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B Brandt

Publications and source records attributed to B Brandt.

At least 73 records · Page 4Linked to original sources

The erbB oncogenes as prognostic markers in oral squamous cell carcinomas.

BACKGROUND: In clinical practice it became clear that conventional prognostic parameters of oral squamous cell carcinomas (OSCC) are of limited value for the prediction of a disease-free survival. The overexpression of erbB oncogenes is of importance for the clinical course of a variety of solid tumors. After discovering amplifications of erbB oncogenes even in OSCC, it was the aim of the present study to clarify the potential of oncogenes as additional prognostic markers. MATERIALS AND METHODS: The amplification of the erbB oncogenes in tumorous tissue of 85 OSCC patients was determined using the double-differential polymerase chain reaction. Histologically healthy mucosa in these patients was also studied. In univariate analysis the amplification of erbB oncogenes with clinical and histopathological prognostic parameters was compared. RESULTS: No significant correlation between common prognostic parameters and erbB-2 amplification was found. Patients whose OSCC tissue showed an average gene copy number for erbB-2 of greater than 1.2, for erbB-3 below 0.11, and a ratio of erbB-1 and erbB-2 below 0.31 had a statistically significant decrease in disease-free survival. Even in histologically healthy oral mucosa from tumor patients an amplification of erbB oncogenes was found. CONCLUSIONS: ErbB oncogene amplifications in oral squamous cell carcinomas play a significant role as a prognostic factor and seem to be effective in predicting decrease in disease-free survival. Genetic abnormalities in tumor-surrounding tissue support the field cancerization hypothesis.

Carcinoma, Squamous Cell↗

Impact of free prostate-specific antigen on discordant measurement results of assays for total prostate-specific antigen.

OBJECTIVES: To determine why various assays for total PSA (t-PSA) produce discordant results in identical serum samples. METHODS: A total of 84 sera from 40 patients with histologically confirmed benign prostatic hyperplasia and from 44 patients with untreated prostate cancer were analyzed with seven assays for t-PSA and the Hybritech research assay for free prostate-specific antigen (f-PSA). Comparison between assays was performed by linear regression of the t-PSA concentrations as well as between the t-PSA concentrations and the f/t-PSA ratios. RESULTS: The coefficients of correlation for the investigated assays versus Hybritech Tandem-E range from 0.96 to 0.99. Nevertheless average PSA concentrations differed significantly from the Tandem-E assay in all assays. Despite a good correlation, some assays showed a regression line with a slope notably different from 1. In these assays, elevated concentrations were observed in sera with a high proportion of f-PSA. CONCLUSIONS: The study illustrates a significant and clinically relevant discordance between reported t-PSA concentrations for identical samples, depending on the assay used and on the contents of f-PSA in the sample. The interpretation of t-PSA concentrations requires awareness of the applied assay as well as the establishment of an assay-specific reference range in order to avoid inappropriate clinical consequences, such as unnecessary biopsies. Respective details must be contained in the laboratory reports. A change of assays without specifically reassessing previously valid reference ranges or the uncritical use of a customarily applied limit of < 4 ng/mL will otherwise be harmful to the patient.

Blood Chemical Analysis↗

Protamine and acute depletion of magnesium limit bone response to parathyroid hormone.

The effect of protamine on calcium homeostasis was studied in nine pediatric patients undergoing cardiopulmonary bypass. Total serum calcium decreased from 8.44 mg/dL to 7.49 mg/dL (P < 0.05) after protamine. Ionized calcium decreased from 1.39 to 1.31 mmol/L (P < 0.05). A bioassay determined the etiology of this response. Bone disks were placed in sera, protamine, parathyroid hormone, parathyroid hormone antibody, or magnesium-depleted solutions, then were incubated in solutions with known calcium content. The change in the media's calcium concentration reflects the bone's response to the initial stimulus. Calcium change is expressed as Experimental delta/Control delta (E/C). Normal bone responds to parathyroid hormone, E/C = 0.59 (P < 0.001). Protamine-treated bone loses this response, E/C = 0.9 (P = not significant [NS]). A parathyroid-hormone-induced osteoblast messenger was found. Protamine-treated bone continued to respond to this messenger, E/C = 0.42 (P < 0.001). Bone showed reversible loss of response to parathyroid hormone after incubation in magnesium-free solution, E/C = 0.93 (P = NS). With reincubation in magnesium, E/C = 0.69 (P < 0.01). Since protamine blocks parathyroid receptors, and magnesium depletion limits the bone's response to parathyroid hormone, this may explain the persistent hypocalcemia seen in some patients undergoing cardiopulmonary bypass.

Adult↗

Electroconvulsive therapy and the elderly client.

Although ECT has been the subject of controversy for decades, ECT has brought increased chances for recovery to many people suffering from severe depression. Crossfield (1988) states the evidence is overwhelming that treatment of some depressive clients with ECT is the best treatment available. Other researchers have found that ECT is equal to, and sometimes superior to, other therapies for major depressive disorders (Gomez & Gomez, 1993). Depression is a treatable condition about which nurses have a responsibility to educate clients and their families (Valente, 1991). If clients and their supportive families and friends are to understand rather than undermine treatment, education about ECT is essential (Valente, 1991). Well-meaning friends and family who are misinformed could strongly discourage ECT, so it is important that their myths about ECT be dispelled (Valente, 1991). Furthermore, if depression in an already at-risk elderly population is not recognized and treated, great suffering will continue to be endured and life-threatening situations may occur. Depression often is manifested differently in older persons than in younger ones. Nurses can improve the quality of care provided to these depressed elderly clients by allowing them to express their fears and anger (Gomez & Gomez, 1993). Furthermore, the nurse's attitude should be hopeful, positive and consistent with them. This action can help clients develop trust with the nurse and further their own quality care. Estimates are that 70% to 90% of individuals who suffer from severe depression and receive ECT do indeed recover (Valente, 1991). ECT should be undertaken only after the outlined treatment protocols have been considered and with the knowledge and understanding of the following statements issued by the United States Department of Health and Human Services in the 1993 Agency for Health Care Policy and Research (AHCPR). First, ECT has not been adequately tested in milder forms of depression. Because of this gap in the research, the efficacy of ECT across the spectrum of depressive symptomatology is unknown. Second, ECT is costly when it entails hospitalization. This factor has great meaning in the changing, increasingly cost-conscious, health care arena. Third, ECT has specific and significant side effects, e.g., short-term retrograde and anterograde amnesia. Not only are these side effects troublesome for inpatient recipients of ECT, but the side effects can be quite dangerous for persons receiving treatment on an outpatient basis. The potential for injury is grave for persons who have memory deficit. Given the present cost-conscious, cost-cutting atmosphere, an anticipated rise in the number of clients receiving ECT on an outpatient basis is a distinct possibility. Fourth, the risks of general anesthesia are present. Age is a well known risk factor for general anesthesia. Fifth, treatment with ECT still carries substantial social stigma for clients. In spite of the increasing acceptance of ECT as a treatment for depression in the elderly, many clients prefer to keep their receipt of treatment secret fearing social repercussions of open discussions with family and friends. Sixth, ECT can be contraindicated when certain other medical conditions are present. Persons suffering from severe cardiac or pulmonary disease are frequently disqualified for treatment due to the risk of receiving anesthesia. Last, people usually require a prophylactic treatment with antidepressant medication, even if a complete, acute phase response to ECT is attained (pp. 26-27).

Aged↗

The spectrum of RB1 germ-line mutations in hereditary retinoblastoma.

We have searched for germ-line RB1 mutations in 119 patients with hereditary retinoblastoma. Previous investigations by Southern blot hybridization and PCR fragment-length analysis had revealed mutations in 48 patients. Here we report on the analysis of the remaining 71 patients. By applying heteroduplex analysis, nonisotopic SSCP, and direct sequencing, we detected germ-line mutations resulting in premature termination codons or disruption of splice signals in 51 (72%) of the 71 patients. Four patients also showed rare sequence variants. No region of the RB1 gene was preferentially involved in single base substitutions. Recurrent transitions were observed at most of the 14 codons within the RB1. No mutation was observed in exons 25-27, although this region contains two CGA codons. This suggests that mutations within the 3'-terminal region of the RB1 gene may not be oncogenic. When these data were combined with the results of our previous investigations, mutations were identified in a total of 99 (83%) of 119 patients. The spectrum comprises 15% large deletions, 26% small length alterations, and 42 % base substitutions. No correlation between the location of frameshift or nonsense mutations and phenotypic features, including age at diagnosis, the number of tumor foci, and manifestation of nonocular tumors was observed.

Adolescent↗

Comparison of central venous catheter dressings in bone marrow transplant recipients.

PURPOSE/OBJECTIVES: To determine the effect of two central venous catheter (CVC) dressing protocols on catheter-related infections in hospitalized patients with long-term tunneled catheters undergoing an autologous bone marrow transplant (BMT), to determine the prevalence of long-term CVC-related infections in this population, and to identify other factors in the study sample related to long-term CVC infection. DESIGN: Experimental. SETTING: BMT unit of a regional oncology center in a tertiary care hospital. SAMPLE: The sample consisted of 101 adult patients with cancer with long-term, tunneled CVCs inserted in the operating room on admission for autologous BMT. METHODS: Patients randomly were assigned to one of two dressing-change procedure groups. The control group received the current standard of care for patients receiving BMT--a dry, sterile gauze dressing (DSGD) changed every 24 hours. The experimental group received Opsite 3000TM (Smith + Nephew Ltd., Massilon, OH) transparent moisture vapor permeable dressings (MVPD) changed weekly. MAIN RESEARCH VARIABLES: CVC infection rates, frequency of IV tubing changes, immune status, duration of catheter use, occurrence and outcome of catheter occlusion, and use of a catheter for total parenteral nutrition. FINDINGS: Researchers determined the difference in CVC-related infections between the two groups and the impact of select variables on CVC-related infection. When all categories of CVC-related infection (i.e., suspected, sepsis, tunnel) were considered, no statistical difference was found in the likelihood of the groups remaining infection-free (p = 0.76) over time. CVC sepsis occurred in one patient in the DSGD group and five patients in the MVPD group; however, this difference was not statistically significant over time (p = 0.067). CONCLUSIONS: Development of CVC sepsis or tunnel infection in close proximity to the time of CVC surgical placement suggests that factors other than the assigned dressing were associated with the occurrence of CVC-related infection in three cases. Although the MVPD group required dressing changes more frequently than every seven days (as specified by the protocol) because of exit-site drainage and nonocclusiveness, transparent dressings were more cost-effective than daily gauze dressings in this population. IMPLICATIONS FOR NURSING PRACTICE: For adults undergoing autologous BMT, either DSGD or transparent CVC dressing can be used safely based on patient preference and skin tolerance to the dressing material.

Adult↗

Discordance of assay methods creates pitfalls for the interpretation of prostate-specific antigen values.

The availability of numerous different assays for the determination of prostate-specific antigen (PSA) has created substantial problems in the interpretation of PSA concentrations. Currently over 60 assays are commercially offered on the European market. The majority of the recently marketed assays are based on the commonly used reference range (< 4 ng/ml), although this rarely has been verified. Some manufacturers avoid specifying the range altogether, while others derive the data from very small collectives. Reference ranges established with sera of young males or even with an unspecified proportion of sera of females are not suitable for assessing the specificity of PSA assays for detecting prostate cancer among males older than age 50 years. Most manufacturers recommend that their assays not be used for diagnostic purposes but only for following up patients previously diagnosed with prostate cancer. Usually the physician remains unaware of this warning as well as of the name of the assay used. Since PSA concentrations may vary in identical samples by a factor of two depending on the assay used, the clinician in charge of interpreting the results needs to be aware of the method used and must have detailed information on the assay-specific reference range.

Humans↗

Results and prognostic factors of splenectomy in idiopathic thrombocytopenic purpura.

BACKGROUND: Splenectomy is the therapy of choice after relapse following different immunosuppressive treatments for idiopathic thrombocytopenic purpura, which is still the most frequent cause of thrombocytopenia. STUDY DESIGN: A prospective clinical study was undertaken to evaluate the rate of complete remission in idiopathic thrombocytopenic purpura after splenectomy, to reveal the influence of preoperative immunosuppression on the postoperative course in groups of patients with different responses to treatment, and to describe possible prognostic factors predicting the postoperative course of idiopathic thrombocytopenic purpura. Difino's classification of remission was used. After fulfilling criteria for admission into the study, 72 patients who had undergone splenectomy (male to female ratio, 1:1.4) were examined. RESULTS: Early postoperative mortality and morbidity rates were 3 percent each. The following degrees of remission were achieved: complete remission, 72 percent; partial remission, 15 percent; partial remission affording further medical support, 6 percent; and no remission, 4 percent. Platelet counts differed significantly between complete and partial remission, but not between patients who did or did not experience a response to different preoperative medical strategies (Tukey-Kramer test, p < .05; t test, not significant). The correlation of megakaryocytopoiesis and the site of thrombocytolysis to the stages of remission was significant (Fisher's exact test). Patients with hyperplasia of splenic follicles had significantly higher platelet counts 2 years after operation than did those without hyperplastic splenic follicles (Student-Newman-Keuls test). CONCLUSIONS: Splenectomy is a low morbidity and low mortality procedure. It is, therefore, a treatment of choice after relapse following immunosuppressive courses. Isolated splenic thrombocytolysis and hyperplasia of megakaryocytopoiesis and of splenic follicles correlated with better postoperative outcome (ie, stable remission and platelet counts) and could serve as possible prognostic factors for the postoperative course in idiopathic thrombocytopenic purpura.

Adolescent↗

An immunological enrichment method for epithelial cells from peripheral blood.

The ability of primary tumours to metastasize accounts for the majority of cancer deaths. The emergence of circulating carcinoma cells in the peripheral blood is supposed to be an indicator for cancer cell spread. We have focused on this phenomenon in order to develop a sensitive technique for enriching epithelial derived cells on the basis of a two-layer density gradient and subsequent immune magnetic cell sorting. Epithelial cells are possess a cytoskeleton containing an assembly of intermediate filaments. During carcinogenesis these filaments do not undergo modifications of antibody binding epitopes such as occur in the protein domains of surface markers. We have developed a two-layer density gradient in which the epithelial cells form a single density band. This was demonstrated by recovery experiments using [3H]thymidine-labelled epithelial cells which showed epithelial cells were enriched within this first step by a factor of 20. In a second step the MACS system was applied. Cells were stained with a performed FITC-conjugated mouse anti-human cytokeratin antibody bound to a rat anti-mouse antibody coupled to superparamagnetic particles (immune paramagnetic separation complex; IPSC) and subjected to high gradient magnetic fields. The two-step procedure was confirmed by dispersing 50 epithelial cells in 5 x 10(5), 5 x 10(6), 5 x 10(7), 5 x 10(8), 5 x 10(9) peripheral blood leucocytes. Specific binding of the preformed IPSC was demonstrated by flow cytometry, confocal laser, fluorescent and electron microscopy. The specificity of the method was further proved by dual staining with IPSC and anti-human PSA antibody of epithelial prostatic cells separated from peripheral blood in vitro. By means of this double-step separation method it was possible to isolate up to 15-20 cells out of 50 epithelial cells originally suspended into 5 x 10(7) to 5 x 10(9) human peripheral blood leucocytes. This represented an enrichment factor between 20,000 and 200,000, depending on the initial cell number. The immunologically captured epithelial cells can be used for further cytogenetic investigations such as in situ hybridization (ISH) and/or polymerase chain reaction (PCR) to detect cancer cell specific gene aberrations. This sensitive combined buoyant density immune magnetic cell separation technique is capable of detecting free carcinoma cells in the peripheral blood.

Animals↗

Double-differential PCR for gene dosage estimation of erbB oncogenes in benign and cancer tissues and comparison to cellular DNA content.

Competitive and differential quantitative PCR methods circumvent the limiting factors of PCR which cause poor reproducibility. We describe the development and performance evaluation of another quantitative PCR method, double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. The ratio of band intensities of the PCR products in silver-stained polyacrylamide gels expresses the average gene copy number (AGCN) per cell of the erbB oncogenes. The coefficient of variability (CV) was less than 25% for an AGCN of 1. The PCR data were in correlation to the results from dot blotting. DNA image analysis did not reveal any correlation between DNA content and gene dosage deviation of the erbB oncogenes. The method was applied to normal breast tissue, benign breast diseases, breast cancer tissue and lymph node metastases. We suggest this method as being reproducible, low cost and rapid, and therefore suitable for clinical studies on erbB oncogene dosage estimation.

Base Sequence↗

Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: double-differential polymerase chain reaction (ddPCR) for clinical diagnosis.

We have determined the average gene copy numbers (AGCN) of the erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the erbB-2 and the erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene HBB, the erbB-1, erbB-2 and erbB-3 oncogenes and the second single-copy reference gene SOD2 under equal reaction conditions. In a retrospective study the AGCN of the erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for erbB-2 of greater than 2.0 and for erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of erbB-1 and erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of erbB oncogenes may not be of prognostic value in untreated lung cancer patients.

Base Sequence↗

Efficacy, safety, and immunogenicity of a meningococcal group B (15:P1.3) outer membrane protein vaccine in Iquique, Chile. Chilean National Committee for Meningococcal Disease.

A meningococcal group B (15:P1.3) outer membrane protein vaccine was tested for efficacy in a randomized, double-blind controlled study in Iquique, Chile. A total of 40 811 volunteers, ages 1-21 years, enrolled in the study. Volunteers received two doses of vaccine six weeks apart by jet injector. Both the experimental vaccine and the control vaccine (Menomune, A, C, Y and W135 meningococcal polysaccharide vaccine) were well tolerated with minor side-effects. Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique. Eighteen cases of group B meningococcal disease were confirmed during the 20 months. Efficacy was estimated to be 51% (p = 0.11) for all ages combined. In children aged 1-4 no protection was evident, but in volunteers aged 5-21 vaccine efficacy was 70% (p = 0.045). The IgG antibody response by ELISA was characterized by a large booster effect after the second dose, followed by a substantial drop in antibody levels by 6 months. The youngest children had the highest responses. The bactericidal antibody response, on the other hand, was characterized by the lack of a significant booster response, higher responses in the older children, and an increase in the geometric mean titer in the later months of the study in the older children.

Adolescent↗

Identification of RB1 germline mutations in Argentinian families with sporadic bilateral retinoblastoma.

Hereditary predisposition to retinoblastoma is caused by germline mutations in the RB1 gene. Most of these mutations occur de novo and differ from one patient to another. DNA samples from 10 families with a child presenting sporadic bilateral retinoblastoma have been analysed for the causative mutation. Using intragenic DNA polymorphisms we detected large deletions in two patients. Heteroduplex and DNA sequence analysis of PCR products from each exon and the promoter region showed small mutations in four patients: a C to T transition in exon 18; 1 bp and 2 bp deletion in exons 20 and 19 respectively; and a 4 bp insertion in exon 7. All these mutations are likely to result in premature termination of transcription. In one of these families, an unaffected carrier was detected. This emphasises the importance of detection of the causative mutation for predictive diagnosis in families with sporadic bilateral retinoblastoma.

Argentina↗

Immunophenotyping of lymphocytes in bronchoalveolar lavage fluid. A new flow cytometric method vs standard immunoperoxidase technique.

Characterizing lymphocyte subsets in bronchoalveolar lavage fluid (BALF) by flow cytometry (FC) proper gating of the lymphocyte subpopulation being analyzed is crucial. In order to test lymphocyte gate quality for the first time we used a DNA-dye to evaluate plasmamembrane integrity and thus to mark off fluorescent but not DNA-containing particles (eg, debris). A comparative prospective study between this newly developed FC technique and a standard peroxidase anti-peroxidase (PAP) method was performed. Samples of BALF from 50 patients with various pulmonary diseases were examined. After determination of the total cell yield, a differential cell count was performed. Subsequently, the immunophenotype of pan T lymphocyte CD3-, T-helper lymphocyte CD4-, and T-suppressor lymphocyte CD8-positive lymphocyte subsets was assessed with FC as well as with the PAP method. Both methods showed excellent correlation (CD3: r = 0.81; CD4: r = 0.97; CD8: r = 0.96; p < 0.05, respectively). Comparing the mean +/- SEM, FC tends to overestimate CD3+ cells (90.6 +/- 1.0% vs 85.8 +/- 1.3%). For CD4 (45.0 +/- 3.4% vs 44.4 +/- 3.4%) and CD8 (48.1 +/- 3.5% vs 46.7 +/- 3.5%), there was good agreement. In a clinical setting, the reliability of both methods was equivalent, and FC using a DNA-dye to test lymphocyte gate quality offered a rapid and reliable determination of lymphocyte subsets in BAL.

Bronchoalveolar Lavage Fluid↗

Molecular analysis and predictive testing in retinoblastoma.

Predictive testing using molecular analysis is an integral part of contemporary retinoblastoma management. We have made extensive use of segregation analysis for risk assessment in both familial and sporadic disease. Investigation of loss of heterozygosity in tumor samples proved to be invaluable for the identification of linkage phase. In many families, however, accurate carrier risk assessment depends on direct identification of the causative R B I mutation. Consequently, we have developed methods for rapid mutation screening. Using these techniques, mutation analysis can now be offered to an increasing number of individuals.

DNA Mutational Analysis↗

[Different determination methods make interpretation of prostate-specific antigen more difficult].

The availability of numerous different assays for the determination of prostate-specific antigen (PSA) hs created substantial problems in the interpretation of PSA concentrations. Presently more than 40 assays are commercially promoted within the German market. The majority of the recently released assays claim the commonly used reference range (< 4 ng/ml) although this has no always been verified. Some companies entirely avoid the specification of reference ranges, others derive the data from very small cohorts. Reference ranges established with sera of young males or even with an unknown proportion of female sera are not valid in assessing the specificity of PSA assays to detect prostate cancer among male individuals between 50 and 80 years of age. Some companies recommend not to apply their assay for diagnostic purposes limit its use to the follow-up of patients previously diagnosed but to as having prostate cancer. This warning usually remains just as unknown to the urologist as the name of the assay used. Since PSA concentrations may vary in identical samples by a factor of 2, depending on the assay used, the clinician interpreting the results needs to be aware of the method applied and must have detailed information about the assay-specific reference range. Without this information, PSA loses its valuable diagnostic and prognostic features. Apart from avoidable worries on the patient's part, evidence of prostate cancer may be missed or unnecessary biopsies may be performed.

Aged↗

[Biochemical prognostic factors of ovarian carcinoma].

In therapy decision and monitoring of ovarian cancer clinicians use clinical and histomorphological criteria. Thus, intensive research in tumor biology of ovarian cancer leads to the development of biochemical parameters and a deeper understanding of proliferation and metastasis in-vitro testing of anticancer drugs is one way to achieve a dynamic model to tumor growth. The expression of the erb B oncogene family, especially erb-B-2, is an important finding for the estimation of the potential of an ovary tumor to grow at metastatic sites. The erb B oncogenes encode membrane-growth-factor-receptors functioning in signal transduction for cell growth stimulation. In several studies disease-free survival of advanced ovarian carcinoma was significantly related to the extent of erb-B-2 amplification and/or over-expression. High erb-B-2 expression in the tumor at time of primary treatment indicated a positive second-look-laparotomy. New experimental approaches for alternative therapies use erb-B-2 as the target for interference of tumor cell proliferation.

Biomarkers, Tumor↗