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Biomedical subjects

M Winkler

Publications and source records attributed to M Winkler.

At least 19 recordsLinked to original sources
PubMed2007

[Primary nasal natural killer/T-cell lymphomas: classification and clinicopathological features].

BACKGROUND: Nasal NK/T-cell lymphomas are rare malignancies in Europe or North America. Histological diagnosis is difficult, because tumors imbedded in large necrotic areas and neoplastic infiltrates may be admixed with small lymphocytes, plasma cells, eosinophils, and histiocytes, and thus the process could be misdiagnosed as chronic inflammation. Progression of the disease leads to septal perforation and may also result in destruction of the hard palate, and if left untreated it ends fatally. This introduced the term "lethal midline granuloma", a term which should not be used any more. MATERIAL AND METHODS: Clinical features, pathohistology, and current classification of primary nasal NK/T-cell lymphomas are described against the background of the recent literature and a case report. RESULTS: Immunophenotyping is essential for the diagnosis. Tumor cells are uniformly infected by Epstein-Barr virus, which could be verified by EBER in situ hybridization. Immunohistochemically, tumor cells are positive for CD56, cytoplasmic CD3epsilon, and CD2 and they express cytotoxic molecules like granzyme B, TIA-1, GMP17, and perforin. Therapeutic options are radio- or radiochemotherapy. On average, 2- and 5-year survival rates of 50% are obtained in stages I and II. The prognosis of advanced tumor stages is very poor. CONCLUSIONS: Immunohistochemical and molecular genetic early diagnosis is of crucial prognostic relevance.

Adolescent↗
PubMed2006

Selectivity of repaglinide and glibenclamide for the pancreatic over the cardiovascular K(ATP) channels.

AIMS/HYPOTHESIS: Sulfonylureas and glinides close beta cell ATP-sensitive K(+) (K(ATP)) channels to increase insulin release; the concomitant closure of cardiovascular K(ATP) channels, however, leads to complications in patients with cardiac ischaemia. The insulinotrope repaglinide is successful in therapy, but has been reported to inhibit the recombinant K(ATP) channels of beta cells, cardiocytes and non-vascular smooth muscle cells with similar potencies, suggesting that the (patho-)physiological role of the cardiovascular K(ATP) channels may be overstated. We therefore re-examined repaglinide's potency at and affinity for the recombinant pancreatic, myocardial and vascular K(ATP) channels in comparison with glibenclamide. METHODS: K(ATP) channel subunits (i.e. inwardly rectifying K(+) channels [Kir6.x] and sulfonylurea receptors [SURx]) were expressed in intact human embryonic kidney cells and assayed in whole-cell patch-clamp and [(3)H]glibenclamide binding experiments at 37 degrees C. RESULTS: Repaglinide and glibenclamide, respectively, were >or=30 and >or=1,000 times more potent in closing the pancreatic than the cardiovascular channels and they did not lead to complete inhibition of the myocardial channel. Binding assays showed that the selectivity of glibenclamide was essentially based on high affinity for the pancreatic SUR, whereas binding of repaglinide to the SUR subtypes was rather non-selective. After coexpression with Kir6.x to form the assembled channels, however, the affinity of the pancreatic channel for repaglinide was increased 130-fold, an effect much larger than with the cardiovascular channels. This selective effect of coexpression depended on the piperidino substituent in repaglinide. CONCLUSIONS/INTERPRETATION: Repaglinide and glibenclamide show higher potency and efficacy in inhibiting the pancreatic than the cardiovascular K(ATP) channels, thus supporting their clinical use.

ATP-Binding Cassette Transporters↗
PubMed2006

FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia in C57/BL6 mice.

BACKGROUND: Organ dysfunction followed by single-organ or even multiorgan failure due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart transplantation. Various approaches had been attempted to prevent this I/RI. One is the administration of FTY720, a synthetic structural analogue of sphingosine, which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of this study was to evaluate the effect of intraoperative FTY720 administration following controlled bilateral kidney ischemia in comparison to steroid or placebo application. METHODS: Male c57BL6/J mice (n = 115; body weight 25 to 30 g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution. Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours. At termination all surviving animals were sacrificed. RESULTS: Following 30 minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed significant protective effects on long-term survival after controlled bilateral warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a significant T-lymphocyte depletion in peripheral blood after FTY720 treatment, which was not observed after steroid or vehicle treatment. CONCLUSION: The improved long-term survival shown in this study might be due to a protective effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte depletion shown in the FACS analysis.

Animals↗
PubMed2006

[Acute superficial thrombophlebitis--therapeutic strategies].

UNLABELLED: Thrombophlebitis (TP) of the superficial venous system is associated to a high percentage with deep venous thrombosis (DVT). References in literature vary between 5 and 65 %, pulmonary embolisms (LE) were described in up to 33 %. PATIENTS: In a retrospective study, 114 patients who had presented themselves with a TP of the superficial venous system between January 1 (st) and December 31 (st) 2004, were analysed in our institution. 50 % (n = 57) exhibited a TP in side branches of the superficial venous system. 19.3 % (n = 22) showed a TP of the great saphenous vein (GSV) of the calf or of the small saphenous vein (SSV) distally, in 28.1 % (n = 32) the GSV or SSV were affected at the thigh or proximally or in total length, 3 patients (2.6 %) exhibited a TP of the arm vein. 11 patients (9.6 %) showed a concomitant DVT. The frequency of DVT depended on the localisation and extension of the TP, and also on additional basic and acute risks for DVT. The incidence of a concomitant DVT was 5.2 % when side branches were affected and amounted to 15.6 % with TP in the area of the GSV or SSV. With varicosis as single risk factor, the frequency of a concomitant DVT was 6 %, varicosis combined with further risks showed a DVT frequency of 15.4 %. RESULTS: All patients were treated with low molecular weight heparin either with prophylactic or therapeutic dosage, depending on localisation, extension and concomitant diseases. 10.5 % of the patients (n = 12) had to undergo urgent surgery with ligation of the sapheno-femoral junction or popliteal junction, if the TP had reached the junction into the deep venous system. By this therapy, we had not to observe any additional DVT. In 9 cases, an extension, respectively a recurrence of the TP could be observed. In each of these cases the dosage of the LMWH had not been adapted to the concomitant risks or had been terminated too early. DISCUSSION: TP of the superficial venous system should be considered and treated as DVT. Consequent anticoagulation is needed, surgery should be performed when the TP reaches the junction into the deep venous system. The duration of the anticoagulation is not quite clear, but is carried out in our institution for three months with therapeutic intention.

Acute Disease↗
PubMed2006

[Post-traumatic cerebral sodium and water wasting syndrome, CSWS--a case review].

The authors present a case-review of a posttraumatic syndrome with natrium ions and water wasting, resulting in hyponatraemia. The patient concerned was a polytraumatized female patient, with a gradual onset of her symptoms, starting from the day 15 following the trauma. A pharmacological treatment failed. The loss of water and ions was supplemented mainly via i.v. route. 54 days later, the patient had no signs of the syndrome and the substitution could be withdrawn.

Brain Injuries↗
PubMed2005

Simultaneous measurement of beta- decay to bound and continuum electron states.

We report the first measurement of a ratio lambda(beta(b))/lambda(beta(c)) of bound-state ((lambda(beta(b))) and continuum-state (lambda(beta(c))) beta(-)-decay rates for the case of bare 207Tl81+ ions. These ions were produced at the GSI fragment separator FRS by projectile fragmentation of a 208Pb beam. After in-flight separation with the Brho-deltaE-Brho method, they were injected into the experimental storage-ring ESR at an energy of 400.5A MeV, stored, and electron cooled. The number of both the 207Tl81+ ions and their bound-state beta(-)-decay daughters, hydrogen-like 207Pb81+ ions, were measured as a function of storage time by recording their Schottky-noise intensities. The experimental result, lambda(beta(b))/lambda(beta(c)) = 0.188(18), is in very good agreement with the value of 0.171(1) obtained from theory employing spectra of allowed transitions.

Journal Article↗
PubMed2005

[Reversible autonomic dysfunction in a young woman with septic multiple organ dysfunction syndrome].

HISTORY: A 24-year-old woman was admitted for treatment of a meningococcal infection accompanied by fulminant autonomic dysfunction. INVESTIGATIONS: Laboratory tests indicated acute renal failure and disseminated intravascular coagulopathy (creatinine 183 mmol, D-dimer 1.52 mg/l). The initial central venous oxygen saturation was 60-65%. The diagnosis of severe septic shock was supported by a high procalcitonin level of 66.7 ng/ml, CRP of 79.8 mg/l, and a WBC count of 12.2 Gpt/l. TREATMENT AND COURSE: Treatment of sepsis with antibiotics (ciprofloxacin, penicillin G, ceftriaxon and erythromycin in standard dosages), activated protein-C, hydrocortisone and GMA-embedded immunoglobulin led to complete cure and restoration of normal autonomic function. CONCLUSIONS: This case shows that even in multiple organ dysfunction syndrome autonomic dysfunction can occur which is improved by adequate treatment.

Adult↗
PubMed2005

Is cervical dilatation during parturition at term associated with apoptosis?

AIMS: Cellular turnover may be involved in remodeling of the cervix during parturition. Therefore, the number and localization of apoptotic and proliferating cells during cervical dilatation at term were determined. METHODS: Biopsy specimens from the lower uterine segment of 36 women undergoing cesarean section with a cervical dilatation of < 2 cm (n = 10), 2- < 4 cm (n = 9), 4-6 cm (n = 8), and > 6 cm (n = 9) were examined for nuclear fragmentation by the TUNEL assay, and for cell survival by the apoptosis-blocking bcl-2. Proliferation was marked by Ki-67, epithelial cells by cytokeratin and leukocytes by CD 45. For quantification of apoptotic and proliferating cells, eight random fields of each specimen stained for TUNEL or Ki-67 were blindly counted by two investigators. For statistical evaluation, 90% confidence intervals based on a Poisson distribution were used; groups with non-overlapping intervals were considered significantly different. RESULTS: Apoptotic cells were found exclusively within the stromal compartment, while bcl-2 was expressed in epithelial cells and leukocytes. Proliferating cells were of stromal and epithelial origin. The number of apoptotic as well as proliferating cells ranged from 0 to 2 cells per high-power field (median number 0) in all groups. The confidence intervals were overlapping for all groups, showing no statistical difference between them. CONCLUSION: Apoptosis does not seem to play a decisive role in the process of cervical dilatation during parturition at term.

Apoptosis↗
PubMed2004

Precision spectroscopy of pionic 1s states of Sn nuclei and evidence for partial restoration of chiral symmetry in the nuclear medium.

Deeply bound 1s states of pi(-) in (115,119,123)Sn were preferentially observed using the Sn(d,3He) pion-transfer reaction under the recoil-free condition. The 1s binding energies and widths were precisely determined and were used to deduce the isovector parameter of the s-wave pion-nucleus potential to be b1=-(0.115+/-0.007)m(-1)(pi). The observed enhancement of |b(1)| over the free piN value (b(free)1/b1=0.78+/-0.05) indicates a reduction of the chiral order parameter, f*pi(rho)2/f2pi approximately 0.64, at the normal nuclear density, rho=rho(0).

Journal Article↗
PubMed2003

Expression of adhesion molecules in the lower uterine segment during term and preterm parturition.

Term and preterm cervical ripening and dilatation have similarities with an inflammatory reaction. Since cell adhesion molecules are involved in this process, investigations on the expression of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and platelet endothelial cell adhesion molecule in the lower uterine segment and in vitro experiments on human umbilical vein endothelial cells were performed. In addition, current reports on expression of endothelial adhesion molecules by the uterine cervix were summarized. Cell adhesion molecule expression by lower uterine segment and uterine cervix in term and preterm parturition was measured using immunohistochemistry, enzyme immunoassay, and Northern blot analysis. Regulation of adhesion molecule expression was evaluated in vitro by indirect immunofluorescence and flow cytometry using human umbilical vein endothelial cells. Investigations in term parturition revealed that intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1 expression increases during parturition. In preterm labor, the expression of endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 in the lower uterine segment increased. Expression of platelet endothelial cell adhesion molecule did not change in term and preterm parturition. Expression of adhesion molecules was localized mainly on lower uterine segment vascular endothelial cells and to a smaller extent on leukocytes. In vitro experiments showed that expression of adhesion molecules by human umbilical vein endothelial cells can be stimulated by tumor necrosis factor-alpha, 17beta-estradiol, prostaglandin E(2), and the antigestagen onapristone. Progesterone exerted no stimulatory effect. Cervical ripening and dilatation during term and preterm parturition are associated with an increased expression of endothelial cell adhesion molecules by lower uterine segment and uterine cervix. The expression can be modulated by pro-inflammatory cytokines, sex hormones, and prostaglandin E(2). Mechanisms controlling the extravasation of leukocytes may play a fundamental role in term and preterm parturition.

Cell Adhesion Molecules↗
PubMed2003

[Importance of allergic systems in infant consultations in the French-speaking community of Belgium].

We carried out an investigation towards more than 300 families in the preventive consultations of the French-speaking Community of Belgium (O.N.E.). More specifically we chose children aged from 11 to 15 month. We used a questionnaire managed by a nurse for the parents to measure the prevalence of asthma and allergic symptoms in these children and to study their risk factors of allergies. 58% of the children have at least a family antecedent of allergy signalled and 82.1% who have a mother who presents asthma antecedents. 55.1% had an allergic symptom during there first year of life. Only 2.9% of the children had a diagnosis of asthma. Moreover the study confirms association between respiratory complaints, cigarette smoking among parents and the presence of domestic animals in the environment of the child. In the families with allergic antecedents, 80.8% respond positive on the fact of take antiallergic measures against 20.2% in the families without allergic antecedents. This work confirms the importance of allergies in preventive consultations of children and shows the necessity to follow regularly the evolution of these health problems in order to inform parents and to carry out preventive actions adapted to the knowledge and the perception of risk of each family.

Anti-Allergic Agents↗
PubMed2002

Inhibition of lotic biofilms by Diclofenac.

Diclofenac, a common drug, was subjected to degradation studies using river biofilms grown in rotating annular reactors. Degradation of diclofenac was possible after acclimatisation as confirmed by liquid chromatography-mass spectrometry analyses. Adapted biofilms showed that degradation down to 10-25% of the initial concentration could be achieved within 4 days. In situ observation by confocal laser scanning microscopy, however, revealed slow biofilm development in the presence of diclofenac compared with control experiments grown in river water only. This was substantiated by low cell counts and isolation of fewer kinds of microorganisms from diclofenac-grown biofilms. Fluorescent in situ hybridisation analyses confirmed the presence of various bacterial groups, especially those belonging to the Cytophaga-Flavobacterium and gamma-Proteobacteria groups, in the biofilms. Quantification of image data indicated a negative effect of diclofenac on the growth of bacteria and algae. This is the first report on degradation of diclofenac by lotic biofilms.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

[Vascular injuries after extremity trauma].

The aim of the present examination was to analyse extremity trauma with additional vascular injuries. Between 1973-2000 78 patients with traumatic peripheral vascular injuries have been treated at the Surgical Department of the University Hospital of Mannheim. In addition to clinical examination Doppler-Duplex ultrasonography (cw-Doppler) was routinely performed. In selected cases either conventional or magnetic resonance angiography completed the diagnostic procedure. Vascular injuries to the upper extremities were found in 46.2 % (n = 36) whereas 53.8 % (n = 42) of the patients suffered from trauma of the lower extremities. The popliteal artery was affected in 28.2 % followed by the brachial artery with 23.1 %. 52.6 % of the patients had interposition of autologous vein for reconstruction. Only 7.7 % of the cases needed interposition of alloplastic material. In general the injured extremity was immobilised by external fixation, followed by secondary vascular reconstruction. An efficient trauma management reduced amputation rate as low as 2.6 %.

Adolescent↗
PubMed2001

Cytomegalovirus early promoter induced expression of hCD59 in porcine organs provides protection against hyperacute rejection.

The critical shortage of human donor organs has generated growing interest for porcine to human xenotransplantation. The major immunological barrier to xenotransplantation is the hyperacute rejection (HAR) response that is mediated by preformed xenoreactive antibodies and complement. A promising strategy to control the complement activation, is the expression of human complement regulatory proteins in transgenic animals. We have used the human early cytomegalovirus (CMV) promoter to drive expression of the human complement regulatory protein CD59 (hCD59) in transgenic pigs. A total of eight live transgenic founder animals was born from which five transgenic lines could be established. mRNA analysis and Western blotting revealed high expression of hCD59 in heart, kidney, skeletal muscle, and skin in animals of lines 1 and 5, as well as in the pancreas of four lines. This pattern of expression was confirmed by immunhistological staining. A cell-specific expression in heart and kidney tissue of transgenic lines 1 and 5 was determined. Primary fibroblasts and endothelial cell cultures derived from the aorta of transgenic pigs showed a significantly diminished sensitivity against the challenge with xenoreactive human antibodies and complement whereas non-transgenic control cells were highly susceptible to complement mediated lysis. Ex vivo perfusion of kidneys with pooled human blood revealed a significant protective effect of hCD59 against HAR. The average survival of transgenic kidneys was significantly extended (P<0.05) over nontransgenic controls (207.5+/-54.6 vs. 57.5+/-64.5 min). These data support the concept that hCD59 protects nonprimate cells against human complement mediated lysis and suggest that donor pigs transgenic for hCD59 could play a crucial role in clinical xenotransplantation. Two of five hCD59 transgenic lines showed strong hCD59 expression in several organs relevant for xenotransplantation and a protective effect against HAR. This indicates that the use of the CMV-promoter can facilitate the selection process for optimized transgene expression.

3T3 Cells↗