高血压患者心率变异性的临床分析

通过对８２例高血压患者和６３例年龄相当的正常人２４小时心率变异性分析的研究表明：（１）高血压患者时域分析和频域分析的各项参数指标均减低。（２）高血压患者植物神经２４小时昼夜变化与正常人有差异，高频部分夜间明显降低，标志副交感神经活动失调（Ｐ＜０．０５）。（３）高血压伴心肌缺血者与无心肌缺血者的高频／低频比值差异有显著性（Ｐ＜０．０５）。     

Surveillance of Mycobacterium tuberculosis susceptibility to second-line drugs in Hong Kong, 1995-2002, after the implementation of DOTS-plus.

OBJECTIVE: To determine the trend in changes in susceptibility of Mycobacterium tuberculosis strains, including to second-line drugs, from patients with a history of previous anti-tuberculosis (TB) treatment in a 'DOTS-Plus' programme. METHODS: A retrospective survey of centralised M. tuberculosis laboratory records of all culture-positive cases over an 8-year period. The drug susceptibility of the isolates was determined using the absolute concentration method. Isolates obtained from patients with a history of previous treatment were further analysed for trends of changes in susceptibility to first- and second-line drugs. RESULTS: Of 1921 patients with a previous history of treatment and positive cultures, 1425 (74.2%) had isolates susceptible to all four first-line drugs, while 176 (9.2%) were multidrug-resistant (MDR-TB). For the MDR-TB group, 101 (57.4%) isolates were sensitive to all second-line drugs, while 30 (17.0%) were resistant to three or more second-line drugs. CONCLUSION: In a DOTS-Plus programme environment where there is strict control on use of second-line drugs, the prevalence of MDR-TB is low amongst retreatment cases and the prudent use of second-line drugs in a population with well functioning DOTS-Plus programme does not generate super-resistant strains. In circumstances where most retreatment strains are still susceptible and good laboratory support for detection of MDR cases is available, retreatment using first-line drugs is feasible.     

Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors. CS1 was expressed at adhesion-promoting uropod membranes of polarized MM cells, and short interfering RNA (siRNA) targeted to CS1 inhibited MM cell adhesion to bone marrow stromal cells (BMSCs). HuLuc63 inhibited MM cell binding to BMSCs and induced antibody-dependent cellular cytotoxicity (ADCC) against MM cells in dose-dependent and CS1-specific manners. HuLuc63 triggered autologous ADCC against primary MM cells resistant to conventional or novel therapies, including bortezomib and HSP90 inhibitor; and pretreatment with conventional or novel anti-MM drugs markedly enhanced HuLuc63-induced MM cell lysis. Administration of HuLuc63 significantly induces tumor regression in multiple xenograft models of human MM. These results thus define the functional significance of CS1 in MM and provide the preclinical rationale for testing HuLuc63 in clinical trials, either alone or in combination.     

Pediatric patients who receive antibiotics for fever and neutropenia in less than 60 min have decreased intensive care needs

Background

Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N.

Procedure

We used Lean‐Methodology and a Plan‐Do‐Study‐Act approach to direct QI efforts and prospectively tracked TTA measures and associated clinical outcomes (length of stay, duration of fever, use of imaging studies to search for occult infection, bacteremia, intensive care unit (ICU) consultation or admission, and mortality). We then performed statistical analysis to determine the impact of our QI interventions on total TTA, sub‐process times, and clinical outcomes.

Results

Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in <60 min nearly 100% of the time. All TTA sub‐process times also improved. Moreover, achieving TTA <60 min significantly reduced the need for ICU consultation or admission (P = 0.003) in this population.

Conclusion

Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes. These data indicate that decreasing TTA to <60 min is achievable and associated with improved outcomes in pediatric patients with cancer and F&N. Pediatr Blood Cancer 2015;62:807–815. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Binding of a hairpin polyamide in the minor groove of DNA: sequence-specific enthalpic discrimination.

Hairpin polyamides are synthetic ligands for sequence-specific recognition in the minor groove of double-helical DNA. A thermodynamic characterization of the DNA-binding properties exhibited by a six-ring hairpin polyamide, ImPyPy-gamma-PyPyPy-beta-Dp (where Im = imidazole, Py = pyrrole, gamma = gamma-aminobutyric acid, beta = beta-alanine, and Dp = dimethylaminopropylamide), reveals an approximately 1-2 kcal/mol greater affinity for the designated match site, 5'-TGTTA-3', relative to the single base pair mismatch sites, 5'-TGGTA-3' and 5'-TATTA-3'. The enthalpy and entropy data at 20 degrees C reveal this sequence specificity to be entirely enthalpic in origin. Correlations between the thermodynamic driving forces underlying the sequence specificity exhibited by ImPyPy-gamma-PyPyPy-beta-Dp and the structural properties of the heterodimeric complex of PyPyPy and ImPyPy bound to the minor groove of DNA provide insight into the molecular forces that govern the affinity and specificity of pyrrole-imidazole polyamides.     

Indications and diagnostic outcome of antineutrophil cytoplasmic antibody testing in hospital medicine: a pattern of over-screening

Clinical Rheumatology - Antineutrophil cytoplasmic antibodies (ANCA) serology can aid in the diagnosis and classification of ANCA-associated vasculitides (AAV). However, it is often ordered in...