Characteristics and outcomes of acute colitis diagnosed on cross-sectional imaging presenting via the emergency department in an Irish academic medical centre.

BACKGROUND AND AIMS: A significant proportion of patients presenting to the Emergency Department with gastrointestinal symptoms that result in cross-sectional imaging receive a radiological diagnosis of colitis. We aimed to review the characteristics, outcomes, and final diagnoses of new emergency department presentations with colitis diagnosed on cross-sectional imaging. METHODS: A radiology database was interrogated to identify patients admitted from the Emergency Department of St James's Hospital whose cross-sectional imaging demonstrated colitis. Baseline demographic data, information on inpatient investigations, final diagnoses, and outcomes were recorded. Adverse outcomes were defined as a requirement for surgery, intensive care unit (ICU) stay, or mortality RESULTS: A total of 118 patients, 67% female, were identified with a median age of 64 years (range 16.9-101.2). Median (range) admission duration was 10 days (1-241). Final colitis diagnoses were infectious (28%), undefined (27%), reactive (18%), inflammatory bowel disease (11%), ischaemic (9%), chemotherapy-associated (3%), diverticular (3%), and medication-associated (1%). Colonic perforation, colectomy, and mortality occurred in 1%, 5%, and 13% of the cohort respectively. On univariate analysis, low haemoglobin, low albumin, high lactate, and male gender were associated with adverse outcomes with the following odds ratios (OR) and 95% confidence intervals (95%CI) were low haemoglobin 1.49 [1.15-1.92] P = 0.002, low albumin 1.16 [1.07-1.25] P = 0.0002, lactate 1.65 [1.13-2.42] P = 0.009, and male gender 3.09 [1.23-7.77] P = 0.019. On multivariate analysis, male gender was associated with adverse outcomes. CONCLUSION: Patients presenting to the Emergency Department with a colitis, requiring an abdominal CT are a heterogenous group with a proportion having concomitant intra-abdominal pathology resulting in critical illness. Hence their is a significant morbidity and mortality observed in this cohort which should not be extrapolated to a general population of patients presenting with colitis. In this cohort of patients, anaemia, hypoalbuminaemia, and elevated lactate in patients presenting to the ED with acute colitis are significantly associated with adverse outcomes. Early recognition of these prognostic factors may identify the cohort of patients who are best managed in a high-dependency setting.

Guidelines for timely initiation of chemotherapy: a proposed framework for access to medical oncology and haematology cancer clinics and chemotherapy services.

These guidelines, informed by the best available evidence and consensus expert opinion, provide a framework to guide the timely initiation of chemotherapy for treating cancer. They sit at the intersection of patient experience, state-of-the-art disease management and rational efficient service provision for these patients at a system level. Internationally, cancer waiting times are routinely measured and publicly reported. In Australia, there are existing policies and guidelines relating to the timeliness of cancer care for surgery and radiation therapy; however, until now, equivalent guidance for chemotherapy was lacking. Timeliness of care should be informed, where available, by evidence for improved patient outcomes. Independent of this, it should be recognised that shorter waiting periods are likely to reduce patient anxiety. While these guidelines were developed as part of a proposed framework for consideration by the Victorian Department of Health, they are clinically relevant to national and international cancer services. They are intended to be used by clinical and administrative staff within cancer services. Adoption of these guidelines, which are for the timely triage, review and treatment of cancer patients receiving systemic chemotherapy, aims to ensure that patients receive care within a timeframe that will maximise health outcomes, and that access to care is consistent and equitable across cancer services. Local monitoring of performance against this guideline will enable cancer service providers to manage proactively future service demand.

The CCR5-delta32 mutation: impact on disease outcome in individuals with hepatitis C infection from a single source.

BACKGROUND AND AIMS: Chemokines are small polypeptides, a major function of which is lymphocyte recruitment and trafficking. The aim of this study was to assess the involvement of inherited variations in CCR2, CCR5, and the ligand RANTES in determining disease outcome in hepatitis C virus (HCV) infected individuals. METHODS: A total of 283 women, all exposed to HCV genotype 1b from a single donor, and including those who had spontaneously cleared the virus and those chronically infected, were genotyped for CCR2, CCR5, and RANTES polymorphisms. The frequencies of these polymorphisms were then compared with disease activity and severity. RESULTS: CCR5, CCR2, and RANTES genotypes were compared with HCV polymerase chain reaction (PCR) status, alanine aminotransferase levels, and liver histology. There was no significant relationship between CCR2 or RANTES polymorphisms and disease outcome or severity. However, CCR5delta32 heterozygotes were more likely to have spontaneous clearance of the virus than those without the mutation (42% PCR negative v 28.3% negative; p = 0.044, odds ratio 1.83 (95% confidence interval 1.1-3.6)). Among the subgroup of DRB1*03011 negative individuals, previously found to be associated with more severe inflammation, the difference in histological inflammatory score (CCR5WT/WT = 4.9 v CCR5delta32/WT = 3.53; p = 0.043) was significant. CONCLUSION: Heterozygosity for CCR5delta32 was shown to be significantly associated with spontaneous hepatitis C viral clearance and with significantly lower hepatic inflammatory scores in subgroups within this cohort. Both controls and the HCV population had similar heterozygosity frequencies.

In vitro micronucleus assay with Chinese hamster V79 cells - results of a collaborative study with in situ exposure to 26 chemical substances.

A collaborative study with 10 participating laboratories was conducted to evaluate a test protocol for the performance of the in vitro micronucleus (MN) test using the V79 cell line with one treatment and one sampling time only. A total of 26 coded substances were tested in this study for MN-inducing properties. Three substances were tested by all 10 laboratories and 23 substances were tested by three or four laboratories in parallel. Six aneugenic, 7 clastogenic and 6 non-genotoxic chemicals were uniformly recognised as such by all laboratories. Three chemicals were tested uniformly negative by three laboratories although also clastogenic properties have been reported for these substances. Another set of three clastogenic substances showed inconsistent results and one non-clastogenic substance was found to be positive by one out of three laboratories. Within the study, the applicability of the determination of a proliferation index (PI) as an internal cytotoxicity parameter in comparison with the determination of the mitotic index (MI) was also evaluated. Both parameters were found to be useful for the interpretation of the MN test result with regard to the control of cell cycle kinetics and the mode of action for MN induction. The MN test in vitro was found to be easy to perform and its results were mainly in accordance with results from chromosomal aberration tests in vitro.

The MHC is a major determinant of viral status, but not fibrotic stage, in individuals infected with hepatitis C.

BACKGROUND & AIMS: In hepatitis C infection, several studies have examined the role of the major histocompatibility complex (MHC) in determining outcome, with variable results. To clarify the importance of MHC, we examined class II DR and DQ antigens in a homogenous cohort of women exposed to hepatitis C genotype 1b from a single inoculum. METHODS: Of 243 participants, 95 had spontaneous viral clearance and 148 are chronically infected. The frequencies of HLA class II DR and DQ antigens were compared between the 2 groups and between liver biopsy findings of 145 chronically infected subjects. RESULTS: DRB1*0101 and DQB1*0501 alleles were more frequent in subjects who sustained viral clearance than in chronically infected subjects (32.3% and 36.8% vs. 8.8% and 14.2%, respectively; P = 0.002). DRB1*03011 and DQB1*0201 occurred more frequently in chronically infected subjects than in those who cleared the virus (41.5% and 42.6% vs. 16.7% and 15.8%, respectively; P = 0.001). Both DRB1*03011 and DQB1*0201 were significantly less frequent in those with higher inflammatory scores on liver biopsy. CONCLUSIONS: We show that in a homogenous cohort of women infected with the same hepatitis C virus, several HLA antigens are associated with either viral clearance or persistence. This suggests a strong role for host immunogenetic factors in determining outcome in hepatitis C infection.

Primary cutaneous B-cell lymphoma: an association of chronic hepatitis C infection.

Primary cutaneous B-cell lymphoma is a low-grade malignancy, distinct from other lymphomas in terms of biological activity and response to treatment. We describe a 77-year-old woman with a five-year history of chronic hepatitis C infection who developed a lower-limb lesion over a period of 3 months which was diagnosed as a high-grade cutaneous B-cell lymphoma. Despite a lack of definitive evidence implicating hepatitis C virus (HCV) in the aetiology of lymphomas, there is considerable research which establishes a strong association between these two diseases. On the basis of published research and the demonstration of HCV RNA in the lymphomatous tissue, we consider this to be a rare case of primary cutaneous lymphoma in association with hepatitis C.

Analysis of stimulatory and inhibitory amino acids for development of hamster one-cell embryos in vitro.

Hamster embryo development to the blastocyst stage in vitro can be modulated by amino acids. This series of experiments employed both empirically and statistically designed approaches to elucidate which of 20 amino acids inhibit or stimulate development and to devise a complement of amino acids that best supports in vitro development of hamster 1-cell embryos. Development and/or mean cell number were significantly inhibited by the presence of leucine, tyrosine, valine, isoleucine, phenylalanine, arginine, methionine, or cysteine (at 0.5 mM) and isoleucine, phenylalanine, or tryptophan (at 0.05 mM). Three amino acids--glutamine, taurine, and glycine--were stimulatory and in combination improved development; the culture medium containing these amino acids was designated Hamster Embryo Culture Medium-5. Moreover, addition of another eight amino acids--asparagine, aspartic acid, serine, glutamic acid, histidine, lysine, proline and cysteine (medium designated HECM-6)--had a significant stimulatory effect on development over previously formulated culture media for hamster embryos. These results demonstrated that amino acids, alone and in combination, can markedly stimulate or inhibit hamster embryo development in vitro up to the blastocyst stage. Embryo transfer experiments showed that HECM-5 and -6 (chemically defined, protein-free culture media) supported normal preimplantation embryo development in vitro. This study also indicates that empirically designed embryo culture media formulations can be as effective as those obtained by application of statistical methodologies.