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R Albert

Publications and source records attributed to R Albert.

At least 37 records · Page 2Linked to original sources
PubMed1998

Differentiation of low-grade non-Hodgkin's lymphomas using paraffin sections by image processing.

In a previous study, we were able to demonstrate that the differentiation of low-grade non-Hodgkin's lymphomas (NHLs) using digital image analysis of touch imprints obtained from native tumor tissue is feasible. The availability of touch imprints in routine diagnostics, however, is restricted. Therefore, we extended our studies toward paraffin sections being used as routine material for histological diagnoses. To identify five types of NHL classified according to the Revised European American Lymphoma classification, paraffin sections (n=53) of NHL and 9 reactive lymphoid tissues (RLTs) were scanned with a color-video-based microscope system and analyzed by digital image processing. A reliable division between benign and neoplastic lymphoproliferations was achieved. We were able to identify 78% of RLTs as benign and 94% of NHLs as neoplastic. The average probability of correct identification into the six subgroups was 66%. In detail, 78% of RLTs, 50% of chronic lymphocytic lymphomas and MALT-type lymphomas, 72% of mantle cell lymphomas, and 67% of follicle center cell lymphoma were classified correctly. Although the method of subclassifying or identifying NHLs on the basis of a computer-mediated assay is still not usable in daily practice, we show that a reliable differentiation between reactive and neoplastic lymphoproliferative lesions can be achieved by analysis of paraffin sections with high-resolution image analysis and that it is possible to define nuclear structures by identifying subtypes of NHL.

Diagnosis, Differential↗
PubMed1998

[Sleep deprivation and subsequent sleep phase advance stabilizes the positive effect of sleep deprivation in depressive episodes].

Approximately 60% of patients with major depression disorder show a beneficial response to total sleep deprivation (TSD), but the positive effect of TSD is short, and naps or the following night's sleep destroy it. Various methods have been tried to stabilize the positive sleep-deprivation effect. A consecutive 1-week advance in the sleep phase stabilized mood in more than 50% of the sleep-deprivation responders. We examined 40 male patients with major depression who in addition to medical treatment took part in a phase advance study to prove possible synergistic effects. About 60% of the patients showed positive mood stabilization after 1-week of treatment when the patients were sleep-deprivation responders. These results support data from other groups.

Adult↗
PubMed1998

[The young Heine. Case history of pseudologia phantastica].

The young Heinrich Heine showed signs of pseudologia phantastica. While studying the diaries of his greatuncle, he identified with the latter. The underlying factors of this psychopathological development are discussed in this paper.

Adolescent↗
PubMed1998

The somatostatin receptor-targeted radiotherapeutic [90Y-DOTA-DPhe1, Tyr3]octreotide (90Y-SMT 487) eradicates experimental rat pancreatic CA 20948 tumours.

Somatostatin receptor-expressing tumours are potential targets for therapy with radiolabelled somatostatin analogues. We have synthesized a number of such analogues in the past and identified [DOTA-dPhe1, Tyr3]octreotide (SMT 487) as the most promising candidate molecule because of its advantageous properties in cellular and in vivo tumour models. In the current paper we describe the radiotherapeutic effect of yttrium-90 labelled SMT 487 in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumour CA 20948. SMT 487 binds with nanomolar affinity to both the human and the rat somatostatin receptor subtype 2 (sst2) (human sst2 IC50=0.9 nM, rat sst2 IC50=0.5 nM). In vivo, 90Y-SMT 487 distributed rapidly to the sst2 expressing CA 20948 rat pancreatic tumour, with a tumour-to-blood ratio of 49.15 at 24 h post injection. A single intravenous administration of 10 mCi/kg 90Y-SMT 487 resulted in a complete remission of the tumours in five out of seven CA 20948 tumour-bearing Lewis rats. No regrowth of the tumours occurred 8 months post injection. Control animals that were treated with 30 microg/kg of unlabelled SMT 487 had to be sacrificed 10 days post injection due to excessive growth or necrotic areas on the tumour surface. Upon re-inoculation of tumour cells into those rats that had shown complete remission, the tumours disappeared after 3-4 weeks of moderate growth without any further treatment. The present study shows for the first time the curative potential of 90Y-SMT 487-based radiotherapy for somatostatin receptor-expressing tumours. Clinical phase I studies with yttrium-labelled SMT 487 have started in September 1997.

Animals↗
PubMed1998

Synthesis and characterisation of [90Y]-Bz-DTPA-oct: a yttrium-90-labelled octreotide analogue for radiotherapy of somatostatin receptor-positive tumours.

An investigation into the in vitro behaviour of two yttrium-90-labelled somatostatin analogues was performed. Further in vivo characterisation was performed with the most promising agent. A new DTPA-octreotide analogue (Bz-DTPA-oct) was synthesised by coupling a bifunctional DTPA chelator to the N-terminal amine of the D-Phe1 of Tyr3-octreotide. This new SRIF analogue and DTPA-octreotide (OctreoScan) were radiolabelled with 90Y prior to serum stability being evaluated. Receptor binding assays were also performed on the two radioligands using rat cortex membranes. The [90Y]-Bz-DTPA-oct was further evaluated in vivo using tumour-bearing rats. The first conjugate (DTPA-octreotide) bound with a high affinity to SRIF receptors and the 90Y complex was relatively stable in human serum (t1/2 3.8 d for 90Y lost to serum proteins). The second conjugate (Bz-DTPA-oct) also exhibited a high binding affinity to SRIF receptors, but it demonstrated an even slower loss of 90Y to serum proteins (t1/2 12.1 d). The in vivo evaluation of the more stable [90Y]-Bz-DTPA-oct showed a very rapid and high accumulation in somatostatin receptor-positive tumours, which after 1 h resulted in tumour/nontumour ratios of 3.8, 21, and 4.9 (for blood, muscle, and liver, respectively). These tumour/nontumour ratios increased, and were by 24 h postinjection 138, 285, and 6.1 (for blood, muscle, and liver). Yttrium-90-labelled Bz-DTPa-oct is rapidly and selectively accumulated in somatostatin receptor-positive tissue. Octadentate Bz-DTPA-oct could be ligand for 90Y radiotherapy of somatostatin receptor-positive tumours and their metastases.

Animals↗
PubMed1998

Transient inhibition of CD28 and CD40 ligand interactions prolongs adenovirus-mediated transgene expression in the lung and facilitates expression after secondary vector administration.

Recombinant adenovirus vectors have been used to transfer genes to the lungs in animal models, but the extent and duration of primary transgene expression and the ability to achieve expression after repeated vector administration have been limited by the development of antigen-specific immunity to the vector and, in some cases, to vector-transduced foreign proteins. To determine if focused modulation of the immune response could overcome some of these limitations, costimulatory interactions between T cells and B cells/antigen-presenting cells were transiently blocked around the time of vector administration. Systemic treatment at the time of primary-vector administration with a monoclonal antibody (MR1) against murine CD40 ligand, combined with recombinant murine CTLA4Ig and intratracheal coadministration of an adenovirus vector transducing the expression of murine CTLA4Ig, prolonged adenovirus-transduced beta-galactosidase expression in the airways for up to 28 days and resulted in persistent alveolar expression for >90 days (the duration of the experiment). Consistent with these results, this treatment regimen reduced local inflammation and markedly reduced the T-cell and T-cell-dependent antibody response to the vector. A secondary adenovirus vector, administered >90 days after the last systemic dose of MR1 and muCTLA4Ig, resulted in alkaline phosphatase expression at levels comparable to those seen with primary-vector administration. Expression of the secondary transgene persisted in the alveoli (but not in the airways) for up to 24 days (the longest period of observation) at levels similar to those observed on days 3 to 4. These results indicate that transient inhibition of costimulatory molecule interactions substantially enhanced gene transfer to the alveoli but was much less effective in the airways. This suggests that there are differences in the efficiency or nature of mechanisms limiting transgene expression in the airways and in the alveoli.

Abatacept↗
PubMed1998

Objective nuclear grading for node-negative breast cancer patients: comparison of quasi-3D and 2D image-analysis based on light microscopic images.

In a retrospective investigation for a new image-analytical nuclear grading method, we used 145 routine hematoxylin and eosin-stained, paraffin-embedded tissue sections from node-negative breast carcinomas. Cell fields of primary tumors were scanned in a light microscope in successive focus levels in 1-micron steps for thick sections (> or = 5 microns: quasi-3D analysis) and in one focus position for thin sections (< 5 microns: 2D analysis). After image-segmentation, nuclear features for texture and chromatin distribution were calculated. A binary classification tree was constructed for determination of two mathematically defined classes of high- and low-risk tumor cell nuclei. After fixing a cut-point for the portion of high-risk tumor cell nuclei per patient, it was possible to distinguish two different groups with significantly different relapse rates of 4.2% and 74.5% in quasi-3D analysis and 0.0% and 52.0% in 2D analysis, respectively. Large differences between quasi-3D and 2D analysis were only present in the classification of nonrelapse patients, whereas nearly all patients with relapse had more than 50% high-risk tumor cell nuclei. The results show that the information in thicker tissue sections contains important additive components in the third dimension, with respect to the detection of chromatin structure and distribution. This advantage should be exploited for the development of an objective image-analytical nuclear grading system as a highly significant prognostic marker.

Adult↗
PubMed1997

The serotonin syndrome and psychosis-like side-effects of fluvoxamine clinical use--an estimation of incidence.

OBJECTIVE: The incidence of the serotonin syndrome or serotonin-syndrome-like side effects during treatment with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine should be evaluated. METHOD: 200 inpatients treated for the first time with fluvoxamine were prospectively evaluated for the occurrence of a serotonin syndrome over a period of 8200 treatment days. Retrospective follow-up data of outpatient treatment covered 8891 days. RESULTS: No full-blown serotonin syndrome occurred, but 3 patients developed a reversible change of mental status with insomnia, agitation, confusion and incoherent thoughts without other symptoms of the serotonin syndrome. CONCLUSIONS: It is concluded that the occurrence of a potentially lethal serotonin syndrome is rare in fluvoxamine treatment psychosis-like syndromes as a side effect of serotonergic stimulation might occur. In the investigated sample the rate was 0.006-0.04 per 100 treatment days.

Adolescent↗
PubMed1997

Synthesis, biodistribution and renal handling of various chelate-somatostatin conjugates with metabolizable linking groups.

A series of DTPA-octreotide conjugates, with various linking groups, were synthesised to investigate the effect of different metabolizable linkers on the renal retention of radioactivity. All these newly synthesised octreotide conjugates retained the high binding affinity of octreotide for the somatostatin (SRIF) receptors either when unlabeled or radiolabeled with 111In. Some of the metabolizable linkers were rapidly degraded in vitro when incubated with a kidney homogenate. However, in vivo, all these conjugates displayed a significantly lower uptake in SRIF receptor-positive tissue compared to two conjugates with short, stable linkers. Additionally, the compounds with a potentially metabolizable linker had a higher whole-body retention of activity as opposed to the three metabolically stable compounds. Several of the linkers gave evidence of cleavage while in circulation in the blood, and it is probable that the lower tumour accumulation of most of the compounds tested was low due to the high enzymatic nature of the exocrine pancreatic tumour model used. In short, no increase in the tumour-to-kidney ratio was achieved with the analogues containing a metabolizable linker. The highest target-to-nontarget tissue ratios were obtained for the DTPA-octreotide conjugates that had short, metabolically stable linkers.

Animals↗
PubMed1997

The concept of uncertainty as applied to chemical measurements.

The calculation of uncertainty as recommended for physical measurements cannot be transferred readily to chemical measurements. Physical measurements and chemical measurements have entirely different error patterns that behave differently on replication. Correctable local bias predominates in physical systems and random error is minor; random error predominates in chemical systems and bias is difficult to identify and eradicate. Therefore bias must be monitored by randomizing in the interlaboratory environment, a concept not handled by the conventional ISO treatment of uncertainty.

Chemistry Techniques, Analytical↗
PubMed1996

New method of nuclear grading of tissue sections by means of digital image analysis with prognostic significance for node-negative breast cancer patients.

To optimize treatment of the individual patient with node-negative breast cancer, objective, reproducible, and standardized prognostic criteria are required. A number of factors have been studied in recent years, but until now it has been possible to obtain information about the risk of recurrence only for some patients belonging to subgroups with special characteristics. We report the establishment of an image analysis method for nuclear grading as an attempt to solve this problem. In a retrospective analysis, we used routine hematoxylin and eosinstained paraffin sections from 54 node-negative patients with surgery between 1980 and 1985. Cell scenes of primary tumors were scanned in a light microscope in successive focus positions to obtain three-dimensional information. After automatic image segmentation, nuclear features were calculated as input for a first binary classification tree to differentiate between tumor and nontumor cells. Tumor nuclei from patients with or without relapse were defined as high-risk or low-risk nuclei, respectively, and were separated with a second tree. Feature values of the measured tumor nuclei from each patient were examined with this second tree to analyze whether the majority of nuclei for each patient were classified as high-risk or low-risk nuclei. Correct classification rates in the two binary cell classification trees were 88.0% and 83.8%, respectively. In the learning sample of our study, all patients with a relapse had the majority of nuclei in the high-risk group, most with more than 80%. Therefore, it seems to be possible to develop an image analytical risk profile system for nuclear grading to provide information on individual prognosis.

Algorithms↗
PubMed1996

Pneumotoxicity and pulmonary clearance of different welding fumes after intratracheal instillation in the rat.

The objectives of this study were to compare different welding fumes in regard to their potential to elicit lung inflammation or injury and to examine possible mechanisms whereby welding fumes may damage the lungs. Fume was collected on filters from conventional spray [mild steel (MS-SPRAY) or stainless steel (SS-SPRAY) electrode wire] or pulsed current [mild steel (MS-PULSE) electrode wire] gas-shielded metal arc welding. Rats were given one of the three welding fume samples by intratracheal instillation (1.0 mg/100 g body wt). Other rats received a relatively inert dust (iron oxide), a pneumotoxic dust (crystalline silica), or a vehicle control (saline). Bronchoalveolar lavage (BAL) was performed 1, 7, 14, and 35 days postinstillation, and indicators of pulmonary damage [cellular differential, albumin, as well as, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), lactate dehydrogenase, and beta-n-acetyl glucosaminidase release] were assessed. One day postinstillation, some evidence of lung inflammation (more neutrophils) was observed for all particle groups, while increased BAL TNF-alpha and IL-1 beta were observed only in the SS-SPRAY and silica groups. By 14 days, lungs appeared normal among the MS-SPRAY, MS-PULSE, and iron oxide groups. At 14 and 35 days postinstillation, elevated pulmonary responses persisted for the animals exposed to silica and the SS-SPRAY welding fume. By 35 days, however, the SS-SPRAY group approached control levels, while the injury induced by silica increased. Using magnetometric estimates of welding fumes, we observed that MS-SPRAY fume was cleared from the lungs at a faster rate than the SS-SPRAY particles. We have demonstrated that the SS-SPRAY fume has more pneumotoxicity than MS fumes. This difference may reflect a greater retention of the SS-SPRAY particles in the lungs and different elemental composition of the fume. The SS-SPRAY fume also had enhanced release of TNF-alpha and IL-1 beta from lung cells soon after fume instillation. In contrast, we saw no influence of the power supply on particle size, composition, or toxicity.

Air Pollutants↗
PubMed1996

Eye-blink rates and depression. Is the antidepressant effect of sleep deprivation mediated by the dopamine system?

A series of studies demonstrated a possible correlation between eye-blink rate and central dopamine activity. The hypothesis has been put forward that the antidepressant effect of sleep deprivation (SD) is mediated by an enhanced dopamine release resulting in an amphetaminelike action of SD. Therefore, the blink rates of 12 drug-naive patients with major depression and 12 healthy controls were compared before and after SD and before and after 2.5 mg bromocriptine as a dopaminergic challenge. The main result of the study was that the depressed patients had a significantly higher increase of blinking after SD both with and without a dopaminergic challenge. Basal eye-blink rate was not different in nonretarded major depression patients compared to controls. Sleep deprivation increased blink rate in depression patients but not in controls, and the increase was proportional to improvements in depressive state after sleep deprivation. Bromocriptine did not increase blink rate 1 hour after application. This result is consistent with the hypothesis that antidepressant SD acts through dopamine release, although it is not conclusive, because other neurotransmitters like acetylcholine may be involved in the regulation of blinking.

Adult↗
PubMed1996

Somatostatin analogues for somatostatin-receptor-mediated radiotherapy of cancer.

The aim of the present study was to selectively target a beta-emitter-labelled octreotide analogue to somatostatin (SRIF)-receptor-expressing tumours and to evaluate the feasibility of SRIF-receptor-mediated radiotherapy by delivering a lethal dose of radiation to the tumour. The most promising compound in a series of DTPA-coupled octreotide analogues was DTPA-benzyl-acetamido-D-Phe1, Tyr3-octreotide (SDZ413). In vitro, SDZ413 binds with nanomolar affinity to SRIF-receptors (IC50 = 4.0 nM) and inhibits growth hormone release from primary cultures of rat pituitary cells with an IC50 of 7.2 nM. Biodistribution studies with [90Y]SDZ413 demonstrated a fast and significant SRIF-receptor-specific accumulation of the labelled conjugate (tumour/muscle ratio after 24 h: 52/1). [90Y]SDZ413 was effective in the radiotherapy of SRIF-receptor-positive tumours in a nude mouse model. A single treatment with [90Y]SDZ413 led to a significant decrease (25%) of tumour mass. This effect was mediated by the intact radioligand, since treatment with [90Y]SDZ978, a derivative of SDZ413 which does not bind with high affinity to SRIF-receptors or with the unlabelled SDZ413 alone, failed to affect tumour growth. These results suggest that receptor-targeted radiotherapy with a 90Y-labelled octreotide analogue represents a new strategy for the treatment of SRIF-receptor-positive tumours that have been previously diagnosed with OctreoScan111 (pentetreotide).

Animals↗
PubMed1996

[Radiotherapy treatment of subfoveal retinal neovascularization: results after two years].

The treatment by radiotherapy (10 Grays) of subfoveal choroidal neovascular membranes is disappointing. Although after one year, 22% of cases had a positive result, after a mean follow up of 2.5 years only 14% of cases had a favourable outcome. The final visual acuity 30 months after treatment was the same as the one observed after 21 months of natural evolution. The well-defined nature of the subretinal new vessels, the presence of a pigment epithelial detachment and the occurrence of a vast hemorrhage were of bad prognosis.

Aged↗
PubMed1995

Combined SSRI-RIMA treatment in refractory depression. Safety data and efficacy.

Eighteen patients with refractory depression (dysthymia with superimposed major depression) were treated with a combination of fluvoxamine and moclobemide for 6 weeks and compared with 18 patients treated with fluvoxamine only. Both groups had improved only slightly after 8 weeks of TCA treatment and 6 weeks of SSRI treatment. Two main observations can be made concerning safety and efficacy. Firstly, side effects in the SSRI-RIMA group were minimal. Secondly, the SSRI-RIMA combination treatment significantly improved depression in refractory depressed patients, with a decrease in depression of about 40%. The SSRI monotherapy group also significantly improved, though only by about 20%, indicating that positive effects of SSRI treatment may still develop even after 12 weeks of treatment. In conclusion, the study gives further support to the hypothesis that SSRI-RIMA combinations may be safe and well tolerated. This treatment may also offer some therapeutic advantages in at least some patients who have not responded to conventional pharmacological treatment.

Adult↗