Murine thymocytes proliferate in direct response to interleukin-7

The ability of interleukin-7 (IL-7) to stimulate murine thymocyte proliferation was investigated. IL-7, either alone or in concert with lectin, induced proliferation of adult thymocytes as well as day 13 fetal and adult CD4-/CD8-thymocytes. The IL-7-induced proliferative response of unfractionated thymocytes could not be inhibited by antibodies to IL-2, or IL-4, IL-6, or the IL-2 receptor. In addition, IL-2, IL-4, and IL-6 were not produced by thymocytes activated with IL- 7, as judged by the absence of biologically active cytokine in IL-7- stimulated culture supernatants. IL-7 could act in concert with IL-2 and IL-4 or with IL-4 to enhance the proliferative response of thymocyte cultures. Thus, IL-7 may cause proliferation of thymocytes directly, not indirectly, through production of IL-2, IL-4, or IL-6. IL- 7 may then play a significant role in differentiation of T lymphocytes.     

Rh E/e genotyping by allele-specific primer amplification

It has been shown that the Rhesus (Rh) blood group antigens are encoded by two homologous genes: the Rh D gene and the Rh CcEe gene. The Rh CcEe gene encodes different peptides: the Rh C, c, E, and e polypeptides. Only one nucleotide difference has been found between the alleles encoding the Rh E and the Rh e antigen polypeptides. It is a C-- >G transition at nucleotide position 676, which leads to an amino acid substitution from proline to alanine in the Rh e-carrying polypeptide. Here we present an allele-specific primer amplification (ASPA) method to determine the Rh E and Rh e genotypes. In one polymerase chain reaction, the sense primer had a 3'-end nucleotide specific for the cytosine at position 676 of the Rh E allele. In another reaction, a sense primer was used with a 3'-end nucleotide specific for the guanine at position 676 of the Rh e allele and the Rh D gene, whereas the antisense primer had a 3'-end nucleotide specific for the adenine at position 787 of the Rh CcEe gene. We tested DNA samples from 158 normal donors (including non-Caucasian donors and donors with rare Rh phenotypes) in these assays. There was full concordance with the results of serologic Rh E/e phenotyping. Thus, we may conclude that the ASPA approach leads to a simple and reliable method to determine the Rh E/e genotype. This can be useful in Rh E/e genotyping of fetuses and/or in cases in which no red blood cells are available for serotyping. Moreover, our results confirm the proposed association between the cytosine/guanine polymorphism at position 676 and the Rh E/e phenotype.     

Double bypass for inoperable pancreatic malignancy at laparotomy: postoperative complications and long-term outcome

INTRODUCTION

Between 4% and 13% of patients with operable pancreatic malignancy are found unresectable at the time of surgery. Double bypass is a good option for fit patients but it is associated with high risk of postoperative complications. The aim of this study was to identify pre-operatively which patients undergoing double bypass are at high risk of complications and to assess their long-term outcome.

METHODS

Of the 576 patients undergoing pancreatic resections between 2006 and 2011, 50 patients who underwent a laparotomy for a planned pancreaticoduodenectomy had a double bypass procedure for inoperable disease. Demographic data, risk factors for postoperative complications and pre-operative anaesthetic assessment data including the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) and cardiopulmonary exercise testing (CPET) were collected.

RESULTS

Fifty patients (33 men and 17 women) were included in the study. The median patient age was 64 years (range: 39–79 years). The complication rate was 50% and the in-hospital mortality rate was 4%. The P-POSSUM physiology subscore and low anaerobic threshold at CPET were significantly associated with postoperative complications (p=0.005 and p=0.016 respectively) but they were unable to predict them. Overall long-term survival was significantly shorter in patients with postoperative complications (9 vs 18 months). Postoperative complications were independently associated with poorer long-term survival (p=0.003, odds ratio: 3.261).

CONCLUSIONS

P-POSSUM and CPET are associated with postoperative complications but the possibility of using them for risk prediction requires further research. However, postoperative complications following double bypass have a significant impact on long-term survival and this type of surgery should therefore only be performed in specialised centres.     

Cannabinoid‐induced effects on the nociceptive system: A neurophysiological study in patients with secondary progressive multiple sclerosis

Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients’ electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double‐blind, placebo‐controlled, cross‐over study we investigated cannabinoid‐induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H‐reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta‐9‐tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid‐induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.     

Anal cancer survival: a socioeconomic analysis

IntroductionSquamous cell carcinoma is the most common variant of anal malignancy. Certain disease-related factors have been established in determining survival. These include tumour size, differentiation and nodal involvement. Other factors such as HIV status, human papillomavirus infection, smoking and socioeconomic disparity may have important roles, however few data are available on the UK population. We aim to correlate social deprivation and survival of anal cancer patients at a tertiary centre.Materials and methodsAll consecutive cases diagnosed with anal squamous cell carcinoma and treated as per local protocol between July 2010 and April 2017 were included. The pathological and demographical details were collected from a prospectively maintained database. Socioeconomic deprivation was defined for each postcode using the Index of Multiple Deprivation decile compiled by local governments in England. Survival was estimated using Kaplan–Meier analysis and Cox regression was used to investigate the effect of different factors on overall survival.ResultsA total of 129 patients with anal squamous cell carcinoma over a median follow-up of 43 months were included. Overall survival for the entire patient cohort was 87.7% (95% confidence interval, CI, 82.0–93.7%), 75.5% (95% CI 67.5–84.5%) and 68.9% (95% CI 59.7–79.6%) at one year, three years and five years, respectively. On multivariate analysis, Index of Multiple Deprivation and income do not significantly influence overall survival (p = 0.79, hazard ratio, HR, 1.07; 95% CI 0.61–1.63), (p = 0.99, HR=1.00; 95% CI 0.61–1.63), respectively. Increased risk of death was observed for male sex (p = 0.02, HR=2.80; 95% CI 1.02–5.50) and larger tumour size (p = 0.01, HR=1.64; 95% CI 1.12–2.41).ConclusionIn contrast to US studies, there is little difference in survival between the least deprived and most deprived groups. We attribute this to equal access to intensity-modulated radiation therapy-based chemoradiotherapy. Thus, a highly effective treatment made available to all mitigates any survival difference between socioeconomic groups.