Falloposcopy.

This review discusses advances in falloposcopy over the past 10 years. Refinements in instrumentation, including fiberoptics, have allowed visualization of the endosalpinx, a portion of the reproductive tract that has evaded endoscopic evaluation. A coaxial system of falloposcopic placement may give way to a linear everting catheter that does not require hysteroscopic guidance. Tubal endoscopic applications are discussed, including correlating hysterosalpingogram findings with those findings at salpingoscopy. Endosalpingeal changes can be quantitated in the presence of hydrosalpinges, and possibly with endometriosis. A scoring system to measure changes has been described. Using this scoring system, endosalpingeal findings at salpingoscopy have been compared with histologic and electron microscopic findings.     

Development of the Home Care Client Satisfaction Instrument

Abstract Client (patient) satisfaction has been studied extensively in the health care sector, yet those receiving home health care services have been the focus of few studies. The purpose of this study was to test the reliability and validity of the Home Care Client Satisfaction Instrument (HCCSI). A total of 400 clients, randomly selected from 20 randomly chosen home care agencies in one state, completed the HCCSI and demographic form. Most respondents were older adults with multiple health problems and their families or informal support systems. Since data were skewed, item analysis was used. The revised instrument (HCCSI-R) is unidimensional and includes 12 items rated on a 5-point Likert scale measuring specific aspects of care. In addition, there are three global measures of satisfaction rated on a 10-point scale. All items except one had significant item-total correlations greater than .59. The total score correlates with likeliness to recommend the agency to others (.37, p = .0001), showing some evidence for criterion-related validity.     

Effects of Posterior Tibial Slope on a Posterior Cruciate Retaining Total Knee Arthroplasty Kinematics and Kinetics

BackgroundIt has been hypothesized that increasing posterior tibial slope can influence condylar rollback and play a role in increasing knee flexion. However, the effects of tibial slope on knee kinematics are not well studied. The objective of this study is to assess the effects of tibial slope on femorotibial kinematics and kinetics for a posterior cruciate retaining total knee arthroplasty design.MethodsA validated forward solution model of the knee was implemented to predict the femorotibial biomechanics of a posterior cruciate retaining total knee arthroplasty with varied posterior slopes of 0°-8° at 2° intervals. All analyses were conducted on a weight-bearing deep knee bend activity.ResultsIncreasing the tibial slope shifted the femoral component posteriorly at full extension but decreased the overall femoral rollback throughout flexion. With no tibial slope, the lateral condyle contacted the polyethylene 6 mm posterior of the midline, but as the slope increased to 8°, the femur shifted an extra 5 mm, to 11 mm posterior of the tibial midline. Similar shifts were observed for the medial condyle, ranging from 7 mm posterior to 13 mm posterior, respectively. Increasing posterior slope decreased the posterior cruciate ligament tension and femorotibial contact force.ConclusionThe results of this study revealed that, although increasing the tibial slope shifted the femur posteriorly at full extension and maximum flexion, it reduced the amount of femoral rollback. Despite the lack of rollback, a more posterior location of condyles suggests lower chances of bearing impingement of the posterior femur and may explain why increasing slope may lead to higher knee flexion.     

The Knoevenagel reaction of malononitrile with acetylacetone: New route of pyrazole,pyrazolo[2,3-C]pyridine,benzene, pyridazine and benzo[C]pyridazine derivatives

The Knoevenagal reaction of malononitrile and acetylacetonegave the acyclic product 3 whichwas separated in a good yield and identified. The reactivity of 3 towards some chemical reagents is studied. Thus, the reaction of 3 with aromatic aldehydes, hydrazines and cyanomethylene derivativesgave products 6–12. Reaction of 3 with benzenediazonium chloridegave the primidine derivative 14.     

Udp-glucuronosyltransferase 2b7 is the major enzyme responsible for gemcabene glucuronidation in human liver microsomes.

The predominant metabolic pathway of gemcabene in humans is glucuronidation. The principal human UDP-glucuronosyltransferases (UGTs) involved in the glucuronidation of gemcabene were determined in this study. Glucuronidation of gemcabene was catalyzed by recombinant UGT1A3, recombinant UGT2B7, and recombinant UGT2B17, as well as by human liver microsomes (HLM). Gemcabene glucuronidation in recombinant UGTs and HLM followed non-Michaelis-Menten kinetics consistent with homotropic activation, but pharmacokinetics in humans were linear over the dose range tested (total plasma C(max), 0.06-0.88 mM). Gemcabene showed similar affinity (S(50)) for recombinant UGTs (0.92-1.45 mM) and HLM (1.37 mM). S-Flurbiprofen was identified as a more selective inhibitor of recombinant UGT2B7-catalyzed gemcabene glucuronidation (>23-fold lower IC(50)) when compared with recombinant UGT1A3- or recombinant UGT2B17-catalyzed gemcabene glucuronidation. The IC(50) for S-flurbiprofen inhibition of gemcabene glucuronidation was similar in HLM (60.6 microM) compared with recombinant UGT2B7 (27.4 microM), consistent with a major role for UGT2B7 in gemcabene glucuronidation in HLM. In addition, 5,6,7,3',4',5'-hexamethoxyflavone inhibited recombinant UGT1A3 and recombinant UGT2B17-catalyzed gemcabene glucuronidation (with 4-fold greater potency for recombinant UGT1A3) but did not inhibit gemcabene glucuronidation in HLM, suggesting that UGT1A3 and UGT2B17 do not contribute significantly to gemcabene glucuronidation. Reaction rates for gemcabene glucuronidation from a human liver bank correlated well (r(2)=0.722, P<0.0001; n=24) with rates of glucuronidation of the UGT2B7 probe substrate 3'-azido-3'-deoxythymidine. In conclusion, using the three independent experimental approaches typically used for cytochrome P450 reaction phenotyping, UGT2B7 is the major enzyme contributing to gemcabene glucuronidation in human liver microsomes.     

Effects of avasimibe on cytochrome P450 2C9 expression in vitro and in vivo.

Avasimibe, an acyl-CoA:cholesterol acyltransferase inhibitor, has been previously shown to be a potent inducer of CYP3A4 and multiple drug resistance protein 1. We have further characterized the drug interaction potential of avasimibe by studying the inductive and inhibitory effect of this compound on major drug-metabolizing enzymes. Enzymes known to be involved in the metabolism of drugs likely to be coadministered with avasimibe, such as CYP1A1/2, CYP2C, and CYP2B6, were evaluated further by microarray analysis, Western immunoblotting, and activity assays, using rifampicin and beta-naphthoflavone as positive controls. No change was observed in CYP1A1/2 mRNA or activity levels after avasimibe treatment. Differential induction of CYP2C9- and CYP2B6-immunoreactive protein and activity was observed depending on drug concentration and donor. Microarray analysis showed a similar increase in CYP2C and CYP2B6 mRNA levels. The inhibition potential of avasimibe on the major drug-metabolizing enzymes was assessed using pooled human liver microsomes. Avasimibe inhibited CYP2C9 (IC50 2.9 microM), CYP1A2 (IC50 13.9 microM), and CYP2C19 (IC50 26.5 microM). A clinical drug interaction study was conducted to determine whether avasimibe might interact with the CYP2C9 substrate warfarin. Volunteers received 750 mg of avasimibe and showed a 54.2% reduction in trough concentrations of S-warfarin and decreased prothrombin times by 12, 15, 19, and 21% on days 6 through 9, respectively. These results demonstrate that avasimibe's inductive spectrum resembles that of rifampin.     

EFAS Score —Validation of Persian Version by the Score Committee of the European Foot and Ankle Society (EFAS)

BackgroundThe Score Committee of the European Foot and Ankle Society (EFAS) developed, validated, and published the EFAS Score in nine European languages (English, German, French, Italian, Polish, Dutch, Swedish, Finnish, Turkish). From other languages under validation, the Persian version finished data acquisition and underwent further validation.MethodsThe Persian version of the EFAS Score was developed and validated in three stages: 1) item (question) identification (completed during initial validation study), 2) item reduction and scale exploration (completed during initial validation study), 3) confirmatory analyses and responsiveness of Persian version (completed during initial validation study in nine other languages). The data were collected pre-operatively and post-operatively at a minimum follow-up of 3 months and mean follow-up of 6 months. Item reduction, scale exploration, confirmatory analyses and responsiveness were executed using classical test theory and item response theory.ResultsThe internal consistency was confirmed in the Persian version (Cronbach’s Alpha 0.82). The Standard Error of Measurement (SEM) was 0.38 and is similar to other language versions. Between baseline and follow-up, 97% of patients showed an improvement on their EFAS score, with excellent responsiveness (effect size 1.93).ConclusionsThe Persian EFAS Score version was successfully validated in patients with a wide variety of foot and ankle pathologies. All score versions are freely available at www.efas.co.