Innate and cognate mechanisms of pulmonary eosinophilia in helminth infection

Passage of helminth larvae through the lungs can cause pulmonary eosinophilia that may have evolved as a means of parasite attrition. If allergic responses represent a misdirected activation of this arm of the immune system, then mechanisms governing eosinophil recruitment during infection would be expected to be closely related to those seen in allergy. We studied primary Necator americanus infection and compared this to multiply-infected or vaccinated mice. The arrival of larvae in the lungs triggered rapid eosinophil recruitment, which was greatly enhanced in previously sensitized mice. Interestingly, the presence of larvae in the lung was sufficient to trigger eosinophil chemoattractant production, including the chemokines eotaxin and MIP-1alpha, and was not enhanced by prior exposure to the parasites. Infection stimulated IL-5 production in all groups; however, this and IgE production were greatly enhanced in sensitized animals. Elevated IL-5 increased bone marrow production of eosinophils, and eosinophilia was abrogated by treatment with anti-IL-5 antibody. Therefore, trapping of larvae in the pulmonary vasculature is sufficient to trigger eosinophil recruitment, by induction of chemokines and IL-5. Primed cognate Th2 immunity does not increase local chemokine production, but does increase IL-5 production, which greatly enhances the availability of eosinophils for recruitment to the lung.     

Classification of R1 resections for pancreatic cancer: the prognostic relevance of tumour involvement within 1 mm of a resection margin

Aims:  The current Royal College of Pathologists guidelines for pancreatoduodenectomy specimen reporting recommend that microscopic evidence of tumour within 1 mm of a resection margin (RM) should be classified as R1. No clinical evidence exists to justify this classification. The aim of this study was to identify the proportion of pancreatoduodenectomy specimens in which 'equivocal' RMs are present (tumour involvement within 1 mm of, but not directly reaching, one or more resection margins) and whether the survival of these patients was similar to that of patients with 'unequivocal' RM involvement.
Methods and results:  Patients with histologically confirmed pancreatic ductal adenocarcinoma undergoing pancreatoduodenectomy between 1997 and 2007 ( n  = 163) were identified from a prospective database. One hundred and twenty-eight cases (79%) were classified as R1. Of these, 57 (45% of all R1 cases) were based on 'equivocal' margin involvement. There was no significant difference in overall survival between equivocal and unequivocal R1 resections (log rank, P  = 0.102). All R1 resections had a poorer survival on univariate (log rank, P  = 0.013), but not multivariate, analysis (Cox, P  = 0.132).
Conclusions:  Our results indicate that cases with microscopic tumour involvement within 1 mm of a resection margin should be considered synonymous with incomplete excision for resected pancreatic cancer.     

Findings from a feasibility study to improve GP elicitation of patient concerns in UK general practice consultations

Objectives

To establish: a) feasibility of training GPs in a communication intervention to solicit additional patient concerns early in the consultation, using specific lexical formulations (“do you have ‘any’ vs. ‘some’ other concerns?”) noting the impact on consultation length, and b) whether patients attend with multiple concerns and whether they voiced them in the consultation.

What adolescents living with long-term conditions say about being involved in decision-making about their healthcare: A systematic review and narrative synthesis of preferences and experiences

Objective

To understand the preferences and experiences of adolescents (age 10–19) with long-term conditions (LTCs) towards involvement in discussions and decisions regarding management of their condition.

Significant ethnic variation in total and free testosterone concentration

OBJECTIVE: Measurement of serum testosterone is an integral part of the assessment of men presenting to endocrine clinics. Little is known about the variation of total bound or bioavailable testosterone by ethnic group. The principal determinant of testosterone bioavailability is SHBG, which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insulin sensitivity. DESIGN: Men of three ethnic groups living in Manchester, UK, were sampled randomly from population registers being of white European (n = 55), Pakistani (n = 50) and African-Caribbean (AfC) origin (n = 75). Circulating serum testosterone and SHBG concentrations were measured and free testosterone calculated. Insulin sensitivity (HOMA-S) and insulin secretory capacity (HOMA-B) were determined from fasting plasma intact insulin and glucose values. RESULTS: Testosterone levels were lower in Pakistani men (mean 14.6 nmol/l, 95% confidence interval 12.6-16.6 nmol/l) than in Europeans (18.7, 16.8-20.6 nmol/l) or AfCs (18.0, 16.4-19.6 nmol/l) (F = 4.8, P = 0.009). Despite SHBG levels also being lower in Pakistani men (22.9, 19.4-26.5 nmol/l) compared with Europeans (28.7, 25.7-31.8 nmol/l) and AfCs (26.9, 23.9-30.0 nmol/l) (F = 3.0, P < 0.05), circulating free testosterone was significantly lower in the Pakistani group (367, 326-408 pmol/l) than in Europeans (455, 416-494 pmol/l) or AfCs (458, 424-492 pmol/l) (F = 6.8, P = 0.001). Pakistani men were on average 4 cm shorter than other groups. However, the lower free testosterone persisted even when adjusted for height or waist-hip ratio. The lower SHBG in the Pakistani men was paralleled by a lower HOMA-S (0.40, 0.25-0.56) compared with Europeans (0.77, 0.61-0.93) and AfCs (0.80, 0.66-0.93) (F = 8.2, P < 0.0001). SHBG correlated positively with HOMA-S (rho = 0.28, P < 0.001) and strongly with total testosterone (rho = 0.54, P < 0.001). There was no difference in insulin secretory capacity (HOMA-B) in Pakistani men compared with Europeans and AfCs. Multiple linear regression analysis showed that total testosterone was independently and negatively related to ln fasting insulin (beta = -0.28, P < 0.001) and age (beta = -0.17, P = 0.02) and positively to ln SHBG (beta = 0.23, P < 0.001) and height (beta = 0.22, P = 0.001). There was no relationship with ethnicity or waist-hip ratio. CONCLUSION: Both total bound and calculated free testosterone were lower in Pakistani men. SHBG levels were also lower in Pakistani men, in keeping with poorer insulin sensitivity. We propose that further work is necessary to establish ethnic-specific ranges for the interpretation of total circulating and free testosterone levels in men.     

CD40 ligand-independent B cell activation revealed by CD40 ligand-deficient T cell clones: evidence for distinct activation requirements for antibody formation and B cell proliferation

We report the capacity of CD40 ligand (CD40L)-negative T cell clones to activate human B cells. CD40L-negative T cells induce a level of B cell proliferation 10–20% of that seen with normal T cells. The signal provided by the negative clones is synergistic with that derived from a CD40L transfectant, and restores B cell proliferation to normal levels, showing that CD40L-negative T cell clones are not inherently inhibitory for B cells. Although their capacity to induce proliferation was much reduced, CD40L-negative T cell clones were still strong inducers of B cell differentiation to plasma cells. This differentiation to plasma cells was inhibited by a CD40L transfectant. The data are discussed with regard to the normal in vivo mechanism for maintaining B cell memory and memory antibody responses to T-dependent antigens.     

Some perinatal characteristics of monozygotic twins who are dichorionic

Zygosity testing of all multiple births allowed the identification of a subgroup of 42 monozygotic twin pairs who have dichorionic placentas, fused and separate. Perinatal outcomes of this group were compared with 110 pairs of monochorionic monozygotic twins and 148 pairs of dizygotic twins. Dichorionic monozygotic twins had the lowest incidence of preterm birth, perinatal mortality, and birth weight discordance. There was an excess of like-sexed over unlike-sexed pairs among the dizygotic twins. © 1995 Wiley-Liss, Inc.