Recurrent 'sterile' verrucous cyst abscesses and epidermodysplasia verruciformis-like eruption associated with idiopathic CD4 lymphopenia

Rupture of follicular (epidermoid) cysts is believed to be the consequence of bacterial infection. We report a 24-year-old man with idiopathic CD4 lymphopenia and chronic Mycobacterium avium intracellulare infection who developed multiple, recurring painful abscesses over the distal extremities that increased in number and severity when systemic steroid and interferon-gamma treatment was instituted for interstitial lung disease. Cultures were consistently negative for microorganisms, but pathological examination revealed ruptured epidermoid cyst walls with human papillomavirus (HPV) viropathic changes (keratinocytes with perinuclear halos and abundant basophilic keratohyaline granules). Cutaneous examination showed numerous, widespread flat-topped papules and achromic macules over the extremities, head and neck. Nested polymerase chain reaction analysis for HPV DNA revealed that the abscess-related cyst walls harboured epidermodysplasia verruciformis (EV)-associated HPV types 20, 24, alb-7 (AY013872) and 80. His cutaneous lesions harboured HPV types 3, 8 and 80. Similar to past reports, our patient developed an EV-like eruption in the setting of immunodeficiency. In this instance, EV-associated HPV infection of the follicular infundibular epithelium or pre-existing cysts in the setting of immunodeficiency may have led to cystic growth, rupture and subsequent painful inflammation.     

甲型H1N1流感患者外周血淋巴细胞变化

目的:寻求甲型H1N1流感患者外周血淋巴细胞与病情的相关性。方法:比较经实时RT-PCR确诊的183例普通型和64例重症型甲型H1N1流感患者外周血淋巴细胞,分析淋巴细胞计数与疾病分型及病情的相关性。结果:治疗前甲型H1N1流感重症型患者淋巴细胞计数[(1.23±0.76)×109L-1]较普通型患者[(1.50±0.59)×109L-1]明显偏低(t=2.958,P<0.01);治疗后患者淋巴细胞计数[(1.92±0.79)×109L-1]较治疗前[(1.27±0.63)×109L-1]明显上升(t=6.33,P<0.01)。结论:淋巴细胞计数对甲型H1N1流感患者临床分型及病情变化有预测作用。     

The death-promoting molecule tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is not required for the development of peripheral lymphopenia or granuloma necrosis during infection with virulent Mycobacterium avium

Disseminated infection with virulent Mycobacterium avium in C57Bl/6 (B6) mice leads to severe lymphocyte depletion in secondary lymphoid organs. In this study, we found an up-regulation of caspase-8 activity in spleen cell extracts from M. avium 25291-infected B6 mice compared to non-infected mice. The activation of this extrinsic apoptotic pathway correlated with an increase in inter-nucleosomal DNA fragmentation in CD4(+) spleen cells, as analysed by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. These data suggest the involvement of death receptors in the induction of lymphocyte loss in the spleen, but previous work has excluded a role for tumour necrosis factor (TNF) receptors and Fas/CD95 in M. avium-induced lymphopenia. TNF-related apoptosis-inducing ligand (TRAIL) is expressed by different cell types of the immune system and induces apoptosis and killing of tumour cells while sparing normal cells. Here we used TRAIL(-/-) mice to determine if the absence of TRAIL prevented M. avium-induced immune pathology. We found that TRAIL-deficient mice still developed splenic lymphopenia during disseminated infection or granuloma necrosis during low-dose infections while exhibiting slightly increased susceptibility to M. avium 25291 when compared to B6 mice. However, in vivo proliferation of less virulent strains of M. avium was not influenced by TRAIL deficiency despite a decrease in interferon-γ production in infected B6.TRAIL(-/-) mice compared to B6 mice. Our results show that TRAIL does not play a significant role in either M. avium-induced pathology or protective immunity.     

Pretreatment neutrophil-to-lymphocyte ratio as an important prognostic marker in stage III locally advanced non-small cell lung cancer: confirmatory results from the PROCLAIM phase III clinical trial

BackgroundNeutrophil-to-lymphocyte ratio (NLR) is an important pretreatment marker of systemic inflammation and tumor aggressiveness. Increased levels of this ratio have been associated with reduced survival in several observational studies of lung cancer. However, supporting analyses from large clinical trial data are lacking.MethodsTo validate the prognostic role of NLR, the current study evaluated data from a randomized phase III study (PROCLAIM; clinicaltrial.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT00686959","term_id":"NCT00686959"}}NCT00686959) of patients with stage IIIA/B, unresectable, non-squamous, non-small cell lung cancer (NSCLC), originally comparing combination pemetrexed-cisplatin chemoradiotherapy with etoposide-cisplatin chemoradiotherapy. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for survival were estimated using a Cox proportional hazards model. Models were adjusted for age, race, sex, stage, treatment, and body mass index (BMI). Patients were followed for a median of 24 months.ResultsIncreased NLR levels at baseline were associated with reduced overall (P_Trend <0.0001) and progression-free survival (P_Trend <0.005). A similar but decreasing linear trend was not observed for lymphocytes count alone.ConclusionsThese findings provide substantiating evidence that NLR, which is routinely available from standard blood testing of patients diagnosed with NSCLC, is an important inflammation-based prognostic marker for survival among patients with locally advanced disease undergoing chemoradiation. Future research will benefit by assessing the prognostic potential of NLR in the context of genetic mutations and molecular markers.     

Streptozotocin-associated lymphopenia in cynomolgus monkeys

Streptozotocin (STZ) is used to induce diabetes in experimental animals. It has a variety of adverse effects, ranging from nausea, emesis, and weight loss to liver damage, renal failure, and metabolic acidosis. STZ also has effects on the immune system, being associated with lymphopenia in rodents, the mechanism of which is not fully understood. We present data on a significant STZ-associated reduction in lymphocyte count in nonhuman primates. We report a significant reduction in absolute lymphocyte count; in 2 monkeys, the lymphopenia persisted for >100 d. However, a significant increase in absolute monocyte count was noted. Furthermore, an increase in serum monocyte chemoattractant protein-1 (MCP-1) was observed. The reduction in lymphocyte numbers may contribute to immunomodulation that may be beneficial to a subsequent islet graft, and may reduce the need for immunosuppressive therapy. The increase in monocytes and MCP-1, however, may be detrimental to the islet graft. Studies are warranted to explore the mechanism by which STZ has its effect.     

匹多莫德对系统性红斑狼疮感染干预的研究

目的 研究早期应用匹多莫德对外周血淋巴细胞减少的系统性红斑狼疮（SLE）干预后感染发生情况及对淋巴细胞亚群和疾病活动度的影响。方法 将SLE治疗过程中外周血淋巴细胞计数减少到0.5×10e9/L以下的患者随机分为干预组和对照组。干预组在外周血淋巴细胞计数减少到0.5×10e9/L时加用匹多莫德，对照组不加用匹多莫德，观察两组患者感染发生率，并观察其对淋巴细胞亚群和SLE疾病活动度(SLEDAI-2000)的影响。结果 干预组26例患者中发生感染6例，感染率为23.08%，而对照组23例患者中发生感染9例，感染率为39.13%，有显著统计学差异（P值<0.01）。干预组外周血淋巴细胞、CD3 T细胞比例、CD4 T细胞比例及CD4 /CD8 比值有明显提高，对CD8 T细胞比例影响不明显。对SLEDAI-2000改善有促进作用（P值<0.01）。 结论 匹多莫德对继发淋巴细胞减少的系统性红斑狼疮感染有很好的预防作用，能有效地调节细胞免疫及体液免疫功能紊乱，增强患者感染免疫反应，促进疾病活动的缓解。     

Schimke immuno-osseous dysplasia: Case report and review

We report on a patient with Schimke immunoosseous dysplasia, an autosomal recessive disorder, and review nine patients from the literature. Manifestations include spondyloepiphyseal dysplasia, lymphopenia, signs of defective cellular immunity, and progressive renal disease. This is the first patient known to have the additional findings of thrombocytopenia and microdontia. © 1993 Wiley-Liss, Inc.