Periprosthetic fractures of the acetabulum

Periprosthetic acetabular fractures during and after total hip replacement occur infrequently. Intraoperative fractures have risen with the use of press fit cementless fixation techniques and postoperative fractures are increasing because of the long-term problems associated with osteolysis. This article outlines the classification and management of these fractures.     

Detection of the tick-borne encephalitis virus (TBEV) in ticks in several federal “Länder” of Germany by means of the polymerase chain reaction (PCR) — Characterization of the virus

Summary The aim of the present study was to analyse the current epidemiological situation with respect to TBE in the new federal Länder of Germany and in Saarland through detection of the TBEV genome in unengorged ticks using an RT-PCR technique. 22,273 ticks (Ixodes ricinus) were collected in the five new Länder (and some in Bavaria and Baden-Württemberg) and divided into 294 pools. It was possible to detect TBEV RNA in six pools of ticks from Mecklenburg Western-Pomerania [4], Brandenburg [1], Thuringia [1] (and in three pools from Bavaria and Baden-Württemberg). The nucleotide sequence data of the PCR products were analysed and compared. In Saarland 8,780 ticks were collected in 70 habitats from all the geographic regions and analysed using the PCR in 21 pools; two pools produced positive PCR signals (Saarlouis, Perl). We cannot as a result make a general recommendation that TBE-immunization be introduced in Saarland and in the new federal Länder of Germany. In Germany, however, TBE immunoprophylaxis in Bavaria and Baden-Württemberg is very important.

---

Nachweis des Virus der Frühsommer-Meningoenzephalitis in Zecken einiger Bundesländer mittels Polymerase-Kettenreaktion und nähere Charakterisierung des Virus

Zusammenfassung Das Ziel der vorgelegten Studie ist die Einschätzung der aktuellen epidemiologischen Situation der Frühsommer-Meningoenzephalitis in den fünf neuen Bundesländern und im Saarland mit Hilfe des Nachweises von FSMEV-RNA in ungesogenen Zecken (Ixodes ricinus) durch eine RT-PCR-Technik. 22 273 Zecken wurden in den fünf neuen Ländern (einige auch in Bayern und Baden-Württemberg) gesammelt und in 294 Pools untersucht. Der spezifische RNA-Nachweis gelang viermal in Zecken aus Mecklenburg-Vorpommern, einmal in solchen aus Brandenburg und einmal aus Thüringen. In Bayern und Baden-Württemberg gelang der Virus-RNA-Nachweis dreimal. Die Sequenzdaten der PCR-Amplifikate zeigten, auch im Vergleich mit denen des Prototypstammes Neudoerfl, den hohen Grad der Konservierung im Bereich der 5 NCR. 8780 saarländische Zecken aus allen Gebieten des Bundeslandes wurden in 21 Pools untersucht, positive PCR-Signale konnten in zwei Pools aus Saarlouis und Perl und Umgebung gefunden werden. Der relativ seltene FSMEV-RNA-Nachweis in den neuen Ländern und im Saarland berechtigt nicht, eine generelle Impfempfehlung für diese Gebiete zu geben. Ein Impfschutz sollte jedoch vor Einreise in die Endemiegebiete Bayerns und Baden-Württembergs bestehen.

     

The importance of the principle of clinical significance-defining significant to whom and for what purpose: a response to tingey, lambert, burlingame, and hansen

Tingey, Lambert, Burlingame, and Hansen (1996) argue that although there are benefits and utility of clinical significance, extensions to the concept proposed a decade ago (Jacobson, Follette, & Revenstorf, 1984a) are necessary. The criticisms of the original paper and subsequent extensions are problematic and fail to appreciate the underlying principle of clinical significance, namely defining for whom and for what purpose significant change would be identified. This paper responds to several of the criticisms outlined in Tingey et al. with regard to operationalizing a comparison group, the perceived limitations of using two distributions, and the problems with their approach of specifying a method for determining whether groups are distinct. We then propose that there is a principle that underlies the concept of clinical significance that should be appreciated. We conclude by describing under what conditions "functional" distributions may be supplemented by including information to allow comparisons of outcomes with the current best available treatment alternative, but offer a cautionary statement about the potential risks run by extensions such as Tingey et al.'s that can obscure the concept of clinical significance to the point that researchers are no longer discussing change in terms meaningful to the client.     

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: FUNCTIONS OF ANGIOTENSIN PEPTIDES IN THE ROSTRAL VENTROLATERAL MEDULLA

• 1 It was first shown several years ago that the rostral part of the ventrolateral medulla (VLM) contains a high density of receptor binding sites for angiotensin II (AngII). In the present paper we briefly review recent studies aimed at determining the actions of both exogenous and endogenous angiotensin peptides in the rostral VLM, as well as their specific sites of action.
• 2 The results of these studies have shown that angiotensin peptides can excite pressor and sympathoexcitatory neurons in the rostral VLM, but do not appear to affect non-cardiovascular neurons in this region.
• 3 It is known that pressor neurons in the rostral VLM include both catecholamine and non-catecholamine neurons. There is evidence that, at least in conscious rabbits, both of these types of neurons are activated by AngII. The specific endogenous angiotensin peptide or peptides that affect pressor neurons in the rostral VLM have not yet been definitively identified.
• 4 It is also possible that different angiotensin peptides may have different effects on pressor neurons in the rostral VLM, mediated by different receptors. Further studies will be needed to define these different functions as well as the specific receptors and cellular mechanisms that subserve them.

     

Treatment of severe sepsis in bone marrow transplant recipients with teicoplanin in combination with β-lactams and aminoglycosides

Summary We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy. All 20 patients included in this study received either an allogeneic (8 patients) or an autologous (12 patients) bone marrow transplant for acute myeloid leucaemia (AML), non-Hodgkin's-lymphoma (NHL, high grade) or other malignant diseases. All patients developing primary septicaemia of unknown origin (18 patients) or catheter-related septicaemia (2 patients) were treated with 400 mg teicoplanin, administered i.v. once daily in combination with a cephalosporin and an aminoglycoside (ceftazidime 2 g i.v., t.i.d.; netilmicin 400 mg once daily). All patients responded to therapy, 19 patients were clinically cured and one patient improved under therapy. The therapeutic regimen was well tolerated; only one adverse drug reaction was observed. We did not observe any delayed take or prolonged neutropenia or thrombocytopenia with this therapeutic regimen when our patients were compared to other bone marrow transplant patients (who did not receive this antimicrobial therapy). Our results suggest that teicoplanin is a potentially effective and well tolerated antimicrobial agent in bone marrow transplant patients with infections not responding primarily to beta-lactams and aminoglycosides.

---

Teicoplanin in Kombination mit -Laktamen und Aminoglykosiden bei Knochenmarktransplantatempfängern mit schwerer Sepsis

Zusammenfassung Wir untersuchten Teicoplanin bei vermuteten grampositiven Infektionen nach ungenügendem Ansprechen auf die anfängliche Kombinationstherapie von -Laktam-Antibiotika und Aminoglykosiden. Alle 20 in dieser Studie erfaßten Patienten wurden entweder allogen (8 Patienten) oder autolog (12 Patienten) transplantiert mit folgenden Grundkrankheiten: akute myeloische Leukämie (AML), Non-Hodgkin-Lymphom (NHL) oder andere maligne Erkrankungen. Alle Patienten, die eine primäre Septikämie unbekannten Ursprungs entwickelten (18 Patienten) oder unter einer Katheter-bedingten Septikämie (2 Patienten) litten, wurden mit 400 mg Teicoplanin behandelt. Die Verabreichung von Teicoplanin erfolgte einmal täglich intravenös in Kombination mit einem Cephalosporin und einem Aminoglykosid (Ceftazidim 2 g i.v., 3 ×/die, Netilmicin 400 mg, 1 ×/die). Alle behandelten Patienten sprachen auf diese Therapie an. 19 Patienten wurden klinische geheilt, ein Patient besserte sich unter dieser Therapie. Die Kombinationstherapie wurde gut vertragen, unerwünschte Arzneimittelwirkungen traten während der Studie nicht auf. Wir beobachteten kein verzögertes Angehen des Knochenmarks oder eine Verlängerung der Thrombozytopenie unter dieser Behandlung im Vergleich zu anderen knochenmarktransplantierten Patienten, die diese antimikrobielle Behandlung nicht erhielten. Unsere Ergebnisse zeigen, daß Teicoplanin ein wirksames und gut verträgliches Antibiotikum für knochenmarktransplantierte Patienten ist, die primär nicht auf die Kombinationstherapie mit -Laktam-Antibiotika und Aminoglykosiden ansprechen.

     

The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective.

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches, to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (P450) probe substrates, inhibitors and inducers and for the development of classification systems to improve the communication of risk to health care providers and to patients. While existing guidances cover mainly P450-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently, and should also be addressed. This article was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience

Combination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.     

Tyrosinämie Typ I

Tyrosinemia type I is an autosomal recessive inherited defect of tyrosine metabolism. The underlying cause is a defect of fumarylacetoacetate hydrolase. The disease affects the liver (acute liver failure, liver cirrhosis, hepatocellular cancer), the kidney (tubulopathy with hypophosphatemic rickets), and the peripheral nervous system (paresthesia, vegetative symptoms, progressive paralysis). Beside the hypertyrosinemia the diagnosis can be made on the basis of urinary excretion of a pathological metabolite of the tyrosine metabolism (succinylacetone). Therapeutic options are a regulated phenylalanine/tyrosine diet, a very effective drug therapy (NTBC) that has been available for several years, and in cases of acute liver failure or end-stage liver cirrhosis a liver transplantation.     

Lactobacillus bei Schwangeren

Ohne Zusammenfassung