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Biomedical subjects

C Rose

Publications and source records attributed to C Rose.

At least 181 records · Page 10Linked to original sources
PubMed1994

The pharmacokinetics of high-dose epirubicin and of the cardioprotector ADR-529 given together with cyclophosphamide, 5-fluorouracil, and tamoxifen in metastatic breast-cancer patients.

A high-pressure liquid chromatographic method for determination of the bisdioxopiperazine derivative ADR-529 (ICRF-187), a compound proven effective in protection against anthracycline-induced cardiotoxicity, has been developed. The limit of quantitation was 5 ng/ml using a narrow-bore 5-microns silica column and UV detection. The method was used for determination of pharmacokinetic profiles of ADR-529 after a 3-weekly i.v. administration of different doses of ADR-529 (600-1000 mg/m2) together with different doses of epirubicin (E, 60-100 mg/m2), fixed-dose cyclophosphamide (C, 600 mg/m2), fixed-dose 5-fluorouracil (F, 600 mg/m2), and daily administration of tamoxifen (T, 30 mg; CEF-T) in the treatment of patients with metastatic breast cancer. Pharmacokinetic parameters for epirubicin were also determined. The aim of the study was to determine (1) whether the pharmacokinetics of ADR-529 as part of a combination with CEF-T changes with increasing doses of ADR-529 and increasing doses of epirubicin and (2) whether the pharmacokinetics of epirubicin in the same combinations is altered with the administration of increasing doses of ADR-529. A total of 82 patients were included. A crossover study including 16 of the patients showed no significant difference in epirubicin pharmacokinetic parameters when epirubicin was given with or without concomitant administration of ADR-529. Apart from minor changes in the distributional half-lives, the pharmacokinetic parameters of epirubicin were not altered with increasing doses of ADR-529, nor were the pharmacokinetic parameters of ADR-529 itself. Escalating doses of epirubicin did not significantly alter the pharmacokinetic parameters of ADR-529 with the exception of a 30% increase in the terminal half-life and a decrease in total body clearance when the epirubicin dose was raised from 60 to 100 mg/m2. We conclude that concomitant administration of ADR-529 does not alter the distribution and elimination of epirubicin in doses suitable for preventing the anthracycline-induced cardiotoxicity.

Aged↗
PubMed1994

Percutaneous vertebroplasty with acrylic cement in the treatment of a Langerhans cell vertebral histiocytosis.

A 25-year-old man developed multiple eosinophilic granuloma of bone including vertebral and sacral localization. Radiotherapy was initially administered. One year later, a relapse occurred in another vertebrae which was previously irradiated. Percutaneous vertebroplasty was, for the first time to our knowledge performed, in this indication, with a good clinical result with follow-up now for one year. We emphasize that such treatment is permissible only in symptomatic, progressive lesions, with threatened decompensation of spinal stability. This technique should be used only on an adult.

Adult↗
PubMed1994

[Predictive signs of cancers in dermatomyositis. Study of 29 cases].

Dermatomyositis (DM) is characterized by an inflammatory myopathy and typical cutaneous lesions. In a retrospective study, 29 adult cases without overlap syndrome were reviewed. Our aim was to define predictive signs of cancer. Ten (four women, six men) of the 29 patients (35%) had DM associated with malignancy. The diagnosis of cancer was made concomitantly in six cases, more than year after (two cases), more than year prior to (two cases) the occurrence of DM. No extensive diagnosis procedures were necessary for identifying the tumors. A paraneoplasic evolution was certain for any patient, probable for six, improbable for fourth. For the group with malignancy: age was higher (P = 0.01), albumin lower (P = 0.04), C reactive protein higher (P = 0.0061). These parameters seem to have predictive value for the presence of malignancy.

Adult↗
PubMed1994

A novel antigen defined by monoclonal antibody CR101 is associated with small cell lung carcinoma.

Small cell lung carcinoma (SCLC) represents about 25% of all lung cancers. Human SCLC shows neuroendocrine features such as the production of neural peptide hormones, marker enzymes and neurosecretory granules, and the expression of neural cell adhesion molecules (NCAMs). Although SCLC is sensitive to both chemotherapy and radiation, prognosis remains poor due to the appearance of post-treatment chemo- and radioresistant variants. Monoclonal antibodies (MAbs) have been developed that bind to SCLC tumor antigens. We have used similar technology to define another SCLC marker designated gP94/115. The MAb CR101 binds to a highly glycosylated, cell-surface antigen associated with SCLC. In vitro expression of the antigen appears to be restricted to cell lines of SCLC origin. Enzymatic removal of the sugars resolves the antigen into two proteins of 94 and 115 kD by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Fluorescence-activated cell sorting (FACS) analysis confirms the antibody's specificity. These results indicate that CR101 may recognize a novel protein expressed by SCLC.

Animals↗
PubMed1994

The construction and characterization of poliovirus antigen chimeras presenting defined regions of the human T lymphocyte marker CD4.

Defined regions of the CDR2-like region of the T cell antigen CD4 that are implicated in the binding of the surface glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) to CD4+ T lymphocytes have been engineered in place of antigenic site 1 of Sabin type 1 poliovirus. The antigenic properties of the recovered chimeric virus particles were investigated using monoclonal antibodies (MAbs) and polyclonal serum to CD4. None of the MAbs tested neutralized the chimeras, presumably because they are directed against conformational determinants of the V1 domain of CD4. In contrast, the three antigen chimeras were neutralized by polyclonal serum to CD4, which suggested that the CD4-derived sequences were presented in a relevant conformation. A panel of six MAbs were raised against one of the chimeras, and the epitopes were mapped by the selection of neutralization-resistant mutants and cross-neutralization studies. Five of the six MAbs reacted with soluble CD4 (sCD4) in ELISA, and one (MAb 1686) bound to CD4 expressed at the surface of HeLa cells. The high affinity interaction between gp120 and sCD4 was not blocked by MAb 1686, and the poliovirus-CD4 chimeras did not interact with gp120. These results demonstrate that poliovirus can be used as an epitope expression vector for the presentation of sequences in an immunodominant location on the virus particle which adopt a native or near-native conformation, and supports the findings of previous studies involving the presentation of epitopes derived from pathogens.

Amino Acid Sequence↗
PubMed1994

Crouzon syndrome is not linked to craniosynostosis loci at 7p and 5qter.

Evidence for linkage has been sought, in four pedigrees with Crouzon syndrome, between polymorphic markers known to be linked to the Saethre-Chotzen locus on 7p and another form of autosomal dominant craniosynostosis on 5q. The data we present exclude Crouzon syndrome as an allelic variant at either of these known craniosynostosis loci.

Chromosomes, Human, Pair 5↗
PubMed1994

Bioaerosols.

Explore the source record for details and available documents.

Aerosols↗
PubMed1994

Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases.

We treated 28 cases of myelodysplastic syndrome (MDS) with neutropenia by very low-dose GM-CSF (0.25 or 0.5 micrograms/kg/day). Median age was 69 years. Nine patients had RA, 18 had RAEB, and one had RARS. Eighteen patients had absolute neutrophil counts (ANC) < or = 0.5 x 10(9)/l, and ten had ANC between 0.5 and 1.0 x 10(9)/l. Ten patients had experienced > or = WHO grade II infection(s) during the preceding 3 months. Eighteen patients (64%) had a response (i.e. ANC at least doubled and > or = 1 x 10(9)/l after 1 month), including 4/8 patients treated at 0.25 mu/kg/day, and 14/20 treated at 0.5 microgram/kg/day (difference not significant). Two of the non-responders obtained a response after dose escalation to 0.5 and 1 microgram/kg/day, respectively. The only prognostic factor of response was FAB subtype (10/11 responses in patients with RA or RARS, vs. 8/17 in RAEB, p = 0.04). Patients with ANC < or = 0.5 x 10(9)/l had a 55% (10/18) response rate, which was not significantly lower than the 80% (8/10) response rate observed in patients with ANC > 0.5 x 10(9)/l. Side-effects were generally moderate, except in three patients where the drug had to be discontinued, including the only patient who progressed to AML. In responders, GM-CSF was continued during 2 to 14 months (median 6), and the response persisted in all but one case, who relapsed after 60 days of treatment. During follow-up, only one responder had > or = WHO grade II infections, as compared to five of the non-responders (of whom two had fatal infectious episodes). In conclusion, very low-dose GM-CSF can durably increase ANC in about two thirds of MDS with neutropenia. Although it remains to be shown in randomized trials that it can reduce the incidence of infections and improve survival in MDS, very low-dose GM-CSF may be an interesting approach in MDS, associated to reasonable cost.

Aged↗
PubMed1993

Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients.

PURPOSE: The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. METHODS AND MATERIALS: One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. RESULTS: Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). CONCLUSION: The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus.

Adult↗
PubMed1993

Occurrence, extent, and implications of pressure waves during excimer laser ablation of normal arterial wall and atherosclerotic plaque.

Ablation of atherosclerotic plaque and normal arterial wall was performed using a Xenon-Chloride Excimer laser with a wave-length of 308 nm and a pulse duration of 115 ns. The light was transmitted via a 600 microns bare fibre and adjusted to an energy density of 3.5J/cm2. The acoustic signals generated by the laser pulse were measured with two types of hydrophones consisting of polyvinylidenefluoride with active diameters of 0.3 mm and 0.5 mm and recorded on a dual channel digital storage oscilloscope using either a 0.5 m coaxial cable or a broadband fibre-optic transmission system. Tissue was retrieved from nine cadaver human aortas and macroscopically classified as either normal or calcified atherosclerotic plaque. Histological analysis (Haematoxylin eosin, elastica van Gieson, and immunohistochemical staining) was carried out after the experiments to verify the macroscopic diagnosis and to correlate the acoustic responses with the tissue characteristics. For normal arterial wall, maximum peak pressure was 1.28 MPa +/- 0.85 MPa, rise time 163 ns +/- 43 ns, and pressure increase 8.2k Pa +/- 5.4k Pa/ns. For calcified, atheromatous segments, a maximum peak pressure of 2.02 MPa +/- 1.16 MPa, a rise time of 69.9 ns +/- 25.8 ns, and a pressure increase of 32.3 kPa +/- 21.3 kPa/ns was found. Statistical analysis showed a significant shorter rise time (P < 0.0001) and a higher pressure increase (P < 0.0001) for calcified tissue in comparison to normal arterial wall, whereas maximum pressures alone did not allow a differentiation of tissue characteristics. Several hundred kPa are generated during Excimer laser ablation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustics↗
PubMed1993

The innervation of the bovine ductus deferens: comparison of a modified acetylcholinesterase-reaction with immunoreactivities of cholinacetyltransferase and panneuronal markers.

The innervation pattern of the bovine deferent duct was studied by acetylcholinesterase (AChE)-histochemistry and by immunohistochemical methods. Using antibodies against protein gene product-9.5 (PGP-9.5) and neuron specific enolase (NSE) the complete innervation pattern can be visualized. Thick nerve bundles in the periductal connective tissue supply the two-layered muscular coat. The inner, mainly circularly arranged muscle bundles are innervated by a particularly dense plexus, whereas the nervous network of the more longitudinally running outer musculature is somewhat looser. Additionally, nerve fibres were observed in the subepithelial space in connection with blood vessels and in close proximity to the basal lamina. An innervation pattern analogous to that of the two panneuronal markers was displayed in the immunoreaction against dopamine-beta-hydroxylase (DBH), indicating that the innervation of the bovine deferent duct is predominantly adrenergic. However, the positive reaction with a monoclonal antibody against cholinacetyltransferase (ChAT) specifically demonstrated for the first time the presence of a cholinergic nerve plexus, restricted to the inner muscular layer and the subepithelial space. A modified, direct-colouring AChE-method is presented, which uses copper chloride as source of cupric ions, acetylthiocholine chloride as substrate and 2-morpholinoethanesulphonic acid (MES) as buffer. After short incubation (1-2 h) our modified method allows the specific visualization of cholinergic nerves, comparable to the results of ChAT-immunoreactivity; following a long incubation time (24 h), it reliably illustrates the autonomous innervation pattern as completely as immunohistochemical panneuronal markers.

Acetylcholinesterase↗
PubMed1993

Information for cancer patients entering a clinical trial--an evaluation of an information strategy.

Informing patients before the start of antineoplastic treatment is important due to the anxiety and uncertainty felt by the patients and the legal aspects of trials. 34 women were interviewed 3 months after receiving information. Results show that the information was well remembered, patients were glad to bring a relative, two consultations with time for deliberation were well-received and that patients viewed written information as an important reinforcement. Overall, information provided was positively evaluated. Detailed information allowed patients to understand and participate in treatment decisions, thereby reducing their pretherapy anxiety. These results support expansion of the structured information programme to include all patients about to begin long-term cancer therapy.

Adult↗
PubMed1993

Decreased efficacy of cyclophosphamide, epirubicin and 5-fluorouracil in metastatic breast cancer when reducing treatment duration from 18 to 6 months.

The impact of treatment duration on survival and progression-free survival is uncertain in metastatic breast cancer. In this trial 359 patients were randomised to receive cyclophosphamide, epirubicin and 5-fluorouracil (CEF) once every 3 weeks for a maximum of 18 months or identical chemotherapy for a maximum of 6 months. Following progressive disease (PD) or severe toxicity CEF was discontinued before the scheduled maximum duration. A second series of CEF continued for a maximum of 12 months was offered to patients with PD more than 3 weeks after completing a maximum of 6 months of CEF. Both groups received tamoxifen (30 mg daily) until PD, and premenopausal patients also received ovarian irradiation. After 6 months 254 evaluable patients were unprogressive. Survival and progression-free survival were significantly longer in 127 patients continuing CEF than in 127 patients interrupting CEF at 6 months (chi 2 = 17.6, P = 0.00003 and chi 2 = 4.7, P = 0.03, respectively). The results of the second series of CEF were discouraging with only one complete response in 44 evaluable patients. In conclusion, prolonged chemotherapy for 18 months is superior to identical chemotherapy for 6 months in the treatment of metastatic breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Short recurrence-free survival associated with high oestrogen receptor levels in the natural history of postmenopausal, primary breast cancer.

The ability of oestrogen and progesterone receptor (ER and PgR, respectively) status to discriminate recurrence-free survival (RFS) among a cohort of consecutively accrued 952 postmenopausal patients has been studied. None of the cohort members investigated were treated with adjuvant therapy. Using a graduated scale of receptor status [low, intermediate and high receptor levels (< 10 vs. 10-107 vs. > or = 108 fmol/mg cytosol protein, respectively)] instead of the more commonly used dichotomous subdivision (positive vs. negative), ER level significantly discriminated between groups of patients with long vs. short RFS. Contrary to our expectations, patients with highest ER levels have as poor a prognosis as ER-negative patients, while patients with intermediate ER levels have longest RFS. The group of patients with ER levels > or = 108 fmol/mg cytosol protein comprises 47% of the cohort. The independent significance of overexpression of ER as a prognostic factor among this patient group is demonstrated in multivariate analysis where ER level is more significant than either grade of anaplasia or tumour size. PgR status did not significantly predict RFS among these patients. While the highest ER levels predispose for poorer prognosis among postmenopausal patients, it is precisely this group that experiences greatest benefit from adjuvant treatment with tamoxifen. Thus, patients who might otherwise go untreated due to their node-negative status can be readily identified and offered adjuvant treatment.

Adult↗