Effects of drilling and stress release on hydraulic properties and porewater chemistry of crystalline rocks

The experimental verification of matrix diffusion in crystalline rocks largely relies on indirect methods performed in the laboratory. Such methods are prone to perturbations of the rock samples by collection and preparation and therefore the laboratory-derived transport properties and fluid composition might not represent in situ conditions. We investigated the effects induced by the drilling process and natural rock stress release by mass balance considerations and sensitivity analysis of analytical out-diffusion data obtained from originally saturated, large-sized drillcore material from two locations drilled using traced drilling fluid. For in situ stress-released drillcores of quartz-monzodiorite composition from the Aspo HRL, Sweden, tracer mass balance considerations and 1D and 2D diffusion modelling consistently indicated a contamination of <1% of the original pore water. This chemically disturbed zone extends to a maximum of 0.1 mm into the drillcore (61.8 mm x 180.1 mm) corresponding to about 0.66% of the total pore volume (0.77 vol.%). In contrast, the combined effects of stress release and the drilling process, which have influenced granodioritic drillcore material from 560 m below surface at Forsmark. Sweden, resulted in a maximum contamination of the derived porewater Cl(-) concentration of about 8%. The mechanically disturbed zone with modified diffusion properties covers the outermost similar to 6 mm of the drillcore (50 mm x 189 mm), whereas the chemically disturbed zone extends to a maximum of 0.3 mm based on mass balance considerations, and to 0.15 mm to 0.2 mm into the drillcore based on fitting the observed tracer data. This corresponds to a maximum of 2.4% of the total pore volume (0.62 vol.%) being affected by the drilling-fluid contamination. The proportion of rock volume affected initially by drilling fluid or subsequently with experiment water during the laboratory diffusion and re-saturation experiments depends on the size of the drillcore material and will become larger the smaller the sample used for the experiment. The results are further in support of matrix diffusion taking place in the undisturbed matrix of crystalline rocks at least in the cm range.

Lower shedding of strongylid eggs by Warmblood horses with recurrent airway obstruction compared to unrelated healthy horses

An association between equine recurrent airway obstruction (RAO) and increased resistance to intestinal parasites has been demonstrated in descendants of an RAO-affected stallion. It was hypothesised that members of another high-incidence RAO family (F) and unrelated RAO-affected Warmblood horses (UA) would shed fewer strongylid eggs than unrelated RAO-unaffected pasture mates (PM) under the same environmental conditions. Faecal worm egg counts were performed on faecal samples (63 F, 86 UA, 149 PM) and classified into three categories: 0, 1-100 and >100 eggs per gram. While results for F did not differ from PM, UA were 2.5-times less likely to shed strongylid eggs than PM. RAO-affected Warmblood horses may be more resistant to strongylid nematodes than unrelated unaffected pasture mates and a family history of RAO does not necessarily confer protection against helminth infections.

Clinical application and reliability of a post abdominal surgery pain assessment scale (PASPAS) in horses

The aim of this study was to refine a multi-dimensional scale based on physiological and behavioural parameters, known as the post abdominal surgery pain assessment scale (PASPAS), to quantify pain after laparotomy in horses. After a short introduction, eight observers used the scale to assess eight horses at multiple time points after laparotomy. In addition, a single observer was used to test the correlation of each parameter with the total pain index in 34 patients, and the effect of general anaesthesia on PASPAS was investigated in a control group of eight horses. Inter-observer variability was low (coefficient of variation 0.3), which indicated good reliability of PASPAS. The correlation of individual parameters with the total pain index differed between parameters. PASPAS, which was not influenced by general anaesthesia, was a useful tool to evaluate pain in horses after abdominal surgery and may also be useful to investigate analgesic protocols or for teaching purposes.

Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas

A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27((Ser15)), p-HSP27((Ser78)), p-HSP27((Ser82)), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82)) and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.

Autotransplant for Hodgkin lymphoma after failure of upfront BEACOPP escalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone)

BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) escalated is the preferred upfront Hodgkin lymphoma (HL) treatment in a number of countries. Upon failure, high-dose chemotherapy with autologous stem cell support (HDT/ASCT) is performed, but its effectiveness has not been verified in this setting. We analyzed all Swiss cases of chemosensitive HL autografted after failure of BEACOPP escalated (n = 22) and compared outcomes with 22 cases of HDT/ASCT following frontline ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) failure. Five-year progression-free survival (PFS) was 76% for ABVD and 42% for BEACOPP escalated (p = 0.029). Two- and 5-year overall survival (OS) was 90% and 71% for ABVD and 72% and 65% for BEACOPP escalated, respectively (p = not significant). Three patients in the ABVD and four in the BEACOPP escalated groups underwent allotransplant for relapse after HDT/ASCT. Grade 3-4 toxicities were comparable in both groups. Three cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) were recorded in the BEACOPP escalated group. The acceptable PFS and OS of chemosensitive patients with HL autografted after failure of upfront BEACOPP escalated seem to justify this approach.

Binding sites of muscarinic and adrenergic receptors in gastrointestinal tissues of dairy cows suffering from left displacement of the abomasum

Muscarinic acetylcholine (M) and adrenergic (AR) receptors mediate gastrointestinal motility. Using radioligand binding assays and real-time polymerase chain reaction, the densities of binding sites and mRNA levels of M(2), M(3), alpha(2AD)- and beta(2)-AR were compared in muscle tissues from the abomasal fundus, pylorus, duodenum, caecum, and external loop of the spiral colon of eight cows with left displacement of abomasum (LDA), and of eight healthy cows. Specific binding of the [(3)H]-ligands to each of the four receptors was competitive and saturable. Binding sites of M(2) (all intestinal sites), M(3) (duodenum and caecum), and of alpha(2AD)-AR (abomasal fundus) were lower (P<0.05) in cows with LDA than in healthy cows. The coefficients of correlation between binding sites and mRNA transcripts of receptors were dissimilar in cows with LDA and healthy cows. The decrease in densities of M (intestine) and of alpha(2AD)-AR (abomasum) receptors suggests their implication in the impairment of motility associated with or leading to LDA.

Development and application of a real-time TaqMan((R)) qPCR assay for detection and quantification of 'Candidatus Mycoplasma haemolamae' in South American camelids

Two alpacas from a herd in southwest Switzerland died for unknown reasons. Necropsy revealed chronic weight loss and pale mucous membranes. Infection with hemotropic mycoplasmas was suspected and subsequently confirmed by molecular methods. In order to investigate the epidemiological situation in this herd, a real-time TaqMan((R)) qPCR assay for the specific detection and quantification of hemoplasma infection in South American camelids was developed. This assay was based on the 16S rRNA gene and amplified 'Candidatus Mycoplasma haemolamae' DNA, but not DNA from other hemoplasmas or non-hemotropic mycoplasma species. The lower detection limit was one copy/PCR, and the amplification efficiency was 97.4%. In 11 out of 24 clinically healthy herd mates of the two infected alpacas, 'Candidatus M. haemolamae' infection was confirmed. No correlation was found between bacterial load and clinical signs or anemia. The assay described herein enables to detect and quantify 'Candidatus M. haemolamae' and may be used in future studies to investigate the prevalence, pathogenesis and treatment follow-up of hemoplasma infections in South American camelids.

Activated coagulation during open and endovascular abdominal aortic aneurysm repair

OBJECTIVE: The study was conducted to determine activation of coagulation in patients undergoing open and endovascular infrarenal abdominal aortic aneurysm repair (EVAR). METHODS: In a prospective, comparative study, 30 consecutive patients undergoing open repair (n = 15) or EVAR (n = 15) were investigated. Blood samples to determine fibrinopeptide A, fibrin monomer, thrombin-antithrombin complex, and D-dimer were taken up to 5 days postoperatively. Routine hematologic and hematochemical parameters as well as clinical data were collected. RESULTS: Both groups showed comparable demographic variables. Operating time was longer in open repair (249 +/- 77 minutes vs 186 +/- 69 minutes, P < .05). Perioperatively elevated markers of coagulation were measured in both groups. Fibrinopeptide A levels did not differ significantly between the groups (P = .55). The levels of fibrin monomer and thrombin-antithrombin complex were significantly higher in patients undergoing EVAR (P < .0001), reflecting increased thrombin activity and thrombin formation compared with open surgery. The D-dimer level did not differ significantly between the groups. These results were also valid after correction for hemodilution. CONCLUSION: These data suggest increased procoagulant activity in EVAR compared with open surgery. A procoagulant state may favor possible morbidity derived from micro- and macrovascular thrombosis, such as in myocardial infarction, multiple organ dysfunction, venous thrombosis and thromboembolism, or disseminated intravascular coagulation.