Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay

The traditional coagulant assay for plasma factor XI suffers from a relatively high coefficient of variation, the need for rare congenitally deficient plasma, and a poor correlation between precision and sensitivity. We have developed a simple functional amidolytic assay for factor XI in plasma using the chromogenic substrate PyrGlu-Pro-Arg- p-nitroanilide (S-2366). After inactivation of alpha 1-antitrypsin, CI inhibitor, and other plasma protease inhibitors with CHCI3, plasma was incubated with kaolin, in the absence of added calcium, which limited the enzymes formed to those dependent on contact activation. Soybean trypsin inhibitor was used to minimize the action of kallikrein on the substrate. Once the reaction was complete, corn trypsin inhibitor was used to inactive factor XIIa, the enzyme generated by exposure of plasma to negatively charged surfaces, which had activated the factor XI. The assay is highly specific for factor XI, since plasma totally deficient in that zymogen yielded only 1%-3% of the enzymatic activity in normal plasma under identical conditions. The requirements for complete conversion of factor XI to XIa in plasma within 60 min were, respectively, factor XII, 0.6 U/ml, and high molecular weight kininogen, 0.2 U/ml. Prekallikrein was not an absolute requirement for complete activation but did accelerate the reaction. The intraassay coefficient of variation was 3.4%, and the mean of 35 normal plasmas was 1.00 U +/- 0.24 SD. In addition, a new rapid radioimmunoassay was devised using staphylococcal protein A as the precipitating agent for a complex of factor XI antigen with monospecific rabbit antibody. The mean was 1.01 U +/- 0.30 SD. The correlation coefficients for amidolytic versus coagulant and amidolytic versus radioimmunoassay were r = 0.95 for the former and 0.96 for the latter. Thus, a simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in our laboratory.     

Understanding the current sexual health service provision for mental health consumers by nurses in mental health settings: Findings from a Survey in Australia and England

Nurses in mental health settings avoid talking to consumers about sexual health concerns. It is unclear whether this avoidance prevents the provision of sexual healthcare. The present study gathered information about how mental health nurses respond to sexual health issues within their routine practice, what issues they address, and their view on their role in promoting sexual health for consumers. A cross‐sectional study using an electronic survey questionnaire, originally generated from a previous study in the united kingdom, was employed. The study occurred in four National Health Service Trusts in England and a national call for participants in Australia. Participants were nurse clinicians (n = 303) who self‐selected by completing surveys available via email and newsletters containing links to the survey. The results demonstrated that mental health nurses do not routinely include sexual health in their practice and are poorly prepared in knowing what to do with a sexual health issue, and what services to assist consumers to use. In conclusion, it has been well established in the literature that mental health consumers experience high sexual health needs that potentially impact on health and recovery. Mental health nurses are ideally placed to promote sexual health and refer consumers to sexual health and family planning services. Training to improve the confidence and responsiveness of mental health nurses to sexual health is an urgent need.     

Safety and Efficacy of Oral Transmucosal Fentanyl Citrate Compared to Morphine Sulphate Immediate Release Tablet in Management of Breakthrough Cancer Pain

Aim:

To compare the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) and oral morphine in Indian patients with breakthrough episodes of cancer pain.

Materials and Methods:

In this randomized, open label, active controlled, clinical study, total 186 patients who regularly experienced 1-4 episodes of breakthrough cancer pain (BTCP) daily, over the persistent pain controlled by taking oral morphine 60 mg/day or its equivalent were randomized to receive either OTFC 200 mcg or oral morphine 10 mg for the treatment of BTCP for 3 days. Improvement in pain as determined by numerical rating scale (NRS) at 5, 15, 30, and 60 minutes of drug administration and percentage of BTCP episodes showing reduction in pain intensity by >33% at 15 minutes were primary efficacy endpoints. Secondary efficacy endpoints were requirement for rescue analgesia and global assessment by physician and patient. Data of both treatment groups were analysed by appropriate statistical test using software, STATISTICA, version 11.

Results:

Patients treated with OTFC experienced significantly greater improvement in pain intensity of breakthrough episodes compared to those treated with oral morphine at all assessment time points (P < 0.0001). 56% of breakthrough pain episodes treated with OTFC showed a greater than 33% reduction in pain intensity from baseline at 15 minutes compared to 39% episodes treated with oral morphine (P < 0.0001). Patient''s and physician''s global assessment favoured OTFC than oral morphine (P < 0.0001). Requirement of rescue analgesia in both the study groups was similar (P > 0.05). Both study drugs were well tolerated.

Conclusions:

OTFC was found to provide faster onset of analgesic effect than immediate release oral morphine in management of breakthrough cancer pain.     

《英国非酒精性脂肪性肝炎肝移植指南》导读

非酒精性脂肪性肝炎（non—alcoholicsteatohepatitis,NASH）现已成为肝移植愈来愈重要的基础肝病。鉴于晚期NASH患者常并存多种影响肝移植转归的临床问题,而至今尚无针对NASH患者进行肝移植的评估和治疗指南,为此英国移植学会（British Transplant Society,BTS）邀请相关专家制定了指南,以指导肝移植前后NASH患者的处理。     

Multimodal imaging for detecting metamorphopsia after successful retinal detachment repair

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate the etiologies of metamorphopsia after successful retinal detachment repair. In this retrospective study, we...     

Comparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4- one iron chelators in overloaded and nonoverloaded mice

Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied using chemical iron quantitation (P less than .001) and with Perls' stain (P less than .01). Liver iron removal with the hydroxypyridinones ranged from 37% with CP20 to 63% with CP51, compared with 46% removal for desferrioxamine (DFO). There was no significant reduction in splenic or cardiac iron with any chelator. There were no deaths in iron-overloaded animals receiving any of the hydroxypyridin-4-ones, but significantly more deaths in the nonoverloaded groups as a whole (P less than .03). No weight loss was observed with any chelator. Significant reductions in hemoglobin and white cell count were observed with CP20(L1). No histologic abnormalities of kidney, spleen, bone marrow, or stifle joints were observed. Intracytoplasmic inclusion bodies were observed in the centrilobular hepatocytes of animals administered each of the hydroxypyridin-4-ones, while the DFO-treated and control groups showed no such changes.     

An evaluation of liposome-based diagnostics of pulmonary and extrapulmonary tuberculosis

ABSTRACT

Introduction: Tuberculosis (TB) is still one of the major global health threats and delayed diagnosis or misdiagnosis continues to fuel the global epidemic. The conventional diagnostic approaches have shortcomings that might hinder the process of diagnosis of the disease and ultimately affect the prognosis.

Area covered: We emphasize on the process of the synthesis of liposomes, its physicochemical properties affecting the formulation and their utilization in the field of molecular diagnostics for TB. The review also sheds a light on other nanoparticle-based molecular diagnostic approaches for TB. Despite the advent of science, we are yet to have a diagnostic tool that is simple, rapid, sensitive, and specific, and most importantly, one that enables us to demarcate patients with active tuberculosis from those with quiescent lesions, prior vaccination, or other diseases.

Expert opinion: The utility of liposomes for diagnostic purposes has been attempted so as to overcome the challenges posed by conventional diagnostic tools for TB. Through this review, we present insights into liposome formulation and selection processes, various studies that report the use of liposome-based diagnostic tools for TB, as well as the limitations associated with the same that can be improvised to make the technology more efficient.     

TV sonographic assessment in postmenopausal asymptomatic women

The aim of this study was to evaluate retrospectively the usefulness of transvaginal sonography for the detection of endometrial disease in postmenopausal women without symptoms. The study involved 750 postmenopausal women aged 52-65 (mean 58.5). None of them were on hormone replacement therapy and all had had amenorrhea for more than two years. Transvaginal sonography was performed in 750 women. An endometrium of < 5 mm and non-measurable (627 women) was not investigated further. The 627 cases of this group were reassessed one year later. In the remaining 123 postmenopausal women with suspicious endometrium > 5 mm, 19 endometrial polyps (7.13%), one cervical polyp with extension in the cavity (0.8%), 90 endometrial atrophies (73.17%), ten atrophic endometritis (8.13%), two simple hyperplasias (1.62%), and one hyperplasia with atypia (0.8%) were found. Transvaginal sonography is an efficient and acceptable noninvasive method for the early detection of endometrial pathology in postmenopausal asymptomatic women.     

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for 65-85 kg; 1200 mg/d for 85-105 kg; 1400 mg/d for 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.     

Irregular dental structures in a benign ovarian cystic teratoma (dermoid cyst): case report

Mature cystic teratomas, often referred to as dermoid cysts, are the most common germ cell tumors of the ovary in women of reproductive age. The gross pathologic appearance of a dermoid cysts is characteristic. Hair follicles, skin glands, muscle, and other tissues lie within the cyst wall. We present a case of a dermoid cyst ovarian tumor in a 24-your-old patient with a tooth lying on each wall. The mass was laparoscopically removed by ovarian cystectomy.