Amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam: quantitative neuropathology,immunohistochemical analysis of neuronal vulnerability,and comparison with related neurodegenerative disorders

Amyotrophic lateral sclerosis/parkinsonism-dementia complex (lytico-bodig) is a chronic neurodegenerative disorder with high prevalence among the native Chamorro population of Guam. Neuropathological, biochemical, and immunohistochemical analyses were performed on a relatively large series of Guamanian cases and compared to Alzheimer's disease cases. Thioflavin S and antibodies to amyloid A4 and tau proteins were used for analysis of pathological changes, and antibodies to the calcium-binding proteins parvalbumin and calretinin, and to a nonphosphorylated epitope on neurofilament protein to study select neuronal populations. A differential distribution of neurofibrillary tangles was observed in the neocortex of Guamanian cases compared to Alzheimer's disease cases, with much higher lesion counts in supragranular than in infragranular layers. Also, Guamanian cases with predominant parkinsonism had generally higher neurofibrillary tangle densities than cases with predominant amyotrophic lateral sclerosis. In addition, there was a certain degree of heterogeneity, qualitatively and quantitatively, in the biochemical distribution of tau proteins among Guamanian and Alzheimer's disease cases as revealed by Western blot analysis. Previous studies have suggested that the clinical symptomatology observed in patients suffering from Alzheimer's disease is related to the dramatic loss of specific corticocortically projecting neurons in the neocortex. Interestingly, a subset of neurofilament-rich pyramidal neurons known to be dramatically affected in Alzheimer's disease appears to be resistant in lytico-bodig. Finally, as in Alzheimer's disease, calcium-binding protein-containing interneurons are not affected. These data suggest that the set of projection neurons affected in Guamanian cases may not correspond to those involved in Alzheimer's disease, and that both disorders are characterized by specific patterns of neuronal vulnerability.Supported by NIH grants AG08802, AG05138 and AG06647, the Brookdale Foundation, and the France-Alzheimer Association     

Plague as a biological weapon: medical and public health management. Working Group on Civilian Biodefense

Objective  The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals following the use of plague as a biological weapon against a civilian population. Participants  The working group included 25 representatives from major academic medical centers and research, government, military, public health, and emergency management institutions and agencies. Evidence  MEDLINE databases were searched from January 1966 to June 1998 for the Medical Subject Headings plague, Yersinia pestis, biological weapon, biological terrorism, biological warfare, and biowarfare. Review of the bibliographies of the references identified by this search led to subsequent identification of relevant references published prior to 1966. In addition, participants identified other unpublished references and sources. Additional MEDLINE searches were conducted through January 2000. Consensus Process  The first draft of the consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group was convened to review drafts of the document in October 1998 and May 1999. The final statement incorporates all relevant evidence obtained by the literature search in conjunction with final consensus recommendations supported by all working group members. Conclusions  An aerosolized plague weapon could cause fever, cough, chest pain, and hemoptysis with signs consistent with severe pneumonia 1 to 6 days after exposure. Rapid evolution of disease would occur in the 2 to 4 days after symptom onset and would lead to septic shock with high mortality without early treatment. Early treatment and prophylaxis with streptomycin or gentamicin or the tetracycline or fluoroquinolone classes of antimicrobials would be advised.      

Retrospective study of plasma exchange in patients with idiopathic rapidly progressive glomerulonephritis and vasculitis

A retrospective study of 48 patients was conducted to evaluate the efficacy of plasma exchange in children with idiopathic rapidly progressive glomerulonephritis (IRPGN), and renal or non-renal vasculitis. All patients were followed up at a single centre over a 15 year period. Treatment consisted of corticosteroids and/or cytotoxic agents. Plasma exchange was used in all patients because of severe renal involvement and/or clinical deterioration. One hundred per cent of patients with renal vasculitis who started plasma exchange within one month of disease onset and 58% of cases with IRPGN had significant improvement in renal function. No relapses of vasculitis were observed after treatment with plasma exchange in patients with renal and non-renal vasculitis. The results suggest that plasma exchange associated with immunosuppressive treatment could be of benefit in cases of IRPGN or vasculitis in terms of both renal and extrarenal recovery.     

Socio-economic effects and cost saving potential of remote patient monitoring (SAVE-HM trial)

Objective

In the SAVE-trial we evaluated the safety, reliability and improvements of patient management using the BIOTRONIK Home Monitoring®-System (HM) in pacemaker (PM) and implanted cardioverter defibrillator (ICD) patients.

Design

115 PM (Module A) and 36 ICD-patients (Module B) were recruited 3 months after implantation.

Patients

65 patients in Module A were randomised to HM-OFF and had one scheduled outpatient clinic follow-up (FU) per year, whereas patients randomised to HM-ON were equipped with the mobile transmitter and discharged without any further scheduled in-office FU. In Module B 18 patients were randomised to HM-OFF and followed by standard outpatient clinic controls every 6 months; 18 patients were randomised to HM-ON receiving remote monitoring plus one outpatient clinic visit per year; unscheduled follow-ups were performed when necessary.

Results

The average follow-up period was 17.1 ± 9.2 months in Module A and 26.3 ± 8.6 months in Module B. In both modules, the number of FUs per year was significantly reduced (Module A HM-ON 0.29 ± 0.6 FUs/year vs HM-OFF 0.53 ± 0.5 FUs/year; p < 0.001; Module B HM-ON 0.87 ± 0.25 vs HM-OFF 1.73 ± 0.53 FU/year, p < 0.001). Cost analysis was significantly lower in the HM-ON group compared to the HM-OFF group (18.0 ± 41.3 and 22.4 ± 26.9€ respectively; p < 0.003). 93% of the unscheduled visits in Module B were clinically indicated, whereas 55% of the routine FUs were classified as clinically unnecessary.

Conclusion

Remote home monitoring of pacemaker and ICD devices was safe, reduced overall hospital visits, and detected events that mandated unscheduled visits.     

Receipt of maintenance therapy is most predictive of survival in older acute lymphoblastic leukemia patients treated with intensive induction chemotherapy regimens

While the prognosis for older adults diagnosed with acute lymphoblastic leukemia (ALL) is frequently poor, long‐term survival can be achieved in patients treated with curative intent. We reviewed the outcomes of 37 patients age ≥60 treated at our institution with either DVP‐ or hyperCVAD‐based chemotherapy regimens from 2003–2011. In this patient population, a complete response rate of 92%, relapse rate of 56% and median overall survival of 18.1 months was experienced. Univariate analysis revealed that receipt of maintenance therapy vs. no maintenance therapy was associated with a statistically‐significant impact on overall survival (p = 0.001, HR 0.15 for death), while disease‐related characteristics including high‐risk white blood cell count at diagnosis and Philadelphia chromosome status as well as treatment‐related factors including chemotherapy regimen or completion of intensive therapy were not. Many patients were unable to initiate or remain on maintenance therapy due to toxicities including infections and cytopenias. Our analysis reveals the benefit of prolonged therapy in the treatment of older adults with ALL as well as the high incidence of treatment‐related toxicity experienced by these patients. Am. J. Hematol. 88:657–660, 2013. © 2013 Wiley Periodicals, Inc.     

新型骨组织工程支架材料β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸的细胞生物相容性

目的:在体外细胞培养条件下,从细胞形态和细胞增殖方面观察新型骨组织工程支架材料β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸的细胞生物相容性。方法:实验于2002-01/2004-01在西安交通大学医学院实验中心及西安交通大学地方病研究所实验室进行。①材料:β-磷酸三钙为兰州交通大学复合材料研究室制备;磷酸纤维平均直径(15.0±1.2)μm,平均体外生物降解率(3.0±0.46)%,拉伸强度(1.0±0.2)GPa,弹性模量(48.0±7.6)GPa;聚左旋乳酸平均分子质量为27.6×104。支架复合物质量比为β-磷酸三钙∶聚磷酸钙纤维∶聚左旋乳酸=2∶3∶5。②实验方法:按复合材料1g∶浸提介质10mL的比例,用含体积分数为0.1的胎牛血清的DMEM37℃条件下浸提24～72h,制备复合支架材料的浸提液,过滤24h内进行试验。将骨髓基质细胞分为3组,分别用支架材料浸提液(实验组)、DMEM培养液(阴性对照组)和6.4g/L苯酚溶液(阳性对照组)培养,同时实验组将浸提液按100%,75%,50%,25%的浓度稀释分别培养。③观察指标:每日使用倒置相差显微镜观察骨髓基质细胞形态变化;用MTT法检测细胞生长及增殖情况,测定A值,计算细胞增殖率。结果:①细胞形态变化:在细胞培养1,2,3d,阳性对照组细胞数量明显减少,细胞固缩甚至崩解,实验组与阴性对照组细胞数量明显增加,细胞形态正常。②细胞生长及增殖情况:在培养各时间点除阳性对照组毒性为4级(细胞增殖率为0～20%)外,其余均为0级(细胞增殖率>80%);除阳性对照组外,各实验组及阴性对照组A值均随培养天数的增加而升高,培养1,2,3天时阳性对照组的A值明显低于其他组(P<0.01),阴性对照组与实验组间无显著差异(P>0.05)。结论:β-磷酸三钙/聚磷酸钙纤维/聚左旋乳酸复合材料对骨髓基质细胞的增殖分化无明显影响,无细胞毒性,有良好细胞生物相容性。     

HLA-B27 associated arthropathies

The association between histo-compatibility antigens and disease is reviewed, in particular that between HLA-B27 and spondylitic disorders, i.e., ankylosing spondylitis, Reiter's arthritis, psoriatic arthritis, and ankylosing hyperostosis. We determined whether the presence of HLA-B27 predicted specific radiographic findings and, conversely, whether specific radiographic changes predicted antigenic status. The prevalences of the HLA-B27 antigen in our patients were: ankylosing spondylitis, 100%; Reiter's arthritis, 93%; psoriatic arthritis, 55%; and ankylosing hyperostosis, 12%. The only specific radiographic finding associated with B27 positivity was severe spondylitis in psoriasis.     

State-of-the-art methodologies in alcohol-related health services research

Many of the failures to replicate clinical findings of treatment efficacy in more realistic field and community settings can be attributed to inappropriate research designs and other methodological shortcomings. In order to increase research designers' awareness of existing methodologies that may be better suited to answer the critical questions inherent in health services research on alcohol-related issues, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) convened an expert conference with three specific goals: (1) to identify the critical issues involved in alcohol services research; (2) to develop a primer that explicated each key area; and (3) to compile the resulting primers into an accessible resource for researchers, policy makers and consumers. The 9 papers in this special supplement are the product of that conference and are organized broadly around three phases of the research process: study design and implementation, data collection and use, and the analysis and interpretation of data. A final summary paper discusses the issues and offers a synthesis of key themes as well as some direction for the future.