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.     

Attempted suicide in bipolar disorder pedigrees: evidence for linkage to 2p12.

BACKGROUND: We are interested in identifying susceptibility genes that predispose subjects to attempted suicide. METHODS: We conducted a secondary analysis of genome-wide linkage data from 162 bipolar pedigrees that incorporated attempted suicide as a clinical covariate. RESULTS: The strongest covariate-based linkage signal was seen on 2p12 at marker D2S1777. The logarithm of odds (LOD) score at marker D2S1777 rose from 1.56 to 3.82 after inclusion of the suicide covariate, resulting in significant chromosome-wide empirically derived p-values for the overall linkage finding (p = .01) and for the change in LOD score after the inclusion of the covariate (p = .02). CONCLUSIONS: The finding on chromosome 2 replicates results from two previous studies of attempted suicide in pedigrees with alcohol dependence and in pedigrees with recurrent early-onset depression. Combined, these three studies provide compelling evidence for a locus influencing attempted suicide on 2p12.     

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.     

Short-stay surgery of inguino-crural hernia

BACKGROUND: To evaluate the hospital stay, morbidity, and patients' compliance for short stay inguinal hernia repair. METHODS: Retrospective analysis of 669 patients (594 men and 75 women) who underwent short stay inguinal hernia repair (706 inguinal and 45 femoral repairs) at the Institute of General Surgery, University of Ferrara. Mean age was 60.7 years (range, 18-84 years). The anesthesia was: loco-regional in 495 patients (74%) and general or epidural in 174 (26%). RESULTS: Mean hospital stay was 1.2 days. Postoperative complications were: three scrotal hematomas, two ischemic orchitis, three prosthetic infections, one local anesthetic intolerance, and three high fever. Eighty-five percent of patients were satisfied of the surgical procedure in short hospital stay. Mean follow-up was 36 months. CONCLUSIONS: Short hospital stay in inguinal hernia repair is safe, effective, and widely accepted by patients.     

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.     

APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study

Asymptomatic Alzheimer''s disease (ASYMAD) subjects are individuals characterized by preserved cognition before death despite substantial AD pathology at autopsy. ASYMAD subjects show comparable levels of AD pathology, i.e. β-amyloid neuritic plaques (Aβ-NP) and tau-neurofibrillary tangles (NFT), to those observed in mild cognitive impairment (MCI) and some definite AD cases. Previous clinicopathologic studies on ASYMAD subjects have shown specific phenomena of hypertrophy in the cell bodies, nuclei, and nucleoli of hippocampal pyramidal neurons and other cerebral areas. Since it is well established that the allele APOε4 is a major genetic risk factor for AD, we examined whether specific alleles of APOE could be associated with the different clinical outcomes between ASYMAD and MCI subjects despite equivalent AD pathology. A total of 523 brains from the Nun Study were screened for this investigation. The results showed higher APOε2 frequency (p < 0.001) in ASYMAD (19.2%) vs. MCI (0%) and vs. AD (4.7%). Furthermore, higher education in ASYMAD vs. MCI and AD (p < 0.05) was found. These novel autopsy-verified findings support the hypothesis of the beneficial effect of APOε2 and education, both which seem to act as contributing factors in delaying or forestalling the clinical manifestations of AD despite consistent levels of AD pathology.