A critical review of the dosage of teicoplanin in Europe and the USA

The glycopeptide antibiotic, teicoplanin, is increasingly used in Europe in the treatment of Gram-positive infection. It is administered as a bolus once daily, it has little potential for nephrotoxicity, and serum monitoring is usually unnecessary. However, poor results were reported in early trials at a daily dose of 200 mg and, more recently, at 400 mg/day in monotherapy of staphylococcal endocarditis. While 400 mg (6 mg/kg day(-1)) is now standard, US trials have tried very high doses in an attempt to improve its efficacy in monotherapy of deep-seated staphylococcal sepsis. European centres continue to use 6 mg/kg day(-1) as the usual maintenance dose and 6-12 mg/kg as the loading dose. For the more difficult cases, teicoplanin is used in combination with other agents. All available published and unpublished literature was reviewed to try to solve these problems. With the exception of endocarditis, failure rates in the 84 European open studies varied more between trials than between the dosages used. In 32 European and eight US randomized trials, a dose of 6 mg/kg day(-1) of teicoplanin was effective, except in staphylococcal endocarditis if teicoplanin was used as monotherapy. In that case, 12 mg/kg day(-1) or more was needed to achieve a cure rate similar to that of vancomycin. Treatment was most successful with trough levels over 20 mg/l. However, lower doses were effective in combination with aminoglycosides, as is common in clinical practice. An open trial suggested that 12 mg/kg day(-1) was needed for treatment of septic arthritis. It is suggested that 6 mg/kg day(-1) of teicoplanin be used for all indications except staphylococcal endocarditis and septic arthritis when it should be given in a dose of 12 mg/kg day(-1) or in combination with other agents.     

Auswirkungen von Argon-Gasembolien während eines PneumoperitoneumsRID="*"ID="*"Die Studie wurde zum Teil gefördert von der DFG (Bo 1329/8–1)

Zusammenfassung. In einer experimentellen Studie wurde bei 10 Schweinen mit einem mittleren K?rpergewicht von 18,9 (15–24) kg eine intraven?se CO₂- oder Argon-Embolie mit 10, 20 und 30 ml Gas durchgeführt. Das invasive Monitoring zeigte bei der Gasembolie mit Argon im Gegensatz zur Gasembolie mit CO₂ einen st?rkeren Anstieg des pulmonal arteriellen Drucks (p < 0,001), einen st?rkeren Abfall des endexspiratorischen CO₂ (p < 0,01), des Herzminutenvolumens (p < 0,01) und des mittleren arteriellen Drucks (p < 0,01). In der Argon-Gruppe (n = 5) starben zwei Tiere nach 20 bzw. 30 ml Bolusgabe. Ein weiteres Tier konnte nach Gabe von 30 ml Bolus erfolgreich reanimiert werden. In der CO₂-Gruppe (n = 5) starb weder eines der Tiere noch war eine Reanimation erforderlich. Wenig l?sliche Gase wie Argon sollten in Situationen mit erh?htem Risiko einer Gasembolie nicht angewendet werden. ID=" Dr. T. Junghans Klinik f&uuml;r Allgemein-, Visceral-, Gef&auml;&szlig;- und Thoraxchirurgie Universit&auml;tsklinikum Medizinische Fakult&auml;t der Humboldt-Universit&auml;t Campus Charit&eacute; Mitte Schumannstra&szlig;e 20/21 D-10117 Berlin     

The effect of 2'-2' difluorodeoxycytidine (dFdC, gemcitabine) on radiation-induced cell lethality in two human head and neck squamous carcinoma cell lines differing in intrinsic radiosensitivity

PURPOSE: The present study investigated in vitro radio-enhancement by gemcitabine (dFdC) in two head and neck squamous cell carcinomas with different intrinsic cellular radiosensitivity. MATERIALS AND METHODS: Radiosensitive (SCC61, SF2=0.16) and radioresistant (SQD9, SF2=0.49) human head and neck squamous cell carcinomas were used. Confluent cells were incubated with dFdC and irradiated in drug-free medium with a single dose of 250 kV X-rays (0-12Gy). Cell survival curves were corrected for the toxicity of the drug alone. RESULTS: In both cell lines, radio-enhancement was observed with 5 microM dFdC incubated for 3 h prior to irradiation. Dose modification factors (DMF) at a surviving fraction level of 0.5 reached 1.3 (95% CI 1.1-1.6) and 1.5 (95% CI 1.4-1.5) for SQD9 and SCC61 cells, respectively. Radio-enhancement was associated with a modest increase in the alpha term of the linear-quadratic model. In SQD9 cells, radio-enhancement increased with dFdC incubation time. At 24h, DMF reached a value of 1.5 (95% CI 0.9-3.2). In SCC61 cells at 24h, DMF reached a value of 1.1 (95% CI 0.9-1.2). In both cell lines, radio-enhancement increased with dFdC concentration up to 5-10 microM from which values it levelled off up to 100 microM. CONCLUSIONS: The data indicated that dFdC induced a modest radio-enhancement in both cell lines. For a short incubation time, dFdC did not radio-enhance preferentially the more radio-resistant cells, whereas the opposite was observed for a longer time. In both cell lines, radio-enhancement was saturated above a dFdC concentration of 5-10 microM.     

The intrarenal vascular lesions associated with primary antiphospholipid syndrome

Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of "primary" APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease.     

Value of German Hospital Diagnosis Statistics in epidemiology-- an analysis with subarachnoid hemorrhage as an example

Due to the Hospital Statistics Regulations of the 10th April 1990, the German Hospital Diagnosis Statistics were introduced in 1993 with the intention to serve as a database of health care decisions. This purpose requires a high-quality collection of epidemiologically relevant data. From 1993 to 1996 we analysed the datasets obtainable for subarachnoid haemorrhage which is coded with ICD 430. A subset concerning the data of 1996 and the Saarland region was compared to the data of the Saarland medical school at Homburg/Saar. Cases treated in the neurosurgical department were critically reviewed. About 20% of the cases coded with ICD 430 showed no subarachnoid haemorrhage. On the other hand, again about 20% of subarachnoid haemorrhage cases were not coded with ICD 430. The statistics comprise duplicates due to transfers between hospitals. The calculation of incidence is not possible because new bleeding cases cannot be outlined. In the present form the German Hospital Diagnosis Statistics are not suitable as a reliable base of health care decisions. This is partly caused by the inadequacy of the ICD-classification but, also, by the criteria for collecting data. We propose several modifications which can improve data quality in order to meet the intended requirements.     

Sacral electrical neuromodulation as an alternative treatment option for lower urinary tract dysfunction

Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.     

Enhanced ornithine decarboxylase activity is associated with attenuated rate of damage evolution and reduction of infarct volume in transient middle cerebral artery occlusion in the rat

Ornithine decarboxylase (ODC) transgenic and alpha-difluoromethyl ornithine (DFMO)-treated rats were exposed to transient middle cerebral occlusion (MCAO) to examine the role of intraischaemic ODC-activity on the evolution of ischaemia-reperfusion damage. Magnetic resonance imaging (MRI) data show that the damage develops slower in ODC transgenic than in DFMO-treated rats, which is not caused by a difference in perfusion. Furthermore, infarct volumes are smaller in the former animals one day later. These data support the idea of endogenous neuroprotective action of ODC.     

Detecting unitary events without discretization of time

Illumination with ultra-violet is used widely in physiological experiments for the photolysis of caged compounds. In the peptidergic cells of the pituitary gland, as well as cultured PC12 cells, ultra-violet light was found to produce changes in a number of membrane properties. Light of sufficient intensity to produce rapid photolysis of commonly used caged compounds induced changes in K+ and Ca2+ current, as well as changes in membrane capacitance. All responses to light showed a rapid timecourse, activating in a few ms and decaying within 10-50 ms after illumination ended. Experiments with radical scavengers and with inhibitors of cytochrome p450 and phospholipase A2 failed to block the light responses. These rapid responses to light emphasize that experiments employing ultra-violet light in the photorelease of physiological and pharmacological agents require special care for control of light artifacts.     

Antipsychotic effects and tolerability of the sigma ligand EMD 57445 (panamesine) and its metabolites in acute schizophrenia: an open clinical trial

Antipsychotic efficacy and side effects of the selective sigma ligand EMD 57445 (panamesine) were investigated in 12 patients (6 males, 6 females) who met DSM-III-R criteria for schizophrenia. A 4-week open clinical study revealed only modest effects of EMD 57445 and its metabolites on positive and negative symptoms of schizophrenia. Extrapyramidal and other side effects were moderate, although a significant increase in mild dyskinetic movements was found. Five patients, four of whom were females, completed the trial. Dropouts were mainly due to treatment failure. Antipsychotic effects were significantly greater in female than male patients.