Biomedical subjects

S Handt

Publications and source records attributed to S Handt.

At least 55 records · Page 3Linked to original sources

PubMed1997

Novel enzyme immunoassay and optimized DNA extraction for the detection of polymerase-chain-reaction-amplified viral DNA from paraffin-embedded tissue.

Four different DNA extraction methods were compared to determine their ability to provide DNA for amplification of viral sequences from paraffin-embedded human tissue samples by polymerase chain reaction (PCR). The suitability of extraction methods was assessed using parameters like DNA yield, length of recovered DNA fragments, and duration. Furthermore, the efficiency of amplifying a human single-copy gene, the beta-globin gene, from DNA samples was tested. The best preservation of DNA molecules could be achieved by binding the DNA onto a silica column before further purification. Viral DNA sequences could be amplified by PCR in DNA extracted from routinely processed paraffin blocks from cases with clinically or morphologically suspected cytomegalovirus or Epstein-Barr virus infections. The PCR products were specified by a novel liquid hybridization assay called PCR-enzyme-linked immunosorbent assay. Using this assay, the time-consuming Southern hybridization could be replaced and the time requirement for the detection of PCR products could be reduced from 1 day to 4 hours. The assay system described here represents a reliable, sensitive, and specific method for the detection of viral DNA from paraffin-embedded tissue samples.

Cytomegalovirus↗

PubMed1996

Plasminogen activator inhibitor-1 secretion of endothelial cells increases fibrinolytic resistance of an in vitro fibrin clot: evidence for a key role of endothelial cells in thrombolytic resistance.

Time-dependent thrombolytic resistance is a critical problem in thrombolytic therapy for acute myocardial infarction. Platelets have been regarded as the main source of plasminogen activator inhibitor-1 (PAI-1) found in occlusive platelet-rich clots. However, endothelial cells are also known to influence the fibrinolytic capacity of blood vessels, but their ability to actively mediate time-dependent thrombolytic resistance has not been fully established. We will show that, in vitro, tumor necrosis factor-alpha-stimulated endothelial cells secrete large amounts of PAI-1 over a period of hours, which then binds to fibrin and protects the clot from tissue plasminogen activator-induced fibrinolysis. In vivo, endothelial cells covering atherosclerotic plaques are influenced by cytokines synthesized by plaque cells. Therefore, we propose that continuous activation of endothelial cells in atherosclerotic blood vessels, followed by elevated PAI-1 secretion and storage of active PAI-1 in the fibrin matrix, leads to clot stabilization. This scenario makes endothelial cells a major factor in time-dependent thrombolytic resistance.

Cells, Cultured↗

PubMed1996

Thalidomide selectively modulates the density of cell surface molecules involved in the adhesion cascade.

The mode of action of thalidomide (THD) in clinical cases of vasculitis is still not clear. Expression of adhesion molecules on endothelial cell lines was therefore assessed in vitro. THD is capable of changing the density of tumor necrosis factor alpha (TNFalpha) induced ICAM-1 (CD54), VCAM-1 (CD106) and E-selectin antigens on HUVEC. Furthermore, modulation of L-selectin (CD62L) by THD can be demonstrated on human leukocytes in vitro. The molecules investigated are involved in the neutrophil-endothelial cell interaction and participate in the adhesion cascade. Blunting of cytokine induced up-regulation of these adhesion molecules may account at least in part for anti-vasculitic effects of thalidomide.

Cell Adhesion↗

PubMed1996

Correlation of histology, cytogenetics and proliferation fraction (Ki-67 and PCNA) quantitated by image analysis in meningiomas.

Sixty meningiomas were classified histologically according to the WHO criteria and analyzed cytogenetically. The Ki-67 and PCNA proliferation fractions (PRFs) were assessed by immunhistochemistry. The staining results were quantified by TV-image analysis (Miamed, Leica, Germany). Within meningiomas of WHO-grade II/III and those with complete or partial deletion of # 1p, we found a significantly higher mean and maximal Ki-67 PRFs than in those of WHO-grade I and those with all other karyotypes. This was not the case for PCNA PRFs. No differences in PRFs were detectable between histological subtypes. Although these results were obtained after measurement of five high power fields (HPFs) only, the heterogeneity of PRF distribution within the tumors was high. Even after the measurement of 100 HPFs, the 95% confidence intervals were in a range of 18% to 34.3% PRF. This finding seems to be responsible for the moderate interobserver reproducibility of image analytical determination of PRF (r = 0.74). Nevertheless, there was a good correlation between subjective and objective image analytical assessment of PRF (r = 0.83). The significance of the maximum Ki-67 PRF per specimen implies the possibility of selecting those areas which show the highest fraction of positively stained nuclei for measurement, avoiding the problem of intraslide heterogeneity. Thus the time needed for image analytical quantification may be reduced.

Biomarkers, Tumor↗

PubMed1996

A small interventional device to occlude persistently patent ductus arteriosus in neonates: evaluation in piglets.

OBJECTIVES: We attempted to evaluate the efficacy and tissue reaction of a new miniature interventional ductal occlusion device in neonatal pigs. BACKGROUND: A variety of devices are used to close persistent ductus arteriosus (PDA) by interventional measures. Because of the size of these devices, they have not been applied to term or preterm neonates. Newborn piglets are comparable in size and fragility to human term and preterm neonates. METHODS: Memory-shaped double-cone stainless steel coils were mounted on a titanium-nickel core wire. A snap-in mechanism attaches the coil to the delivery wire, allowing intravascular coil retrieval and repositioning. The system was placed through a 3F Teflon catheter. Two piglet models of PDA were used: 1) ductal patency maintained by stents (n = 6), and 2) ductal patency produced by angioplasty (n = 7) to avoid stent-coil interaction. RESULTS: Placement of the coils within the PDA was possible in all piglets. Before final detachment, the coils were retrieved or repositioned, or both, up to eight times. In all but two piglets the ductus was closed within 1 h of the procedure. The coils were never dislocated and caused no infections or relevant aortic and pulmonary artery obstruction (95% confidence interval for missing complications [0 of 13] extends to 23%). Histologic and electron microscopic studies revealed endothelial coverage of the implants and histiocytic reaction but no local or systemic inflammation or erosion of the implant. CONCLUSIONS: The device was effective in experimental models of PDA. The information obtained warrants initial trials of the device in neonates.

Animals↗

PubMed1996

Enhanced occlusion of vessels combining retrievable, detachable coils as differential electrodes with percutaneous, intravascular radiofrequency electrocoagulation. An experimental study.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility to accelerate occlusion of high-velocity flow vessels by a combination of transcutaneous coil placement and application of radiofrequency current. METHODS: Piglets (n = 8) were anesthetized and acutely instrumented via cutdowns in both carotid and one brachial arteries. Two identical cylindrically shaped coils (length, 3 mm; outer diameter, 2.4 mm; inner diameter, 1.4 mm) were mounted on titanium-nickel core wire and placed via 3-French Nylon catheters in both iliac arteries. The coils were kept connected to the delivery wire, which is isolated from the surrounding tissue by the catheter. The first-placed system served as control, the contralateral coil was connected to a radiofrequency generator closing electrical circuit via an external indifferent electrode. Angiograms via the brachial artery demonstrated the adequate placement of the coils and the status of the iliac arteries without and with current application. In 6 of the 8 cases, 25 watts of radiofrequency current were applied repeatedly over 10 seconds to the coil on one side at 4-minute intervals until occlusion was demonstrated. In 2 of 8 cases. 25 watts were applied continuously over 30 seconds. The coils were detached from the wire the catheters removed. Additional angiograms were performed after 5, 15, 45, and 60 minutes to show the patency of the control setting. RESULTS: Complete occlusion was achieved in all cases after a maximum of three consecutive applications of current for 10 seconds. The control remained patent for a minimum of 45 minutes. On gross and histologic examination the arteries on both sides remained intact. Disruption and charring occurred only after continuous application of current over 30 seconds. CONCLUSIONS: It is feasible to use detachable coils in conjunction with high-frequency electrocoagulation to promote coil fixation and accelerate occlusion of vessels with high blood flow.

Angiography↗

PubMed1996

Prostate-specific antigen: insufficient discrimination between benign prostatic hyperplasia and organ-confined prostate cancer.

OBJECTIVE: Discrimination of patients with benign prostatic hyperplasia (BPH) from those with cancer of the prostate (CaP) is crucial to the management of these diseases. At present, a number of new treatment modalities for symptomatic BPH, which include various nonsurgical treatment modalities, are being discussed. Prior to treatment, it is important to exclude those patients with CaP. In the present study we examined retrospectively the serum prostatic-specific-antigen (PSA) values in both patient groups in order to determine whether serum PSA identifies those patients harboring organ-confined CaP. PATIENTS AND METHODS: Group 1 consisted of 121 patients with histologically confirmed BPH as determined from pathological analysis of the surgically removed specimens. Group 2 included 69 patients with organ-confined CaP, confirmed pathologically from the analysis of the radical prostatectomy specimens. PSA serum concentration was analyzed in both groups. RESULTS: The median PSA level was 3.96 ng/ml (range: 0.5-31.2 ng/ml) in the BPH group and 7.8 ng/ml (range: 0.7-37.7 ng/ml) in the CaP group. In spite of a statistically significant difference (p = 0.0001), serum PSA values overlapped considerably in both groups. CONCLUSIONS: Serum PSA demonstrated only a limited ability to discriminate between BPH and organ-confined CaP. Therefore some patients with symptomatic BPH undergoing nonsurgical treatment may harbor clinically significant CaP despite "normal' serum PSA values. Furthermore, PSA-based screening may overlook a significant percentage of patients in whom a rectal digital examination would detect CaP.

Aged↗

PubMed1996

Clinical use of prostate-specific antigen and prostate-specific antigen density in the staging of patients with cancer of the prostate.

OBJECTIVE: To examine the efficacy of prostate-specific antigen (PSA) and prostate-specific antigen density (PSAD) in staging patients undergoing radical prostatectomy for clinically localized prostate cancer (CaP). PATIENTS AND METHODS: Prostate gland volumes were estimated in patients with clinically localized CaP (n = 119) performing transrectal ultrasound and employing the prolate ellipse formula. PSA was determined using an enzyme immunoassay. All patients underwent laparoscopic pelvic lymphadenectomy followed by radical perineal prostatectomy in No disease. The PSA density was calculated relating the Serum PSA to the sonographically estimated prostate volume. RESULTS: The pathological examination of the prostatectomy specimens revealed a pT2 tumor in 52 cases (43.7%) and a pT3 tumor in 41 cases (34.5%). In 26 patients (21.8%) the histological examination demonstrated metastases to the lymph nodes. Patients with a pT2No CaP demonstrated a median PSA level of 8.95 ng/ml and a median PSAD of 0.3, those with a pT3No CaP demonstrated a median PSA level of 12.3 ng/ml and a median PSAD of 0.38 and those with a T2-3pN + revealed a median PSA level of 22.9 ng/ml and a median PSAD of 0.7. CONCLUSIONS: Both marker, serum PSA as well as PSAD, did not sufficiently distinguish patients with organ-confined cancer from those with extracapsular tumor extension. In contrast, PSAD levels seem to provide useful additional information in the staging of patients with clinically localized CaP with regard to the lymph node status.

Aged↗

PubMed1996

Metabolic imaging of untreated prostate cancer by positron emission tomography with 18fluorine-labeled deoxyglucose.

PURPOSE: We evaluated positron emission tomograph (PET) with 18fluorine (18F)-labeled deoxyglucose for metabolic grading of untreated primary prostate cancer, and differentiation of benign and malignant prostatic disease. MATERIALS AND METHODS: A total of 48 patients with untreated prostate cancer of different stages and 16 with histologically confirmed benign prostatic hyperplasia (BPH) underwent static PET after intravenous injection of 150 to 300 MBq. 18F-deoxyglucose. 18F-deoxyglucose accumulation was quantitated by calculating differential uptake ratios and prostate-to-skeletal muscle ratios. RESULTS: Low 18F-deoxyglucose uptake was noted in the majority of primary tumors (81%). 18F-deoxyglucose accumulation did not correlate with increasing tumor grade or stage. There was a significant overlap in uptake values in BPH and malignant prostatic disease. A trend towards statistical significance was noted with lower prostate-to-skeletal muscle ratios in patients with BPH (p < 0.07). Increased 18F-deoxyglucose accumulation was detected in some patients with BPH and malignant prostatic disease, as well as in those with lymph node and bone metastases of prostate cancer. CONCLUSIONS: 18F-deoxyglucose PET does not allow for metabolic labeling in the majority of untreated primary prostate cancers. BPH and primary prostate cancer cannot be reliably differentiated on the basis of PET. Increased 18F-deoxyglucose accumulation occurs in some primary prostate tumors and in metastatic deposits of prostate cancer.

Antimetabolites↗

PubMed1995

[Displacement margins and edge contour: informative criteria of tumor dignity in ultrasound mammography].

88 patients with ultrasonically detected breast tumours were examined at the Department of Obstetrics and Gynaecology of the Technical University Aachen (RWTH) in the context of a prospective study. Ultrasonic contour characteristics and marginal zone displacement properties were evaluated with regard to their usefulness as criteria for detecting malignancy. using a highresolution hand-held 10 Mhz scanner. With regard to marginal zone displacement as a sign of benignancy, a sensitivity of 67.6% and specificity of 86.3% were found (positive and negative predictive value reaching 89.3% and 86.3%, respectively). A sensitivity of 84.3% and specificity of 86.5% could be demonstrated when an ill-defined, jagged contour was taken as a sign of malignancy. A well-defined, smooth contour resulted in a sensitivity and specificity of 62.2% and 100%, respectively, when used as criterion for benignancy. No clear indication could be found to support the use of an ill-defined but smooth contour as a sign of benignancy. 56.3% showing the aforementioned characteristic were benign, the rest (43.7%) were malignant neoplasias. The evaluation of ultrasonic contour characteristics and marginal zone displacement properties are hence fundamental criteria to augment other characteristic tumour signs in the ultrasonic diagnosis of breast pathology.

Adenocarcinoma, Scirrhous↗

PubMed1995

Evaluation of patients with diseases of the prostate using prostate-specific antigen density.

OBJECTIVE: To compare the efficacy of two tests, prostatic-specific antigen (PSA) and the PSA/prostate volume ratio (PSAD), as diagnostic and staging markers to discriminate patients with benign prostatic hyperplasia (BPH) from patients with cancer of the prostate (CaP). PATIENTS AND METHODS: Prostate gland volumes were estimated in 60 patients with BPH and 88 patients with clinically organ-confined CaP by performing transrectal ultrasonography (TRUS) and using the prolate ellipse formula. Serum PSA concentration was determined using an enzyme immunoassay. In patients with BPH, the prostates were removed either by transurethral resection or retropubic prostatectomy. Patients with CaP underwent laparoscopic pelvic lymphadenectomy followed by radical perineal prostatectomy. PSAD was calculated by relating the serum PSA level to the TRUS-estimated prostate volume. RESULTS: The median PSA level was 4.4 ng/mL in patients with BPH, 9.3 ng/mL in patients with CaP-NO disease and 24 ng/mL in those with CaP-N+ disease. However, imposing a PSA limit of 4 ng/mL for the diagnosis of CaP gave a positive predictive value of only 64.8%, whereas a limit of 10 ng/mL gave a positive predictive value of 71.4%. In contrast, the median PSAD was 0.086 ng/mL/cm3 in patients with BPH, but was 0.295 ng/mL/cm3 in patients with NO-disease and 0.775 ng/mL/cm3 in those with N(+)-disease. With a limit of 0.15 ng/mL/cm3 the positive predictive value of PSAD was 81%. Furthermore, a limit of 0.6 ng/mL/cm3 revealed a positive predictive value of 81% for the diagnosis of metastatic lymph node involvement. CONCLUSIONS: There was a considerable overlap of PSA concentrations in patients with BPH and CaP, and PSA was not sufficiently accurate to distinguish between them. In contrast, PSAD enhanced the discrimination between BPH and CaP and may provide additional information about the status of the lymph nodes in patients with CaP.

Aged↗

PubMed1995

Determination of prostate gland volume by transrectal ultrasound: correlation with radical prostatectomy specimens.

Estimation of the prostate gland volume employing transrectal ultrasound provides important additional information in patients with benign and malignant diseases of the prostate. Twenty-five patients underwent transrectal ultrasound of the prostate prior to radical prostatectomy for organ-confined cancer of the prostate. The prostate gland volume was calculated employing two different methods. The prostate specimen weights were compared with the results of each of the volume estimation method. The prolate ellipse formula, widely used as an alternative to planimetry, demonstrated a correlation coefficient of r2 = 0.831. However, a variation of the prolate ellipse formula expressed as (width x width x height) x pi/6, which is easier to perform as described by Terris and Stamey, exhibited a correlation coefficient of r2 = 0.829. It appears to be a reliable means of estimating prostate gland volume, especially in cases in whom the original formula is difficult to apply.

Aged↗

PubMed1994

[Laser thermal venous obliteration: experimental results in the rat model].

In an animal study, thermal laser application was tested for inducing venous thrombosis. In 54 rats, metal-tipped laser catheters ("hot tip") were trans-jugularly inserted into the distal inferior caval vein which was thermally damaged by laser pulses of 4-7 W. Suitable energy levels were defined in an acute experiment in 25 rats. Chronic experiment with 29 rats included survival time of two weeks after laser application, autopsy and histological work-up of the caval vein. In 27 rats, laser application was successfully performed and induced thrombosis in 17 animals. Perforation of the caval vein occurred in 10 rats. Thermal laser application is capable of inducing venous thrombosis. The power ranges inducing thrombosis or thermal perforation are, however, too narrow to allow safe clinical application of this technique.

Animals↗

PubMed1993

[Acute plasma cell leukemia. Clinical course during high-dose melphalan therapy].

A 29-year-old woman, with a slightly elevated temperature for 3 weeks, increasing dyspnoea at rest, markedly reduced general condition and in heart failure, was found to have a leucocytosis of 100,000/microliters, anaemia (haemoglobin 6.3 g/dl) and thrombocytopenia (41,000/microliters). There were 62% plasma cells in the blood smear. Immunoelectrophoresis of serum and urine revealed kappa-light chains and immunocytology demonstrated IgG-kappa. There was no radiological evidence of osteolysis, while ultrasound examination showed multiple abdominal lymphomas and marked hepatosplenomegaly. Bone marrow smear showed a 90% infiltration of plasma cells. High-dosage melphalan treatment (single intravenous injection of 140 mg/m2) resulted in complete remission after myelodepression over several weeks. Two extramedullary recurrences 5 and 12 months after the diagnosis had been made were successfully treated with high-dosage melphalan, but it was associated with severe and long-lasting myelodepression. Septicaemia with renal and hepatic failure developed and the patient died 6 weeks after the third course of high-dosage melphalan, 14 months after the diagnosis.

Acute Disease↗

PubMed1993

Regulation of fibrinolysis by platelet-released plasminogen activator inhibitor 1: light scattering and ultrastructural examination of lysis of a model platelet-fibrin thrombus.

We have investigated the role of plasminogen activator inhibitor 1 (PAI-1) in the regulation of fibrinolysis using a model thrombus composed of thrombin-stimulated platelets, fibrin(ogen), plasminogen, and recombinant tissue-type plasminogen activator. Laser light scattering kinetic measurements showed that clot lysis was significantly delayed both by thrombin-stimulated platelets and their cell-free releasate. This delay in lysis was almost fully reversed by the addition of a PAI-1-specific monoclonal antibody that blocks the ability of PAI-1 to inhibit plasminogen activators. Lysis half-times exhibited a linear dependence on the concentration of PAI-1 antigen present, as determined by enzyme-linked immunosorbent assay (ELISA). Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting confirmed the presence of PAI-1 antigen in the platelet releasates. Scanning electron micrographs of the model thrombus components sampled late in lysis showed considerable unproteolyzed fibrin still attached to platelets. Immunogold cytochemistry detected large amounts of PAI-1 antigen in the partially lysed platelet-fibrin thrombi. This PAI-1 appeared to be bound to the fibrin network rather than to the platelet surface itself. We conclude that the residual clots observed late in lysis represent platelet-associated fibrin to which platelet-released PAI-1 has bound, rendering it less susceptible to degradation.

Adult↗

PubMed1993

[The echo-dense edge and hyper-reflective spikes: sensitive criteria for malignant processes in breast ultrasound].

At the Department of Gynaecology of the RWTH-Aachen, 110 patients with palpatory and/or mammographic suspect findings were sonographically examined. By using a high resolution 10 MHz-probe with a freely mobile transducer, a new method of differential diagnostic criteria was established, pertaining to the edge of the tumour. The high echogenetic halo and the hyperdense spikes proved to be most important differential diagnostic tools in assessing sonographically suspect tumours.

Adenofibroma↗

PubMed1993

Somatostatin receptor scintigraphy in malignant lymphoma: first results and comparison with glucose metabolism measured by positron-emission tomography.

Somatostatin receptor scintigraphy with 111In-labeled octreotide was performed in 22 patients with suspected or known malignant lymphoma. The majority of extra-abdominal lesions (21/24 = 87.5%) were correctly localized, however, only one of nine intraabdominal lymphomas could be detected. No significant correlation was found between scintigraphic results and histological type of lymphoma. Metabolic imaging by positron-emission tomography with 18F-labeled deoxyglucose yielded a higher rate of detection of lymphoma manifestations (92% vs 64%) and better tumor contrast. Further prospective studies are needed to establish the clinical relevance of somatostatin receptor scintigraphy in malignant lymphoma.

Adult↗

PubMed1993

Prevalence of Helicobacter pylori in patients with chronic renal failure.

The prevalence of Helicobacter pylori (H. pylori) was investigated in 164 consecutive patients with different degrees of renal function; group I (normal renal function) n = 84, group II (chronic renal failure, CLCR > or = 5 < 90 ml/min) n = 45, group III (haemodialysis therapy) n = 35, to test the hypothesis that the resulting different concentrations of urea in the gastric juice would have an influence on the colonization of the gastric mucosa by these urea-splitting bacteria. As every individual method for the detection of H. pylori shows disadvantages, the results of the detection methods used (urease test, Warthin-Starry stain, bacterial cultivation, direct examination of the processed sample by phase-contrast microscopy) were combined in a cumulative evaluation. These calculated cumulative indices for the antrum and corpus showed no statistically significant differences between the studied groups. The prevalence of H. pylori ranged from 34 to 54%. The histopathological findings were similar in all groups. In spite of the fact that patients with renal dysfunction had significantly higher levels of serum gastrin (P < 0.05), there was no influence on the gastric juice pH value. The relationship between the cumulative index and ammonia concentration in gastric juice was found to be linear (P < 0.05). The higher urea levels in the blood and gastric juice of patients with renal failure do not seem to be a risk factor for infection with H. pylori.

Ammonia↗