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Biomedical subjects

R Linder

Publications and source records attributed to R Linder.

At least 19 recordsLinked to original sources
PubMed2003

[Local recurrence of breast cancer. Isolated local recurrence located at the skin of the latissimus dorsi donor flap after breast reconstruction].

The reasons for local recurrence of breast cancer are currently unknown. Inadequate resection (not RO), undetected multifocal tumors, or absence of postoperative radiation are discussed. Secondary multifocal tumors as well as ipsilateral secondary tumors have been described as potential origins. Partial local recurrences can be considered a sign for general metastasis with an isolated local "reproduction" of the initial tumor. In our patient the observation of isolated local recurrences of the initial breast cancer, located at the skin of the latissimus dorsi donor flap, may be helpful in clarifying the ongoing controversial discussion. Our case study shows that the local recurrence occurred exactly at the initial location of the primary tumor independent of the local epidermal situation. We assume that activated vertical connections exist between the fascial lymphatic system and the dermal lymphatic plexus that "directed" the way to the body wall.

Adenocarcinoma↗
PubMed2003

Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

AIM: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD. METHODS AND RESULTS: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01. CONCLUSION: Myocardial cell injury was related to a high degree of inflammation, only some of which is an acutephase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.

Adult↗
PubMed2002

Predicting Type 2 diabetes using an electronic nose-based artificial neural network analysis.

Diabetes is a major health problem in both industrial and developing countries, and its incidence is rising. Although detection of diabetes is improving, about half of the patients with Type 2 diabetes are undiagnosed and the delay from disease onset to diagnosis may exceed 10 yr. Thus, earlier detection of Type 2 diabetes and treatment of hyperglycaemia and related metabolic abnormalities is of vital importance. The objectives of the present study were to examine urine samples from Type 2 diabetic patients and healthy volunteers using the electronic nose technology and to evaluate possible application of data classification methods such as self-learning artificial neural networks (ANN) and logistic regression (LR) in comparison with principal components analysis (PCA). Urine samples from Type 2 diabetic patients and healthy controls were processed randomly using a simple 8-sensors electronic nose and individual electronic nose patterns were qualitatively classified using the "Approximation and Classification of Medical Data" (ACMD) network based on 2 output neurons, binary LR analysis and PCA. Distinct classes were found for Type 2 diabetic subjects and controls using PCA, which had a 96.0% successful classification percentage mean while qualitative ANN analysis and LR analysis had successful classification percentages of 92.0% and 88.0%, respectively. Therefore, the ACMD network is suitable for classifying medical and clinical data.

Aged↗
PubMed2001

Improved differentiation between Churg-Strauss syndrome and Wegener's granulomatosis by an artificial neural network.

OBJECTIVE: To examine the operating characteristics of the American College of Rheumatology (ACR) classification criteria for Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), and to develop and validate improved criteria for distinguishing CSS from WG. METHODS: The ACR classification criteria for WG and CSS were applied to 40 consecutive CSS patients age- and sex-matched with 40 patients with WG. Forty-three clinical, laboratory, and biopsy parameters were assessed. Artificial neural networks (ANNs) were trained and tested with all 43 parameters (set A) and with 15 solely clinical parameters documented at the initial manifestation of the disease (set B). The ANNs were trained with data from the first 27 CSS and 27 WG patients and validated with data from the next 13 consecutive CSS and 13 WG patients. To compare the ANNs with established methods, traditional format and classification tree criteria were generated using the same data sets. RESULTS: Fourteen of 40 CSS patients fulfilled the ACR criteria for WG, while 4 WG patients met the ACR criteria for CSS. The ANN, in contrast, reliably distinguished all CSS cases from WG cases (parameter set A, accuracy 100%). For parameter set B, the ANN achieved an accuracy of 100% in the training phase and 96% for validation. The newly formulated traditional format and classification tree criteria reached an accuracy of 81% and 88%, respectively. CONCLUSION: The ACR criteria for WG do not reliably differentiate between CSS and WG (specificity 65%). An ANN, however, could be trained to correctly allocate all but 1 patient on the basis of clinical data. Indeed, the ANN applied in this study proved superior to established methods of classification. We suggest that an ANN may be effectively applied in the classification of systemic vasculitides.

Churg-Strauss Syndrome↗
PubMed2001

Coagulation activity and clinical outcome in unstable coronary artery disease.

In the current study, we investigated molecular markers of coagulation activity, ie, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, soluble fibrin (SF), and D-dimer, and their relation to death, myocardial infarction, and refractory angina during and after anticoagulant treatment in unstable coronary artery disease. Patients with unstable coronary artery disease (N=320) were randomized to a 72-hour infusion with either inogatran, a low-molecular-mass direct thrombin inhibitor, or unfractionated heparin. During the 30-day follow-up, a 40% lower event rate was seen in patients with high compared with low baseline levels of TAT or SF. High baseline levels of coagulation activity were correlated with a larger decrease during treatment. Patients with decreased compared with raised F1+2 or TAT levels after 6 hours of treatment had a 50% lower event rate at 30 days (F1+2, P=0.04; TAT, P=0.02). At the cessation of antithrombin treatment, there was a clustering of cardiac events that tended to be related to a rise in the levels of TAT and the other markers. During long-term follow-up (median, 29 months), there was a relation between higher baseline levels of D-dimer (P=0.003) and increased mortality. High baseline levels of molecular markers of coagulation activity might identify patients with a thrombotic condition (as the major cause of instability) who are good responders to anticoagulant therapy, with a larger decrease in coagulation activity during treatment and a decreased risk of ischemic events. However, this early benefit is lost during long-term follow-up when high baseline levels of coagulation activity are associated with a raised risk of early reactivation and increased mortality.

Adult↗
PubMed2000

Artificial neural networks for classifying olfactory signals.

For practical applications, artificial neural networks have to meet several requirements: Mainly they should learn quick, classify accurate and behave robust. Programs should be user-friendly and should not need the presence of an expert for fine tuning diverse learning parameters. The present paper demonstrates an approach using an oversized network topology, adaptive propagation (APROP), a modified error function, and averaging outputs of four networks described for the first time. As an example, signals from different semiconductor gas sensors of an electronic nose were classified. The electronic nose smelt different types of edible oil with extremely different a-priori-probabilities. The fully-specified neural network classifier fulfilled the above mentioned demands. The new approach will be helpful not only for classifying olfactory signals automatically but also in many other fields in medicine, e.g. in data mining from medical databases.

Algorithms↗
PubMed1999

Thrombin inhibitors suppress the thrombin-thrombomodulin-mediated generation of activated protein C.

In the treatment of unstable coronary artery disease, direct thrombin inhibitors have shown no or only limited benefit as compared with heparin, despite theoretical advantages. One explanation may be that the direct thrombin inhibitors to a greater extent than heparin have an inhibiting effect on the generation and activity of activated protein C. In the present study, this hypothesis was tested in an in vitro, "purified" system, where human protein C underwent activation to activated protein C by the thrombin-thrombomodulin complex. Direct thrombin inhibitors, inogatran and hirudin, unfractionated heparin+antithrombin, or dalteparin+antithrombin, were added to the system before activation to evaluate their inhibitory effect on the generation of activated protein C. At inhibitor concentrations well below the achieved plasma levels in major clinical trials, the thrombin-thrombomodulin-mediated activation of protein C was inhibited by all the studied inhibitors in a dose-dependent manner, but, contrary to our hypothesis, to a greater extent by unfractionated heparin+antithrombin and dalteparin+antithrombin than by the direct thrombin inhibitors, hirudin and inogatran. Despite difficulties to draw conclusions for the in vivo situation, the in vitro inhibition, by all studied inhibitors, of the generation of activated protein C, found in this study may be a possible explanation for ongoing cardiovascular events despite adequate treatment with thrombin inhibitors, in patients with unstable coronary artery disease. This inhibition of the generation of activated protein C may also contribute to the rebound in cardiovascular events after withdrawal of effective antithrombotic treatment.

Antithrombins↗
PubMed1999

The effect of a low molecular mass thrombin inhibitor, inogatran, and heparin on thrombin generation and fibrin turnover in patients with unstable coronary artery disease.

AIM: This study evaluated a novel specific thrombin inhibitor, inogatran, in comparison with unfractionated heparin, with regard to markers for coagulation activity in patients with unstable coronary artery disease. METHODS AND RESULTS: In the Thrombin Inhibition In Myocardial Ischaemia (TRIM) study patients were randomized to one of three different doses of inogatran or to unfractionated heparin, given intravenously over 72 h. In a subpopulation of 320 patients, markers for coagulation activity were measured at baseline, during and after the study infusion. Prothrombin fragment 1 + 2, indicating thrombin generation, decreased in the low, medium and high dose inogatran groups and in the heparin group during the first 6 h of treatment by 12%, 15%, 21% and 26%, respectively. From 6 h to 72 h after the start of infusion the levels changed by -7%, -6%, -4% and +34%, respectively. The increase in the heparin group continued after the infusion was stopped. Thrombin-antithrombin complex, also indicating thrombin generation, decreased by 0%, 2%, 18% and 22%, respectively, during the first 6 h of treatment. During the same period soluble fibrin, an intermediate in fibrin formation, increased both in the low and medium inogatran group by 9%, while a decrease by 4% and 18%, respectively, was seen in the high dose inogatran group and in the heparin group. Fibrin dissolution, as measured by fibrin D-dimer, decreased during the first 24 h of treatment by 20%, 18%, 18% and 20%, respectively. The first 24 h after discontinuation of infusion, fibrin D-dimer increased by 6%, 23%, 25% and 44%, respectively. After 72 h, at the end of infusion, patients treated with inogatran, to a larger extent than those given heparin, had suffered from death, myocardial infarction or refractory angina pectoris. After 7 days this trend was less marked. CONCLUSION: The more pronounced decrease in thrombin generation and fibrin turnover during the first 6 h of infusion, and the later increase in thrombin generation and fibrin turnover, in the heparin group, as compared to the inogatran groups, may be related to the lower clinical event rate during infusion with heparin compared with inogatran and the recurrence of ischaemic events, early after cessation of heparin infusion.

Aged↗
PubMed1999

Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease.

UNLABELLED: Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e. death, myocardial (re-)infarction or refractory angina. Methods and Results One thousand two hundred and nine patients with unstable coronary artery disease were randomized to 72 h infusion with inogatran, a low molecular mass direct thrombin inhibitor, or unfractionated heparin. During 30 days follow-up there was no significant difference between inogatran and unfractionated heparin treatment as regards clinical outcome. 11.6% of the 464 inogatran treated patients with activated partial thromboplastin time above the median at 6 h (44 s) had a clinical event in 7 days, and 6.6% of the 423 patients with activated partial thromboplastin time below the median (P=0.01). After 30 days the event rate was still 41% higher in the inogatran patients with activated partial thromboplastin time above the median (P=0.06). Activated partial thromboplastin time in quartiles indicated a direct relationship between higher activated partial thromboplastin time and worse outcome. In contrast, during heparin infusion there was a trend for improved clinical outcome with activated partial thromboplastin time above the median, but this benefit was lost after cessation of treatment. CONCLUSIONS: Higher activated partial thromboplastin time levels during inogatran treatment are related to increased risk of death, myocardial infarction or refractory angina. This might, at least in part, be explained by differences in anticoagulant mechanisms between direct thrombin inhibitors and heparin, and further emphasizes the poorly defined optimal activated partial thromboplastin time range during treatment with direct thrombin inhibitors in unstable coronary artery disease.

Adult↗
PubMed1998

Human pathogenic virus-associated pseudolymphomas and lymphomas with primary cutaneous manifestation in humans and animals.

The etiologic role of viruses in cutaneous lymphoproliferative disorders is still controversial. In benign cutaneous pseudolymphomas of the human skin, human T-cell leukemia/lymphoma virus (HTLV) type I (HTLV-I), varicella zoster virus, Epstein-Barr virus (EBV), and human herpesvirus (HHV) 6 (HHV-6) are the viruses most often identified, whereas in malignant lymphoproliferation human immunodeficiency virus type 1 (HIV-1), HTLV-I/II, and EBV are more common. Coinfections with more than one virus species have occurred in a number of cases. HHV-8 in association with a lymphoproliferative lesion appears to be indicative of a malignant cutaneous lymphoma rather than of pseudolymphoma. Negative results are of no diagnostic value because of the relatively low number of virus-positive cases: a considerable proportion of studies (with a large number of subjects) have documented virus-negative findings. Perhaps with the exception of HIV-1, findings of viral infections seem to indicate secondary rather than primary infections. Reports on animal models associated with human pathogenic viruses are scarce.

Animals↗
PubMed1998

[Effect of dressing materials on wound healing].

In the early 1970s, a major revolution in the management of wounds began. Simple woven absorbents that kept the wound as dry as possible were superseded by occlusive dressings that provided moist wound healing. The wound healing process is influenced by control of moisture content, thermal properties, gaseous permeability, pH effects, and impermeability to micro-organisms. Low adherence of the dressing provides protection of the newly formed tissue and relieves the patient's pain during removal.

Bandages↗
PubMed1997

Oxidation of macrophage membrane cholesterol by intracellular Rhodococcus equi.

Phagocytic uptake by cultured mouse macrophages (PD388D1) of a virulent strain (ATCC 33701) of Rhodococcus equi producing substantial cholesterol oxidase was accompanied by intracellular survival of the bacteria, and enzymatic oxidation of macrophage membrane cholesterol. A non-virulent strain (4219) lacking cholesterol oxidase was largely eliminated from the macrophages and did not bring about oxidation of membrane cholesterol. When R. equi 33701 was co-phagocytosed with Corynebacterium pseudotuberculosis there was a significant enhancement (10-fold) in the amount of oxidation product (4-cholesten-3-one) generated. R. equi and C. pseudotuberculosis are cooperative partners in the hemolysis of sheep erythrocytes, traceable to the cholesterol oxidase of the former, and phospholipase D of the latter. Results are discussed relative to the role of cooperative cytotoxins in damage to host tissue by bacterial pathogens.

Animals↗
PubMed1997

[Value of preoperative diagnosis in struma surgery].

To determine the usefulness of so-called routine diagnostic procedures prior to thyroid operations, in 2007 consecutive patients undergoing thyroid surgery from 1976 until 1991, the results of 1833 scintigraphy examinations, 1358 tracheal X-rays, 773 ultrasound examinations, 302 fine-needle aspiration biopsies (FNAB), and 73 frozen sections (FS) performed during operation were evaluated. Scintigraphy and ultrasound showed similar positive predictive values, ranging between 85% and 95%, in detecting thyroid nodules. The sensitivity of FNAB and FS were 44% and 83%, respectively. Mechanical alteration of the trachea was found to correlate to a high degree with severe postoperative respiratory disorders, requiring prolonged ventilation or tracheotomy either during primary surgery or as a secondary procedure.

Biopsy, Needle↗
PubMed1996

[Therapeutic concepts and long-term outcome in thyroid gland carcinoma].

UNLABELLED: Data of all (n = 131) patients carrying thyroid carcinoma and operated on between January 1st, 1979, and September 30th, 1994 in our center were analyzed retrospectively. Patient's files were reviewed concerning histological diagnosis, TNM-classification, operation procedure and complications. Follow-up data were obtained in all cases from local cancer registry as well as from personal records. Statistical analysis was performed using PCS-software (TopSoft, Hannover). RESULTS: Follow-up data from 3-191 months (mean: 50.4 mo.) postoperatively were obtained from 72 patients with papillary thyroid carcinoma (PTC) including 27 cases of occult papillary thyroid carcinoma (oPTC, < 1.5 cm), 30 patients with follicular thyroid carcinoma (FTC), 10 patients with medullary thyroid carcinoma (MTC) and 19 patients carrying anaplastic tumor (ATC). In case of oPTC 51.8% of the patients received total thyroidectomy or lobectomy and contralateral near-total resection. In PTC, both procedures were performed in 68.9% combined with neck dissection in 31%. Radioiodine treatment was given to 59.7%. Treatment of FTC consisted mainly of thyroidectomy (60%) followed by radioiodine therapy (76.7%). In patients with MTC preference was given to thyroidectomy and bilateral neck dissection, more recently completed by mediastinal lymph node dissection. 90% of the patients with ATC were inoperable. No patient received chemotherapy pre- or postoperatively, respectively. Five-and 10-year survival of patients with PTC (oPTC) was 91.6% (93.7%) and 80.2% (93.7%), respectively. Corresponding data for FTC were 70.5% and 50.3%, and 71.6 % and 47.9%, for MTC respectively. ATC showed 10.3% 3-year survival. CONCLUSIONS: Despite therapy of choice was not performed in all patients, our long-term results generally confirm those reported by others. Despite of this, limited radical therapy should be restricted to oPTC in our opinion. In case of MTC presenting rising or elevated tumor markers postoperatively, early mediastinal lymph node dissection should be considered.

Adenocarcinoma, Follicular↗