Neutralization of endogenous NGF prevents the sensitization of nociceptors supplying inflamed skin

Evidence suggests that nerve growth factor (NGF) is an important mediator in inflammatory pain states: NGF levels increase in inflamed tissue, and neutralization of endogenous NGF prevents the hyperalgesia which normally develops during inflammation of the skin. Here we asked whether NGF contributes to sensitization of primary afferent nociceptors, which are an important component of pain and hyperalgesia in inflamed tissue. An in vitro skin nerve preparation of the rat was used to directly record the receptive properties of thin myelinated (Adelta) and unmyelinated (C) nociceptors innervating normal hairy skin, carrageenan-inflamed skin and carrageenan-inflamed skin where endogenous NGF had been neutralized by application of a trkA-IgG (tyrosine kinase Aimmunoglobulin G) fusion molecule. Following carrageenan inflammation, there was a marked increase in the proportion of nociceptors which displayed ongoing activity (50% of nociceptors developed spontaneous activity compared to 4% of nociceptors innervating normal uninflamed skin), and this was reflected in a significant increase in the average ongoing discharge activity. Spontaneously active fibres were sensitized to heat and displayed a more than twofold increase in their discharge to a standard noxious heat stimulus. Furthermore, the number of nociceptors responding to the algesic mediator bradykinin increased significantly from 28% to 58%. By contrast, the mechanical threshold of nociceptive afferents did not change during inflammation. When the NGF-neutralizing molecule trkA-IgG was coadministered with carrageenan at the onset of the inflammation, primary afferent nociceptors did not sensitize and displayed essentially normal response properties, although the inflammation as evidenced by tissue oedema developed normally. We therefore conclude that NGF is a crucial component for the sensitization of primary afferent nociceptors associated with tissue inflammation.     

Mast cell-associated Renaut bodies in the peroneal nerve of a dog with a history of mastocytosis

Multiple Renaut bodies were identified by light microscopy in the biopsied common peroneal nerve of a dog with generalized neuropathy, hypothyroidism and a history of cutaneous mastocytosis. In addition, numerous granulated cells were associated with most of the Renaut bodies. Electron microscopic examination confirmed these to be mast cells, both central and peripheral to Renaut bodies, a phenomenon never previously reported. Endoneurial fibrosis, myelinated fiber loss, as well as evidence of axonal degeneration, demyelination and remyelination were observed. 'Vacuolation' of endoneurial fibroblasts was also present. The location of these Renaut bodies in the common peroneal nerve, and the absence of any documented or expected nerve compression, implicates other etiological factors. These observations are the first to report an association between mast cells and Renaut bodies. It is possible that mast cells, at least in this case, are involved in the formation of Renaut bodies.     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

Abortion utilization: does travel distance matter?

The further a woman must travel in order to obtain an abortion, the less likely she is to get one. Distance is especially disadvantageous to blacks, and most so to black teenagers. Distance discourages use among rural as well as urban women. Opening new clinics increases abortion use in nearby communities.     

GD2抗体达妥昔单抗β治疗神经母细胞瘤的临床应用专家共识（2021年版）

神经母细胞瘤(neuroblastoma,NB)是儿童最常见的颅外实体肿瘤,临床表现及预后具有高度异质性。低危患儿预后较好,高危患儿即使接受化疗、放疗、手术、造血干细胞移植等多种方法的综合治疗,长期存活率仍不足50%。探索潜在的治疗靶点对于提高高危患者的生存率具有重要意义。双唾液酸神经节苷脂抗原GD2在NB细胞高表达,达妥昔单抗β可与NB细胞膜表面过表达的GD2特定靶点结合,触发抗体依赖性细胞介导的细胞毒性作用和补体依赖的细胞毒性效应,通过双重免疫机制而发挥抗肿瘤作用。通过总结国外多项关键临床研究,并结合在海南和天津医疗先行区的上市前初步应用经验,我们对达妥昔单抗β的安全性、有效性、适用人群及使用方法进行总结和推荐,提出本共识,旨在为临床医师提供指导与帮助。     

Knowledge and Attitudes About Pre-Exposure Prophylaxis Among Young Adults Experiencing Homelessness in Seven U.S. Cities

Purpose

Evidence suggests that young adults experiencing homelessness (YEH) are at elevated risk of HIV compared to housed youth. Given the limited research on pre-exposure prophylaxis (PrEP) awareness among YEH, this study examined their PrEP knowledge and attitudes.

Histological patterns of gastritis in H. pylori-infected individuals with a family history of gastric cancer

OBJECTIVE: Different types of chronic gastritis, including antral predominant, corpus predominant, and multifocal pangastritis, are associated with Helicobacter pylori infection. Specific patterns of H. pylori gastritis that might characterize individuals with family histories of noncardia gastric cancer (GC) were investigated. METHODS: Histopathological changes associated with H. pylori gastritis were assessed in 111 individuals with family histories of GC and in 77 without from a region with high prevalence of H. pylori infection and GC. Gastric biopsies were taken from 12 sites (antrum, five; corpus, six; and cardia, one). RESULTS: Individuals (age < 36 yr) with family histories of GC developed pangastritis and had higher H. pylori bacterial scores (p < 0.05) in the gastric corpus, whereas those without family histories of GC typically had antral predominant gastritis. The correlation between density of polymorphonuclear leukocytes and density of H. pylori at each biopsy site was statistically significant (p < 0.01). Pangastritis was associated with a higher density of lymphoid aggregates and follicles (p < 0.05) in the corpus of younger individuals (age < 36) and in the antrum of older individuals (age > or = 48) with positive family histories of GC. CONCLUSIONS: Pangastritis and high lymphoid follicle density associated with H. pylori infection were found in patients with family histories of GC. Because a family history of gastric carcinoma is associated with increased risk of gastric cancer development, characterization of histological patterns of gastritis may be applicable to gastric cancer screening and surveillance, especially in relatively young at-risk populations.