Development of a real-time PCR detection method for a FCGR2A polymorphism in the LightCycler and application in the heparin-induced thrombocytopenia syndrome

ObjectiveThe FcγRIIa receptor is responsible for the activation of platelets by antibodies in heparin-induced thrombocytopenia (HIT). The c.497G > A polymorphism in the corresponding FCG2RA gene (H131R) has been implicated in the HIT syndrome and we aimed at its rapid and reliable determination.Design and methodsWe designed a novel asymmetric real-time PCR method in the LightCycler that uses two hybridization probes and is followed by melting curve analysis. Seventy-one post-cardiac-surgery HIT Greek patients well ascertained by clinical data, immunological and functional tests (PAT, CD62P-selectin and microparticle flow cytometric detection) were studied, along with a clinically relevant group of 49 thrombocytopenic control patients and 119 healthy subjects.ResultsThe developed method has excellent analytical characteristics (linear and efficient amplification, precision), has wide ΔT_m between the two alleles H and R (11.53 °C), and is in 100% concordance with validated controls and another commonly used screening method. The RR percentage increased from 10% in the control populations to 24% in the HIT patient group.ConclusionThe described method is technically simple, robust, fast, and accurate. A statistically significant difference was found in the comparison between the groups of HIT patients and healthy subjects [RR vs. RH+ HH, χ² test, p  =  0.01, OR (95% C.I.) 2.81 (1.21–4.68)]. The RR frequency in the Greek population was found to be the lowest among Caucasians.     

Emerging treatments for ulcerative colitis: a systematic review

Objectives: Various investigational medicinal products have been developed for ulcerative colitis (UC). Our aim was to systematically evaluate novel pharmacological therapeutic agents for the treatment of UC.

Material and methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. A search of the medical literature was conducted in the MEDLINE database for original research papers published between 01 January 2010 and 31 October 2014.

Results: Twenty one studies, including 11,524 adults were analyzed. Thirteen different novel therapeutic drug options were identified. Vedolizumab and golimumab were superior to placebo as induction and maintenance therapy. Tofacitinib showed dose related efficacy for induction therapy. Etrolizumab showed higher clinical remission rates compared to placebo. Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may become a mesalamine alternative for mild to moderate UC. PF00547,659 was well tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept, rituximab and visilizumab did not lead to improved outcomes compared to placebo. Higher concentration of BMS 936557 was associated with improved efficacy compared to placebo. Basiliximab did not enhance corticosteroid efficacy.

Conclusions: Patients with UC might achieve clinical response or remission by utilizing some of these agents with a favorable side effect profile. Further studies are needed to evaluate their short- and long-term efficacy and safety.     

Esophageal motility: assessment with synchronous video tape fluoroscopy and manometry

Synchronous video tape fluoroscopy and manometry of the esophagus was performed in 11 subjects (seven men and four women; mean age, 49 years). Four had normal and seven had abnormal esophageal motility (diffuse esophageal spasm, n = 4; nonspecific esophageal motility disorder, n = 3) that was shown by previous manometry. A digital timer appeared on the video tape recording and marked the manometric tracing synchronously. Alternate 5-mL and 10-mL barium boluses were recorded for a total of 10 swallows per patient. Video tape examinations were reviewed prospectively, and the status of primary peristalsis and presence and severity of tertiary activity were noted. A total of 98 swallows (58 normal, 40 abnormal) were correlated, and a 96% agreement was found in assessing primary peristalsis. Overall results of fluoroscopic examinations of each subject during all swallows showed complete agreement with those of manometry; segregating the swallows into groups of five showed 92% concordance. Severe tertiary activity was invariably seen with abnormal primary peristalsis at fluoroscopy.     

The Effects of Age,Adiposity, and Physical Activity on the Risk of Seven Site‐Specific Fractures in Postmenopausal Women

Risk factors for fracture of the neck of the femur are relatively well established, but those for fracture at other sites are little studied. In this large population study we explore the role of age, body mass index (BMI), and physical activity on the risk of fracture at seven sites in postmenopausal women. As part of the Million Women Study, 1,154,821 postmenopausal UK women with a mean age of 56.0 (SD 4.8) years provided health and lifestyle data at recruitment in 1996 to 2001. All participants were linked to National Health Service (NHS) hospital records for day‐case or overnight admissions with a mean follow‐up of 11 years per woman. Adjusted absolute and relative risks for seven site‐specific incident fractures were calculated using Cox regression models. During follow‐up, 4931 women had a fracture of the humerus; 2926 of the forearm; 15,883 of the wrist; 9887 of the neck of the femur; 1166 of the femur (not neck); 3199 a lower leg fracture; and 10,092 an ankle fracture. Age‐specific incidence rates increased gradually with age for fractures of forearm, lower leg, ankle, and femur (not neck), and steeply with age for fractures of neck of femur, wrist, and humerus. When compared to women with desirable BMI (20.0 to 24.9 kg/m²), higher BMI was associated with a reduced risk of fracture of the neck of femur, forearm, and wrist, but an increased risk of humerus, femur (not neck), lower leg, and ankle fractures (p < 0.001 for all). Strenuous activity was significantly associated with a decreased risk of fracture of the humerus and femur (both neck and remainder of femur) (p < 0.001), but was not significantly associated with lower leg, ankle, wrist, and forearm fractures. Postmenopausal women are at a high lifetime risk of fracture. BMI and physical activity are modifiable risk factors for fracture, but their associations with fracture risk differ substantially across fracture sites. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)     

Achilles tendon: US diagnosis of pathologic conditions. Work in progress

Twenty-three patients were prospectively examined with ultrasound (US) for acute or recurrent Achilles tendon symptoms. Three types of pathologic conditions of the Achilles tendon were found: tendinitis/tenosynovitis, acute tendon trauma, and postoperative changes. US appears to enable differentiation of these conditions and to contribute to the diagnosis of a broad range of Achilles tendon disorders.     

Infected aortoiliofemoral grafts: magnetic resonance imaging

Three patients with proved infected aortoiliofemoral grafts were examined by magnetic resonance (MR) imaging using a spin echo technique. MR clearly identified the perigraft abscess, the involvement of adjacent structures, and the longitudinal extent of the process in all patients. The MR findings were: Abscesses create a high signal intensity, somewhat less than fat. The perigraft abscess has a great contrast with the signal void of flowing blood in the graft. Inflammatory changes cause an inhomogeneous intermediate signal, slightly more intense than muscle. Both abscesses and edematous areas increase their signal intensity with long repetition rates and long echo delays. Areas of gas appear black. They cannot be distinguished from calcified plaques. Additional information is gained about the graft patency. Although the specificity has to be proved, MR imaging is sensitive in the detection of infected grafts and for defining the longitudinal extent of the perigraft abscess.     

Asymptomatic total hip prosthesis: natural history determined using Tc- 99m MDP bone scans

A prospective study was performed with 97 patients who had undergone total hip replacement surgery and who were not experiencing pain or other symptoms or problems. The study was intended to determine the normal postoperative appearance of radionuclide scans of the hip following administration of technetium-99m methylene diphosphonate. Five areas of the prostheses were evaluated. Results showed that 6 months after implantation activity around the lesser trochanter and prosthesis shaft became insignificant. Activity around the acetabulum, greater trochanter, and prosthesis tip stabilized approximately 2 years after surgery; approximately 10% of patients in the study had persistent activity in these areas. Familiarity with this normal progression is fundamental to interpretation of postoperative bone scans in patients with total hip prosthesis.