Identification of antiarrhythmic drugs and their metabolites in urine

Identification of the antiarrhythmic drugs ajmaline, aprindine, diltiazem, disopyramide, flecainide, gallopamil, lidocaine, lorcainide, mexiletine, phenytoin, prajmaline, propafenone, quinidine, sparteine, tocainide and verapamil and their metabolites in urine is described. After acid hydrolysis of the conjugates, extraction and acetylation, the urine samples were analysed by computerized gas chromatography-mass spectrometry. Using ion chromatography with the selective ions m/z 58, 72, 84, 86, 136, 224, 266, and 426, the possible presence of antiarrhythmic drugs and/or their metabolites was indicated. The identity of positive signals in the reconstructed ion chromatograms was confirmed by a visual or computerized comparison of the stored full mass spectra with the reference spectra. The ion chromatograms, reference mass spectra and gas chromatographic retention indices (OV-101) are documented. The method presented is integrated in a general screening procedure (general unknown analysis) for several groups of drugs.     

Microscopic haematuria as a relative contraindication for tranexamic acid

Tranexamic acid has been advocated for patients with severe bleeding tendency due to thrombocytopenia not responding to platelet transfusions. Macroscopic haematuria is a well-known contraindication for its use in such patients. We present three clinical cases with microscopic haematuria, in whom tranexamic acid caused problems of clot formation in the urinary tract, indicating that microscopic haematuria should also be considered as a contraindication for tranexamic acid.     

Attachment loss and serum antibody levels against autologous and reference strains of Actinobacillus actinomycetemcomitans in untreated localized juvenile periodontitis patients

Abstract Immunological data have been suggested to be a potential tool in the diagnosis, classification and monitoring of periodontal diseases. However, the role of circulating antibodies in periodontal patients is poorly understood. Patients suffering from localized juvenile periodontitis (LJP) are often reported to show high titers of serum IgG antibodies against Aetinobaeillus actinomycetemcomitans (A. actinomycetemcotnitans), but several affected patients do not. Most studies use well-known reference strains of the bacterium for testing against the patients' sera. The aim of the present investigation was to study the relationship between serum IgG antibody levels to autologous A. actinomycetemcomitans strains and clinical attachment loss (CAL). In addition, we wanted to assess the patients’serum titers against 4 well-known reference strains of the bacterium as well as their general potential immunoglobulin response. Intravenous blood samples were taken from 23 LJP patients and 10 healthy individuals, and autologous A. actinomycetemcomitans strains were cultured from 18 of the L.JP patients. CAL was measured at 4 different sites around ail present teeth and assessed as a % of teeth with at least 1 site moderately ≥2<5 mm) or severely (≥5 mm) involved. An enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the serum titers of IgG antibodies to A. actinomycetemcomitans antigens. No significant correlation was found between serum IgG antibody titers to autologous strains and CAL. However, there was a trend that low responders had more moderately affected teeth than had high responders and patients with undetectable A. actinomycetemcomitans levels, which is in agreement with a hypothetically protective role of the antibodies. The total counts of immunoglobulin assessed in all participants showed that the predominant class was IgG and the reference group displayed significantly less (p<0.05) IgG and IgG1 counts than the LJP patients. Both the reaction pattern against reference and autologous strains varied widely. We conclude that the specific antibody response against A. actinomycetemcomitans shows a weak correlation to clinical attachment levels in LJP patients.     

Biological characteristics of newly diagnosed poor prognosis acute myelogenous leukemia

A pilot study was conducted of the biological characteristics of the leukemia cells of newly diagnosed patients with poor prognosis acute myelogenous leukemia (AML). This study included measurements of the pretherapy proliferative rate of the leukemia cells in vivo, assessment of differentiation in vivo during remission induction therapy, and the level of expression of the fms, myc, and IL1β genes in pretherapy leukemia cells. Short cell cycle times were characteristic of the best prognostic category and were associated with a rapid reduction in marrow leukemia cells in cytosine arabinoside (araC)-sensitive patients. Expression of c-fms was associated with rapid reduction in marrow leukemia cells during araC therapy and with a successful treatment outcome. Expression of the IL1β gene was associated with short remissions. These studies suggest that when compared to newly diagnosed standard prognosis AML, the leukemia of poor prognosis patients is more likely to exhibit long cell cycle times, low levels of fms expression, and is less likely to be associated with myeloid differentiation during remission induction therapy. © 1993 Wiley-Liss, Inc.     

Phase I trial of the polyelectrolyte carbetimer administered i.v. once every four weeks

Summary Carbetimer, a new synthetic low molecular weight polyelectrolyte with a novel structure displayed antitumor activiy in a number of animal tumor model systems and in vitro investigations. Based on these findings it was brought to a phase I clinical trial in patients with advanced malignant disease after failure of conventional treatment or with no conventional treatment available. Forty-eight patients received 98 courses. The schedule was a one hour i.v. infusion every four weeks. The starting dose was 180 mg/m² and dose escalation was performed according to a modified Fibonacci formula up to 16,690 mg/m². At least three patients were treated at each dose level and each patient was eligible to receive repeat courses at the same dose, until progressive disease or dose-limiting toxicity intervened. No hematological toxicity was encountered. Some adverse effects such as reversible proteinuria, hypercalcaemia, pain at infusion site, nausea and vomiting and fatigue were seen partly in a dose-related manner but did not represent the maximum tolerated dose (MTD). The limiting toxicity at the highest dose level of 16,690 mg/m² consisted of ocular symptoms (light flashes) accompanied by a modest decrease of blood pressure and nausea or vomiting during a one hour infusion. 16,690 mg/m²/1 hour was considered the MTD. There were four deaths on study, all considered diseaserelated. Fourteen patients had stable disease for more than two courses, which, however, could also be explained by the natural course of disease. No clear-cut antitumor responses were noted in our study center.The recommended dose for phase II trials derived from our results is 12,550 mg/m²/2 hours. However, with regard to experiences in other phase I studies, the subsequent phase II studies will be performed with a dose of 6,500 mg/m².