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Biomedical subjects

C Marx

Publications and source records attributed to C Marx.

At least 19 recordsLinked to original sources
PubMed2005

[The 12th amendment to the German Drug Law. Chances and obstacles for investigator-initiated clinical trials].

The European Union's so called Clinical Trials Directive 2001/20/EC was implemented in national law in Germany in August 2004, leading to the 12th amendment of the German Drug Law (Arzneimittelgesetz). The directive is intended to harmonize the clinical trial's regulatory environment across the European Union and to improve protection of human subjects. It lays down the principles and guidelines of Good Clinical Practice (GCP). As the regulation applies to all clinical trials on medicinal products for human use, and as only non-interventional studies are excluded, academic, investigator-initiated clinical trials will also have to comply with the EU clinical trials directive implemented in the German Drug Law. In an investigator-initiated trial in which the investigator takes the responsibility of a sponsor, the investigator-sponsor must take total legal and financial responsibility for the clinical trial. Since publicly funded clinical trials make a large contribution to improved care, concern has been expressed that non-commercial research projects will be reduced and the vital medical research conducted at academic institutions curtailed. Nonetheless GCP ensures a valid study design, qualified data management, analysis and monitoring of the trial and thereby promotes more valid data and protection of study participants. The trials are more likely to lead to reliable results leading to new therapies, strategies or a better understanding of diseases. What is needed, therefore, is an increase in public funding and the establishment of clinical trial units/organizations associated with the universities or hospitals where independent researchers have the possibility to obtain theoretical advice and practical help, professional training and support. In the end, the directive may serve as a stimulus to build a better national research environment and to promote public funding, and may lead to fewer but more valid clinical trials.

Clinical Trials as Topic↗
PubMed2005

Bosentan therapy for portopulmonary hypertension.

The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported. In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for >1 yr with bosentan. After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310+/-102 m at baseline to 388+/-81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6+/-3.5 to 16.6+/-2.8 mL.min(-1).kg(-1). Pulmonary vascular resistance fell from 944+/-519 to 635+/-321 dynes.s.L(-1). The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury. In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.

Adult↗
PubMed2004

Long term survival in primary pulmonary hypertension.

The mean survival of patients with severe primary pulmonary hypertension (PPH) is < 3 years without appropriate treatment. There are no long term reports on the spontaneous course of mild PPH over a longer period. Stable long term follow up is described of a 39 year old patient with PPH without treatment over a 30 year period. PPH had been diagnosed 30 years previously after right heart catheterisation (mean pulmonary artery pressure 35 mm Hg) and 30 years later, repeated measurements showed nearly unchanged haemodynamic parameters. Further examinations confirmed the diagnosis of PPH. It is suggested that PPH with modestly limited physical activity (New York Heart Association functional class II) does not always seem to coincide with progression of the disease and, therefore, it may be feasible to withhold treatment while closely monitoring these patients.

Adult↗
PubMed2004

Severe pulmonary hypertension in chronic idiopathic myelofibrosis.

BACKGROUND: Chronic myeloproliferative disorders (CMPD) seem to be associated with an increased risk for pulmonary hypertension (PH). CASE REPORT: A patient with history of chronic idiopathic myelofibrosis (CIMF) presented with progressive dyspnea (New York Heart Association class III). Until this time he had not received specific treatment for CIMF. Echocardiography and rightheart catheterization confirmed PH. Further diagnostic procedures excluded a specific cause of PH. Therefore, primary PH was assumed. 2 years later he presented again with progressive dyspnea due to a progress of PH. A few days later the patient died from acute posterior myocardial infarction. Pathologic examination of the lung showed an obstruction of the small vessels by conglomerates of megakaryocytes. DISCUSSION: We conclude that PH developed secondarily due to CMPD. PH should be suspected in patients with CMPD and should influence the decision for treatment of CMPD.

Chronic Disease↗
PubMed2003

Is the "blooming sign" a promising additional tool to determine malignancy in MR mammography?

The aim of this study was to evaluate potential diagnostic relevance of blooming effect for verification of suspicious breast lesions in MR mammography (MRM). The MRM examinations of 1035 patients, all following the same imaging protocol (from 1994 to 2001) were retrospectively evaluated by two experienced radiologists in consensus. A total of 817 lesions showed a focal enhancement; of these, 793 were histologically verified after surgical intervention so that 514 malignant and 279 benign lesions could be evaluated. Using a 1.5-T Gyroscan ACS II-imager (Philips, Hamburg, Germany) and a double breast coil with the patient lying in a prone position, 0.1 mmol/kgbw Magnevist (Schering, Berlin, Germany) were injected into the cubital vein to obtain dynamic axial and coronal T1-weighted fast-field-echo images every minute up to 7 min after bolus injection. Blooming sign describes a progradient unsharpness of lesion borders initially sharply shaped and fast enhancing 7 min after bolus injection; 324 of 514 (63.0%) malignant lesions and 41 of 279 (14.7%) benign lesions revealed a blooming sign (sensitivity 63.0%, specificity 85.3%, accuracy 70.9%, positive predictive value 88.8%, negative predictive value 56.0%). Forty-one of 279 benign lesions showed a blooming sign; of these, there were 4 of 86 (4.7%) fibroadenomas, 2 of 21 (9.5%) phylloides tumours, 11 of 38 (28.9%) papillomas, 3 of 9 (33.3%) radial scars, 2 of 19 (10.5%) mastitis, 1 of 4 (25%) galactophoritis, 1 of 3 (33.3%) ADH and 19 of 99 (17.2%) mastopathic proliferations, respectively. Blooming sign is a phenomenon which should be taken into account when diagnosing MR mammographies because it might increase the ability to discriminate uncertain breast lesions; however, this effect can only be used as an additional item to other well-known effects such as plateau, washout and cancer corner.

Adult↗
PubMed2003

[Evaluation of the primary diagnosis with a CAD-system in mammography].

PURPOSE: To assess the capability of the computer assisted detection (CAD) system to classify calcifications that are histologically verified as malignant and benign or are proven benign by magnification and follow up mammography. MATERIALS AND METHODS: Three groups of microcalcifications (MC) with and without associated masses were enrolled in the study. The cancer group included 141 screen-detected breast cancer cases. One benign group comprised 109 cases with histologically benign specimens obtained through a minimally invasive breast biopsy. A second benign group included 72 lesions with MC that appeared benign on magnification/compression views and were confirmed to be benign on follow-up mammograms over a period of at least 1.5 years. All mammograms were evaluated with a CAD system (Second Look version 3.5, CADx Medical Systems, Canada). RESULTS: CAD correctly detected 125 of 141 (89 %) cancer cases. Of the 16 false negative cases, CAD marked the location of the MC (which were associated with malignant mass) with a mass mark in 12 cases. For benign cases, CAD did not correctly mark the microcalcifications in 59 of the 109 lesions confirmed benign histologically (54.1 %) and in 39 of the 72 lesions established benign mammographically (54.2 %). Adenosis introduced the highest rate of falsely marked microcalcifications (62 %). CONCLUSION: Due to its limited specificity, CAD can still not be recommended for the primary classification of microcalcifications as malignant or benign. Nevertheless, the low false negative rate and rather high detection rate of malignant findings indicate some value of CAD for an independent second reading.

Adenocarcinoma↗
PubMed2003

Compression of the sciatic nerve by wear debris following total hip replacement: a report of three cases.

Pain in the distribution of the sciatic nerve is common in the elderly. In the presence of a long-standing joint replacement, consideration should be given as to whether compression might be due to an extraspinal cause. We present three women, in whom a mass of wear debris from a previous total hip replacement caused compression of the sciatic nerve posterior to the hip. The symptoms were relieved immediately following operation.

Aged↗
PubMed2002

Thymus size at birth is associated with infant mortality: a community study from Guinea-Bissau.

UNLABELLED: A few studies have suggested that thymus atrophy is associated with severe malnutrition and increased morbidity; however, no study of thymus size has been undertaken in countries with high mortality. This study examined the relation between thymus size at birth and subsequent mortality in an urban West African community. The size of the thymus was assessed by sonography as a volume estimate, the thymus index. A total of 278 children born at the local health centre in Bandim in Bissau, Guinea-Bissau, was enrolled in the study. Children were followed to the age of 2 y. Thymus size at birth was associated with most strongly weight, as well as with length and arm circumference. Controlling for weight and other risk factors, boys had larger thymus indices than girls [means ratio (MR) = 1.07, 95% confidence interval (95% CI) 1.01-1.14)]. Thymus size was also associated with prematurity, ethnic group, season and investigator, but not with birth order, mother's age, socioeconomic factors or the use of health services. Infant mortality was 117/1000. In a multivariate analysis, excluding premature infants and adjusting for age, gender, ethnic group, season of birth and investigator, higher birthweight (MR = 0.35, 95% CI 0.16-0.74) and larger thymus size (MR = 0.17, 95% CI 0.06-0.48) were independently associated with lower infant mortality. When both indices were estimated in the same model, the thymus index was associated with infant mortality (MR = 0.27, 95% CI 0.07-1.00), whereas birthweight had a non-significant effect (MR = 0.59, 95% CI 0.24-1.47). After 1 y of age neither birthweight nor thymus size at birth was associated with mortality. CONCLUSION: As all deaths were due to infectious diseases, thymus size at birth may be an important predictor of immune competence. Future studies should examine the determinants of thymus growth.

Analysis of Variance↗
PubMed2001

Tumour detection rate of a new commercially available computer-aided detection system.

The aim of this study was to determine the tumour detection rate and false positive rate of a new mammographic computer-aided detection system (CAD) in order to assess its clinical usefulness. The craniocaudal and oblique images of 150 suspicious mammograms from 150 patients that were histologically proven to be malignant were analysed using the Second Look CAD (CADx Medical Systems, Quebec, Canada). Cases were selected randomly using the clinic's internal tumour case sampler. Correct marking of the malignant lesion in at least one view was scored as a true positive. Marks not at the location of the malignant lesion were scored as false positives. In addition, mammograms with histologically proven benign masses ( n=50) and microcalcifications ( n=50), as well as 100 non-suspicious mammograms, were scanned in order to determine the value of false-positive marks per image. The 150 mammograms included 94 lesions that were suspicious due to masses, 26 due to microcalcifications and 30 showed both signs of malignancy. The overall sensitivity was 90.0% (135 of 150). Sensitivity on subsets of the data was 88.7% (110 of 124) for suspicious masses (MA) and 98.2% (55 of 56) for microcalcifications. Eight of 14 false-negative cases were large lesions. The overall false-positive rate was observed as 0.28 and 0.97 marks per image of microcalcifications and masses, respectively. The lowest false-positive rates for microcalcifications and MA were observed in the cancer subgroup, whereas the highest false-positive rates were scored in the benign but mammographically suspicious subgroups, respectively. The new CAD system shows a high tumour detection rate, with approximately 1.3 false positive marks per image. These results suggest that this system might be clinically useful as a second reader of mammograms. The system performance was particularly useful for detecting microcalcifications.

Adenocarcinoma↗
PubMed2001

Preventing recurrence of reflex sympathetic dystrophy in patients requiring an operative intervention at the site of dystrophy after surgery.

The development of reflex sympathetic dystrophy (RSD) is a common complication after surgery. Exacerbation or recurrence of RSD is a major concern after a second intervention at the site of previous surgery and consecutive RSD. It is unclear whether the risk of recurrent RSD can be reduced by using appropriate precautions. The objective of our study was to examine, in a case series of consecutive patients, whether recurrences in patients with a history of RSD after surgery, who were reoperated at the same location, can be avoided by using a standardised intervention protocol containing perioperative calcitonin prophylaxis. None of the patients experienced a recurrence of RSD. We concluded that the recurrence of RSD in patients requiring operative intervention at the site of former dystrophy after surgery appears to be unlikely with careful perioperative management.

Adult↗
PubMed2000

Cellular immune-endocrine interaction in adrenocortical tissues.

BACKGROUND: The detection of important immunocompetence-like features on endocrine steroid cells raises questions about direct intercellular communication between the adrenal and immune systems. This article summarizes our recent work and new data on immune-adrenal interactions. MATERIALS AND METHODS: RT-PCR and immunohistochemistry were performed to examine MHC class II (HLA-DR) expression in adrenocortical tumours. Coculture systems of NCI-H295 adrenocortical carcinoma cells and HLA-matched lymphocytes were used to examine effects on steroid production and survival of lymphocytes. RESULTS: HLA-DR m-RNA is found in both benign and malignant adrenals, except the NCI-H295 cell line. Under direct coculture conditions with NCI-H295 cell line, spontaneous apoptosis of immune cells was reduced. Synthesis of cortisol and especially of dehydroepiandrosterone production of tumour cells was markedly increased. Differences by separating CD4- and CD8- T cells were not detected. CONCLUSIONS: Direct cellular contact between lymphocytes and adrenocortical cells seems to be involved in the peripheral regulation of androgen synthesis in the adrenal. The molecular basis of this interaction is not known. With regard to normal adrenals, ligation of MHC class II antigens could be a potential mechanism for a peripheral regulation of androgen secretion.

Adrenal Cortex Neoplasms↗
PubMed2000

[Perfusion parameters in MRI diagnosis of pancreas transplants].

PURPOSE: Evaluation of the role of perfusion parameters in the detection of circulatory disturbance and chronic rejection in patients after pancreas transplantation. MATERIALS AND METHODS: 70 examinations of 39 patients after pancreas transplantation were performed. Using a dynamic gadolinium-enhanced Turbo-FLASH-sequence, we evaluated the perfusion parameters in a group of patients with chronic rejection, with circulatory disturbance, and in a control group with normal organ function. RESULTS: There were statistically significant differences of the perfusion parameters in patients with chronic rejection and circulatory disturbance compared to the control group. CONCLUSION: Dynamic MRI can help detect patients with chronic rejection and circulatory disturbance and should therefore be part of the routine follow-up in patients after pancreas transplantation.

Adult↗
PubMed2000

[MR morphology of primary aneurysmal bone cysts: a retrospective analysis of 38 cases].

PURPOSE: To define MR imaging characteristics of primary aneurysmal bone cyst. MATERIALS AND METHODS: MR imaging studies of 38 patients with histologically proven primary aneurysmal bone cyst were reviewed with reference to morphological features, signal characteristics, and patterns of contrast-enhancement. RESULT: Most lesions were well marginated towards bone and soft tissues (95%), either surrounded by a complete (84%) or incomplete (16%) rim of low signal intensity on images of all pulse sequences. Frequent features were polycyclic margins (84%), cortical expansion (87%), cystic spaces (100%), contrast-enhancing cyst walls (100%), internal septations (89%), fluid levels (71%) and diverticula-like projections of cyst walls (68%). Solid tissue components could be identified by MR imaging in all lesions which, on pathological examination, contained larger portions of solid material (18%). Edema of surrounding soft-tissues was observed in 29% of the cases. CONCLUSIONS: Primary aneurysmal bone cysts demonstrate a relatively uniform MR imaging appearance, which reflects the patho-anatomic composition of the lesion.

Adolescent↗
PubMed2000

Hepatic lesion detection and characterization: value of nonenhanced MR imaging, superparamagnetic iron oxide-enhanced MR imaging, and spiral CT-ROC analysis.

PURPOSE: To determine the accuracy for detection and characterization of focal hepatic lesions of nonenhanced, superparamagnetic iron oxide (SPIO)-enhanced, or a combination of nonenhanced and SPIO-enhanced MR imaging and contrast-enhanced spiral computed tomography (CT). MATERIALS AND METHODS: Spiral CT and T2-weighted SPIO-enhanced (ferucarbotran-enhanced) MR imaging were performed in 35 patients within 2 weeks before surgery for malignant hepatic lesions. Only malignant lesions with histopathologic proof were considered. A total of 875 images with and 800 images without focal lesions were presented to five readers, who were asked to assess the presence and characterization of lesions by using a five-point confidence scale. Receiver operating characteristic analysis was performed. RESULTS: Nonenhanced and SPIO-enhanced images together and SPIO-enhanced images alone yielded the best performance for lesion detection. No differences were found among all imaging techniques with regard to lesion characterization (benign vs malignant). The combined approach resulted in larger area under the ROC curve (A(z) = 0.9062) and accuracy (85.3%) (P < 0.02), as compared with SPIO-enhanced MR imaging (A(z) = 0.8667; accuracy, 73.1%). CONCLUSION: SPIO-enhanced T2-weighted MR imaging was more accurate than nonenhanced T1-weighted and T2-weighted MR imaging and contrast-enhanced spiral CT for the detection of focal hepatic lesions. The combined analysis of nonenhanced and SPIO-enhanced images was more accurate in the characterization of focal hepatic lesions than was review of SPIO-enhanced images alone.

Contrast Media↗
PubMed1999

Overexpression of thioredoxin h leads to enhanced activity of starch debranching enzyme (pullulanase) in barley grain.

Biochemically active wheat thioredoxin h has been overexpressed in the endosperm of transgenic barley grain. Two DNA constructs containing the wheat thioredoxin h gene (wtrxh) were used for transformation; each contained wtrxh fused to an endosperm-specific B(1)-hordein promoter either with or without a signal peptide sequence for targeting to the protein body. Twenty-two stable, independently transformed regenerable lines were obtained by selecting with the herbicide bialaphos to test for the presence of the bar herbicide resistance gene on a cotransformed plasmid; all were positive for this gene. The presence of wtrxh was confirmed in 20 lines by PCR analysis, and the identity and level of expression of wheat thioredoxin h was assessed by immunoblots. Although levels varied among the different transgenic events, wheat thioredoxin h was consistently highly expressed (up to 30-fold) in the transgenic grain. Transgenic lines transformed with the B(1)-hordein promoter with a signal peptide sequence produced a higher level of wheat thioredoxin h on average than those without a signal sequence. The overexpression of thioredoxin h in the endosperm of germinated grain effected up to a 4-fold increase in the activity of the starch debranching enzyme, pullulanase (limit dextrinase), the enzyme that specifically cleaves alpha-1,6 linkages in starch. These results raise the question of how thioredoxin h enhances the activity of pullulanase because it was found that the inhibitor had become inactive before the enzyme showed appreciable activity.

Glycoside Hydrolases↗
PubMed1999

Cisplatin-resistant bladder carcinoma cells: enhanced expression of metallothioneins.

Cisplatin is one of the most potent cytotoxic drugs and in chemotherapy has ameliorated numerous tumors. Nevertheless, resistance to cisplatin is a problem that is encountered in the chemotherapy of urologic tumors, especially transitional cell carcinomas. In order to improve definition of the mechanisms of cisplatin-resistance we established a series of cisplatin-resistant sublines from the cell line RT 112 in increasing concentrations of cisplatin. The most resistant subline CP3 is approximately 10 times more resistant than the parental line and shows a 10-fold cross-resistance against methotrexate, whereas vinblastine and doxorubicin are equally effective in the parental and sublines. Combined treatment of CP3 cells with cisplatin and buthionine sulfoximine (BSO) does not result in enhanced cell kill, thereby ruling out glutathione as a resistance mechanism. However, in comparison with parental cells, CP3 cells are about 1.5 times more resistant against cadmium. On the protein level, the cisplatin-resistant cells reveal an enhanced expression of metallothionein II (MTII), but not MTI, suggesting that the cisplatin resistance we observed in these sublines is at least partly mediated by MTII. These sublines will in the future serve as valuable tools for the analysis of cisplatin resistance, especially in view of metallothionein-mediated resistance mechanisms.

Antineoplastic Agents↗