Biomedical subjects

C Busch

Publications and source records attributed to C Busch.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1998

[Is resection of colorectal liver metastases still justified in very elderly patients?].

Between 1987 and 1996 302 patients were treated for colorectal liver metastases. Out of this pool 252 completely documented cases were analysed. Forty-five patients (18%) of this population were 70 years or older at time of admission. In this population 17 major resections and 8 minor liver resections were performed. In 9 patients irresectable metastases were diagnosed during treatment of the primary tumor. In 3 cases laparotomy had to be finished as exploration. Eight patients were treated without surgery. Mortality after liver resection was 4%, morbidity 28%. The 5-year-survival-rate (Kaplan-Meier) of the R0 resected patients (n = 21) was 44%. Comparison between the elderly patients and the younger population shows no significant differences in type and extent of treatment or in stage of disease. Survival, morbidity and mortality after liver resection also show no significant differences. These results show that even in elderly patients liver resection for colorectal metastases can be performed efficently and with a curative intention.

Adult↗

PubMed1998

Postoperative infection after transsternal thymectomy for myasthenia gravis: a retrospective analysis of 125 cases.

The present study was conducted in an attempt to clarify the extent to which the preoperative severity of myasthenia gravis and immunosuppression favor postoperative infection. A retrospective analysis was carried out on 125 consecutive patients who had undergone transsternal thymectomy for myasthenia gravis between 1976 and 1995. The preoperative severity of myasthenia was graded by a modified version of Osserman's classification. The incidence of postoperative pneumonia among patients with Osserman's class 1, class 2, class 3, and class 4 disease were 0%, 10%, 21%, and 44%, respectively, showing a marked increase with the preoperative severity of myasthenia; however, postoperative wound infection and mediastinitis were unrelated to the preoperative severity of myasthenia. With every increment in Osserman class, there was an appreciable, though insignificant, rise in the frequency of preoperative immunosuppression. There was no significant association between postoperative infection and preoperative immunosuppression. These findings indicate that a poor preoperative clinical status has a greater impact on the risk of postoperative pneumonia than immunosuppression, and therefore, every effort should be made to decrease the preoperative severity of myasthenia. Promoting the widespread use of plasmapheresis seems particularly important for this purpose.

Adult↗

PubMed1998

The value of the ratio of free-to-total prostate specific antigen for staging purposes in previously untreated prostate cancer.

PURPOSE: We analyzed the use of the ratio of free-to-total prostate specific antigen (PSA), also termed percentage of free PSA, for predicting tumor stage, volume and grade in patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 515 consecutive patients underwent further prostate evaluation due to elevated PSA (greater than 4.0 ng./ml.) or abnormal digital rectal examination. Prostate cancer was diagnosed in 307 patients (59.6%), including 170 (55.4%) who underwent radical retropubic prostatectomy. Data on pathological stage, Gleason grade, and total and Gleason grade 4 cancer volume were available in all patients. In the remaining 208 men (40.4%) benign prostate hyperplasia was diagnosed. Total and free PSA was measured in preoperative serum. RESULTS: Total PSA was significantly higher (p <0.0001) in the 71 men with stage pT3 tumors than in the 91 with pT2 disease. Eight patients had stage pT4 tumors. Cancer volume correlated well with advancing pathological stage (p <0.0001) and total PSA (p <0.0001). The free-to-total PSA ratio was not significantly different (p = 0.93) in stages pT2 and pT3 tumors, and it did not correlate with total (p = 0.71) or pure Gleason grade 4 (p = 0.94) cancer volume. However, the ratio of free-to-total PSA tended to decrease (p = 0.07) in tumors of increasing Gleason grade. CONCLUSIONS: The ratio of free-to-total PSA does not help in the preoperative prediction of final tumor stage and volume. However, disease grading may alter the free-to-total PSA ratio.

Biomarkers, Tumor↗

PubMed1998

Estimation of prostate cancer volume by multiple core biopsies before radical prostatectomy.

OBJECTIVES: To investigate whether tumor volume, an important prognostic factor in prostate cancer, could be estimated from the amount of cancer in multiple core biopsies. METHODS: In 80 men, transrectal ultrasound-guided biopsies were taken from focal lesions detected by ultrasound and 8 to 10 standardized positions, including sextant biopsies (apex, midmedial, base) and midlateral and transition zone biopsies. The cancer length in the biopsies was measured. After radical prostatectomy, the prostates were totally embedded, whole-mounted, and tumor volume was measured planimetrically. RESULTS: The tumor volume correlated significantly with the total cancer length of all biopsies (r = 0.56) and of the sextant biopsies (r = 0.39). It was found that midlateral and transition zone biopsies provided independent information when included in a multiple regression model with tumor volume as the dependent variable and the sextant biopsies as explanatory variables. All men (n = 6) with less than 3 mm cancer length in only one positive biopsy and a Gleason score less than 7 had a tumor volume less than 1 mL. Nine of 10 men with less than 7 mm of cancer in one positive biopsy and Gleason score less than 7 had tumors smaller than 1 mL. Sextant biopsies did not reliably predict cancer volumes less than 1 mL. CONCLUSIONS: The cancer yield of 8 to 10 biopsies correlated better with the volume of prostate cancer than sextant biopsies. This extended biopsy protocol could be used to predict cancers of less than 1 mL in volume.

Adult↗

PubMed1998

Morbidity after transsternal thymectomy for myasthenia gravis: a changing perspective?

A detailed assessment of recent changes in morbidity and mortality after transsternal thymectomy for myasthenia gravis is pending. To this end, a retrospective analysis was carried out of morbidity and mortality rates in 125 patients subjected to transsternal thymectomy for myasthenia gravis in the periods 1976-85 (1st decade) and 1986-95 (2nd decade). Composition of patients did not change much over time, except for more concomitant preoperative disease in the second decade (p = 0.001). None the less, complication rates were not higher, nor did the pattern of complications alter. Mortality was nil in both decades. There was no difference over the decades as to length of ventilation, intensive care treatment, or overall hospitalization. Most complications did not reveal a monocausal relationship, suggesting that a combination of risk factors was implicated. Further reductions in future morbidity rates after transsternal thymectomy for myasthenia gravis seem unlikely as patient preoperative state is unlikely to improve. In the light of the deteriorating preoperative patient condition, constant postoperative morbidity rates indicate that patient care has in fact improved.

Adult↗

PubMed1998

Benign epithelioid schwannoma.

Benign schwannoma (neurilemoma) has various morphologic patterns that may cause problems in differential diagnosis. Although an epithelioid variant of malignant schwannoma simulating carcinoma and melanoma is well recognized, a benign counterpart has not yet been defined. In the current study, we describe five cases of benign epithelioid schwannoma that were in the subcutis (four cases) and the neck of the urinary bladder (one case). The tumors occurred in adults 28-73 years of age, were 1-4.5 cm in diameter, were well circumscribed and cellular, and were composed of epithelioid cells arranged in cords and nests. The benign nature of the lesions was evident by a constellation of features, including small size, sharp circumscription, bland morphology, low proliferative activity (four of five had < or =1% Ki67 immunostaining), and a benign clinical course after either marginal or intralesional excision. All cases had some features of classic schwannoma light microscopically and a high degree of Schwann cell differentiation both ultrastructurally and immunohistochemically. The recognition of benign epithelioid schwannoma is important because it may be misinterpreted as a malignant neuroectodermal, mesenchymal, epithelioid, or melanocytic tumor.

Adult↗

PubMed1998

Increased formation of reactive oxygen species after permanent and reversible middle cerebral artery occlusion in the rat.

In barbiturate-anesthetized rats, we induced 3 hours of permanent middle cerebral artery occlusion (MCAO) by an intraluminal thread (n = 6), or 1 hour MCAO followed by 2 hours of reperfusion (n = 6). Through a closed cranial window over the parietal cortex, the production of reactive oxygen species (ROS) was measured in the infarct border using online in vivo chemiluminescence (CL) while monitoring the appearance of peri-infarct depolarizations (PID). The borderzone localization of the ROS and direct current (DC) potential measurements was confirmed in additional experiments using laser-Doppler scanning, mapping regional CBF changes through the cranial window after permanent (n = 5) or reversible (n = 5) MCAO. CL measurements revealed a short period (10 to 30 minutes) of reduced ROS formation after vessel occlusion, followed by a significant increase (to 162 +/- 51%; baseline = 100%; P < .05) from 100 minutes of permanent MCAO onward. Reperfusion after a 1-hour period of MCAO led to a burst-like pattern of ROS production (peak: 489 +/- 330%; P < .05). When the experiments were terminated 3 hours after induction of MCAO, CL was still significantly increased above baseline after permanent and reversible MCAO (to 190 +/- 67% and 211 +/- 64%, respectively; P < .05). Simultaneous DC potential recordings detected 6.4 +/- 2.7 PID in the first, 4.7 +/- 2.3 in the second, and 2.8 +/- 2.0 in the third hour after permanent MCAO. In animals with reversible MCAO, PID were abolished from 15-minutes recirculation onward. There was no temporal relationship between ROS production and peri-infarct DC potential shifts. In conclusion, using a high temporal resolution ROS detection technique (CL), we found that permanent MCAO (after an initial decrease) was accompanied by a steady increase of ROS production during the 3-hour observation period, while reperfusion after 1 hour of MCAO produced a burst in ROS formation. Both patterns of ROS production were not related to the occurrence of PID.

Acridines↗

PubMed1998

Chimeric clostridial cytotoxins: identification of the N-terminal region involved in protein substrate recognition.

Clostridium sordellii lethal toxin is a member of the family of large clostridial cytotoxins that glucosylate small GTPases. In contrast to Clostridium difficile toxins A and B, which exclusively modify Rho subfamily proteins, C. sordellii lethal toxin also glucosylates Ras subfamily proteins. By deletion analysis and construction of chimeric fusion proteins of C. sordellii lethal toxin and C. difficile toxin B, we localized the enzyme activity of the lethal toxin to the N terminus of the holotoxin and identified the region involved in protein substrate specificity. The toxin fragment of the N-terminal 546 amino acid residues of C. sordellii lethal toxin glucosylated Rho and Ras subfamily proteins, as the holotoxin did. Deletion of a further 30 amino acid residues from the C terminus of this active fragment drastically reduced glucotransferase activity and blocked glucohydrolase activity. Exchange of amino acid residues 364 through 516 of lethal toxin for those in the active toxin B fragment (1 to 546) allowed glucosylation of Ras subfamily proteins. In contrast, the chimera with amino acids 1 to 364 from toxin B, 365 to 468 from lethal toxin, and 469 to 546 from toxin B exhibited markedly reduced modification of Ras subfamily proteins, whereas modification of Rac and Cdc42 was hardly changed. The data indicate that the region of amino acid residues 364 through 516 primarily defines the substrate specificity of C. sordellii lethal toxin.

Bacterial Proteins↗

PubMed1998

Automatic quantification of immunohistochemically stained cell nuclei based on standard reference cells.

A fully automatic method for quantification of images of immunohistochemically stained cell nuclei by computing area proportions, is presented. Agarose embedded cultured fibroblasts were fixed, paraffin embedded and sectioned at 4 microm. They were then stained together with 4 microm sections of the test specimen obtained from bladder cancer material. A colour based classifier is automatically computed from the control cells. The method was tested on formalin fixed paraffin embedded tissue section material, stained with monoclonal antibodies against the Ki67 antigen and cyclin A protein. Ki67 staining results in a detailed nuclear texture with pronounced nucleoli and cyclin A staining is obtained in a more homogeneously distributed pattern. However, different staining patterns did not seem to influence labelling index quantification, and the sensitivity to variations in light conditions and choice of areas within the control population was low. Thus, the technique represents a robust and reproducible quantification method. In tests measuring proportions of stained area an average standard deviation of about 1.5% for the same field was achieved when classified with classifiers created from different control samples.

Automation↗

PubMed1998

Automatic quantification of microvessels using unsupervised image analysis.

An automatic method for quantification of images of microvessels by computing area proportions and number of objects is presented. The objects are segmented from the background using dynamic thresholding of the average component size histogram. To be able to count the objects, fragmented objects are connected, all objects are filled, and touching objects are separated using a watershed segmentation algorithm. The method is fully automatic and robust with respect to illumination and focus settings. A test set consisting of images grabbed with different focus and illumination for each field of view, was used to test the method, and the proposed method showed less variation than the intraoperator variation using manual threshold. Further, the method showed good correlation to manual object counting (r = 0.80) on an other test set.

Automation↗

PubMed1997

Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer.

BACKGROUND: Current methods of disease staging often fail to detect small numbers of tumor cells in lymph nodes. Metastatic relapse may arise from these few cells. METHODS: We studied 1308 lymph nodes from 68 patients with esophageal cancer without overt metastases who had undergone radical en bloc esophagectomy. A total of 399 lymph nodes obtained from 68 patients were found to be free of tumor by routine histopathological analysis and were studied further for isolated tumor cells by immunohistochemical analysis with the monoclonal anti-epithelial-cell antibody Ber-EP4. This antibody did not stain lymph nodes from 24 control patients without carcinoma. RESULTS: Of the 399 "tumor free" lymph nodes, 67 (17 percent), obtained from 42 of the 68 patients, contained Ber-EP4-positive tumor cells. Fifteen of 30 patients who were considered free of lymph-node metastases by histopathological analysis had such cells in their lymph nodes, and 5 of the 15 had small primary tumors. Ber-EP4-positive cells found in "tumor free" nodes were independently predictive of significantly reduced relapse-free survival (P=0.008) and overall survival (P=0.03). They predicted relapse both in patients without nodal metastases (P=0.01) and in those with regional lymph-node involvement (P=0.007). All 12 patients whose lymph nodes were negative on both histopathological and immunohistochemical analysis and who were available for follow-up survived without recurrence. The presence of micrometastatic tumor cells in bone marrow had no additional prognostic value. CONCLUSIONS: Immunohistochemical examination of lymph nodes may improve the pathological staging of esophageal cancer.

Adenocarcinoma↗

PubMed1997

Expression of p21 and mutant p53 gene products in residual prostatic tumor cells after radical radiotherapy.

BACKGROUND: In a previous study, sextant core biopsies revealed residual tumor in the prostate in 37/55 investigated patients, with an average of 6.8 years after external beam radiation therapy (RRT). More than half of the biopsies exhibited Ki-67 and PCNA proliferation activity. METHODS: The present study aims at further characterizing residual tumor cells post-RRT by investigating whether the tumor cells exhibit immunohistochemical expression of p21 and mutant p53 gene products, which reflect the state of cell cycle regulatory mechanisms. RESULTS: Positive p53 staining was observed in 11% and p21 positivity in 47% of biopsies. The proportion of positively stained cells was low for both antigens. The staining patterns point to the existence of wild-type p53-dependent, as well as alternative pathways for p21 protein induction. CONCLUSIONS: A low proportion of tumor cells exhibited p53 protein accumulation post-RRT. G1 arrest, as assessed by p21 immunoexpression, was demonstrated in a low percentage of tumor cells in < 50% of post-RRT biopsies, indicating that the vast majority of residual tumor cells following RRT escape the G1/S checkpoint control and propagate into S-phase, presumably with a maintained malignant potential.

Adenocarcinoma↗