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Biomedical subjects

W Albrecht

Publications and source records attributed to W Albrecht.

At least 37 records · Page 2Linked to original sources

Investigation of plasma protein adsorption on functionalized nanoparticles for application in apheresis.

Particles with specific ligands for the adsorption of plasma proteins can be used in therapeutic or preparative apheresis. The development of these particles may benefit from an improved knowledge of the relationship between protein adsorption and the structure of ligands. Nanoparticles were functionalized with aliphatic diamines of increasing chain length; with the amino acids lysine, tryptophan, histidine, and their corresponding amines; and with tryptophan and histidine spaced with diamines of different length. Suitable protocols were developed for the washing of particles and the subsequent desorption of proteins adsorbed from human plasma. The adsorption pattern, as well as the quantification of the overall adsorption of proteins on these modified particles, was investigated with gel electrophoresis. This was followed by immunoblotting which yielded specific assessments of bound human serum albumin and fibrinogen. The comparison of protein adsorption with surface charge density and measured hydrophobicities yielded no simple correlations although in general more hydrophobic ligands bound higher quantities of protein. The detection of human serum albumin yielded similar results because it was observed for overall protein adsorption while the adsorption of fibrinogen expressed a different pattern. In this case, particular nanoparticles functionalized with aliphatic diamines bound significantly higher amounts of fibrinogen than all other ligands.

Adsorption↗

Functionality of MDCK kidney tubular cells on flat polymer membranes for biohybrid kidney.

The prerequisite for the development of a biohybrid artificial kidney, is a substrate for confluent growth of renal cells forming an epithelial monolayer without any leaks. Conventional cell culture supports cannot be adapted for this purpose, because they lack adequate mechanical properties and thermal stability. From two suitable materials, polysulfone and polyacrylonitrile, two permeable polymeric membranes have been produced that were, according to ISO 10993-5, not cytotoxic. Cloned Madin Darby Canine Kidney (MDCK) cells (an established renal cell line) were cultured on the surface of the plastic materials, and on conventional cell culture supports. With all materials, assays of mitochondrial and lactate dyhydrogenases exhibited similar proliferation and the viability of the MDCK cells. Transmission electron microscopy showed the expression of a normal morphology of kidney tubular cells. Perfect barrier function, consequent on the formation of intercellular junctions in a confluent tight epithelium, was visualized in electron micrographs, and quantified by measurement of the transepithelial resistance. The uniformity of the cells grown was demonstrated in samples by electron microscopy and in the whole epithelium by intravital impedance analysis. It was concluded that polymeric membranes produced from polysulfone or polyacrylonitrile are appropriate substrates in the design of biohybrid kidney devices.

Journal Article↗

Fertility after chemotherapy for testicular germ cell cancer.

OBJECTIVE: To investigate the impact of cytostatic chemotherapy on long-term fertility in patients with testicular germ cell cancer. BACKGROUND: Many patients with testicular germ cell cancer show impaired spermatogenesis before undergoing cytotoxic chemotherapy. The known infertility before treatment and the reversibility of the fertility problems observed in some of them after successful anticancer treatment so far have prevented an assessment of the true impact of chemotherapy on long-term fertility. The introduction of a wait-and-see strategy (surveillance) for patients with testicular cancer and recent prospective trials comparing patients with and without cytotoxic chemotherapy now have provided the means for estimating the extent to which chemotherapy itself affects long-term fertility. RESULT(S): Whether spermatogenesis is impaired irreversibly by chemotherapy is determined by the cumulative dose of cisplatin. At cumulative doses > 400 mg/m2, irreversible impairment of gonadal function should be expected. CONCLUSION(S): At cumulative cisplatin doses < 400 mg (equivalent to 4 courses of state-of-the-art treatment), chemotherapy is unlikely to cause irreversible damage to fertility.

Antineoplastic Agents↗

Testis-preserving surgery in bilateral testicular germ cell tumours.

OBJECTIVE: To evaluate the indications, techniques and outcome of organ-preserving tumour enucleation in patients with bilateral testicular germ cell tumours (BTGCT) rather than standard bilateral radical orchidectomy which results in loss of fertility and a lifelong requirement for androgen replacement. PATIENTS AND METHODS: In 13 patients with BTGCT of 6-30 mm in diameter, the tumours were enucleated under cold ischaemia after inguinal testicular exploration, and biopsies of the tumour bed and the peripheral parenchyma were taken. Histology of the orchidectomy specimen revealed a seminoma in four cases, an embryonal carcinoma in three, a teratocarcinoma and a mixed-germ cell tumour in two each, and a mature teratoma in one. Histology of the enucleated tumours showed a seminoma in seven cases, an embryonal carcinoma in five and a mature teratoma in one. Six of the 13 patients underwent testicular radiation (20 Gy) for carcinoma in situ (CIS) and five patients had adjuvant local therapy. Six months postoperatively a testicular biopsy was taken to determine the success of therapy. RESULTS: The median follow-up was 62 months (range 14-163) and the 13 patients are currently free of disease; one patient had local recurrence 9 months after tumour enucleation but after orchidectomy the patient is free of disease after a follow-up of 156 months. Serum concentrations of luteinizing hormone and testosterone were within the normal range in all patients and no androgen substitution was necessary. A testicular biopsy taken 6 months post-operatively revealed Sertoli cells only in all patients who had received radiation therapy. CONCLUSIONS: These results suggest that organ-sparing surgery in patients with BTGCT represents a new therapeutic approach with endocrinological and psychological advantages. In our experience, enucleation resection of testicular tumours is possible with certain prerequisites, i.e. the tumour is organ-confined with no infiltration of the rete testis, multiple biopsies of the tumour bed and peripheral parenchyma should be taken, any associated CIS treated by radiation therapy, and patients must be followed closely.

Carcinoma in Situ↗

Contact activation of plasmatic coagulation on polymeric membranes measured by the activity of kallikrein in heparinized plasma.

Kallikrein is involved in the generation of bradykinin during extracorporal circulation, that is believed to play an important role in cases of anaphylactic shock during hemodialysis. Therefore, a method for the assessment of kallikrein generation was developed, based on the chromogenic substrate S-2302. Comparison of kallikrein-like activity on glass using citrate or heparinized plasma demonstrated enhanced activity in the presence of heparin. The applicability of the assay, and the time course of kallikrein generation was demonstrated with glass and cuprophan. Membranes based on pure polyacrylonitrile, or its copolymers differing in their content of acrylic acid, 2-hydroxyethyl acrylate, and allylsulphonate were investigated with respect to kallikrein-like activity, and physicochemical surface properties. It was found that high content in 2-hydroxyethyl acrylate, and acrylic acid caused a substantial activation of the contact system while low content in allylsulphonate (less than 2 mol%) did not result in enhanced kallikrein-like activity. The activating materials were characterized to be highly wettable, and had the most negative zeta potentials.

Acrylates↗

Morphological evidence for a different fibronectin receptor organization and function during fibroblast adhesion on hydrophilic and hydrophobic glass substrata.

A polyclonal antibody against the beta 1 subunit of the fibronectin (FN) receptor was used to mimic the early events of integrin receptor functioning to study the initial cellular processes during the organization of FN matrix on biomaterials. Hydrophilic glass and hydrophobic octadecylsilane (ODS) surfaces have been applied as models for different biocompatible materials. By immunofluorescence we could demonstrate that FN receptors organize on the dorsal cell surface of adhering fibroblasts in a specific linear pattern along with actin filaments, but only if the cells were attached to hydrophilic glass. In contrast, FN receptors were not reorganized on hydrophobic octadecylsilane (ODS). In parallel experiments, FN matrix formation after 72 h of incubation on the same substrata has been analyzed microscopically, and quantified by cell ELISA, in order to be further correlated with the integrin receptor functioning in contact with the biomaterials. It was found that FN structuring and the amount of FN matrix have been significantly diminished on ODS that was related to the observed changes in integrin receptor functioning. To learn more about the mechanism of this phenomenon, desorption of 125I-FN from these substrata was studied and found to be significantly decreased on hydrophobic ODS. As a consequence, FN receptor (function) might be arrested on the ventral cell surface, thus the important role of beta 1 integrins in the positional organization of the FN matrix may be disturbed. In light of these facts, antibody-induced clustering of FN receptor can be considered as a useful model for studying the early steps of FN matrix formation on biomaterials.

Adsorption↗

Adjuvant chemotherapy for high-risk clinical stage I nonseminomatous testicular germ cell cancer: long-term results of a prospective trial.

PURPOSE: To assess the impact of short-term adjuvant chemotherapy on relapse rates, treatment-related morbidity, and long-term toxicity in patients with clinical stage I nonseminomatous testicular germ cell tumor (NSGCT I) who carry a high risk of relapse, ie, who show blood-vessel invasion (VI) by the primary tumor. PATIENTS AND METHODS: From January 1985 to January 1995, 42 NSGCT I patients with VI were treated with two courses of cisplatin, etoposide, and bleomycin (PEB) after orchidectomy. Of these, 29 patients with a follow-up time of more than 2 years are the subject of this report. NSGCT I patients without VI were assigned to a surveillance program and served as controls for the assessment of long-term toxicity. RESULTS: During a median follow-up time of 79 months (range, 27 to 119), two patients relapsed. One developed fully differentiated mature teratoma; the other was a true chemotherapy failure and again developed embryonal carcinoma. Twenty-seven patients (93%) are alive without evidence of disease; one patient (3%) died of progressive testicular cancer and another of lung cancer. The two courses of PEB did not cause any severe acute adverse reactions. The assessment of late sequels of adjuvant chemotherapy based on clinical and laboratory evidence of cardiovascular and pulmonary disease, fertility, and secondary neoplasms, as well as on a psychosocial questionnaire, did not show any significant disadvantages versus the control group. CONCLUSION: Adjuvant chemotherapy with two courses of PEB is an effective and reasonable treatment option for patients with clinical stage I NSGCT who carry a high risk of relapse. No adverse late sequelae were detected within a median follow-up time of more than 6 years.

Adolescent↗

Acute and chronic anti-inflammatory properties of [2,2-dimethyl-6-(4- chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl]-acetic acid.

The carrageenan-induced paw oedema in the rat was chosen as the experimental model for acute antiphlogistic activity. ED50 values of 3 mg/kg p.o. for indometacin and of 17 mg/kg p.o. for [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2, 3-dihydro-1H-pyrrolizine-5-yl]-acetic acid (ML 3000) at calculated plasma levels (micrograms/ml) of approximately 5.0 and 20.0 were recorded for indometacin and ML 3000, respectively. The activity ratio of indometacin: ML 3000 is therefore about 1:6 with regard to the oral dose and about 1:4 with regard to the calculated plasma level. Indometacin is more potent than ML 3000 on the one hand, but on the other hand ML 3000 is better tolerated by the stomach in this experimental study: the ulcerogenic dose UD50 (indometacin) is 7 mg/kg p.o., whereas ML 3000 is tolerated well up to the highest tested dose of 100 mg/kg p.o. The adjuvant arthritis in the rat served as the model for chronic antiphlogistic activity. ML 3000 at doses of 20 mg/kg/d p.o. and higher, and indometacin at a dosage of 2 mg/kg/d p.o. produced a similar rate of reduction of the adjuvant-induced secondary lesions and paw swelling of the injected and uninjected paws, following prophylactic as well as therapeutic treatment with the compounds.

Acetates↗

Cluster analysis of MCMI and MCMI-II on chronic PTSD victims.

A cluster analysis was used to identify groups of inpatients with confirmed post-traumatic stress disorder (PTSD) due to combat. In Study 1 the MCMI was administered to 256 subjects, in addition to the MMPI, PTSD measures, and background variables. Three clusters resulted: a Traumatic Personality (8-2), Schizoid Influence (8-2-1), and Antisocial Influence (8-6). Comparison on the MCMI symptom scales, MMPI, and PTSD scales showed that the Antisocial Influence cluster was "healthier" on all measures. The Schizoid Influence was most psychopathological. In Study 2 the MCMI-II was administered to 136 new subjects who met the same criteria as in Study 1. Four clusters resulted: Global (1-2-6A-6B-8A-8B), Subclinical (1), Aggressive (6A-6B-8A), and Detached/Self-defeating (1-2-8A-8B).

Adult↗

Management of ureteric stones.

Based on experience with over 2,000 patients, the treatment of ureteric stones today relies on extracorporeal shock wave lithotripsy (ESWL) in situ and ureteroscopy with semirigid, ultrathin ureteroscopes combined with pneumatic or laser lithotripsy. All stones in the upper and larger stones in the distal third of the ureter are preferably treated by ESWL in situ, whereas smaller stones in the distal ureter are better treated by endoscopy. Midureteric stones continue to be the domain of primary ureteroscopy; in cases of moderate obstruction in asymptomatic patients, it may also be acceptable to wait for the stone to pass into the distal ureter spontaneously to be treated by ESWL in situ there. Manipulation of the stone back into the kidney and treating it by ESWL there (push back/ESWL) offers no advantage over ESWL in situ, as results are not better yet morbidity is higher. 'Blind' instrumentation has lost all justification, and incisional ureteric lithotomy is no longer indicated but in exceptional cases.

Endoscopy↗

[Topical immunotherapy (KLH) vs. chemotherapy (Ethoglucid) in prevention of recurrence of superficial bladder cancer. A prospective randomized study].

A prospective randomized controlled study on the effect of KLH (keyhole limpet hemocyanin) versus etoglucid in the prevention of recurrences in primary and recurrent superficial transitional cell carcinoma of the bladder (stage pTa-pT1, grades 1-3 according to the recommendations of UICC and WHO) after complete transurethral resection of the tumor started in 198. Patients in group 1 (n = 76) were immunized with 1 mg KLH intracutaneously, after which they received bladder instillations of 30 mg (30 ml) KLH weekly for 6 weeks and then monthly for 1 year. Patients in group 2 (n = 85) received weekly bladder instillations of 0.565 g etoglucid (50 ml 1% solution) for 6 weeks and then monthly for 1 year. The percentage of recurrences, recurrence rate, disease-free interval and tumor progression rate were evaluated for both treatment groups. The end-point of the study was progression in stage or grade or more than two recurrences during the observation period. The shortest follow-up was 12 months, the mean follow-up, 27.5 months. No statistically significant differences were found between the two groups in percentage of recurrences (43.4% KLH-53.9% etoglucid), recurrence rate (4.4 KLH-3.9 etoglucid), mean disease-free interval (12.1 months KLH-13.6 months etoglucid) or progression rate (6.5% KLH-9.4% etoglucid).

Adjuvants, Immunologic↗

Prospective, randomized trial to evaluate high-versus low-dose interferon-alpha 2b versus conventional chemotherapy in prevention of the recurrence of superficial transitional cell carcinoma of the urinary bladder.

Forty-four patients with superficial bladder cancer were randomized to receive 10 MU (14 patients) or 100 MU (14 patients) of interferon (IFN)-alpha 2b or 1.3 g ethoglucid (16 patients) instilled into the bladder once weekly for 10 weeks and then monthly for 1 year. Efficacy (evaluated in 34 patients who completed the course of treatment), based on recurrence rate and time to first recurrence, was similar in the three groups. No systemic toxicity of treatment was seen. Severe chemocystitis occurred in some patients who received ethoglucid (three had to discontinue treatment), while no local toxicity was seen with IFN-alpha 2b treatment.

Adult↗