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Biomedical subjects

C Busch

Publications and source records attributed to C Busch.

At least 73 records · Page 4Linked to original sources

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↗

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↗

[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↗

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↗

Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects.

Ambulatory blood pressure (ABP) monitoring is increasingly used to evaluate the blood pressure of children and adolescents. The upper normal ABP values in the pediatric age group are still unknown, because reference values based on a sufficiently high number of healthy children have not yet been published. In this multicenter trial, we pooled ABP records of 1141 healthy children and adolescents with a body height between 115 and 185 cm. The study was carried out by seven centers according to a common protocol. The 50th percentile for 24-hour systolic ABP increased moderately with height, from 103 to 113 mm Hg in girls and from 105 to 120 mm Hg in boys. The 50th percentile for diastolic 24-hour means was 66 +/- 1 mm Hg, irrespective of height or gender. Diastolic daytime means were 73 +/- 1 mm Hg, which is remarkably high compared with reference values for casual blood pressure. The mean nocturnal systolic and diastolic ABP (midnight to 6 AM) was 13% +/- 6% and 23% +/- 9% lower compared with the daytime means (8 AM to 8 PM), respectively. This multicenter study provides well-based limits of normal ABP in mid-European children.

Adolescent↗

Phase II studies on prostate cancer.

OBJECTIVES: To evaluate different study designs and the general utility of phase II trials on prostate cancer. METHODS: Extensive literature studies and correspondance within the working group during 1 year were summarized in a preliminary manuscript. The manuscript was finalized at a 1 day meeting and is presented here as a consensus document. RESULTS: The main objectives of phase II studies are to assess whether a treatment is sufficiently active to justify comparative phase III studies, and to obtain further information on adverse reactions. Bidimensionally measurable lesions are traditionally studied, allowing objective criteria for response and progression to be applied. However, as skeletal metastases do not fulfill the criteria for such lesions, the majority of patients with metastatic prostate cancer are not eligible for traditionally-designed phase II trials. Therefore, ancillary response parameters, especially serum prostate-specific antigen (PSA), have been proposed for use. For the evaluation of adverse reactions, the criteria of the World Health Organization were proposed for use. A review of various statistical designs was presented, with a focus on their advantages and disadvantages in phase II trials. CONCLUSIONS: The role of PSA in phase II trials has not yet been firmly established. Further study of its correlation with other endpoints is needed. In future phase II trials, a shift to softer endpoints than traditionally used may enhance the process of evaluation of new antitumor drugs. Phase II studies may even be replaced by early phase III studies, especially in situations where new drugs do not have very heavy adverse effects.

Clinical Trials, Phase II as Topic↗

The sextant protocol for ultrasound-guided core biopsies of the prostate underestimates the presence of cancer.

OBJECTIVES: The aim of this prospective study was to evaluate the sensitivity of the sextant biopsy protocol compared with a more extensive procedure for the detection of prostate cancer and to define a biopsy model with the minimal number of biopsies necessary to maintain diagnostic accuracy. METHODS: A total of 512 consecutive patients with suspected prostate cancer were examined with transrectal ultrasound (TRUS) and underwent TRUS-guided core biopsy. All patients had 8 or 10 standardized biopsy samples taken, with the number depending on the size of the gland. Additional biopsy samples were taken from hypoechoic or hyperechoic lesions located outside the predetermined location for the standardized biopsies (ie, target biopsies). The sensitivity of the detection of cancer for different combinations of biopsy samples was analyzed and compared with that of our model with 8 to 10 biopsies. RESULTS: In all, 276 cancers were detected, of which 88 (32%) had an isoechoic appearance. Sensitivity was 59% for focal lesions detected by TRUS, 85% to 97% for different combinations of systematic biopsy samples, and 93% to 98% for a combination of systematic and target biopsy samples. The sensitivity for the standard sextant protocol was 85%. By adding target biopsies, the sensitivity increased to 93%. CONCLUSIONS: The standard sextant protocol leaves 15% of cancers undetected compared with results obtained from a more extensive biopsy procedure. By combining systematic and target sampling, the sensitivity increases; however, a major concern is that the clinical importance of cancers detected by multiple biopsies needs to be evaluated.

Adult↗

KAMEDIN: a telemedicine system for computer supported cooperative work and remote image analysis in radiology.

The software system KAMEDIN (Kooperatives Arbeiten und MEdizinische Diagnostik auf Innovativen Netzen) is a multimedia telemedicine system for exchange, cooperative diagnostics, and remote analysis of digital medical image data. It provides components for visualisation, processing, and synchronised audio-visual discussion of medical images. Techniques of computer supported cooperative work (CSCW) synchronise user interactions during a teleconference. Visibility of both local and remote cursor on the conference workstations facilitates telepointing and reinforces the conference partner's telepresence. Audio communication during teleconferences is supported by an integrated audio component. Furthermore, brain tissue segmentation with artificial neural networks can be performed on an external supercomputer as a remote image analysis procedure. KAMEDIN is designed as a low cost CSCW tool for ISDN based telecommunication. However it can be used on any TCP/IP supporting network. In a field test, KAMEDIN was installed in 15 clinics and medical departments to validate the systems' usability. The telemedicine system KAMEDIN has been developed, tested, and evaluated within a research project sponsored by German Telekom.

Humans↗

Morphometric studies of intra-prostatic volume relationships in localized prostatic cancer.

OBJECTIVES: To further characterize patterns of tumour growth and the distribution of markers for the aggressiveness of prostate cancer by assessing the relationships among the volume of the 'index' tumour and that of the remaining foci, with pathological (pT) stage, histological grade and DNA ploidy, and with the amount of low- and high-grade prostatic intraepithelial neoplasia (PIN). MATERIALS AND METHODS: Eighty-eight step-sectioned total prostatectomy specimens were analysed. The Gleason score, tumour stage and DNA ploidy (by flow cytometry) of multiple samples were determined. Tumour and PIN areas were outlined and their volumes estimated by computerized planimetry. RESULTS: The pT stage, Gleason sum and DNA nondiploidy increased, and PIN volumes decreased, with increasing volume of the index tumour focus (P < 0.01), but did not differ significantly between uni- and multifocal tumours. However, PIN volumes were significantly larger in multifocal cases with an index tumour volume of > 3 mL than in unifocal tumours > 3 mL (P < 0.05). Small volume, unifocal tumours had little PIN. The most malignant features of each case were always represented in the index tumour but not generally in the remaining foci. CONCLUSIONS: The volume distribution, related to multicentricity and its concomitant PIN volumes, indicates that large index tumours, uni- or multifocal, of medium or high grade, are associated with low PIN volumes. However, multifocal medium- and high-grade tumours with small index tumour volumes have higher PIN volumes. Small, single tumours are of low-grade and may represent the slowly progressing cancers possibly resembling those found in autopsy studies.

Aged↗

Effect of androgen deprivation on epithelial and mesenchymal tissue components in localized prostate cancer.

OBJECTIVE: To measure the area distribution of epithelial and mesenchymal components in the prostate of patients with localized prostate cancer after temporary androgen deprivation. PATIENTS AND METHODS: Surgical specimens from 38 patients treated with the gonadotrophin-releasing hormone agonist triptorelin for 3 months before radical prostatectomy were examined (group I). Specimens from a second group of 54 patients who underwent the same surgical procedure with no prior therapy were used as controls (group 2). The specimens were serially step-sectioned and whole-mount tissue sections prepared. The epithelial, smooth muscle and connective tissue components were stained separately with immunohistochemical and histochemical techniques, respectively. Using colour-based image analyses, the tissue components were classified into three categories, displayed in different colours. The percentage of tumour areas occupied by cancer epithelial cells, connective tissue and smooth muscle was determined. RESULTS: In specimens from group 1, the cancer epithelium was sparse and scattered throughout the tumour area. A mean (SD) of 21 (11)% of the area was occupied by cancer cells, compared with 40 (11)% in the corresponding material from group 2 (P < 0.001). The connective tissue/smooth muscle ratio in stroma (about 1:1) was similar in both groups. CONCLUSIONS: Neoadjuvant hormone treatment of patients with localized prostate cancer was associated with a marked reduction in tumour density and thus in the total amount of cancer epithelium.

Androgen Antagonists↗

Heparin inhibits leukocyte rolling in pial vessels and attenuates inflammatory changes in a rat model of experimental bacterial meningitis.

Heparin is a natural proteoglycan that was first described in 1916. In addition to its well characterized effect on blood coagulation, it is becoming clear that heparin also modulates inflammatory processes on several levels, including the interference with leukocyte-endothelium interaction. Anecdotal observations suggest a better clinical outcome of heparin-treated patients with bacterial meningitis. The authors demonstrate that heparin, a glycosaminoglycan, inhibits significantly in the early phase of experimental pneumococcal meningitis the increase of 1) regional cerebral blood flow (125 +/- 18 versus 247 +/- 42%), 2) intracranial pressure (4.5 +/- 2.0 versus 12.1 +/- 2.2 mm Hg), 3) brain edema (brain water content: 78.23 +/- 0.33 versus 79.49 +/- 0.46%), and 4) influx of leukocytes (571 +/- 397 versus 2400 +/- 875 cells/microL) to the cerebrospinal fluid compared with untreated rats. To elucidate the possible mechanism of this observation, the authors investigated for the first time leukocyte rolling in an inflammatory model in brain venules by confocal laser scanning microscopy in vivo. Heparin significantly attenuates leukocyte rolling at 2, 3, and 4 hours (2.8 +/- 1.3 versus 7.9 +/- 3.2/100 microm/min), as well as leukocyte sticking at 4 hours (2.1 +/- 0.4 versus 3.5 +/- 1.0/100 microm/min) after meningitis induction compared with untreated animals. The authors conclude that heparin can modulate acute central nervous system inflammation and, in particular, leukocyte-endothelium interaction, a key process in the cascade of injury in bacterial meningitis. They propose to evaluate further the potential of heparin in central nervous system inflammation in basic and clinical studies.

Animals↗

Image analysis based grading of bladder carcinoma. Comparison of object, texture and graph based methods and their reproducibility.

The possibility that computerized image analysis could increase the reproducibility of grading of bladder carcinoma as compared to conventional subjective grading made by pathologists was investigated. Object, texture and graph based analysis were carried out from Feulgen stained histological tissue sections. The object based features were extracted from gray scale images, binary images obtained by thresholding the nuclei and several other images derived through image processing operations. The textural features were based on the spatial gray-tone co-occurrence probability matrices and the graph based features were extracted from the minimum spanning trees connecting all nuclei. The large numbers of extracted features were evaluated in relation to subjective grading and to factors related to prognosis using multivariate statistical methods and multilayer backpropagation neural networks. All the methods were originally developed and tested on material from one patient and then tested for reproducibility on entirely different patient material. The results indicate reasonably good reproducibility for the best sets of features. In addition, image analysis based grading showed almost identical correlation to mitotic density and expression of p53 protein as subjective grading. It should thus be possible to use this kind of image analysis as a prognostic tool for bladder carcinoma.

Humans↗

Image transfer and computer-supported cooperative diagnosis.

The KAMEDIN system was designed as a low-cost communication tool as part of a computer-supported cooperative work project that included synchronized user interaction, telepointing and audioconferencing. During a five-month field trial, it was used for medical image transfer and cooperative diagnosis in 14 clinics and medical departments in Germany. During the field test, 297 teleconsultations were performed via ISDN and 875 MByte of data were transferred. An image compression ratio of 2-3 was obtained, so that the total quantity of data transferred corresponded to 14,000-21,000 magnetic resonance images or 3500-5250 computerized tomography images. Furthermore, 694 local sessions were conducted for the preparation of teleconsultations and the review of transferred images. Participants learned to handle the KAMEDIN system in a few hours. This was mainly owing to the design of the user-oriented graphical user interface and the restriction of the system to a set of essential image-processing functions.

Computers↗

Prospective randomized study of drainage and resection on non-occlusive segmental portal hypertension in chronic pancreatitis.

BACKGROUND: In chronic pancreatitis, compression of the splenic vein and superior mesenteric vein (SMV) by an inflammatory mass may cause segmental portal hypertension. Drainage and resection are the principles of surgery for chronic pancreatitis. This study was devised to evaluate the effect of drainage and resection on venous splanchnic blood flow in patients with non-occlusive segmental portal hypertension. METHODS: In 14 of 30 patients with chronic pancreatitis predominantly involving the pancreatic head, segmental portal hypertension due to compression of the splenic vein and SMV was detected by means of indirect splenomesentericoportography and Doppler ultrasonography. None of these 14 patients had symptomatic gastric fundic varices. They were allocated randomly to surgical drainage or resection. Median follow-up was 30 (range 12-48) months. RESULTS: In the resection group, mean(s.d.) splenic vein blood flow increased from 316(46) ml/min before operation to 396(57) ml/min at follow-up (P < 0.01). In the drainage group, preoperative splenic vein blood flow (318(37) ml/min) was not increased after operation (322(37) ml/min). Mean(s.d.) SMV flow increased from 292(42) ml/min before operation to 436(64) ml/min at follow-up (P < 0.01) in the resection group. In the drainage group mean(s.d.) SMV blood flow was 296(32) ml/min before operation and 314(34) ml/min at follow-up. No patient developed fundic gastric varices during follow-up. CONCLUSION: In non-occlusive segmental portal hypertension due to chronic pancreatitis, resection, but not drainage, restores normal venous splanchnic blood flow.

Adult↗

Assessment of proliferation indicators in residual prostatic adenocarcinoma cells after radical external beam radiotherapy.

BACKGROUND: Fifty-five patients who had received radical external beam radiotherapy (RRT) for clinically staged, localized prostatic adenocarcinoma were examined with systematic sextant mapping with the help of transrectal ultrasound-guided core biopsies. The average follow-up after RRT was 6.8 years. Residual cancer was found histopathologically in 67% (37/55) of the patients investigated. METHODS: In the present report, the viability of these tumor cells was studied using immunohistochemical staining methods with the monoclonal antibodies MIB1 and PC10, which are specific for the proliferation-associated antigens Ki-67 and PCNA. RESULTS: Available data concerning proliferating activity in the pretreatment situation in 12 of these patients revealed that proliferating activity was substantially reduced in the majority of cases after RRT. Post-RRT, Ki-67, and PCNA activity was nonetheless found to varying degrees in 64% and 94% of the 36 evaluable tumor-harboring specimens, respectively. In the majority of cases, the proportion of proliferating cells, designated "score", was low. However, Ki-67 scores of up to 8% and PCNA scores of up to 50% were obtained in 35% (8/23) and 97% (33/34) of the specimens, respectively, with proliferative activity. There was no significant correlation between tumor grade and proliferative score in the follow-up biopsies. In the 36 cases investigated, endocrine treatment did not influence the proliferation results. CONCLUSIONS: The present study demonstrates a proliferative capacity in residual tumor cells in a long-term follow-up after RRT, suggesting that these cancer cells might have a biological significance.

Adenocarcinoma↗