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Biomedical subjects

K Hartmann

Publications and source records attributed to K Hartmann.

At least 91 records · Page 5Linked to original sources

[Clostridium difficile associated diarrhea in cephalosporin administration: experiences of the Swiss Adverse Drug Reaction Reporting System 1981-1995].

20-25% of antibiotics-associated diarrhea cases are caused by infection with toxin-producing Clostridium difficile. Since the advent of broad-spectrum antibiotics Clostridium difficile-associated diarrhea has been observed both in ambulatory practice and as a nosocomial infection in medical and nursing institutions. Clindamycin, aminopenicillins, and cephalosporines are by far the most common triggers for this infection. We reviewed all cases of Clostridium difficile-associated diarrhea due to cephalosporines which were reported to the Swiss Drug Monitoring Center (SANZ) between 1981 and 1995. 87 cases were reported (0.9% of 9720 spontaneous reports in this period), 69 (79%) of which were considered to be due to cephalosporines. In 74% of the cases the indication for the antibiotic treatment was an upper respiratory tract infection. 61 patients received cephalosporines by oral route and 9 patients by intravenous route. Two patients had to be hospitalized. There were no deaths. The pathogenesis, clinical picture, and therapy of Clostridium difficile-associated diarrhea is discussed. We conclude from these cases in the spontaneous reporting system of SANZ that Clostridium difficile infection due to cephalosporines is a frequent occurrence. Because the course can be severe, cephalosporines should be used restrictively.

Adolescent↗

[Placebo-controlled double-blind study on the efficacy of a paramunity inducer in the treatment of naturally FeLV-infected cats].

The study involved 120 cats, of which 60 were treated with Baypamun HK and 60 cats received a preparation of virus free cell culture medium. Therapeutic efficacy was determined by monitoring the general status of health, body weight, skin, lymph nodes, oral cavity, the presence of the p27 antigen and the FeLV p27 antigen concentration in serum. No statistically significant differences between both groups could be demonstrated neither for clinical nor for virologic parameters. Remission of the viremia occurred in 11.7% of the cats treated with Baypamun HK and in 6.7% of the cats treated with placebo. The FeLV p27 antigen level decreased by an average of 7.2% with Baypamun HK and by an average of 5.1% with placebo.

Adjuvants, Immunologic↗

[Comparative investigation of the efficacy of two nucleocapsid analogs in FIV infected cats].

Antiviral activity of the acyclic nucleoside phosphonates 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) against feline immunodeficiency virus (FIV) was investigated in field cats. The study was designed as a placebo-controlled double-blind study enrolling 27 FIV infected cats. Nine cats received PMEA at a dosage of 10 mg/kg body weight, nine cats received FPMPA at a dosage of 25 mg/kg body weight. A variety of parameters were established to evaluate the therapeutic efficacy of the compounds. The improvement was monitored by different aspects: clinical status, index of Karnofsky modified for the cat, laboratory parameters, immunological parameters, surrogate markers, and a virological parameter. Concerning the clinical and immunological parameters cats of both treatment groups disclosed a relevant improvement. Efficacy of antiviral treatment was a little bit higher in the cats treated with PMEA than in the animals injected with FPMPA. However, side effects were also more prominent in the PMEA treated group.

Adenine↗

[Liver injury caused by coumarin anticoagulants: experience of the IKS (Intercanton Monitoring Station) and the SANZ (Swiss Center for Drug Monitoring)].

Drug-induced liver diseases are potentially avoidable. Hepatotoxic drugs can mimic virtually any form of liver disease. Among all voluntary adverse drug reaction reports to central registries, 4-7% refer to drug-induced liver diseases. We analyze all cases of coumarin-induced hepatic injuries reported on a voluntary basis to the Swiss Drug Monitoring Centre (SANZ) and the Pharmacovigilance Centre (IKS) from 1981 to 1995. During this period the SANZ collected 9720 reports, 674 of which (6.9%) referred to the liver and the biliary tract. In only 11 reports an oral anticoagulant was involved. In 8 cases we assumed at least a possible causal relationship. 2 more cases were reported directly to the IKS. Among these 10 cases 7 were related to phenprocoumon and 3 to acenocoumarol. In 4 cases elevated concentrations of liver enzymes were measured 2-7 days after the beginning of therapy. In the remaining 6 cases the clinical picture was so severe that the patients had to be hospitalized. These 10 cases are discussed and compared with the cases published in the literature. According to our data, hepatic disorders induced by coumarin-anti-coagulants are rare. If hepatitis is diagnosed in a patient treated with oral anticoagulants, the differential diagnosis of a coumarin-induced hepatic injury has to be considered. Crossreactions between the coumarin derivatives phenprocoumon and acenocoumarol are possible.

Acenocoumarol↗

[Ulcer drugs: profile of side effects of proton-pump blockers in comparison to H2 blockers in the spontaneous reporting system].

Inhibition of gastric acid secretion by drugs remains the most important rational approach to the treatment of acid related diseases. Histamine H2-antagonists and more recently the proton pump blockers have become the first line treatment for acid peptic diseases. Proton pump blockers bind specifically to the proton pump of the parietal cells and thus inhibit the final acid secretion independently from the activating stimuli. Because of this specific mechanism fewer adverse effects on other systems in the body are expected with proton pump blockers than with histamine antagonists. An analysis of the spontaneous reports which the Swiss Drug Monitoring Center (SANZ) received from 1981 to 1995 showed striking differences in the adverse drug reaction profile: hypersensitivity reactions with fever and anaphylactic reactions, liver disorders such as cholestatic hepatitis, most with severe progression and requiring hospitalization, as well as endocrine disorders were reported more frequently with histamine antagonists, skin reactions and joint disorders, however, were reported more often with proton pump blockers. Our data also support the conclusion that adverse drug reactions to proton pump blockers and histamine antagonists are rare in the spontaneous reporting scheme (reporting rate < 1%). There was a somewhat higher rate of serious reports with histamine antagonists. These data do not allow conclusions concerning long-term effects or effects with larger than recommended dosages.

Anti-Ulcer Agents↗

[Thromboembolic events in women treated with hormones. Acute cerebrovascular thrombosis in 2 young women receiving ovulation inhibitors, and experiences of SANZ (Swiss Drug Monitoring Center) 1991-1995].

We describe 2 young patients with severe cerebrovascular thrombotic events whose only risk factor was intake of oral contraceptives. A 41-year-old woman suffered thrombosis of the basilar artery and remained disabled with a locked-in syndrome; a 23-year-old woman had thrombosis of the sinus sagittalis. These 2 cases and the current discussion regarding the use of hormones either as oral contraceptives or hormonal replacement therapy with estrogens and/or progestins prompted a review of the literature and a review of all spontaneous reports from 1991 to 1995 to SANZ (Schweizerische Arzneimittel-Nebenwirkungs-Zentrale), the Swiss Drug Side Effects Monitoring Center. The spontaneous reporting under this system does not allow conclusions on prevalence and incidence of adverse events. In these 5 years 33 vascular events associated with different hormones were reported. There were 28 reports of venous thrombosis of the lower and upper limb or pulmonary embolisms, and 5 reports of cerebrovascular complications. In 9 of 33 cases the hormones were used as hormonal replacement therapy and in 24 of 33 cases as oral contraceptives. In half of these women other risk factors for thromboembolic events such as overweight, family history of thrombosis and immobilization were known. Complications occurred with different preparations containing different estrogens and progestins. According to the literature, third generation progestins seem to involve a slightly increased risk of venous thromboembolism but a reduced risk of arterial thromboembolic events, which was confirmed by the SANZ data (17 of all 24 cases). Increasing age and rising estrogen dosage of oral contraceptives are associated with increased risk of vascular events. Although thromboembolic events also occur during hormonal replacement therapy with naturally occurring estrogens, the prophylactic potential of these drugs with regard to osteoporosis and cardiovascular events certainly outweighs this risk.

Adult↗

Feline immunodeficiency virus infection--causative agent of an acquired immunodeficiency syndrome in cats.

An ideal animal model for human immunodeficiency virus (HIV) infection in man should be caused by a genetically similar virus, it should cause as nearly identical clinical signs as possible, the pathogenesis of the resulting disease should be similar, and the model should be easily accessible to all researchers. Feline immunodeficiency virus (FIV) meets all these criteria. FIV is particularly useful as an animal model for investigation of the pathogenesis of lentivirus infections like cofactor studies, as well as for vaccine strategies, and drug testing in vitro and in vivo.

Animals↗

[Drug-induced taste disorders].

Taste disorders may have diverse uncomfortable consequences such as reduced quality of life, weight loss and possibly professional disability. The sense of taste depends on many factors. Thus various conditions may cause taste disorders, drugs being one of them. The list of drugs being able to cause taste disorders as adverse drug reaction is long and there are many such cases reported to the Swiss Drug Monitoring Center (SANZ). The possibility of an unwanted side effect should be taken into account if a patient complains about taste disorders, such as reduced or changed sense of taste.

Adult↗

[Side effects of drugs on the respiratory tract: experiences of the Swiss Drug Monitoring Center from 1991 to 1995].

Between 1991 and 1995 about 3% of the unwanted drug-induced side effects reported to the Swiss Drug Monitoring Center (SANZ) concerned pulmonary disturbances (144 out of a total of 4824 reports). The most frequent reports were those about cough and taste disorders caused by ACE-inhibitors, smell disorders caused by antimicotics, and asthma attacks caused by nonsteroidal antirheumatics or betablocking eye drops. 33% of these unwanted side effects have been classified as severe. By spontaneous reporting a correct calculation of incidence is not possible. The reports, however, have signal function. Precise case analysis, temporary correlations (reaction and exposure time and onset of reaction), exclusion of other causes for the disease, comparisons between similar cases and critical study of literature concerning drug-related side effects are still the most important foundations for diagnosis.

Drug Monitoring↗

[Exacerbation of pseudoparalytic myasthenia gravis following azithromycin (Zithromax)].

We report the case of a 25-year-old female patient with severe aggravation of myasthenia gravis due to azithromycin which was prescribed for an influenza syndrome. One hour after the intake of 500 mg azithromycin the patient developed weakness of the legs and respiratory distress due to respiratory muscle failure. She was hospitalized in a comatose state and required intubation and mechanical ventilation for six days. Acute worsening of myasthenia gravis was observed in this patient in 1986 after parenteral administration of erythromycin. Erythromycin causing aggravation of myasthenia gravis by interfering with neuromuscular transmission is reported in the literature. The close temporal relationship between the intake of azithromycin and severe worsening of myasthenia gravis in our patient suggests that azithromycin, a new azalid-antibiotic of the macrolid group, can exacerbate myasthenia gravis. We conclude that azithromycin should be added to the list of drugs to be used with caution in patients with myasthenia gravis.

Adult↗

Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours.

The proto-oncogene c-kit and its ligand stem-cell factor (SCF) may play an important role in the development of normal and malignant testicular tissue. This study investigates the presence of SCF and c-kit protein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non-seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an immunohistochemical approach. Out of 9 testicular cancer specimens classified as pure seminomas, 7 (78%) showed a strong immunohistochemical reaction for both SCF and c-kit protein on the surface of the tumour cells. Fourteen non-seminomatous germ-cell tumours composed of embryonal carcinoma were completely negative for both SCF and c-kit proteins and only faint positivity was found in 6 tumours (26%). Differentiated teratomatous structures within the specimens on non-seminomatous tumours showed a strong immunohistochemical reaction for SCF and c-kit protein in 8 of 11 (73%) cases. All three testicular cancer cell lines showed only faint staining reactions for c-kit protein and none for SCF. No secretion of SCF by the three lines in vitro was detected. The addition of high concentrations of SCF (100 ng/ml) to the testicular cancer cell lines in culture conditions without fetal calf serum resulted in a 1.4 to 3-fold growth stimulation compared to cell growth in serum-free medium alone. This effect was not detectable when the cells were cultured in serum-containing media. In the normal testicular tissue the germ-cells displayed a strong immunohistochemical reaction for c-kit protein while SCF positivity was found at the tubular membrane and on the surface of Sertoli cells. The SCF/c-kit system may possess a regulatory function in normal testicular tissue by possibly providing the microenvironment necessary for spermatogenesis. With the development of testicular cancer, this regulatory system seems to be lost, particularly in non-seminomatous germ-cell tumours. A growth-stimulatory effect of high concentrations of SCF on non-seminomatous testicular cancer cell lines can be detected only in culture conditions with serum-free media. The effects achievable by the combination of SCF with other growth factors need to be further studied, as well as the role of the c-kit/SCF regulatory system for normal spermatogenesis and its possible implications for the understanding and treatment of male infertility.

Germinoma↗

Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance.

A differing individual expression of fructosyllysine-specific receptors has been found on the monocytes of 90 insulin-dependent diabetic patients and 101 healthy control subjects. The degree of receptor expression is neither age- nor sex-dependent; however, in the diabetic group it correlates significantly with the severity and age of onset of diabetic microangiopathy. To interpret the results of the human study, spontaneously diabetic and non-diabetic BB/OK rats were used to estimate tissue content of glucose-modified proteins and capillary basement membrane thickness in relation to the receptor expression on macrophages. In non-diabetic and diabetic rats no correlation was found between receptor expression and tissue content (i.e. artery, nerve) of fructosyllsine and fluorescent advanced glycation end products. However, animals which express the fructosyllysine receptor showed a greater increase in muscle capillary basement membrane thickness. There are indications that fructosyllysine receptor expression is positively associated with indices of diabetic complications such as microangiopathy and/or capillary basement membrane thickening.

Adult↗

Statewide assessment of a behavioral intervention to reduce cigarette smoking by pregnant women.

OBJECTIVE: Smoking in pregnancy is the foremost cause of preventable perinatal mortality. We have demonstrated that a behavioral intervention can alter smoking in pregnant women. We tested the utility of this intervention at multiple sites in varied settings across a suburban-rural state. STUDY DESIGN: We performed a prospective cohort study at 10 prenatal care sites across North Carolina. Carbon monoxide manometry was used to verify cessation; self-report confirmed reduction. Each site enrolled smokers for 1 year. Four outcome predictor variables were studied: clinic volume, prevalence of smoking, physician versus nonphysician intervenors, and public versus private clinics. RESULTS: Smoking prevalence varied from 4% to 85%. Biologically confirmed quit rates ranged from 0% to 45%. The prevalence of smoking within a clinic's population was able to explain differences in reduction (p < 0.01) of smoking between sites. CONCLUSION: We have demonstrated the effectiveness of an intervention to alter smoking behavior in pregnancy. It appears that this technique has the greatest utility in clinics with a high prevalence of smoking.

Behavior Therapy↗

Comparison of T-cell subpopulations in cats naturally infected with feline leukaemia virus or feline immunodeficiency virus.

T-cell subsets were studied by flow cytometry in 58 feline leukaemia virus (FeLV)-positive cats with naturally acquired FeLV infection to determine whether the changes in CD4+ or CD8+ T cell populations differed from those observed in 55 feline immunodeficiency virus (FIV)-positive cats with naturally acquired FIV infection. The sole criterion for inclusion into the study was seropositivity. Mean (SD) CD4+ T cell values of FeLV positive cats were decreased to 31.1 (8.0) per cent and their CD8+ T cell values were increased to 22.8 (6.3) per cent in comparison with uninfected control cats (37.9 [9.5] per cent CD4+; 15.2 [6.3] per cent CD8+). The CD4+/CD8+ ratio was reduced to 1.5 (0.7), compared with 3.0 (1.5) in 39 FeLV-and FIV-negative control cats. Differences from control values were significant, but there was no significant difference between CD4+ and CD8+ lymphocytes of FeLV-versus FIV-infected cats. These findings indicate that FeLV and FIV have similar effects on T lymphocyte subsets. Both retrovirus infections can induce immunodeficiency, both viruses infect a broad range of lymphohaemopoietic cells, despite having different primary target cells, and can induce the killing of lymphocytic cells in vitro. It is concluded that a decreased CD4+/CD8+ ratio is not restricted to FIV infections but may also occur in FeLV infection.

Animals↗

Effects of maternal smoking on amniotic fluid volume and fetal urine output.

The purpose of this study was to assess the effects of maternal smoking on amniotic fluid volume and fetal urine output. Seventeen women (10 smokers and 7 non-smokers) were serially assessed through pregnancy. Smoking status was determined by self-report and carbon monoxide manometry. Amniotic fluid volume was assessed by sonographically measuring the maximum vertical pocket, the amniotic fluid index, and the two dimensions of the largest pockets. The coronal area formula was used to calculate bladder volume at 5-minute intervals for 20 minutes. Urine output was calculated from serial measurements of bladder volume. The mean gestational age of the first session was 26.8 (2.7) weeks, of the second session 32.4 (1.6) weeks, and of the last session 36.9 (2.1) weeks. In the univariate analysis there were no differences between smokers and non-smokers at any of the three visits for gestational age, fetal weight, maximum vertical pocket, amniotic fluid index, two-dimensional maximum pocket, and urine output. In the regression model, while controlling for gestational age, smoking status could not predict significant differences in any parameter. Maternal smoking does not appear to affect either amniotic fluid volume or fetal urine output.

Amniotic Fluid↗

Histamine releasability of basophils and skin mast cells in chronic urticaria.

In order to clarify the pathogenetic role of basophils and mast cells in chronic urticaria, histamine and leukotriene (LT)C4 release was examined in washed mixed leukocytes (n = 8) and skin mast cells (n = 5) from patients with chronic urticaria and compared with the same cells from normal controls (n = 9). Anti-IgE-stimulated basophil histamine release was significantly reduced in urticaria patients (median 2.9% vs 15.1% in normal controls), whereas histamine release to A23187, FMLP, and PAF, as well as anti-IgE-induced LTC4 release, showed no differences in both groups. In contrast, anti-IgE-stimulated skin mast cells from urticaria patients reacted similarly to those of controls (median histamine release 11.4% vs 14.2% in normal controls). Pretreatment of the cells with interleukin (IL)-3 upregulated responsiveness of basophil histamine release to anti-IgE in urticaria patients (median histamine release 14.3%), but pretreatment with the H2-antagonist cimetidine showed no effect. These data show that reduced basophil histamine releasability in chronic urticaria is not H2 mediated. It is a stimulus-, mediator-, and cell type-restricted phenomenon that can, at least partially, be reversed in the presence of the cytokine IL-3.

Adult↗

[Age dependency of laboratory values in dogs and cats. II. Electrolytes in serum].

Significant age dependent differences in dogs were found in sodium, potassium, calcium, chloride, and inorganic phosphorus, whereas in cats only potassium, chloride, and inorganic phosphorus were found to be age dependent. In both species special reference values must be established for different age groups. The higher reference values of potassium in young dogs and cats should be considered in cases of rehydration.

Aging↗

Antiretrovirus specificity and intracellular metabolism of 2',3' -didehydro-2',3'-dideoxythymidine (stavudine) and its 5'-monophosphate triester prodrug So324.

2',3'-Didehydro-2',3'-dideoxythymidine (d4T) and its lipophilic 5'-monophosphate triester prodrug, So324, were evaluated for their antiretroviral and metabolic properties in four different animal species cell lines. The antiretrovirus activity of So324 was approximately 4-10-fold greater than that of d4T against human immunodeficiency virus types 1 and 2 and simian immunodeficiency virus in human T lymphocyte CEM and MT-4 cells and against feline immunodeficiency virus in feline Crandell kidney cells, 50-fold greater against visna virus in sheep choroid plexus cells, but 5-fold inferior against murine (Moloney) sarcoma virus in murine embryo fibroblast (C3H) cells. Although the administration of both d4T and So324 resulted in the formation of the 5'-monophosphate (d4T-MP), 5'-diphosphate, and 5'-triphosphate in the different cell lines, a new d4T metabolite markedly accumulated in So324-treated cells and exceeded d4T-TP levels by 13-242-fold depending on the cell line used. This metabolite could be identified as alaninyl d4T-MP. Alanyl d4T-MP may be considered to be an intracellular depot form of d4T and/or d4T-MP, which may account for the superior antiretroviral activity of the lipophilic d4T-MP triester So324 compared with d4T.

3T3 Cells↗