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Biomedical subjects

J Bauer

Publications and source records attributed to J Bauer.

At least 397 records · Page 22Linked to original sources
PubMed1993

Oral ondansetron in the prophylaxis of nausea and vomiting induced by cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in women with breast cancer. Results of a prospective, randomized, double-blind, placebo-controlled study.

BACKGROUND: The combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) is a widely used chemotherapy regimen in breast cancer patients. However, the control of nausea and vomiting induced by oral CMF is a rarely examined problem. Therefore we felt a randomized, placebo controlled study justified in order to improve currently available antiemetic therapy. SUBJECTS AND METHODS: In a randomised double-blind trial ondansetron given orally, 8 mg three times a day for 15 days, was compared with placebo in 82 breast cancer patients receiving chemotherapy with CMF (cyclophosphamide 100 mg/m2 orally days 1-14, methotrexate 40 mg/m2 i.v. days 1 and 8 and 5-fluorouracil 600 mg/m2 i.v. days 1 and 8). The patients recorded nausea and the number of vomits and retches daily on diary cards. Forty-two patients received ondansetron and 40 received placebo. RESULTS: Significantly more patients who received ondansetron experienced neither vomiting nor retching (emesis) compared to those receiving placebo over a 15 day treatment period (60% vs. 35%, p = 0.027). The difference, with 95% confidence limits, was estimated at 25 (4.45%). Furthermore, there was a trend in favour of ondansetron in the control of nausea. Ondansetron was well tolerated, with 25 patients (59%) reporting at least 1 adverse event compared to 18 patients (45%) receiving placebo (p = 0.191). CONCLUSION: The results indicate that ondansetron given orally for 15 days is safe and effective in the control of emesis induced by CMF. It is however too early to recommend ondansetron as standard antiemetic therapy for oral CMF, as the treatment of nausea and vomiting in this setting has not been studied thoroughly enough.

Administration, Oral↗
PubMed1993

Disseminated melanoma, preclinical therapeutic studies, clinical trials, and patient treatment.

Disseminated malignant melanoma is a very resistant tumor to therapy. Mechanisms of resistance to chemotherapy may be due to glutathione reductase and O6 alkyltransferase, two enzymes especially able to detoxify from alkylation. An interesting model is represented by dacarbazine in the treatment of melanoma with nitrosourea derivatives. Cytokines may come to play an increasing role in the combination with chemotherapy; interferon-alpha and interleukin-2, for example, seem to potentiate the action of chemotherapy in well-designed clinical protocols. Moreover, tumor necrosis factor-alpha was shown to be active in combination therapy with interferon-gamma and chemotherapy when administered by isolation perfusion. Targeting with monoclonal antibodies or melanocyte-stimulating hormone-alpha conjugated to cytotoxic agents represents a promising area. The discovery of a gene, designated MAGE1, coding for a peptide presented by HLA-A1 and able to specifically activate cytotoxic T lymphocytes may represent a unique approach to specific active immunotherapy for melanoma. The interference with integrins and adhesion molecules may play a role in the prevention of metastases. Some preclinical models seem to validate this approach. Current treatment of disseminated malignant melanoma involves chemotherapy often associated with other cytotoxic agents or cytokines, which may potentiate the antitumor effect. Other therapeutic issues reviewed concern targeting and immunotherapy. This review ends with a survey of biologic factors that may constitute new approaches to melanoma therapy.

Antineoplastic Agents↗
PubMed1993

Cytokine production during sleep and wakefulness and its relationship to cortisol in healthy humans.

A growing body of evidence indicates that cytokines, especially interleukin-1 beta, are involved in the regulation of sleep and wakefulness. The aim of the present pilot study was to investigate the relationship between interleukin-1 beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation of sleep and wakefulness. Four healthy male volunteers were investigated. After one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by means of a mobile long-term EEG and blood samples were drawn every 45 min for the analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of cytokines whole blood cultures were established. After 48 h of incubation in the presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were measured in the culture supernatants using specific immunodetection assays. Methods of stochastic time series analysis were adopted to evaluate the biochemical data. Our results show the capability of cultured blood cells to produce cytokines upon endotoxin challenge to be at a maximum around the time of sleep onset and during the first hours of sleep, declining during the night to a minimum level in the morning hours. The opposite was observed for cortisol. The analysis of autocorrelation functions gives evidence of a 24-hour rhythm of cortisol and cytokines. The results indicate that the cytokines IL-1 beta and gamma-IFN may play a role in sleep regulation.

Adult↗
PubMed1993

Intraperitoneal carboplatin in advanced ovarian carcinoma.

24 patients with advanced epithelial ovarian cancer, who demonstrated a clinical complete or partial response to the induction of intravenous chemotherapy, underwent implantation of a subcutaneous semipermanent port-and-catheter system (Port-A-Cath) for intraperitoneal chemotherapy, which consisted of carboplatin 300 mg/m2 every 4 weeks. The median survival was 27.4 months for minimal residual disease versus 8 months for bulky disease (p = 0.0054). The median progression-free interval was 15.7 months for minimal residual disease versus 1.8 months for bulky disease (p = 0.008). There were 3 complications (12.5%) related to the catheter: 1 perforation of the large bowel and 2 catheter inflow obstructions. Myelosuppression, especially a grade 3 leucopenia in 5 patients (25%) and a grade 4 thrombopenia in 3 patients (15%), was the dose-limiting toxicity. Even with maximum cytoreductive surgery and second-line intraperitoneal carboplatin-based chemotherapy, the 5-year progression-free survival (4.1%) remains very small.

Aged↗
PubMed1993

[Pathologico-anatomic and mycotoxicologic studies of aspergillosis in birds].

4.0% of all birds (n = 11249) examined post mortem at the Institute of Avian Diseases, Oberschleissheim, showed fungal infections of the respiratory tract. Clinical and histopathological findings to date have suggested toxin production in Aspergillus fumigatus infections. To obtain detailed information, preselected tissues from the lungs and air sacs (n = 17) were examined by culture and fluorescence microscopy. In 12 cases gliotoxin (0.1-0.45 mg/kg) was found in the A. fumigatus infected tissues. The importance of gliotoxin, which showed strong cytotoxic effects in cell cultures, is discussed.

Air Sacs↗
PubMed1993

[The "trout phenomenon": a rare symptom of epileptic seizures].

Petechial eruptions may be the consequence of tonic-clonic seizures. Usually they are located on face, neck or breast. We report on a 25-year-old male patient suffering from unclassified seizures occurring at night. Seizure frequency was one a month over a six-month period. Following the seizures he regularly observed periocular petechial eruptions which disappeared within three days. EEG, MRI and laboratory investigations, including a hematological screening, were normal. We diagnosed an epileptic disorder and treated the patient with phenobarbitone. Within the next seven months he remained free of seizures. The petechial eruptions probably resulted from capillary bleedings during the tonic phase of a tonic-clonic seizure.

Adult↗
PubMed1993

Gold-induced colitis: a case report and review of the literature.

A case of severe colitis requiring subtotal colectomy following administration of 35 mg Solganal b for intractable arthritis is described. Abdominal pain and watery diarrhea developed six weeks after the last dose of gold. Colonoscopy revealed mucosal edema and ulceration of the entire colon. Supportive measures failed and the patient required subtotal colectomy. Review of the literature revealed 29 cases, ranging in severity from limited ileal involvement to fulminant panenteritis. Most of the patients responded to intravenous fluids, steroids, and antibiotics, but four required surgery. The case described is notable for the delay in appearance of abdominal symptoms following the cessation of gold therapy. The mechanism of injury is unknown. Abdominal complaints in a patient who has received gold therapy, especially parenteral, merit strict attention, even if occurring several weeks after the final dose, and the diagnosis of gold colitis should be entertained.

Acute Disease↗
PubMed1993

[Correlation between chronic hyperplastic laryngitis and infection with human papillomaviruses].

Cancer of the larynx is one of the most prevalent tumors of the head and neck, with its prognosis dependent on early diagnosis. A number of authors have now reported a connection between head and neck cancers and infection with human papilloma virus (HPV). A large number of these tumors has been found to be HPV 16/18 positive, with results ranging from 10% to 75% positive. It is currently known that viral infection alone cannot realize an oncogenic potential and there have to be exogenous and/or endogenous factors as well. Further, little is known about the prognosis of epithelial lesions which undergo malignant conversion. The aim of our study was to determine whether the HPV 16/18 content in biopsies of chronic hyperplastic inflammations of the larynx was a prognostic factor for later malignancy. The polymerase chain reaction (PCR) was used to examine 150 laryngeal biopsies from 132 men and 18 women. Additionally, historical data, including information about regular alcohol and nicotine consumption, were examined for an association with HPV 16/18. Three different groups were found to be at risk for developing a carcinoma of the larynx from the 91 patients positive for HPV 16/18 (10 women and 81 men). These included: (1) HPV 16/18 positive patients not exposed to exogenous irritants (6 women and 9 men); HPV 16/18 positive smokers (1 woman and 37 men); (3) HPV 16/18 positive smokers and regular alcohol drinkers (3 women and 35 men). During the 3 1/2 years of our study one woman and one man from the first group developed a cancer of the larynx.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1993

[Perioperative use of ampicillin/sulbactam, cefoxitin and piperacillin/ metronidazole in elective colon and rectal surgery. A prospective randomized quality assurance study of 422 patients].

As has been proved before, antibiotic prophylaxis is highly effective in lowering wound infection rates in colorectal surgery. In order to establish quality control, we checked the effectiveness of three different prophylactic antibiotic regimes in 422 patients in a prospective and randomized trial. Between the three groups were no significant differences as regards age, type of operation and risk factors like adipositas and diabetes. The wound infection rate according to CDC-criteria was from 7.0 to 9.5%. We did not find a significant difference between the three antibiotic regimes. It is therefore our conclusion, that in our setting each of the three different types of antibiotics is of equal value. This means, on the other hand, that the cheapest one is enough.

Aged↗
PubMed1993

[The effectiveness of tilmicosin in respiratory diseases of swine].

Within the scope of the clinical evaluation of Tilmicosin in Enzootic Pneumonia of pigs, nasal swabs from 78 animals were taken, before and after oral medication of different doses (0, 100, 200, 300 mg Tilmicosin/kg dry food), and examined bacteriologically for Pasteurella multocida, Bordetella bronchiseptica und Haemophilus parasuis. The bacteria aforementioned were isolated from the nasal secretions of 83% of the pigs, 14 days after crowding without any prophylactic regime. It could be demonstrated, that pigs with clinical symptoms of Enzootic Pneumonia had a 50% higher prevalence-rate of multi-colonization with pneumotropic bacteria than healthy animals. Feeding 300 mg Tilmicosin/kg food for 9 and 14 days respectively, resulted in elimination of Pasteurella spp. and Haemophilus spp. The rate of newly Bordetella bronchiseptica infected pigs was lower than in the placebo-group. Parallel to these bacteriological results improvement of clinical signs and increased daily weight gain were observed.

Animals↗
PubMed1993

Myopic children show insufficient accommodative response to blur.

PURPOSE: The study was performed to establish the relationship between the slope of the accommodative response function and refractive error in children. METHODS: Using an autorefractor, accommodative responses were measured in children under the following conditions. The subjects wore their best subjective refraction to view targets (a 3 x 3 array of 20/100 letters) displayed at seven distances (4.0 to 0.25 m). They viewed letters placed at 4.0 m through a series of negative lenses and letters placed at 0.25 m through a series of positive lenses. RESULTS: Myopic children accommodate significantly less than emmetropic children for real targets at near distances. Compared with emmetropic subjects, myopic children use blur poorly to increase accommodation, as shown by shallow slopes of the accommodative response functions for negative lenses. However, with positive lenses, requiring relaxation of accommodation, there is no significant difference in slope between myopic and emmetropic children. CONCLUSIONS: Blur is not an effective stimulus for accommodation in myopic children.

Accommodation, Ocular↗
PubMed1992

The human hepatoma Hep3B cell line as an experimental model in the study of the long-term regulation of acute-phase proteins by cytokines.

The regulation of the synthesis by the cytokines interleukin-1 (IL-1) and IL-6 of the positive acute-phase protein alpha 1-acid glycoprotein (AGP) and of the negative acute-phase protein alpha 2-HS glycoprotein (AHSG) has been studied in a long-term culture system of the human hepatoma cell line Hep3B. The culture system contained 30 nM-sodium selenite as the only supplement. This allowed maintenance of the synthesis of the proteins under study at a near steady state for over 3 months. An increase in AGP mRNA and a decrease in AHSG mRNA were observed when cells were treated for two successive 48 h-periods with monocyte-conditioned medium. A return to basal levels was obtained after cessation of the cytokine addition. Two further additions of cytokines led to alterations in mRNA levels similar to those observed following the first cytokine treatment. The amounts of AGP and AHSG secreted were altered in accordance with the mRNA modifications. These results suggest that new cytokine receptors were being constantly synthesized during cell culture. When cytokines were present in the culture medium for 10 days, maximum alterations in AGP and AHSG synthesis were obtained following 2 and 4 days of treatment respectively, but further alterations in protein levels could not be observed afterwards. Expression of IL-6 receptor mRNA was not up-regulated by cytokines, but only by 1 microM-dexamethasone. Our results show that, in this long-term culture system, cytokines induce a response in hepatoma cells similar to that observed in vivo during human inflammatory states. This model could be used to evaluate the effects of agonists or antagonists of cytokines responsible for the hepatic acute-phase protein response.

Acute-Phase Proteins↗
PubMed1992

Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells.

The gene for the beta A4-amyloid precursor protein (APP) consists of 19 exons which code for a typical N- and O-glycosylated transmembrane protein with four extracellular domains followed by the transmembrane domain and a short cytoplasmic domain. The beta A4-amyloid sequence is part of exons 16 and 17. Several APP isoforms can be generated by alternative splicing of exons 7 and 8, encoding domains with homologies to Kunitz-type protease inhibitors and the MRC OX-2 antigen, respectively. The mechanism by which the pathological beta A4 is generated is unknown, it is however a critical event in Alzheimer's disease and is distinct from the normally occurring cleavage and secretion of APPs within the beta A4 sequence. We report here for the first time considerable APP mRNA expression by rat brain microglial cells. In addition we showed by S1 nuclease protection and polymerase chain reaction analysis of reverse transcribed RNA (RT-PCR) that T-lymphocytes, macrophages, and microglial cells expressed a new APP isoform by selection of a novel alternative splice site and exclusion of exon 15 of the APP gene. This leads to a transmembrane, beta A4 sequence containing APP variant, lacking 18 amino acid residues close to the amyloidogenic region. The use of this novel alternative splice site alters the structure of APP in close proximity to the beta A4 region and thus may determine a variant, potentially pathogenic processing of leukocyte-derived APP in brain.

Amyloid beta-Protein Precursor↗
PubMed1992

Pharmacokinetics of pamidronate in patients with bone metastases.

BACKGROUND: Pamidronate is a second-generation bisphosphonate used in the treatment of tumor-induced hypercalcemia and in the management of bone metastases from breast cancer, myeloma, or prostate cancer. The pharmacokinetics of pamidronate is unknown in cancer patients. PURPOSE: To determine the influence of the rate of administration and of bone metabolism, we studied the pharmacokinetics of pamidronate at three different infusion rates in 37 patients with bone metastases. METHODS: Three groups of 11-14 patients were given 60 mg pamidronate as an intravenous infusion over a period of 1, 4, or 24 hours. Urine samples were collected in the three groups of patients. Plasma samples were obtained only in the 1-hour infusion group. The assay of pamidronate in plasma and urine was performed by high-performance liquid chromatography with fluorescence detection after the derivatization of pamidronate with fluorescamine. RESULTS: The body retention (BR) at 0-24 hours of pamidronate represented 60%-70% of the administered dose and was not significantly modified by the infusion rate. In particular, the BR at 0-24 hours was not reduced at the fastest infusion rate. Among patients, a threefold variability in BR at 0-24 hours occurred, which was related directly to the number of bone metastases and, to some extent, to creatinine clearance. At 60 mg/hour, the plasma kinetics followed a multiexponential course characterized by a short distribution phase. The mean (+/- SD) half-life of the distribution phase was 0.8 hour (+/- 0.3), the mean (+/- SD) of the area under the curve for drug concentration in plasma x time at 0-24 hours was 22.0 +/- 8.8 mumol/L x hours, and the mean (+/- SD) of the maximum plasma concentration was 9.7 mumol/L (+/- 3.2). Pharmacokinetic variables remained unchanged after repeated infusions applied to four patients. Clinically, the three infusion rates were equally well tolerated without significant toxicity. CONCLUSIONS: The 1-hour infusion rate could be proposed as kinetically appropriate for the administration of pamidronate to patients with metastatic bone diseases.

Aged↗
PubMed1992

In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression, G-proteins, and integrins.

The EA hy926 cell line is a continuous, clonable, human cell line that displays a number of features characteristic of vascular endothelial cells (Edgell et al., 1983). Here we report that when EA hy926 cells (EA cells) are plated on an extracellular matrix material [Matrigel], they undergo a process of morphological re-organization leading to the formation of a complex network of cord or tubelike structures. These events seem to resemble, in some respects, an in vitro process of angiogenesis. The morphological re-arrangement occurs within a 12-16 hr period and seems to require expression of new messenger RNA and protein, since it is completely blocked when actinomycin D or cycloheximide are present at the time the cells are plated on Matrigel. This is not due to overt toxicity of the drugs, since exposure of cells to actinomycin D at 2 hr or more after plating on Matrigel has little effect on the formation of the tubelike structures. The process of Matrigel-induced tube formation also apparently involves a G-protein mediated signal. Treatment of the EA cells with pertussis toxin completely blocks the process and causes the ADP-ribosylation of a 42 kD protein that is recognized by an antibody to Gi-alpha subunits. In contrast, concentrations of pertussis toxin sufficient to block tube formation have only modest effects on the adhesion or motility of EA cells on purified matrix components such as laminin or collagen IV. The process of Matrigel-induced tube formation also involves integrins since monoclonal antibodies to integrin alpha 6 or beta 1 subunits can completely block the process. The concentrations of anti-integrin antibodies needed to block tube formation are much lower than those required to block cell adhesion on purified matrix components and are sufficient to occupy less than 10% of the alpha 6 or beta 1 subunits available at the cell surface. These results suggest that integrins may be involved in this potential model of angiogenesis in processes beyond their usual role in cell adhesion. Based on these results, it seems likely that the EA hy 926 cell line will prove to be a useful model for in vitro study of angiogenic processes.

Antibodies↗
PubMed1992

The effect of a synthetic GnRH analogue on catamenial epilepsy: a study in ten patients.

Ten female patients suffering from catamenial epilepsy were treated with a synthetic analogue of the gonadotrophin releasing hormone (GnRH) in addition to antiepileptic drugs. Three of the patients became seizure free, in four patients seizure frequency decreased and in one patient seizures were of shorter duration. In only two of the patients was there no therapeutic effect. Adverse effects, including hot flushes, headache and increase in weight, were noticed in eight patients. These results support the hypothesis that treatment with a synthetic GnRH analogue might be helpful in patients with intractable catamenial epilepsies.

Adult↗