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Biomedical subjects

D Hartmann

Publications and source records attributed to D Hartmann.

At least 163 records · Page 9Linked to original sources
PubMed1986

Dissociation of therapeutic and toxic effects of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose in tumor-bearing mice.

In this paper, we describe a study of the therapeutic parameters (dose and schedule) and immunomodulatory activity (macrophage, natural killer cell, and T-cell number and function) of polyinosinic-polycytidylic acid admixed with poly-L-lysine and solubilized with carboxymethyl cellulose [poly(I,C)-LC] in the treatment of MBL-2 tumor ascites. Tumor-bearing mice received an optimal therapeutic protocol [100 micrograms poly(I,C)-LC administered twice a wk], a maximum tolerated dose [50 micrograms poly(I,C)-LC administered daily], or the optimal immunomodulatory protocol for normal mice [10 micrograms poly(I,C)-LC administered daily]. The percentage of tumor-associated macrophages and their cytotoxic activity correlated with host survival. In addition, splenic T-cell activity correlated with host survival, and splenic natural killer cell function had a near significant correlation with host survival. These results indicate that the optimal dose and schedule of poly(I,C)-LC for immunomodulation in tumor-bearing animals are also the optimal therapeutic protocol but have less toxicity than the maximum tolerated dose.

Animals↗
PubMed1985

Unaltered immunocompetence in patients with non-disseminated breast cancer at the time of diagnosis.

Immunologic parameters were examined preoperatively in 104 patients with breast cancer, staged according to the TNM classification and in 95 age-matched healthy women. The immunologic evaluation in the peripheral blood included lymphocyte and monocyte counts, determination of E-rosette-forming T-lymphocytes (SER+) and B-lymphocytes (MER+), T-lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin), lymphocyte transformation test with phytohemagglutinin (PHA) and concanavalin A (ConA), and colony formation of T-lymphocytes in agar (T-lymphocyte colony-forming cells, [TL-CFC]). Two age groups (Group A: 30-50 years; Group B: 51-70 years) and the different tumor stages (Stage I-IV) were analyzed. Patients and controls did not differ in the absolute numbers of lymphocytes, T- and B-cells. In patients of Group B, the absolute number of monocytes was increased slightly in Stage II and III and significantly in Stage IV (P less than 0.05). Similarly, the lymphocyte response to PHA was significantly reduced in Stage IV Group B only (P less than 0.05). ConA-induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age-matched controls in whom T-lymphocyte subsets were determined, the absolute numbers of T-cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or lectin fractionation with soybean agglutinin were similar. This study demonstrates that in patients with early breast cancer (Stage I-III), immunocompetence as defined by either functional in vitro studies or surface marker analysis is not significantly altered at the time of diagnosis. In contrast, patients with advanced disease (Stage IV) show a significant increase in the absolute number of monocytes and a depressed PHA responsiveness of mononuclear cells.

Adult↗
PubMed1985

Optimization of an immunotherapeutic protocol with poly(I,C)-LC.

The development of successful immunotherapeutic protocols requires new therapeutic strategies as well as the development of clinically predictive tumor models and protocols. A bell-shaped response curve is observed with many biological response modifiers (BRMs), not only for immunomodulation, but also for therapeutic activity. Although most BRMs, including poly(I,C)-LC, are toxic at high doses, the administration of nontoxic doses by an optimal protocol and route of injection results in significant therapeutic benefit and increased immunomodulation in tumor-bearing animals compared to the administration of a maximum tolerated dose (MTD). We suggest that Phase II clinical trials using an optimal immunomodulatory protocol may result in increased therapeutic activity compared to protocols based on the MTD.

Animals↗
PubMed1984

Human B-like lymphoblastoid cell lines obtained by long-term culture of normal spleen leukocytes.

B-like lymphoblastoid cell lines were obtained by long-term culture of human spleen leukocytes in RPMI 1640 medium containing human plasma fraction instead of whole foetal calf serum. These cell lines, which did not form E-rosettes had membrane immunoglobulins, and expressed Epstein-Barr virus antigens. Most synthesized intracytoplasmic immunoglobulins and were shown to be diploid and to remain so after subcultures. All produced interferon upon induction with Sendai virus.

B-Lymphocytes↗
PubMed1983

[Intact cellular immune response in patients with locally metastasizing breast carcinoma at the time of diagnosis].

Reduced cellular immune response is well documented in patients with advanced breast cancer. To investigate immunocompetence at the time of diagnosis, 104 patients with breast cancer staged according to the TNM classification were studied preoperatively and compared with 95 age matched healthy women. Tests of blood mononuclear leukocytes included lymphocyte and monocyte counts, determination of rosette forming T (SER +) and B (MER +) lymphocytes, T lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin, SBA), lymphocyte transformation tests with PHA and ConA and colony formation of T cells in agar (TL-CFC). Two age groups (A: 30-50, B: 51-70 years) and the different tumor stages (I-IV) were analyzed. Patients and controls did not differ in absolute numbers of lymphocytes, T and B cells. In patients of group B the absolute number of monocytes was slightly increased in stages II and III and significantly in stage IV (p less than 0.025). Similarly, the lymphocyte response to PHA was significantly reduced in stage IV group B only (p less than 0.05). ConA induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age matched controls, in whom T lymphocyte subsets were determined, the relative numbers of T cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or SBA were similar. In conclusion, in breast cancer, at the time of diagnosis, blood T lymphocyte populations and functions are not altered except in elderly patients with disseminated disease. The monocytosis and reduced PHA responsiveness observed in the latter group may be related phenomena.

Adult↗
PubMed1983

[Fibrotic interstitial pneumopathies. Collagenolytic activity of the alveolar fluid].

Collagenolytic enzyme release in alveolar structures is probably one of the initial events leading to impaired balance between collagen synthesis and degradation in the connective matrix of the lung, resulting in pulmonary fibrosis. The collagenolytic activity was determined in the bronchoalveolar fluid of 40 normal subjects or patients with miscellaneous pulmonary diseases and was found to be present in seventeen, viz.: 7/7 patients with interstitial fibrosis, irrespective of its origin: 4/4 patients with radiation pneumonitis; 4/15 patients with sarcoidosis and 2/2 patients with transient eosinophilic pneumopathy. There was no evidence of fibrosis in the 23 patients who showed no collagenolytic activity. Thus, collagenolytic enzymes are present in the alveolar structures of patients with interstitial pulmonary diseases of diverse origin capable of leading to fibrosis. Monitoring the release of this enzyme by bronchoalveolar lavage could be useful to evaluate the risk of fibrosis in such patients.

Collagen↗
PubMed1983

The role of the penetrating wound in the development of sympathetic ophthalmia experimental observations.

Clinical observations have established that sympathetic ophthalmia (SO) develops after a penetrating wound but not subsequent to often more severe intraocular disturbances such as extensive photocoagulation. A feature of the penetrating wound that appears important in the pathogenesis of SO is the access it provides for intraocular antigens to reach regional lymph nodes. The intraocular compartment has no lymphatic drainage and appears to function like a number of alymphatic biologic sites. In an experimental model of SO, subconjunctival injection of retinal S antigen in one eye induced a bilateral sympathetic uveitis, whereas intraocular injection in one eye was ineffective in inducing sympathetic disease.

Animals↗
PubMed1983

Hypertrophic repair of articular cartilage in experimental osteoarthrosis.

Section of the anterior cruciate ligament has been performed in the knee of 11 mature dogs. The macroscopically normal cartilage from patella and femoral trochlea of animals killed from 2 to 32 weeks after operation was used for histological, histomorphometrical, and biochemical analysis. Previously undescribed degenerative lesions of the superficial matrix were observed, and there was evidence for secondary healing of these lesions. An early and progressive decrease in superficial cell density and a later progressive increase in cartilage thickness without any change in the cell density of the middle and deep cartilage layers was found. A slight increase in water content with no reduction in glycosaminoglycan content was observed. The results suggest that joint laxity results initially in superficial degenerative changes and later in hypertrophic regenerative changes due to cell proliferation and increased matrix synthesis. Hypertrophic remodeling of articular cartilage in response to abnormal mechanical stresses is postulated.

Animals↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1982

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↗