CD4+T-bet+, CD4+pSTAT3+ and CD8+T-bet+ T cells accumulate in peripheral blood during NZB treatment

Circulating T cells and monocytes expressing T-bet, pSTAT1 and pSTAT3 increase in relapsing-remitting multiple sclerosis (RRMS) during relapse. Natalizumab (NZB) is an effective drug in RRMS, but exacerbation of the disease after its discontinuation has been described in some patients. The aim of this research was to study the effect of NZB treatment on circulating lymphomonocyte subpopulations expressing T-bet, pSTAT1, pSTAT3 and CD4+CD25+Foxp3+ regulatory T cells. Flow cytometry was used to evaluate the percentages of circulating CD4+ and CD8+ T cells, CD14+ monocytes and B cells expressing T-bet, pSTAT1, and pSTAT3, and CD4+CD25+Foxp3+ regulatory T cells from RRMS patients before and after 6-12 NZB infusions. In NZB-treated RRMS patients, the percentages of CD4+pSTAT1+ and CD8+pSTAT1+ T cells, CD14+pSTAT1+ monocytes, CD4+T-bet+, CD8+T-bet+ and CD4+pSTAT3+ T cells and CD14+pSTAT3+ monocytes increased after 12 drug infusions and were similar to those observed in untreated relapsing RRMS patients. Otherwise in vitro NZB exposure of peripheral blood mononuclear cells from untreated RRMS patients and controls had no effect. It was concluded that NZB treatment determines an accumulation of CD4+pSTAT1+, CD8+pSTAT1+, CD4+T-bet+, CD8+T-bet+ and CD4+STAT3+ T cells in peripheral blood that may account for the exacerbation of the disease observed in some patients after the discontinuation of the drug.     

Progressive ascending myelopathy: atypical forms of multiple sclerosis or what else?

The spinal cord can be affected by multiple heterogeneous disorders often difficult to diagnose. We describe ten patients affected by a progressive ascending myelopathy with a poor prognosis. The patients, during the follow-up period, underwent neurological examinations, cerebrospinal fluid analysis, hematological, microbiological, auto-antibodies screening, brain and spinal cord magnetic resonance imaging (MRI) and electroneurophysiological study. At disease onset spinal cord MRI showed ≥1 myelopathic lesions extended for <2 segments and then evidenced a progressive spinal cord atrophy without any new lesion. All patients showed an increase of the visual evoked potential P100 latency. All of them showed two or more clinical recurrences of myelitis and then, after a period ranging from 3 to 5 years from the disease onset, a progressive course. Five patients became unresponsive to intravenous high-dose steroid treatments and/or intravenous immunoglobulins and to any other therapeutic attempts, developed a progressive ascending myelopathy to tetraplegia and died from respiratory failure. The other five patients are in progressive phase of the disease with an initial involvement of the upper limbs and show mild cervical spinal cord atrophy at MRI, configuring the early stage of an ascending progressive myelopathy. In our opinion, the more suitable diagnosis is an atypical form of MS although is not possible to exclude a new nosological entity that could be included in the expanding range of spinal cord diseases.     

Strategies to reduce pulmonary complications after esophagectomy

Esophagectomy,the surgical removal of all or part of the esophagus,is a surgical procedure that is associated with high morbidity and mortality.Pulmonary complications are an especially important postoperative problem.Therefore,many perioperative strategies to prevent pulmonary complications after esophagectomy have been investigated and introduced in daily clinical practice.Here,we review these strategies,including improvement of patient performance and technical advances such as minimally invasive surgery that have been implemented in recent years.Furthermore,interventions such as methylprednisolone,neutrophil elastase inhibitor and epidural analgesia,which have been shown to reduce pulmonary complications,are discussed.Benefits of the commonly applied routine nasogastric decompression,delay of oral intake and prophylactic mechanical ventilation are unclear,and many of these strategies are also evaluated here.Finally,we will discuss recent insights and new developments aimed to improve pulmonary outcomes after esophagectomy.     

Cutaneous manifestations of HIV—a detailed study of morphological variants,markers of advanced disease,and the changing spectrum

Background

Cutaneous manifestations are early and easily identifiable markers of human immunodeficiency virus (HIV) infection. They can help in predicting severity and progress of the disease and can be correlated well with CD4 counts. This study was undertaken to study the cutaneous manifestations of HIV infection and to correlate them with CD4 counts. It also aimed to study the changing spectrum of these manifestations and describe cutaneous manifestations seen in advanced disease.

Method

A total of 234 HIV-positive patients not on anti-retroviral therapy, who attended the outpatient department or were admitted as inpatients at Military Hospital, Shillong during the period between May 2008 and October 2009 were included. Cutaneous, mucosal, and genitourinary manifestations in these patients were studied in detail and were correlated with CD4 counts.

Results

Infections were the most common group of mucocutaneous manifestations, while onychomycosis was the commonly observed individual manifestation. A different set of cutaneous markers for advanced HIV disease was observed and new parameters for therapy were also arrived at.

Conclusion

Specific morphological variants of cutaneous markers may provide a better clue to early diagnosis of HIV and can help in diagnosing advanced stages of the disease. Fresh cutaneous markers are required for indicating cut-off levels of CD4 count at 350/μL for starting therapy.     

HPLC分离测定格列齐特片及其有关物质

目的：建立新的HPLC法分离测定格列齐特征及其有关物质。方法：色谱条件为：Shim-Pack VP-ODS(5um,150mm*4.6mm i.d.)色谱柱;甲醇－0．02mol/L磷酸（用三乙胺调节PH至3．5）,（70：30）为流动相;检测波长为229nm。结果：在50－300ug;/ml的浓度范围内线性关系良好。r=0.9999(n=6);平均回收率为100．5％,RSD为0．17％（n=6),重复进样RSD为0．12％（n=6),格列齐特及其有关物质得到基线分离。结论：本法简便,快速,准确,适用于格列齐特及其制剂的质量控制。     

Modeling the growth of Yersinia enterocolitica in donated blood

BACKGROUND: Sepsis and death subsequent to the transfusion of blood containing Yersinia enterocolitica is an increasing problem. The organisms probably originate from bacteremia in the donor and can subsequently multiply at low temperature. STUDY DESIGN AND METHODS: Reported here are experiments with a strain of Y. enterocolitica associated with a case of transfusion-associated bacteremia. RESULTS: It was found that the rapid early killing of Y. enterocolitica injected into donated blood does not require viable phagocytes and can be explained by complement-mediated killing. Complement resistance in Y. enterocolitica is known to be plasmid-coded. It is expressed at 37 degrees C, but not at 20 degrees C, and is favored by calcium-deficient culture media. Y. enterocolitica organisms induced to express complement resistance were still killed in donated blood, though the initial rate was slower. Such organisms multiplied in plasma at 37 degrees C, but were killed after 6 hours of incubation at 20 degrees C, presumably because complement resistance genes are switched off at this temperature. CONCLUSION: This experiment is thought to reflect the natural history of Y. enterocolitica contamination of blood, in which complement-resistant organisms in the donor blood encounter lower temperatures after donation. These observations suggest that the practice of plasma depletion may have contributed to the increased incidence of mortality due to Y. enterocolitica contamination of donated blood.