Mitochondrial DNA Haplogroups M7b1 ' 2 and M8a Affect Clinical Expression of Leber Hereditary Optic Neuropathy in Chinese Families with the m.11778G -> A Mutation

Leber hereditary optic neuropathy (LHON) is the most extensively studied mitochondrial disease, with the majority of the cases being caused by one of three primary mitochondrial DNA (mtDNA) mutations. Incomplete disease penetrance and gender bias are two

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPELC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-I-127 iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 mu g/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10626 +/- 2886 mu g/L and 528 +/- 191 mu g/L, and the terminal elimination half-lives (T,12) were 6.3 +/- 0.9 h and 5.5 +/- 1.0 h, respectively. After sc, T-max was 0.25-2 h, and the absolute bioavailability was 49% +/- 13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50 of 0.33 mu g/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T-1/2 of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50 in vitro.

Gross clinical signs and haematological changes associated with artifical infection of Edwardsiella tarda in Koi Carp

The occurrence of diseases is a significant setback for successful aquafarming. One of the common fish bacterial disease syndromes, Edwardsiellosis is caused by Edwardsiella tarda, a gram-negative, rod shaped bacterium associated with several diseases of marine and fresh water fish. In this study, an attempt was made to observe and analyze the onset of clinical symptoms and certain haematological parameters in Koi Carp, Cyprinus carpio L., following artificial infection with Edwardsiella tarda. The disease progress was observed and the clinical symptoms were monitored over a period of 15 days following infection. Fish were sampled at three day intervals to analyse the haematological parameters: total erythrocyte counts (RBC), total leucocyte counts (WBC), haemoglobin content and differential leucocyte count. Clinical symptoms observed included: erratic swimming behaviour, loss of appetite, haemorrhages, dropsy and exophthalmia. There was a significant decrease in the total RBC and haemoglobin levels by the 3rd and 6th day post infection, and an increase thereafter. WBC counts were higher in all infected groups in comparison to the control group. A significant increase in the number of neutrophils was found in the infected group up to the 9th day and a decrease thereafter. The lymphocyte number was significantly less up to the 12th day while the monocyte counts were significantly higher up to the 12th day post infection. The results showed that the bacterium, E. tarda, is pathogenic to Koi Carp. The hematological changes and clinical signs in infected fish reported in this paper will be helpful in the identification and the control of this infection.

In vitro activities of small peptides from snake venom against clinical isolates of drug-resistant Mycobacterium tuberculosis

The recent re-emergence of tuberculosis, especially the multidrug-resistant cases, has highlighted the importance of screening effective novel drugs against Mycobacterium tuberculosis. In this study, the in vitro activities of small peptides isolated from snake venom were investigated against multidrug-resistant M. tuberculosis. Minimum inhibitory concentrations (MICs) were determined by the Bactec TB-460 radiometric method. A small peptide with the amino acid sequence ECYRKSDIVTCEPWQKFCYREVTFFPNHPVYLSGCASECTETNSKWCCTTDKCNRARGG (designated as vgf-1) from Naja atra (isolated from Yunnan province of China) venom had in vitro activity against clinically isolated multidrug-resistant strains of M. tuberculosis. The MIC was 8.5 mg/l. The antimycobacterial domain of this 60aa peptide is under investigation. (C) 2003 Elsevier Science B.V. and the International Society of Chemotherapy. All rights reserved.

Imaging the femoral cortex: thickness, density and mass from clinical CT.

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm(2)) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex.

Imaging the femoral cortex: Thickness, density and mass from clinical CT

There is growing evidence that focal thinning of cortical bone in the proximal femur may predispose a hip to fracture. Detecting such defects in clinical CT is challenging, since cortices may be significantly thinner than the imaging system's point spread function. We recently proposed a model-fitting technique to measure sub-millimetre cortices, an ill-posed problem which was regularized by assuming a specific, fixed value for the cortical density. In this paper, we develop the work further by proposing and evaluating a more rigorous method for estimating the constant cortical density, and extend the paradigm to encompass the mapping of cortical mass (mineral mg/cm 2) in addition to thickness. Density, thickness and mass estimates are evaluated on sixteen cadaveric femurs, with high resolution measurements from a micro-CT scanner providing the gold standard. The results demonstrate robust, accurate measurement of peak cortical density and cortical mass. Cortical thickness errors are confined to regions of thin cortex and are bounded by the extent to which the local density deviates from the peak, averaging 20% for 0.5mm cortex. © 2012 Elsevier B.V.

A clinical system for three-dimensional extended-field-of-view ultrasound.

OBJECTIVE: This work is concerned with the creation of three-dimensional (3D) extended-field-of-view ultrasound from a set of volumes acquired using a mechanically swept 3D probe. 3D volumes of ultrasound data can be registered by attaching a position sensor to the probe; this can be an inconvenience in a clinical setting. A position sensor can also cause some misalignment due to patient movement and respiratory motion. We propose a combination of three-degrees-of-freedom image registration and an unobtrusively integrated inertial sensor for measuring orientation. The aim of this research is to produce a reliable and portable ultrasound system that is able to register 3D volumes quickly, making it suitable for clinical use. METHOD: As part of a feasibility study we recruited 28 pregnant females attending for routine obstetric scans to undergo 3D extended-field-of-view ultrasound. A total of 49 data sets were recorded. Each registered data set was assessed for correct alignment of each volume by two independent observers. RESULTS: In 77-83% of the data sets more than four consecutive volumes registered. The successful registration relies on good overlap between volumes and is adversely affected by advancing gestational age and foetal movement. CONCLUSION: The development of reliable 3D extended-field-of-view ultrasound may help ultrasound practitioners to demonstrate the anatomical relation of pathology and provide a convenient way to store data.

Leadership of healthcare commissioning networks in England: a mixed-methods study on clinical commissioning groups.

To explore the relational challenges for general practitioner (GP) leaders setting up new network-centric commissioning organisations in the recent health policy reform in England, we use innovation network theory to identify key network leadership practices that facilitate healthcare innovation.

Multiplex detection of mutations in clinical isolates of rifampin-resistant Mycobacterium tuberculosis by short oligonucleotide Ligation assay on DNA chips

A new approach, short-oligonucleotide-ligation assay on DNA chip (SOLAC), is developed to detect mutations in rifampin-resistant Mycobacterium tuberculosis. The method needs only four common probes to detect 15 mutational variants of the rpoB gene within 12 h. Fifty-five rifampin-resistant M. tuberculosis isolates were analyzed, resulting in 87.3% accuracy and 83.6% concordance relative to DNA sequencing.

The development of long - Term ambulatory pH monitoring system and its clinical application

This paper introduced a long-term ambulatory intragastric pH monitoring system, which is designed for prolonged ambulatory studies of Gastroesophageal Reflux Diseases. The whole system is composed of the gastric catheter with two pH sensors, a small data logger (Microdatalog), and a notebook PC. In this paper, the design of monitoring system hardware and software are described in detail. Clinical applications reveal good results.

重离子束治疗皮肤恶性肿瘤的初步临床结果；Clinical trial of carbon ion radiotherapy for malignant neoplasm of skin

目的:评价重离子束对皮肤恶性肿瘤放射治疗的近期疗效和毒副反应。方法:29例皮肤恶性肿瘤患者分6批接受重离子束放射治疗,其中恶性黑色素瘤13例,皮肤鳞癌及Bowen’s病各6例,基底细胞癌2例,其他皮肤恶性肿瘤2例。照射总剂量(50～70)GyE/(6～12)d,单次剂量5.5～11.67GyE,1f/d,连续治疗。采用RTOG标准和WHO近期疗效标准分别评价毒副反应和近期疗效。结果:截止2009-05,中位随访时间为13.5个月(1～25个月),随访率为100%。29例患者中完全缓解(CR)24例(82.8%),部分缓解(PR)5例(17.2%),有效率(RR)为100%,中位生存时间为22.8个月(95%CI:20.6～24.9)。皮肤反应0度11例(37.9%),Ⅰ度9例(31.0%),Ⅱ度6例(20.7%),Ⅲ度2例(6.9%),Ⅳ度1例(3.4%);血液毒副反应治疗前后无明显改变。结论:重离子束(12C6+)放射治疗皮肤恶性肿瘤近期疗效好,并发症轻,远期疗效、晚期副反应等尚需进一步长期全面的观察和更多的研究提供依据。