Coexisting carcinoid tumors in familial adenomatous polyposis-associated upper intestinal adenomas

Upper gastrointestinal polyps and extraintestinal tumors are well recognized in association with familial adenomatous polyposis (FAP). Although carcinoid tumors have been reported in association with sporadic colonic neoplasms and ulcerative colitis, to date, carcinoids have not been reported in association with FAP. We report a patient with FAP who has recurrent carcinoid tumors located at the bases of duodenal adenomas. The genetic basis of carcinoid neoplasms is still uncertain. This report may represent the clinical effect of the APC gene mutation on the enterochromaffin cell line manifesting as recurrent carcinoid tumors in physical association with intestinal adenomas. Future genetic analysis and epidemiological studies may be of value in determining whether a true association exists.     

Prognostic and aetiological factors in chronic thromboembolic pulmonary hypertension

Several prognostic variables have previously been identified in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Specific medical conditions have also been associated with the development and prognosis of CTEPH. Using a national registry, the current authors have assessed the prognostic value of a larger number of variables and have also attempted to validate the clinical importance of previously identified aetiological factors. Baseline information for all 469 CTEPH patients diagnosed in the UK pulmonary hypertension service between January 2001 and June 2006 was collected from hospital records. Although univariate analysis confirmed the prognostic importance of pulmonary resistance, in multivariate analysis gas transfer and exercise capacity predicted pulmonary endarterectomy perioperative mortality. Cardiac index and exercise capacity independently predicted outcome in patients with nonoperable disease. Previous splenectomy was noted in 6.7% of patients, being significantly more common in patients with nonoperable than operable disease (13.7 versus 3.6%). Medical risk factors were not found to predict mortality. In a large national cohort, predictors of outcome in patients with both operable and nonoperable chronic thromboembolic pulmonary hypertension have been identified. These may be useful in planning treatment. The aetiological importance of previously identified medical risk factors has been confirmed, although the current authors were unable to validate their prognostic strength.     

Vertically acquired HIV diagnosed in adolescence and early adulthood in the United Kingdom and Ireland: findings from national surveillance

Objective

The aim of the study was to describe the characteristics of young people with vertically acquired HIV diagnosed aged ≥13 years.

Methods

A retrospective review of HIV diagnoses reported to well‐established national paediatric and adult HIV surveillance systems in the United Kingdom/Ireland was conducted.

Results

Forty‐two young people with vertically acquired HIV diagnosed aged ≥13 years were identified; 23 (55%) were female, 40 (95%) were black African and 36 (86%) were born in sub‐Saharan Africa. The median age at HIV diagnosis was 14 years (range, 13–20 years). Half of the patients presented with symptoms; the remainder were screened for HIV following diagnosis of a relative. The median CD4 count at diagnosis was 210 cells/μL (range, 0–689 cells/μL), 12 patients (29%) were diagnosed with AIDS at HIV diagnosis or subsequently, and 34 (81%) started combination antiretroviral therapy (ART), most (31 of 34) within a year of diagnosis.

Conclusion

A small number of young people with vertically acquired HIV survive childhood without ART and are diagnosed at age ≥13 years in the United Kingdom/Ireland. Half of the patients were asymptomatic, highlighting the importance of considering HIV testing for all offspring of HIV‐infected women, regardless of age or symptoms. Increased awareness among clinicians and parents is required to reduce delayed presentation with advanced disease and to avoid onward transmission as these young people become sexually active.     

Cephalic tetanus

Neurocritical Care -     

Why would laser acupuncture improve menopausal symptoms?

O'Brien KA, Varigos E, Black C, Komesaroff PA. Laser acupuncture does not improve menopausal symptoms. Menopause 2010; 17: 636–41.     

A common intracellular allosteric binding site for antagonists of the CXCR2 receptor

Background and purpose:

We have previously shown that SB265610 (1-(2-bromo-phenyl)-3-(7-cyano-3H-benzotriazol-4-yl)-urea) behaves as an allosteric, inverse agonist at the C-X-C chemokine (CXCR)2 receptor. The aim of this study was to determine whether SB265610, in addition to two other known antagonists, bind to either of the two putative, topographically distinct, allosteric binding sites previously reported in the Literature.

Experimental approach:

Ten single point mutations were introduced into the CXCR2 receptor using site-directed mutagenesis. Three CXCR2 antagonists were investigated, SB265610, Pteridone-1 (2-(2,3 difluoro-benzylsulphanyl)-4-((R)-2-hydroxy-1-methyl-ethylamino)-8H-pteridin-7-one) and Sch527123 (2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5-methyl-furan-2-yl)-propyl]amino]-3,4-dioxo-cyclobut-1enylamino}-benzamide), and the effect of these mutations on their binding affinity and ability to inhibit interleukin-8-stimulated binding of [³⁵S]GTPγS was examined.

Key results:

Seven of the nine mutations introduced into the C-terminal domain and intracellular loops of the receptor produced a significant reduction in affinity at least one of the antagonists tested. Of those seven mutations, three produced a significant reduction in the affinity of all three antagonists, namely K320A, Y314A and D84N. In all but one mutation, the changes observed on antagonist affinity were matched with effects on inhibition of interleukin-8-stimulated [³⁵S]GTPγS binding.

Conclusions and implications:

These antagonists bind to a common intracellular, allosteric, binding site of the CXCR2 receptor, which has been further delineated. As many of these mutations are close to the site of G protein coupling or to a region of the receptor that is responsible for the transduction of the activation signal, our results suggest a molecular mechanism for the inhibition of receptor activation.     

Challenges of Francisella classification exemplified by an atypical clinical isolate

The accumulation of sequenced Francisella strains has made it increasingly apparent that the 16S rRNA gene alone is not enough to stratify the Francisella genus into precise and clinically useful classifications. Continued whole-genome sequencing of isolates will provide a larger base of knowledge for targeted approaches with broad applicability. Additionally, examination of genomic information on a case-by-case basis will help resolve outstanding questions regarding strain stratification. We report the complete genome sequence of a clinical isolate, designated here as F. novicida-like strain TCH2015, acquired from the lymph node of a 6-year-old male. Two features were atypical for F. novicida: exhibition of functional oxidase activity and additional gene content, including proposed virulence determinants. These differences, which could potentially impact virulence and clinical diagnosis, emphasize the need for more comprehensive methods to profile Francisella isolates. This study highlights the value of whole-genome sequencing, which will lead to a more robust database of environmental and clinical genomes and inform strategies to improve detection and classification of Francisella strains.     

老年冠心病患者抑郁与肿瘤坏死因子-α水平有相关性

目的: 调查住院老年冠心病患者的抑郁情绪；初步探讨老年冠心病患者肿瘤坏死因子（TNF）的改变及抑郁对TNF的影响。方法: 连续收集2008年8月～11月住院的老年冠心病患者214例。根据中国精神疾病分类与诊断标准第三版（CCMD-3），将纳入患者分为冠心病并发抑郁组54例，冠心病不伴抑郁组160例。测量各生化指标，ZUNG抑郁自评量表得分和TNF值，观察各组血清TNF水平及血清TNF水平与抑郁得分的相关性。结果: 冠心病并发抑郁症组TNF值高于冠心病非抑郁组（P<0.05）；TNF与抑郁得分呈正相关（r=0.424，P<0.01）。控制白细胞计数与C-反应蛋白后，TNF仍与抑郁得分呈正相关（r=0.344，P=0.000）。结论: 老年冠心病并发抑郁患者TNF水平增高。