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Biomedical subjects

S Winkler

Publications and source records attributed to S Winkler.

At least 109 records · Page 6Linked to original sources

Prediction of graft dysfunction by analysis of liver biopsies after cold storage.

Failure of the hepatic allograft continues to be a serious life-threatening risk for the recipient. Because no effective method of extracorporeal support is available for these patients, early retransplantation is the only alternative that offers the potential for survival. The aim of this prospective analysis was to search for a predictor of primary non-function of hepatic allografts before reperfusion. From March to June 1993 we investigated 19 liver biopsies which were obtained during the preparation of the donor liver in the back table bath immediately before the implantation of the organ. All organs were preserved by UW solution. Biopsies were stored at -80 degrees C, the working-up process was started by dividing the biopsy into several portions for the determination of fat (petrol-ether extraction), water (weighing before thawing and after drying) and free amino acids (OPA-HPLC method). Graft function was categorized into three groups: (1) good function; (2) fair function; (3) primary non-function (PNF). In addition to known risk factors for delayed graft function such as a long stay of the donor in intensive care and a prolonged anhepatic period of the recipient, we were able to demonstrate that organs with malfunction had a higher fat and water content. Donor livers developing PNF showed a trend towards higher total and subdivided amino acids, which could be explained by the incapacity of the liver to utilize available substrates for gluconeogenesis.

Biopsy↗

The effect of soldering, electrowelding, and cast-to procedures on the accuracy of fit of cast implant bars.

The effect of three different connecting procedures on the accuracy of fit of cast implant bars over their supporting abutments was investigated. Thirty Hader implant bars were waxed on a master cast over two abutment analogs and cast in a type IV gold alloy. The bars were sectioned and divided into three groups of ten implant bars according to the connecting procedure that was to be followed. Group 1 bars were connected by soldering, Group 2 bars were connected by electrowelding, and Group 3 bars were connected with the cast-to procedure. The accuracy of fit of each group of bars was measured at the gold cylinder-abutment interface in microns using a stereomicroscope. The use of the cast-to procedure resulted in a more accurate fit as compared with the soldering and the electrowelding techniques.

Analysis of Variance↗

A simplified method for measuring photomicrographs.

An accurate technique that simplifies measurements of two- and three-dimensional specimens is presented. Photomicrographs of a microruler and of the specimens of a research project were made at the same magnification. A ruler with the exact dimensions of the photographic prints of the microruler was generated through computer graphics and printed as a transparency. After verification, the ruler was used to measure specimens directly on the photomicrographs.

Dental Prosthesis Design↗

The use of casting investments for soldering gold implant bars: a pilot study.

The use of gypsum- and phosphate-bonded casting investments for soldering gold implant bars was investigated. Eighteen gold implant bars were sectioned and divided into two groups of nine specimens each. One group of bars was invested with gypsum-bonded investment and the other group invested with phosphate-bonded investment. The accuracy of fit of each group was measured at the gold cylinder-abutment interface in microns using a stereomicroscope. The use of gypsum-bonded investment resulted in a more accurate fit as compared with phosphate-bonded investment.

Analysis of Variance↗

Microfilarial clearance in loiasis involves elevation of Th1 and Th2 products and emergence of a specific pattern of T-cell populations.

Diethylcarbamazine (DEC) induced clearance of microfilaraemia in loiasis is associated with severe posttreatment reactions. To define the switch from hypo- to hyper-responsiveness associated with DEC treatment, phenotypic alterations of T-lymphocytes, characterized by flow cytometry, and cytokines, determined by enzyme linked immunosorbent assay, were monitored in a microfilaraemic patient. In contrast to reports on onchocerciasis and lymphatic filariases, no elevation of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha was observed. The most severe side effects coincided with an elevation of interferon (IFN)-gamma on day 3, followed by IL-10, transforming growth factor (TGF)-beta 2 and macrophage inflammatory protein-1 alpha (MIP-1 alpha) peaking on day 5. Phenotypically, T-cell activation markers CD38, CD54 and CD25 were significantly expressed before treatment, with high CD38 expression still existing one year after clearance of microfilaraemia. Treatment-related increases were observed with anti-CD122, anti-HLA-DR and anti-CD69. CD28 was expressed before treatment on almost 100% of CD4+ and CD8+ T cells and dropped to 20% by day 5, reaching again baseline levels on day 21. Furthermore, there emerged 20% TCR alpha beta+/CD3+ T cells and 10% anti-beta V5(c)+ T cells, altogether indicating a specific pattern of T-helper (Th) 1 and Th2 cytokines as well as expansion of certain pauciclonal T-cell populations in response to microfilarial clearance.

Adult↗

Gastric mucormycosis due to Rhizopus oryzae in a renal transplant recipient.

Gastric mucormycosis is a rare disease with a reported fatal outcome of 98%. Manifestations range from colonization of peptic ulcers to infiltrative disease with vascular invasion and dissemination. In our renal transplant patient a deep gastric ulceration infected with Rhizopus oryzae (class Zygomycetes), which is known to be an agent of mucormycosis, was diagnosed in the early posttransplant period after antirejection therapy. The infection was successfully managed with amphotericin B and omeprazole.

Adult↗

Serum levels of erythropoietin in acute Plasmodium falciparum malaria.

The pathophysiologic backgrounds of anemia in malaria are complex and multifactorial. The purpose of the present study was to measure serum concentrations of erythropoietin (EPO) and to evaluate the adequacy of EPO production in patients suffering from acute Plasmodium falciparum malaria. Fifteen patients with complicated malaria were included in the study. Serum samples were taken on the day of admission, and days 7, 14, 21 and 28. Serum EPO concentrations were measured using an enzyme-linked immunosorbent assay. The median serum EPO concentration was 15.6 mU/ml on the day of admission (range 0.5-567) mU/ml, 10.6 mU/ml (1.2-863) on day 7, 11.8 mU/ml (0.5-72.8) on day 14, 10 mU/ml (0.5-74.6) on day 21, and 8.3 mU/ml (2.2-61.6) on day 28. Inadequate EPO production was found in 46.6% of the patients on the day of admission, which increased to 67% and 68% on days 7 and 14, and reached a maximum of 80% on day 21. Almost 54% of patients had inadequate EPO production on day 28. Our data indicate inadequate EPO production in patients suffering from acute P. falciparum malaria, which might contribute to the prolonged anemia observed in these patients.

Acute Disease↗

[African eye worm as initial manifestation of loaiasis].

HISTORY AND CLINICAL FINDINGS: A 23-year-old woman suddenly had the sensation of a foreign body in her right eye. On looking into the mirror she saw what looked like a moving worm-like structure in the lateral angle of the eye. The patient had visited Cameroon 2 years previously. TESTS: On ophthalmological examination with a slit-lamp a transparent worm, 6-7 cm long, was seen. Laboratory tests showed an eosinophilia of 13%, C-reactive protein slightly raised to 1.25 mg/dl and IgG of 2100 mg/dl (IgE was normal at 33 U/ml). Giemsa staining of a whole-blood drop contained numerous microfilaria typical of Loa loa (2000/ml). Filaria serology with antigen of Dipetalonema vitae (Acanthocheilonema) gave a positive response. TREATMENT AND COURSE: The worm was removed surgically and, after a test dose, diethylcarbamazine, 6 mg/kg daily), was administered. Although methylprednisolone (initially 20 mg daily) was given concurrently, a fever of 38,5 degrees C developed on the 4th day. At the same time, streaky cutaneous eruptions were noted over the left lower arm and left knee bond. These two signs, which were due to two adult worms, disappeared within 2 days. On the 5th day the patient complained of headache, nausea and sensitivity to light, and she had meningism. The symptoms were treated with paracetamol and diazepam and quickly improved. The patient was discharged after 3 weeks. Further treatment cycles with diethylcarbamazine are planned.

Acetaminophen↗

Influence of glutamine on the phenotype and function of human monocytes.

Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.

Adenosine Triphosphate↗

Arginase release following liver reperfusion. Evidence of hemodynamic action of arginase infusions.

Immediately after hepatic reperfusion in human orthotopic liver transplantation, high amounts of arginase are released from the graft, thereby influencing nitric oxide metabolism. This metabolic alteration may be one component of the ischemia-reperfusion syndrome in OLT with its hemodynamic disturbances (e.g., systemic hypotension, pulmonary hypertension). The aim of this study was to compare hemodynamic and metabolic changes following OLT in the pigs with those obtained under arginase infusions in catheterized, anesthetized pigs. Following liver revascularization in the pigs, plasma arginase concentrations increased from 48 +/- 19 IU/L to 2613 +/- 944 IU/L, resulting in a drop in plasma levels of L-arginine (-87%) and in a drop in nitrite (-82%) and nitrate (-53%) concentrations. Of the measured organ-specific hemodynamic alterations, the mean pulmonary arterial pressure increased from 17 +/- 2 mmHg to 30 +/- 5 mmHg, whereas the flow/pressure index of the portal vein decreased about 60%. A primed continuous infusion of arginase (25,000 IU) increased plasma arginase levels to a maximum of 3,690 +/- 962 IU and evoked a decrease of L-arginine, but did not alter plasma nitrite or nitrate levels. The administration of arginase in healthy pigs did not influence cardiac output, mean arterial pressure, heart rate, or total peripheral resistance, but led to an increase of mean pulmonary arterial pressure from 19 +/- 3 to 48 +/- 5 mmHg and to a reduction of arterial hepatic blood flow from 229 +/- 65 ml/min to 154 +/- 41 ml/min. From this we conclude that high levels of liver arginase cause hemodynamic alterations in the lung and the liver. We hypothesize that the pulmonary hypertension and the reduced hepatic blood flow found during the immediate reperfusion period after OLT are possibly related to the increased arginase release due to the hepatic damage of the graft.

Animals↗

Serum CD44 splice variants in cervical cancer patients.

Aberrant expression of the cell adhesion molecule CD44 has been detected in human tumours and has been shown to be associated with metastasis and poor prognosis in human malignancies. We evaluated serum levels of different soluble CD44 molecules (CD44 standard form and CD44 splice variants v5 and v6) in cervical cancer patients stage IB to IIIB. Two-hundred three serum samples were analysed. Serum levels of CD44st and CD44v5 showed no significant correlation with the presence or absence of cervical cancer. The splice variant CD44v6 showed a mean concentration of 227.3 +/- 90.9 (minimum 71.4, maximum 543.9) ng/ml when tumour was present and a mean concentration of 198.7 +/- 135.4 (minimum 67.2, maximum 696.3) ng/ml in cases of complete remission (P-value = 0.0001). However, in this preliminary study the sensitivity/specificity characteristic of CD44v6 was poor.

Adenocarcinoma↗

Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines.

The effects of 1 alpha,25-dihydroxyvitamin D3/calcitriol on the expression of Fc receptors (FcR) for IgA (Fc alpha R), IgE (Fc epsilon RII), and IgG (Fc gamma R) on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac-6, in combination with various cytokines, was examined by flow cytometry. On both monocyte-derived macrophages and the myelomonocytic cell lines, Fc alpha R/CD89 expression was induced by calcitriol alone and additively in combination with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor. Constitutive and interleukin-4 (IL-4)-driven Fc epsilon RII/CD23 expression was markedly diminished on calcitriol-treated U937 cells and monocytes. Fc epsilon RII was also triggered by IFN-gamma, TNF-alpha, and IL-6 on all the cell lines, an effect blocked by calcitriol. On monocytes, the basal level and IFN-gamma-induced Fc gamma RI/CD64 expression was down-regulated by calcitriol and IL-4. The expression of Fc gamma RII/CD32 on monocytes was strongly suppressed by calcitriol. Transforming growth factor-beta induced Fc gamma RIII/CD16 on monocytes, an effect opposed by calcitriol. The ability of calcitriol-treated monocytes to phagocytose IgG-sensitized ox erythrocytes was diminished. Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates Fc alpha R, Fc epsilon RII, Fc gamma RI, and Fc gamma RII expression on human mononuclear phagocytes, as well as Fc gamma R-mediated phagocytosis.

Calcitriol↗

Acute effects of insulin-like growth factor I on interorgan glucose and lactate flux in protein-catabolic dogs.

Insulin-like growth factor-I (IGF-I) is a potent protein-anabolic hormone with a glucose-lowering effect and is therefore a possible agent for treating catabolic patients. In this study we investigated the effect of recombinant human (rh) IGF-I on the interorgan flux of glucose under hypo- and normoglycemic conditions in catabolic, anaesthetized, and catheterized dogs. We administered a primed (40 micrograms/kg) continuous (1.5 micrograms.kg-1.min-1) infusion of rhIGF-I (Kabi Biopharma, Stockholm, Sweden) for 180 min together with either a saline (0.9% NaCl) or an amino acid solution (2.2 mg AA.kg-1.min-1 solution of Vamin, Kabi Nutrition, Stockholm, Sweden). RhIGF-I administration lowered plasma glucose levels for approximately 50% of the baseline (P < 0.001) and stimulated glucose uptake from skeletal muscle about twofold (P < 0.01), but did not modify glucose balances across the gut and liver. The same effects were found when infusing rhIGF-I together with AA. A co-infusion of rhIGF-I and glucose to maintain normoglycemic conditions stimulated glucose uptake from skeletal muscle by about fivefold (P < 0.001) and glucose uptake across the gut by about 50%, but reduced the hepatic glucose liberation (-65%; P < 0.01). The rhIGF-I infusion did not alter arterial lactate levels, but stimulated lactate release from skeletal muscle (P < 0.05) and lactate uptake across the liver (P < 0.05). We conclude that rhIGF-I reduces plasma glucose levels mainly by stimulating glucose uptake across skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunohistochemical and serological evaluation of CD44 splice variants in human ovarian cancer.

The surface glycoprotein CD44 is widely distributed in different tissues. In contrast to healthy tissue, tumour samples show a more complex pattern of CD44 expression, indicating a loss of splice control. Beside cell-surface expression, the measurement of soluble CD44 in serum of cancer patients could be useful in early diagnosis and assessment of disease status. We evaluated the surface expression of CD44 isoforms in 22 ovarian cancer patients by means of immunohistochemistry. Additionally, we investigated 134 serological samples of these patients for the occurrence of CD44 isoform expression. For CD44 standard, CD44v5 and CF44v6 mean serum levels in patients with clinically detectable or non-detectable ovarian cancer were 422.4 +/- 143.8 ng ml-1 and 547.4 +/- 148.2 ng ml-1, 12.3 +/- 7.9 ng ml-1 and 21.9 +/- 12.2 ng ml-1 and 105.5 +/- 37.9 ng ml-1 and 144.9 +/- 50.9 ng ml-1 respectively (P-values not significant). CD44 surface proteins containing epitopes encoded by splice variants CD44v5, CD44v6 and CD44v7-8 were immunohistochemically detected in 9% (n = 2), 13% (n = 3) and 4% (n = 1) of the 22 tumour samples respectively. In the present study we showed that in ovarian cancer CD44 isoforms CD44v5 and CD44v6 are expressed in very low amounts by the tumours. In accordance with this, we found that the presence of tumour is not associated with higher serum levels of CD44standard, CD44v5 and CD44v6 in preoperative serum samples in ovarian cancer patients.

Adult↗

Resistance of nitrogen metabolism to growth hormone treatment in the early phase after injury of patients with multiple injuries.

OBJECTIVES AND DESIGN: Several studies have shown an anticatabolic effect of recombinant human growth hormone (rhGH) in surgical patients. We investigated, in a prospective, randomized, double blind, and placebo-controlled study, the effect of r-hGH on hormone and nitrogen metabolism in 14 patients with multiple injuries in the early phase of injury. MATERIALS AND METHODS: All patients were treated in the intensive care unit, had mechanical ventilation, and were highly catabolic, with a mean daily nitrogen loss of 13.2 +/- 1.8 g. r-hGH was given subcutaneously (once a day, at 8 PM) in a dosage of 0.2 IU/kg.d for seven days, starting on the second day after injury. RESULTS: Administration of r-hGH evoked a significant increase in plasma concentrations of GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding-protein-3 (IGFBP-3). No significant differences were found for either daily or cumulative nitrogen balances (-103.1 +/- 14 g for patients receiving r-hGH and -92.1 +/- 18.1 for those with placebo). r-hGH therapy did not affect skeletal muscle extracellular water, nor did it affect plasma or muscle concentrations of total free amino acids or glutamine. Plasma albumin, prealbumin, and retinol-binding protein concentrations were also unchanged by r-hGH therapy, as were the urinary excretion of potassium and urea. CONCLUSIONS: We conclude that elevated plasma levels of GH, insulin, and IGF-I are unable to effect a protein anabolic drive in patients with multiple injuries during the early postinjury phase and assume that this r-hGH resistance to nitrogen metabolism takes place at the level distal to IGF-I.

Adult↗

Dual-tray impression technique for implant-retained overdentures.

Accurately recording implant positions and the edentulous areas during the fabrication of implant-retained overdentures can be a difficult task. A modification of the dual or split-tray technique is suggested for implant-retained overdentures. This procedure permits the construction of the prosthesis on one master cast and the use of two impression materials with different properties incorporated into a single impression to correspond with the needs of specific anatomic areas of the mouth.

Dental Casting Technique↗

Connecting implant framework segments.

Indexing and soldering an implant bar can be a troublesome procedure. The expansion of the soldering investment may result in an inaccurate fit of the implant framework over the abutments or the implant heads. To overcome the distortion of the implant framework during soldering, a simple procedure for connecting the implant framework parts is described where the connector joints are cast-to rather than soldered.

Dental Casting Technique↗