Clinical Manifestations and Case Management of Ebola Haemorrhagic Fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect

Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs

Renal dysplasia (RD) in dogs is a complex disease with a highly variable phenotype and mode of inheritance that does not follow a simple Mendelian pattern. Cox-2 (Cyclooxgenase-2) deficient mice have renal abnormalities and a pathology that has striking similarities to RD in dogs suggesting to us that mutations in the Cox-2 gene could be the cause of RD in dogs. Our data supports this hypothesis. Sequencing of the canine Cox-2 gene was done from clinically affected and normal dogs. Although no changes were detected in the Cox-2 coding region, small insertions and deletions of GC boxes just upstream of the ATG translation start site were found. These sequences are putative SP1 transcription factor binding sites that may represent important cis-acting DNA regulatory elements that govern the expression of Cox-2. A pedigree study of a family of Lhasa apsos revealed an important statistical correlation of these mutant alleles with the disease. We examined an additional 22 clinical cases from various breeds. Regardless of the breed or severity of disease, all of these had one or two copies of the Cox-2 allelic variants. We suggest that the unusual inheritance pattern of RD is due to these alleles, either by changing the pattern of expression of Cox-2 or making Cox-2 levels susceptible to influences of other genes or environmental factors that play an unknown but important role in the development of RD in dogs

Deciphering the pathogenesis of tendinopathy: a three-stages process

Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments

Measurement of melatonin in body fluids: Standards, protocols and procedures

Abstract: The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6‐ sulphatoxymelatonin in urine, is a defining feature of suprachiasmatic nucleus function, the endogenous oscillatory pacemaker. These measurements are useful to evaluate problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. Additionally, they have become an important tool for psychiatric diagnosis, its use being recommended for phase typing in patients suffering from sleep and mood disorders. Thus, the development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids of animals emerges as necessary. Due to its low concentration and the co‐existence of many other endogenous compounds in blood, the determination of melatonin has been an analytical challenge. This review discusses current methodologies employed for detection and quantification of melatonin in biological fluids and tissues

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Evidence for the non-glycoprotein nature of high molecular weight glutenin subunits of wheat

An isolation and purification procedure for wheat high molecular weight glutenin subunits (HMW-GS) involving no steps expected to cause deglycosylation of glycoproteins was developed to allow removal of the maximum amount of carbohydrates not covalently linked to HMW-GS. Flour was defatted and then extracted with 50% n-propanol (50% n-PrOH) to remove arabinogalactans and glucose-containing material. HMW-GS were extracted with 50% n-PrOH containing 5% beta-mercaptoethanol, precipitated in 60% n-PrOH, alkylated and recovered by precipitation. The partially purified HMW-GS were separated by cation exchange chromatography and resulting fractions purified by RP-HPLC. The purified HMW-GS contained only 0.1% of glucose (corresponding to 51-59 monosaccharide residues per 100 HMW-GS molecules) and no other amino or neutral sugars. The HMW-GS gave a positive reaction in a periodate-digoxigenin glycan detection assay when labelled in solution (with or without periodate oxidation) but not when labelled directly on-the-blot. HMW-GS expressed in Escherichia coli a micro-organism without glycosylation capabilities, reacted in an identical way. Possible reasons are given for the difference in results obtained after labelling in solution or on-the-blot. No positive reaction between the purified HMW-GS and mannose-specific Galanthus nivalis agglutinin was observed. The presence of N-acetylglucosamine in HMW-GS has been previously reported(20). Since neither mannose nor N-acetylgalactosamine were found in the HMW-GS, and these proteins lack the sequon necessary for N-glycosylation, only O-linked GlcNAc moieties are possible. This modification could not be detected using a galactosyltransferase labelling assay. Taken together these results suggest that HMW-GS are not glycosylated. (C) 1996 Academic Press Limitedstatus: publishe

On the presence and activities of proteolytic enzymes in vital wheat gluten

Two vital wheat gluten samples were submitted to an Osborne type fractionation. The proteolytic activities of the resulting fractions were evaluated. Gluten contained endoproteolytic, exoproteolytic, carboxypeptidase, aminopeptidase and N alpha-benzoylarginine-p-nitroanilide hydrolase activities. After extraction with 0.5 M NaCl, and subsequently with 70% (v/v) ethanol, little activity remained in the extracted gluten. Upon autodigestion of gluten no (microbial) enzymes were released. High specificities of gluten-associated proteolytic enzymes were noted and their effects were clearly visible on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The sum of lysine, leucine, phenylalanine, tyrosine and arginine accounted for ca. 40-44% of the released amino acids, while they only make up ca. 18% of vital gluten proteins. Good correlations were found between the proportions of the amino acids released by the different Osborne fractions as a result of autodigestion, indicating that the gluten hydrolysing enzymes found in the different Osborne fractions are probably the same. Autodigestion of gluten proteins was reduced by ca. 73-76% upon addition of pepstatin A (0.2 mM), an inhibitor of aspartic proteases, and by c. 39-41% by phenylmethylsulphonylfluoride (1.0 mM), a serine protease inhibitor. (C) 1997 Academic Press Limited.status: publishe

Heat-induced changes in sodium dodecyl sulphate-sedimentation volume and functionality of vital wheat gluten

Sodium dodecyl sulphate-sedimentation volumes (SDS-SV) were determined as a function of heating time and temperature for two vital wheat gluten samples. The SDS-SV initially increased as a function of heating time when dry gluten was heated at 80 degrees C. However, after reaching a maximum value, further heat treatment resulted in decreased SDS-SV. The heat-induced changes in the gluten occurred more rapidly with increasing heating temperature. Farinograph and Mixograph rheological properties and breadmaking performance of mixtures of a standard flour (96.0%) and heat-treated (80 degrees C) gluten (4.0%) were evaluated as a function of heating times leading to higher SDS-SV values. Although Farinograms, Mixograms and SDS-SV measurements suggested important changes when dry gluten was heated at 80 degrees C; none of these changes affected breadmaking quality in a straight-dough breadmaking test. (C) 1997 Academic Press Limited.status: publishe

Endoxylanases and arabinoxylans in gluten isolated in a batter system

status: publishe