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Biomedical subjects

B Richter

Publications and source records attributed to B Richter.

At least 19 recordsLinked to original sources
PubMed2002

Reliability of causes of death in persons with Type I diabetes.

AIMS/HYPOTHESIS: To compare causes of death assessed by a clinical review committee, the information given on death certificates, and ICD-codes provided by the State Documentation Office in deceased persons with Type 1 (insulin-dependent) diabetes mellitus. METHODS: A cohort of 3674 patients were monitored for 10+/-3 (mean +/- SD) years. Vital status and end-stage diabetic complications were documented for 97%; 251 patients had died. Causes of death were assessed by a clinical review committee and compared to the information provided by death certificates and ICD-9 codes. RESULTS: The review committee defined a leading cause of death in 94% of cases, whereas death certificates were available for 73% and ICD-codes for 79% of patients; 10% of death certificates could not be evaluated due to insufficient information. Diabetes was mentioned on 71% of death certificates, and renal disease in 75% of cases with renal replacement therapy. There was acceptable agreement between the committee, death certificates and ICD-codes only for deaths due to neoplasma, and between the committee and death certificates for deaths due to acute myocardial infarction, cerebrovascular events and accidents. In only one out of four deaths due to hypoglycaemia and in four of seven deaths due to ketoacidosis was this diagnosis mentioned on the death certificate. No death due to hypoglycaemia or ketoacidosis and 41% due to suicide were identifiable by ICD-codes. CONCLUSION/INTERPRETATION: Reliance on death certificates or ICD-codes as the only sources of information on the cause of specific mortality does not provide data of sufficient reliability for evaluation of clinical outcome in Type I diabetes.

Adult↗
PubMed2002

'Human' insulin versus animal insulin in people with diabetes mellitus.

BACKGROUND: Human insulin was introduced for the routine treatment of diabetes mellitus in the early 1980s without adequate comparison of efficacy to animal insulin preparations. First reports of altered hypoglycaemia awareness after transfer to human insulin made physicians and especially patients uncertain about potential adverse effects of human insulin. OBJECTIVES: To assess the effects of different insulin species by evaluating their efficacy (in particular glycaemic control) and adverse effects profile (mainly hypoglycaemia). SEARCH STRATEGY: A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on human versus animal insulin was performed using the Cochrane Library (issue 2, 2002), Medline (1966 to May, 2002) and Embase (1974 to February, 2002). We also searched reference lists and databases of ongoing trials. Date of latest search: May 2002. SELECTION CRITERIA: We included randomised controlled clinical trials with diabetic patients of all ages that compared human to animal (for the most part purified porcine) insulin. Trial duration had to be at least one month in order to achieve reliable results on the main outcome parameter glycated haemoglobin. DATA COLLECTION AND ANALYSIS: Trial selection as well as evaluation of study quality was performed by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and by Jadad. MAIN RESULTS: Altogether 2156 participants took part in the 45 randomised controlled studies that were discovered through extensive search efforts. Though many studies were of a randomised, double-blind design, most studies were of poor methodological quality. Purified porcine and semi-synthetic insulin were most often investigated. No significant differences in metabolic control or hypoglycaemic episodes between various insulin species could be elucidated. Insulin dose and insulin antibodies did not show relevant dissimilarities. REVIEWER'S CONCLUSIONS: A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety.

Animals↗
PubMed2002

Chemotherapy versus hormonal treatment in platinum- and paclitaxel-refractory ovarian cancer: a randomised trial of the German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) Study Group Ovarian Cancer.

BACKGROUND: The majority of patients with ovarian cancer are not cured by first-line treatment. Until now, no study could demonstrate any substantial benefit when exposing ovarian cancer patients to second-line chemotherapy. However, most treatment regimens induce toxicity, thus negatively influencing the quality of rather limited life spans. Here we evaluate whether a second-line chemotherapy can offer any benefit compared with a less toxic hormonal treatment. PATIENTS AND METHODS: Patients with ovarian cancer progressing during platinum-paclitaxel containing first-line therapy or experiencing relapse within 6 months were eligible. Patients were stratified for response to primary treatment (progression versus no change/response), and measurable versus non-measurable disease. Treatment consisted of either treosulfan 7 g/m5 infused over 30 min or leuprorelin 3.75 mg injected subcutaneously or intramuscularly. Both regimens were repeated every 4 weeks. RESULTS: This study began in late 1996, and after 2.5 years accrual an interim analysis was performed when several investigators reported their concern about a suspected lack of efficacy. Following this analysis the recruitment was stopped early and the 78 patients already enrolled were followed up. The majority of patients received treatment until progressive disease was diagnosed or death occurred. Treatment delay was observed rarely and dose reduction was performed only in the treosulfan arm in 5% of 150 courses. Overall, both treatment arms were well tolerated. No objective responses were observed. The median survival time was 36 and 30 weeks in the treosulfan and leuprorelin arms, respectively. Overall survival did not differ between patients with relapse 3-6 months after first-line chemotherapy compared with patients with progressive disease within 3 months. CONCLUSIONS: The selected patient population represents a subgroup with extremely poor prognosis. Accordingly, results were not impressive. Both treatment arms showed favourable toxicity data, but failed to show remarkable activity, thus adding only limited evidence to the issue of whether patients with refractory ovarian cancer might benefit from second-line chemotherapy. Even stratified analysis did not identify any subgroup of patients in whom the administration of second-line chemotherapy could demonstrate a clinically relevant survival benefit.

Adult↗
PubMed2001

cAMP-dependent phosphorylation of CYP2B1 as a functional switch for cyclophosphamide activation and its hormonal control in vitro and in vivo.

An important feature of cytochrome P450 (CYP) 2B1 is its high ability to convert the prodrug cyclophosphamide (CPA) to therapeutically cytotoxic metabolites, resulting in interstrand DNA-cross-linking and cell death. We have examined whether and how the phosphorylation of CYP2B1 influences CPA metabolic activation in vitro and in vivo. We found first that only part of the total CYP2B1 pool undergoes phosphorylation. This part is fully inactivated. Second, phosphorylation of CYP2B1 in intact hepatocytes reduced by up to 75% toxification of CPA to mutagenic metabolites (totally dependent on the same preferentially CYP2B-catalyzed 4-hydroxylation of CPA as is the generation of highly cytotoxic species). Third, the phosphoacceptor-serine 128 of CYP2B1 in the consensus sequence for interaction with the protein kinase A represents an on/off switch for the activation of CPA depending on the phosphorylation conditions in the cell. Fourth, evidence is presented that the above-described events also occur in vivo. In conclusion, a successful therapy with CPA, helped by forced expression of CYP2B1 in tumor cells (as recently proposed) will, in addition, be profoundly modified by its phosphorylation status.

Animals↗
PubMed2001

A screen for mutations in human homologues of mice exencephaly genes Tfap2alpha and Msx2 in patients with neural tube defects.

BACKGROUND: Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2alpha and Msx2, which are expressed in the developing neural tube. METHODS: A single-strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2alpha and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRalpha, and PAX1 already shown to be related to NTD. RESULTS: Two TFAP2alpha point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9-bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2alpha and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2alpha polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57-5.39). CONCLUSIONS: Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases.

Alleles↗
PubMed2001

Saliva testing after single and chronic administration of dihydrocodeine.

In the present study, concentrations of dihydrocodeine and its metabolites in saliva and serum were compared after single low-dose and chronic high-dosage administration of the drug. In the first investigation, blood and saliva were collected periodically from six subjects after oral administration of 60 mg dihydrocodeine. In the second study, 20 subjects on oral dihydrocodeine maintenance provided single samples of blood and saliva simultaneously. Serum protein binding of salivary analytes and their recovery from the adsorbing material of the collection device as well as pH values of saliva samples were determined. The fluids were analyzed for dihydrocodeine and the major metabolites by high-performance liquid chromatography. In the single dose study dihydrocodeine was the only analyte found in saliva for up to 12-24 h post-dose. The half-life of dihydrocodeine in saliva was about twice that found in blood. The ratios of saliva/serum concentrations ranged from 1.2 to 17.0. After chronic high-dosage use, dihydrocodeine was the main salivary analyte and N-nordihydrocodeine was present in a few samples. Saliva/serum concentration ratios of dihydrocodeine were strongly dependent on the pH value of saliva and, to a lesser extent, on serum-protein binding. The saliva/serum ratios were more similar after chronic administration. The data suggest a passive diffusion process as the underlying mechanism for the transport of dihydrocodeine into saliva. After both single and chronic use, the presence of the drug in saliva can be used as evidence of recent substance administration.

Biotransformation↗
PubMed2001

Interaction of folate and homocysteine pathway genotypes evaluated in susceptibility to neural tube defects (NTD) in a German population.

Neural tube defects (NTD) are likely to result from an interaction of several genes and environmental factors. Because periconceptional folate intake reduces the NTD risk in the fetus, and because mothers of children with NTD showed elevated plasma homocysteine levels, gene polymorphisms of the folate and homocysteine pathway, such as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C-->T, MTHFR 1298A-->C and cystathionine beta-synthase (CBS) 844ins68, have been implicated in the etiology of NTD. Several studies have demonstrated that these polymorphisms may indeed be associated with NTD in some populations. In order to evaluate the role of these polymorphisms and their interaction in NTD, we genotyped 417 individuals for case-control studies and 129 families for transmission disequilibrium tests. We are the first to present detailed data on MTHFR haploid genotypes in combination with CBS 844ins68. The MTHFR risk genotype 677CT/1298AC, known to be associated with decreased enzyme activity and increased homocysteine, was found significantly more often in patients than in controls (P = 0.02). A CBS insertion allele in addition to MTHFR 677CT/ 1298AC heterozygosity or MTHFR 677TT/1298AA homozygosity did not result in an increased risk for NTD. This is in agreement with the recently reported homocysteine-lowering effect of the CBS 844ins68 allele in carriers of MTHFR variants.

Alleles↗
PubMed2001

The need for psychosocial support in parents with cochlear implanted children.

OBJECTIVE: The aim of the study was to assess the need of parents with Cochlear implanted children for psychosocial support, based on psychic symptoms reported by these parents and their motivation to make use of psychosocial interventions. METHODS: Fifty seven mothers and 46 fathers of 57 Cochlear implanted children were evaluated separately, employing validated questionnaires (Symptom Checklist-90-R and Questionnaire on Psychosocial Support). RESULTS: 26% of the mothers and 25% of the fathers showed severe psychic symptoms as reflected in the Symptom Checklist-90-R. Fifty nine percent of the mothers and 60% of the fathers were highly motivated to participate in psychosocial interventions--especially in the form of further information on their children's ailment and in parents' groups. CONCLUSIONS: The data presented suggest that there is a need for psychosocial support in 18% of the parents; 8% of the parents show high psychic stress, but low motivation. The rest of the parents are not in need of support; nevertheless, 42% of the parents are highly motivated in favor of psychosocial interventions.

Adult↗
PubMed2001

[Evaluation of a structured education program for adult outpatient asthmatics].

BACKGROUND AND METHODS: The efficacy of a structured education programme (AFAS) unter outpatient conditions was evaluated in a pilot study including 25 mild to severely ill adult asthmatics (age 41 +/- 2 yrs.) over a period of two and a half years. The main teaching items of the programme are: self-control of the disease with regular peak flow measurements, monitoring of symptoms with a patient diary, effects and side effects of the treatment, correct inhalation technique of asthma medication and the ability of self-management with regard to the actual degree of airflow limitation by the patients. RESULTS: After AFAS the knowledge of the patients regarding the disease as well as the medication increased significantly. There was an improvement of drug therapy: before AFAS only 52% of the patients used inhaled steroids on a regular basis with regard to 96% one and two years after participation of AFAS (p < 0.01). The self-control of the disease was improved: before AFAS no patient measured peak flow during acute dyspnoea, compared with 88% (p < 0.001) and 75% (p < 0.001) one and two years after AFAS, respectively. The number of severe asthma-attacks decreased significantly from 10.7 +/- 2.5 per patient and year before education to 1.3 +/- 0.2 (p < 0.001) after the first year and to 2.0 +/- 0.3 (p < 0.05) after the second year. The total number of hospital days due to asthma decreased from 219 days in the year before the participation in AFAS to zero (p < 0.001) in the first year after the education and to 17 days (p < 0.001) after the second year. CONCLUSIONS: The efficacy of patient education with AFAS is still evident two years after the course, but a reduction of self-control of the disease was observed during the follow-up period. In conclusion, structured education programmes for adult asthmatics can be effective even under outpatient conditions.

Adolescent↗
PubMed2001

Probiotics--compensation for lactase insufficiency.

Yogurt and other conventional starter cultures and probiotic bacteria in fermented and unfermented milk products improve lactose digestion and eliminate symptoms of intolerance in lactose maldigesters. These beneficial effects are due to microbial beta-galactosidase in the (fermented) milk product, delayed gastrointestinal transit, positive effects on intestinal functions and colonic microflora, and reduced sensitivity to symptoms. Intact bacterial cell walls, which act as a mechanical protection of lactase during gastric transit, and the release of the enzyme into the small intestine are determinants of efficiency. There is a poor correlation between lactose maldigestion and intolerance; in some studies, low hydrogen exhalation without significant improvement of clinical symptoms was observed. Probiotic bacteria, which by definition target the colon, normally promote lactose digestion in the small intestine less efficiently than do yogurt cultures. They may, however, alleviate clinical symptoms brought about by undigested lactose or other reasons.

Animals↗
PubMed2001

The Nucleus Contour electrode array: a radiological and histological study.

OBJECTIVES: To evaluate the handling and insertion trauma of the recently developed Nucleus perimodiolar Contour electrode array (Cochlear Ltd., Pty, Lane Cove, New South Wales, Australia) in human temporal bones compared with the Nucleus standard straight electrode array. STUDY DESIGN: E-perimental control group. METHODS: Twenty-nine fresh-frozen bones were implanted with different electrode arrays by an experienced cochlear implant surgeon, and evaluated both radiologically and histologically. RESULTS: Intracochlear insertion of the standard Nucleus straight electrode array was found to be atraumatic, confirming previous findings in the literature. Insertion of the Nucleus Contour electrode array resulted in instances of localized basilar membrane penetration causing the electrode array to move from the scala tympani into the scala vestibuli. However, this trauma did not result in any observable damage to the osseous spiral lamina or the modiolus. Basilar membrane penetration was observed in six of eight cochlear bones when a standard cochleostomy size (approximately 0.8 mm) and site (anterior and superior to the round window) were used. However, when the surgical technique was modified to use a slightly larger cochleostomy ( approximately 1.8 mm) situated closer to the round window and employ a partial stylet withdrawal technique during electrode insertion, the frequency of penetrations was restricted to two of seven bones. This trauma rate is comparable to that observed with other cochlear implants designs. CONCLUSIONS: Following our results, the design of the Nucleus Contour electrode appears to fulfill the safety requirements for an intracochlear electrode array, provided that the surgical insertion technique is modified in the manner outlined.

Basilar Membrane↗
PubMed2001

Cochlear structures after implantation of a perimodiolar electrode array.

OBJECTIVE: A perimodiolar prototype electrode array has been evaluated on 12 human temporal bone specimens. To achieve modiolar proximity, a fine Teflon positioner is attached to the tip and base of a conventional Nucleus 22 electrode array. METHODS: Intracochlear electrode position was examined by macroscopic preparation and confirmed by a cochlear view x-ray after insertion into human temporal bones. The temporal bones were examined with light microscopy for intracochlear trauma after insertion, explantation, and re-implantation of the perimodiolar array. RESULTS: Macroscopic preparation and x-ray confirmed close proximity of the intracochlear electrodes to the modiolar wall. In some bones, electrode insertion and positioning was performed without significant damage to intracochlear structures, but explantation caused varying degrees of trauma depending on the explantation technique used. Re-implantation and repeat explantation appeared to destroy most of the intracochlear architecture. CONCLUSIONS: The perimodiolar electrode array prototype with Teflon positioner cannot be recommended for clinical use, especially in children in whom the possibility for re-implantation is high.

Child↗
PubMed2001

Epiglottic tuberculosis: differential diagnosis and treatment. Case report and review of the literature.

A case of a 40-year-old man with tuberculous involvement of the epiglottis suffering from unsuspected pulmonary tuberculosis is described. The laryngeal lesions were primarily considered to be highly suspicious for a neoplastic process rather than an infectious one. After diagnosis, the patient was treated according a standard protocol and followed up for a period of 2 years. He is still free of disease. The clinical presentation, diagnosis, pathological findings, and therapy of the condition are described. The differential diagnosis and management of epiglottic tuberculosis are reviewed and discussed. Even though these cases are rare, otorhinolaryngologists should keep in mind the possibility of tuberculosis in the differential diagnosis of laryngeal tumors, as the incidence of tuberculosis in developed countries is steadily increasing.

Adult↗