Resveratrol and liver disease: from bench to bedside and community

Liver diseases incorporate several maladies, which can range from benign histological changes to serious life‐threatening conditions. These may include inborn metabolic disease, primary and metastatic cancers, alcoholic cirrhosis, viral hepatitis and drug‐induced hepatotoxicity. Liver disease remains a major cause of morbidity and mortality with significant economic and social costs. Several novel approaches are currently being studied which may provide a better therapeutic outcome. The use of naturally occurring phytochemicals, some of them obtained from dietary sources, in the amelioration of illness have recently gained considerable popularity. These agents, having anti‐oxidant and anti‐inflammatory properties, provide a safe and effective means of ameliorating chronic disease. Resveratrol, a grape polyphenol, has shown considerable promise as a therapeutic agent in the treatment of the aforementioned liver ailments. Several studies have highlighted the hepatoprotective properties of resveratrol. Resveratrol has been shown to prevent hepatic damage because of free radicals and inflammatory cytokines, induce anti‐oxidant enzymes and elevate glutathione content. Resveratrol has also been shown to modulate varied signal transduction pathways implicated in liver diseases. This review critically examines the current preclinical in vitro and in vivo studies on the preventive and therapeutic effects of resveratrol in liver diseases. The review highlights the pharmacological mechanisms involved in mediating the aforementioned effects. Toxicity, pharmacokinetics and clinical bioavailability of resveratrol are also reviewed in this article. The challenges involved, future directions and novel approaches such as site‐specific drug delivery in the use of resveratrol for the prevention and treatment of liver disease are also discussed.     

Quality and safety of fresh-frozen plasma inactivated and leucoreduced with the Theraflex methylene blue system including the Blueflex filter: 5 years' experience

BACKGROUND AND OBJECTIVES: The objective of this paper is to present 5 years' experience of pathogen inactivation of fresh-frozen plasma with the methylene blue system in a blood centre in Athens. MATERIALS AND METHODS: Eight thousand and five hundred units treated by methylene blue and 54 435 untreated were issued for transfusion in four hospitals during the period 2000-2005. Eighty-eight units were evaluated for changes in coagulation factor activity and cytokine concentrations following treatment. RESULTS: Coagulation factor losses were in the accepted range. Adverse reactions were 1 : 8500 with treated and 1 : 2177 with untreated units. The five serious reactions were all in untreated units. No seroconversions for infectious diseases were reported. CONCLUSIONS: Methylene-blue-treated fresh-frozen plasma is safer than the untreated product even in patients who require large quantities of plasma transfusion.     

Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11

We report a patient with a clinical and molecular diagnosis of LEOPARD syndrome (LS) associated with multiple granular cell tumors (MGCT). Bidirectional sequencing of exons 7, 12, and 13 of the PTPN11 gene revealed the T468M missense mutation in exon 12. This mutation has been previously reported in patients with LS. To our knowledge, this is the first report of MGCT associated with molecularly characterized LS and provides the first molecular evidence linking granular cell tumors (GCT) to the Ras/mitogen-activated protein (MAP) kinase pathway. We propose that MGCT can be associated with LS. Analysis of GCT from this case tested negatively for loss of heterozygosity (LOH) at the PTPN11 and NF1 loci and did not show deletions of the PTEN gene. The absence of LOH of PTPN11 supports published functional data that T468M is a dominant-negative mutation.     

Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations

Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan–Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9–50.8). The risk to males is 26.5% (95% CI 22.6–30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.     

Development and validation of the Montreal cognitive assessment for people with hearing impairment (MoCA-H)

Background

Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment.

Methods

We adapted existing MoCA 8.1 items for people with hearing impairment by presenting instructions and stimuli in written rather than spoken format. One Attention domain and two Language domain items required substitution by alternative items. Three and four candidate items respectively were constructed and field-tested along with the items adapted to written form. We used a combination of individual item analysis and item substitution to select the set of alternative items to be included in the final form of the MoCA-H in place of the excluded original items. We then evaluated the performance and reliability of the final tool, including making any required adjustments for demographic factors.

Results

One hundred and fifty-nine hearing-impaired participants, including 76 with normal cognition and 83 with dementia, completed the adapted version of the MoCA. A further 97 participants with normal hearing completed the standard MoCA as well as the novel items developed for the MoCA-H to assess score equivalence between the existing and alternative MoCA items and for independence from hearing impairment. Twenty-eight participants were retested between 2–4 weeks after initial testing. After the selection of optimal item set, the final MoCA-H had an area under the curve of 0.973 (95% CI 0.952–0.994). At a cut-point of 24 points or less sensitivity and specificity for dementia was 92.8% and 90.8%, respectively. The intraclass correlation for test–retest reliability was 0.92 (95%CI 0.78–0.97).

Conclusion

The MoCA-H is a sensitive and reliable means of identifying dementia among adults with acquired hearing impairment.     

Evaluation of sexual function in hypertensive men receiving treatment: a review of current guidelines recommendation

IntroductionIt has been suggested that some classes of antihypertensive drugs may induce or exacerbate sexual and/or erectile dysfunction (ED) more than others. Sexually related side effects of antihypertensive treatment may compromise patient's and partner's quality of life. Often, these side effects can lead to withdrawal or poor compliance with therapy resulting in abnormal blood pressure and associated morbidity.AimThe aim of this study was to evaluate whether hypertension clinical practice guidelines (CPGs) address ED and/or other sexual issues as either an adverse outcome of chosen therapy or as a factor to consider in treatment decision.MethodsHypertension CPGs were identified by searching PubMed (from 2000 to current), the World Wide Web, bibliographies of retrieved guidelines, and official home pages of major medical societies.Main Outcome MeasuresThe main outcome measures used for this study were guidelines assessment using a set of author‐determined survey questions.ResultsTwelve CPGs were identified and analyzed. From these 12, only three emphasized the importance of assessing sexual function prior to initiation and/or follow‐up of antihypertensive therapy; only five described potential sexual side effects associated with some drugs; only two provided specific management recommendations on commencing antihypertensive therapy in sexually active men or those with preexisting ED and address the timeline of the potential drug‐induced impairment of sexual function.ConclusionsOnly a minority of CPGs for the treatment of hypertension consider ED or other sexual issues as either an adverse outcome or as a factor to consider in treatment. Sexual function is an important aspect of quality of life for both the individual and his partner. It is therefore imperative to select therapy with the least possible potential for causing sexual sequelae and enable the best achievable balance between therapeutic efficacy, quality of life, and therapeutic compliance. Based on these results, our proposed algorithm attempts to effectively apply available evidence to clinical practice. Karavitakis M, Komninos C, Theodorakis PN, Politis V, Lefakis G, Mitsios K, Koritsiadis S, and Doumanis G. Evaluation of sexual function in hypertensive men receiving treatment: A review of current guidelines recommendation. J Sex Med 2011;8:2405–2414.     

Rapid sequence intubation without a neuromuscular blocking agent in a 14-year-old female patient with myasthenia gravis

The anesthesia care of a 14-year-old female patient with an acute exacerbation of myasthenia gravis (MG) and a full stomach who required emergency surgery for placement of a hemodialysis catheter is described. A nonventilated rapid sequence induction was successful with the use of propofol, lidocaine, remifentanil, cricoid pressure and no neuromuscular blocking agent. Although the use of combinations of i.v. anesthetic agents have been suggested for tracheal intubation without the need for neuromuscular blocking agents, none of these techniques has been advocated for rapid sequence intubation. We review existing literature on the topic of tracheal intubation using remifentanil and propofol without a neuromuscular blocking agent and on the topic of tracheal intubation of patients with MG using i.v. anesthesia and no neuromuscular blocking agents.     

Predicted versus executed surgical orthognathic treatment

ObjectivesThis study aimed to analyse combined surgical-orthodontic treatment plans, compare them with the actual surgery performed, and define factors resulting in changes of the original plan during orthodontic pre-surgical preparation.Study designThe clinical files of 312 orthognathic surgery patients, operated between January 2008 and December 2010, were retrospectively reviewed. Of these 312 patients, 129 had a bimaxillary operation. One hundred sixty patients had osteotomy of the lower jaw only and 23 had osteotomy of the upper jaw only. Factors analysed in the study include Angle Class malocclusion, patient sex, and age. Lip-to-incisor relationship, overjet, overbite and midline deviations of the upper and lower jaw were recorded. Effects of surgical assisted rapid palatal expansion (SARPE) on the eventual surgery were also investigated. Reasons for changing the original treatment plan at the time of the finished pre-surgical-orthodontic alignment were analysed.ResultsThe original treatment plan was changed in 42 of the 312 patients (13.5%). Changes occurred generally in case of a larger interval between set-up of the first treatment plan and the eventual operation (average 22.4 versus 16.4 months for patients with changed versus unchanged treatment plan, respectively). All Class I patients had surgery performed as planned. Class III patients had a significantly higher rate of altered treatment plan (27.3%) than Class II patients (7.6%). More men (52.4%) saw their treatment plan changed, although there were more women than men in the study population (59.6 versus 40.4%).ConclusionOne in seven patients (13.5%) had a different operation than was planned at the start of treatment. Class III patients with small overjet and overbite commonly have a treatment plan for a monomaxillary operation that, after decompensation, needs to be adapted to a bimaxillary operation.     

Validation of anatomical landmarks-based registration for image-guided surgery: An in-vitro study

IntroductionPerioperative navigation is a recent addition to orthognathic surgery. This study aimed to evaluate the accuracy of anatomical landmarks-based registration.Materials and methodsEighty-five holes (1.2 mm diameter) were drilled in the surface of a plastic skull model, which was then scanned using a SkyView cone beam computed tomography scanner. DICOM files were imported into BrainLab ENT 3.0.0 to make a surgical plan. Six anatomical points were selected for registration: the infraorbital foramena, the anterior nasal spine, the crown tips of the upper canines, and the mesial contact point of the upper incisors. Each registration was performed five times by two separate observers (10 times total).ResultsThe mean target registration error (TRE) in the anterior maxillary/zygomatic region was 0.93 ± 0.31 mm (p < 0.001 compared with other anatomical regions). The only statistically significant inter-observer difference of mean TRE was at the zygomatic arch, but was not clinically relevant.ConclusionWith six anatomical landmarks used, the mean TRE was clinically acceptable in the maxillary/zygomatic region. This registration technique may be used to access occlusal changes during bimaxillary surgery, but should be used with caution in other anatomical regions of the skull because of the large TRE observed.