(CA)n-dinucleotide repeat at the PDEB locus in 4p16.3.
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Biomedical subjects
Publications and source records attributed to B Weber.
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We describe the clinicopathological features of six patients, two with rheumatoid arthritis and four with osteoarthritis, in whom intake of sustained-release diclofenac for one or more years was associated with ulceration and or stricture of the ascending colon. All were referred for further evaluation of anemia and changes in bowel habits. Three had chronic watery diarrhea, one suffered from progressive constipation and subsequently needed a right hemicolectomy because of complete intestinal obstruction. In five patients, colonoscopy revealed single to multiple semilunar ulcers, predominantly localized on the crest of the haustra of the ascending colon. In five of six cases the lumen was narrowed, from slight accentuation of the haustrum to almost pinhole-like concentric stenosis. All except one patient had multiple diaphragm-like strictures. The macroscopic and microscopic appearances closely resembled those of similar lesions previously described in the terminal ileum in patients treated with nonsteroidal anti-inflammatory drugs. It appears that the slow-release form of a nonsteroidal anti-inflammatory drug, such as sustained-release diclofenac, predisposes to manifestations of such lesions in the ascending colon.
A two-site monoclonal antibody (MoAb) ELISA has been developed for the quantification of the Phleum pratense major allergen, Phl p V. The assay is based on two MoAbs which recognize different non-overlapping epitopes on the Phl p V molecule; one antibody (1D11) was immobilized on the solid phase and the other (3B2) was biotinylated. An affinity-purified Phl p V preparation (purity of 95%) was used as standard. The assay has a sensitivity of 10 ng/ml of allergen and is suitable for the detection of group V allergen in aqueous grass extracts. The specificity of the assay was investigated with 14 grass pollen and five non-grass pollen extracts. Different levels of group V allergen were detected in extracts of grasses, but not in non-grasses. The assay gives a good correspondence with allergenic activity of extracts as determined by ELISA inhibition using serum pool of allergic patients. The results indicate that the two-site MoAb ELISA could be very useful in the standardization of allergenic extracts from grass pollen.
The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH < 4.0, p < 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p < 0.01), upright reflux (p < 0.05), supine reflux (p < 0.001), and postprandial reflux (p < 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p < 0.01), supine reflux (p < 0.05), and postprandial reflux (p < 0.05). Cisapride also reduced both the number (p<0.01) and duration (p<0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p<0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.
PURPOSE: We assessed the feasibility of noninvasive metabolic monitoring of cancer chemohormonotherapy using sequential quantitative positron emission tomographic (PET) scans of tumor glucose metabolism with the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS: Eleven women with newly diagnosed primary breast cancers larger than 3 cm in diameter beginning a chemohormonotherapy program underwent a baseline and four follow-up quantitative PET scans during the first three cycles of treatment (days 0 to 63). Tumor response was sequentially determined clinically, radiographically, and then pathologically after nine treatment cycles. RESULTS: Eight patients had partial or complete pathologic responses. Their maximal tumor uptake of FDG assessed by PET decreased promptly with treatment to the following: day 8, 78 +/- 9.2% (P < .03); day 21, 68.1 +/- 7.5% (P < .025); day 42, 60 +/- 5.1% (P < .001); day 63, 52.4 +/- 4.4% (P < .0001) of the basal values. Tumor diameter did not decrease significantly during this period through 63 days. Prompt decreases in the FDG influx rate (K) from basal levels (from .019 to .014 mL/cm3/min) after 8 days of treatment (P < .02) and in the estimated rate of FDG phosphorylation to FDG-6-phosphate (k3) from .055 to .038 min-1 after 8 days of treatment (P < .02) to .029 +/- .004 min-1 at 21 days) (P < .02) were observed. Three nonresponding patients had no significant decrease in tumor uptake of FDG (81 +/- 18% of basal value), influx rate (.015 to .012 mL/cm3/min), or tumor size (81 +/- 12% of basal diameter) comparing basal versus 63-day posttreatment values. CONCLUSION: Quantitative FDG PET scans of primary breast cancers showed a rapid and significant decrease in tumor glucose metabolism after effective treatment was initiated, with the reduction in metabolism antedating any decrement in tumor size. No significant decrease in FDG uptake (SUV) after three cycles of treatment was observed in the nonresponding patients. FDG PET scanning has substantial promise as an early noninvasive metabolic marker of the efficacy of cancer treatment.
Some kind of anaesthesia could be able to be used as theoretical models to build both hypothesis about awakening and methods for its study. There are codified anaesthesia for short operations, using few drugs with well known pharmacology. Studying awakening requires circumstantial screens to identify awake marks. Such a screen has been used for some years in this type of anaesthesia given for voluntary pregnancy termination. Similar but not identical marks are observed while the subject drop asleep and awake. They seem approximate marks observed with other screens used for coma awakening survey. But an interpretation of this marks, necessarily cautious, is usable only inside these anaesthetic conditions; if so, psychological explanations appears no more but no less useful than bio-pharmacological one.
We report the application of a modified Western blot (WB) micromethod basically relying on a diffusion-blotting technique (Modi-blot) combined with an immunological detection system using monoclonal antibodies and a biotinavidin amplification step for the detection of IgM antibodies against coxsackieviruses B1 (CBV1), CBV2 and CBV4. Fifty-one adult patients with clinical signs of coxsackievirus B infection (e.g. myocarditis and meningitis) were investigated. The test revealed a total of 31 (60%) IgM positives. The majority of IgM antibodies were group reactive (22/31). Type-specific antibodies could be recognized in 9 cases (3 with CBV1, 5 with CBV2 and 1 with CBV4). The highest rate of antibody prevalence was found in sera from patients with acute meningitis (12/14). Controls [healthy adults (n = 13) and individuals with other infections (n = 13)] were all negative for specific IgM against coxsackievirus B1, B2 and B4. Further WB tests of 8 IgM positive specimens with coxsackievirus B4 revealed specific IgA responses in all cases, reinforcing the evidence for a recent infection. In addition, the patterns of IgG antibody subclasses, also investigated in this group, showed a clear predominance of specific IgG1 and IgG3 antibodies.
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Seventy-seven pre-treated patients with advanced breast cancer were administered a combination chemotherapy with cisplatin 50 mg/sqm d1, 5-fluorouracil 300 mg/sqm/d protracted continuous infusion d1-d28, allopurinol 600 mg/d po d1-d28, q29d. Overall response rate was 26%, median survival time 46 weeks, survival rate 43.3% at 1 year, 20.2% at 2 years, 10.6% at 3 years. Response rate was rather high in CNS and meningeal involvement (6/10).
Human T-lymphoid MOLT-4 cells were grown continuously for more than 1 year in medium containing either 3'-azido-2',3'-dideoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) or 2',3'-dideoxycytidine (ddC) at concentrations similar to peak plasma levels found in clinical trials in patients with AIDS. To test antiviral activities of the nucleoside analogs against HIV-1 in the cell sublines designated MOLT-4r-AZT, MOLT-4r-ddI and MOLT-4r-ddC, the number of infected cells, p24 HIV-1 antigen in culture medium and syncytium formation of infected cultures were determined. The results showed that anti-HIV-1 activities of AZT, ddI and ddC were significantly decreased in the resistant MOLT-4 cell sublines grown continuously with the respective nucleoside analog, probably due to the development of cell populations resistant to the drugs.
When compared with systemic therapy, hepatic arterial chemotherapy significantly increases the response rate for hepatic metastases from colorectal carcinomas. However, only 2 studies showed a significant prolongation of survival. In our study on 54 patients tumor related characteristics and the response to regional chemotherapy were correlated to the success of the treatment. In a linear discriminant analysis the response to regional chemotherapy was the main prognostic factor for the 1-year survival, rate, followed by positive lymph nodes in the Lig. hepatoduodenale. The other pretherapeutic factors such as liver involvement and CEA rate were of less importance.
The present case report describes a 69 year old man who was admitted because of severe pain in the right upper abdomen by condition after a Billroth II resection of the stomach and a obstructive icterus. The reason was a common bile duct stone with a central shell splinter. Due to purulent cholangitis with inflammatory stenosis of the distal ductus choledochus endoscopic removal of the stone was only successful in repeated attempts.
A relatively simple, sensitive and rapid high-performance liquid chromatographic method is described for measuring the anticancer drug 5-fluorouracil (5-FU) in human plasma and urine. The procedure includes liquid-liquid extraction using ethyl acetate-methanol (95:5) and preparative column chromatography to separate 5-FU from constituents normally occurring in these biological samples. The columns contained a specially modified form of diatomaceous earth, which requires no pre-conditioning washes. Reversed-phase high-performance liquid chromatography was performed on a C18 column (70 mm x 4.6 mm I.D.) with a mobile phase of water-methanol (95:5) and ultraviolet detection (268 nm). The overall recovery from plasma and urine was 91 and 94%, respectively, at the concentration of 50 ng/ml. The determination limit of the assay for 5-FU was 10 ng/ml of plasma and urine. Concentrations of 5-FU between 10 and 500 ng/ml were measured in plasma and urine with a relative standard deviation of 6.8%. In order to evaluate the procedure, plasma and urine samples from three patients treated with 5-FU by continuous intravenous perfusion, were investigated.
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We report on the requirements that have to be met to combine a standard-dose chemotherapy regimen with broad antitumor activity with the mobilization of peripheral blood hematopoietic progenitor cells. Thirty-two cancer patients were given a 1-day course of chemotherapy consisting of etoposide (VP16), ifosfamide, and cisplatin (VIP; n = 46 cycles), followed by the combined sequential administration of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Control patients received GM-CSF alone or were treated without cytokines. Maximum numbers of peripheral blood progenitor cells (PBPC) were recruited on day 13 to 17 after chemotherapy, with a median of 418 CD34+ cells/microL blood (range, 106 to 1,841) in IL-3/GM-CSF-treated patients, 426 CD34+/microL (range, 191 to 1,380) in GM-CSF-treated patients, and 46 CD34+/microL (range, 15 to 148) in patients treated without cytokines. In parallel, there was an increase in myeloid (10,490 colony-forming unit-granulocyte-macrophage [CFU-GM]/mL blood; range, 1,000 to 23,400), as well as erythroid (10,660 burst-forming unit-erythroid [BFU-E]/mL blood; range, 3,870 to 24,300) and multipotential (840 CFU-granulocyte, erythrocyte, monocyte, megakaryocyte [GEMM]/mL blood; range, 160 to 2,070) progenitor cells in IL-3 plus GM-CSF-treated patients. In GM-CSF-treated patients, significantly less precursor cells of all lineages were mobilized, particularly multipotential progenitors (400 CFU-GEMM/mL blood; range, 200 to 2,150). Only small numbers of CD34+ cells and clonogenic progenitor cells could be recruited in intensively pretreated patients. Our data document that after standard-dose chemotherapy-induced bone marrow hypoplasia, IL-3 plus GM-CSF can be used to recruit PBPC, which might shorten the hematopoietic recovery after high-dose chemotherapy in chemosensitive lymphomas or solid tumors.
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The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.
Basic features and techniques of percutaneous endoscopic laser discectomy are described and the results in 6 patients reported. Indications are: discogenic radicular symptoms, caused by disc protrusions, which do not respond to conservative treatment. Contra-indications are: major neurological deficit, segmental instability and spondylolisthesis, extruded disc prolapse, narrow spinal canal or lateral recess.