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"text": "\n187406\nRevisiting the vascularity of the keratinized gingiva in the maxillary esthetic zone.\n\nMikecs, B\n\nVág, J\n\nGerber, G\n\nMolnár, B\n\nFeigl, G\n\nShahbazi, A\n\nBeiträge in Fachzeitschriften\nISI:000635208900004\n33766000.0\n10.1186/s12903-021-01445-y\nPMC7995803\nThe active arterial-to-arterial collaterals are a significant factor in the prevention of ischemia and extensive tissue necrosis in the case of arterial blockage of various tissues. The present study investigates the mucogingival vasculature in the maxillary esthetic zone mucosa in human cadavers and functionally evaluates the area, which is supplied by the terminal arterioles, on the individual level.\n In the human cadaver study, macroscopic arterial analyses of the anterior maxillary vestibule in 7 specimens were scrutinized by latex milk injection. The tracks of the mucosal branches in relation to the mucogingival junction were investigated. In the functional study, individual gingival blood flow (GBF) changes were measured by laser speckle contrast imaging (LSCI) in 31 young subjects with healthy gingiva before and during 30-s compressions. This was conducted with a ball-shaped condenser. The data was analyzed by the linear mixed model.\n The vertically aligned branches of the superior labial artery (SLA) divided into small, slightly deviating sub-branches near the mucogingival junction. These arteries created collateral plexuses and supplied the attached gingiva. The compression of these branches resulted in ischemia coronally with significant individual variation. The ischemia was either apico-mesial, apico-distal, or straight apical to the compression. A significant correlation was found between the ischemic area and the magnitude of the decrease in GBF (r = 0.81, p < 0.001). In males, 77% of the subjects, and 50% of the female subjects had an ischemic response in either region. The horizontal extension of the ischemic area ranged between 0.26 mm and 8.76 mm. Males had significantly higher baseline GBF and larger ischemia than females. At the base of the papilla, significant restoration of GBF was observed during compression in males, but not in females.\n The arcade anastomoses formed by the small arteries in the keratinized gingiva of the upper esthetic zone explain the consequences of vertical incisions. The considerable individual variations in ischemic responses might be the reason for unexpected surgical outcomes in some cases. Furthermore, there is increasing evidence that men have different vascular reactivity and/or regulation of collateral circulation than women, which may affect wound healing.\n\n\n"
},
{
"text": "\n4327\nMelanoma with benign melanocytic naevus components: reappraisal of clinicopathological features and prognosis.\n\nKaddu, S\n\nSmolle, J\n\nZenahlik, P\n\nHofmann-Wellenhof, R\n\nKerl, H\n\nBeiträge in Fachzeitschriften\nISI:000176468600011\n12140384.0\n10.1097%2F00008390-200206000-010.1097%2F00008390-200206000-00011\nNone\nThe clinicopathological features and prognosis of primary cutaneous malignant melanoma with benign melanocytic naevus (BMN) components are still under debate. The purpose of this study was to characterize further the clinical and histopathological features of naevus-associated melanomas, with emphasis on the BMN components, and to examine their prognosis based on a large series. Following a histopathological review of 667 consecutive cases of primary cutaneous melanoma, 148 melanomas with BMN components (22.1%) were identified for further study. A control group of 519 melanomas without BMN components seen in a similar period were also studied. Clinically, patients with melanomas containing BMN components (n = 148; age range 25-86 years, mean age 54 +/- 16 years; male to female ratio 1:1.02) presented with tumours located mainly on the trunk (34.5%), followed by the upper extremities (24.3%), lower extremities (20.3%), and head and neck (14.2%). Compared with tumours without BMN components (n = 519; age range 19-89 years, mean age 57 +/- 15 years; male to female ratio 1:1.3), melanomas with BMN components occurred in slightly younger individuals (P = 0.027). Histopathologically, BMN components mainly showed features of acquired naevi (total 87 cases; dysplastic, 80 cases; banal, seven cases) or congenital naevi (total 57 cases; superficial, 56 cases; deep, one case), but a minority of these lesions (four cases) could not be further subcategorized. Generally, melanomas containing BMN components were relatively thinner than melanomas without BMN components (mean Breslow index 0.95 +/- 0.83 mm and 1.3 +/- 1.6 mm, respectively) (P = 0.015). The follow-up data available in 69 patients with naevus-associated melanomas consistently revealed a relatively good outcome (5 year metastasis-free survival rate 93.75%), although no statistical difference in prognosis was observed between this group and a subset of 283 melanomas patients without BMN components stratified by tumour thickness. We conclude that BMN components in naevus-associated melanomas constitute a heterogeneous group morphologically, consisting mainly of dysplastic and superficial congenital naevi. This finding indicates a more important role for superficial congenital naevus as a precursor lesion of naevus-associated melanomas than presently recognized. Patients with naevus-associated melanomas generally show a good clinical outcome, reflecting their small Breslow index.\n\nHofmann-Wellenhof, Rainer\n\nKaddu, Steven\n\nKerl, Helmut\n\nSmolle, Josef\n\n\n"
},
{
"text": "\n64538\nThe influence of alcohol consumption on the risk of vertebral deformity. European Vertebral Osteoporosis Study Group.\n\nNaves Diaz, M\n\nO'Neill, TW\n\nSilman, AJ\n\nBeiträge in Fachzeitschriften\nISI:A1997WL67300011\n9102066.0\n10.1007/BF01623463\nNone\nThe influence of alcohol consumption on the risk of osteoporosis is not well established. The aim of this study was to determine the relationship between frequency of alcohol consumption and the risk of vertebral deformity across different European populations. A population survey method was used. Men and women aged 50 years and over were recruited from population-based sampling frames in 36 centres from 19 European countries. Subjects were invited to attend by letter of invitation for an interviewer-administered questionnaire and lateral spinal radiographs. Vertebral deformity was defined morphometrically using the McCloskey-Kanis method. Data from 14237 individuals were available for this analysis. Alcohol consumption was compared between the 809 men and 884 women with vertebral deformity and the 5905 men and 6639 women without vertebral deformity. The frequency of alcohol intake was greater in men than women. Overall, there was no detectable association between frequency of alcohol intake and vertebral deformity in either men or women. Stratification by age showed that women 65 years and over who took alcohol on more than 5 days per week had a reduced risk of vertebral deformity compared with those taking alcohol less than once per week. This protection was most obvious after adjusting for age, centre, body mass index, smoking, current level of physical activity and previous fractures (odds ratio [OR] = 0.65; 95% confidence intervals [CI] = 0.43, 0.99). There was a smaller and non-significant protective effect amongst men aged 65 years and over and this was most apparent amongst moderately frequent drinkers (1-4 days per week) (OR = 0.81; 95% CI = 0.62, 1.08). There was no association between the occurrence of vertebral deformity and frequency of alcohol consumption in younger men and women. Overall, the effects of the frequency of alcohol consumption on vertebral deformity were modest. In older women, regular consumption on more than 5 days per week is associated with a reduced risk. Further, prospective data are required to confirm these findings. It is also necessary to investigate, in terms of amount of alcohol consumed, at what level the benefits of regular intake are obviated by the increased risks from alcohol excess.\n\nWeber, Kurt\n\n\n"
},
{
"text": "\n86679\nPluriformity of inflammation in multiple sclerosis shown by ultra-small iron oxide particle enhancement.\n\nVellinga, MM\n\nOude Engberink, RD\n\nSeewann, A\n\nPouwels, PJ\n\nWattjes, MP\n\nvan der Pol, SM\n\nPering, C\n\nPolman, CH\n\nde Vries, HE\n\nGeurts, JJ\n\nBarkhof, F\n\nBeiträge in Fachzeitschriften\nISI:000253489800020\n18245785.0\n10.1093/brain/awn009\nNone\nGadolinium-DTPA (Gd-DTPA) is routinely used as a marker for inflammation in MRI to visualize breakdown of the blood-brain barrier (BBB) in multiple sclerosis. Recent data suggest that ultra-small superparamagnetic particles of iron oxide (USPIO) can be used to visualize cellular infiltration, another aspect of inflammation. This project aimed to compare the novel USPIO particle SHU555C to the longitudinal pattern of Gd-DTPA enhancement in multiple sclerosis. Nineteen relapsing-remitting patients were screened monthly using Gd-enhanced MRI. In case of new enhancing lesions, USPIO were injected and 24 h later, MRI was performed and blood was collected to confirm USPIO loading of circulating monocytes. Lesion development was monitored by 3 monthly Gd-DTPA-enhanced scans and a final scan 7-11 months after injection. USPIO-enhancement was observed as hyperintensity on T1-weighted images, whereas no signal changes were observed on T2-weighted-gradient-echo images. In 14 patients with disease activity, 188 USPIO-positive lesions were seen, 144 of which were Gd-negative. By contrast, there were a total of 59 Gd-positive lesions, 15 of which were USPIO negative. Three patterns of USPIO-enhancement were seen: (i) focal enhancement; (ii) ring-like enhancement and (iii) return to isointensity of a previously hypointense lesion. The latter pattern was most frequently observed for lesions that turned out to be transiently hypointense on follow-up scans, and ring-enhancing lesions were less likely to evolve into black holes at follow-up than lesions without ring-like USPIO-enhancement; we speculate this to be associated with repair. In 4% of the USPIO-positive/Gd negative lesions, USPIO-enhancement preceded Gd-enhancement by 1 month. USPIO-enhancement remained visible for up to 3 months in 1.5% of all USPIO-positive lesions. In 29% of the lesions enhancing with both contrast agents, USPIO-enhancement persisted whereas Gd-enhancement had already resolved. In conclusion, the new nano-particle SHU555C provides complementary information to Gd-enhanced MRI, probably related to monocyte infiltration. The use of USPIO-enhanced MRI is likely to lead to more insight in the pluriformity of inflammation in multiple sclerosis.\n\n\n"
},
{
"text": "\n95908\nEffect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial.\n\nComi, G\n\nMartinelli, V\n\nRodegher, M\n\nMoiola, L\n\nBajenaru, O\n\nCarra, A\n\nElovaara, I\n\nFazekas, F\n\nHartung, HP\n\nHillert, J\n\nKing, J\n\nKomoly, S\n\nLubetzki, C\n\nMontalban, X\n\nMyhr, KM\n\nRavnborg, M\n\nRieckmann, P\n\nWynn, D\n\nYoung, C\n\nFilippi, M\n\nBeiträge in Fachzeitschriften\nISI:000271591300029\n19815268.0\n10.1016/S0140-6736(09)61259-9\nNone\nBACKGROUND: Glatiramer acetate, approved for the treatment of relapsing-remitting multiple sclerosis, reduces relapses and disease activity and burden monitored by MRI. We assessed the efficacy of early treatment with glatiramer acetate in delaying onset of clinically definite multiple sclerosis. METHODS: In this randomised, double-blind trial, undertaken in 80 sites in 16 countries, 481 patients presenting with a clinically isolated syndrome with unifocal manifestation, and two or more T2-weighted brain lesions measuring 6 mm or more, were randomly assigned to receive either subcutaneous glatiramer acetate 20 mg per day (n=243) or placebo (n=238) for up to 36 months, unless they converted to clinically definite multiple sclerosis. The randomisation scheme used SAS-based blocks stratified by centre, and patients and all personnel were masked to treatment assignment. The primary endpoint was time to clinically definite multiple sclerosis, based on a second clinical attack. Analysis was by intention to treat. A preplanned interim analysis was done for data accumulated from 81% of the 3-year study exposure. This study was registered with ClinicalTrials.gov, number NCT00666224. FINDINGS: All randomly assigned participants were analysed for the primary outcome. Glatiramer acetate reduced the risk of developing clinically definite multiple sclerosis by 45% compared with placebo (hazard ratio 0.55, 95% CI 0.40-0.77; p=0.0005). The time for 25% of patients to convert to clinically definite disease was prolonged by 115%, from 336 days for placebo to 722 days for glatiramer acetate. The most common adverse events in the glatiramer acetate group were injection-site reactions (135 [56%] glatiramer acetate vs 56 [24%] placebo) and immediate post-injection reactions (47 [19%] vs 12 [5%]). INTERPRETATION: Early treatment with glatiramer acetate is efficacious in delaying conversion to clinically definite multiple sclerosis in patients presenting with clinically isolated syndrome and brain lesions detected by MRI. FUNDING: Teva Pharmaceutical Industries, Israel.\n\nFazekas, Franz\n\n\n"
},
{
"text": "\n128990\nThe three-dimensional morphometry of the odontoid peg and its impact on ventral screw osteosynthesis.\n\nPuchwein, P\n\nJester, B\n\nFreytag, B\n\nTanzer, K\n\nMaizen, C\n\nGumpert, R\n\nPichler, W\n\nBeiträge in Fachzeitschriften\nISI:000318314300018\n23539707.0\n10.1302/0301-620X.95B4.30949\nNone\nVentral screw osteosynthesis is a common surgical method for treating fractures of the odontoid peg, but there is still no consensus about the number and diameter of the screws to be used. The purpose of this study was to develop a more accurate measurement technique for the morphometry of the odontoid peg (dens axis) and to provide a recommendation for ventral screw osteosynthesis. Images of the cervical spine of 44 Caucasian patients, taken with a 64-line CT scanner, were evaluated using the measuring software MIMICS. All measurements were performed by two independent observers. Intraclass correlation coefficients were used to measure inter-rater variability. The mean length of the odontoid peg was 39.76 mm (SD 2.68). The mean screw entry angle α was 59.45° (SD 3.45). The mean angle between the screw and the ventral border of C2 was 13.18° (SD 2.70), the maximum possible mean converging angle of two screws was 20.35° (SD 3.24). The measurements were obtained at the level of 66% of the total odontoid peg length and showed mean values of 8.36 mm (SD 0.84) for the inner diameter in the sagittal plane and 7.35 mm (SD 0.97) in the coronal plane. The mean outer diameter of the odontoid peg was 12.88 mm (SD 0.91) in the sagittal plane and 11.77 mm (SD 1.09) in the coronal plane. The results measured at the level of 90% of the total odontoid peg length were a mean of 6.12 mm (SD 1.14) for the sagittal inner diameter and 5.50 mm (SD 1.05) for the coronal inner diameter. The mean outer diameter of the odontoid peg was 11.10 mm (SD 1.0) in the sagittal plane and 10.00 mm (SD 1.07) in the coronal plane. In order to calculate the necessary screw length using 3.5 mm cannulated screws, 1.5 mm should be added to the measured odontoid peg length when anatomical reduction seems possible. The cross-section of the odontoid peg is not circular but slightly elliptical, with a 10% greater diameter in the sagittal plane. In the majority of cases (70.5%) the odontoid peg offers enough room for two 3.5 mm cannulated cortical screws.\n\nPuchwein, Paul\n\n\n"
},
{
"text": "\n147623\nThe cytotoxicity of the α1-adrenoceptor antagonist prazosin is linked to an endocytotic mechanism equivalent to transport-P.\n\nFuchs, R\n\nStracke, A\n\nEbner, N\n\nZeller, CW\n\nRaninger, AM\n\nSchittmayer, M\n\nKueznik, T\n\nAbsenger-Novak, M\n\nBirner-Gruenberger, R\n\nBeiträge in Fachzeitschriften\nISI:000366962000003\n26449523.0\n10.1016/j.tox.2015.09.008\nPMC4671317\nSince the α1-adrenergic antagonist prazosin (PRZ) was introduced into medicine as a treatment for hypertension and benign prostate hyperplasia, several studies have shown that PRZ induces apoptosis in various cell types and interferes with endocytotic trafficking. Because PRZ is also able to induce apoptosis in malignant cells, its cytotoxicity is a focus of interest in cancer research. Besides inducing apoptosis, PRZ was shown to serve as a substrate for an amine uptake mechanism originally discovered in neurones called transport-P. In line with our hypothesis that transport-P is an endocytotic mechanism also present in non-neuronal tissue and linked to the cytotoxicity of PRZ, we tested the uptake of QAPB, a fluorescent derivative of PRZ, in cancer cell lines in the presence of inhibitors of transport-P and endocytosis. Early endosomes and lysosomes were visualised by expression of RAB5-RFP and LAMP1-RFP, respectively; growth and viability of cells in the presence of PRZ and uptake inhibitors were also tested. Cancer cells showed co-localisation of QAPB with RAB5 and LAMP1 positive vesicles as well as tubulation of lysosomes. The uptake of QAPB was sensitive to transport-P inhibitors bafilomycin A1 (inhibits v-ATPase) and the antidepressant desipramine. Endocytosis inhibitors pitstop(®) 2 (general inhibitor of endocytosis), dynasore (dynamin inhibitor) and methyl-β-cyclodextrin (cholesterol chelator) inhibited the uptake of QAPB. Bafilomycin A1 and methyl-β-cyclodextrin but not desipramine were able to preserve growth and viability of cells in the presence of PRZ. In summary, we confirmed the hypothesis that the cellular uptake of QAPB/PRZ represents an endocytotic mechanism equivalent to transport-P. Endocytosis of QAPB/PRZ depends on a proton gradient, dynamin and cholesterol, and results in reorganisation of the LAMP1 positive endolysosomal system. Finally, the link seen between the cellular uptake of PRZ and cell death implies a still unknown pro-apoptotic membrane protein with affinity towards PRZ. \n Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.\n\nAbsenger-Novak, Markus\n\nBirner-Grünberger, Ruth\n\nKolesnik, Tatjana\n\nSchittmayer-Schantl, Matthias\n\nStracke, Anika\n\n\n"
},
{
"text": "\n148979\nThe effects of age on health-related quality of life in cancer populations: A pooled analysis of randomized controlled trials using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 involving 6024 cancer patients.\n\nQuinten, C\n\nCoens, C\n\nGhislain, I\n\nZikos, E\n\nSprangers, MA\n\nRingash, J\n\nMartinelli, F\n\nEdiebah, DE\n\nMaringwa, J\n\nReeve, BB\n\nGreimel, E\n\nKing, MT\n\nBjordal, K\n\nFlechtner, HH\n\nSchmucker-Von Koch, J\n\nTaphoorn, MJ\n\nWeis, J\n\nWildiers, H\n\nVelikova, G\n\nBottomley, A\n\nPROBE\n\nEORTC Clinical Groups\n\nBeiträge in Fachzeitschriften\nISI:000365624500011\n26602015.0\n10.1016/j.ejca.2015.08.027\nNone\nCancer incidence increases exponentially with advancing age, cancer patients live longer than in the past, and many new treatments focus on stabilizing disease and HRQOL. The objective of this study is to examine how cancer affects patients' HRQOL and whether their HRQOL is age-dependent.\n Data from 25 EORTC randomized controlled trials was pooled. EORTC QLQ-C30 mean scores for the cancer cohort and five general population cohorts were compared to assess the impact of cancer on patients' HRQOL. Within the cancer cohort, multiple linear regressions (two-sided level P-value = 0.05 adjusted for multiple testing.) were used to investigate the association between age and HRQOL, adjusted for gender, WHO performance status (PS), distant metastasis and stratified by cancer site. A difference of 10 points on the 0-100 scale was considered clinically important.\n Cancer patients generally have worse HRQOL compared to the general population, but the specific HRQOL domains impaired vary with age. When comparing the cancer versus the general population, young cancer patients had worse financial problems, social and role functioning, while the older cancer groups had more appetite loss. Within the cancer cohort, HRQOL was worse with increasing age for physical functioning and constipation, and better with increasing age for social functioning, insomnia and financial problems (all p < 0.05).\n HRQOL is impaired in cancer patients compared to the general population, but the impact on specific HRQOL domains varies by age. Within the cancer population, some HRQOL components improve with age while others deteriorate. Optimal care for older cancer patients should target HRQOL domains most relevant to this population.\n Copyright © 2015 Elsevier Ltd. All rights reserved.\n\nGreimel, Elfriede Renate\n\n\n"
},
{
"text": "\n151521\nIs the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults.\n\nZimmermann, E\n\nÄngquist, LH\n\nMirza, SS\n\nZhao, JH\n\nChasman, DI\n\nFischer, K\n\nQi, Q\n\nSmith, AV\n\nThinggaard, M\n\nJarczok, MN\n\nNalls, MA\n\nTrompet, S\n\nTimpson, NJ\n\nSchmidt, B\n\nJackson, AU\n\nLyytikäinen, LP\n\nVerweij, N\n\nMueller-Nurasyid, M\n\nVikström, M\n\nMarques-Vidal, P\n\nWong, A\n\nMeidtner, K\n\nMiddelberg, RP\n\nStrawbridge, RJ\n\nChristiansen, L\n\nFTO-Mortality Collaborating Group\n\nKyvik, KO\n\nHamsten, A\n\nJääskeläinen, T\n\nTjønneland, A\n\nEriksson, JG\n\nWhitfield, JB\n\nBoeing, H\n\nHardy, R\n\nVollenweider, P\n\nLeander, K\n\nPeters, A\n\nvan der Harst, P\n\nKumari, M\n\nLehtimäki, T\n\nMeirhaeghe, A\n\nTuomilehto, J\n\nJöckel, KH\n\nBen-Shlomo, Y\n\nSattar, N\n\nBaumeister, SE\n\nSmith, GD\n\nCasas, JP\n\nHouston, DK\n\nMärz, W\n\nChristensen, K\n\nGudnason, V\n\nHu, FB\n\nMetspalu, A\n\nRidker, PM\n\nWareham, NJ\n\nLoos, RJF\n\nTiemeier, H\n\nSonestedt, E\n\nSørensen, TIA\n\nBeiträge in Fachzeitschriften\nISI:000351612400006\n25752329.0\n10.1111/obr.12263\nPMC4564522\nPreviously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169, 51 adult Caucasians among whom 27, 00 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169, 51; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152, 31; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48, 92; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes. \n © 2015 World Obesity.\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n155866\nNegative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantation.\n\nMehrabi, A\n\nGolling, M\n\nKashfi, A\n\nBoucsein, T\n\nSchemmer, P\n\nGutt, CN\n\nSchmidt, J\n\nBüchler, MW\n\nKraus, TW\n\nBeiträge in Fachzeitschriften\nISI:000226594900008\n15666391.0\n10.1002/lt.20299\nNone\nCatecholamines are often administered during and after liver transplantation (LTx) to support systemic perfusion and to increase organ oxygen supply. Some vasoactive agents can compromise visceral organ perfusion. We followed the hypothesis that the vasculature of transplanted livers presents with a higher sensitivity, which leads to an increased vulnerability for flow derangement after application of epinephrine (Epi) or norepinephrine (NorEpi). Hepatic macroperfusion and microperfusion during systemic Epi or NorEpi infusion were measured by Doppler flow and thermodiffusion probes in porcine native, denervated, and transplanted livers (n = 16 in each group). Epi or NorEpi were infused (n = 8 in each subgroup) in predefined dosages (low dose = 5 microg/kg/minute and high dose = 10 microg/kg/minute) over 240 minutes. Systemic cardiocirculatory parameters were monitored continuously. Hepatic perfusion data were compared between all groups at comparable time points and dosages. In all native, denervated, and transplanted liver groups, Epi and NorEpi induced an inconsistent rise of mean arterial pressure and heart rate shortly after onset of infusion in both dosages compared with baseline. No significant differences of cardiovascular parameters at comparable time points were observed. In native livers, Epi and NorEpi induced only temporary alterations of hepatic macrocirculation and microcirculation, which returned to baseline 2 hours after onset of infusion. No significant alterations of hepatic blood flow were detected after isolated surgical denervation of the liver. By contrast, transplanted livers showed a progressive decline of hepatic macrocirculation (33-75% reduction) and microcirculation (39-58% reduction) during catecholamine infusions in a dose-dependent fashion. Characteristics of liver blood flow impairment were comparable for both vasoactive agents. In conclusion, pronounced disturbances of hepatic macrocirculation and microcirculation were observed during systemic Epi and NorEpi infusion after LTx compared with native and denervated livers. Microcirculation disturbances after LTx might be explained by impairment of hepatic blood flow regulation caused by an increased sensitivity of hepatic vasculature after ischemia-reperfusion and by lengthening of vasopressor effects caused by reduced hepatocyte metabolism. Clinicians should be aware of this potentially hazardous effect. Therefore, application of catecholamines after clinical LTx should be indicated carefully.\n\nSchemmer, Peter\n\n\n"
},
{
"text": "\n177356\nLong-term clinical outcomes of imiquimod 5% cream vs. diclofenac 3% gel for actinic keratosis on the face or scalp: a pooled analysis of two randomized controlled trials.\n\nGollnick, H\n\nDirschka, T\n\nOstendorf, R\n\nKerl, H\n\nKunstfeld, R\n\nBeiträge in Fachzeitschriften\nISI:000486313800001\n31407414.0\n10.1111/jdv.15868\nNone\nActinic keratosis (AK) is an early in situ epidermal cancer which can progress to invasive squamous cell carcinoma (SCC). Imiquimod 5% cream (IMIQ) and diclofenac 3% gel (DIC) are frequently used to treat AK; however, their long-term effects following repeated treatment cycles have never been compared.\n To compare IMIQ and DIC in the treatment of AK with respect to the risk of change to grade III AK or invasive SCC, after 3 years.\n Data were pooled from two randomized, active-controlled, open-label, multicentre, multinational, phase IV studies (Clinicaltrials.gov NCT00777127/NCT01453179), with two parallel groups. Studies were conducted between 2008 and 2015 and were almost identical in design. Patients eligible for inclusion were immunocompetent adults with 5-10 visible AK lesions on the face/scalp and grade I/II AK. The primary endpoint was inhibition of histological change to grade III AK or invasive SCC in the study treatment area, observed until month 36. Patients applied either IMIQ or DIC for a maximum of six treatment cycles.\n In total, 479 patients (IMIQ 242; DIC 237) were included in the full analysis set. Histological change to grade III AK or invasive SCC was observed until month 36 in 13 (5.4%) patients treated with IMIQ, compared with 26 (11.0%) patients treated with DIC (absolute risk difference -5.6% [95% confidence interval -10.7%, -0.7%]). Time to histological change was greater in the IMIQ group than the DIC group (P = 0.0266). Frequency of progression to invasive SCC was lower with IMIQ than with DIC at all time points. Initial clearance rate was higher in the IMIQ group compared with the DIC group, while recurrence rate was lower. Both treatments were well tolerated.\n Over 3 years, IMIQ was superior to DIC in clearing AK lesions and preventing histological change to grade III AK or invasive SCC and recurrence.\n © 2019 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.\n\nKerl, Helmut\n\n\n"
},
{
"text": "\n1174\nHemodynamic effects of different modes of mechanical ventilation in acute cardiac and pulmonary failure: an experimental study.\n\nZobel, G\n\nDacar, D\n\nRödl, S\n\nBeiträge in Fachzeitschriften\nISI:A1994PK86500019\n7924375.0\nNone\nNone\nOBJECTIVE: To determine the hemodynamic effects of four different modes of mechanical ventilation in an animal model of acute cardiac and pulmonary failure. DESIGN: Prospective, randomized, crossover design. SETTING: University research laboratory. SUBJECTS: Twelve piglets weighing 10 to 16 kg. INTERVENTIONS: The experimental protocol consisted of three stable 30-min periods: when ventricular and pulmonary functions were normal (control), after the induction of acute cardiac failure by the administration of a beta-adrenergic receptor blocker, and after pulmonary failure induced by repeated lung lavage. Modes of mechanical ventilation included controlled mechanical ventilation, high-frequency oscillation, synchronized high-frequency jet ventilation, and external negative pressure oscillation combined with pressure support ventilation. Each mode of respiratory support was randomly and sequentially applied to each animal with the assessment of cardiopulmonary function at the end of each period. MEASUREMENTS AND MAIN RESULTS: Continuous monitoring included electrocardiogram, right atrial, left ventricular end-diastolic, pulmonary arterial, intrathoracic aortic, arterial, esophageal, and transpulmonary pressures and arterial and mixed venous oxygen saturation measurements. In addition, cardiac output using the thermodilution technique was measured intermittently. Whereas in the control period cardiac index was significantly (p < .05) higher during synchronized high-frequency jet ventilation (193 +/- 19.3 mL/kg/min) than during controlled mechanical ventilation (151 +/- 12.1 mL/kg/min) and high-frequency oscillation (151 +/- 18.1 mL/kg/min), there was no significant hemodynamic difference between the four modes of mechanical ventilation in the cardiac and pulmonary failure periods. In the pulmonary failure period, transpulmonary pressure was significantly higher during high-frequency oscillation (7.1 +/- 1.6 mm Hg) than during controlled mechanical ventilation (5.6 +/- 0.6 mm Hg), high-frequency ventilation (4.1 +/- 0.4 mm Hg), and external negative pressure oscillation combined with pressure support ventilation (5.3 +/- 0.5 mm Hg). CONCLUSIONS: Synchronized high-frequency ventilation improves cardiac performance in control conditions. No hemodynamic difference is present between the four modes of mechanical ventilation in the cardiac and pulmonary failure periods. External negative pressure oscillation combined with pressure support ventilation has moderate hemodynamic advantages over controlled mechanical ventilation and high-frequency oscillation in different clinical settings, but it also results in a deterioration of pulmonary gas exchange during the pulmonary failure period.\n\nRoedl, Siegfried\n\n\n"
},
{
"text": "\n126960\nLow vitamin D levels are associated with impaired virologic response to PEGIFN + RBV therapy in HIV-hepatitis C virus coinfected patients.\n\nMandorfer, M\n\nReiberger, T\n\nPayer, BA\n\nFerlitsch, A\n\nBreitenecker, F\n\nAichelburg, MC\n\nObermayer-Pietsch, B\n\nRieger, A\n\nTrauner, M\n\nPeck-Radosavljevic, M\n\nVienna HIV &\n\nLiver Study Group\n\nBeiträge in Fachzeitschriften\nISI:000312542900011\n23238552.0\n10.1097/QAD.0b013e32835aa161\nNone\nBackground: Low 25-hydroxyvitamin D [25(OH)D] levels are commonly found in HIV-hepatitis C virus (HCV) coinfected patients and are associated with liver fibrosis. No association between 25(OH)D levels and response to pegylated interferon alpha-2a/2b plus ribavirin (PEGIFN + RBV) has yet been reported for HIV-HCV coinfected patients. Design: Epidemiological characteristics, HIV and HCV infection parameters, liver biopsies, as well as data on virologic response was available in 65 patients who received chronic hepatitis C (CHC) therapy with PEGIFN + RBV within a prospective trial. 25(OH)D levels were retrospectively assessed using stored screening serum samples obtained within 35 days prior to CHC treatment. Methods: According to their 25(OH)D levels, patients were assigned to the normal (>30 ng/ml; D-NORM), the insufficiency (10-30 ng/ml; D-INSUFF), or the deficiency (<10 ng/ml; D-DEF) group. HCV-GT 1/4, high HCV-RNA load (>6 x 10(5) IU/ml), advanced liver fibrosis (METAVIR F3/F4), and IL28B rs12979860non-C/C were considered as established risk factors for treatment failure in HIV-HCV coinfected patients. Results: Thirty-seven (57%) and 15 (23%) patients presented with D-INSUFF and D-DEF, respectively, whereas only 13 (20%) patients had normal 25(OH) D levels. Substantial differences in cEVR (D-NORM 92% vs. D-INSUFF 68% vs. D-DEF 47%; P = 0.008) and SVR (D-NORM 85% vs. D-INSUFF 60% vs. D-DEF 40%; P = 0.029) rates were observed between 25(OH)D subgroups. Especially in difficult-to-treat patients with multiple (three to four) established risk factors, low 25(OH)D levels were clearly associated with lower rates of SVR [patients without 25(OH)D deficiency 52% vs. D-DEF 0%; P = 0.012]. Conclusion: Low 25(OH)D levels may impair virologic response to PEGIFN + RBV therapy, especially in difficult-to-treat patients. Vitamin D supplementation should be considered and evaluated prospectively in HIV-HCV coinfected patients receiving CHC treatment. (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:227-232\n\nObermayer-Pietsch, Barbara\n\n\n"
},
{
"text": "\n127564\nIs there Unity in Europe? First Survey of EUPSA Delegates on the Management of Gastroschisis.\n\nZani, A\n\nRuttenstock, E\n\nDavenport, M\n\nAde-Ajayi, N\n\nBeiträge in Fachzeitschriften\nISI:000315021100005\n23093440.0\n10.1055/s-0032-1326954\nNone\nAim To report the first European survey on the current management of gastroschisis and ascertain the degree of variability between centers. Methods A 10-question survey was administered at the 2011 European Paediatric Surgeons' Association (EUPSA) Congress. Questionnaires were completed by 205 delegates from 39 countries. A total of 21 responses (10%) were incomplete and voided. The remaining 184 were divided on the basis of following region of practice: Western Europe (WE, n = 102), Eastern Europe (EE, n = 59), and non-European countries (n = 23). Differences between WE and EE were analyzed using contingency tests. p < 0.05 was considered significant. Results A total of 15% WE and 2% EE responders work in centers where antenatal magnetic resonance imaging scans are routinely used. Nonplanned delivery is the most popular approach (WE 46%, EE 58%). Primary closure is the preferred choice (WE 92%, EE 86%), and it is achieved by operative fascial closure in the majority (WE 80%, EE 75%) rather than by Bianchi technique (WE 20%, EE 25%). Staged reduction and closure is less popular (WE 8%, EE 14%), and it is achieved by custom-made silo (WE 25%, EE 12.5%), preformed silo (PFS) followed by surgical closure (WE 63%, EE 75%), or PFS followed by sutureless closure (WE 12%, EE 12.5%). Objection to PFS in WE is mainly related to surgeons' lack of confidence in the technique (40%), whereas in EE it is due to unavailability and high cost (62%, p = 0.01). In case of associated intestinal atresia, immediate resection and anastomosis is preferred by 60% of WE surgeons versus 35% of EE surgeons (p = 0.03), who equally favor primary closure and delayed surgery (33%). Nutrition is preferably delivered by peripheral long line in WE (64%) and by central line inserted in the first week of life in EE (62%, p = 0.003). Conclusions Primary fascial closure is currently the preferred method of gastroschisis closure across Europe. Aspects of care such as strategy for intestinal atresia and delivery of parenteral nutrition differ significantly between WE and EE. Economic considerations appear to influence management strategy particularly in EE. A Europe-wide audit appears warranted to identify whether this survey reflects actual practice.\n\n\n"
},
{
"text": "\n157124\nST-segment depression in hypertensive patients is linked to elevations in blood pressure, pulse pressure and double product by 24-h Cardiotens monitoring.\n\nUen, S\n\nBaulmann, J\n\nDüsing, R\n\nGlänzer, K\n\nVetter, H\n\nMengden, T\n\nBeiträge in Fachzeitschriften\nISI:000183338600023\n12714873.0\n10.1097/01.hjh.0000059023.82022.78\nNone\nVarious statements are made concerning peaks of heart rate (HR), blood pressure (BP) and double product (product of HR and systolic BP) as triggers for ST-segment depression. The aim of the present study was to identify determinants of ST-segment depression with a new ambulatory device for simultaneous 24-h electrocardiogram (ECG) and BP monitoring.\n A total of 63 treated patients (63 +/- 9 years, 33 women and 30 men) with arterial hypertension and ischemic heart disease were studied with a new ambulatory 24-h BP measurement (ABPM) device evaluated according to the BHS protocol (Cardiotens, Meditech, Hungary). This device allows simultaneous ST-segment analysis with extra BP recordings triggered by episodes of ST-segment depression.\n ST-segment (Holter ECG) depression (> 1 mm and > 60 s) was demonstrated in 26 patients with a mean duration of 4.95 +/- 2.6 min and a peak in the early morning hours. All ST-segment depressions were silent and occurred during a significant increase of BP (15 +/- 11 mmHg systolic and 10 +/- 5 mmHg diastolic, compared with the mean ABPM values) and a significant increase of the double product from 10 921 +/- 2 395 (24-h mean) to 14 515 +/- 2329 (during ST-depression). The recorded systolic and diastolic BP (SBP, DBP) values from the pre ST-event were significant higher compared with 24-h values (153 +/- 19 versus 145 +/- 22 mmHg systolic, 83 +/- 12 versus 78 +/- 14 diastolic). The mean pulse pressure (PP) value in the group with ST-depression was significantly higher than in the group without ST changes (69 +/- 16 versus 58 +/- 10 mmHg; P < 0.005). A total of 73% of patients with ST-events compared with 35% without ST-events showed a PP >or= 60 mmHg (P = 0.025).\n Simultaneous ABPM and ST-segment analysis identifies episodes of silent myocardial ischemia during increases of BP and HR. Hypertensive patients with ischemic heart disease and ST events show higher mean pulse pressure values than are observed in patients without events. A PP of >or= 60 mmHg is linked to an increased risk of silent myocardial ischemias.\n\n\n"
},
{
"text": "\n159040\nQuantitative analysis of axon collaterals of single pyramidal cells of the anterior piriform cortex of the guinea pig.\n\nYang, J\n\nLitscher, G\n\nSun, Z\n\nTang, Q\n\nKishi, K\n\nOda, S\n\nTakayanagi, M\n\nSheng, Z\n\nLiu, Y\n\nGuo, W\n\nZhang, T\n\nWang, L\n\nGaischek, I\n\nLitscher, D\n\nLippe, IT\n\nKuroda, M\n\nBeiträge in Fachzeitschriften\nISI:000394695100001\n28178946.0\n10.1186/s12868-017-0342-7\nPMC5299671\nThe role of the piriform cortex (PC) in olfactory information processing remains largely unknown. The anterior part of the piriform cortex (APC) has been the focus of cortical-level studies of olfactory coding, and associative processes have attracted considerable attention as an important part in odor discrimination and olfactory information processing. Associational connections of pyramidal cells in the guinea pig APC were studied by direct visualization of axons stained and quantitatively analyzed by intracellular biocytin injection in vivo.\n The observations illustrated that axon collaterals of the individual cells were widely and spatially distributed within the PC, and sometimes also showed a long associational projection to the olfactory bulb (OB). The data showed that long associational axons were both rostrally and caudally directed throughout the PC, and the intrinsic associational fibers of pyramidal cells in the APC are omnidirectional connections in the PC. Within the PC, associational axons typically followed rather linear trajectories and irregular bouton distributions. Quantitative data of the axon collaterals of two pyramidal cells in the APC showed that the average length of axonal collaterals was 101 mm, out of which 79 mm (78% of total length) were distributed in the PC. The average number of boutons was 8926 and 7101, respectively, with 79% of the total number of boutons being distributed in the PC. The percentage of the total area of the APC and the posterior piriform cortex occupied by the average distribution region of the axon collaterals of two superficial pyramidal (SP) cells was about 18 and 5%, respectively.\n Our results demonstrate that omnidirectional connection of pyramidal cells in the APC provides a substrate for recurrent processes. These findings indicate that the axon collaterals of SP cells in the PC could make synaptic contacts with all granule cells in the OB. This study provides the morphological evidence for understanding the mechanisms of information processing and associative memory in the APC.\n\nGaischek, Ingrid\n\nLippe, Irmgard\n\nLitscher, Gerhard\n\n\n"
},
{
"text": "\n162530\nIntracystic interferon-alpha in pediatric craniopharyngioma patients: an international multicenter assessment on behalf of SIOPE and ISPN.\n\nKilday, JP\n\nCaldarelli, M\n\nMassimi, L\n\nChen, RH\n\nLee, YY\n\nLiang, ML\n\nParkes, J\n\nNaiker, T\n\nvan Veelen, ML\n\nMichiels, E\n\nMallucci, C\n\nPettorini, B\n\nMeijer, L\n\nDorfer, C\n\nCzech, T\n\nDiezi, M\n\nSchouten-van Meeteren, AYN\n\nHolm, S\n\nGustavsson, B\n\nBenesch, M\n\nMüller, HL\n\nHoffmann, A\n\nRutkowski, S\n\nFlitsch, J\n\nEscherich, G\n\nGrotzer, M\n\nSpoudeas, HA\n\nAzquikina, K\n\nCapra, M\n\nJiménez-Guerra, R\n\nMacDonald, P\n\nJohnston, DL\n\nDvir, R\n\nConstantini, S\n\nKuo, MF\n\nYang, SH\n\nBartels, U\n\nBeiträge in Fachzeitschriften\nISI:000410404200020\n28499018.0\n10.1093/neuonc/nox056\nPMC5596165\nCraniopharyngiomas are frequent hypothalamo-pituitary tumors in children, presenting predominantly as cystic lesions. Morbidity from conventional treatment has focused attention on intracystic drug delivery, hypothesized to cause fewer clinical consequences. However, the efficacy of intracystic therapy remains unclear. We report the retrospective experiences of several global centers using intracystic interferon-alpha.\n European Société Internationale d'Oncologie Pédiatrique and International Society for Pediatric Neurosurgery centers were contacted to submit a datasheet capturing pediatric patients with cystic craniopharyngiomas who had received intracystic interferon-alpha. Patient demographics, administration schedules, adverse events, and outcomes were obtained. Progression was clinical or radiological (cyst reaccumulation, novel cysts, or solid growth).\n Fifty-six children (median age, 6.3 y) from 21 international centers were identified. Median follow-up from diagnosis was 5.1 years (0.3-17.7 y). Lesions were cystic (n = 22; 39%) or cystic/solid (n = 34; 61%). Previous progression was treated in 43 (77%) patients before interferon use. In such cases, further progression was delayed by intracystic interferon compared with the preceding therapy for cystic lesions (P = 0.0005). Few significant attributable side effects were reported. Progression post interferon occurred in 42 patients (median 14 mo; 0-8 y), while the estimated median time to definitive therapy post interferon was 5.8 (1.8-9.7) years.\n Intracystic interferon-alpha can delay disease progression and potentially offer a protracted time to definitive surgery or radiotherapy in pediatric cystic craniopharyngioma, yet demonstrates a favorable toxicity profile compared with other therapeutic modalities-important factors for this developing age group. A prospective, randomized international clinical trial assessment is warranted.\n © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com\n\nBenesch, Martin\n\n\n"
},
{
"text": "\n179908\nThe CoDiNOS trial protocol: an international randomised controlled trial of intravenous sildenafil versus inhaled nitric oxide for the treatment of pulmonary hypertension in neonates with congenital diaphragmatic hernia.\n\nCochius-den Otter, S\n\nSchaible, T\n\nGreenough, A\n\nvan Heijst, A\n\nPatel, N\n\nAllegaert, K\n\nvan Rosmalen, J\n\nTibboel, D\n\nCDH EURO Consortium\n\nBeiträge in Fachzeitschriften\nISI:000512774800277\n31694851.0\n10.1136/bmjopen-2019-032122\nPMC6858099\nCongenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on 'trial and error'. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.\n In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018-2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided) <0.05 is considered significant in all analyses.\n Ethics approval has been granted by the ethics committee in Rotterdam (MEC-2017-324) and the central Committee on Research Involving Human Subjects (NL60229.078.17) in the Netherlands. The principles of the Declaration of Helsinki, the Medical Research Involving Human Subjects Act and the national rules and regulations on personal data protection will be used. Parental informed consent will be obtained.\n NTR6982; Pre-results.\n © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.\n\nUrlesberger, Berndt\n\n\n"
},
{
"text": "\n185363\nPlate versus intramedullary fixation of two-part and multifragmentary displaced midshaft clavicle fractures - a long-term analysis.\n\nChan, G\n\nKorac, Z\n\nMiletic, M\n\nVidovic, D\n\nPhadnis, J\n\nBakota, B\n\nBeiträge in Fachzeitschriften\nNone\n29122117.0\n10.1016/S0020-1383(17)30734-9\nNone\nSurgical fixation of displaced midshaft clavicle fractures is predominantly achieved with intramedullary (IM) or plate fixation. Both techniques have potential pitfalls: plate fixation involves greater periosteal stripping and protuberance of the implant, whereas IM fixation may be associated with implant-related complications, such as migration or skin irritation, which may lead to further surgery for implant removal. The aim of this study was to compare these two methods in simple (Robinson 2b.1) and multifragmentary (Robinson 2b.2) displaced midshaft clavicle fractures.\n A total of 133 consecutive patients who underwent surgical fixation for a displaced midshaft clavicle fracture with either IM fixation using a 2.5-mm Kirschner wire or plate fixation using an 8-hole Dynamic Compression Plate (DCP) were retrospectively reviewed. Follow-up was a minimum of 1 year. The patients were allocated into two injury groups: displaced simple 2-part fractures (64 IM vs. 16 DCP) and displaced multifragmentary fractures (27 IM vs. 26 DCP). The major observed outcome measures were: infection rate, non-union rate, reoperation rate and postoperative range of motion (ROM).\n Rates of non-union for displaced 2-part fractures were 2/64 (3.13%) with IM fixation and 0/16 (0.00%) with plate fixation (p = 0.477). For displaced multifragmentary fractures, rates of non-union were 2/27 (7.41%) with IM fixation and 0/26 (0.00%) with plate fixation (p = 0.161). No significant difference was observed between the two fixation modalities in patient-reported time to regain ROM on the injured side for displaced 2-part fractures (p = 0.129) and displaced multifragmentary fractures (p = 0.070). Deep infection rate was zero (p = 1.000) overall in the study, and reoperation rate for IM and plate fixation, respectively, was 3.13% and 6.25% in the Robinson 2b.1 group (p = 0.559) and 7.41% and 7.69% in the Robinson 2b.2 group (p = 0.969).\n IM fixation of displaced midshaft clavicle fractures (Robinson 2b.1) has an equivalent non-union rate to plate fixation and similarly low complication and reoperation rates. For displaced midshaft multifragmentary clavicle fractures (Robinson 2b.2), the higher non-union rates observed with IM fixation leads us to recommend consideration of plate fixation for Robinson 2b.2 fractures.\n © 2017 Elsevier Ltd. All rights reserved.\n\n\n"
},
{
"text": "\n2832\nVascular bed-dependent roles of the peptide CGRP and nitric oxide in acid-evoked hyperaemia of the rat stomach.\n\nHolzer, P\n\nWachter, C\n\nJocic, M\n\nHeinemann, A\n\nBeiträge in Fachzeitschriften\nISI:A1994PR82700016\n7532714.0\n10.1113/jphysiol.1994.sp020385\nPMC1155830\n1. Acid back-diffusion through a disrupted gastric mucosal barrier is known to increase gastric mucosal blood flow via a neural mechanism. The present study examined how the acid-evoked change in the gastric microcirculation compares with blood flow changes in the left gastric artery, one of the major arteries supplying the stomach, and whether the dilator mediators in the left gastric artery are identical to those in the gastric mucosa. 2. The experiments were performed on rats anaesthetized with urethane. Blood flow in the left gastric artery was measured by the ultrasonic transit time shift technique, and blood flow in the gastric mucosa was assessed by the hydrogen gas clearance method. 3. Gastric acid back-diffusion evoked by perfusion of the stomach with 15% ethanol in 0.15 M HCl increased blood flow in the left gastric artery by a factor of 4.7, which was significantly larger than the 2.9-fold increase in blood flow through the gastric mucosa. Blood pressure and heart rate were not altered appreciably. 4. The acid-evoked hyperaemia in the left gastric artery was left unaltered by atropine and the substance P receptor antagonist RP-67580. 5. The calcitonin gene-related peptide (CGRP) antagonist CGRP (8-37) had no effect on gastric blood flow but prevented the dilator action of CGRP and inhibited the acid-evoked hyperaemia in the gastric mucosa to a larger degree than the hyperaemia in the left gastric artery. 6. Blockade of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester (L-NAME) caused constriction of the left gastric artery and the gastric mucosal microvessels. The acid-evoked vasodilatation in the gastric mucosa was blocked by L-NAME, whereas the dilator response in the left gastric artery was not significantly depressed. 7. The data show that the gastric hyperaemic response to acid back-diffusion results from dilatation of mucosal microvessels and extramural arteries. The dilator mechanisms, however, differ between the two vascular beds. CGRP and nitric oxide are important vasodilator mediators in the gastric mucosa but are of less relevance in the left gastric artery.\n\nHeinemann, Akos\n\nHolzer, Peter\n\n\n"
}
]
}