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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 181 records · Page 10Linked to original sources

Phase II study of doxifluridine in advanced colorectal adenocarcinoma.

Doxifluridine, a new fluoropyrimidine derivative, was tested in a cooperative phase II trial by the Swiss Group for Clinical Cancer Research in advanced measurable colorectal cancer. The drug was given in a five consecutive day schedule by a bolus intravenous injection at a dose of 4 g/m2 per day and repeated every three to four weeks. Of 42 eligible patients, 40 had no previous chemotherapy. Response was defined in 27 patients having received two or more courses of doxifluridine. Seven responses (26%) were observed. Responses were seen only in sigmoid and rectum primary tumors. Toxicity consisted mainly of leukopenia (53% of the evaluable patients), nausea and vomiting (38%). Other toxicities such as dermatitis, myocardial injury, and hair loss were also observed. Doxifluridine has therapeutic activity, albeit limited, in advanced rectosigmoid adenocarcinoma.

Adenocarcinoma↗

Pasteurella pneumotropica and the prevalence of the AHP (Actinobacillus, Haemophilus, Pasteurella)-group in laboratory animals.

134 bacterial isolates originally identified as Pasteurella pneumotropica were cultured from healthy, ill or dead mice, rats, hamsters, guinea pigs, rabbits and cats originating from 7 conventional laboratory animal facilities. They occurred seldom in pure culture and were found in a variety of organs. Thorough identification (41 criteria) revealed that only 83 isolates (62%) were P. pneumotropica and could be subdivided into 3 biotypes. 3 isolates were P. aerogenes, 1 was P. ureae, 11 (8%) were qualified as Actinobacillus spp. and 13 (10%) as Haemophilus spp. Close relationship of the 3 genera--the 'AHP-group' --made the differentiation difficult. 23 atypical cultures were discarded at the beginning of the study as not belonging to the 'AHP-group'. Two-thirds of isolates were associated with inflammation or suppuration; Haemophilus spp. seemed to be more pathogenic than Pasteurella and Actinobacillus species.

Actinobacillus↗

Single dose kinetics of mefloquine in man. Plasma levels of the unchanged drug and of one of its metabolites.

Oral single dose kinetics of mefloquine was investigated in 16 male volunteers, 3 Caucasians and 13 African natives. Unchanged mefloquine (= M) and one of its metabolites (= MM) were measured in the plasma. The apparent half-life of absorption of M ranged from 0.36 to 2.0 h, its terminal half-life of elimination from 15 to 33 days. Assuming complete systemic availability, an apparent volume of distribution of 14-29 liters x kg-1 and a total clearance of 18-39 ml x min-1 were derived. MM given orally to mice or rats showed at equal dose the same tolerance as mefloquine. Following oral administration of M to man, plasma levels of MM surpassed those of M, resulting in a 2.4-5.1 larger AUC. However, because of its much smaller apparent volume of distribution, MM may be anticipated to represent only a small percentage of the dose and therefore to contribute only to a minor extent towards the unwanted side effects of the drug.

Adult↗

[Bacterial infection and the regulation of in vivo granulopoiesis].

The mechanism which regulates granulopoiesis was investigated in C 57 BL mice injected i.p. with E.coli. The positive and negative feedback arm of the regulation was studied by correlating the number of bacteria, the number of granulocytes, serum CSF levels and the number of CFU-C in the bone marrow.

Animals↗

On the requirements of ascorbic acid in man: steady-state turnover and body pool in smokers.

The time course of radioactivity in plasma and urine after oral administration of a single dose of (1-14 C) ascorbic acid has been followed in healthy male volunteers smoking more than 20 cigarettes per day. The investigation was carried out under steady state conditions with regard to ascorbic acid plasma levels at intakes of about 30 to 180 mg/day. Smokers had a higher metabolic turnover than that found for nonsmokers. It was concluded, as a consequence, that a daily intake of at least 140 mg is required for smokers to reach steady state concentrations and total body pools comparable to nonsmokers for whom a daily intake of about 100 mg was previously reported to be appropriate.

Adult↗

[Anatomical and histological study of osteochondral and costal cartilage autografts in the dog].

A macroscopic and microscopic anatomical study of the knees of 10 Beagles showed that thin osteo-chondral autografts taken from another joint healed perfectly macroscopically and almost perfectly histologically, if they fitted very well (figure 2). Rib cartilage grafts fitted perfectly to a dog's knee were not successful unless the perichondrium was turned towards the bone, in which case cartilage proliferated on the surface (figure 4). There was very little loss of substance but trans-chondro-osseus perforation also revealed a chondrogenic mode (figure 4). No trace was found in the literature of work concerning a comparison of these two types of grafts in the same experiment.

Animals↗

Pharmacokinetic and clinical observations on prolonged administration of flunitrazepam.

Eight patients were given flunitrazepam 2 mg orally, once daily for 28 consecutive days. The time-course of the plasma concentration of unchanged flunitrazepam and its principal metabolites were studied in detail after the first and last doses. Additional blood samples were collected immediately before administration of the tablet on days 4, 7, 11, 14, 18, 21 and 25. Clinically there were not changes during the trial period in the onset of sleep, duration of sleep, depth of sleep measured as number of spontaneous awakenings, or in the patients' condition on awakening. The time-course of the plasma concentration of flunitrazepam could be described by a three-compartment model, assuming that the rate constants remained unchanged during treatment. Maximal plasma concentrations of unchanged flunitrazepam, found two hours after intake, reached 10-15 ng/ml after the first and 15-20 ng/ml after the last dose. The beta-half-life was found to be between 20 and 36 h.

Adolescent↗

Absorption of large, single, oral intakes of ascorbic acid.

A male non-smoking volunteer increased his daily intake of ascorbic acid continuously by ingesting in a single, oral dose 1, 2, 3, 4 and 5 g crystalline ascorbic acid. The dose was always kept constant for 2 days and was taken with breakfast. During the regimen of ascorbic acid ingestion blood samples were taken and all urine was collected. Then, with a 5 g dose of ascorbic acid 8.17 micro Ci (170 microgram) (1-14C)ascorbic acid was ingested. Following the labelled dose radioactivity was determined in plasma, urine, and faeces. Daily ingestion of 5 g ascorbic acid was continued for 10 days. During the whole experiment the ascorbic acid concentrations in plasma and in urine were determined. The urinary excretion of unmetabolized unlabelled ascorbic acid per day was taken as index for the absorption of ascorbic acid. It decreased from 75% (1 g), 44.0% (2 g), 39%, (3g), 28% (4 g) to 20% (5 g) of the ingested ascorbic acid. The linearisation of the relationship between ingested dose and the excreted amount in urine yielded a maximum amount of 1160 mg ascorbic acid which can be absorbed in 24 h under the conditions of the experiment. The experiment with (1-14C)ascorbic acid revealed that a single oral dose of 5 g ascorbic acid is absorbed to 22.2%, in the faeces collected up to 117 h following ingestion of label only 2.8% of the radioactivity could be recovered. Several possibilities are discussed regarding the fate of the remaining unabsorbed (1-14C)ascorbic acid.

Adult↗

Human melanoma tumor-specific antigens (II): Comparison of antigens from tumor cell plasma membranes of five melanoma patients.

Plasma membranes were purified from tumor tissue of five malignant melanoma patients. The purified membranes were solubilized by sonication in KC1 in the presence of Triton X 100. The soluble membranes that were obtained by this procedure contained human melanoma tumor-specific antigens. The antigens were separated from the other soluble plasma membrane proteins by chromatography on affinity columns made from the patients' tumor-specific pre-absorbed IgG coupled to Sepharose 4B. Specific antigens which were eluted from these affinity columns with potassium thiocyanate were determined by crossover immunoelectrophoresis. The five tumors appear to have a similar complement of melanoma tumor-specific plasma membrane-associated antigens.

Antigens, Neoplasm↗

Pathological cell aggregates in bone marrow cultures from patients with various hematological diseases.

Non-clonal growth of macroscopic cell aggregates in methylcellulose cultures of abnormal marrow is described. They were seen in all patients with Graft-versus-Host Disease, graft rejection, and autoimmune disease presumably directed against hemopoietic cells, we found them in 35% of patients with primary hematological neoplasias and rarely in patients with solid tumors. They were never encountered in 80 healthy controls. The aggregates originated from small cell clumps which sedimented with the "buffy coat" in contrast to normal bone marrow particles. They contained tumor cells, grafted myeloid cells, or target cells of autoimmune disease in association with a widely varying amount of macrophages. Preliminary results suggest that the frequency of macrophages within the aggregates correlates inversely with the aggressiveness of the clinical condition. We propose that appearance of such aggregates in an indicator of immune activation; we expect that further quantitation of the phenomenon will reveal important clinical correlations and provide a model for the study of host defense to "foreign" cells.

Anemia, Hemolytic, Autoimmune↗

[Immune profile in patients with Hodgkin's disease in long-term remission after cytostatic chemotherapy].

13 patients in complete and prolonged remission after treatment with cytostatic chemotherapy for disseminated Hodgkin's disease have been investigated for immune competence by a total of 27 immunological parameters. 11 patients had abnormal values for lymphocyte populations, lymphocyte function and skin tests. The immune profile described is suitable for long-term evaluation of patients under immunosuppressive therapy.

Adolescent↗