Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea.

Auto-adjustable continuous positive airway pressure (APAP) devices are an emerging treatment alternative to fixed-pressure continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea syndrome. They have been engineered to automatically adjust the pressure to the optimal level on a continuous basis. However, not all APAP technologies use the same algorithm. Three different APAP devices (Autoset Spirit, Breas PV 10i and RemStar Auto) were compared in a randomised crossover trial in patients already established on fixed-pressure CPAP therapy. The outcome measures were compliance, quality of life and side-effects. Twenty-seven middle-aged patients (25 male) previously diagnosed with severe obstructive sleep apnoea syndrome (median (interquartile range) apnoea/hypopnoea index 48 (29-76)), established on CPAP therapy for >3 yrs, were randomised to each APAP device for 4 weeks. Mean pressure and patient compliance were significantly lower on the Breas PV 10i than on the other APAP devices. The devices were similar in terms of quality of life, daytime sleepiness and upper airway side-effects, but patients evaluated them significantly differently in terms of device features, sleep quality and pressure comfort, with the Breas PV 10i being the least popular. Auto-adjustable positive airway pressure devices differ in pressure delivery and patient compliance in obstructive sleep apnoea syndrome patients.     

The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system white matter. The association of the disease with MHC genes, the inflammatory white matter infiltrates, similarities with animal models, and the observation that MS can be treated with immunomodulatory and immunosuppressive therapies support the hypothesis that autoimmunity plays a major role in the disease pathology. Evidence supports activated CD4⁺ myelin-reactive T cells as major mediators of the disease. In addition, a renewed interest in the possible contribution of B cells to MS immunopathology has been sparked by nonhuman primate and MS pathological studies. This review focuses on the immunopathology of MS, outlining the hypothetical steps of tolerance breakdown and the molecules that play a role in the migration of autoreactive cells to the CNS. Particular focus is given to autoreactive T cells and cytokines as well as B cells and autoantibodies and their role in CNS pathogenesis in MS.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Multigenic control of skin tumor susceptibility in SENCARA/Pt mice

Skin tumors induced in mice by initiation-promotion (2 microg DMBA-2 microg TPA) protocols were found to be under multigenic control. Eighty- one N2 mice from the cross (BALB/cAnPt x SENCARA/Pt)F1 x SENCARA/Pt that were either solidly resistant (no papillomas) or highly susceptible (> or = 7 papillomas/mouse) were subjected to a 'genome scan' using 89 microsatellite markers to check for associations with susceptible and resistant phenotypes. A locus on Chr 5 (Skts4) was found to control the susceptibility of SENCARA/Pt mice and the resistance of BALB/cAnPt mice to papilloma formation. In addition, higher than expected linkage scores were seen for the markers D9Mit271, D11Mit268 and D12Mit56. Further work is required to establish whether genes determining papilloma formation are located in these regions of the genome. In general, no evidence was seen for loss of heterozygosity in microsatellite markers on Chrs 5, 9 and 11 in 17 microdissected papillomas from (BALB/c x SENCARA)F1 hybrid mice.      

The prognostic importance of different definitions of worsening renal function in congestive heart failure

BACKGROUND: Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). METHODS AND RESULTS: The patient population was 49% female, aged 67 +/- 15 years. Twenty-three percent had a prior history of renal failure, 73% had known depressed ejection fraction, and 63% had known CHF. On admission to the hospital, 47% were receiving ACE inhibitors, 22% beta-blockers, 70% diuretics and 6% NAID's. 72% developed increased serum creatinine during the hospitalization, with 20% developing an increase of > or = 0.5 mg/dL. Worsening renal function predicted both in-hospital mortality and length of stay > 10 days. Even an increased creatinine of 0.1 mg/dL was associated with worse outcome. Sensitivity for death decreased from 92% to 65% as the threshold for increased creatinine was raised from 0.1 to 0.5 mg/dL, with specificity increasing from 28% to 81%. At a threshold of a 0.3 mg/dL increase, sensitivity was 81% and specificity was 62% for death and 64% and 65% for length of stay >10 days. Adding a requirement of final creatinine of > or = 1.5 mg/dL improved specificity. CONCLUSIONS: This analysis demonstrates that any detectable decrease in renal function is associated with increased mortality and prolonged hospital stay. This suggests that therapeutic interventions which improve renal function might be beneficial.