Biomedical subjects

C Busch

Publications and source records attributed to C Busch.

At least 55 records · Page 3Linked to original sources

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↗

PubMed1997

Characterization of residual tumor cells following radical radiation therapy for prostatic adenocarcinoma; immunohistochemical expression of prostate-specific antigen, prostatic acid phosphatase, and cytokeratin 8.

BACKGROUND: Our knowledge about the nature and biological activity of tumor cells residing in the prostate gland after radical radiotherapy (RRT) is limited. METHODS: In the present study, residual tumor in core biopsies taken from 37 patients after an average of 6.8 years follow-up after radiation, were investigated with immunohistochemistry for the biochemical markers prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and the epithelial marker, cytokeratin 8 (CK8). RESULTS: Tumor cells were cytokeratin-positive in 33 of 34 evaluable specimens (97%). PSA and PAP were expressed in the tumor cells in 94% (34/36) and 81% (30/37) of cases, respectively. No significant correlation was observed between PSA/PAP expression and tumor grade after treatment. Endocrine treatment administered in addition to RRT in 12 of the 37 patients did not affect the expression of PSA or PAP. The expression of both biochemical markers was reduced after radiotherapy in 10 of the 12 cases for which pre- and post-treatment specimens were available. CONCLUSIONS: Tumor cells retain their epithelial characteristics immunohistochemically after radiation, though their morphology sometimes suggests an altered phenotype after treatment. PSA and PAP reactivity was demonstrated in tumor cells nearly 7 years after radiotherapy, which indicates that these cells maintain their biochemical integrity and protein synthesis to a certain extent. Furthermore, endocrine treatment did not abolish PSA or PAP expression in the tumor cells. Whether PSA and PAP immunoexpression provides independent prognostic information needs to be further investigated.

Acid Phosphatase↗

PubMed1997

Localization of the glucosyltransferase activity of Clostridium difficile toxin B to the N-terminal part of the holotoxin.

Clostridium difficile toxin B that is one of the largest cytotoxins (270 kDa) known acts on Rho subfamily proteins by monoglucosylation (Just, I., Selzer, J., Wilm, M., von Eichel-Streiber, C., Mann, M., and Aktories, K. (1995) Nature 375, 500-503). By deletion analysis we identified the enzyme and cytotoxic activity of the toxin to be located at the N terminus of the holotoxin. A 63-kDa fragment of toxin B covering the first 546 amino acid residues glucosylated Rho, Rac, and Cdc42, but not Ras, by using UDP-glucose as a cosubstrate. As known for the holotoxin, glucosylation by the toxin fragment was favored with the GDP-bound form of the low molecular mass GTPases. Microinjection of the toxin fragment into NIH-3T3 cells induced rounding up of cells and redistribution of the actin cytoskeleton. In contrast, a toxin fragment encompassing the first 516 amino acid residues was at least 1000-fold less active than toxin fragment 1-546 and cytotoxically inactive. The data give direct evidence for location of the enzyme activity of C. difficile toxin B at the N-terminal 546 amino acids residues and indicate a functionally and/or structurally important role of the region from amino acid residues 516 through 546 for enzyme and cytotoxic activities.

3T3 Cells↗

PubMed1997

Rapid Ca2+-dependent NO-production from central nervous system cells in culture measured by NO-nitrite/ozone chemoluminescence.

We have established simple and reliable measurement of constitutive nitric oxide (NO) synthase-dependent nitrite formation in supernatants from primary central nervous system (CNS) cells in culture using NO-ozone chemoluminescence. We found that: (1) astrocytes, endothelial cells and cerebellar granule cells produce NO upon stimulation with the calcium ionophore A23187 (1 microM); (2) application of 100 microM glutamate for 2 min results in NO-production in cerebellar granule cells and cortical neurons. NO-formation upon application of 50 mM KCl was found in cortical neurons; (3) in cultivated cerebral endothelial cells, an inducible form of NO-synthase (iNOS) is found under standard culture conditions. This induction was blocked by dexamethasone applied for at least 48 h and stimulation of constitutive NOS was detectable while iNOS was inhibited. The activity of iNOS was selectively inhibited by application of aminoguanidine for 48 h. Our results suggest that all major CNS cells implied in cerebral blood flow regulation and neurovascular coupling are capable of rapidly producing the vasodilator NO upon intracellular increases of the universal second messenger calcium.

Animals↗

PubMed1997

Neo-adjuvant GnRH therapy and radical prostatectomy: effects on tumorous and benign tissue volumes - a morphometric study.

UNLABELLED: The effect on tumour and prostate volumes of a 3-month course of neo-adjuvant hormone therapy was studied using computerised planimetry on serially sectioned specimens obtained by radical prostatectomy. Fifty-four specimens from patients not receiving pre-treatment were compared to 38 specimens from patients given the gonadotropin-releasing hormone (GnRH) analogue triptorelin for 3 months before the operation. Glandular volume and volume of the index tumour was determined. To determine the position of the index tumour within the gland, the centre of mass of the tumour was identified and the distance to the gland margin calculated. This value (M1) represents the sum of the tumour radius and the various amounts of normal tissue. The amount of surrounding tissue could be approximated by correlating M1 to the corresponding tumour volume. RESULTS: The two groups differed significantly in total gland volumes, but not in tumour volumes. M1 was strongly correlated to the tumour volume in the treatment group (r = 0.73), whereas in the control group the correlation was found to be significantly weaker (r = 0.44), indicating that there was less tissue surrounding the tumour in the pre-treated group. In a multiple regression analysis of all 92 patients, index tumour volume was found to be associated with total gland volume, DNA ploidy pattern, tumour grade but not whether or not pre-treatment was given. This study found that the volumes of the single largest tumour focus were not significantly affected by hormonal pre-treatment, and that "the prostate condenses around the tumour rather than that the tumour shrinks back into the prostate". However, the precise relationship between tumour epithelial volume and stroma with or without neo-adjuvant hormonal pre-treatment remains to be clarified.

Gonadotropin-Releasing Hormone↗

PubMed1997

[Possible applications of the KAMEDIN teleradiology system with special reference to an economic analysis].

INTRODUCTION: Different concepts and applications of teleradiology systems have been realised. However, their cost-effectiveness is still questionable. Therefore, a cost-benefit analysis of three different scenarios of the new teleradiology system Kamedin (Kooperatives Arbeiten und rechnergestützte Medizinische Diagnostik auf innovativen Netzen der Deutschen Telekom) was performed. METHODS: CT examinations were transmitted from an Advantage Windows (GE) workstation to a Kamedin workstation using DICOM 3 protocol. Afterwards a teleconference was established with a Kamedin workstation in the intensive care unit within the hospital via FDDI/Ethernet, with an external workstation in a radiology department 6 km away via ISDN and with a Kamedin PC located with radiologist on duty 22 km away via ISDN. On average, 36 CT slices per patient were transferred. A break-even analysis was performed with respect to costs of hardware, software, support, use of ISDN and staff, as well as benefits like the decrease in transportation or film documentation costs. RESULTS: Owing to the different reductions in transportation costs, two applications (intensive care unit and external PC) showed a break-even of 1817 and 528 teleconferences/year, respectively. Further optimisation of cost-effectiveness is possible on condition that existing hardware can be used and an automatic data transfer without staff control is available. When all optimisation factors were combined, the break-even decreased to a minimum of 167 and 77 teleconferences/ year, respectively. CONCLUSION: Teleconferences with high image quality can be set up between workstations and PCs using the Kamedin system. Depending on the possible decrease in transportation costs, teleconferencing is cost-effective under certain conditions. Teleradiology has additional advantages, such as the acceleration and optimisation of patient management.

Computer Communication Networks↗

PubMed1997

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation.

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3-24.3 (median 15.0) years who had been transplanted 1.5-8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m2. Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants.

Adolescent↗