Search PubMed⌕ Search

Biomedical subjects

R Fischer

Publications and source records attributed to R Fischer.

At least 379 records · Page 21Linked to original sources

Classification of Hodgkin's disease biopsies by a panel of four histopathologists. Report of 1,140 patients from the German National Trial.

First results from reviewing the diagnostic biopsies of Hodgkin's lymphomas (HL) are reported. Biopsies from 1,140 patients were evaluated by consensus diagnoses according to an extended classification of the British National Lymphoma Investigation. 95 of the recruited cases (8.3%) were omitted and not approved as Hodgkin's lymphoma. The remaining 1,045 biopsies were classified as follows: Lymphocytic predominance 31 (2.7%); Nodular sclerosis (NS) 660 (57.9%), Mixed cellularity (MC) 159 (13.9%); Lymphocytic depletion 8 (0.7%); unclassifiable Hodgkin's 148 (13.0%). The unproved Hodgkin's cases [95 (8.3%)] were divided into non-Hodgkin's lymphomas 32 (1.9%), uncertain due to inadequate techniques 32 (2.8%), borderline between Hodgkin's- and Non-Hodgkin's lymphoma 23 (2.0%). Major dissent on this question involved 17 cases (1.5%) and 1 case which was non-malignant. All unclassifiable, borderline or dissent cases were reassessed after the histologic techniques were improved, and immunophenotyping and clinical data reevaluated. The rate of agreement among the observers was about 81.6%, varying between 23.8% in grade 2 NS to 85.0% in both NS groups. Only 62.8% of all primary diagnoses were approved by the final diagnoses of the panel. Important differences in the classification of the British National Lymphoma Investigation concerns the NS-group and mainly its grade 2 subtype. MC was identical in both classifications. Clinico-pathologic correlation of actuarial survival times revealed a significantly worse outcome of MC vs NS, < 20% after 80 months observation. Only slightly significant better survivals were found in grade 1 vs grade 2 NS. Significant differences in unclear compared to all Hodgkin's, were found and the worst survival was in the NHL group.

Biopsy↗

In vivo binding of radiocesium by two forms of Prussian blue and by ammonium iron hexacyanoferrate (II).

The effect of two forms of Prussian blue, soluble K3 Fe[Fe(CN)6] and insoluble Fe4[Fe(CN)6]3, and of ammonium iron hexacyanoferrate (II) (NH4Fe[Fe(CN)6] on intestinal radiocesium absorption was investigated in rats, pigs, and humans. In rats 5 mg of antidote administered 2 min before 134Cs tracer reduced radiocesium absorption to 2.4-6.3% of the oral dose. In pigs fed with Chernobyl-contaminated whey under normal feeding conditions for a 27 day period, radiocesium activity concentration was reduced from 360 Bq/kg in control animals to 10-30 Bq/kg by 5 g antidote/d. In man 1 g of oral Prussian blue diminished the cesium absorption from a 134Cs-labelled test meal to 5.6-6.4% of the controls. The inhibitory effects of colloidally soluble K3 Fe[Fe(CN)6] and of (NH4Fe[Fe(CN)6] were similar with slightly less inhibition by the insoluble Fe4[Fe(CN)6]3.

Administration, Oral↗

[Monoclonal antibodies (MIB 1, PC 10, 486p and p53) as prognostic factors for recurrent urothelial carcinoma of the urinary bladder].

Using an immunohistochemical method expression of PCNA, Ki-67, 486p and p53 antigen was investigated in paraffin sections of 119 patients with primary transitional cell carcinoma of the bladder. The purpose of this study was to detect recurring G1 and G2 bladder tumours compared with non-recurrent tumours. A relative large fraction of labelled cells for PCNA and Ki-67 was found in recurring G1 and G2 carcinomas. Moreover, recurrent transitional cell carcinomas showed a more positive staining pattern for 486p and p53, in contrast to non-recurrent carcinomas. Immunohistochemistry of these four antigens seems to yield additional information about the possibility of recurrence in G1 and G2 bladder carcinomas, thus allowing early, i.e. more aggressive, therapy.

Antibodies, Monoclonal↗

Effects of combined administration of interleukin-6 and granulocyte colony-stimulating factor on recovery from radiation-induced hemopoietic aplasia.

Hemopoietic aplasia is the primary limitation of drug and radiation cancer therapies. We have previously demonstrated that, individually, both interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF) can accelerate recovery from radiation-induced hemopoietic aplasia. In vitro studies suggest that IL-6 affects cells early in the hemopoietic hierarchy, while G-CSF affects more committed progenitor cells. Because these cytokines may also affect different cell populations in vivo, we hypothesized that the use of these agents in combination may further enhance recovery from hemopoietic aplasia. Female B6D2F1 mice were exposed to a high sublethal 7.75 Gy dose of 60Co radiation. Following irradiation, mice were administered subcutaneous injections of either saline, 500 micrograms/kg of recombinant human IL-6 once daily on days 1-6, 125 micrograms/kg of recombinant human G-CSF once daily on days 1-17, or both cytokines as described. Peripheral white blood cell (WBC), red blood cell (RBC), and platelet (PLT) counts, as well as femoral and splenic granulocyte-macrophage colony-forming cell (GM-CFC) and day-12 spleen colony-forming unit (CFU-S) contents were evaluated on days 7, 10, 14, 17 and 21 postirradiation. IL-6 treatment alone slightly accelerated postirradiation recovery of most hemopoietic parameters, while G-CSF treatment dramatically enhanced recovery of all hemopoietic parameters evaluated. Co-administration of IL-6 and G-CSF further enhanced the hemopoietic recovery. The most notable effects in combination-treated mice were on recoveries of bone marrow and splenic CFU-S, which were significantly enhanced above those in G-CSF-treated irradiated mice as early as day 10 postirradiation. Although by day 14 postirradiation, splenic GM-CFC and CFU-S recoveries in both G-CSF- and combination-treated mice had surpassed unirradiated control values, combination-treated mice exhibited a greater overshoot. These studies demonstrate the ability of IL-6 treatment to enhance G-CSF-mediated acceleration of multilineage recovery following radiation-induced hemopoietic aplasia.

Animals↗

Erythropoiesis in CML--immunomorphometric quantification, PCNA-reactivity, and influence on survival.

An immunohistochemical and morphometric analysis was performed on trephine biopsy specimens in 60 patients with chronic myeloid leukemia (CML) to quantify erythropoiesis and its proliferation capacity and to assess the stainable marrow iron (hemosiderin). For this purpose, an elaborate double-immunostaining technique was applied. This included a monoclonal antibody (PC10) that is directed against proliferating cell nuclear antigen (PCNA), followed by an antibody against glycophorin C (Ret40f), to identify all nucleated erythroid precursor cells. Additionally, morphometric data were derived from immunostaining of megakaryocytes (CD61) and macrophages (PG-M1), including its hemosiderin-laden subpopulation. Finally the determination of argyrophilic (reticulin) fiber density was carried out. In comparison with a control group (15 patients) without any hematologic disorder, in CML patients morphometric evaluation showed a significant reduction in the number of erythroblasts and normoblasts. This feature was associated with a PCNA-labeling index within the normal range and a decreased stainable marrow iron (number of hemosiderin-storaging macrophages). Several parameters were established to exert a predictive value on survival. A worsening of prognosis was associated with a decrease in the number of erythroid precursors (< 460/mm2), a low hemoglobin level (< 10 g/dl), a high megakaryocyte count (> 50 cells/mm2), an increased density of reticulin fibers (> 30 i x 10(2)/mm2) and splenomegaly (> 15 cm below costal margin). Our findings are in keeping with results obtained from in vitro studies of cell proliferation in CML, which is not significantly altered in comparison with the normal bone marrow. Finally, the present data, although derived from a small group of patients, emphasize the impact of histologic variables to be included in one of the major clinical trials on prognosis in CML.

Bone Marrow↗

[Burns in workers in Switzerland: epidemiology and financial sequelae].

A complete statistical evaluation of epidemiologic data and costs of burn injuries in 1984 with a follow-up for 5 years is presented, considering a collective of 1.77 million workers in Switzerland. The majority of burns are minor injuries; only about 5% of the burn victimes are admitted to a hospital, 0.2% die. Only one fifth of the costs caused by burns are due to medical treatment and rehabilitation. All other expenses result from continuation of payments of salaries and annuities. The few treatments of severely burnt patients in the burn units cause effective costs higher than the tariff paid by the insurance. Even so, the predominant portion of the enormous costs is taken up by wages while off work and annuities. As our conclusion we stress the importance of primary care for all severe burns including all burns of the hands in a specialized centre. Any economic effort for primary burn treatment, however high it may be, is justified if the duration of rehabilitation and invalidity can thus be reduced.

Accidents, Occupational↗

[Technique of inverted stripping in varicose vein surgery].

Invaginative Stripping reduces invasivity in varicose veins surgery. Therefore this technique meets increasing popularity. With invaginative stripping however the saphenous vein sometimes tears off. This can be prevented in part of the cases by cutting the branches of the saphenous vein during stripping with the "sickle" (Fig. 1). If this does not work then the remaining parts of the saphenous vein must be stripped in the conventional manner with a stripper head. But: How can the stripper be introduced again into the stripper canal? One end of the tie which is used to knot the saphenous vein to the stripper is left long. In this way the long end of the tie remains in the stripper canal after invaginative stripping. This tie then can be used to pull another stripper into the stripper canal. In order to prevent the ordinary tip of the stripper to be caught in the subcutaneous tissue a special tip is used which we call "dolphin" (Fig. 4). It is a fish-shaped gadget with a mouth or a hook on one side for the tie and a thread at the other side so that the second stripper can be screwed to it. Another possibility is to pull a second stripper after the first one by means of the "torpedo" (Fig. 2) whenever invaginative stripping is intended. The second stripper then can be used for conventional stripping if necessary.

Equipment Design↗

Lung injury from gut ischemia: insensitivity to portal blood flow diversion.

Gut ischemia/reperfusion (I/R) appears to produce pulmonary vascular injury through endotoxin release and cytokine activation. The ability of hepatic reticuloendothelial cells to clear bacterial products may also be impaired during I/R. To test this, diversion of the splanchnic blood flow from the liver into the systemic circulation was performed via a microsurgical portacaval transposition in anesthetized Sprague-Dawley rats (275-375 g). Shunted animals underwent portacaval transposition and were allowed to recover for 7-10 days; sham animals underwent exploration but no shunt was created. The I/R animals were subjected to 60 minutes of reperfusion. All shunts were patent at autopsy. Pulmonary vascular permeability was assessed by measuring tissue retention of Evans blue dye. Gut I/R produced significant increases in pulmonary vascular permeability (46.2% +/- 11.0% vs. 16.4% +/- 3.8% [I/R vs. control]; p < 0.05) regardless of the presence of hepatic bypass (32.7% +/- 9.0% vs. 10.0% +/- 1.4% [I/R vs. control]; p < 0.05). These data indicate that a mediator or mediators of gut origin are responsible for pulmonary vascular permeability changes following gut I/R and are not appreciably modulated by the liver.

Animals↗

[Endoscopic perforant vein revision. Current status].

Blind dissection of incompetent perforators is common practice for vein surgeons. Since many years some of them have been trying to do this endoscopically by means of the proctoscope or other endoscopes used for different purposes. At present, however, several surgeons are developing special instruments for this type of endoscopy. Lately some of these surgeons came together to work up their experiences and to study the probable future of the method. It permits the diagnosis and at the same time the treatment of incompetent perforators. It allows the healthy ones to be spared. All this can be done from a small incision distant to the site of the perforators where the skin often presents with trophic changes. However, general or regional anesthesia as well as the bloodless limb technique are prerequisites. As any endoscopy also this one has its specific dangers and complications and therefore has to be learned and performed carefully.

Angioscopes↗

A prototype multidisciplinary cancer screening clinic for the military medical facility.

Optimal treatment of cancer depends upon early diagnosis. With an aging retiree and dependent population, cancer diagnosis and management must be addressed by military medical treatment facilities (MTFs) in a coherent and cost-effective fashion. A prototype multidisciplinary cancer screening clinic is described which interdigitated MTF and local American Cancer Society resources. Sites screened included breast, prostate, skin, cervix, and oral cavity, with mammograms, prostate-specific antigens, PAP smears, and physical exams, as appropriate. Of 194 patient contacts over a 4-hour period, eight cancers were found and subsequently treated (five skin, three prostate). Patient selection criteria, screening results by site, lessons learned, and recommendations for future clinics are discussed. The multidisciplinary screening clinic is readily applicable to the MTF setting, cost-effective, and provides an invaluable service to eligible patients.

Ambulatory Care Facilities↗

Detection of hematogenous micrometastasis in patients with prostate cancer.

The goal of this study was to determine if patients with stage D0-3 prostatic adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain reaction amplification of prostate-specific antigen mRNA, which is exclusively expressed by prostatic epithelial cells, was used to detect circulating prostatic cells. Peripheral venous blood was obtained from 17 control and 12 prostate cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases, four patients (stage D1-3) tested positive for prostate-specific antigen RNA, indicating the presence of circulating micrometastasis. The 17 negative controls all tested negative. Contrary to a long held hypothesis, these data point to the possibility that hematogenous metastasis may be a relatively early event in the natural history of human prostate cancer. These findings may have an important impact on our understanding and treatment of prostate cancer.

Base Sequence↗

Mannitol-specific enzyme II of the phosphoenolpyruvate-dependent phosphotransferase system of Staphylococcus carnosus. Sequence and expression in Escherichia coli and structural comparison with the enzyme IImannitol of Escherichia coli.

The enzyme IImannitol (EIImtl) of the phosphoenolpyruvate-dependent phosphotransferase system (PTS) catalyses the uptake and concomitant phosphorylation of mannitol by bacteria; it is specified by the gene mtlA. MtlA is located near the genes mtlF and mtlD in the staphylococcal genome, encoding the enzyme IIImtl and the mannitol-1-phosphate dehydrogenase, respectively. We present the cloning of the whole operon by a novel complementation system which is generally suitable for cloning Gram-positive PTS genes. The nucleotide sequence of a 2.5-kbp subclone spanning mtlA has been determined. From the deduced amino acid sequence, it is predicted that the membrane-protein EIImtl consists of 505 amino acid residues (54112 Da). The protein has the expected hydropathy profile of an integral-membrane protein. The NH2-terminal part of the enzyme resides within the membrane, whereas the COOH-terminus of the enzyme has the properties of a soluble protein. Comparison with the known amino acid sequence of EIImtl of Escherichia coli [Lee, C. A. & Saier, M. H. (1983) J. Biol. Chem. 258, 10761-10767] showed significant similarity. The motif containing the cysteine, which is the putative second phosphorylation site in EIImtl of E. coli [Pas, H. H. & Robillard, G. T. (1988) Biochemistry 27, 5835-5839], is well conserved in EIImtl of Staphylococcus carnosus. Chemical modification of the single active site cysteine residue by Ellman's reagent leads to total inactivation, which can be reversed by treatment with 2-mercaptoethanol.

Amino Acid Sequence↗

Impaired cytokine production in whole blood cell cultures from patients with colorectal carcinomas as compared to benign colorectal tumors and controls.

Cytokine production was investigated in whole blood cell cultures from 74 patients with colorectal carcinomas, 20 patients with benign colorectal tumors, and 314 healthy controls. In the 4 day post induction supernatants the levels of IFN-gamma, IL-1-alpha, IL-2, and TNF-alpha were measured by a sensitive immunoassay. In the blood cell cultures of the patients with colorectal carcinomas significantly lower values of IFN-gamma (P less than or equal to .001), IL-1-alpha (P less than or equal to .001), and IL-2 (P less than or equal to .01) were found as compared to the patients with benign tumors and the controls, although total and differential leukocyte counts were similar in all three groups. A linear correlation between the levels of IFN-gamma and IL-1-alpha and the tumor stages could be shown. Our results suggest that a growing tumor burden may induce increasing immunological deficiencies as reflected by a decreasing cytokine production of the immune cells.

Adult↗