The relationship of three-dimensional joint space width on weight-bearing CT with pain and physical function

Limitations of plain radiographs may contribute to poor sensitivity in the detection of knee osteoarthritis and poor correlation with pain and physical function. Three-dimensional (3D) joint space width (JSW), measured from weight-bearing computed tomography (CT) images, may yield a more accurate correlation with patients’ symptoms. We assessed the cross-sectional association between 3D JSW and self-reported pain and physical function. Five hundred twenty eight knees (57% women) were analyzed from Multicenter Osteoarthritis Study participants. An upright weight-bearing CT scanner was used to acquire bilateral, weight-bearing, fixed-flexion images of the knees. A 3D dataset was reconstructed from cone beam projections and JSW was calculated across the joint surface. The percentages of the apposed medial tibiofemoral joint surface with JSW less than 2.0 and 2.5 mm, respectively, were calculated. Pain and physical function were measured using Western Ontario and McMaster Universities Osteoarthritis Index. Participants who reported greater pain severity tended to have a greater joint area with JSW less than 2.0 mm (P = .07 for the highest vs the lowest tertile). Participants who reported greater functional limitations had a greater joint area with JSW less than 2.0 mm (P = .02 for the highest vs the lowest tertile). There appears to be an association between the medial tibiofemoral area with JSW less than 2.0 mm and pain and physical function.     

Structural requirements for imidazo[1,2-a]pyrazine derivatives as Aurora A kinase inhibitors and validation of the model

Aurora kinases belong to the family of serine/threonine kinases. They are divided into three subclasses, Aurora A kinase, Aurora B kinase, and Aurora C kinase and are reported to be vital for cell proliferation. Abnormal expression of these enzymes leads to cancer. Predictive CoMFA and CoMSIA based quantitative structure activity relationship models have been developed on 51 imidazo[1,2-a]pyrazine derivatives reported previously by Merck Research Laboratories. AutoDock was used for docking of the most active compound (34) and the conformation thus obtained was used for the alignment of 3D structures. The developed (CoMSIA-SEHD) model showed good predictive ability with predictive squared correlation coefficient (r ²) value of 0.752. The best model was validated systematically using different validation parameters. The CoMSIA model gave useful information to understand features required to modify and develop new potential Aurora kinase inhibitors.     

A new class of bactericidal agents against S. aureus,MRSA and VRE derived from bisindolylmethane

A series of bisindolylmethanes (BIMs) (1a–7j) including hybrid BIMs 6a–6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a–6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting MIC as well as MBC values equal to or less than that of ciprofloxacin (0.5–2 μg/mL) against Staphylococcus aureus, MRSA and VRE. Compound 2m was selected further to study the effect of N,N′ disubstitution towards antibacterial and antitumor activity. It was observed that substitution at N,N′ position (7a–7j) of 2m diminishes its antibacterial activity though in vitro antitumour activity against a panel of prostate, cervical and lung cancer cell lines remains more or less intact.     

Balloon mitral valvotomy: comparison between antegrade Inoue and retrograde non-transseptal techniques

AIMS: The results of percutaneous mitral valvotomy performed by theantegrade transseptal method using the Inoue balloon (n=1000;group 1) and by the retrograde non-transseptal technique usinga polyethylene balloon (n=100; group 2) were compared in a retrospective,non-randomized study. METHODS AND RESULTS: Both the groups were similar with respect to baseline characteristics.The success rate was 95% in group 1 and 93% in group 2. Therewas a significant increase in mitral valve area estimated byGorlin's equation (Group 1: from 0·8 ± 0·5to 2·1 ± 0·8 cm²; Group 2: from 0·8± 0·3 to 1·9 ± 0·8 cm², bothP<0·001) and by Doppler echocardiography using thepressure half-time method (Group 1: from 0·9 ±0·4 to 2·2 ± 0·6 cm²; Group 2: from0·9 ± 0·3 to 2·0 ± 0·7cm², both P<0·001). However, the calculated immediatepost-valvotomy mitral valve area was larger with the Inoue technique(2·1 ± 0·8 vs 1·9 ± 0·8cm²; P<0·02). Results were considered optimal whenthe mitral valve area increased to 1·5 cm², the percentageincrease was 50, and mitral regurgitation was 2/4. Out of thetotal successful procedures, optimal results were obtained in95% patients in Group 1 and 94% in Group 2. Incidence of significantmitral regurgitation (grade 3/4) was similar in two groups (Group1: 4% vs Group 2: 5%, P=ns). A significant left to right atrialshunt (Qp/Qs 1·5:1) in 2·5% and tamponade in2% of cases occurred exclusively with the Inoue technique, whileconduction disturbances, such as transient (<24 h) left bundlebranch block (28%) and complete heart block (2%) were notedwith the retrograde technique (Group 2). Local complicationswere significantly higher in Group 2 (3% vs 0·5%, P<0·01).The procedure time with the Inoue technique was shorter thanwith the retrograde (Group 1: 15 ± 8, range 10 to 35min; Group 2: 22 ± 14, range 15 to 45 min, P=0·05).Echocardiographic follow-up at 1 year showed no significantdifference in mitral valve area between the two groups (Group1 (n=300): 1·8 ± 0·8 vs Group 2 (n=60):1·9 ± 0·9 cm²; P=0·3). CONCLUSION: Balloon mitral valvotomy using the Inoue balloon and the retrogradenon-transseptal technique results in significant immediate haemodynamicand symptomatic improvement. The Inoue technique achieved alarger immediate post-valvotomy mitral valve area, but the differencewas not apparent at 1 year follow-up. Incidence of significantmitral regurgitation was similar with both the techniques; however,local complications occurred more frequently with the retrogradetechnique. Both techniques may complement each other in technicallydifficult cases.     

Effects of gonadotropins and adenocorticotropin on plasmatic steroids of the catfish, Heteropneustes fossilis (Bloch).

The levels of some steroids in the plasma of female catfish were estimated following a single injection of porcine ACTH, ovine LH, or partially purified salmon gonadotropin (SG-G100) during the spawning and postspawning seasons. In the regressed catfish, injection of either LH or SG-G100 resulted in a three- to fourfold increase, compared to uninjected controls, in plasmatic cortisol for at least 1 hr. Injection of LH and ACTH resulted in two- and fourfold increases, respectively, of plasma cortisol levels as compared to saline-injected controls for both regressed and gravid fish. The concentration of plasma cortisol after ACTH treatment was higher than after LH or SG-G100. Gonadectomy did not influence the effect of LH on plasma cortisol concentration, and 20 min after injection, the cortisol concentration was identical to that of the intact fish. These results show that in the gravid catfish, as in the regressed ones, the increase in plasmatic cortisol after injection of LH or SG-G100 results principally from the activation of the interrenal. The concentrations of 11-deoxycortisol, 11-deoxycorticosterone, and 17α-hydroxy-20β-dihydroprogesterone were low in all samples and there was no evidence of an effect related to the injected hormone. Testosterone concentrations in the plasma of gravid fish injected with LH increased over the 1-hr sampling time and all values were higher than those recorded for saline- or ACTH-injected fish. Since the levels of cortisol and testosterone in the plasma of gravid catfish increase following gonadotropin administration, they may either singly or synergistically play a role in oocyte maturation.     

Use of narrow band imaging in assessing duodenal villous atrophy

Background and Objective

Narrow band imaging endoscopy with magnification (NBI-ME) has already been established in Barrett’s esophagus, stomach, and colonic mucosa, but limited work has been done in the mucosal evaluation of duodenum. A study was done to determine the correlation between NBI and histology in grading villous architecture in varied etiology.

Method

A prospective observational study comprising 105 subjects with suspected malabsorption. The presence of a diagnosed celiac disease, severe life threatening comorbidity, or pregnancy was considered as exclusion criteria. Standard endoscopy (SE), NBI-ME, multiple duodenal biopsies with histopathological examination were done in all.

Results

Fifty-one patients had celiac disease while 54 patients comprised mainly functional dyspepsia, iron deficiency anemia, tropical malabsorption syndrome, and irritable bowel syndrome. Four NBI-ME image subtypes of villous morphology have been proposed (NBI type I/II/III/IV). NBI-ME had 95 % sensitivity, 90.2 % specificity, 91.2 % positive predictive value, and 94.2 % negative predictive value for diagnosing altered villous morphology. Intraobserver kappa agreement coefficient (κ) for NBI-ME was 0.83 while interobserver agreement was 0.89 (95 % CI 0.8–0.97).

Conclusion

NBI-ME has good performance characteristics and very good kappa intra/interobserver agreement coefficient for varied subtypes of villous morphology. NBI-ME is most useful for obtaining a targeted biopsy which can be missed by conventional white light endoscopy.     

Pulmonary endarterectomy for saddling pulmonary embolism by Aspergillus fungus in an immunocompetent patient

We present a case of Tricuspid valve Aspergillus endocarditis with saddle shaped massive pulmonary embolism occurring in an immunocompetent host. The patient was managed uniquely by pulmonary endarterectomy (PEA) and combination antifungal chemotherapy with Liposomal amphotericin-B + caspofungin.     

Mid-term Results of Laparoscopic Sleeve Gastrectomy and Roux-en-Y Gastric Bypass in Adolescent Patients

The prevalence and severity of obesity in children and adolescents has been increasing in recent years at an unprecedented rate. Morbidly obese children will almost certainly develop severe comorbidities as they progress to adulthood, and bariatric surgery may provide the only alternative for achieving a healthy weight. The aim of this study was to assess the long-term outcomes and safety of laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) as new treatment modalities for morbidly obese adolescents. We conducted a retrospective review of a prospectively collected database of all adolescent patients who underwent LSG and RYGB under IRB protocol at the Bariatric and Metabolic Institute in Cleveland Clinic Florida between 2002 and 2011. Patients were also contacted by phone, adhering to HIPAA regulations, and were asked to answer a survey. Eighteen adolescents had a bariatric procedure performed at this institution. The mean age was 17.5 years, the average weight was 293.1 lbs, and the average BMI was 47.2 kg/m². The mean follow-up period consisted of 55.2 months. The postoperative weight at 55 months follow-up was 188.4 lbs and average BMI was 30.1 kg/m². Fifteen of the patients were available for follow-up. Thirteen out of 16 (81 %) comorbidities in patients available for follow-up were in remission following rapid weight loss. The long-term follow-up and perioperative morbidity shown in this study suggest that LSG and LRYGB appear to be safe and effective operations in morbidly obese adolescents.     

Clinical relevance of major histocompatibility complex class I chain–related molecule A (MICA) antibodies in live donor renal transplantation – Indian Experience

Antibody-mediated rejections (AMR) in the absence of circulating anti-HLA-DSA have highlighted the role of non-HLA antibodies, particularly those directed against endothelial cells. Of these, MICA (major histocompatibility complex class I chain–related molecule A) antibodies are the most notable and important because of their potential in promoting graft rejections. Limited studies have focused on the impact of MICA donor-specific antibodies (DSA) on graft outcome as compared to those that are not donor-specific (NDSA). We evaluated pre- and post-transplant sera at POD 7, 30, 90, 180 and the time of biopsy from 206 consecutive primary live donor renal transplant recipients for anti-MICA and anti-HLA antibodies using single antigen bead assay on a Luminex platform. Recipients who developed MICA antibodies and their donors were phenotyped for MICA alleles. For the purpose of antibody analysis, patients were categorized into three major groups: biopsy-proven AMR, acute cellular rejection (ACR) and those with no rejection episodes (NRE). During the mean follow-up period of 17.37 ± 6.88 months, 16 of the 206 recipients developed AMR, while ACR was observed in only 13 cases. A quarter (25%) of the AMR cases had anti-MICA antibodies as compared to 7.7% of those experiencing ACR and 6.2% of the NRE group. Allelic typing revealed that all MICA Ab +ve AMR cases were due to the presence of donor-specific antibodies. MICA-DSA even in the absence of HLA-DSA was significantly associated with AMR but not with ACR when compared with the NRE group (P = <.01).