Outcomes of patients with non-lower gastrointestinal cancer diagnosed via the lower gastrointestinal two-week-wait service.

INTRODUCTION: Patients referred via lower gastrointestinal two-week-wait (LGI-2WW) services deemed at 'low risk' of LGI cancer may have delayed or no investigation. However, 20% of patients diagnosed with cancer via the LGI-2WW have non-LGI cancer. This study investigates the outcomes in this under-reported group. METHODS: A retrospective analysis of patients referred to a UK LGI-2WW service with a non-LGI cancer diagnosis (International Classification of Diseases 10th revision) between 1 January 2015 and 31 December 2018. The primary outcome was all-cause mortality. Statistical analysis was undertaken using Kaplan-Meier survival curves with generalised log-rank test and binomial logistic regression of pre-investigation information to predict death. A p-value of < 0.05 represented statistical significance. RESULTS: In total, 140 patients were diagnosed with non-LGI cancer (of 10,155 patients referred via the LGI-2WW pathway). Median follow-up was 13 months (range 0-65 months). Thirty-five patients (35/140; 25%) did not meet LGI-2WW referral criteria. Median survival varied by cancer site (upper gastrointestinal: 43/140 patients, median survival 4 months; gynaecological: 25/140, 25 months; haematological: 22/140, < 50% died; urological: 21/140, 47 months; unknown primary: 12/140, 3 months; lung: 10/140, 17 months; breast: 3/140, 5 months; retroperitoneal: 2/140, 9 months; brain: 1/140, 4 months; adrenal: 1/140, 52 months). Binomial logistic regression was statistically significant (chi-squared goodness-of-fit test = 12.334; p = 0.03); but the presence of comorbidity was the only significant predictive factor of death (p = 0.03). CONCLUSIONS: Patients with non-LGI cancers cannot be easily predicted and have a poor prognosis. Pathways to streamline investigations for LGI cancer should include computed tomography scans for patients at 'low risk' of LGI cancer to ensure that non-LGI cancers are diagnosed.

The role of attentional breadth in perceptual change detection.

Previous research has shown that changes to scenes are often surprisingly hard to detect. The research reported here investigated the relationship between individual differences in attention and change detection. We did this by assessing participants' breadth of attention in a functional field of view task (FFOV) and relating this measure to the speed with which individuals detected changes in scenes. We also examined how the salience, meaningfulness, and eccentricity of the scene changes affected perceptual change performance. In order to broaden the range of individual differences in attentional breadth, both young and old adults participated in the study. A strong negative relationship was obtained between attentional breadth and the latency with which perceptual changes were detected; observers with broader attentional windows detected changes faster. Salience and eccentricity had large effects on change detection, but meaning aided the performance of young adults only and only when changes also had low salience.

Thrombocytopenia following autologous bone marrow transplantation: evidence for autoimmune aetiology and B cell clonal involvement.

Thrombocytopenia outlasting anaemia and neutropenia is a well recognised sequel of autologous bone marrow transplantation (BMT) but the pathogenesis remains unclear. Autoimmune destruction of platelets has been suggested as a possible mechanism. We studied 5 patients who had undergone autologous BMT and were found to have persistent thrombocytopenia (< 150 x 10(9)/l) 6 months from transplantation with a normal haemoglobin level and granulocyte count. Apart from a mild reduction in the megakaryocyte numbers in one case, no other quantitative or qualitative defects of the megakaryocyte lineage were present to explain the peripheral thrombocytopenia. Two cases had positive anti-platelet autoantibodies. Immunoglobulin heavy chain gene rearrangement studies of peripheral blood and bone marrow mononuclear cells using the polymerase chain reaction showed evidence of clonal rearrangement in one of the two cases with positive anti-platelet autoantibodies. Our results support the previous reports that anti-platelet antibody-mediated destruction of platelets may play a role in the pathogenesis of post-autologous BMT thrombocytopenia. Furthermore, the demonstration of a clonal B cell expansion in one of the cases with anti-platelet antibodies suggests an aetiological link between clonal B cells, autoantibody production and thrombocytopenia.

Anti-immunoglobulin and anti-CD40 stimulation induces CD25 expression by resting human tonsillar B lymphocytes.

In this report, the effect of ligation of a number of B-cell surface molecules upon expression of CD25, the 55-kDa inducible component of the IL-2 receptor complex found on T and B lymphocytes, is reported. IL-4 is the only cytokine apparently capable of promoting CD25 expression in human high-density quiescent tonsillar B cells; neither IL-10 nor IL-13 could induce CD25 expression. Cross-linking of the antigen receptors or CD40 with antibody elicited CD25 expression in a dose-dependent manner. Stimulation with anti-CD40 promoted CD25 expression in approximately 25% of B cells, while anti-Ig caused 80% or more of cells to become CD25+. In experiments where the stimuli were used in combination, some additive effects upon CD25 expression were noted, but no obvious synergistic effects could be detected.

Liver regeneration: a comparison of in situ hybridization for histone mRNA with bromodeoxyuridine labeling for the detection of S-phase cells.

We developed an in situ hybridization technique for measurement of proliferative cell numbers through detection of histone mRNA in routinely fixed, paraffin-embedded tissue sections. Histone gene expression is coordinated with the cell cycle, and the increase in expression during S-phase permits unambiguous identification of cells undergoing DNA replication. Histone mRNAs were identified in routinely processed rat liver tissue by non-isotopic in situ hybridization with digoxigenin-labeled oligonucleotide probes. Specific hybrids were detected with alkaline phosphatase-labeled anti-digoxigenin antibody and visualized by BCIP-nitroblue tetrazolium indicator substrate. Unequivocal cytoplasmic labeling was observed in various cell types in the liver remnant during the first 72 hr after a two-thirds partial hepatectomy. The spatial and temporal patterns of histone labeling were almost identical to those obtained by staining with an antibody to bromodeoxyuridine. The identification of histone mRNA appears to be a reliable marker of the S-phase fraction, a technique with the further advantage that the tissue does not have to be first exposed to a nucleotide analogue. Hence, retrospective studies are possible. The probes can be applied to human and animal cells and tissues because the nucleotide sequences of histone genes are conserved.

In situ and slot hybridization analysis of RNA in colorectal tumours and normal colon shows distinct distributions of mitochondrial sequences.

cDNA clones of mRNAs with an abnormal abundance in familial adenomatous polyposis were used to examine the levels and distribution of the mRNAs in tissues from 15 patients with colorectal cancer. Of 12 cloned sequences studied by slot hybridization, one was substantially reduced in tumours compared with normal tissue. Sequence analysis showed this to code for IgA. In situ hybridization was consistent with slot hybridization and immunohistochemistry. Two mitochondrially encoded sequences had distinct distributions detected by in situ hybridization but did not have detectable quantitative differences in whole tumour or mucosa extracts.

A comparison of two anaesthetic techniques for daycase arthroscopy.

A randomised, double-blind study of 100 patients admitted for daycase arthroscopy was undertaken. Fifty patients received alfentanil 500 micrograms and midazolam 5 mg, and 50 received alfentanil 500 micrograms alone, in each case 2 minutes before induction of anaesthesia with methohexitone. Anaesthesia was maintained in both groups with nitrous oxide, oxygen and enflurane. Recovery was assessed quantitatively by measuring time to when they awoke and by a comparison of pre- and postoperative performance of p-deletion and postbox tests. Qualitative assessment of recovery and of postoperative pain was also undertaken. Patients completed a questionnaire to record the incidence of any anaesthetic-related symptoms on the first and second postoperative days. Patients who received midazolam required a reduced dose of methohexitone but their initial recovery time was prolonged significantly. The incidences of anaesthetic-related side effects and postoperative pain were similar in the two groups and while the questionnaires did not reveal any statistically significant differences in symptoms on the first 2 postoperative days, the results indicated that patients who received a larger induction dose of methohexitone were subjectively drowsier on the first day after operation.

Anaesthesia for outpatient termination of pregnancy. A comparison of two anaesthetic techniques.

Inhalation anaesthesia with enflurane was compared with i.v. fentanyl for outpatient termination of pregnancy. Blood loss was greater in the enflurane group with a geometric mean loss of 73.0 ml compared with 43.9 ml in the fentanyl group. There was a greater frequency of nausea nd vomiting in the fentanyl group and no reduction in abdominal pain or need for analgesia after operation. A close relationship was found between blood loss and duration of the procedure but not between blood loss and gestational age or gestational age and anaesthetic time. Either technique is satisfactory for outpatient termination of pregnancy in unpremedicated patients. Despite the greater blood losses with enflurane, it is a safe and reliable method of anaesthesia for this procedure, but the concentration and duration of administration should be kept to a minimum.

Susceptibility of Naegleria fowleri to delta 9-tetrahydrocannabinol.

Growth of the pathogenic amoeboflagellate Naegleria fowleri is inhibited by delta 9-tetrahydrocannabinol (delta 9-THC). delta 9-THC is amoebostatic at 5 to 50 micrograms/ml. delta 9-THC prevents enflagellation and encystment, but does not impair amoeboid movement. Calf serum at 10 and 20% (vol/vol) reduces the antiamoeba activity of delta 9-THC. Only 1-methoxy delta 8-tetrahydrocannabinol, of 17 cannabinoids tested, failed to inhibit growth of N. fowleri. Antinaeglerial activity was not markedly altered by opening the pyran ring, by converting the cyclohexyl ring to an aromatic ring, or by reversing the hydroxyl and pentyl groups on the benzene ring. delta 9-THC prevented the cytopathic effect of N. fowleri on African green monkey (Vero) cells and human epithelioma (HEp-2) cells in culture. delta 9-THC afforded modest protection to mice infected with N. fowleri.