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Biomedical subjects

A Graf

Publications and source records attributed to A Graf.

At least 19 recordsLinked to original sources

Characterisation of microstructures formed in isopropyl palmitate/water/Aerosol OT:1-butanol (2:1) system.

The aim of this work was to determine the type and microstructure of microemulsion samples formed in IPP/water/AerosolOT:1-butanol (2:1) systems as a case study for the investigation of microemulsions. The concentration of the surfactant/cosurfactant mixture was kept constant while the ratio of water to oil was varied. Several techniques were used to investigate the types and phase transitions of the microemulsion formulations. The experimental methods used included visual observation cross-polarized light microscopy (PLM) appearance, conductivity, viscosity, cryo-field emission scanning electron microscopy (cryo-FESEM), differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and fluorescence resonance energy transfer (FRET). Taken together, the results of the various techniques imply that the systems investigated are undergoing two transitions as a function of water concentration. Between 10-15%w/w of water, the systems change from headgroup hydrated surfactant solutions in oil (or possibly very small reversed micellar systems) to w/o microemulsions. These systems then change to o/w microemulsions between 25-30%w/w of water. The transitions however, appear to be gradual, as for example the DSC data indicates a transition between 15-20%w/w of water. Furthermore, for some methods the changes observed were very weak, and only with supportive data of other techniques can the phase behaviour of the microemulsion systems be interpreted with confidence. Interestingly, no indication of the presence of a bicontinuous intermediate microstructure was found. Liquid crystal formation was detected in samples containing 55%w/w of water.

1-Butanol↗

Perfusion-contractility matching during Fontan circulation.

We investigated the relationship between coronary perfusion pressure (CPP) and myocardial contractility and the effects of an acute elevation of right atrial pressure (RAP) on this relationship in an experimental model of Fontan circulation in 6 anesthetized open-chest dogs with isolated perfused coronary arteries. The relationship between CPP and Ees could be described by biphasic J-shaped curves which were nearly identical before and under Fontan circulation. While above a "critical" CPP (72 +/- 9 mmHg vs. 81 +/- 8 mmHg, n.s.) the changes of CPP did not affect Ees, below this level the decrease of CPP resulted in a progressive decrease of Ees. Under Fontan circulation, the progressive increase of RAP did not influence Ees at CPP = 100 mmHg, led to a moderate decrease of Ees at CPP = 75 mmHg and severe decrease at CPP = 60 mmHg. Thus, both coronary arterial and venous pressure affect myocardial contractility after Fontan procedure.

Animals↗

The effects of light therapy on mini-mental state examination scores in demented patients.

BACKGROUND: Preliminary evidence suggests that demented patients may experience beneficial effects of light therapy. The authors tested whether bright light therapy (BLT) is capable of improving cognitive functions in patients with Alzheimer-type dementia (AD) or vascular dementia (VD). METHODS: Twenty-three patients with AD or VD were randomly assigned to either evening BLT or dim light therapy (DLT). Effects of light therapy on cognitive functions were assessed before and after light therapy using Mini-Mental State Examination (MMSE) scores. Body temperature rhythm (BTR) was additionally recorded pre- and posttreatment. RESULTS: Irrespective of their diagnosis, patients treated with BLT (p =.0012) but not with DLT (p =.73) showed a statistically significant increase in MMSE total scores after light therapy. Evening BLT simultaneously induced a significant phase delay of 56 min on BTR (p =.025). CONCLUSION: Our preliminary results suggest that short-term evening BLT may exert beneficial effects on cognitive functioning in patients with dementia.

Aged↗

The Ca2+-binding proteins S100A8 and S100A9 are encoded by novel injury-regulated genes.

To gain insight into the molecular mechanisms underlying cutaneous wound repair, we performed a large scale screen to identify novel injury-regulated genes. Here we show a strong up-regulation of the RNA and protein levels of the two Ca(2+)-binding proteins S100A8 and S100A9 in the hyperthickened epidermis of acute murine and human wounds and of human ulcers. Furthermore, both genes were expressed by inflammatory cells in the wound. The increased expression of S100A8 and S100A9 in wound keratinocytes is most likely related to the activated state of the keratinocytes and not secondary to the inflammation of the skin, since we also found up-regulation of S100A8 and S100A9 in the epidermis of activin-overexpressing mice, which develop a hyperproliferative and abnormally differentiated epidermis in the absence of inflammation. Furthermore, S100A8 and S100A9 expression was found to be associated with partially differentiated keratinocytes in vitro. Using confocal microscopy, both proteins were shown to be at least partially associated with the keratin cytoskeleton. In addition, cultured keratinocytes efficiently secreted the S100A8/A9 dimer. These results together with previously published data suggest that S100A8 and S100A9 are novel players in wound repair, where they might be involved in the reorganization of the keratin cytoskeleton in the wounded epidermis, in the chemoattraction of inflammatory cells, and/or in the defense against microorganisms.

Activins↗

Downregulation of myocardial contractility via intact ventriculo--arterial coupling in the brain dead organ donor.

OBJECTIVE: To test the hypothesis that altered loading conditions play a key role in hemodynamic instability and cardiac dysfunction in the brain dead (BD) organ donor. METHODS: BD was induced by inflation of a subdural balloon catheter. In the first part of the study, left ventricular function was assessed in a canine in situ cross-circulated heart model (n=6). Pre- and afterload and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In the second part of the study, hearts (n=6) were investigated in vivo allowing the interaction between left ventricular contractility and arterial load. Left ventricular pressure--volume loops were obtained by a combined conductance-pressure catheter and the slope of the endsystolic pressure--volume relationship (Ees), arterial elastance (Ea), stroke work (SW), pressure--volume area, ventriculo--arterial coupling ratio (VAC) and mechanical efficiency (Eff) were calculated. RESULTS: Induction of BD led to a hyperdynamic response in both models with a significant increase of most hemodynamic parameters. In the in situ isolated heart model, left ventricular contractility returned to baseline without any further deterioration. In contrast, in the intact circulation the hemodynamic parameters declined significantly in comparison to baseline 4 h after BD (Ees: 4.07+/-0.51 vs. 8.06+/-1.09 mmHg/ml, P<0.05, Ea: 3.17+/-0.39 vs. 4.42+/-0.30 mmHg/ml, P<0.05). However, VAC (0.78+/-0.09 vs. 0.65+/-0.14 n.s.) and Eff (73.4+/-2.1 % vs. 76.8+/-3.7 %, n.s.) remained constant over the time. CONCLUSION: BD induction leads to an initial hyperdynamic reaction followed by hemodynamic instability. The facts that no cardiac dysfunction occurred if loading conditions were kept constant and the ventriculo--arterial coupling ratio and mechanical efficiency remained constant in the intact animal model indicate that decreased contractility reflects to decreased arterial elastance after brain death. Therefore, reduced contractile function after brain death at a decreased afterload may contribute to stroke work optimization.

Animals↗

Short- and long-term results after thrombolytic treatment of deep venous thrombosis.

OBJECTIVES: The goal of this study was to assess the short- and long-term efficacy of different thrombolytic therapy regimens in patients with leg or pelvic deep venous thrombosis (DVT). BACKGROUND: It is unclear whether locoregional or systemic thrombolysis is superior in treating acute leg DVT or even whether lysis is more effective than anticoagulation therapy in preventing postthrombotic syndrome. METHODS: A total of 250 patients averaging 40 years of age with acute DVT were randomized into five groups to receive full heparinization (1,000 IU/h) and compression treatment, with four groups also administered locoregional tissue plasminogen activator (20 mg/day) or urokinase (100,000 IU/day) or systemic streptokinase (3,000,000 IU daily) or urokinase (5,000,000 IU daily). All groups then received anticoagulation and compression treatment for one year. Primary efficacy criteria included the change after one year in the number of closed vein segments and the occurrence of postthrombotic syndrome. RESULTS: Systemic thrombolytic therapy significantly reduced the number of closed vein segments after 12 months in patients with acute DVT compared with conventional treatment (p < 0.05). Postthrombotic syndrome also occurred with less frequency in systemically treated patients versus controls (p < 0.001). High-dose thrombolysis led to better rates of complete recanalization after seven days (p < 0.01) than locoregional lysis. However, 12 patients receiving thrombolysis (9 systemic, 3 local) suffered major bleeding complications; 9 patients on systemic treatment developed pulmonary emboli. CONCLUSIONS: Systemic thrombolytic treatment for acute DVT achieved a significantly better short- and long-term clinical outcome than conventional heparin/anticoagulation therapy but at the expense of a serious increase in major bleeding and pulmonary emboli. Given the inherent risks for such serious complications, systemic thrombolysis, although effective, should be used selectively in limb-threatening thrombotic situations.

Adult↗

Prognostic significance of tumor angiogenesis in primary fallopian tube cancer.

Tumor angiogenesis has been found to be prognostically significant in many types of malignant tumors. We assessed tumor vascularity in 43 cases of histologically proven primary fallopian tube cancer, FIGO stage I-IV, using the highly specific endothelial cell marker CD34. Microvessel count was determined by counting CD34-positive cells at 200 x magnification. The 5-year disease-free survival probability was 43.8% (+/- 11.5%) in 24 patients whose tumors had a microvessel count < or = 19 microvessels/field and 19.7% (+/- 9.5%) in the > 19 microvessels/field group (P = 0.046). Stage and microvessel count were statistically significant for disease-free survival in univariate analysis. Therefore, a larger sample size would be required to detect an independent and statistically significant prognostic effect of microvessel density in primary fallopian tube cancer in multivariate analysis.

Adult↗

[Diagnostic imaging in staging of gynecologic carcinomas].

The prognosis in patients with gynecologic cancers depends not only on the stage but also on a wide spectrum of other findings. Cross-sectional imaging modalities, including sonography, CT and MRI, have increasingly been used for optimal treatment planning in gynecologic cancers. Their staging criteria are based on the well-established FIGO staging system. CT and MRI compete with sonography, which plays a pivotal role in the evaluation of the female pelvis. This paper reviews the role of sonography, CT and MRI in the staging of gynecologic malignancies. It puts the emphasis on MRI, which has been established as imaging modality of choice in the preoperative evaluation of cervical and endometrial cancer, and which seems slightly superior to CT in the staging of ovarian cancer.

Diagnostic Imaging↗

Hemodynamic effects of double bolus reteplase versus alteplase infusion in massive pulmonary embolism.

BACKGROUND: Thrombolytic agents are given in massive pulmonary embolism to dissolve or reduce the clot and normalize hemodynamics. Comparative clinical studies have shown that administration of a 2-hour infusion of alteplase is more effective than urokinase over a 12-hour period. Reteplase is a new generation thrombolytic with a longer half-life that can be administered more conveniently as a double bolus. We compared efficacy and safety of reteplase with the approved regimen of alteplase in massive pulmonary embolism. METHODS: Thirty-six patients were enrolled and randomly assigned: 23 received reteplase and 13 received alteplase along with intravenous heparin. Reteplase was administered as 2 intravenous bolus injections of 10 U 30 minutes apart, and alteplase was administered as an intravenous infusion of a total dose of 100 mg over a 2-hour period, including an initial 10-mg bolus. Diagnosis of pulmonary embolism was confirmed by selective pulmonary angiography. Hemodynamic monitoring was conducted during the first 24 hours after administration. The primary end point was change in total pulmonary resistance. Secondary variables were pulmonary pressure, cardiac index, clinical parameters, and adverse events. RESULTS: The primary parameter of total pulmonary resistance showed a significant decrease after just 0.5 hours in the reteplase group and after 2 hours in the alteplase group, with a further decrease persisting for up to 24 hours in both treatment groups. A similar pattern was seen in other directly measured hemodynamic parameters, especially mean pulmonary artery pressure and cardiac index; there was no significant difference between reteplase and alteplase. There was also no apparent difference between the treatment groups with respect to safety, and no stroke or intracranial hemorrhage occurred. The rate of bleedings and the incidence of nonhemorrhagic adverse events were as expected for patients with pulmonary embolism treated with a thrombolytic agent. CONCLUSIONS: Reteplase is suitable for treatment of massive pulmonary embolism with a standard double bolus 10 + 10 U. Efficacy of reteplase appeared to be at least as good at decreasing pulmonary vascular resistance as that of the approved alteplase regimen of 100 mg infusion over a 2-hour period.

Adult↗

[Fibrinolytic, revascularizing therapy of peripheral arterial occlusive disease].

Thrombo-embolic events are the primary or secondary cause for occlusions of peripheral arteries. The systemically applied fibrinolysis rarely resulted in revascularization. The local application of plasminogen activators leads to better results. Combined with interventionally techniques 70-80% of the acute und subacute occlusions can be opened an the necessity of angio-surgical interventions can be reduced by about 50%. The technical procedure of the local fibrinolysis and the dosages of the applied activators are presently not standardized. Therefore the results of 13 reports between the years 1995-1998 including 4 prospective studies are not comparable. According to the present experiences, acute und subacute incomplete ischemia syndromes are to be seen as indication for local lysis. Especially for patients whose constitution is not optimal for surgery, local fibrinolysis is an alternative to surgical revascularization. Further studies are necessary to optimize the therapy.

Angioplasty, Balloon↗

[In situ PCR and PCR in situ hybridization of paraffin-embedded tissue. New diagnostic possibilities in pathology].

In situ polymerase chain reaction (PCR) and PCR in situ hybridization are new diagnostic tools in dermatopathology. These techniques can combine the sensitivity of PCR with the advantage of in situ hybridization to localize specific cellular structures. With optical control of the PCR reaction product in these techniques, false-positive results due to contamination can be minimized. Several working protocols have been established which allow detection of DNA and RNA sequences in a rapid and reproducible manner. Two different methods have been established to detect the amplification product, the indirect PCR in situ hybridization (PCRisHyb), and the direct in situ PCR (isPCR). An easy and reproducible method for PCRisHyb and isPCR in formalin-fixed and paraffin-embedded tissue is described and the two techniques are compared. Using both isPCR and PCRisHyb, the amplification product can be visualized with an optimal morphological preservation of the tissue. Indirect PCRisHyb showed a slightly higher specificity whereas direct isPCR was the quicker, easier and less expensive method.

Chickenpox↗

Automated high-resolution polymerase chain reaction fragment analysis: a method for detecting T-cell receptor gamma-chain gene rearrangements in lymphoproliferative diseases.

Southern blot analysis and the polymerase chain reaction (PCR) are powerful tools for detecting clonal antigen receptor gene rearrangements. However, a number of limitations restrict the predictive value of the results obtained by these techniques as they are commonly used. We describe a new method, automated high-resolution PCR fragment analysis, that can partially overcome many of the limitations of analyzing the T-cell receptor (TCR) gamma-chain gene. Analysis of TCR-gamma is performed using PCR with four sets of primers, previously described by others, specific for all variable (V) and joining (J) regions of the TCR gamma-chain gene. In addition, the four V region primers are 5' end-labeled with a fluorescent compound, 5-carboxyfluorescein. After amplification, the labeled PCR products are separated with an automated sequencing system, ABI 373 (Applied Biosystems, Weiterstadt, Germany). With the help of the Gene-Scan software ABI 672 (Applied Biosystems) and fluorescent-labeled DNA length markers, the exact size of each peak can be displayed and analyzed. The resolution of this method allows separation of PCR products differing in length by as little as 1 bp. Semiquantitative estimation of specific clones also can be performed. Infiltrate-specific gene rearrangement patterns can be identified and recognized in different tissue specimens at the time of diagnosis or in subsequent biopsy specimens. We conclude that automated high-resolution PCR fragment analysis allows more accurate and convenient analysis of the TCR gamma-chain gene.

Automation↗

Conservative treatment of cervical pregnancy by curettage and local prostaglandin injection.

Recently, various conservative regimens for the treatment of cervical pregnancy have been introduced to preserve fertility in young women, with methotrexate being one of the most widely used drugs. The success of conservative treatment depends on early preoperative diagnosis. We report three cases of first trimester cervical pregnancy, successfully treated by curettage to evacuate the conceptus, followed by local prostaglandin instillation to prevent severe haemorrhage. In one patient, intra-amniotic instillation of hyperosmolar glucose was necessary to terminate fetal cardiac activity. beta-Human chorionic gonadotrophin returned to normal within 3 weeks in one patient and within 7 weeks in another, both of whom became pregnant again within 1 year, resulting in term deliveries. The third patient was lost to follow-up after 1 week. The advantage of prostaglandin and curettage is the absence of major side-effects to the mother or the fetus of a subsequent pregnancy. The management strategies used in the treatment of cervical pregnancies and the results obtained since the introduction of methotrexate in 1989 are discussed in the context of previously published literature. The incidence of subsequent pregnancies among women treated medically versus women treated surgically is reported.

Adult↗

[Detection of clonality of cutaneous T-cell lymphomas using polymerase chain reaction].

Differentiation of a cutaneous lymphoma from a reactive lymphoid infiltrate is a demanding challenge for the pathologist. In this retrospective study we examined 24 paraffin-embedded tissue samples from lesions diagnosed as lymphomas and 7 control samples of skin affected by benign changes and with pronounced lymphoid infiltrates for clonal rearrangement of the gamma T-cell-receptor. Using PCR technology we demonstrated clonality in 22 cases of lymphoma (92%). Thus, the primer combination used in this study covering the four main groups (I-IV) of the variable region of the gamma T-cell receptor gene allows high sensitivity. No clonality was demonstrable in any of the 7 control cases. This study demonstrates the growing importance of PCR technology for the diagnosis of lymphoma.

Cell Transformation, Neoplastic↗

The relation between depth of trophoblastic invasion and beta-HCG levels in tubal pregnancies.

beta-HCG (human chorionic gonadotropin) values of over 2500 I.U./l are associated with higher failure rates for therapy with prostaglandin F2 alpha in tubal pregnancies. The purpose of our study was to ascertain if the 2500 I.U./l limit correlates with histopathology. We therefore compared the pre-operative beta-HCG-values and intraluminal and extraluminal trophoblast growth in tubal pregnancy. Purely intraluminal trophoblast was significantly more frequent in patients of group I (beta-HCG < 2500 I.U./l), while group II patients (beta-HCG > 2500 I.U./l) almost exclusively had extraluminal growth (P = 0.0045). Since the efficacy of prostaglandin F2 alpha therapy depends on intact tubal musculature the correlation of the beta-HCG threshold level with histopathologic findings may explain the high failure rate in patients with beta-HCG values above 2500 I.U./l.

Chorionic Gonadotropin↗

[Histopathologic findings of the trophoblast and tubal wall after medicamentous therapy of tubal pregnancies].

The purpose of the study was to evaluate the effects of drug therapy on the throphoblast and on the tubal wall when protaglandin F2 alpha (PGF2 alpha) was administered in cases of tubal pregnancies. 42 patients were divided into two groups: women of group I (n = 30) were secondarily treated by surgery because of raising serum HCG levels. Group II (n = 12) consisted of patients who were operated on because of acute symptoms (abdominal pains, intraabdominal haemorrhage), despite already failing HCG values. In group I in 66% (n = 20) of the histological specimens an intact (vital) trophoblast was found. Five cases (17%) showed partly necrotic gestational tissue, whereas in another five cases (17%) the whole trophoblast was necrotic. In patients of group II all ectopic pregnancies showed histological signs of necrosis. In the histopathology of the Fallopian tubes no signs of trophic regression could be found. However, ten out of 22 cases showed ruptured tubal pregnancies. In this analysis we could show that the instillation of PGF2a electively destroys the ectopic trophoblast and does not exercise any necrotic action on the tubal wall.

Abortifacient Agents, Nonsteroidal↗