Biomedical subjects

K Hartmann

Publications and source records attributed to K Hartmann.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Drug-induced discoloration of the teeth and gingiva].

For this article all cases of suspected drug-induced discolouration of teeth and gingiva reported between 1.1.1989 and 31.5.1997 have been collected. As far as documented all discolourations were reversible and represented exclusively undesired but not serious adverse drug effects. In the literature such events are usually not mentioned. Thus, sense and intention of this work is to draw attention to certain adverse effects that are hitherto not well known.

Adolescent↗

PubMed1998

Karnofsky's score modified for cats.

The index of Karnofsky evaluating quality of life was originally developed by David A. Karnofsky in 1948. It determines the ability of a patient to carry on normal activities in life by using a scale from 0 to 100%. This index was modified for the cat. The index enables judgment of life quality and well-being in cats which is very difficult to interpret. Objectivity is given by a classification orientated in details concerning general condition as well as eating, playing, sleeping, and social behavior.

Animals↗

PubMed1998

[Differences in the relative incidence of adverse drug reactions in relation to age? An evaluation of the spontaneous reporting system of SANZ (Swiss Drug Monitoring Center)].

The risk of presenting adverse drug reactions (ADR) is greater for elderly patients. Chronological age is not an independent risk factor for ADRs, but age-dependent factors such as polymedication, multiple diseases and changes in pharmacokinetics and pharmacodynamics seem to be responsible for the risk of developing more adverse drug reactions. We analyzed the ADRs spontaneously reported to the Swiss Drug Monitoring Centre (SANZ) between 1981 and 1995. Age-specific relative incidences of the reported ADRs affecting different organ systems were calculated. For elderly patients we found a decrease in the relative incidence of dermatological ADRs and an increase in neuropsychic and hematological ADRs. The incidence of serious ADRs increased by 8.7% in older patients (> 70 years). The results of this analysis of spontaneous reports were inconsistent with results from epidemiological studies. The possibility and reasons for under-reporting ADRs occurring in elderly patients are discussed.

Adolescent↗

PubMed1998

Efficacy of the acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) against feline immunodeficiency virus.

The acyclic nucleoside phosphonates (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were evaluated for their efficacy and side effects in a double-blind placebo-controlled trial using naturally occurring feline immunodeficiency virus (FIV)-infected cats. This natural retrovirus animal model is considered highly relevant for the pathogenesis and chemotherapy of HIV in humans. Both PMEA and FPMPA proved effective in ameliorating the clinical symptoms of FIV-infected cats, as measured by several clinical parameters including the incidence and severity of stomatitis, Karnofsky's score, immunologic parameters such as relative and absolute CD4+ lymphocyte counts, and virologic parameters including proviral DNA levels in peripheral blood mononuclear cells (PBMC) of drug-treated animals. In contrast with PMEA, FPMPA showed no hematologic side effects at a dose that was 2.5-fold higher than PMEA.

Adenine↗

PubMed1998

Production and pre-clinical significance of haematopoietic peptide growth factors (HPGF) in human non-seminomatous germ cell tumour cell lines.

Peptide growth factors involved in the regulation of haematopoiesis (HPGF), for example granulocyte-colony-stimulating factor (G-CSF) and granulocyte/macrophage-colony-stimulating factor (GM-CSF), are of clinical importance in the treatment of testicular germ cell tumour (GCT) patients with modern chemotherapy regimens since they ameliorate chemotherapy-induced neutropenia. Aberrant expression of and/or response to HPGF has been reported in several solid tumour types although no data are available on GCT with the exception of those on stem cell factor (SCF). The aims of this pre-clinical study were twofold: (1) to screen a panel of human non-seminomatous (NS)GCT for the production of HPGF and (2) to test the effects of G-CSF or SCF on the growth of NSGCT cell lines in vitro, and on the growth kinetics of two human NSGCT xenograft models. HPGF concentrations in cell culture supernatant from 11 NSGCT cell lines growing under routine culture conditions were measured by enzyme-linked immunosorbent assay. The growth kinetics of cell lines was quantified in vitro using the sulphorhodamine B assay. The growth kinetics of nude mouse NSGCT xenografts was followed by measuring tumour volumes every 2-3 days over days 1-30, following daily subcutaneous injection of nude mice (days 1-14). The cell lines produced G-CSF (1/11 cell lines), GM-CSF (2/11), SCF (2/11), M-CSF (6/11). and interleukin-6 (9/11). Growth stimulation of cell line H12.1 by SCF was observed in vitro, but no statistically significant differences in NSGCT xenograft tumour volume (VT) or relative VT (r VT) in treated groups were observed on days 14 or 29 compared to the control. The change in rVT of H12.1 xenografts treated with G-CSF alone compared to control (rVT/rVT,c) was 0.96 on day 29. The values for rVT/rVT,c for H12.1 xenografts treated with G-CSF in combination with low- or high-dose SCF were, respectively, 1.67 or 1.7 compared to 1.19 for SCF-treated mice. The results are in agreement with clinical data to date where no observations have been reported of stimulation or inhibition of tumours in patients receiving treatment with G-CSF. Before any clinical trials are initiated in GCT patients treated with G-CSF in combination with SCF, further pre-clinical experiments with this tumour type are recommended to investigate this phenomenon further in a greater number of NSGCT cell lines in vitro and in vivo and with a wider range of SCF/G-CSF schedules. The potential relevance of secretion of HPGF in NSGCT cell lines in vitro to the pathobiology of GCT in patients is also a subject of interest for future research.

Animals↗

PubMed1998

Feline immunodeficiency virus infection: an overview.

In 1987, Pedersen et al. (1987) reported the isolation of a T-lymphotropic virus possessing the characteristics of a lentivirus from pet cats in Davis, California. From the first report onwards, it was evident that in causing an acquired immunodeficiency syndrome in cats, the virus was of substantial veterinary importance. It shares many physical and biochemical properties with human immunodeficiency virus (HIV), and was therefore named feline immunodeficiency virus (FIV). This article reviews recent knowledge of the aetiology, epidemiology, pathogenesis, clinical signs, diagnosis, prevention, and treatment options of FIV infection.

Animals↗

PubMed1998

Fas ligand (FasL, CD95L, APO-1L) expression in murine mast cells.

Fas ligand (FasL, CD95L, Apo-1L), a type II membrane protein belonging to the tumour necrosis factor family, induces apoptosis in Fas-bearing cells. As murine mast cells have been shown to express Fas antigen, we hypothesized that mast cells might also express FasL. To explore this possibility, we first demonstrated FasL mRNA in mast cells by reverse transcription-polymerase chain reaction and FasL protein by immunoblot analysis. FasL protein was shown to be exclusively located within the cell by flow cytometry. In agreement with this observation, bone marrow cultured mast cells were unable to kill Jurkat T cells. Our results demonstrate that FasL is expressed in murine mast cells and suggest that this murine mast cell FasL is not lytic, owing to the intracellular localization.

Animals↗

PubMed1997

Fas (CD95, APO-1) antigen expression and function in murine mast cells.

As an extension of the observation that mast cells undergo apoptosis following growth factor deprivation, we hypothesized that mast cells might also undergo apoptosis in response to activation through Fas Ag (CD95, APO-1), thus providing an additional pathway that could contribute to the regulation of mast cell numbers. Surface expression of Fas Ag was studied by flow cytometry, and apoptotic changes following treatment with anti-Fas mAb were analyzed using flow cytometric analysis of PI uptake and TUNEL staining, DNA electrophoresis, and electron microscopy. Murine bone marrow-cultured mast cells (BMCMC) and peritoneal mast cells, as well as two mast cell lines (C57 and MCP-5), constitutively expressed Fas Ag. Aggregation of Fas Ag with anti-Fas mAb resulted in the characteristic changes of apoptosis in C57 mast cells. BMCMC were resistant to anti-Fas mAb alone, but after the addition of actinomycin D also exhibited apoptosis in response to anti-Fas treatment. In addition, actinomycin D alone induced apoptosis. Stem cell factor, TGF-beta, and Fc epsilon RI aggregation enhanced Fas expression. However, Fas-mediated apoptosis was not augmented by Fc epsilon RI aggregation, and stem cell factor and TGF-beta partially protected BMCMC against Fas-mediated cytotoxicity. Finally, C57 mast cells were highly susceptible to killing by a Fas ligand-bearing CTL hybridoma, while BMCMC were relatively resistant, consistent with the results using anti-Fas mAb. Thus, induction of mast cell apoptosis by activation of the Fas pathway provides an additional mechanism by which mast cell numbers may be regulated in biologic systems.

Animals↗

PubMed1997

C3a and C5a stimulate chemotaxis of human mast cells.

The factors that control migration of mast cells to sites of inflammation and tissue repair remain largely undefined. Whereas several recent studies have described chemotactic factors that induce migration of murine mast cells, only stem cell factor (SCF) is known to induce migration of human mast cells. We report here that the anaphylatoxins C3a and C5a are chemotactic factors for the human mast cell line HMC-1, human cord blood-derived mast cells (CBMC) and cutaneous mast cells in vitro. The presence of an extracellular matrix protein, laminin, was required for chemotaxis in response to complement peptides. Migration of mast cells towards C3a and C5a was dose-dependent, peaking at 1 microg/mL (100 nmol/L), and was inhibited by specific antibodies. Pretreatment with pertussis toxin inhibited the anaphylatoxin-mediated migration of HMC-1 cells, indicating that Gi proteins are involved in complement-activated signal transduction pathways in human mast cells. Both C3a and C5a also induced a rapid and transient mobilization of intracellular free calcium ([Ca2+]i) in HMC-1 cells. Besides SCF, other chemotactic factors tested, such as interleukin-3, nerve growth factor, transforming growth factor beta, RANTES (regulated upon activation, normal Tcell expressed and secreted), monocyte chemotactic protein-1 (MCP-1), MCP-2, MCP-3, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta, failed to stimulate migration of human mast cells. In summary, these findings indicate that C3a and C5a serve as chemotaxins for human mast cells. Anaphylatoxin-mediated recruitment of mast cells might play an important role in hypersensitivity and inflammatory processes.

Calcium↗

PubMed1997

Signal generation in a non-EU country.

One of the most important objects of post-marketing surveillance is the early detection of serious, unknown and unexpected adverse events. As spontaneous reported adverse events vary considerably in their signal-generating value the Swiss Drug Monitoring Center SANZ implemented an early signal detection system in 1991. With a set of screening criteria the individual case reports are automatically checked by the system and read into a signal file. Subsequently these potential signals are processed to quantify the signal generating value of the particular case. According to the screening criteria 2072 (53%) of the reported cases were considered as potential signals. After validating and quantifying their signal value 27% (565) were drug-related and unlabelled, 8% (173) were also rated as serious. On the basis of these cases 114 labelling changes were made. Some of the most interesting cases are discussed. This computer-assisted early signal generation model in a small country with 7 million inhabitants has a high detectability of new, rare, serious and quality of life affecting adverse drug reactions (ADRs). These newly detected ADRs must be interpreted in cognizance of the limitations and restrictions of spontaneous reporting and do not allow pharmacoepidemiologic conclusions.

Journal Article↗

PubMed1997

Transdermal nicotine replacement in pregnancy: maternal pharmacokinetics and fetal effects.

OBJECTIVE: Our purpose was to measure any short-term effects that the transdermal nicotine replacement system may have in pregnancy and to verify salivary nicotine and cotinine levels during patch placement. STUDY DESIGN: After customary smoking cessation efforts had failed, six prenatal patients between 28 and 37 weeks' gestation who smoked between one and two packs per day were enrolled in this prospective study. The patients were admitted to the General Clinical Research Center for a period of 21 hours. During hospitalization we performed maternal and fetal assessments including vital signs, biophysical profile and electronic fetal monitoring, amniotic fluid index, and umbilical artery Doppler examinations. Salivary samples for cotinine and nicotine levels were collected at standard intervals. RESULTS: There were no measurable differences in fetal or maternal well-being. During patch use salivary nicotine levels increased as expected, to a mean value of 19.0 +/- 13.5 micrograms/L at 480 minutes. Salivary cotinine concentrations remained low (approximately 50 micrograms/L) and varied little during the 480-minute period that the patch was worn. Overall, patients were satisfied with the transdermal patches. CONCLUSION: There were no adverse maternal or fetal effects from the transdermal nicotine replacement system over the 6-hour period. Salivary nicotine concentrations were consistent with those seen in nonpregnant adults. Surprisingly, salivary cotinine concentrations were much lower than those seen in smoking nonpregnant adults.

Administration, Cutaneous↗

PubMed1997

Toxicity associated with high dosage 9-[(2R,5R-2,5-dihydro-5-phosphonomethoxy)-2-furanyl]adenine therapy off attempts to abort early FIV infection.

9-[(2R,5R-2,5-dihydro-5-phosphonomethoxy)-2-furanyl]adenine, or D4API, was tested in the feline immunodeficiency virus (FIV) infection model and found to be significantly more inhibitory in vitro than its parent compound 9-phosphonylmethoxethyl adenine (PMEA). Cytotoxicity was less than for PMEA or azidothymidine (AZT) for culture periods of 7 days, but more toxic after 10 days. D4API was rapidly absorbed by cats following subcutaneous inoculation, with a plasma half-life of less than 1 h after intravenous inoculation and between 2 and 3 h after subcutaneous injection. Peripheral blood mononuclear cells collected from cats given a single dose of D4API were refractory, however, to FIV infection in vitro for up to 24 h. Given its prolonged intracellular phase and high selectivity index, high dose D4API therapy was tested for its ability to abort an acute (i.e. 2 week) FIV infection. A divided daily dose of D4API, which was one-fourth the toxic dose and 125 times the concentration that would totally inhibit virus replication in vitro, completely abrogated the anticipated viremia and antibody responses. Unfortunately, a majority of treated/uninfected and treated/infected test cats died acutely of drug toxicity after 47 days of treatment. Toxicity in vivo mirrored what was observed in vitro, being precipitous and cumulative in nature. Toxic signs included widespread hepatic and lymphoid necrosis. A surviving treated/FIV infected cat remained healthy to day 175 when the study was terminated; antibodies appeared 2 months later than in untreated/infected cats and virus was only detectable at low levels on day 175. In contrast, untreated/infected cats were viremic and antibody positive from 3 to 4 weeks post-infection onwards. Therefore, it was possible to alter, but not abort, an early FIV infection with prolonged, high-dose D4API treatment.

Adenine↗

PubMed1997

Individual differences in the memory representation of emotional episodes: exploring the cognitive processes in repression.

Two studies investigated the influence of a repressive coping style on the availability and accessibility of emotion memories. In Study 1 participants rated the presence and intensity of emotions in several scenarios and then estimated the frequency of emotions in the scenarios. Repressors did not process the scenarios more superficially. Repressors indicated the presence of unpleasant emotions in the scenarios less frequently, but not less intensely. The frequency differences accounted for most of the repression effects in the latter frequency judgments. In Study 2 participants judged the frequency of emotions twice a day for 2 weeks and then judged the frequency of emotions for the 1st and 2nd week. Repression effects in the frequency judgments did not increase with longer retention intervals. The results indicate that a repressive coping style influences mainly the experience of emotions but not so much the accessibility of emotion memories.

Adaptation, Psychological↗

PubMed1997

Evidence for binding of in vitro glycated low-density lipoproteins by fructosyllysine-specific sites on macrophages and U937 monocyte-like cells.

Early development of arteriosclerosis is a main late complication of diabetes mellitus. Although its uptake by LDL receptors is impaired, glycated LDL is thought to play a role in foam cell formation from macrophages. In the present study we show binding of glycated LDL (8-9 mol fructosyllsine/mol apo B) to macrophages and to the monocyte-like cell line U937. The binding involves fructosyllysine-specific binding sites, as well as LDL and scavenger receptors. Fructosyllysine and glycated albumin were competitors for binding of 125I-labelled glycated LDL by macrophages and U937 cells. Scatchard analysis of binding data using a two ligands binding model showed a linear plot with Ka = 2.6 x 10(7) M-1 for U937 cells, which lack scavenger receptors. On U937 cells only the 200 kDa fructosyllysine-specific receptor protein and the 165 kDa LDL receptor were involved in binding glycated LDL as evidenced by ligand blotting. U937 cell uptake and degradation of glycated LDL was mediated by fructosyllysine-specific and LDL receptors. Binding of glycated LDL by macrophages via fructosyllysine-specific sites could be demonstrated in only 6 from 35 rats investigated, indicating that the receptor is not expressed in each individual. Whether the fructosyllysine-specific receptor mediated pathway is relevant for uptake and degradation of glycated LDL in vivo is yet to be determined.

Animals↗

PubMed1997

Antiretroviral activities of acyclic nucleoside phosphonates [9-(2-phosphonylmethoxyethyl)adenine, 9-(2-phosphonylmethoxyethyl)guanine, (R)-9-(2-phosphonylmethoxypropyl)adenine, and MDL 74,968] in cell cultures and murine sarcoma virus-infected newborn NMRI mice.

From a side-by-side comparative study, the acyclic nucleoside phosphonates (R)-9-(2-phosphonylmethoxypropyl)adenine [(R)-PMPA] and 9-(2-methylidene-3-phosphonomethoxypropyl)guanine (MDL 74,968) proved more selective in their inhibitory effect on human immunodeficiency virus types 1 and 2, feline immunodeficiency virus, and Moloney murine sarcoma virus (MSV) in cell cultures than the 9-(2-phosphonylmethoxyethyl) derivatives of adenine (PMEA) and guanine (PMEG). In particular, PMEG proved quite toxic. PMEA, (R)-PMPA, and MDL 74,968 afforded a marked delay in MSV-induced tumor initiation in MSV-infected newborn NMRI mice and substantially delayed associated animal death at doses as low as 4 to 10 mg/kg of body weight. Treatment of the NMRI mice with PMEA, (R)-PMPA, and MDL 74,968 at 25 or 50 mg/kg resulted in a high percentage of long-term survivors.

Adenine↗

PubMed1997

Enhanced P-selectin expression in chronic and dermographic urticaria.

In both chronic and dermographic urticaria, superficial perivascular leukocytic infiltrations are seen histologically in lesional skin. We have therefore investigated the role of endothelial adhesion molecule expression in these diseases. E-selectin, P-selectin, ICAM-1 and VCAM-1 expression was examined immunohistologically, and the serum levels of the soluble forms of these adhesion molecules were determined by EIA in patients with chronic urticaria, dermographic urticaria as well as in healthy controls (n = 8 in each group) and subjects with symptomatic allergic rhinitis (n = 7) for comparison. A significant increase (p<0.01) was observed for soluble P-selectin in dermographic urticaria (mean 487+/-44 ng/ml) and chronic urticaria (mean 464+/-74 ng/ml) compared to healthy controls (mean 149+/-15 ng/ml) and rhinitis subjects (mean 177+/-30 ng/ml). In contrast, the other adhesion molecules were not significantly elevated in both urticaria groups. Immunohistologically, a strong expression of P-selectin was found in superficial vessels of lesional and nonlesional skin in dermographic urticaria with only a mild increase of the other adhesion molecules studied, supporting the findings observed with the soluble forms in the patients' sera. Since an alteration of soluble P-selectin was not seen in symptomatic allergic rhinitis, an unspecific effect due to inflammation appears to be unlikely. These results therefore point to a potentially relevant role of the endothelial P-selectin expression in the evolution of urticarial whealing.

Case-Control Studies↗

PubMed1997

[Canine hypothyroidism: detection of anti-thyroglobulin autoantibodies].

An enzyme-linked immunosorbent assay was established to detect autoantibodies in canine patients with hypothyroidism. Thyroglobulin, purified from thyroid glands of euthanized, healthy dogs, was used as antigen. Utilizing this test system, sera of 39 patients with hypothyroidism were screened for the presence of thyroglobulin specific autoantibodies. Positive titers were found in 38% of these dogs, whereas 18 out of 72 patients (25%) with other internal diseases showed a positive reaction. In addition 21 healthy dogs were tested for the presence of anti-thyroglobulin autoantibodies. Three dogs were found to be positive in the ELISA. Development of autoantibody titers was followed up in four cases over a period of one year. A steady decline of autoantibody titers was observed in three patients with hypothyroidism, whereas titers of one healthy dog remained high over this period.

Animals↗

PubMed1997

[Long-term changes in availability of domestic nursing care based on family structure changes--a model calculation].

A central hypothesis in German family sociology is the observation of a disruption of family structures. If this disintegration prevails up to highest ages it must, among others, lead to an increasing inability to perform nursing care within families. The most important person in case of a need for nursing care is the spouse. The main topic of this paper is to determine whether demographic and familiar developments in Germany will increase or decrease the share of men and women at higher ages with a living spouse within the next decades. In spite of a slowly increasing share of the never-married and the divorced, on the average elderly men and women will be married to a greater and widowed to a much lesser proportion within the next decade. The Dutch LIPRO-model is used to calculate the exact numerical developments. The surprising result is primarily due to the fact that the actual high shares of the widowed are a consequence of distortions caused by the two World Wars. During the next few decades, these unusual developments will disappear even among the most elderly.

Aged↗