Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial.

BACKGROUND: Due to potential proarrhythmic side-effects levo-alpha-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. METHODS: ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. RESULTS: Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409s +/- 0.022s versus 0.418s +/- 0.028s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1). CONCLUSIONS: In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.

[Pros and cons of preservatives in eyedrops. Questionnaire for practitioners and experimental studies with reference to the requirements of the German Pharmacopoeia of August 1978]. / Wert und Unwert von Konservierungsmitteln in Augentropfen. Praxisumfragen und experimentelle Untersuchungen zur Forderung des DAB 8/78.

The first part of this paper deals with the regulations in the DAB 8/78 stating that eye-drops are to be preserved. A questionnaire prepared by the German Association of Ophthalmologists is analyzed. The four questions put to 353 ophthalmologists and answered by 350 of these concern the need for unpreserved eye-drops because of the danger of allergization; the expiry date once the bottle has been opened; infections due to eye-drops without preservatives; and the need for eye-drops made up by pharmacists. The second part deals with studies on the pH-values of lacrimal fluid in cases of normal and decreased lacrimation, as well as with the bactericidal action of the normal tear fluid containing lysozyme and lactotransferrine and various eye-drops containing preservatives. The authors conclude that the general addition of preservatives to eye-drops, especially to those containing antiphlogistic and astringent substances, is unnecessary. Concerning the expiry date on the bottle, it is suggested that the period of use be extended to three months, thus helping to cut costs.

[Changes in the cornea following complicated pseudophakia and subsequent keratoplasty (clinical and scanning electron microscope findings)]. / Veränderungen der Hornhaut nach komplizierter Pseudophakie und anschliessender Keratoplastik (klinische und REM-Befunde).

An anterior chamber lens (Binkhorst four-loop lens) became dislocated seven weeks after implantation. It was relocated in the right position by means of a small incision. In the course of the following 8 weeks the cornea opacified from the top downward. A penetrating keratoplasty was performed. Intraoperatively it was found that a strand of vitreous had pushed forward between the iris and the lens and was adhering to the back of the cornea. The piece of cornea removed was prepared for the scanning electron microscope. The microscopic findings are described in detail. They correspond exactly to the clinical diagnosis of complete tearing of the endothelium, considerable bullous changes in the parenchyma and degenerative changes in the epithelium. The scanning electron microscope reveals how severe pathologic changes in the cornea can become if a strand of the vitreous becomes adherent to the endothelium.

[Multiple vitelliform retinal cysts]. / Multiple vitelliforme Netzhautzysten.

The authors report on a case of multiple vitelliform retinal cysts which were observed by chance during an examination for an expert opinion on a bulbar contusion. It is shown that these cysts are hard to recognize by simple ophthalmoscopy, but may be visualized by fluorescein angiography in the form of bright circular areas, sometimes differently colored. The developmental mechanism is illustrated with histologic pictures.

[Etiology and pathogenesis of recurrent erosions of the cornea. A scanning and transmission electron microscopy study]. / Atiologie und Pathogenese der rezidivierenden Erosion der Hornhaut. Eine raster- und transmissionselektronenmikroskopische Studie.

Scratched off corneae of 2 patients were examined under the scanning electron and the transmission electron microscope. Whereas in the scanning electron microscope the expected picture of the destruction of the epithelium in the upper zones of the cornea could be presented in the 1st case, the histological picture of the 2nd case shows in the transmission electron microscope the reaction of the influence of the noxa to the texture of the epithelial cells, to the protoplasm, and to the nucleus of the concerned epithelial cell.

[Electron-microscopic examinations in cases of keratitis dendritica (author's transl)]. / Elektronenmikroskopische Untersuchungen bei Keratitis dendritica.

Scanning electron-microscopic and transmission electron-microscopic examination of cornea affected with herpes simplex (DNS) and which developed the clinical picture of keratitis dendritica, showed typical test results, which are described in detail. The ultramicroscopic findings show that the metabolism of the epithelial cells is of considerable degree. It was proved that there were virus particles in the protoplasm of the epithelial cells. A comparison with a case of zoster keratitis showed the same morphological changes.

[The "typical senile cataract" examined under the scanning electron microscope (author's transl)]. / Der "typische graue Altersstar" im Rasterelektronen mikroskop (REM).

Lenses suffering from "typical senile cataract" prepared by "critical point drying"and by sprinkling with gold, were examined under the scanning electron microscope. The images thus obtained gave a three-dimensional representation of structural changes within the lens determined in histological investigations performed with the light microscope.

[Total aniridia: a problem of bulbus rupture (author's transl)]. / Die totale Aniridie als Folge einer Bulbusruptur.

In two cases of total aniridia after contusion of the eyeball, small perforating wounds near the limbus were found. The entire iris can only have become detached from the eye as a result of this very small wound. The theory concerning the cause of total traumatic aniridia is discussed.

[Risk of transmission of hepatitis B through contact lens fitting set]. / Das Risiko einer Ubertragung von Hepatitis B durch Kontaktlinsenanpassung.

8 out of 19 cases of acute or chronic hepatitis, with positive hepatitis B surface antigen (HBsAg) had HBsAg-positive tears. In 25 healthy HBsAg carriers, no HBsAg was found in the tears. The HBsAg concentration in the tears of hepatitis patients was less than 1% of the HBsAg in their blood. Contact lenses (soft hydrophilic, silicone) experimentally contaminated with HBsAg were practically free of it after the usual cleaning and washing with a commercial contact lens cleaning fluid. No adsorption of HBsAg was found on hydrophilic soft lenses; a minimal adsorption on silicone lenses could not be entirely excluded, but practically it was without any importance. In 14 samples of 79 storage fluids of a contact lens fitting set HBsAg was found. The cause of this contamination is not clear.

[The modified performance of the goniotrepanation with scleral flap after J. Fronimopoulos (author's transl)]. / Modifizierte Ausführung der Goniotrepanation mit Skleradeckel nach J. Fronimopoulos.

In a small group of patients goinotrepanation was performed with the scleral flap shaped to include a scleral tag. This operation method has no disadvantages when compared to the classical methods. In addition, in some cases the diameter of the trepanation can be reduced by the use of a scleral tag because of the favourable flowing relationships for the filter fluid.

[Observations on the treatment of glaucoma with clonidin (author's transl)]. / Beobachtungen bei der Behandlung des Glaukoms mit Clonidin

Observations on 50 patients treated for up to 2 1/2 years with clonidin revealed very variable side-effects. A large proportion of these patients remained free from side-effects. In a second, bigger group the side-effects decreased so markedly during the treatment, that this drug could be used again. The effects of this drug on the patients are reported in each case.