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Biomedical subjects

E Richter

Publications and source records attributed to E Richter.

At least 91 records · Page 5Linked to original sources
PubMed1999

A case of intestinal Mycobacterium simiae infection in an SIV-infected immunosuppressed rhesus monkey.

Although Mycobacterium simiae was identified and classified more than three decades ago, only a few cases are mentioned in the current literature. After experimental simian immunodeficiency virus infection, a 9-year-old female rhesus monkey (Macaca mulatta) developed progressive immunosuppression and gastrointestinal disease very similar to the clinical and pathomorphologic features of Johne's disease, which is caused by M. paratuberculosis. Acid-fast-positive bacteria reacted immunohistochemically with antibodies against M. paratuberculosis and M. bovis but were not useful for differentiation because of a high degree of cross-reactivity. In contrast to immunohistochemistry and histopathology, biochemical methods and cycle sequencing analysis of the 16S ribosomal RNA identified M. simiae as the disease-causing pathogen. This case demonstrates the importance of molecular biological methods for the diagnosis of M. simiae infection in monkeys.

Animals↗
PubMed1999

Metabolism and disposition of 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) in rhesus monkeys.

Metabolism and disposition of the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent rodent lung carcinogen, were studied in rhesus monkeys. In three males receiving a single i.v. dose of [5-3H]NNK (0.72 mCi; 4.6-9.8 microg/kg), urine was collected for 10 days. Within the first 24 h, 86.0 +/- 0.7% of the dose was excreted. NNK-derived radioactivity was still detectable in urine 10 days after dosing (total excretion, 92.7 +/- 0.7%). Decay of urinary radioactivity was biexponential with half-lives of 1.7 and 42 h. Metabolite patterns in urine from the first 6 h closely resembled those reported previously for patas monkeys; end products of metabolic NNK activation represented more than 50% of total radioactivity. At later time points, the pattern shifted in favor of NNK detoxification products (60-70% of total radioactivity in urine), mainly 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its O-glucuronide conjugates. One female rhesus monkey received a single i.v. dose of [5-3H]NNK (1.72 mCi; 28.4 microg/kg) under isoflurane anesthesia; biliary excretion over 6 h (0.6% of the dose) was 10 times less than predicted by our previously reported rat model. No preferential excretion of NNAL glucuronide was observed in monkey bile. Collectively, these results suggest that the rhesus monkey could be a useful model for NNK metabolism and disposition in humans.

Animals↗
PubMed1999

[Side effects of postoperative radiochemotherapy with amifostine versus radiochemotherapy alone in head and neck tumors. Preliminary results of a prospective randomized trial].

PURPOSE: Experimental and clinical data suggest a reduction of radiation-induced acute toxicity by amifostine. We investigated this issue in a randomized trial comparing radiochemotherapy (RCT) versus radiochemotherapy and amifostine (RCT + A) in patients with head and neck cancer. PATIENTS AND METHODS: Forty-seven patients with pharyngeal or laryngeal cancer (T1-2 N1-2 G3, T3-4 N0-2 G1-3) were randomized to receive RCT alone (21 patients) or RCT + A (21 patients). Patients were irradiated up to 60 Gy (R0) or 70 Gy (R1/2). Chemotherapy consisted of 70 mg/m2 carboplatin and was administered over 5 days in the 1st and 5th week of the radiotherapy course. 250 mg amifostine were applied daily just before each radiotherapy session. Acute toxicity was evaluated according to the Common Toxicity Criteria (CTC). As for xerostomia no patients with laryngeal cancer were assessed because in these cases only small volumes of the salivary glands were within the treatment volume. To evaluate the overall toxicity a summarized CTC score of all observed side effects was calculated. RESULTS: Forty-two patients were evaluable. Clinical characteristics (age, sex, Karnofsky index, tumor-staging) were well balanced in both treatment groups (Tables 2 and 3). Amifostine provided reduction in xerostomia and mucositis (Figures 5 and 6) but had no obvious influence on Karnofsky index, body weight, cutaneous side effects and alopecia (Figures 1 to 4). CONCLUSIONS: According to our preliminary results amifostine has a radioprotective effect on salivary glands. Mucositis can be reduced during radiochemotherapy. At this point of patient accrual the difference between both groups are statistically not significant. To improve the radioprotective effects of amifostine in clinical practice the application of a higher dose (> 250 mg) seems to be necessary.

Adenocarcinoma↗
PubMed1998

Substituted 4-acylpyrazoles and 4-acylpyrazolones: synthesis and multidrug resistance-modulating activity.

A series of 4-acyl-3-pyrazolone derivatives with a 3-substituted 2-hydroxy-3-aminopropyl chain attached to pyrazole N-1 (7-20) as well as isomeric 4-acyl-5-(3-substituted 3-amino-2-hydroxypropoxy)pyrazole derivatives (5, 6) were synthesized, and their multidrug resistance (MDR)-modulating activity was measured using the daunomycin efflux assay. Reaction of N1-substituted 4-acyl-3-pyrazolones (tautomer to 4-acyl-5-hydroxypyrazoles) with excessive epichlorohydrin and successive treatment with an appropriate amine resulted in N-alkylation and thus afforded the target pyrazolone derivatives 7-20. In contrast, O-alkylation occurred upon reaction with 1 equiv of epichlorohydrin and subsequent treatment with amine leading to the corresponding 4-acyl-5-pyrazolyl ethers 5 and 6. QSAR studies showed a good correlation of MDR-modulating activity with lipophilicity of the compounds. Inclusion of hydrogen bond acceptor strength and steric parameters as descriptors led to a QSAR equation with remarkably increased predictive power (r2cv = 0.92). Additionally, ortho substitution of the propanolamine side chain and the acyl moiety is favorable. Detailed NMR spectroscopic investigations were carried out with the title compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Trends and outcomes of outpatient mastectomy in elderly women.

BACKGROUND: Considerable public attention has focused on the use of outpatient mastectomy and has resulted in numerous legislative proposals to mandate a minimum hospital stay following mastectomy. To date, only limited scientific data are available regarding the use and the outcomes of outpatient mastectomy. The purpose of this study was to provide population-based information on trends and outcomes for outpatient mastectomy in elderly women. METHODS: Medicare data for elderly women with fee-for-service coverage were examined for trends and regional variation in the use of outpatient mastectomy. Logistic regression was used to identify patient and provider characteristics associated with having an outpatient mastectomy, and outcomes were assessed by calculating the risk of being rehospitalized and the reasons for rehospitalization. RESULTS: From 1986 through 1995, the proportion of mastectomies performed on an outpatient basis increased from virtually 0% to 10.8%. Outpatient mastectomies were more likely to be performed on women with no coexisting health problems in hospitals that were for-profit or non-teaching or in large metropolitan statistical areas. Women undergoing outpatient mastectomy had substantially higher rates of rehospitalization within 30 days than women with a 1-day stay in the hospital. Both groups had comparable rates of rehospitalization for complications definitely related to their surgery. The percentage of women who required rehospitalization was low, and the actual number of women rehospitalized was relatively small. CONCLUSIONS: We conclude that the risks from outpatient mastectomy are modest, although ongoing monitoring of outcomes and assessment of patient satisfaction are needed.

Aged↗
PubMed1998

Synthesis and pharmacological activity of the stereoisomers of GP-88, a propafenone-type modulator of multidrug resistance.

All four stereoisomers of the propafenone-type MDR-modulator GP-88 (1) were synthesized using a combined approach with chiral pool building blocks and an acetalic protective group, which allows not only diastereoseparation but also assignment of absolute configuration via NMR spectroscopy. Those isomers with different configuration on the center of chirality in the propanolamine side chain showed statistically different PGP-inhibitory activity. Generally, the (R)-configured isomers were by a factor of nearby two higher active than the (S)-isomers. No differences in activity were observed for isomers with different configuration on the benzylic center of chirality.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Injury prevention.

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Accidents, Traffic↗
PubMed1998

Clinical use of a simulation-multileaf collimator.

BACKGROUND: At the University of Lübeck, radiotherapy is delivered by a 6/18-MV linear accelerator. Using the integrated multileaf collimator, irradiation of individually shaped treatment fields is possible in place of alloy blocks. Due to unsatisfactory pretherapeutic review of the radiation-field-specific multileaf collimator (MLC) configuration, we developed a simulation-multileaf collimator (SMLC) and assessed its feasibility at different tumor sites. MATERIAL AND METHODS: The SMLC is made of a perspex carrier with 52 horizontal sliding leaves. The position of each leaf is calculated by a 3D treatment-planning computer. The technician manually adjusts the leaves according to the beams-eye-view plot of the planning computer. Consequently, the SMLC is mounted on the therapy simulator at a distance of 64.8 cm from the focus. The treatment fields and the position of the leaves are documented by X-ray films. RESULTS: Using the SMLC, radiation oncologists are able to review exactly the leaf configuration of each MLC-shaped radiation field and to correlate the MLC-shaped radiation field with the treated volume, the organs at risk and the port films acquired by the Portal Vision system. CONCLUSION: The SMLC is a new tool to review radiation planning that uses an MLC in daily routine. The use of the SMLC improves the documentation and the quality assurance. It accelerates the treatment field review at the linear accelerator by comparing the SMLC simulator films with the portal images.

Calibration↗
PubMed1998

[Spinal metastases of malignant gliomas].

PURPOSE: Extracranial metastases of malignant gliomas are rare. We report 2 cases with spinal metastases in patients suffering from glioma. PATIENTS AND METHOD: Two patients (33 and 57 years old) developed spinal canal metastases of a glioblastoma multiforme and anaplastic astrocytoma Grade III respectively 25 and 9 months after surgical resection and radiotherapy. Both metastases were confirmed pathohistologically. RESULTS: Intraspinal metastases were irradiated with a total dose of 12.6 Gy and 50 Gy. Treatment withdrawal was necessary in one patient due to reduced clinical condition. Regression of neurological symptoms was observed in the second patient. CONCLUSIONS: Spinal spread of malignant glioma should be considered during care and follow-up in glioma patients with spinal symptoms.

Adult↗
PubMed1998

Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver.

The tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a strong lung carcinogen in all species tested. To elicit its tumorigenic effects NNK requires metabolic activation which is supposed to take place via alpha-hydroxylation, whereas N-oxidation is suggested to be a detoxification pathway. The differences in the organ specific metabolism of NNK may be crucial for the organotropy in NNK-induced carcinogenesis. Therefore, metabolism of NNK was investigated in the target organ lung and in liver of Fischer 344 (F344) rats using the model of isolated perfused organs. High activity to metabolize 35 nM [5-3H]NNK was observed in both perfused organs. NNK was eliminated by liver substantially faster (clearance 6.9 +/- 1.6 ml/min, half-life 14.6 +/- 1.2 min) than by lung (clearance 2.1 +/- 0.5 ml/min, half-life 47.9 +/- 7.4 min). When the clearance is calculated for a gram of organ or for metabolically active cell forms, the risk with respect to carcinogenic mechanisms was higher in lung than in liver. The metabolism of NNK in liver yielded the two products of NNK alpha-hydroxylation, the 4-oxo-4-(3-pyridyl)-butyric acid (keto acid) and 4-hydroxy-4-(3-pyridyl)-butyric acid (hydroxy acid). In lung, the major metabolite of NNK was 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone (NNK-N-oxide). Substantial amounts of metabolites formed from methyl hydroxylation of NNK, which is one of the two possible pathways of alpha-hydroxylation, were detected in lung but not in liver perfusion. Formation of these metabolites (4-oxo-4-(3-pyridyl)-butanol (keto alcohol), and 4-hydroxy-4-(3-pyridyl)-butanol (diol) can give rise to pyridyloxobutylating of DNA. When isolated rat livers were perfused with 150 microM NNK, equal to a dosage which is sufficient to induce liver tumors in rat, glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased when compared to the concentration of 35 nM NNK. Nevertheless, the main part of NNK was also transformed via alpha-hydroxylation for this high concentration of NNK.

Animals↗
PubMed1998

Effect of nicotine or cotinine on metabolism of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver.

The scope of the present study was to investigate whether nicotine or cotinine will affect the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated perfused rat lungs and livers and to study the effect of starvation on pulmonary metabolism of NNK. NNK metabolism was investigated in isolated perfused liver and lung of male F344 rats perfused with 35 nM [5-3H]NNK in presence of a 1400-fold excess of the main tobacco alkaloid nicotine and its metabolite cotinine. In perfused rat livers, nicotine and cotinine inhibited NNK elimination and metabolism and led to a substantial increase of elimination half-life from 14.6 min in controls to 25.5 min after nicotine and 36.6 min after cotinine co-administration, respectively. In parallel, the pattern of NNK metabolites was changed by nicotine and cotinine. The pathway of alpha-hydroxylation representing the metabolic activation of NNK was decreased to 77% and 85% of control values, whereas N-oxidation of NNK and glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased 2.6- and 1.2-fold in presence of nicotine and cotinine, respectively. When isolated rat lungs were perfused with 35 nM NNK for 3 h neither the elimination nor the pattern of metabolites were substantially affected due to co-administration of 50 microM nicotine or cotinine. Cytochrome P450 2E1 is known to participate in the activation of NNK and can be induced by starvation. However, isolated rat lungs from male Sprague Dawley rats perfused with [1-14C]NNK at about 2 microM for 3 h, revealed only small differences in pulmonary elimination and pattern of NNK metabolites between fed and starved animals. These results suggest that nicotine and its main metabolite cotinine inhibit the metabolic activation of NNK predominantly in the liver whereas activation in lung, a main target organ of NNK induced carcinogenesis, remained almost unaffected.

Animals↗
PubMed1998

Salivary gland scintigraphy using technetium-99m-pertechnetate after autotransplantation of the submandibular salivary gland in the correction of dry eye.

The aim of the study was to determine whether salivary gland scintigraphy using technetium-99m pertechnetate is suitable for checking the vitality and function after autotransplantation of the submandibular salivary gland in patients with dry eye syndrome. To this end, 56 scintigraphic studies in 20 patients have so far been performed. In addition, these scans were evaluated by a region of interest (ROI) technique in order to examine tracer uptake in the early and late stages after surgery. We have been able to prove that in this special respect, too, the salivary gland scintigraphy is suitable for assessing reliably the vitality and function of the transplanted gland. The secretion into the eye and thus the patency of the efferent duct can also be displayed. This proved to be particularly valuable in those cases in which at first no secretion could be seen in the clinical examination. In patients with uncertain excretory function, we were able to distinguish between non-vitality and lack of patency of the secretory duct. Using ROI evaluation, no significant decrease in the salivary function has been detected in long-term follow-up, now extending to 1 year after surgery.

Adolescent↗
PubMed1998

Drug monitoring during the treatment of AIDS-associated Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole.

OBJECTIVE: To monitor trimethoprim and sulfamethoxazole plasma levels in patients with AIDS-associated Pneumocystis carinii pneumonia. METHOD: Trimethoprim-sulfamethoxazole steady-state plasma concentrations were measured by high-pressure liquid chromatography during 37 episodes of Pneumocystis carinii pneumonia in patients with AIDS. Initially, 15-23 mg/kg/day trimethoprim and 75-115 mg/kg/day sulfamethoxazole were given i.v. Assuming a therapeutic range for trimethoprim from 4 to 10 microg/ml, the doses were adjusted if trimethoprim levels were found to be outside this range. RESULTS: Mean concentrations were 6.7+/-3.3 g/ml for trimethoprim and 187+/-56 microg/ml for sulfamethoxazole. A widespread inter-patient range was found and could be decreased after dose adjustment. Enzyme inducing co-medication did not influence plasma concentrations. In patients with coexisting chronic liver disease, significantly increased sulfamethoxazole plasma levels were observed. A correlation could be demonstrated between serum creatinine and trimethoprim plasma levels. Adverse reactions associated with co-trimoxazole occurred during 65% of treatment periods and increased with increasing trimethoprim-sulfamethoxazole levels, as well as increasing length of treatment. Therapy only had to be prematurely discontinued in one patient. Overall mortality was 2.7% CONCLUSION: Monitoring of co-trimoxazole levels during the treatment of P. carinii pneumonia in AIDS may help in reducing the high variability of plasma-concentrations and in avoiding severe side-effects especially associated in patients with chronic liver disease or renal failure.

AIDS-Related Opportunistic Infections↗
PubMed1998

Mycobacterium ulcerans infection in a child from Angola: diagnosis by direct detection and culture.

Buruli ulcer, caused by Mycobacterium ulcerans, is a chronic ulcerative skin disease, found predominantly in central and west Africa and Australia. A boy of 2.5 years of age from Angola was admitted to our hospital with severe kwashiokor and a large ulcer with undermined edges on the left side of the thorax. Further examination revealed anaemia, hypoproteinaemia, bacterial superinfection of the ulcer and intestinal parasites. Histological analysis showed acid-fast bacilli and histopathological changes typical of Buruli ulcer. M. ulcerans was detected by PCR and culture. The patient was treated by surgical excision of diseased skin, followed by split-skin grafting. He also received antibiotic therapy (ciprofloxacin, clarithromycin, rifabutin, and dapsone). After six months, the child was discharged from hospital in good condition. This is the first published case of Buruli ulcer from Angola.

Angola↗
PubMed1998

Private health insurance and veterans use of Veterans Affairs care. RATE Project Committee. Rate Alternative Technical Evaluation.

OBJECTIVES: This study examined the effect of private health insurance on the use of medical, surgical, psychiatric, and addiction services for patients eligible for publicly supported care. METHODS: The authors assembled administrative databases describing 350,000 noninstitutionalized veterans who had been discharged from a Veterans Affairs (VA) inpatient medicine or surgery bed section during a 1-year period. Patient use of care was followed for 1 year after the index discharge. Patient insurance information came from Medical Care Cost Recovery Billing and Collection files obtained separately from each of 162 VA Medical Centers. Distances between VA and non-VA sources of care were estimated from the Health Care Financing Administration's Hospital Distance File. RESULTS: Insured patients were less likely to seek surgical care but were 12 times (65 years of age and older) and 73 times (63 years of age and younger) more likely to initiate outpatient medical visits than were their counterparts, adjusted for patient demographic, diagnostic, and index facility characteristics. Patients who had private health insurance also were 3.4 (> or = 65) and 2.6 (< or = 64) times less likely to use VA surgical care in response to changes in available surgical staff-to-patient ratios than were their uninsured counterparts. CONCLUSIONS: Private health insurance may substitute (reduce) or complement (increase) the continued use of publicly supported health care services, depending on patient age, care setting, and service type.

Adult↗