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Biomedical subjects

H P Benn

Publications and source records attributed to H P Benn.

14 recordsLinked to original sources

Active uptake of serotonin as viability parameter of stored platelets.

The platelet-plasma serotonin (5-HT) exchange in different apheresis products and platelet concentrates (PCs) from buffy coats was studied for quality control over a period of 7 days. In PCs with steadily decreasing pH due to inappropriate gas exchange the platelet 5-HT concentration increases significantly (> 10% positive netto uptake) during the 1st day of storage. Thereafter platelet serotonin drops rapidly with t1/2 = 1 day at pH < 6.5, but platelet counts were constant and 5-HT uptake was inhibited concomitantly. Plasma 5-HT increases as pH decreases. This can be enforced by competitive inhibition of serotonin uptake due to imipramine which also moderates the total 5-HT loss. However, in PC with stable pH the operative 5-HT pump keeps steady-state conditions. The efficacy of the transmembrane uptake mechanism can be adequately monitored by the assessment of the 5-HT platelet/plasma ratio as a new platelet viability parameter.

Blood Platelets↗

Detection of HLA antibodies by an enzyme-linked photometric immune phagocytosis inhibition test.

The immune phagocytosis inhibition test (IPI) has been described as a sensitive method for the detection of cytotoxic and non-cytotoxic HLA antibodies. We performed a photometric IPI and compared this technique with the conventional microscopic IPI. In further investigations we used the photometric IPI in comparison with the lymphocytotoxicity test (LCT) for the detection of HLA antibodies. The photometric IPI showed a high correlation to the microscopic IPI. In tests with different known HLA antibodies the photometric IPI reached a sensitivity of 85.1% versus 80.5% in the LCT, and a specificity of 92.3 versus 100% in the LCT. Diluted patient sera showed a higher sensitivity in the photometric IPI. We conclude that the photometric IPI can be used as a convenient and sensitive technique for the detection of HLA antibodies.

Autoantibodies↗

Screening for hereditary hemochromatosis in prospective blood donors.

Prospective blood donors (n = 1,265, mean age 26 years) were screened for elevated serum ferritin and serum iron. Final diagnosis for hereditary hemochromatosis was made by liver iron concentration (noninvasive biomagnetometry), transferrin saturation, and 59Fe absorption in 3 male subjects. This preliminary result confirms for the first time the current frequency estimation of homozygous hemochromatosis (0.2-0.6%) in a group of young North-Germans.

Adult↗

[Measurement of alloreactive anti-recipient helper T-cell precursors after allogenic bone marrow transplantation].

Acute graft-versus-host disease (GvHD) is a severe complication after allogenous bone marrow transplantation (BMT). The compatibility of major histocompatibility complex antigens (MHC) is the strongest stimulus for GvHD, which also occurs in patients with a genetically MHC-identical sibling donor. In such cases it would be helpful to recognize anti-recipient (interleukin-2-producing) T-lymphocyte precursors to detect a minor histocompatibility antigen (mH), which escapes from typing methods. To quantitate the alloreactive immune response initiating acute GvHD, we established the helper T-lymphocyte precursor test (HTL-p) as described by Theobald et al. in 'GvHD direction', using a limiting dilution assay. Serial dilutions of the donor peripheral blood mononuclear cells (PBMCs) were cultured for 14 days with constant numbers of stimulator PBMCs from the recipient, followed by an unspecific restimulation step with phytohemagglutinin (PHA) or specific restimulation with EBV-transformed blast cells from the recipient. The Il-2 production of specific T cells was assessed by addition of CTLL-16 cells, whose proliferation was measured by an ELISA. We suppose that the HTL-p test is a good tool for measuring the number of anti-recipient T-lymphocyte precursors as a predictive value for the intensity of GvHD.

Bone Marrow Transplantation↗

[Enzyme immunoassay for the determination of serotonin in stored platelet concentrates].

A new enzyme immunoassay (EIA) was applied on measurements of serotonin (5-HT) in stored platelet concentrates (PC). PC were prepared by apheresis of two separators (Cobe, Fresenius) or from buffy coats and stored for a period of 7 days at 22 degrees C and agitating. Measurements were done in pellets and suspension medium (plasma). Detection of 5-HT was specific and sensitive within the bounds of 2 and 1,000 ng/10(9) PLT.

Blood Component Removal↗

Effect of concomitantly administered cimetidine or ranitidine on the pharmacokinetics of the 5-HT2-receptor antagonist ritanserin.

The effects of concurrent administration of either cimetidine 800 mg once daily or ranitidine 300 mg once daily on the single-dose pharmacokinetics of ritanserin 10 mg were investigated in an open, randomized three-way cross-over, controlled investigation in 9 healthy volunteers. Concurrent administration of cimetidine had no significant effect on the area under the plasma concentration-time curve of ritanserin compared with control experiments. The maximum plasma concentration of ritanserin was decreased significantly (105.0 +/- 9.2 versus 125.0 +/- 13.8 ng/mL; P = .0039), whereas time to reach maximal concentration (tmax) of ritanserin was only slightly but not significantly increased, if the subjects were pretreated with cimetidine. After concurrent ingestion of ranitidine, only a trend to a decrease in the maximum plasma concentration of ritanserin was observed. Time to achieve the maximum plasma concentration, terminal half-life of elimination, and the total area under the plasma concentration-time curve of ritanserin were not altered in comparison with control experiments. The results of the study show that concurrent treatment with cimetidine 800 mg once daily or ranitidine 300 mg once daily has no apparent effect on the systemically available amount of ritanserin after a single oral dose of 10 mg. Both H2-antagonists cause a significant (cimetidine) or borderline significant (ranitidine) decrease of the maximum plasma concentration of ritanserin and a slight but not significant increase in tmax (cimetidine). These effects are of minor clinical importance and seem most likely be due to a decrease of the rate of absorption of ritanserin during concurrent administration of cimetidine/ranitidine.

Adult↗

Crystalline and amorphous gold in chrysiasis.

Skin biopsy specimens from five patients (three females and two males) treated parenterally with gold were investigated using transmission electron microscopy. X-ray microanalysis and electron diffraction were used to determine the dermal heavy metal content. Additional sections were stained for light microscopic examination. The amount of elemental gold administered to the patients over a period of years to alleviate rheumatoid arthritis lay between a minimum of 4.0 g and a maximum of 10.0 g. In one and the same patient dermal histiocytic gold aggregations in sun-exposed areas of skin displayed a different pattern and divergent physiochemical states from the gold deposits in non-UV-exposed skin, where aurosome-like amorphous formations are found in the cells of the upper dermis. Additional spherical particles are associated predominantly with phagolysosomes in melanophages beneath solar-irradiated epidermis. Convergent beam electron diffraction proves the crystalline nature of the spherical auriferous deposits. The occurrence of skin rash was not related to different physicochemical states of the precious metal.

Aged↗

Prevention of an early re-occlusion after thrombolytic therapy of acute myocardial infarction by ketanserin.

A problem after successful thrombolytic therapy of acute myocardial infarction is the early occurrence of re-occlusions. An incidence between 10 and 30% is reported. All efforts made so far to reduce the re-occlusion rate using a variety of agents have been disappointing. In a pilot study 20 patients with acute myocardial infarction were treated, in whom a successful lytic therapy with urokinase or rt-PA was documented by means of coronary angiography 90 min after the beginning of treatment. Subsequently the patients were heparinised (thrombin time greater than 30 s), and in addition the selective serotonin-2 receptor-blocking agent ketanserin was given intravenously (4 mg/h). After 24 h the occurrence of early reocclusions was investigated by control angiography. None of the 20 patients showed reocclusions. The degree of stenosis in the infarcted vessel was 72% immediately after lytic therapy, and 68% after 24 h. These preliminary results may suggest a possible reduction in the re-occlusion rate after thrombolytic therapy with a combination of heparin and ketanserin.

Adult↗

Pharmacokinetics of auranofin a single dose study in man.

Three days after cholecystectomy 7 patients were given a single dose of auranofin (5 tablets Ridaura = 4.35 mg gold). Gold was detected in samples of blood, plasma, urine, bile and feces. The determinations were carried out using instrumental neutron activation analysis. The mean gold concentrations reached maximum in blood and plasma after 2 h and in urine and bile after 16 h. The mean terminal half-lives were 7.6 days (blood), 15 days (plasma) and 6.5 days (bile). Cumulative amounts of gold excreted in bile, urine, and feces were 1.6, 4 and 40%, respectively.

Aged↗

Does active rheumatoid arthritis affect intestinal iron absorption?

One of the causes of anaemia in rheumatoid arthritis is thought to be defective iron absorption. In this study the 59Fe absorption in patients with active rheumatoid arthritis is measured and correlated with the results for bone marrow iron stores (and in some cases with the iron stores in the terminal duodenum), which were assessed simultaneously with semiquantitative methods, and with the serum ferritin concentration. In 11 patients with rheumatoid arthritis and increased bone marrow iron stores, iron absorption was decreased. In five patients it was normal and in three further patients, whose bone marrow iron stores were depleted, iron absorption was maximally increased. According to the results both intestinal malabsorption and defective iron absorption can be excluded as causes.

Adult↗

Whole body elimination routes of gold in humans after a single-dose application of the antirheumatic auranofin.

After removal of the gallbladder (cholecystectomy) 7 patients were administered the antirheumatic agent Auranofin in its commercially available tablet form (Ridaura) 3 d postoperative. The single dose consisted of 5 tablets (4.35 mg of gold). Gold was determined in samples of blood, plasma, urine, bile, and feces (1-2 mL and 2.5 g, respectively). The specimens were drawn 10 min to 8 d p.a. and on d 14 p.a. The determinations were performed by instrumental neutron activation analysis (INAA). The limit of detection was less than 1 ng of gold. The courses of the mean gold concentrations show maxima after 1.9 h in blood and plasma, and after 16 h in urine and bile. The mean half-lives (terminal phases) are 7.6 d (blood), 23 d (plasma), and 6.5 d (bile).

Aged↗

[Blocking of S2 receptors--a new treatment principle in generalized tendomyopathy (fibromyalgia)?].

In a pilot study, the effectiveness of the S2-receptor blocker ketanserin was investigated in patients receiving concurrent physiotherapy for primary fibromyalgia. This combined treatment was compared with physiotherapy alone. In the group treated with ketanserin, a significant reduction in spontaneous pain was observed, and the painfulness of "tender points" also decreased markedly. The patients experienced a significant improvement in the quality of sleep, the feeling of being rested after sleep, and psychological well-being in the evening. Significant improvement was also recorded on the Zerssen Mood Scale and the Erlanger Anxiety Scale. In the group receiving physiotherapy alone, the improvements were far less marked and usually were below the significance level. These results are now being verified in a double-blind, randomized trial.

Dose-Response Relationship, Drug↗

[Biliary, renal and fecal elimination and distribution of gold after a single oral administration of auranofin, quantified by the instrumental neutron activation analysis method].

Three days after cholecystectomy, seven patients received a single dose of auranofin (5 tablets Ridaura = 4.35 mg gold). At defined time points thereafter the gold content in samples of blood, plasma, urine, bile, and feces was determined by instrumental neutron activation analysis (INAA). Maxima of the mean gold concentrations in blood (140 +/- 42 ng/ml) and plasma (173 +/- 54 ng/ml) are found 2 h after oral administration of the antirheumatic agent, after 16 h in urine (43 +/- 28 ng/ml) and bile (65 +/- 50 ng/ml), and after 24 h in erythrocytes (greater than 200 ng/ml). The mean terminal half-lives are 7.6 days (blood), 15 days (plasma), 5 days (erythrocytes), and 6.5 days (bile). The cumulative biliary gold excretion within 8 days after the administration of auranofin was 1.6%, compared with 4% and 40% for renal and fecal elimination, respectively. The gold concentration in plasma is always higher than that in bile. There is a close correlation between the areas under the concentration curves (AUC) in bile and plasma (r = 0.864).

Administration, Oral↗