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J Reuter

Publications and source records attributed to J Reuter.

At least 19 recordsLinked to original sources
PubMed2007

[Erythema annulare centrifugum Darier. Successful therapy with topical calcitriol and 311 nm-ultraviolet B narrow band phototherapy].

Erythema annulare centrifugum is an acute dermatosis of unclear etiology, which presents with annular erythematous lesions with marginal scale. Therapeutically, systemic and topical glucocorticosteroids are used primarily. We treated a patient with large lesions in the area of the thighs resistant to a therapy with topical glucocorticosteroids, with topical calcitriol in combination with 311 nm ultraviolet B narrow band phototherapy. After four weeks of treatment the skin lesions had cleared nearly completely without any side effects. The combination topical vitamin D3-analogue calcitriol and 311 nm ultraviolet B narrow band phototherapy was effective and can be regarded as a useful alternative to glucocorticosteroids for erythema annulare centrifugum.

Administration, Topical↗
PubMed2006

Continuous renal replacement therapy in patients following traumatic injury.

In critically injured patients, the incidence of acute renal failure has been reported to occur in as many as 31% of patients. The use of CRRT modalities for patients following traumatic injuries is becoming more common, albeit slowly, and this therapy may impact upon long-term recovery of renal function and mortality. Historical studies investigating the early use of intermittent dialysis reported significant improvement in survival in patients who were dialyzed earlier and more vigorously than in control subjects. Early trauma patients also showed improved survival following war injuries when dialyzed prophylactically. Although there is a growing acceptance in favor of earlier renal replacement therapy, the published consensus and the practice in many centers has been to dialyze/filter relatively ill rather than relatively healthy patients. The R Adams Cowley Shock Trauma Center (STC) in Baltimore, Maryland, USA, admits over 8,000 trauma patients each year. Within the STC, a program of continuous renal replacement therapy was established in the early 1980's. We review both historical and current literature on the use of renal replacement therapies after traumatic injury, and suggest some future areas of investigation and indications for these modalities.

Acute Kidney Injury↗
PubMed2003

Infrequent mutation of the tumour-suppressor gene Smad4 in early-stage colorectal cancer.

Smad4 is a candidate tumour-suppressor gene identified recently on chromosome 18q21.1. Both alleles are inactivated in nearly one-half of pancreatic carcinomas, but its role in the tumorigenesis of other tumours is still unknown. The aim of this study was to investigate the potential involvement of the Smad4 locus in early-stage colorectal cancers (stages I-III) in tumour samples from a randomised multicentre trial. Of a large collection of DNA samples, 73 with a loss of one allele of the Smad4 gene were analysed for the presence of point mutations in the remaining gene. Patients, from whom biopsies were isolated, were part of a previous randomised multicentre study of the Swiss Group for Clinical Cancer Research on the benefit of adjuvant chemotherapy (SAKK study 40/81). Mutation analysis was restricted to the highly conserved C-terminal domain (exons 8, 9, 10 and 11) of Smad4, using PCR and single-strand conformational variant analysis. Two of the 73 patients (3%) with loss of one allele of Smad4 had a point mutation in the remaining allele. These results indicate that whereas Smad4 point mutations are prevalent in pancreatic carcinoma, they are infrequent in early stages (I-III) of colorectal cancer.

Clinical Trials as Topic↗
PubMed2002

SMAD4 is a predictive marker for 5-fluorouracil-based chemotherapy in patients with colorectal cancer.

The gene for the transducer of transforming growth factor-beta/bone morphogenetic protein signalling SMAD4, a potential suppressor of colorectal carcinogenesis, is located at the chromosomal region 18q21. In order to evaluate the clinical relevance of SMAD4 deletion, gene copy alterations were determined by copy dosage using real-time quantitative PCR in 202 colorectal tumour biopsies from a previous randomised study of adjuvant chemotherapy. Patients with normal SMAD4 diploidy turned out to have a three-fold higher benefit of 5-fluorouracil-based adjuvant chemotherapy with a border line significance (overall survival: 3.23, P=0.056; disease-free survival: 2.89, P=0.045). These data are consistent with the previous observation that patients whose cancer had retention of the 18q21 region had a significantly higher benefit from 5-fluorouracil-based therapy. Moreover, these results may provide a refinement at the gene level of the clinical relevance of 18q21 deletion, thereby suggesting SMAD4 as a predictive marker in colorectal cancer. This data also indicate that integrity of this component of the transforming growth factor-beta/bone morphogenetic protein signalling pathway may be a critical factor for benefit of chemotherapy in patients with colorectal cancer.

Antimetabolites, Antineoplastic↗
PubMed2001

Combined copy status of 18q21 genes in colorectal cancer shows frequent retention of SMAD7.

Deletions of chromosome band 18q21 appear with very high frequency in a variety of carcinomas, especially in colorectal cancer. Potent tumor suppressor genes located in this region encode transforming growth factor beta (TGF-beta) signal transducers SMAD2 and SMAD4, and inactivation of either one leads to impaired TGF-beta-mediated cell growth/apoptosis. Following the assignment of SMAD7 to 18q21, we first refined the SMAD7 gene position within this region by genetically mapping SMAD7 between SMAD2 and SMAD4. Further, to compare the respective frequencies of genetic alterations of these three SMAD genes in colorectal cancer, we undertook a large-scale evaluation of the copy status of each of these genes on DNA samples from colorectal tumor biopsy material. Among a subset of 233 DNA samples for which data were available for all four genes, SMAD4, SMAD2, and the nearby gene DCC showed high deletion rates (66%, 64%, and 59%, respectively), whereas SMAD7 was deleted in only 48% of the tumors. Unexpectedly, we found some gene duplications; SMAD7 appears to be more frequently amplified (10%) than the three other genes (4-7%). Compiled data for SMAD genes in each tumor show that the most common combination (26% of all the tumors) consists of the simultaneous deletions of SMAD2 and SMAD4 associated with normal diploidy or even duplication of SMAD7. Since SMAD7 normally counteracts SMAD2 and SMAD4 in TGF-beta signaling, we hypothesize that the tumor might not benefit from simultaneous SMAD7 inactivation, thereby exerting selective pressure to retain or even to duplicate the SMAD7 gene.

Chromosome Deletion↗
PubMed2000

P21 gene expression as an indicator for the activity of adenovirus-p53 gene therapy in non-small cell lung cancer patients.

Alterations in the tumor suppressor gene p53 lead to impaired cell cycle control, allowing for the development and growth of tumors. To restore a loss of p53 function, we performed a phase I study of intratumoral gene therapy with adenovirus expressing wild-type p53 in patients with non-small cell lung cancer carrying mutations in the p53 gene. Furthermore, in a phase II study, gene therapy was complemented with simultaneous cisplatin/vinorelbine treatment. Biopsies were obtained from all treated patients before and 24-48 hours after gene therapy to study changes in the expression of p53 target genes. We report here that in most of the cases, the target gene p21 was up-regulated, especially when injection of higher doses of p53-expressing adenovirus was combined with simultaneous chemotherapy, whereas Pig3, previously reported to be highly up-regulated by p53, generally did not show a clear increase. Interestingly, a clear p21 gene response was observed only in tumors showing stabilization or regression. We conclude that p21 appears to be up-regulated after adenovirus-mediated p53 gene transfer and is the most sensitive marker tested for biological response to gene therapy in the small cohort of non-small cell lung cancers that were studied.

Adenoviridae↗
PubMed1999

Gene therapy with cytokine-transfected xenogenic cells (Vero-IL-2) in patients with metastatic solid tumors: mechanism(s) of elimination of the transgene-carrying cells.

Eleven patients with advanced cancer were treated in a clinical gene therapy trial by repeated intra- tumoral injections with different doses of xenogenic fibroblasts secreting high amounts of human interleukin-2 (Vero-IL2). Treatments in a total of 14 courses were well tolerated and resulted in clinical responses and measurable biological effects. Together with increases in serum interleukin-2 (IL-2), modifications of the V-beta T cell receptor repertoire and induction of intratumoral T-cell infiltration were observed. When the intratumoral expression of endogenous cytokine genes and the persistence of the IL-2 transgene at the application site and in peripheral blood were investigated, rapid disappearance of the transgene at the application site appeared to be the most prominent biological effect. Tests detecting a single Vero-IL2 cell against a background of 10(5) non-transfected cells were not able to demonstrate significant expression of exogenous IL-2 (i.e. the transgene or transgene-carrying cells) in tumor biopsies or blood at different times. Therefore, further studies were performed to evaluate the mechanism(s) involved in the rapid disappearance of xenogenic carrier cells in more detail. We show here that significant in vitro cytotoxicity against transgene-carrying Vero cells can be observed in peripheral blood of all the patients before treatment as well as in healthy controls. "Cold" target inhibition shows that significant killing of Vero-IL2 cells is mediated by natural killer (NK) cells. This was confirmed by showing that established CD3(-)/CD16(+)/CD56(+) peripheral blood NK cell clones kill both K562 and Vero-IL2 target cells. The failure of other mechanisms (complement, antibody-dependent cell cytotoxicity or cytotoxic T lymphocytes) to destroy xenogenic, histoincompatible Vero cells in vitro suggests that NK cells also might be responsible for the killing of Vero-IL2 in vivo and for the failure to detect the transgene at the application site. These results might also be of importance for some aspects of the current discussion of xenotransplantation.

Adult↗
PubMed1998

bcl-2 expression is reciprocal to p53 and c-myc expression in metastatic human colorectal cancer.

Apoptosis (programmed cell death) inhibition may be an important mechanism by which gastrointestinal mucosal cells containing damaged DNA evade normal clearance mechanisms and grow to become invasive tumours. Since bcl-2 is an apoptosis inhibitor, bcl-2 mRNA expression was measured in 21 metastases of colorectal cancer using reverse transcription-polymerase chain reaction analysis. The mean bcl-2 mRNA expression (0.45 U, P < 0.0001) was lower than that of normal mucosal controls (= 1 U). p53 expression was inversely correlated with bcl-2 expression (P = 0.021) in 19 evaluable samples, and in tumours where p53 expression was over twice that of normal colonic mucosal values, bcl-2 mRNA was significantly decreased (mean 0.30, P = 0.0052). c-myc was also inversely correlated with bcl-2 expression (P = 0.025). Decreased bcl-2 expression in metastatic colorectal cancer may be partly due to allelic loss, given the proximity of bcl-2 to the frequently deleted DCC gene on chromosome 18q. However, the inverse correlation to p53/c-myc suggests an active downregulation of bcl-2, possibly following delegation of its apoptosis inhibiting role to other genes.

Apoptosis↗
PubMed1997

MTS1 expression and prognosis in acute myeloid leukemia.

MTS1, a tumor suppressor gene located on chromosome 9p21, has been shown to be altered in a number of human tumor cell lines, primary solid tumors, and leukemias. In this study we found low expression of MTS1 in lymphocytes from seven of nine healthy donors, but in none of eight granulocyte samples from the same controls, suggesting a physiological role of MTS1 in peripheral blood cells capable of proliferation, but not in end-stage differentiated cells. We detected MTS1 mRNA expression in 38 of 57 patients (66%) with acute myelogenous leukemia (AML) treated in a standardized clinical protocol. No deletion of the MTS1 gene was found in any of the AML samples tested. There was no significant association between expression of MTS1 and response to therapy, progression-free, or overall survival. Except for a negative correlation between MTS1 level and leukocyte count at diagnosis (p = 0.03), there was also no association with any of the known prognostic parameters in AML. We conclude that MTS1 shows a significantly higher expression in leukemic than in normal peripheral blood cells, that deletion of MTS1 is not a frequent event in AML, and that its expression is not significantly correlated with outcome of the disease.

Cyclin-Dependent Kinase Inhibitor p16↗
PubMed1997

Topoisomerase II alpha mRNA and tumour cell proliferation in non-Hodgkin's lymphoma.

AIMS: To elucidate potential mechanisms of drug resistance, levels of topoisomerase II alpha mRNA, a target for cytostatic drugs, were measured in cryopreserved tumour tissue from 36 patients with non-Hodgkin's lymphoma. To evaluate the potential association between topoisomerase II alpha and cell proliferation, Ki-67 immunostaining was also assessed. METHODS: The study population comprised 13 patients with low grade and 20 with high grade non-Hodgkin's lymphoma. Three patients had recurrent disease. Topoisomerase II alpha mRNA was quantitated by using reverse transcription polymerase chain reaction (RT-PCR) and the PCR product measured by using HPLC. The MIB-1 monoclonal antibody was used for Ki-67 immunostaining. RESULTS: Levels of topoisomerase II alpha mRNA correlated strongly with the Ki-67 labelling index and were higher in high grade than in low grade lymphomas. Patients in complete clinical remission of high grade lymphoma had a higher Ki-67 labelling index and tended to have higher topoisomerase II alpha mRNA levels. CONCLUSIONS: Although topoisomerase II alpha mRNA levels may be indicative of sensitivity to drugs, it is more likely that they reflect the proliferation status of the cell, which in turn involves a large number of additional molecular systems that influence response to treatment.

Adolescent↗
PubMed1997

mRNA expression, measured by quantitative reverse transcriptase polymerase chain reaction, of five putative drug resistance parameters, in normal and leukaemic peripheral blood and bone marrow.

Using a quantitative reverse transcriptase PCR assay, the mRNA expression of five putative drug resistance-related genes were assessed in normal peripheral (n = 14) and bone marrow (n = 4) mononuclear cells from healthy donors and patients with acute myeloid leukaemia (n = 11). The mRNA levels of MDR1, the multidrug resistance-associated protein and glutathione-S-transferase pi were equally expressed in both compartments. Bcl-2 mRNA was slightly higher in the leukaemic marrow samples. However, topoisomerase II alpha mRNA levels were found to be much higher in normal and leukaemic marrow cells compared to peripheral blood (p < 0.01), which may, in part, reflect the different proliferation pattern of the mononuclear cells in the two compartments. Such findings could be important for researchers using bulk assays in a mix of samples from peripheral blood or bone marrow to investigate prognostic factors in patients with leukaemia.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

[Standardization of the Kent Infant Development Scale: implications for primary care pediatricians].

OBJECTIVE: The purpose of this study was the standardization of an infant assessment protocol based on behavioral observations of Spanish parents. The Kent Infant Development (KIDS) scale was translated into Spanish and named "Escala de Desarrollo Infantil de Kent" (EDIK). PATIENTS AND METHODS: The EDIK normative data were collected from the parents of 662 healthy infants (ages 1 to 15 months) in pediatric clinics. Infants born more than 2 weeks premature or who had serious physical or neurological illness were not included. RESULTS: EDIK raw scores of Spanish infants were converted to developmental ages by comparing them with the number of behaviors for each age group in the normative sample. We obtained the mean score and standard deviation for the full scale and different domains (cognitive, motor, social, language, and self-help). CONCLUSIONS: This study shows that EDIK is sensitive to differences in ages and a good instrument that allows one to make a classification between normal infants or those at risk. It should prove useful in developmental pediatric practice.

Ambulatory Care↗
PubMed1997

Five putative drug resistance parameters (MDR1/P-glycoprotein, MDR-associated protein, glutathione-S-transferase, bcl-2 and topoisomerase IIalpha) in 57 newly diagnosed acute myeloid leukaemias. Swiss Group for Clinical Cancer Research (SAKK).

UNLABELLED: Using a modified quantitative reverse transcriptase (RT) PCR assay in 57 patients with acute myeloid leukaemia (AML) from a Swiss Phase III multicentre study (SAKK 30/85), we measured the m-RNA expression of the genes from the multidrug resistance gene 1 (MDR1), the multidrug resistance associated protein (MRP), glutathione-S-transferase (GST) pi, bcl-2 and topoisomerase (topo) IIalpha. P-glycoprotein (p-gp) was measured by Western blot, and GST activity by functional assays. To analyse progression-free (PFS) and overall survival (OS), parameters were prospectively divided into "low" and "high" groups, according to their median values (exceptions: MDR1 and p-gp). Median follow-up was 60 months. RESULTS: MDR1- and MRP mRNA levels correlated with each other (r=0.54, Spearman), FABM4/M5 and extramedullary disease. "Low" bcl-2-mRNA predicted longer PFS: 22 months vs. 7 months (median,p=0.02, log rank), and longer OS: 64 months vs. 14 months (p=0.06). "Low" topo IIalpha predicted poorer outcome: median PFS 9 vs. 19 months (p=0.03); median survival 12 months vs. "not reached" (p=0.03). An improved outcome tendency, albeit nonsignificant, was seen in p-gp-negative patients. In a Cox model adjusted for age, performance status, presence of Auer rods, FAB type and clinical response, bcl-2 and topo IIalpha mRNA levels retained their predictive values.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

[A new method for evaluating psychomotor development based on information from parents. The Spanish version of the Kent Infant Development Scale].

OBJECTIVE: The purpose of this dissertation research was to design, standardize and validate the Spanish version of the Kent Infant Development Scale (KIDS). PATIENTS AND METHODS: This questionnaire is based on information obtained from the parents. It was translated into Spanish and named "Escala de Desarrollo Infantil de Kent" (EDIK). The EDIK normative data were collected from the parents of 662 healthy infants (ages 1 to 15 months) in pediatric clinics in Catalonia (Spain). RESULTS: Test-retest reliability (r = 0.99; p < 0.001), interjudge reliability (r = 0.98; p < 0.001) and internal consistency (Cronbach alpha = 0.9947) were determined. An "r' of 0.96 was obtained when EDIK scores were compared to their estimated developmental ages obtained from the Denver Developmental Scale. The correlation of the infants' chronological age and their EDIK was 0.96 (p < 0.001). CONCLUSIONS: The high reliability and validity correlation coefficients demonstrate the sound psychometric properties of the EDIK. It appears to be a useful and acceptable instrument in measuring the developmental status of infants by using the reports of their parents.

Adult↗
PubMed1995

Nonradioactive quantification of mdr1 mRNA by polymerase chain reaction amplification coupled with HPLC.

We describe a new strategy for quantifying mRNA by using polymerase chain reaction (PCR) coupled with HPLC. PCR-amplified products are directly analyzed with a specific HPLC column and are quantified by standardization against a housekeeping gene, beta-actin. To evaluate the experimental conditions, we examined the multidrug-resistance-associated mdr1 gene expression in two drug-sensitive cell lines (RPMI-8226 and KB-3-1) and in their drug-resistant sublines. This revealed a significant overexpression of the mdr1 gene in chemoresistant sublines that paralleled the degree of in vitro drug resistance and the amounts of mRNA determined by other methods. Results were consistently reproducible, with imprecision (CV) < 25%. The reverse transcription option PCR/HPLC protocol described here is a sensitive, nonradioactive method for quantifying mdr1 mRNA in cell lines or clinical tumor samples, and can be applied to the simultaneous quantification of several mRNA species.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

What every dentist should know about practice purchase.

Anyone considering the purchase of a dental practice should heed the 'caveat emptor' maxim since there is a serious risk of dental practice bankruptcy in the present economic environment. To minimise this risk, the purchaser must be equipped with the necessary knowledge and information to ensure purchase terms are sound. This article aims to give guidance on how to assess value and associated risks in the purchase of goodwill and equipment, and sets out the main points to consider in evaluating a practice account prior to acquisition.

Financial Management↗