Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Effect of short daily home haemodialysis on quality of life, cognitive functioning and the electroencephalogram.

BACKGROUND: End-stage renal disease patients have a poor quality of life (QoL), suffer from impaired cognitive functioning, and their electroencephalogram (EEG) shows abnormalities. Conventional haemodialysis (CHD) only partially restores these disorders. Short daily haemodialysis (SDHD) has been reported to improve QoL, but effects on cognitive functioning and EEG have yet to be described. METHODS: Of the 13 patients (11 male, 2 female, age 45.5 +/- 8.1 years), 11 completed the Kidney Disease Quality of Life and Affect Balance Scale questionnaires, 10 underwent neuropsychological testing, and all 13 underwent EEG examination. For the neuropsychological assessments, nine patients (six male, three female, age 45.4 +/- 12.6) who remained on the CHD schedule, served as controls. The dialysis schedule of thrice-a-week for 4 h was changed in the experimental group to six times a week for 2 h (SDHD) over a period of 6 months and back to thrice a week for 4 h. RESULTS: When on SDHD, patients rated several dimensions of health-related QoL as being improved. After resuming CHD, one of these dimensions again decreased and several others worsened even lower than baseline. Cognitive functioning did not change when compared with control data. On the EEG, alpha peak frequency increased slightly when on SDHD but decreased significantly after resuming CHD. CONCLUSIONS: SDHD improves health-related QoL, but has no clear effects on cognitive functioning and EEG. Resumption of CHD after SDHD decreases aspects of QoL and EEG alpha peak frequency but has no effect on cognitive functioning.     

How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene.

The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications.     

[3H]Ketanserin labels 5-HT2 receptors and α1-adrenoceptors in human and pig brain membranes

The binding characteristics of [3H]ketanserin (a reported selective radioligand for serotonin 5-HT2 receptors) and [125I]BE 2254 (which labels selectively alpha 1-adrenoceptors) were characterized in brain frontal cortex membranes of pig and man. Saturation experiments indicated that both radioligands label apparently a homogeneous class of binding sites in human and pig fontal cortex membranes. Competition experiments with [125I]BE 2254 using 17 agonists and antagonists showed monophasic and steep curves in human and pig frontal cortex membranes. The pharmacological profile of these sites is typical of alpha 1-adrenoceptors. In competition experiments with [3H]ketanserin, most of the tested compounds displayed shallow or biphasic curves. In particular, alpha 1-adrenoceptor-selective antagonists (prazosin, WB 4101, BE 2254...) displaced with nanomolar affinity about 15 and 40% of the specific [3H]ketanserin binding in human and pig frontal cortex membranes, respectively. The minor component of [3H]ketanserin binding correlated highly significantly with [125I]BE 2254 binding in both membrane preparations. The major component of [3H]ketanserin binding to pig and human frontal cortex membranes correlated significantly with [3H]ketanserin binding in rat brain cortex membranes (which is essentially to 5-HT2 receptors). The present data demonstrate that [3H]ketanserin in nanomolar concentrations binds significantly to alpha 1-adrenoceptors in human and pig frontal cortex membranes; this suggests a rather limited degree of selectivity of ketanserin for 5-HT2 receptors in pig and human tissues.     

Detection of circulating human platelet fragments by using monoclonal antibodies against platelet glycoprotein IIb-IIIa complex

A radioimmunoassay (RIA) for the detection of platelets and platelet fragments was developed. A sandwich of two monoclonal antibodies directed against the platelet-specific glycoprotein complex IIb-IIIa (GP IIb-IIIa) was used in this assay. A discontinuous 7.5-20% (v/v) albumin gradient was applied to separate platelets and their fragments of various sizes. In platelet suspensions fractionated in this way, we observed that particles smaller than normal platelets still carried the GP IIb-IIIa antigens. This procedure enabled us to detect platelet-derived particles in platelet-rich plasma from thrombocytopenic patients.     

Severe Electrolyte Disturbances in Lethal Subclavian Catheter Dialysis

Abstract: Syncope, irreversible shock, and respiratory and circulatory arrest developed in a 54-year-old diabetic man chronically dialyzed with a subclavian catheter (SC) minutes after the end of a dialysis session. Resuscitation attempts remained unsuccessful. During the resuscitation attempt, a blood analysis showed severe hyponatremia, acidosis, and hypochloremia. Respiratory and cardiac arrest developed during dialysis in a 64-year-old woman on chronic SC dialysis. Resuscitation was unsuccessful; chloremia levels were 79 mEq/L, and calcemia levels were 20 mg%. Both patients were dialyzed with a standard dialysate solution. The reasons for the electrolyte disturbances could not be explained technically. The autopsy showed myocardial perforation by the SC and accumulation in the pericardium of the fluids administered during the resuscitation attempt (e.g., glucose 5%, bicarbonate, Ca gluconate, human albumines), thus explaining the erroneous electrolyte results. The reason for the perforation was a too-rigid central femoral vein catheter, erroneously labeled a subclavian catheter by the supplying firm. Because of a syndrome of progressive vena subcla-via and vena cava sclerosis with insufficient arterial phase flow and venous-phase bleeding around the puncture site during single-needle dialysis, the original SC had to be replaced by a longer one with the tip located in the atrium (this SC was actually a femoral catheter). Analysis of the fluid aspirated through the SC can determine the diagnosis in sudden death of SC dialysis patients.