of arrhythmia that was maintained 1.5 years later. High throughput genetic analysis found a sodium channel gene (LQT3) mutation. Disappearance of the 2:1 atrioventricular block and QTc shortening (from 740 ms(1/2) to 480 ms(1/2)), however, was achieved when mexiletine was added to propranolol. This effect was considered to be possibly genotype related. Early onset forms of long QT syndrome may benefit from advanced genotyping.

Ventricular aneurysm or diverticulum? Clinical differential diagnosis.

Intrathoracic ventricular aneurysms and diverticula can be differentiated by several criteria. Contractility is the only reliable parameter: aneurysms expand, whereas diverticula contract during ventricular systole.

Levofloxacin pharmacokinetics and serum bactericidal activities against five enterobacterial species.

After oral administration of 500 mg of levofloxacin to 12 volunteers, we investigated the pharmacokinetics and serum bactericidal activities (SBAs) against five strains of members of the family Enterobacteriaceae. Pharmacokinetic data were as follows: maximum concentration in serum, 6.36 +/- 0.57 mg/liter; area under the concentration-time curve, 43.6 +/- 6.23 mg. h/liter; elimination half-life 4.23 +/- 0.87 h. SBAs were present for 24 h against Escherichia coli and Citrobacter freundii. The SBAs at 1, 12, and 24 h after administration against E. coli were 1:108, 1:29, and 1:7, respectively, and those against Citrobacter freundii were 1:74, 1:25, and 1:7, respectively. The SBAs were present for 12 h against the other three organisms tested. The SBAs against Serratia marcescens were 1:28 and 1:9 at 1 and 12 h, respectively; the SBAs against Klebsiella pneumoniae were 1:25 and 1:7 at 1 and 12 h, respectively; and the SBAs against Enterobacter cloacae were 1:24 and 1:10 at 1 and 12 h, respectively.

In vitro effects of interleukin-10, prednisolone, and GM-CSF on the non-specific immune function of human polymorphonuclear leucocytes and monocytes.

A wide range of immune-modulating effects make IL-10 a potential therapeutic option in the treatment of numerous diseases pathophysiological based on a dysregulation of cytokine production. The background of this study was to investigate, whether the beneficial effects of a therapeutic immunosuppression with IL-10 may be countered by an increased risk for infections due to impaired effector cell functions of unspecific immunity. We demonstrated the in vitro effects of IL-10 on phagocytosis (P), intracellular killing (K), and chemotactic activity (C) by human neutrophils (PMN) and monocytes (MON) using Candida albicans as test strain and compared the results to the effects of prednisolone and GM-CSF. IL-10 reduced significantly the intracellular killing rate of PMN compared to untreated phagocytes (60 +/- 16% versus 68 +/- 13%, mean +/- SD, p = 0.0002). High dose IL-10 (100 ng/ml) had a stimulating effect on the percentage of phagocytizing MON (70.2 +/- 12.7% vs. 66.9 +/- 14.2%, p = 0.0436), without impairing intracellular killing. Prednisolone reduced significantly the Candida uptake by MON (57 +/- 18.1% vs. 66. 9 +/- 14.2%, p = 0.0019). In contrast to prednisolone, neither MON nor PMN chemotaxis was suppressed by IL-10. In conclusion, IL-10 had only marginal immunosuppressive effects on the unspecific immunity compared to prednisolone.