Biomedical subjects

C Busch

Publications and source records attributed to C Busch.

At least 37 records · Page 2Linked to original sources

PubMed2000

Intraepithelial lesions of urinary bladder: morphologic considerations.

Urological pathologists representing the World Health Organization and the International Society of Urological Pathology have reached a new consensus on the definitions of flat, non-invasive lesions of the urothelium. Lesions are classified as: (1) carcinoma in situ (CIS); (2) dysplasia; (3) atypia of unknown significance; and (4) reactive atypia. These terms are intended to describe a histological spectrum of architectural and cytological abnormalities ranging from the unequivocally malignant (CIS) through the probably neoplastic (dysplasia) to the benign (atypia). The biological potential of these lesions in individual patients cannot be accurately predicted, although the degree of risk for an adverse outcome is very likely to be proportional to the degree of architectural and cytological anaplasia. It is likely that each phenotype has two biological potentials: dynamic and effete. It should be emphasized that most of our knowledge concerning these lesions in humans has been obtained from studies of groups of patients who have already developed a papillary or nodular, invasive or non-invasive urothelial carcinoma, as descriptions of primary CIS, dysplasia, and atypia are uncommon. Future knowledge in this area might be enhanced by attention to the following: better definitions of terms and more accurate application of words such as bladder cancer, early lesion, tumor progression, precursor, and premalignant; increased understanding of the biological processes underlying phenotypic changes; development of models (probably computer-based) with the capacity to factor in the complexities of human carcinogenesis in an ongoing fashion, as new information becomes available.

Biopsy↗

PubMed1999

Distribution of prostasomes in neoplastic epithelial prostate cells.

BACKGROUND: Prostasomes are a secretory product from the prostate. We aimed to investigate whether the distribution and amount of prostasomes in normal prostate epithelium were influenced by the dedifferentiation occurring in adenocarcinomas of the human prostate gland. METHODS: Transurethrally resected material from 11 patients with prostatic carcinoma of various malignancy grades, material from two lymph node metastases, and benign tissue from 10 total prostatectomies were subjected to immunohistochemical staining, using a mouse monoclonal antibody against human prostasomes (mAb78). RESULTS: Immunostaining of low-grade carcinoma was similar to that of normal prostate gland which displayed a cytoplasmic granular staining of the apical (luminal) aspects of the secretory epithelial cells. In moderately well and poorly differentiated adenocarcinoma, the amount of stained components decreased, and the staining pattern became more heterogeneous. In multilayered glandular structures, the staining was concentrated at the lumen, leaving most other cells negative. The neoplastic cells of lymph node metastases of prostate carcinoma differed in amount and distribution of immunostained prostasomes. CONCLUSIONS: The antigen recognized in the prostasomes by mAb78 was expressed in benign prostate tissue, prostate cancer, and to a lesser degree in lymph node metastases. There was a tendency towards decreased expression with increasing tumor grade.

Adenocarcinoma↗

PubMed1999

Correlation of thymic pathology with HLA in myasthenia gravis.

The aim of this study was to investigate associations between thymic pathology and HLA in myasthenia gravis. HLA typing was performed in 95 of 125 Caucasian patients who underwent transsternal thymectomy for myasthenia gravis between 1976 and 1995. Multiple comparison procedures applied within each HLA locus demonstrated significant correlations between the ancestral suprahaplotype A1 B8 DRB1*0301 DRB3*0101 DQA1*0501 and thymic hyperplasia and between HLA-A24 and thymoma. A weaker association was found between A3 and thymic atrophy and thymolipoma. On logistic discriminant analysis, HLA-B8 (P = 0.001) and HLA-A3 (P = 0.028) were identified as the only significant classifiers to jointly provide a good discriminator between the thymic pathologies. When the suitability of HLA for detection of thymoma was examined in a second logistic regression analysis, both HLA-A24 (OR 9.7; 95% CI [1.6, 73.7]) and HLA-B8 (OR 0.1; 95% CI [0.0, 0.5]) were significant predictive factors. The above correlations between thymic pathology and HLA-A3, HLA-A24, and HLA-B8 (but not MHC class II alleles) suggest an involvement of MHC class I restricted T cells in myasthenic autoimmunity that may partially be reflected by thymic pathology.

Adult↗

PubMed1999

Activity of standard and investigational cytotoxic drugs in primary cultures of tumor cells from patients with kidney and urinary bladder carcinomas.

PURPOSE: In vitro tumor models could support the process of development of new cytotoxic drugs and selection of suitable drugs for the individual patient. We investigated whether the testing of tumor cells from patients with kidney or urinary bladder carcinoma by fluorometric microculture cytotoxicity assay (FMCA) could provide clinically relevant data for these tumor types. MATERIALS AND METHODS: A total of 45 tumor samples from patients with kidney or urinary bladder carcinoma were compared with 247 samples of other tumor types with respect to sensitivity to 8 standard and 6 investigational cytotoxic drugs in the FMCA, a 72 hour assay based on the concept of total cell kill. In bladder carcinomas, sensitivity to standard drugs was correlated to various tumor characteristics. RESULTS: The technical success rate for kidney and bladder carcinomas was high; approximately 90% of the samples could be analyzed successfully. Kidney carcinomas were highly resistant to standard drugs and bladder carcinomas essentially as sensitive as carcinomas of the breast and ovary but with a steeper dose-response relationship. In bladder carcinoma there was no clear relationship between tumor stage, grade, ploidy, mitoses or p53 expression and drug sensitivity. Except for suramin, kidney carcinomas were poorly sensitive to the investigational drugs CdA, gemcitabine, paclitaxel, vinorelbine and topotecan. In bladder carcinomas paclitaxel, gemcitabine and suramin showed promising activity. CONCLUSIONS: The FMCA seems suitable for cytotoxic drug sensitivity testing of urinary tract carcinomas. This technique may have a role in new drug development in these tumor types.

Antineoplastic Agents↗

PubMed1999

Three-dimensional computer reconstruction of prostate cancer from radical prostatectomy specimens: evaluation of the model by core biopsy simulation.

OBJECTIVES: A technique was developed for three-dimensional (3D) modeling of prostate cancer and transrectal biopsies. To test the model, the cancer yield of a simulated 10-biopsy protocol was compared with a simulated sextant protocol and with preoperative biopsies regarding cancer detection and correlation with tumor volume. METHODS: Transrectal ultrasound-guided core biopsies were taken from 81 men according to a standardized 10-biopsy protocol that included sextant biopsies. The patients underwent radical prostatectomy and specimens were step-sectioned and whole-mounted. Cancer and the prostate capsule were outlined on the slides and the regions transferred to a computer software program developed by our group. A 3D volume of each prostate was reconstructed from the sections. Virtual core biopsy needles imitating the positions of the real biopsies were inserted into the prostate and the cancer yield was calculated. Only the standardized positions were considered in this study (ie, additional biopsies from hypoechoic foci were not accounted for). RESULTS: Of the cancers detected with 10 standardized virtual biopsies, 24% would have remained undetected with sextant biopsies. The cancer yield of 10 virtual biopsies correlated with the preoperative biopsies (r = 0.64) and with the tumor volume (r = 0.56). A multiple regression analysis showed that the cancer yield of a simulation of 10 biopsies correlated better with tumor volume than did a simulation of sextant biopsies (P = 0.02). CONCLUSIONS: We conclude that computer-assisted 3D reconstruction of prostate cancer can be used as a model for evaluation and optimization of biopsy protocols.

Adult↗

PubMed1999

Biopsy protocol stability in a three-dimensional model of prostate cancer: changes in cancer yield after adjustment of biopsy positions.

OBJECTIVES: Transrectal ultrasound-guided prostate biopsies are often taken according to a systematic, standardized schedule. The diagnostic stability of this system was evaluated by moving the biopsies in a three-dimensional (3D) model. METHODS: A computerized 3D reconstruction was made from each of 75 radical prostatectomy specimens. Simulated core biopsies imitated a standardized 10-biopsy protocol, including sextant biopsies. In total, 30,000 biopsies were generated by moving the standardized biopsies 1, 2, 3, and 4 mm (parallel needle shifts) or 5 degrees, 10 degrees, 15 degrees, and 20 degrees(rotation of the needle tip) in a random direction. RESULTS: The diagnosis of the individual biopsy changed from cancer to benign or vice versa in 4.9% to 1 5.7% after 1 to 4-mm parallel needle shifts and 2.0% to 7.5% after 5 degrees to 20 degrees rotations. The corresponding figures for the final diagnosis of the 10-biopsy set were 0.8% to 9.6% and 0.5% to 3.2%. Transition zone biopsies containing cancer changed to benign more often than the other biopsies (P <0.001). Parallel needle shifts of 2 mm changed the diagnosis more often than the 15 degrees rotation (9.4% and 5.9%, respectively, P <0.001), although conveying the same overall needle shift. CONCLUSIONS: The cancer yield of prostate biopsies is influenced even by small changes in needle positions. The transition zone biopsies are most likely to change from cancer to benign when moved. Changing the insertion point of the needle has a higher impact on cancer yield than rotating the tip.

Adult↗

PubMed1999

Modeling prostate cancer distributions.

OBJECTIVES: To use computer-assisted three-dimensional (3D) reconstruction to study cancer distribution in the prostate. The distributions have been determined using data from 81 prostates surgically removed because of cancer. METHODS: The pattern of distribution was determined by reshaping (morphing) all prostates in the same size category (small, medium, large) into the same shape and by overlayering the 3D distribution of all cancers into a "unit prostate." Also, the pattern of 3D distribution was defined for small, medium, and large volume cancers. RESULTS: The study yielded a clear, visual "scatter diagram" representation of the statistics of prostate cancer distribution. It confirmed previous general knowledge: small cancers are mainly found in the lower one third and principally in the dorsolateral part of the gland. CONCLUSIONS: This report is part of the investigations preliminary to establishing an optimal protocol for needle biopsy of prostate cancer.

Adult↗

PubMed1999

Automatic quantification of microvessel density in urinary bladder carcinoma.

Seventy-three TUR-T biopsies from bladder carcinoma were evaluated regarding microvessel density, defined as microvessel number (nMVD) and cross-section endothelial cell area (aMVD). A semi-automatic and a newly developed, automatic image analysis technique were applied in immunostainings, performed according to an optimized staining protocol. In 12 cases a comparison of biopsy material and the corresponding cystectomy specimen were tested, showing a good correlation in 11 of 12 cases (92%). The techniques proved reproducible for both nMVD and aMVD quantifications related to total tumour area. However, the automatic method was dependent on high immunostaining quality. Simultaneous, semi-automatic quantification of microvessels, stroma and epithelial fraction resulted in a decreased reproducibility. Quantification in ten images, selected in a descending order of MVD by subjective visual judgement, showed a poor observer capacity to estimate and rank MVD. Based on our results we propose quantification of MVD related to one tissue compartment. When staining quality is of high standard, automatic quantification is applicable, which facilitates quantification of multiple areas and thus, should minimize selection variability.

Humans↗

PubMed1999

DNA fingerprinting reveals polygyny in the subterranean rodent Ctenomys talarum.

DNA fingerprinting was used to characterize patterns of paternity in two populations of Ctenomys talarum from Buenos Aires Province, Argentina. The multilocus probe PV47-2 was used to detect variation in genomic DNA extracted from 12 females, their 32 offspring, and 14 putative sires. For 11 out of 12 litters examined, a single male capable of providing all nonmaternal bands was identified. Within each study population, individual males sired more than one litter, suggesting that C. talarum is polygynous. No evidence of multiple paternity of litters was found. High band-sharing values among females suggest that further research is needed to assess the population genetic structure of this species.

Animals↗

PubMed1999

Respiratory chain inhibition induces tolerance to focal cerebral ischemia.

The authors show that the inhibitor of the succinate dehydrogenase, 3-nitroproprionic acid (3-NPA), which in high doses and with chronic administration is a neurotoxin, can induce profound tolerance to focal cerebral ischemia in the rat when administered in a single dose (20 mg/kg) 3 days before ischemia. Infarcts were approximately 70% and 35% smaller in the 3-NPA preconditioned groups of permanent and transient focal cerebral ischemia, respectively. This regimen of 3-NPA preconditioning neither induced necrosis, apoptosis, or any other histologically detectable damage to the brain, nor did it affect behavior of the animals. 3-NPA led to an immediate (1-hour) and long-lasting (3-day) decrease in succinate dehydrogenase activity (30% reduction) throughout the brain, whereas only a short metabolic impairment occurred (ATP decrease of 35% within 30 minutes, recovery within 2 hours). The authors found that 3-NPA induces a burst of reactive oxygen species and the free radical scavenger dimethylthiourea, when administered shortly before the 3-NPA stimulus, completely blocked preconditioning. Inhibition of protein synthesis with cycloheximide given at the time of 3-NPA administration completely inhibited preconditioning. The authors were unsuccessful in showing upregulation of mRNA for the manganese superoxide dismutase, and did not detect increased activities of the copper-zinc and manganese superoxide dismutases, prototypical oxygen free radicals scavenging enzymes, after 3-NPA preconditioning. The authors conclude that it is possible to pharmacologically precondition the brain against focal cerebral ischemia, a strategy that may in principal have clinical relevance. The data show the relevance of protein synthesis for tolerance, and suggests that oxygen free radicals may be critical signals in preconditioning.

Animals↗

PubMed1999

Recurrence and progression in low grade papillary urothelial tumors.

PURPOSE: We report long-term followup data on patients with World Health Organization (WHO) grade I bladder tumors, and determine whether histopathological subgrouping as papillary neoplasm of low malignant potential and low grade papillary carcinoma is of clinical value. MATERIALS AND METHODS: All 680 patients in western Sweden with first diagnosis of bladder carcinoma in 1987 to 1988 were registered and followed for at least 5 years. Of the tumors 255 (37.5%) were stage Ta, WHO grade I. Tumors were further classified as papillary neoplasm of low malignant potential in 95 patients and low grade papillary carcinoma in 160 according to WHO and the International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the bladder. RESULTS: Mean age of patients at first diagnosis of low grade papillary carcinoma was 69.2 years, which was 4.6 years higher than those with papillary neoplasm of low malignant potential (p<0.005). During a mean observation time of 60 months our 255 patients underwent 577 operations for recurrences and had 1,858 negative cystoscopies. The risk of recurrence was significantly lower in patients with papillary neoplasm of low malignant potential compared to those with low grade papillary carcinoma (35 versus 71%, p<0.001). The risk of recurrence was higher in patients with multiple tumors at first diagnosis as well as those with recurrence at the first followup after 3 to 4 months. Stage progressed in 6 patients (2.4%), all with low grade papillary carcinoma at diagnosis. CONCLUSIONS: More than 90% of patients with stage Ta, WHO grade I have a benign form of bladder neoplasm, and few have truly malignant tumors. Future research should focus on reducing the number of recurrences and followup cystoscopies, and finding methods to identify malignant tumors so that pertinent treatment can be instituted. Subgrouping of WHO grade I bladder tumors as papillary neoplasm of low malignant potential and low grade papillary carcinoma seems to add valuable prognostic information.

Carcinoma, Papillary↗

PubMed1999

How important is the route of reconstruction after esophagectomy: a prospective randomized study.

OBJECTIVE: A prospective randomized trial was performed to compare retrosternal and posterior mediastinal gastric tube reconstruction with regard to postoperative function and quality of life. METHODS: Twenty-six patients were randomly allocated to either retrosternal (n = 14) or posterior mediastinal (n = 12) reconstruction after gastric tube formation. Radionuclide transit studies were applied to obtain objective functional data and a standardized quality-of-life assessment was performed. RESULTS: Retrosternal reconstruction showed an increased morbidity (15 vs 13 major complications) and mortality (14.2 vs 8.3%). Radionuclide clearance in the supine position was delayed in the gastric tube in general, compared with normal controls (retention index > 40% vs < 10%). There was a significantly higher retention (p < 0.005) in the retrosternal group in the middle third of the tube and the whole tube after intake of the liquid tracer. The retention of the first solid tracer was also higher in the retrosternal group in the middle third of the tube (p = n.s.) and was significantly higher in the whole tube after 30 (p < 0.05) and 60 (p < 0.01) s. This had no significant impact on the patients' quality of life. CONCLUSIONS: The posterior mediastinal route of reconstruction is recommended but curative resection (R0) is mandatory to avoid possible complications due to local tumor relapse. After incomplete resection (R1 or R2) we recommend retrosternal reconstruction for better palliation.

Adenocarcinoma↗

PubMed1999

5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. Swedish-Norwegian Bladder Cancer Study Group.

PURPOSE: We report the 5-year followup of a randomized comparison of mitomycin C and bacillus Calmette-Guerin (BCG) in patients with superficial bladder carcinoma. Recurrence, progression and survival rates, crossover results, prognostic factors and long-term side effects were analyzed. MATERIALS AND METHODS: A total of 261 patients were enrolled in the study, and the inclusion criteria were primary Tis, dysplasia G2, T1 G3 and multiple recurrent Ta/T1 G1-2 disease. Intravesical instillations of 40 mg. mitomycin C and 120 mg. Pasteur BCG, Danish strain 1331, were given for 2 years. RESULTS: After a median followup of 64 months 101 of the 250 evaluable patients (42%) were disease-free. A significant difference was noted in disease-free survival with BCG (p = 0.04), which was most pronounced for stage Tis disease. No difference in tumor progression, or crude or corrected survival was found between the 2 arms. Crossover treatment was successful in 39% of patients with second line BCG and 19% with second line mitomycin C. Independent risk factors for progression were initial p53 status and stage. Only the completion of treatment was predictive of outcome for patients treated with BCG. Bladder shrinkage occurred in 2.4% of patients. CONCLUSIONS: Therapy with BCG was superior to mitomycin C for recurrence prophylaxis but no difference was found for progression and survival.

Adjuvants, Immunologic↗

PubMed1998

The impact of HLA on long-term outcome after thymectomy for myasthenia gravis.

In a retrospective series of 86 patients with myasthenia gravis, the only factors predictive of improvement in muscular strength after transsternal thymectomy were preoperative severity of myasthenia (90% versus 54%, p = 0.0014) and HLA-B8 (79% versus 50%, p = 0.0060) in bivariable and multivariable analyses. Both factors were not interrelated (p = 0.824). The statistical effect of HLA-B8 was independent from preoperative severity of disease. Typing for HLA-B8 may thus be a valuable adjunct in predicting the benefit of thymectomy in myasthenia. The observation that an MHC class I allele is associated with clinical improvement after thymectomy suggests that the clinical course of myasthenia may be influenced by class I restricted T-cells.

Alleles↗

PubMed1998

A common motif of eukaryotic glycosyltransferases is essential for the enzyme activity of large clostridial cytotoxins.

A fragment of the N-terminal 546 amino acid residues of Clostridium sordellii lethal toxin possesses full enzyme activity and glucosylates Rho and Ras GTPases in vitro. Here we identified several amino acid residues in C. sordellii lethal toxin that are essential for the enzyme activity of the active toxin fragment. Exchange of aspartic acid at position 286 or 288 with alanine or asparagine decreased glucosyltransferase activity by about 5000-fold and completely blocked glucohydrolase activity. No enzyme activity was detected with the double mutant D286A/D288A. Whereas the wild-type fragment of C. sordellii lethal toxin was labeled by azido-UDP-glucose after UV irradiation, mutation of the DXD motif prevented radiolabeling. At high concentrations (10 mM) of manganese ions, the transferase activities of the D286A and D288A mutants but not that of wild-type fragment were increased by about 20-fold. The exchange of Asp270 and Arg273 reduced glucosyltransferase activity by about 200-fold and blocked glucohydrolase activity. The data indicate that the DXD motif, which is highly conserved in all large clostridial cytotoxins and also in a large number of glycosyltransferases, is functionally essential for the enzyme activity of the toxins and may participate in coordination of the divalent cation and/or in the binding of UDP-glucose.

Amino Acid Sequence↗

PubMed1998

Expression of epidermal growth factor receptor in urinary bladder cancer metastases.

Bladder cancers frequently exhibit an increased number of epidermal growth factor receptors (EGFR) in comparison to normal urothelium. The EGFR could potentially be a target for toxic conjugates. The aim of our study was to compare the expression of EGFR in metastases with concurrent or primary tumour in the urinary bladder using immunohistochemical techniques and a monoclonal antibody. Tumour material from 20 patients was investigated. The majority (13/20) of the metastases were homogeneously stained and showed a moderate to strong membranous staining for EGFR. The expression of EGFR in primary bladder tumours and metastases was similar. There was no indication that tumour tissue exposed to chemotherapy or radiation had a decreased number of EGFR. Targeting of the EGFR thus seems potentially applicable to metastatic disease.

Aged↗

PubMed1998

Surgical treatment of piles: prospective, randomized study of Parks vs. Milligan-Morgan hemorrhoidectomy.

PURPOSE: The present prospective, randomized clinical trial compares the outcome of surgical hemorrhoidectomy according to Parks and Milligan-Morgan in terms of hospital stay, duration of incapacity to work, symptom relief, length of morbidity, and patient convenience. METHODS: Thirty-four consecutive patients with third or fourth degree internal hemorrhoids were randomly allocated to the two groups. Before surgery, all patients were interviewed using a standard questionnaire, followed by rectal examination. All patients underwent a follow-up interview and examinations 1, 2, 4, 8, and 12 weeks after the operation. RESULTS: No serious postoperative complications were seen. Length of hospital stay (3.2 days for Parks hemorrhoidectomy vs. 4.6 days for Milligan-Morgan hemorrhoidectomy; 95 percent confidence interval, 0.2 and 2.6, respectively; P = 0.02) and mean duration of incapacity to work (12.3 days for Parks hemorrhoidectomy vs. 20.2 days for Milligan-Morgan hemorrhoidectomy; 95 percent confidence interval, 5.7 and 10.2, respectively; P < 0.001) differed significantly between the Milligan-Morgan and Parks patients. Until two weeks after the operation, Milligan-Morgan hemorrhoidectomy patients experienced significantly more pain. CONCLUSIONS: Our study confirms that both operations are safe, easy to perform, and lead to satisfactory results. However, the Parks procedure is the preferred option, because it minimizes patients' postoperative discomfort, is more economic, has a significantly reduced hospital stay, and has a shorter time for return to work.

Female↗

PubMed1998

Evaluation of an intensive strategy for follow-up and surveillance of primary breast cancer.

BACKGROUND: Controversies over the frequency and intensity of the follow-up care of breast cancer patients exist. Some physicians have adopted an intensive approach to follow-up care that consists of frequent laboratory tests and routine imaging studies, including chest radiographs, bone scans, and CT scans, whereas others have established a minimalist approach consisting of only history, physical examinations, and mammograms. OBJECTIVES: Our objective was to evaluate the role of intensive follow-up on detection of breast cancer recurrence and to examine the impact of follow-up on overall survival. METHODS: During a 10-year period (1986-1996), 129 patients with recurrent disease were identified from a prospective database of 1898 breast cancer patients. The patients with recurrent disease were divided into minimalist or intensive groups according to method of detection. RESULTS: Twenty-seven of 126 (21%) patients were assigned to the intensive method of detection group (LFT, CEA, CA 15-3, chest radiograph, CT scan, and bone scan); 99 of 126 (79%) patients were assigned to the minimal detection group (history, physical examination, and mammography). Distant disease to the bone was the most common initial tumor recurrence, at 27%. History, physical examination, and mammography detected recurrent cancer in approximately the same amount of time as LFTs, tumor markers, CT scans, and chest radiographs (P = .960). When the recurrent patients were divided into intensive and minimalist groups and analyzed by time to detection of recurrence, there was no significant difference between the time to detection in those recurrences detected by intensive methods and those recurrences detected by minimalist methods (P = .95). The independent variables age, tumor size, type of surgery, number of positive nodes, time to recurrence, method of detection, and site of recurrence (regional or distant) were subject to univariate and multivariate analysis by the Cox proportional hazards model. Only two variables had an impact on survival by multivariate analysis: early timing of the recurrence (P = .0011) and the site of the recurrence (P = .02). Timing was defined as early (< or =365 days from the time of diagnosis to recurrence) or late (> or =365 days from the time of diagnosis to recurrence). Early recurrence was the first variable found to be significant on stepwise forward regression analysis. The primary site of recurrence was significant at step two. The method of detection--intensive or minimal--did not significantly affect survival (P = .18). CONCLUSIONS: There is no survival benefit to routine intensive follow-up regimens in detecting recurrent breast cancer. Expensive diagnostic tests such as bone scans, CT scans, and serial tumor markers are best used for detection of metastasis in symptomatic patients.

Breast Neoplasms↗