High-definition optical magnification with digital chromoendoscopy detects gastric mucosal changes in dyspeptic-patients

BACKGROUND Accurate detection of gastric infection by Helicobacter pylori(H.pylori) and premalignant lesions are important for effective provision of treatment,preventing the development of gastric neoplasia.Optical enhancement systems with optical magnification improved the identification of mucosal superficial and vascular patterns in patients with dyspepsia.AIM To evaluate an optical enhancement system with high-definition magnification,for diagnosis of normal gastric mucosa,H.pylori-associated gastritis,and gastric atrophy.METHODS A cross-sectional,nonrandomized study from November 2015 to April 2016 performed in a single-tertiary academic center from Ecuador.Seventy-two consecutive patients with functional dyspepsia according to the Rome III criteria,were tested for H.pylori using a stool antigen test and were assigned to an Hp+group or an Hp-control group.Esophagogastroduodenoscopy with highdefinition optical magnification and digital chromoendoscopy was performed,and patients were classified into 4 groups,in accordance to the microvasculararchitecture pattern of the mucosa.Interobserver and intraobserver agreement among operators were calculated.RESULTS Of the 72 participants,35 were Hp+ and 37 were Hp-.Among 10 patients with normal mucosal histology in biopsy samples,90% had a Type I pattern of microvascular architecture by endoscopy.Among participants with type IIa and type IIb patterns,significantly more were Hp+ than Hp-(32 vs 8),and most(31 out of 40) had histological diagnoses of chronic active gastritis.Two of the three participants with a histological diagnosis of atrophy had a type III microvascular pattern.The type I pattern predicted normal mucosa,type IIa–IIb predicted H.pylori infection,and type III predicted atrophy with sensitivities of 90.0%,91.4%,and 66.7%,respectively.The intraobserver and interobserver agreements had kappa values of 0.91 and 0.89,respectively.CONCLUSION High-definition optical magnification with digital chromoendoscopy is useful for diagnosis of normal gastric mucosa and H.pylori-associated gastritis with high accuracy,but further studies are needed to determine whether endoscopic diagnosis of gastric atrophy is feasible.     

Nitric oxide and macrophage antiviral extrinsic activity

In this study we evaluated the relationship between nitric oxide (NO) and macrophage antiviral extrinsic activity. Macrophages activated by intraperitoneal injection of herpes simplex virus-2 (HSV-2), showed both extrinsic antiviral activity and high nitrite production in contrast to non-activated, resident macrophages. The extrinsic antiviral activity was observed in cultures of Vero cells infected with HSV-1 and HSV-2. The NO inhibitor N-monomethyl-l-arginine acetate (l-NMA) impaired the antiviral activity of HSV-elicited macrophages. The effect was dose dependent and correlated with a reduction of nitrite in the culture media. The effect of l-NMA was reversed by the addition of l-arginine. These data indicate that NO could be responsible for the described activity. Furthermore, l-NMA treatment resulted in the aggravation of HSV-1-induced keratitis in the mouse model, supporting a defensive role of NO in the pathogenesis of HSV-1 corneal infection.     

Severe congenital muscular dystrophy in a Mexican family with a new nonsense mutation (R2578X) in the laminin alpha-2 gene

The congenital muscular dystrophies (CMDs) are a heterogeneous group of autosomal recessive disorders. Approximately one half of cases diagnosed with classic CMD show primary deficiency of the laminin alpha2 chain of merosin. Complete absence of this protein is usually associated with a severe phenotype characterized by drastic muscle weakness and characteristic changes in white matter in cerebral magnetic resonance imaging (MRI). Here we report an 8-month-old Mexican female infant, from a consanguineous family, with classical CMD. Serum creatine kinase was elevated, muscle biopsy showed dystrophic changes, and there were abnormalities in brain MRI. Immunofluorescence analysis demonstrated the complete absence of laminin alpha2. In contrast, expression of alpha-, beta-, gamma-, and delta-sarcoglycans and dystrophin, all components of the dystrophin-glycoprotein complex, appeared normal. A homozygous C long right arrow T substitution at position 7781 that generated a stop codon in the G domain of the protein was identified by mutation analysis of the laminin alpha2 gene ( LAMA2). Sequence analysis on available DNA samples of the family showed that parents and other relatives were carriers of the mutation.     

Mutual link among the approaches to clipping of basilar aneurysms

Abstract

We report on a series of 48 patients, ages 74 to 20 year, with hypophyseal adenomas. Of these, 46 (96%) had secreting tumors, 3 had Cushing’s disease, 9 had somatotrophinomas, and 34 (29 females and 5 males) had prolactinomas. Thirty cases were diagnosed as intrasellar adenomas (62%) while the remaining eighteen (38%) presented extrasellar expansion. Of 9 acromegalic patients, 7 had typical clinical and biochemical features while 2 were exclusively prognatic with normal basal GH levels, but abnormal dynamic tests. Prolactinomas were npninvasive in women and faster growing and more extensive in men. Forty seven patients underwent surgery. Five of these required craniotomy and the rest were approached through the sphenoidal bone (TSf). Remission was achieved in Cushing’s disease, acromegaly, and female intrasellar prolactinomas. Larger tumors such as nonsecreting adenomas and male prolactinomas showed poor results after undergoing subtotal resections, with persistance of endocrinological disturbances. From our findings it appears that these tumors are not more aggressive in youths than in adults. Because there was a close relationship between tumor size, invasiveness, and the patients, final outcome, we conclude that early diagnosis and treatment is essential. Frequent complaints in adolescents such as irregular menses, retarded puberty, and growth disorders should be thoroughly investigated and not merely considered as transient or ‘functional’ [Neural Res 1998; 20: 415–417]     

Associations of Uncertainty With Psychological Health and Quality of Life in Older Adults With Advanced Cancer

ContextOlder adults with advanced cancer face uncertainty related to their disease and treatment.ObjectivesTo evaluate the associations of uncertainty with psychological health and quality of life (QoL) in older adults with advanced cancer.MethodsSecondary cross-sectional analysis of baseline data from a national clustered geriatric assessment trial. Patients 70 years and older with advanced cancer considering a new line of chemotherapy were recruited. We measured uncertainty using the modified nine-item Mishel Uncertainty in Illness Scale. Dependent variables included anxiety (Generalized Anxiety Disorder-7), depression (Generalized Depression Scale-15), distress (distress thermometer), QoL (Functional Assessment of Cancer Therapy—General), and emotional well-being (Functional Assessment of Cancer Therapy—General subscale). We used multivariate linear regression analyses to evaluate the association of uncertainty with each dependent variable. We conducted a partial least squares analysis with a variable importance in projection (VIP) plot to assess the contribution of individual variables to the model. Variables with a VIP <0.8 were considered less influential.ResultsWe included 527 patients (median age 76 years; range 70–96). In multivariate analyses, higher levels of uncertainty were significantly associated with greater anxiety (β = 0.11; SE = 0.04), depression (β = 0.09; SE = 0.02), distress (β = 0.12; SE = 0.02), as well as lower QoL (β = ?1.08; SE = 0.11) and emotional well-being (β = ?0.29; SE = 0.03); the effect sizes were considered small. Uncertainty items related to disease and treatment were most strongly associated with psychological health and QoL scores (all VIP >0.8).ConclusionUncertainty among older patients with advanced cancer is associated with worse psychological health and QoL. Tailored uncertainty management strategies are warranted.     

Impact of Breast Density Legislation on Breast Cancer Risk Assessment and Supplemental Screening: A Survey of 110 Radiology Facilities

Breast density notification laws, passed in 19 states as of October 2014, mandate that patients be informed of their breast density. The purpose of this study is to assess the impact of this legislation on radiology practices, including performance of breast cancer risk assessment and supplemental screening studies. A 20‐question anonymous web‐based survey was emailed to radiologists in the Society of Breast Imaging between August 2013 and March 2014. Statistical analysis was performed using Fisher's exact test. Around 121 radiologists from 110 facilities in 34 USA states and 1 Canadian site responded. About 50% (55/110) of facilities had breast density legislation, 36% of facilities (39/109) performed breast cancer risk assessment (one facility did not respond). Risk assessment was performed as a new task in response to density legislation in 40% (6/15) of facilities in states with notification laws. However, there was no significant difference in performing risk assessment between facilities in states with a law and those without (p < 0.831). In anticipation of breast density legislation, 33% (16/48), 6% (3/48), and 6% (3/48) of facilities in states with laws implemented handheld whole breast ultrasound (WBUS), automated WBUS, and tomosynthesis, respectively. The ratio of facilities offering handheld WBUS was significantly higher in states with a law than in states without (p < 0.001). In response to breast density legislation, more than 33% of facilities are offering supplemental screening with WBUS and tomosynthesis, and many are performing formal risk assessment for determining patient management.     

Effects of D-003 on hepatic drug-metabolizing enzyme activities in rats

D-003 is a mixture of very-long-chain aliphatic acids with cholesterol-lowering and concomitant anti-platelet effects. The microsomal cytochrome P-450 system comprises a superfamily of proteins present in hepatic and extrahepatic tissues that is responsible for the metabolism of many drugs. The present study was undertaken to investigate the effects of D-003 on in vivo drug-metabolizing hepatic enzymes. Two experimental series (n = 6 animals/group) were performed. In the first series rats were randomly distributed in one control and two groups treated with D-003 at 1,000 and 2,000 mg/kg for 14 days. In the second one they were distributed in one control and three groups treated with D-003 (250, 500, and 1,000 mg/kg) for 6 months. All treatments were orally administered by gastric gavage. Control rats were orally treated only with acacia gum/water vehicle. The content of microsomal P-450, b (5) cytochromes, total sulfhydryl groups, nonprotein sulfhydryl groups, and protein-bound sulfhydryl groups as well as the activities of NADPH cytochrome c reductase, aminopyrine demethylase, dimethylnitrosamine N-demethylase, 7-ethoxyresorufin O-deethylation, 7-pentoxyresorufin O-depentylation, and cytosolic glutathione S-transferase were assessed. D-003 administered up to 2,000 mg/kg or 1,000 mg/kg during 14 days or 6 months did not affect the activities of the hepatic drug-metabolizing enzymes investigated. It is concluded that D-003 is not metabolized by the liver cytochrome system and that potential risk derived from drug-to-drug interactions between D-003 and concomitant drugs appears to be low.     

Enhancement of purinergic neurotransmission by galantamine and other acetylcholinesterase inhibitors in the rat vas deferens

Galantamine, a mild acetylcholinesterase inhibitor and an allosteric ligand of nicotinic receptors, enhanced in a concentration-dependent manner the amplitude of purinergic twitch contractions of the electrically stimulated rat vas deferens (0.2 Hz, 1 ms, 60 V). Other acetylcholinesterase inhibitors also increased the twitches, showing a hierarchy of potencies of galantamine>physostigmine>tacrine>rivastigmine=donepezil. The potentiations seem to be unrelated to the ability to inhibit acetylcholinesterase, since the hierarchy of potencies to block the enzyme in vas deferens was tacrine>physostigmine>rivastigmine>donepezil>galantamine. Acetylcholine also increased the twitches; such effect was produced by a low range of concentrations of acetylcholine (10(-10)-10(-7) M). This facilitatory effect of acetylcholine on twitches was significantly potentiated by galantamine (10(-7)-10(-6) M), but not by rivastigmine or donepezil. A striking enhancement of twitches was also caused by charybdotoxin, a blocker of high-conductance Ca2+-activated K+ channels, and by 4-aminopyridine, a non-specific blocker of K+ channels; in addition, apamin, a blocker of small-conductance Ca2+-activated K+ channels, induced a lower potentiation. The antagonist mecamylamine (10(-7)-10(-6) M) reduced by 80% the potentiation by galantamine, indicating the involvement of nicotinic receptors. Therefore, it is suggested that, besides an inhibition of acetylcholinesterase, some additional mechanisms, such as blockade of Ca2+-dependent K+ channels, or activation of nicotinic receptors of nerve terminals, might be involved in twitch potentiation. These results are relevant in the context of the clinical use of galantamine to improve cognition and behaviour in patients with Alzheimer's disease.     

Ovarian carcinoma expresses the NKG2D ligand Letal and promotes the survival and expansion of CD28- antitumor T cells

The role of the NKG2D immunoreceptor and its ligands in antitumor immune response is incompletely understood. Here, we report that effector immune cells infiltrating ovarian carcinoma are mostly CD8+ lymphocytes lacking CD28 but expressing the NKG2D costimulatory receptor. Human ovarian carcinoma expresses the novel NKG2D ligand lymphocyte effector cell toxicity-activating ligand (Letal). Letal was found to be an independent prognosticator of improved survival in advanced ovarian cancer. Higher levels of tumor-derived Letal were associated with stronger lymphocyte infiltration. Letal exerted marked costimulatory effects and induced type-1 polarization in CD8+CD28- tumor-infiltrating lymphocytes ex vivo. Letal engagement increased the expression of the glucose transporter Glut-1, enhanced glucose up-take, and protected CD8+ lymphocytes from cisplatin-induced killing. Letal also down-regulated the expression of Fas in CD8+ cells and rendered them resistant to Fas ligand-induced apoptosis. Our results indicate that Letal promotes tumor immune surveillance by promoting the survival and intratumoral expansion of antitumor cytotoxic lymphocytes. We propose that Letal could be used for the ex vivo expansion of apoptosis-resistant tumor-reactive cytotoxic lymphocytes for adoptive transfer.