cyp51A-Based Mechanisms of Aspergillus fumigatus Azole Drug Resistance Present in Clinical Samples from Germany

Since the mid-1990s, a steady increase in the occurrence of itraconazole-resistant Aspergillus fumigatus isolates has been observed in clinical contexts, leading to therapeutic failure in the treatment of aspergillosis. This increase has been predominantly linked to a single allele of the cyp51A gene, termed TR/L98H, which is thought to have arisen through the use of agricultural azoles. Here, we investigated the current epidemiology of triazole-resistant A. fumigatus and underlying cyp51A mutations in clinical samples in Germany. From a total of 527 samples, 17 (3.2%) showed elevated MIC₀ values (the lowest concentrations with no visible growth) for at least one of the three substances (itraconazole, voriconazole, and posaconazole) tested. The highest prevalence of resistant isolates was observed in cystic fibrosis patients (5.2%). Among resistant isolates, the TR/L98H mutation in cyp51A was the most prevalent, but isolates with the G54W and M220I substitutions and the novel F219C substitution were also found. The isolate with the G54W substitution was highly resistant to both itraconazole and posaconazole, while all others showed high-level resistance only to itraconazole. For the remaining six isolates, no mutations in cyp51A were found, indicating the presence of other mechanisms. With the exception of the strains carrying the F219C and M220I substitutions, many itraconazole-resistant strains also showed cross-resistance to voriconazole and posaconazole with moderately increased MIC₀ values. In conclusion, the prevalence of azole-resistant A. fumigatus in our clinical test set is lower than that previously reported for other countries. Although the TR/L98H mutation frequently occurs among triazole-resistant strains in Germany, it is not the only resistance mechanism present.     

Renal function during treatment with adefovir plus peginterferon alfa-2a vs either drug alone in hepatitis B/D co-infection

Long-term safety of treatment with hepatitis B virus (HBV) polymerase inhibitors is a concern. Adefovir dipivoxil (ADV) therapy has previously been associated with impairment of renal function. Limited data are available on the safety of combination therapy with nucleos(t)ide analogues and interferon alfa (IFNα). The aim of this analysis was to assess the renal function during combination therapy with peginterferon alfa-2a (PegIFNα-2a) plus ADV vs either drug alone in patients with hepatitis B/D co-infection. We performed a retrospective analysis of renal function data of patients treated in the Hep-Net/International Delta Hepatitis Intervention Trial 1(HIDIT-1-trial), a European multicenter study to investigate the efficacy of 48 weeks of therapy with PegIFNα-2a+ADV vs either drug alone in 90 patients with chronic hepatitis B/D co-infection. Glomerular filtration rates (GFR) were calculated by Cockcroft-Gault (CG), abbreviated Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. After 48 weeks of therapy GFR values were significantly lower in patients receiving adefovir-containing treatment vs PegIFNα-2a alone [mean difference 16.1 mL/min (CG) and 10.2 mL/min (MDRD), respectively, P < 0.05] while no differences were observed between patients receiving adefovir alone vs combination treatment. Twenty-four weeks after treatment GFR values did not differ between treatment arms. A decrease in GFR ≥ 20% was observed more often in patients during adefovir-containing treatment vs PegIFNα-2a alone (P < 0.05) which was confirmed by Kaplan-Meier analysis. Adefovir-containing but not PegIFNα-2a treatment was associated with a decrease in GFR values in about one-fifth of patients. Combination treatment of PegIFNα-2a+ADV in chronic hepatitis B/D co-infection did not lead to any further impairment of kidney function.     

Die Wertigkeit der Strahlenbehandlung im Vergleich zur extrakorporalen Stoßwellentherapie (ESWT) beim Supraspinatussehnensyndrom

BACKGROUND AND AIM: Supraspinatus tendinitis is usually treated by antiinflammatoric drugs, local injections, physiotherapy or low-dose irradiation. A novel approach is the use of Extracorporeal Shock Wave Therapy (ESWT) if conservative therapies have failed. So far there has been no controlled study comparing the effectiveness of ESWT with an established conservative method of therapy such as X-ray stimulation radiotherapy. PATIENTS AND METHOD: 30 patients with chronic supraspinatus tendinitis were admitted into the prospective randomized study. After randomization the patients were treated either with X-ray stimulation radiotherapy with 6 x 0.5 Gy on the ICRU reference point (1 fraction/day) with cobalt 60 gamma rays or three times with 2000 pulses (energy flux density ED+ 0.1 mJ/mm2) in 1 week intervals using a Storz Minilith SL1. Primary endpoint was the age-corrected constant score 3 months after intervention. RESULTS: Acute side effects caused by the irradiation were not observed, as expected. One patient described pain and one patient showed a moderate skin irritation after ESWT. In the radiotherapy group average the age-corrected constant score improved from 47.6 through 79.5 points to 87.4 points. In the ESWT group it rose from 50.1 points before ESWT to 91.4 points after 12 weeks and 97.8 after 52 weeks. CONCLUSION: No statistically significant differences were proven between ESWT and radiotherapy. ESWT appears to be equivalent but not superior to radiotherapy in treating chronic supraspinatus tendinitis syndrome. A comprehensive randomized study is, however, necessary to ensure the equivalence of ESWT.     

Marknagelung geschlossener Oberschenkelschaftbrüche

Antegrade femoral nailing with interlocking nails is the most common surgical treatment for diaphseal fractures of the femur. It can be performed with or without reaming of the shaft. The decision on whether or not reaming is indicated must be made with reference to each patient's specific problems to avoid complications. Since there is a higher risk of pulmonary complications when the reamed technique is used, unreamed nailing should be preferred in cases of multiple injuries. The different surgical tehcniques for nailing are presented, as are the disadvantages of each.     

Osteochondrale Läsionen am Talus und ihre Therapieoptionen

We examined a number of osteochondral lesions of the talar dome. The mechanism of their development, the diagnostic procedures needed and the treatment options are reviewed. We present our experience of diagnosis and treatment, the main focus being on arthroscopic treatment. The results obtained in our own small patient population are reported. Statistical analysis is not appropriate in view of the small population.     

Periodontitis Prevalence and Severity in Adults: A Cross‐Sectional Study in Norwegian Circumpolar Communities

Background: The aim of this study is to describe the prevalence, severity, and extent of periodontitis in the adult population of circumpolar communities in Norway using data from the Tromstannen–Oral Health in Northern Norway study. Methods: In this cross‐sectional survey, data were collected from a randomized population sample (aged 20 to 79 years) in Northern Norway. Periodontal conditions were assessed for 1,911 dentate adults with a full‐mouth periodontal examination. Probing depth (PD) and bleeding on probing were measured at six sites per tooth. Radiographic bone loss (BL) was examined using orthopantomograms. Results: According to the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions, 49.5% of participants had periodontitis, and 9.1% had severe periodontitis. Periodontitis prevalence and severity increased with age. Extent of BL and PD ≥4 mm also increased with age, but more rapidly and to a greater extent for BL. Prevalence of periodontitis was higher among men and varied between urban and rural areas. Periodontitis prevalence was positively associated with smoking, lower levels of education, and income. Conclusions: This study reveals a high burden of periodontitis among adults living in circumpolar communities in Norway. The results showed sociodemographic disparities regarding periodontitis and highlights the importance of further investigation of factors influencing periodontal health.     

Haemodynamische Wirkung von 2-Amino-6-methylheptan-(+)-campher-10-sulfonat

Zusammenfassung Die haemodynamische Wirkung von 2-Amino-6-methylheptan-(+)-campher-10-sulfonat (AMC) wurde an 7 erwachsenen narkotisierten Hunden mit Körpergewicht zwischen 16 und 23 kg experimentell studiert. Die Verbindung wurde i. v. in einer Dosierung von 0,10–2,0 mg/kg Körpergewicht in 1% Lösung appliziert.Bei 6 Tieren konnten die Versuche ausgewertet werden. Es wurden mittels eines elektromagnetischen Flowmeters das Herzzeitvolumen, der Durchfluß in ml/min in der A. fem. und der Koronararterie gemessen. Über ein Statham-Element erfolgte die fortlaufende Messung des arteriellen Druckes. AMC erhöht den mittleren Blutdruck durchschnittlich um 15–35 mmHg. Das Herzzeitvolumen wies eine Zunahme von 4,4% auf. Gleichzeitig nahm der Koronardurchfluß und der A. fem.-Durchfluß um 25,2 bzw. 19,6% zu. Als optimal erweist sich eine i. v. Dosierung von 0,50 mg/kg Körpergewicht.Zum Vergleich wurde Alupent als rein sympathicomimetischer -Stimulator herangezogen. Die Ergebnisse zeigen, daß AMC ein sympathikomimetisches Amin ist, das vorwiegende -Stimulation und schwächere -Stimulation bewirkt. Diese Eigenschaften lassen annehmen, daß die Verabreichung dieses Medikamentes eine sinnvolle Therapie sowohl chronischer als auch akuter Zustände einer Kreislaufinsuffiziens darstellt.

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Summary The hemodynamic effect of 2-Amino-6-methylheptan-(+)-campher-10-sulfonat (AMC) was studied in 7 adult, healthy dogs weighing 16–35 kg, using the electromagnetic flowmeter and the Statham-Element. AMC was given intravenous in doses 0,10–2,0 mg/kg 1% solution.AMC increased the mean blood pressure 15–35 mmHg with increasing cardiac output of 4,4%, Coronarflow of 25,2% and femoralflow of 19,6%.To compare, Alupent was used as a purely sympathomimetic amine. The results show that AMC is a sympathomimetic which causes a predominantly -stimulating and a weaker -stimulating. These qualities of AMC let one suppose that this compound with its well compatible intravenous injection is a useful medicine to attend both cronic and acute states of cardiovascular insufficiency.

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Mit 7 Abbildungen und 2 Tabellen     

Which Radiographic Parameters Are Linked to Failure of a Dynamic Spinal Implant?

Background  

Knowledge about factors leading to failure of posterior dynamic stabilization implants is essential to design future implants and establish surgical indications. Therefore, we analyzed an implant for single-level or hybrid configuration (adjacent to spondylodesis), which was recalled due to high failure rates.