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Biomedical subjects

B Richter

Publications and source records attributed to B Richter.

At least 19 recordsLinked to original sources

Synthesis and properties of a novel family of fluorous triphenylphosphine derivatives

A novel approach to the preparation of perfluorotail-functionalized triarylphosphines using a p-silyl substituent as the branching point has been developed. This approach enabled the attachment of between three and nine perfluorotails per phosphorus atom, resulting in the production of highly fluorous tris[p-(1H,1H,2H, 2H-perfluoroalkylsilyl)aryl]phosphines, P[C(6)H(4)-p-SiMe(3)(-)(n)()(CH(2)CH(2)C(x)()F(2)(x)()(+1))(n)()](3) (n = 1, 2, 3; x = 6, 8), containing between 50 and 67 wt % fluorine. (31)P NMR studies indicate that the phosphorus atoms, and consequently the sigma-donor and pi-acceptor properties of these phosphines, are not influenced by the electron-withdrawing perfluoroalkyltails. The fluorous triarylphosphines are readily soluble in fluorous solvents and display fluorous phase preference in several fluorous biphasic systems. The phase partitioning of these fluorous ligands, as well as their donor properties, is discussed in relation to their potential for fluorous biphasic catalyst separation.

Journal Article↗

Atomic structure of the polar NiO(111)- p(2x2) surface

Using grazing-incidence x-ray diffraction, the p(2x2) surface structures of the single crystal NiO(111) and a 5 monolayer thick NiO(111) film on Au(111) were both shown to exhibit locally the theoretically predicted octopolar reconstruction, with some important differences. The single crystal exhibits a single Ni termination with double steps. The thin film exhibits both possible terminations (O and Ni) and single steps. These surfaces were found to be nonreactive with respect to hydroxylation.

Journal Article↗

[Psychological stress, knowledge and treatment expectation of parents with a child managed by cochlear implant].

UNLABELLED: ESTABLISHED KNOWLEDGE: It is known that parents of hard-of-hearing children suffer from an increase in psychosocial stress. SCIENTIFIC QUESTION: How does the psychosocial situation of parents with children who have cochlear implants change during rehabilitation? AIM OF STUDY: It was the aim of this study to demonstrate how parents evaluate retrospectively their own psychological well-being during the process of rehabilitation. METHODS AND RESULTS: We interviewed 87 parents by questionnaires which were mailed to them. Fifty-seven mothers and 46 fathers responded (59% return rate). Parents reported a significant increase in stress, as perceived by themselves, after the time of diagnosis. Of the parents, 25% continued to suffer from psychic stress during rehabilitation as could be demonstrated by the SCL-90-R questionnaire criteria. The expectations by parents were realistic prior to implantation but thereafter increased significantly with time. CONCLUSIONS: The psychological state of parents during the critical phase, after a diagnosis of deafness has been made for their child, has to be considered. Even after an initial phase of shock, parents seemed to be stressed to an extent that required therapeutic intervention.

Adaptation, Psychological↗

Effects of on-demand beta2-agonist inhalation in moderate-to-severe asthma. A randomized controlled trial.

BACKGROUND: The appropriate use of short-acting beta2-agonist inhalation in asthma has been the subject of controversy in recent years. Limited information is available for the group of moderate to severe asthmatics with high intake of bronchodilator inhalants and continuous anti-inflammatory protection. OBJECTIVE: To investigate the effects of beta2-agonist reduction in marked asthma treated with multiple asthma medications. DESIGN: Randomized, controlled single-blind, cross-over trial. SETTING: Outpatient clinic at a university medical centre. SUBJECTS: A total of 80 adult patients with moderate-to-severe asthma. INTERVENTIONS: In a 1-year study patients were assigned to on-demand vs. regular beta2-agonist inhalation treatment. MAIN OUTCOME MEASURES: Asthmatic episodes (primary outcome), symptoms, peak expiratory flow rates (PEF) and drug use were recorded daily. Bronchodilator and airway responsiveness, lung function indices and quality of life were assessed during five clinic visits. Also, practicability of beta2-agonist tapering in multimedicated asthmatics was analysed. RESULTS: More than 80% of moderate-to-severe asthmatics were able to reduce their beta2-agonist intake by >/=50%. Puffs per day of active therapy decreased from 7.9 in regular to 3.3 in on-demand treated patients (P = 0.0001). The type of beta2-agonist used (salbutamol/fenoterol) had no significant impact on the study findings. Almost all parameters of control of asthma improved during the on-demand treatment period. CONCLUSION: On-demand inhalation of short-acting beta2-agonists in moderate-to-severe asthma is safe, and even in severe asthma a reduction from regular to on-demand beta2-agonist inhalation is possible, with improved asthma control.

Acute Disease↗

Esophageal atresia in Bremen, Germany--evaluation of preoperative risk classification in esophageal atresia.

BACKGROUND/PURPOSE: The current study enrolled 113 patients with esophageal atresia (EA) accompanying tracheoesophageal fistula (TEF) (Vogt type IIIb) who were treated at the Central Hospital St. Jürgen Strasse, Department of Pediatric Surgery in Bremen, Germany between 1978 and 1997. METHODS: These EA patients were classified into patients preoperatively complicated by respiratory distress syndrome (RDS) or pneumonia and those without complications. In each group, risk factors were classified according to the risk classification described by Spitz et al, and the prognoses and therapeutic problems were evaluated. Based on these results, a new preoperative risk classification consisting of risk factors described by Spitz et al supplemented with RDS and pneumonia was evaluated. RESULTS: When the prognoses of EA were evaluated, the survival rate was markedly decreased when RDS or pneumonia alone or more than 2 of 3 factors including major cardiac anomalies and low birth weight were present as preoperative risk factors. Concerning therapeutic problems, the necessity of treatment with delayed primary repair tended to increase when RDS or pneumonia was present as risk factors. However, it was suggested that secure and safe blockage of TEF was still difficult during the initial surgery. CONCLUSIONS: During selection of therapeutic strategies for EA, RDS and pneumonia are still considered to be essential as preoperative risk factors for EA. Our new preoperative risk classification consisting of risk factors described by Spitz et al supplemented with RDS and pneumonia appears to clearly reflect the prognoses and therapeutic problems of EA.

Child↗

[Parotid involvement in cat scratch disease: a differential diagnosis with increased significance].

BACKGROUND: Bartonella henselae is the causative agent of cat-scratch disease (CSD), an inflammatory infection of the lymph nodes. So far, only few cases of atypical manifestations in the head and neck, especially manifestations in the parotid gland have been reported. PATIENTS AND METHODS: Between January 1997 and June 1999 seven patients with manifestations of CSD in the parotid gland were observed at the ENT-department Freiburg. The positive diagnosis was confirmed serologically by an indirect immunofluorescence assay and by detection of Bartonella henselae-DNA with PCR-amplification and subsequent hybridization or sequencing. RESULTS: An intraglandular abscessed lymphadenitis was found in five patients, two of these cases were based on a Parinaud's oculoglandular syndrome. A diffuse affection of the parotid gland, initially misinterpreted as a parotid tumor, was seen in two patients. CONCLUSIONS: Antibiotic treatment is recommended in order to reduce the duration of the disease, in cases of pain and lymph node abscesses. In uncommon manifestations of CSD, the nosological assignment can be difficult on the basis of the heterogeneous symptomatic in the individual patient and the CSD diagnosis can only be confirmed by serology or PCR-based techniques. CSD should be considered in the differential diagnosis of all equivocal masses in the head and neck, even in unusual localisations like the parotid gland.

Abscess↗

Working conditions on stage: climatic considerations.

Singers and actors frequently complain about dusty and dry theater environments, which they believe induce respiratory tract indispositions and decrements in vocal performance. In the literature to date, extremely few quantitative data exist about actual climatic conditions on stage. A previous study by our group in an unhumidified theater found that it had too high temperatures, too dry and too dusty air, based on German occupational guidelines for the generic workplace. In the present study, humidification units were installed in the same theater, and the environmental measures were repeated. The primary findings indicated that, following the activation of the humidification units, temperatures, humidities and fine dust concentrations were improved and generally within acceptable ranges for the generic workplace, although not always optimal. Where unacceptable performance environments exist, special care should be taken to counsel performers with regard to possible prophylactic measures such as individual steam inhalation and fluid intake.

Air↗

Mouse ten-m/Odz is a new family of dimeric type II transmembrane proteins expressed in many tissues.

The Drosophila gene ten-m/odz is the only pair rule gene identified to date which is not a transcription factor. In an attempt to analyze the structure and the function of ten-m/odz in mouse, we isolated four murine ten-m cDNAs which code for proteins of 2,700-2, 800 amino acids. All four proteins (Ten-m1-4) lack signal peptides at the NH2 terminus, but contain a short hydrophobic domain characteristic of transmembrane proteins, 300-400 amino acids after the NH2 terminus. About 200 amino acids COOH-terminal to this hydrophobic region are eight consecutive EGF-like domains. Cell transfection, biochemical, and electronmicroscopic studies suggest that Ten-m1 is a dimeric type II transmembrane protein. Expression of fusion proteins composed of the NH2-terminal and hydrophobic domain of ten-m1 attached to the alkaline phosphatase reporter gene resulted in membrane-associated staining of the alkaline phosphatase. Electronmicroscopic and electrophoretic analysis of a secreted form of the extracellular domain of Ten-m1 showed that Ten-m1 is a disulfide-linked dimer and that the dimerization is mediated by EGF-like modules 2 and 5 which contain an odd number of cysteines. Northern blot and immunohistochemical analyses revealed widespread expression of mouse ten-m genes, with most prominent expression in brain. All four ten-m genes can be expressed in variously spliced mRNA isoforms. The extracellular domain of Ten-m1 fused to an alkaline phosphatase reporter bound to specific regions in many tissues which were partially overlapping with the Ten-m1 immunostaining. Far Western assays and electronmicroscopy demonstrated that Ten-m1 can bind to itself.

Alkaline Phosphatase↗

[Otorhinolaryngologic findings in Horton temporal arteritis. Review of the literature and case report].

Otorhinolaryngological findings of a temporal arteritis frequently occur in the beginning and/or course of the disease. A purulent sinusitis can be a sign of recurrence of the arteritis and was diagnosed in a 77-year-old woman with known disease that had been biopsied 6 years earlier. Puncture of the maxillary sinus was considered necessary, but no bacteria were found in purulent sinus discharge. When antibiotic treatment failed to bring about a resolution of the inflammatory condition, steroid therapy was begun and the patient recovered within a few days in response to this treatment. The clinical findings in this case show that early diagnosis and treatment by the otorhinolaryngologist are necessary in order to prevent severe complications of the disease.

Aged↗

[Objective auditory brainstem response threshold deficits in patients with cerebellopontine angle tumors].

The established criteria of auditory brainstem responses (ABR) such as JV latency, JI-V interpeak latency and interaural differences of latency or amplitude have been found to be sensitive for detecting tumors of the cerebellopontine angle if a response is present. However, the ABR can be absent in cases of acoustic neuromas because of desynchronization, even though pure-one audiometry indicates that responses should be present. This retrospective study compared the ABR and pure-tone thresholds in 234 cases with cerebellopontine angle tumors and a control group of 181 cases with sensory hearing losses in order to quantify threshold discrepancies. The average deficit of the objective ABR threshold (DOABRT) to the subjective pure-tone threshold for those frequencies between 1-6 kHz was 3.6 dB for the control group (ABR and pure tone thresholds very close) and 31.2 dB for the tumor group (ABR threshold much higher than the pure-tone threshold). ABR thresholds 30 dB higher than the high-frequency pure tone thresholds were found in 40.6% of the tumor group and in none of the control group. Thus, deficits of the ABR threshold >30 dB can be considered to be an additional criterion for detecting retrocochlear disease and increases ABR sensitivity for tumor detection even if responses are absent.

Adolescent↗

First-line chemotherapy with epirubicin, paclitaxel, and carboplatin for advanced ovarian cancer: a phase I/II study of the Arbeitsgemeinschaft Gynäkologische Onkologie Ovarian Cancer Study Group.

PURPOSE: Despite the progress that has been achieved over the years, survival rates in patients with advanced ovarian cancer are still disappointing. New methods to improve the efficiency of first-line chemotherapy are warranted. One method to improve results is to add more non-cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines are among the candidates for incorporation as the "third drug" into first-line regimens for advanced ovarian cancer. PATIENTS AND METHODS: We performed a phase I/II trial with escalating doses of epirubicin (60, 75, and 90 mg/m2) combined with fixed doses of paclitaxel and carboplatin in 27 previously untreated patients with advanced gynecologic malignancies. RESULTS: Dose-limiting toxicity occurred at dose level 2 (75 mg/m2 epirubicin) and consisted of myelosuppression (neutropenia, thrombocytopenia). No dose-limiting, nonhematologic toxicities were observed. The maximum tolerable dose was epirubicin 60 mg/m2 (E) combined with a 3-hour infusion of paclitaxel 175 mg/m2 (T) and carboplatin AUC 5 (Carbo). Preliminary analysis indicated promising activity against ovarian cancer. CONCLUSION: The three-drug combination ET-Carbo, given according to the outlined dose and schedule, should be considered for further phase III evaluation. A randomized German-French intergroup trial comparing ET-Carbo with carboplatin-paclitaxel has already been initiated.

Adult↗

Reoperation as treatment of relapse after subtotal thyroidectomy in Graves' disease.

BACKGROUND AND METHODS: In Graves' disease radioiodine is the recommended treatment for relapses after subtotal thyroidectomy. If patients reject radioiodine, hyperthyroidism is managed with antithyroid drugs; surgery is generally not considered as an alternative. Here we retrospectively analyzed 30 consecutive patients with Graves' disease who had recurrent hyperthyroidism after subtotal thyroidectomy. RESULTS: On relapse after the first operation, the patients were initially treated by medication; 25 opted for definitive treatment (19 for reoperation and 6 for radioiodine). Operations consisted of 10 unilateral and 8 bilateral resections (total or near-total with capsular remnants of < 1 g) and 1 transsternal approach (because of dystopic intrathoracic thyroid tissue). The decision between a unilateral and a bilateral reintervention was based on the ultrasonographic determination of remnant volumes. These size estimates were valid because they were significantly correlated to the weight of the resected remnants (r = 0.92, slope = 0.95). Eighteen of the 19 patients were adequately treated by this approach. Unilateral resection was performed in 1 patient with a remaining contralateral remnant of 5.4 mL; this patient had a second relapse. The complication rate was low (2 cases of transient recurrent nerve injury and 1 of transient hypocalcemia). CONCLUSION: Provided that no contraindication is present, reoperation is safe, effective, and expeditious in recurrent hyperthyroidism. Because the likelihood of a recurrence depends on the total remnant size, the goal is to keep it below 2 g. Preoperative ultrasonography can effectively guide the decision between a unilateral and a bilateral resection.

Adult↗

Differential modulation of CYP2E1 activity by cAMP-dependent protein kinase upon Ser129 replacement.

Many toxic compounds are activated by cytochrome P450 (CYP) 2E1 to reactive metabolites, which represents a potential hazard for cellular homeostasis. Therefore knowledge about CYP2E1 regulation could be of great biological importance. It has been shown that CYP2E1 is controlled transcriptionally and post-translationally by phosphorylation. In the present study we investigated the role of serine-129 (Ser129) in the protein kinase A (PKA) recognition sequence motif Arg-Arg-Phe-Ser129. To gain further insights into the possible relevance of Ser129 for CYP2E1 function, Ser129 was replaced by alanine (Ala) or glycine (Gly) by site-directed mutations of the cDNA coding for CYP2E1. The mutant cDNAs were transfected into Chinese hamster lung fibroblast V79 cells. Despite the mutation in the PKA phosphorylation motif, all strains produced catalytically active CYP2E1. However, there was a marked change in the substrate preference: The Gly129-containing strains hydroxylated p-nitrophenol (PNP) to a markedly higher extent than the wild-type cDNA-containing cells, while they demethylated N-nitrosodimethylamine (NDMA) to a markedly lower extent than the wild-type cells. All the strains activated NDMA to mutagenic products. Treatment with the membrane-permeating cAMP derivative db-cAMP reduced markedly both the PNP hydroxylase and the NDMA demethylase activities as well as the mutation frequency induced by NDMA in the Ser129-containing strain. This decrease in activity was not accompanied by a decrease in CYP2E1 content. In addition, the catalytic activities of CYP2E1 were decreased in microsomes from rat hepatocytes treated with db-cAMP. Also in this case, the decrease in activities was not accompanied by a decrease in enzyme protein. These findings argue that involvement of Ser129 and its phosphorylation is not in determining CYP2E1 protein level, but rather in controlling its catalytic activity. In contrast, in the strains containing Ala129 or Gly129, treatment with db-cAMP caused a marked increase in both PNP hydroxylase and NDMA demethylase. In these strains a similar db-cAMP-mediated increase was also observed in the mutation frequency, resulting from the treatment with the promutagen NDMA, which is activated by CYP2E1. Our results show that CYP2E1 in V79 cells responds in two separate ways to db-cAMP exposure depending on the amino acid residue present in the PKA recognition sequence. The enzyme is committed to a negative regulation by db-cAMP if Ser129 is the target amino acid for PKA, leading to a decrease in the metabolic activation to mutagenic and carcinogenic species. On the other hand, Ala129 or Gly129 substitution directed CYP2E1 toward a positive regulation by increasing its catalytic activities and metabolic activation to mutagenic intermediates in the presence of db-cAMP. We also obtained evidence that cAMP-mediated downregulation of wild-type (Ser129) CYP2E1 was not accompanied by its destruction but instead by its stabilization, which shows that Ser129 is not involved in CYP2E1 degradation but dictates requirements for its specific activities.

Amino Acid Substitution↗