Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery.

BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery. METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis. RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin. CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

Beta-blocker Therapy is Associated with Decreased 1-year Mortality After Emergency Laparotomy in Geriatric Patients.

BACKGROUND AND AIMS: Emergency laparotomy is associated with a great risk of mortality in the elderly. The hyperadrenergic state induced by surgical trauma may play an important role in the pathophysiology of this increased risk. Studies have shown that beta-blocker exposure may be associated with decreased morbidity and mortality in the perioperative period. We aimed to study the effect of beta-blocker on mortality in geriatric patients undergoing emergency laparotomy. MATERIAL AND METHODS: This is a retrospective study of patients who underwent emergency laparotomy between 1 January 2015 and 31 December 2016 at a single institution. The outcomes of interest were the association between post-operative complications and in-hospital and 1-year mortality in patients on beta-blocker therapy (BB(+)) and those who were not (BB(-)). The Poisson regression analysis was used to evaluate the association. RESULTS: A total of 192 patients were included of whom 62 (32.2%) had pre-operative beta-blocker therapy with continued exposure during their hospital stay. The in-hospital mortality was 17.7% in the BB(+) and 23.8% in the BB(-) cohorts (p = 0.441). One-year mortality was significantly lower in the BB(+) group compared to the BB(-) group (30.6% versus 47.7%; p = 0.038). After adjusting for confounders, the incidence of deaths during 1 year post-operatively decreased by 35% in the BB(+) group (incidence rate ratio = 0.65, p = 0.004). No significant differences in the incidence of post-operative complications between the two groups could be measured. CONCLUSION: Beta-blocker therapy may be associated with reduced 1-year mortality following emergency laparotomy in geriatric patients.

ß-Blocker after severe traumatic brain injury is associated with better long-term functional outcome: a matched case control study.

PURPOSE: Severe traumatic brain injury (TBI) is the predominant cause of death and disability following trauma. Several studies have observed improved survival in TBI patients exposed to ß-blockers, however, the effect on functional outcome is poorly documented. METHODS: Adult patients with severe TBI (head AIS ≥ 3) were identified from a prospectively collected TBI database over a 5-year period. Patients with neurosurgical ICU length of stay <48 h and those dying within 48 h of admission were excluded. Patients exposed to ß-blockers ≤ 48 h after admission and who continued with treatment until discharge constituted ß-blocked cases and were matched to non ß-blocked controls using propensity score matching. The outcome of interest was Glasgow Outcome Scores (GOS), as a measure of functional outcome up to 12 months after injury. GOS ≤ 3 was considered a poor outcome. Bivariate analysis was deployed to determine differences between groups. Odds ratio and 95% CI were used to assess the effect of ß-blockers on GOS. RESULTS: 362 patients met the inclusion criteria with 21% receiving ß-blockers during admission. After propensity matching, 76 matched pairs were available for analysis. There were no statistical differences in any variables included in the analysis. Mean hospital length of stay was shorter in the ß-blocked cases (18.0 vs. 26.8 days, p < 0.01). The risk of poor long-term functional outcome was more than doubled in non-ß-blocked controls (OR 2.44, 95% CI 1.01-6.03, p = 0.03). CONCLUSION: Exposure to ß-blockers in patients with severe TBI appears to improve functional outcome. Further prospective randomized trials are warranted.

Tracking particle size distributions in a moving bed biofilm membrane reactor for treatment of municipal wastewater.

A study has been conducted to investigate the effect of loading rates on membrane fouling in a moving bed biofilm membrane reactor process for municipal wastewater treatment, especially analysing the fate of submicron colloidal particles and their influence on membrane fouling. Two operating conditions defined as low and high organic loading rates were tested where the development and fate of the particulate material was characterised analysing the particle size distributions throughout the process. Analysis of the membrane performance showed higher fouling rates for the high-rate conditions. The fraction of colloidal submicron particles was higher in the membrane reactor indicating that fouling by these particles was a dominant contribution to membrane fouling.

Detection of foot-and-mouth disease virus in nasal swabs of asymptomatic cattle by RT-PCR within 24 hours.

A method for extracting RNA from animal-derived materials that provides foot-and-mouth disease viral template suitable for Tth polymerase-dependent synthesis of cDNA and subsequent PCR is described. Viral genomes were detected in less than 24 h. Nasal swabs that can be easily and repeatedly collected, proved suitable for virus detection by PCR, even during the asymptomatic stages of infection.

Differentiation of classical swine fever virus (CSFV) strains using monoclonal antibodies against structural glycoproteins.

Two panels of monoclonal antibodies (mAbs) against the classical swine fever virus (CSFV) envelope glycoproteins E2 (12 mAbs) and E0 (11 mAbs) were established and tested by immunoperoxidase binding assay against 135 pestivirus strains and isolates. Variability of the binding pattern was demonstrated for CSFV and also for bovine viral diarrhea virus (BVDV) strains and isolates. The panels of mAbs against E2 and E0 led to very different reactivity patterns. Particular mAbs against E2 reacted with (i) all CSFV isolates, (ii) only 4 out of 126 CSFV isolates, or (iii) about 90% of the tested CSFV isolates and 78% of ruminant pestivirus isolates. Anti CSFV E0 mAbs allowed the detection of a greater variability among the CSFV strains and isolates than the anti E2 mAbs. None of the 11 anti E0 mAbs recognized an epitope conserved for CSFV or showed crossreactivity with ruminant pestiviruses. The use of both panels of mAbs against two CSFV structural glycoproteins led to the discrimination of 21 antigenic types of CSFV strains and isolates. The described panels can be used to trace the origin of CSFV after outbreaks of the disease.

Inactivation of viruses in liquid manure.

The stability of some viruses and methods of virus inactivation in liquid manure are reviewed. The authors discuss experimental data on the stability of foot and mouth disease virus, classical swine fever virus, Aujeszky's disease virus, African swine fever virus, swine influenza virus, porcine paramyxovirus, bovine virus diarrhoea virus and transmissible gastroenteritis of pigs virus. Recommendations and practical advice are given for the choice and application of chemical disinfectants for slurry.

[Classical swine fever]. / Klassische Schweinepest.

The principles of aetiology, pathogenesis, diagnosis and immunology of classical swine fever as well as control measures are described. This review focuses on new diagnostic methods, immune reactions and possibilities for control of CSF in the context of the current eradication plans.

[Quality management in the serodiagnosis of European swine fever: results of comparative tests]. / Qualitätsmanagement bei der Serodiagnostik der Europäischen Schweinepest (ESP): Ergebnisse von Ringversuchen.

In the course of inter-laboratory quality management comparative serological tests on classical swine fever (CSF) are conducted once per year. Results from tests carried out in 1994 and 1995 indicate that most regional diagnostic laboratories were able to classify the test sera correctly as CSF-positive, bovine viral diarrhea (BVD)-positive and negative, respectively. Difficulties were encountered in the differential diagnosis of CSF and BVD in neutralisation tests. There is a need to improve the standardization of CSF serology on the basis of a well established method in order to ensure reliability of test results and to enable comparison of results obtained from different laboratories.

[Comparison of different BVD virus strains for their use in the differential diagnosis of classical swine fever--an attempt to standardize neutralization tests]. / Vergleich verschiedener BVDV-Stämme für Zwecke der Differentialdiagnose in der KSP-Serologie--ein Beitrag zur Standardisierung des Neutralisationstestes.

Six bovine virus diarrhoea (BVD) virus strains were tested in the neutralization test for their use in the differential diagnosis in classical swine fever (CSF) serology. The aim of the investigation was to find a suitable BVD virus strain guaranteeing a safe differentiation of CSF- and BVD virus induced antibodies using permanent cell cultures (PK-15, MDBK). For test purposes the neutralizing antibody titres of 73 defined test sera were titrated against the CSF virus strain Alfort/187 as well as the BVD virus strains Grub, Paplitz, NADL, 1138/69, Stendal, 10421/Han 94). Tests were repeated fivefold. The level of mean antibody titres, the differences in titre to the homologous pestivirus strain, the standard deviation and the variation coefficient served as test criteria. The BVD virus strains Grub and NADL yielded the best results. In view of harmonization and standardization the BVD virus strain NADL in connection with a standard protocol for neutralization tests is recommended for the differential diagnosis in CSF serology. Due to the adaptation of the permanent cell-lines PK-15 and MDBK to horse serum a further source of contamination with non cytopathogenic BVD viruses under routine conditions can be excluded.

Effect of inhibitors of methylation on early and late interferon synthesis in bovine kidney cell cultures.

In virus infected bovine kidney cell cultures mainly late interferon is produced starting at about 4 hr after infection. Poly rI:poly rC induced cells as well as interferon pretreated virus infected cells produce early interferon starting immediately after induction. In infected cells the proportion of early interferon increases with time of interferon pretreatment, while late interferon is decreasing. Production of late interferon is selectively inhibited by cycloleucine, an inhibitor of S-adenosylmethionine (SAM) biosynthesis, whereas early interferon synthesis is not affected by the drug. Likewise, late interferon production is reduced much stronger than early interferon production by a combination of adenosine, L-homocysteine thiolactone, and erythro-9[3-(2-hydroxynonyl)]-adenine (EHNA) inducing in cells an accumulation of S-adenosylhomocysteine which inhibits SAM mediated methylation reactions. Inhibition of late interferon synthesis by cycloleucine is time and dose dependent and partially reversible. Cycloheximide equally blocks both early and late interferon production. Inhibition of incorporation of methyl groups into cellular RNA by the methylation inhibitors used is demonstrated by labeling with [methyl-3H] methionine and 3H-uridine. The results indicate that the synthesis of functional mRNA for early and late interferon is differentially sensitive to inhibition of methylation. The data suggest that, if early and late interferon is coded by the same structural gene, two different pathways are available for the cell to synthesize one species of mRNA.

Assay of bovine interferons in cultures of the porcine cell line IB-RS-2.

An assay for bovine interferons has been developed using the porcine cell line IB-RS-2 and a bovine enterovirus, CBV-D, as challenge virus. The method is based on estimation of cytopathic effect measured by uptake of neutral red. Teh assay is simple, sensitive, and reproducible. A comparative test of different viruses in IB-RS-2 cells and secondary calf kidney cells revealed that the sensitivity of a virus to interferon can vary up to 1,000-fold in the two cell systems. Vesicular stomatitis virus was found to be rather insensitive to interferon in IB-RS-2 cells.

Inhibitors of foot-and-mouth disease virus. Temperature-dependence of the effect of guanidine on virus growth.

In suspended secondary calf kidney cells infected with foot-and-mouth disease virus (FMDV) the temperature range for optimal virus growth is shifted down by 3 to 5 degrees C in the presence of 1--2 mM guanidine. For some virus strains this shift is so effective that at infraoptimal temperatures virus yield in guanidine-treated cells exceeds that of the corresponding control by more than one log10. On the contrary, at supraoptimal temperatures inhibition of virus growth by the drug is strongly enhanced. At a concentration of 1 to 2 mM guanidine virus yield reduction or enhancement is based on a decrease in increase, respectively, of the number of virus producing cells (infective centers; I.C.), while virus yield per I.C. is less affected. Besides this "thermomimetic" effect virus production is inhibited by guanidine depending on the concentration of this substance. A mutant of FMDV strain O1L, resistant to 4.2 guanidine, did not differ from the original virus in its antigenic behaviour in the passive immunohemolysis test.

Multiplication and distribution of Aujeszky's disease (pseudorabies) virus in vaccinated and non-vaccinated pigs after intranasal infection.

The primary sites of Aujeszky's disease virus (ADV) multiplication in intranasally (i.n.) infected pigs were found to be in the nasopharyngeal, tracheal and pulmonary regions. From the second day post infection (DPI) onward ADV invaded the central nervous system and other organs. The virus was isolated from the nasopharyngeal region for at least 2 weeks. In serum ADV was present with low levels from DPI 1 to DPI 7. In pigs vaccinated with an inactivated vaccine and then challenged the distribution of ADV was rather similar to that in non-vaccinated animals, in spite of the presence of neutralizing antibodies. The virus titres in the organs generally were lower than in non-vaccinated animals up to DPI 7. Thereafter, titre differences were no longer significant. Virus was isolated from the tonsils and the lungs for at least 2 weeks. Interferon production in vaccinated infected pigs was significantly lower than in non-vaccinated infected pigs. Though multiplication and dissemination of ADV occurred, vaccinated pigs did not show clinical symptoms of Aujeszky's disease. Traces of ADV were detected in a small percentage of white blood cells (WBC) of non-vaccinated infected pigs. ADV was isolated from the lymphocyte-enriched and polymorphnuclear leukocyte-enriched fractions, but not from the monocyte-enriched fractions, apparently on account of the small cell number. Multiplication of ADV was demonstrated in cultured WBC from some of the vaccinated and non-vaccinated infected animals.

Amino acid changes outside the G-H loop of capsid protein VP1 of type O foot-and-mouth disease virus confer resistance to neutralization by antipeptide G-H serum.

Antiserum to a peptide corresponding to the 135-154 sequence of capsid protein VP1 of the foot-and-mouth disease virus O1 Kaufbeuren was raised in a pig. Although this serum contained neutralizing antibodies, the pig showed clinical symptoms after challenge. Virus isolated from this pig was identified as a mutant, with changes at positions 50, 198 and 211 of VP1 and at position 209 of VP2. This mutant, as well as a plaque isolate of it, differing from the challenge virus at positions 198 on VP1 (alanine being substituted for glutamic acid) and 209 on VP2 (histidine being substituted for tyrosine) resisted neutralization by the anti-peptide serum also in vitro. The same was observed with the O1 Kaufbeuren-related strain O1 Burgwedel, isolated from cattle in the field. It had substitutions only at positions 43 and 101 on VP1. The results show that neutralization epitopes flanking positions 145-147 on VP1 are modulated by other capsid protein parts. These parts seem to be important for neutralization escape in natural FMDV host species.

Identification of foot-and-mouth disease virus replication in vaccinated cattle by antibodies to non-structural virus proteins.

Antibodies raised in cattle against foot-and-mouth disease virus by vaccination or by experimental infection were distinguished. Vaccination elicited only antibodies to virus capsid proteins and the polymerase 3D. Virus replication in cattle elicited additional antibodies directed against the non-structural proteins 2B, 2C, 3AB1, and/or 3C irrespective of prior vaccination or whether the cattle exhibited symptoms of disease. Non-permissive mice inoculated with virus responded in the same way, indicating that antibodies raised due to the transient presence of antigen are safely recognized by the method applied which was radioimmunoprecipitation. All kinds of infections were thus detected and it was possible to differentiate between cattle exposed or not exposed to challenge in the field, and further between protected animals and possible virus carriers.

A second envelope glycoprotein mediates neutralization of a pestivirus, hog cholera virus.

Several monoclonal antibodies (MAbs) raised against hog cholera virus (HCV) reacted with the HCV structural glycoprotein gp44/48 and neutralized the virus. The presence of HCV gp44/48 on the viral surface was directly demonstrated by immunogold electron microscopy. Eight anti-HCV gp44/48 MAbs were tested by immunoperoxidase assay against a panel of pestivirus strains. Each MAb showed a distinct pattern of reactivity with HCV strains. It is suggested that the MAbs are well suited for epidemiological investigations of HCV outbreaks.