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Biomedical subjects

C Conrad

Publications and source records attributed to C Conrad.

At least 19 recordsLinked to original sources
PubMed1999

Pre-operative MR-mammography in breast cancer patients.

AIMS: Pre-operatively, to exclude multiple invasive tumours not discovered by mammography and sonography in patients referred for breast conservation surgery. METHODS: A supplementary MR-mammography was offered to all patients with mammographic and/or sonographic ascertained tumours less than 2 cm in diameter. RESULTS: Forty patients were offered this additional examination. In accordance with the MR diagnosis, 51% of the planned surgical procedures were changed. Nine patients had more than one invasive tumour, and in four patients the tumour was >2cm in diameter. One patient had no tumour at all, and in four patients the MR-mammography suggested benign fibroadenomas, which resulted in small excisions. One patient with a suspect MR-mammography presented sclerosing adenosis at surgery. Three patients had to be excluded due to MR problems. Ten patients preferred mastectomy, although the MR-mammography had shown only a single invasive tumour. CONCLUSION: MR-mammography is recommended as a pre-surgical diagnostic procedure in patients allocated to breast conservation surgery.

Adult↗
PubMed1999

Evaluation of sleep architecture and cyclic alternating pattern rates in depressed insomniac patients treated with nefazodone hydrochloride.

The standard methods of scoring sleep patterns do not ensure an accurate clinical impression of sleep quality. This is important especially in depressed insomniacs because persistent poor sleep increases the likelihood of recurrent depressive episodes. Changes in cyclic alternating patterns (CAP) in sleep have been shown to reflect corresponding changes in sleep quality. We evaluated the effects of nefazodone on CAP and standard sleep architecture in depressed insomniacs. The study was a single-center, single-blind, 6-week treatment of nefazodone hydrochloride followed by placebo withdrawal in 16 subjects meeting the DSM-IV criteria for depression who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale, with insomnia-related items 4, 5, and 6 having a total score of 3 or greater. A mean daily dose of 339.1 +/- 141.7 mg at endpoint of nefazodone significantly reduced Hamilton Depression Scores from 21.7 +/- 3.0 on baseline to 5.8 +/- 5.3 (P <.05) by the end of the study. Polysomnography showed an improvement in sleep latency and sleep efficiency (P <.05), but no alterations in rapid-eye-movement or slow-wave sleep. Subjective estimates of sleep quality improved throughout the study, but CAP rates did not show a significant improvement. The disparity between CAP rates and sleep quality in depressed insomniacs is discussed.

Adult↗
PubMed1999

Potency testing of anti-lymphocyte globulins: in vitro alternatives for the monkey skin graft assay.

Anti-lymphocyte globulins (ALG) are immunosuppressive agents of animal origin currently used in clinical organ transplantation and for the treatment of severe aplastic anaemia. The potency of each batch is tested in vivo using primates as recipients for allogeneic skin grafts. The two in vitro methods commonly used are (i) a cytotoxic assay and (ii) the rosette inhibition assay, both of which are evaluated by microscopy. In addition to animal welfare aspects, these methods require considerable experience, are difficult to validate, and the information as to the biological potency of the sera is questionable. The aim of our study is a better characterization of the biological properties of ALG in order to subsequently define an in vitro alternative for the potency test in monkeys. Several antibody specificities directed against functional molecules on T-cells, B-cells, NK-cells, macrophages as well as non-lineage specificities can be identified in competition assays with monoclonal antibodies. The cytotoxic capacity of ALG in the presence or absence of complement as well as DNA-fragmentation characteristic for apoptosis can be analysed by flow cytometry using propidiumiodide- (PI) incorporation. Immunoprecipitation of cell lysate with ALG and subsequent incubation with radioactive ATP (kinase-assay) shows specific bands which seem to be identical between different batches of one product.

Animal Testing Alternatives↗
PubMed1998

Different cleavage specificities of RNases III from Rhodobacter capsulatus and Escherichia coli.

23S rRNA in Rhodobacter capsulatus shows endoribonuclease III (RNase III)-dependent fragmentation in vivo at a unique extra stem-loop extending from position 1271 to 1331. RNase III is a double strand (ds)-specific endoribonuclease. This substrate preference is mediated by a double-stranded RNA binding domain (dsRBD) within the protein. Although a certain degree of double strandedness is a prerequisite, the question arises what structural features exactly make this extra stem-loop an RNase III cleavage site, distinguishing it from the plethora of stem-loops in 23S rRNA? We used RNase III purified from R.capsulatus and Escherichia coli, respectively, together with well known substrates for E.coli RNase III and RNA substrates derived from the special cleavage site in R.capsulatus 23S rRNA to study the interaction between the Rhodobacter enzyme and the fragmentation site. Although both enzymes are very similar in their amino acid sequence, they exhibit significant differences in binding and cleavage of these in vitro substrates.

Bacterial Proteins↗
PubMed1998

Differences in a dinucleotide repeat polymorphism in the tau gene between Caucasian and Japanese populations: implication for progressive supranuclear palsy.

Previous studies of a tau polymorphism in Caucasian subjects with progressive supranuclear palsy (PSP) showed an over-representation of one genotype, A0/A0, versus normal control subjects. This result suggested that tau may be playing a genetic role in the progression of PSP. This study examines whether the over-representation of A0/A0 is Caucasian-specific or universal to PSP. Unfortunately, we found this dinucleotide repeat was relatively non-polymorphic in Japanese subjects. As a result, the genotypes were virtually the same, A0/A0, between Japanese PSP and control subjects. However, this outcome, albeit negative, does suggest two possible roles of the tau gene in PSP pathogenesis: (1) the role of this dinucleotide repeat in PSP may be different between Caucasian and Japanese populations or (2) this repeat may not be causal for PSP but represents a marker for other molecular genetic risk factors within or close to the tau gene on chromosome 17.

Alzheimer Disease↗
PubMed1998

Rapid fragmentation of vimentin in human skin fibroblasts exposed to tamoxifen: a possible involvement of caspase-3.

Tamoxifen (TAM), an anti-estrogen compound, is widely used for chemotherapy of breast cancer, although the molecular mechanisms underlying TAM cytotoxicity are obscure. Here, we show that TAM dramatically caused degradation of vimentin (VIM) in human skin fibroblasts, in a time and dose dependent manner. Addition of caspase-3 inhibitor, Z-DEVD-FMK, inhibited formation of some fragments of VIM, and caspase-3 was proteolytically activated by TAM treatment. Expression of functional estrogen receptors were negative in these cells, and neither transcription nor protein synthesis was required for TAM-induced degradation of VIM. Moreover, quinestrol, an ethinyl estradiol derivative, weakly degraded VIM, whereas neither estradiols nor estriol had any effects. Taken together, TAM may induce fragmentation of VIM associated with an activation of caspase-3, which may be attributed to non-genomic actions of TAM.

Antineoplastic Agents, Hormonal↗
PubMed1998

CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize beta1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion.

Cell migration may depend on integrin-mediated adhesion to and deadhesion from extracellular matrix ligands. This concept, however, has not yet been confirmed for T lymphocytes migrating in three-dimensional extracellular matrices. We investigated receptor involvement in T cell migration combining a three-dimensional collagen matrix model with time-lapse videomicroscopy, computer-assisted cell tracking and confocal microscopy. In collagen lattices, the migration of CD4+ T cells (1) involved interactions with collagen fibers at the leading edge and uropod likewise, (2) occurred independently of the co-clustering of beta1, beta2, or beta3 integrins with F-actin, focal adhesion kinase, and phosphotyrosine at interactions with collagen fibers, (3) was counteracted by high-affinity beta1 integrin binding induced by antibody TS2/16; however, (4) the migration could not be blocked by a combination of adhesion-perturbing anti-beta1, -beta2, -beta3, and alpha v integrin antibodies. Integrin blocking neither affected cell polarization, interaction with fibers, beta1 integrin distribution, migration velocity, path structure, nor the number of locomoting cells in spontaneously migrating or concanavalin A-activated cells. Hence, T lymphocytes migrating in three-dimensional collagen matrices may utilize highly transient interactions with collagen fibers of low adhesivity, thereby differing from focal adhesion-dependent migration strategies employed by other cells.

Antibodies, Monoclonal↗
PubMed1998

[Comparison between steam and gas sterilized optics. Costs, availability, maintenance].

METHODS: In a 300-bed acute-care hospital we compared optical instruments employed, for orthopedic, urological and gynecological operations during their use in practice. The comparison between 33 ethylene oxide(EO)-sterilized optical instruments and 14 steam-sterilized optical instruments took into account the following criteria: frequency of use; availability; sterilization cycles; kind, cost and number of repairs. RESULTS: The 33 EO-sterilized optical instruments were handled 1043 times and were repaired 10 times (at a cost of up to 2000 SFR). The 14 steam-sterilized optical instruments were treated 1101 times and were repaired 8 times (2000 SFR). The total costs were 77,000 SFR for the 14 steam-sterilized instruments and 132,000 SFR for the 33 EO-sterilized instruments. INTERPRETATION: Steam-sterilization is a reasonable, safe and fast method of sterilizing optical instruments. We prefer this method, given its advantages (less toxicity, personal care and pollution control).

Cost-Benefit Analysis↗
PubMed1998

Use of amoxicillin-clavulanate and resistance in Escherichia coli over a 4-year period.

OBJECTIVE: To reduce the use of amoxicillin-clavulanate after high-resistance rates in Escherichia coli were detected. DESIGN: Intervention study; the interventions were introduced successively over a 4-year period while closely monitoring the resistance patterns. SETTING: A 260-bed acute-care hospital in Switzerland. INTERVENTIONS: Introduction of therapeutic guidelines for specific departments or indications, which proposed alternative antibiotics to amoxicillin-clavulanate. The perioperative prophylactic use of amoxicillin-clavulanate was eliminated completely. RESULTS: The absolute amount of amoxicillin-clavulanate consumed decreased by 23%, from 24.8 g per 100 patient days in 1992 to 18.5 g per 100 patient days in 1995. The number of courses, a parameter that takes the prophylactic use into account, decreased by 62% from 2.3 per 100 patient days in 1992 to 0.9 per 100 patient days in 1995. The percentage of sensitive strains increased from 54.9% (n=512) in 1992 and 54.0% (n=506) in 1993 to 72.1% (n=546) in 1994 and 83.1% (n=668) in 1995. No major changes were detected for other antimicrobials, such as cotrimoxazole, tetracycline, or cefuroxime, used in this 4-year period. CONCLUSIONS: A decrease in the use of amoxicillin-clavulanate was followed by an increase in susceptibility of E coli to it. It was not possible to prove a causative relationship. Only a temporal association was discovered. The reduction of the use of amoxicillin-clavulanate was achieved through the implementation of treatment guidelines, facilitated through a close collaboration among the clinical pharmacists, the infection control practitioner, the microbiology laboratory, and the physicians in charge of the respective departments.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1997

Neuropsychological profiles in schizophrenia: paranoid versus undifferentiated distinctions.

Research on schizophrenia has searched for subtype-specific cognitive dysfunction to elucidate the neurodevelopmental underpinnings of the disorder. The neuropsychological distinctions between 21 paranoid and 15 undifferentiated schizophrenics were studied. The paranoid group had significantly better Verbal IQ, executive functioning on the Wisconsin Card Sorting Test, and memory for spoken language on the Sentence Repetition Test compared to undifferentiated schizophrenics. While the paranoid subtype showed trends toward better performance on a wide variety of tasks, both subtypes showed impairments on tasks requiring continuous auditory attention and fine motor speed and coordination. Despite the paranoid subjects' more intact verbal skills, both groups showed significant deficits in verbal learning on the Rey Auditory Verbal Learning Test. This suggests that temporal-hippocampal system dysfunction may be a common denominator in both schizophrenic subtypes. These findings were not accounted for by subtype differences in the level of education, depression or severity of illness.

Adult↗
PubMed1997

Genetic evidence for the involvement of tau in progressive supranuclear palsy.

A dinucleotide repeat polymorphism in a tau intron was identified and used in a case-control study to analyze the genetic association of tau with several neurodegenerative diseases with tau pathology. Subjects with the homozygous tau AO alleles were excessively represented in the progressive supranuclear palsy (PSP) group, compared with the age-matched healthy control group. Consequently, this allele is more frequently found in PSP than in a group of healthy subjects. This trend was not found in Alzheimer's disease or parkinsonism-dementia complex of Guam, both of which are accompanied by major tau pathology. The result suggests a possible involvement of tau in the pathogenesis of PSP.

Base Sequence↗
PubMed1997

The treatment of recurrent cerebral gliomas with all-trans-retinoic acid (tretinoin).

Malignant gliomas continue to be a significant source of mortality in young and middle aged adults. The introduction of new treatment strategies and multidisciplinary approaches has improved the outcome of patients with these tumors only slightly. Because retinoic acid has growth inhibitory activity against glioma and neuroblastoma cells in cultures, we assessed the efficacy of all-trans-retinoic acid in the treatment of recurrent cerebral gliomas. Thirty-six patients with recurrent cerebral gliomas were entered in the study and treated with 120 or 150 mg/ m2/day of all-trans-retinoic acid as a single agent. The drug was given for 3 weeks followed with one week of rest. Two blocks of 4 weeks constituted one course of treatment. One (3%) of 34 evaluable patients had a minor response and 14 (41%) had stable disease. In the rest of the patients (56%), tumors continued to progress despite treatment. The median time to progression of all evaluable patients was 8 weeks, and for the responders was 17 weeks. The higher dose level (150 mg/m2) was associated with high incidence of headache, which responded to dose reduction. The lower dose level was very well tolerated, with mild, mainly dermatological toxicity. All-trans-retinoic acid as a single agent has no significant activity against recurrent cerebral gliomas.

Adolescent↗
PubMed1996

Identification and analysis of the rnc gene for RNase III in Rhodobacter capsulatus.

The large subunit ribosomal RNA of the purple bacterium Rhodobacter capsulatus shows fragmentation into pieces of 14 and 16S, both fragments forming the functional equivalent of intact 23S rRNA. An RNA-processing step removes an extra stem-loop structure from the 23S rRNA [Kordes, E., Jock, S., Fritsch, J., Bosch, F. and Klug, G. (1994) J. Bacteriol., 176, 1121-1127]. Taking advantage of the fragmentation deficient mutant strain Fm65, we used genetic complementation to find the mutated gene responsible for this aberration. It was identified as the Rhodobacter homologue to mc from Escherichia coli encoding endoribonuclease III (RNase III). The predicted protein has 226 amino acids with a molecular weight of 25.5 kDa. It shares high homology with other known RNase III enzymes over the full length. In particular it shows the double-stranded RNA-binding domain (dsRBD) motif essential for binding of dsRNA substrates. The Fm65 mutant has a frame shift mutation resulting in complete loss of the dsRBD rendering the enzyme inactive. The cloned Rhodobacter enzyme can substitute RNase III activity in an RNase III deficient E. coli strain. Contrary to E. coli, the Rhodobacter mc is in one operon together with the lep gene encoding the leader peptidase.

Amino Acid Sequence↗
PubMed1996

High-resolution fluorescence in situ hybridization of RBM- and TSPY-related cosmids on released Y chromatin in humans and pygmy chimpanzees.

Applying two-colour fluorescence in situ hybridization (FISH) we simultaneously hybridized RBM- and TSPY-related cosmids to Y chromosomes in prophase and to released Y chromatin in interphase nuclei of man and pygmy chimpanzee. Whereas, even on prophasic Y chromosomes, no resolution of the overlapping RBM and TSPY signal clusters could be achieved, the RBM and TSPY signals are completely separated from each other in our maximum released Y chromatin stretches in interphase nuclei. These results unequivocally lend support to the view that the RBM and TSPY families have an interspersed organization on the Y chromosomes of man and higher apes. Thus, the distribution of RBM and TSPY signals might well go back to a common organization of these genes next to each other on an ancient Y chromosome.

Animals↗
PubMed1996

Intensive care unit stay is prolonged in chronic alcoholic men following tumor resection of the upper digestive tract.

BACKGROUND: The prevalence of chronic alcohol misuse in patients with oral, pharyngeal, laryngeal or esophageal carcinomas exceeds 60%. No data is available, to our knowledge, on the morbidity and mortality of chronic alcoholics in surgical intensive care units (ICU) following tumor resection. We investigated whether the subsequent ICU stay in chronic alcoholics following tumor resection was prolonged and whether the incidence of pneumonia and sepsis was increased. METHODS: 213 patients with carcinomas of the upper digestive tract were evaluated regarding their drinking habits. Chronic alcoholics met either the DSM-III-R criteria for alcohol abuse or dependence. Conventional laboratory markers and serum carbohydrate-deficient transferrin were determined preoperatively. Major intercurrent complications during ICU stay such as an alcohol withdrawal syndrome, pneumonia and sepsis as well as the frequency of death were documented. RESULTS: Patients did not differ significantly between groups regarding age or APACHE score on admission to the ICU.121 patients were diagnosed as being chronic alcoholics, 39 as being social drinkers and 61 as being non-alcoholics. In chronic alcoholics the frequency of death was significantly increased. Due to the increased incidence of pneumonia and sepsis the ICU stay was significantly prolonged in chronic alcoholics by approximately 8 days. CONCLUSIONS: The increased mortality and morbidity rate demonstrates that chronic alcoholics undergoing major tumor surgery have to be considered as high-risk patients during their postoperative ICU stay. Further studies are required with respect to the immuno-competence of chronic alcoholics and the prevention of alcohol withdrawal syndrome, pneumonia and sepsis in these patients.

APACHE↗