New insights into the role of lipoprotein(a)-associated lipoprotein-associated phospholipase A2 in atherosclerosis and cardiovascular disease

Lipoprotein(a) [Lp(a)] plays an important role in atherosclerosis. The biological effects of Lp(a) have been attributed either to apolipoprotein(a) or to its low-density lipoprotein-like particle. Lp(a) contains platelet-activating factor acetylhydrolase, an enzyme that exhibits a Ca2+-independent phospholipase A2 activity and is complexed to lipoproteins in plasma; thus, it is also referred to as lipoprotein-associated phospholipase A2. Substrates for lipoprotein-associated phospholipase A2 include phospholipids containing oxidatively fragmented residues at the sn-2 position (oxidized phospholipids; OxPLs). OxPLs may play important roles in vascular inflammation and atherosclerosis. Plasma levels of OxPLs present on apolipoprotein B-100 particles (OxPL/apolipoprotein B) are correlated with coronary artery, carotid, and peripheral arterial disease. Furthermore, OxPL/apolipoprotein B levels in plasma are strongly correlated with Lp(a) levels, are preferentially sequestered on Lp(a), and thus are potentially subjected to degradation by the Lp(a)-associated lipoprotein-associated phospholipase A2. The present review article focuses specifically on the characteristics of the lipoprotein-associated phospholipase A2 associated with Lp(a) and discusses the possible role of this enzyme in view of emerging data showing that OxPLs in plasma are preferentially sequestered on Lp(a) and may significantly contribute to the increased atherogenicity of this lipoprotein.     

Poorly differentiated carcinoma of the rectum with aberrant immunophenotype： A case report

We report a case of a poorly differentiated epithelial tumour of the rectum with a highly pleomorphic morphology and an aberrant immunophenotype, including the expression of epithelial markers, the focal parameter of neuroendocrine differentiation, and the unexpected detection of CD-117 overexpression. A 69-year-old man was admitted to our clinic complaining of rectal bleeding and weight loss. Colonoscopy showed an ulcerative bleeding mass located about 8 cm from the anal verge. Abdominal and pelvis CT scans demonstrated a large low-density lesion with extracanalicular growth from the middle rectum, with local lymph-node spread, and without tumour infiltration of other pelvic organs, or evidence of distant intraabdominal spread. The patient underwent a low anterior resection for rectal cancer together with wide resection of lymph nodes. In immunohistochemical analysis, pankeratin and Epithelial Membrane Antigen （EMA） immunolabeling proved the epithelial nature of the tumor cells. Chromogranin A and Leukocyte Common Antigen （LCA） were negative, whereas CD-56 expression was scanty and Neuron Specific Enolase （NSA） was heavily and diffusely expressed. Ki67 immunoexpression was particularly increased. Interestingly, the intense c-kit immunoreactivity （100%） was a common feature. The above phenotypic and immunohistochemical profile was consistent with an anaplastic carcinoma of the large intestine, with focal neuroendocrine differentiation and diffuse immunoreactivity to c-kit protein. Given the resistance of this tumor to conventional chemotherapy and radiation, the incidence of the c-kit alteration may represent a novel approach to a gene-directed treatment using a c-kit inhibitor （STI571） similar to that which has been proposed in GISTs.     

Recovery rates and functional results after repair for rectovaginal fistula in Crohn’s disease: a comparison of different techniques

Background and objectives Rectovaginal fistulas (RVF) in Crohn’s disease continue to be a challenging problem. Several operations are often necessary to attain definitive healing of the disease process. There are no guidelines concerning optimal therapeutic approaches. Endoanal mobilization techniques such as the advancement flap technique were considered the therapy of choice for many years, but are now regarded ever more critically. We have implemented several less aggressive closure techniques that take account of the anatomy and morphology of the anorectum. The long-term results are presented in this paper. Materials and methods The method used was observational analysis with a standard protocol of all patients with RVF and Crohn’s disease treated surgically at a single institution. Results/Findings Between January 1985 and December 2002, we treated 72 patients with low rectovaginal fistulas. The operations comprised 56 procedures performed in 37 women presenting with RVF. The patients’ median age was 34.6 ± 10 years; the follow-up period was 7.15 years (10 months–18 years). Several techniques were performed: transverse transperineal repair (n = 20), endoanal direct closure multilayer without flap (n = 15), anocutaneous flap (n = 14), and advancement mucosal or full-thickness flap (n = 7). Diverting ileostomies were created in 28 patients (76%). Recovery was achieved with the initial repair in 19 patients (51.4%). An additional 12 patients underwent repeat procedures (2–5), with an overall success rate of 27:37 (73%). The rate of recurrence was 30% during a follow-up period of 7.1 years. The rate of proctectomy was 13.5%. The success rates for each of the techniques in the above group were 70, 73, 86, and 29%, respectively. They were significantly higher with the direct closure and anocutaneous flap technique than with the advancement flap technique. However, the transperineal repair led to decreased postoperative resting pressures. In the advancement flap technique, the resting and squeezing pressure decreased significantly. The risk of developing a suture line dehiscence leading to a persisting fistula was higher in the advancement flap procedure with 43%. Interpretation/conclusion Techniques with a low degree of tissue mobilization such as the direct closure and anocutaneous flap show higher success rates without significant postoperative changes in continence and manometric outcome. Impaired continence was observed only in the advancement flap group, resulting in significant changes in manometric values and recovery rates. The authors prefer to apply the direct multilayer closure technique without flap.     

Evaluation of a conventional ELISA (Novitec) and a near patient immunochromatographic test (Stick H. pyl) for Helicobacter pylori antigen detection in stool

BACKGROUND/AIMS: The detection of Helicobacter pylori (H. pylori) antigen in stool by conventional ELISA is a reliable non-invasive method for the diagnosis of H. pylori infection in untreated patients. Recently, rapid in-office stool tests have been developed for the same purpose. METHODOLOGY: We have prospectively evaluated the performances of a commercially available enzyme-linked immunoassay (Novitec EIA) and a rapid near-patient immunochromatographic stool test (Stick H. pyl) for the detection of H. pylori stool antigen. Fifty H. pylori positive and 50 negative patients were included. H. pylori infection was diagnosed by using histology, rapid urease test and urea breath test. Patients were classified as positive if two of the three tests were positive and negative if all the three tests were negative. Testing was carried out according to the manufacturer's instructions. RESULTS: Novitec EIA had 8% equivocal results. If they were interpreted as negative the sensitivity, specificity, positive predictive value, negative predictive value and overall diagnostic accuracy were 82%, 86%, 86%, 83% and 84% and if as positive 88%, 76%, 79%, 86% and 82% respectively. ROC curve analysis showed a cut-off value of 0.144 for our population. The corresponding numbers for this cut-off value were: 82%, 94%, 93%, 84% and 88%. The respective numbers for Stick H. pyl were 78%, 78%, 76%, 78% and 79%. CONCLUSIONS: Novitec EIA performed well in this cohort of Greek patients and demonstrated a high specificity and positive predictive value when we adjusted the cut-off at 0.144. Performance of Stick H. pyl was sub-optimal.     

Prominent phenotypic variability associated with mutations in Progranulin

Mutations in progranulin (PGRN) are associated with frontotemporal dementia with or without parkinsonism. We describe the prominent phenotypic variability within and among eight kindreds evaluated at Mayo Clinic Rochester and/or Mayo Clinic Jacksonville in whom mutations in PGRN were found. All available clinical, genetic, neuroimaging and neuropathologic data was reviewed. Age of onset ranged from 49 to 88 years and disease duration ranged from 1 to 14 years. Clinical diagnoses included frontotemporal dementia (FTD), primary progressive aphasia, FTD with parkinsonism, parkinsonism, corticobasal syndrome, Alzheimer's disease, amnestic mild cognitive impairment, and others. One kindred exhibited maximal right cerebral hemispheric atrophy in all four affected individuals, while another had maximal left hemisphere involvement in all three of the affected. Neuropathologic examination of 13 subjects revealed frontotemporal lobar degeneration with ubiquitin-positive inclusions plus neuronal intranuclear inclusions in all cases. Age of onset, clinical phenotypes and MRI findings associated with most PGRN mutations varied significantly both within and among kindreds. Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals.     

Dexamethasone decreases the transmesothelial electrical resistance of the parietal and visceral pleura

The effect of dexamethasone on the transmesothelial electrical resistance (R _TM) of sheep pleura was investigated by Ussing chamber experiments. Our results show that dexamethasone decreases the R _TM of sheep pleurae, in part by stimulation of glucocorticoid receptors. This finding may be of importance in regard to the faster resolution of corticosteroid-treated pleural effusions.     

Agenesis of the corpus callosum associated with narcolepsy-cataplexy

We describe a 24-year-old man with episodes of intense desire to sleep for periods ranging from 2min to 3h, episodes of generalized weakness and inability to speak without alteration of consciousness, frequent hypnagogic hallucinations during sleep and occasionally transient paralysis of limbs upon awakening. Brain MRI demonstrated elevation of the third ventricle, a characteristic lack of depiction of the corpus callosum and extension of the bihemispheric fissure to the third ventricle. We assume that structural changes of the base of frontal lobes, diencephalon and brainstem, can be accountable for symptomatic narcolepsy and cataplexy.     

Impact of cancer patients' disease awareness on their family members' health‐related quality of life: a cross‐sectional survey

Background: Conflicting results exist concerning disease knowledge and patients' quality of life (QOL) while there is very limited information concerning the impact of awareness on caregivers' health‐related quality of life. The aim of this study was to explore the influence of disease awareness on both cancer patients and their caregivers during the period of chemotherapy. Materials and Methods: Two hundred and twelve cancer patient–caregiver dyads completed the QOL SF‐36 instrument on the day of chemotherapy. Hierarchical multiple linear regression analysis was performed. Results: Physical component parameters were significantly higher in the family members (p<0.001), while their mental component was lower than cancer patients. Younger patients, females, and of higher educational status were more frequently aware of their disease status while patients with gastrointestinal cancer were more likely to be unaware. Disease knowledge seems to exert a negative influence on patients' physical and mental parameters while lack of awareness affects adversely caregivers' vitality, social function, emotional role, and mental health. Multiple regression analysis confirmed disease awareness affected reversely patients' and caregivers' mental QOL while the counter‐influence of the dyad was revealed. Conclusions: A holistic approach to cancer management should be followed. Patient's treatment is the major medical concern, but health system and professionals should be involved in the mental and physical support of caregivers as well. Tailored interventions that focus on the support of the dyad patient–caregiver should be developed. Copyright © 2010 John Wiley & Sons, Ltd.