Racial and Ethnic Differences in Treatment and Outcomes of Severe Aortic Stenosis: A Review.

Aortic stenosis (AS) is among the most common valvular heart diseases encountered in the United States. In this review the authors examine differences between racial and ethnic groups in the epidemiology and management of severe AS, explore potential explanations for these findings, and discuss the implications for improving the delivery of care to racially and ethnically diverse populations. Underrepresented racial and ethnic groups experience a paradoxically lower prevalence or incidence of AS relative to white subjects, despite having a higher prevalence of traditional risk factors. Historically, UREGs with severe AS have had lower rates of both surgical and transcatheter aortic valve replacement and experienced more post-surgical complications, including, bleeding, worsening heart failure, and rehospitalization. Last, UREGs with severe AS have an increased risk for morbidity and mortality relative to white patients. To date much of the research on AS has examined black-white differences, so there is a need to understand how other racial and ethnic groups with severe AS are diagnosed and treated, with examination of their resulting outcomes. Overall, racial and ethnic disparities in health care access and care delivery are a public health concern given the changing demographics of the U.S. population. These differences in AS management and outcomes highlight the need for additional research into contributing factors and appropriate interventions to address the lower rates of aortic valve replacement and higher morbidity and mortality among UREGs.

Incidental splenic littoral cell angioma complicating a case of Rolon cancer: A case report.

Littoral cell angioma (LCA) is a recently described rare generally benign primary vascular neoplasm of the spleen originating from the lining cells of the splenic red pulp sinuses that is usually discovered incidentally. LCA may be associated with epithelial malignancies and may itself also have malignant potential. We report the case of a 71-year-old woman who presented with intraoperative bleeding from the spleen during sigmoidectomy for colonic adenocarcinoma. Histopathological examination of the removed spleen revealed multiple haemorrhagic lesions diagnosed as littoral cell angioma. This case has been reported due to its rarity and to highlight how its accidental detection, unique and unexpected presentation complicated a case of colonic carcinoma. Individuals diagnosed with this tumour must be carefully evaluated to exclude primary, secondary and synchronous malignancies.

Binge eating and other eating behaviors among patients on treatment for psychoses in India.

OBJECTIVE: 'Medication-induced eating disorder' is implicated as one of the reasons for the weight gain seen in psychotic patients. The aim of this study was to examine the prevalence of binge eating disorder (BED), binge spectrum and other eating behaviors in patients on treatment for non-affective psychoses in India. METHOD: An outpatient cross-sectional study of 73 participants. RESULTS: Most of the binge spectrum behaviors occurred in patients on treatment for more than 2 years and on concomitant antidepressant medication. Patients admitted to obesogenic eating behaviour more readily than actual calorie intake. BED was absent in our sample. CONCLUSION: While binge spectrum eating behaviors were noted in many patients, the absence of BED was striking and could be due to cultural factors. Binge spectrum eating behaviors could be treatment emergent or linked particularly to the improvement from psychoses and post psychotic depression.

Differential effects of MPEP and diazepam in tests of conditioned emotional response and Pavlovian-to-instrumental transfer suggests 'anxiolytic' effects are mediated by different mechanisms.

BACKGROUND: The selective mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is reported to be anxiolytic in several animal models of anxiety, including the conditioned emotional response (CER) paradigm. Suppression of responding during conditioned stimulus (CS) presentation in CER may reflect behavioural competition between lever pressing and adopting a shock-avoidance posture, or it may alternatively reflect altered value of the food reward following its association with a footshock, thus reducing its ability to motivate responding. If this is the case, then drugs that reduce the CER may interfere with the mechanism by which CSs are able to motivate responding, rather than by reducing anxiety. The standard test of the ability of Pavlovian cues to motivate responding is the Pavlovian-to-instrumental transfer (PIT) paradigm and it has recently been suggested that CER may be 'negative PIT'. MATERIALS AND METHODS: We compared the effect of MPEP (0, 3, 10 and 30 mg/kg) and diazepam (0, 1, 3 and 10 mg/kg) in CER and PIT. RESULTS: Both MPEP and diazepam significantly reduced conditioned suppression in the CER paradigm. MPEP, but not diazepam, significantly reduced PIT. CONCLUSION: The findings support the hypothesis that MPEP may reduce expression of anxiety in the CER paradigm by interfering with the way in which emotionally salient cues are able to affect behaviour, but do not support such an analysis of the effect of diazepam. Diazepam and MPEP may therefore achieve their effects in CER by influencing different psychological processes.

Inpatient management of psoriasis: a multicentre service review to establish national admission standards.

BACKGROUND: Some patients with psoriasis may require hospital admission to stabilize their condition, although the role of inpatient management is changing given recent advances in therapeutic options, emphasis on community-based care for chronic conditions and limited healthcare resources. There is a need for evidence-based national standards for inpatient management of psoriasis taking account of factors that predict length of stay. OBJECTIVES: To determine which factors predict length of stay for patients with psoriasis requiring inpatient hospital care with a view to setting evidence-based standards for inpatient psoriasis management. METHODS: A multicentre service review was conducted on all psoriasis admissions over a 9-month period in four dermatology centres in the U.K. We collected data on admission, at discharge and, where possible, at 3 months following discharge. Psoriasis severity was assessed using four validated scoring systems, including Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index. We also recorded length of stay and treatment details. RESULTS: Length of stay varied widely between the four centres, but was similar in the two centres which received a high proportion of tertiary referrals for severe psoriasis (mean 19.7 days, range 1-78, analysis of variance P=0.002). Disease severity, measured by PASI, on admission (mean 15.7, interquartile range 8.3-20.8) was significantly higher in the tertiary centres (P<0.0001). However, there was no significant difference in PASI between centres on discharge. The admission PASI was significantly associated with length of stay (r=0.2, P=0.02). There was no significant correlation between other measures of disease severity and length of stay. CONCLUSIONS: Disease severity on admission for patients with psoriasis is greater in tertiary referral centres for psoriasis and is directly associated with length of stay. Length of stay should be used in conjunction with clinical measures such as PASI improvement to set national standards for quality in secondary care.

Neither antioxidants nor COX-2 inhibition protect against esophageal inflammation in an experimental model of severe reflux.

BACKGROUND: Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities. MATERIALS AND METHODS: Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring. RESULTS: Esophagitis was present in all 63 animals completing the study and was severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups. CONCLUSIONS: In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.

Neither antioxidants nor COX-2 inhibition protect against esophageal inflammation in an experimental model of severe reflux.

BACKGROUND: Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities. MATERIALS AND METHODS: Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring. RESULTS: Esophagitis was present in all 63 animals completing the study and severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups. CONCLUSIONS: In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.

Comparative assessment of two indices of drug induced permeability changes in the perfused rat intestine.

In the present study, two indices of acute intestinal permeability changes were investigated as measurements of drug induced intestinal damage. The first method was based on 14C-polyethylene glycol (PEG) 4000 permeability assessment and the second was based on histological evaluation of the intestine. The test compounds were ibuprofen, ketoprofen and naproxen and the alanine, glycine and phenylalanine amide derivatives of ibuprofen. Perfusion studies were carried out using a rat model. Post-perfusion, the gut was fixed and tissue changes were assessed and scored. Ibuprofen, ketoprofen and naproxen altered the barrier properties of the intestine to PEG 4000 with significantly higher scores (p<0.05) for gastrointestinal toxicity relative to blank buffer. For ketoprofen, PEG 4000 permeability and intestinal damage scores increased with increasing ketoprofen concentration. Ibuprofen amide derivatives did not induce significant histological damage or PEG 4000 permeability when compared with ibuprofen. A correlation coefficient of 0.91 is obtained when intestinal damage scores are plotted against PEG 4000 permeability for all compounds. Both indices are proposed as rapid and useful measures of drug induced acute intestinal damage.

Passive immunisation of hamsters against Clostridium difficile infection using antibodies to surface layer proteins.

Clostridium difficile is a major cause of antibiotic-associated diarrhoea and the primary cause of pseudomembraneous colitis in hospitalised patients. We assessed the protective effect of anti-surface layer protein (SLP) antibodies on C. difficile infection in a lethal hamster challenge model. Post-challenge survival was significantly prolonged in the anti-SLP treated group compared with control groups (P=0.0281 and P=0.0283). The potential mechanism of action of the antiserum was shown to be through enhancement of C. difficile phagocytosis. This report indicates that anti-SLP antibodies can modulate the course of C. difficile infection and may therefore merit closer investigation for use as constituents of multi-component vaccines against C. difficile associated diarrhoea.

Detection of a tyrosine phosphatase LAR on intestinal epithelial cells and intraepithelial lymphocytes in the human duodenum.

Studies of tyrosine phosphorylation in the human duodenum have indicated that proliferating cells in the middle portion of the duodenal crypt were devoid of this feature, suggesting that tyrosine kinase activation is not a dominant factor in crypt cell proliferation, and that consequently tyrosine phosphatase activity may be a more critical factor in crypt cell development. We investigated the expression of the leukocyte common antigen-related receptor (LAR) family of tyrosine phosphatases. A flow cytometry system was used to examine cells from the surface, mid-portion, and lower part of the crypt. Individual cell populations were immunostained with anti-LAR antibodies using phycoerythrin-conjugated anti-CD3 to discriminate between epithelial cells (CD3-) and intraepithelial lymphocytes (CD3+). Epithelial cells expressed LAR throughout the crypt. Expression of LAR was maximal in the mid-portion of the crypt with lower expression at the top of the villi. Intraepithelial lymphocytes expressed low levels of LAR at the tips of the villi with stronger expression extending towards the base of the crypt. These findings were confirmed by immunohistochemistry on paraffin-fixed sections. Of note, peripheral blood lymphocytes expressed less LAR than IEL. These observations suggest the possibility that tyrosine phosphatase LAR may be of importance in the regulation of crypt cell proliferation. Moreover, as the extracellular domain of LAR has homology with adhesion molecules, the finding of this molecule on IEL could suggest a possible functional role in homing of this unique lymphocyte.

Distinct MHC class I and II alleles are associated with hepatitis C viral clearance, originating from a single source.

The role of cytotoxic T lymphocyte responses, restricted by human leukocyte antigen (HLA) class I alleles, is recognized as highly significant in the successful clearance of hepatitis C virus (HCV). The frequency of class I alleles in females inoculated with HCV genotype 1b from a single source was examined for an association with outcome. Class I typing was performed using polymerase chain reaction sequence-specific primers in 227 female subjects: 141 had chronic infection and 86 had viral clearance. Statistical analysis included chi(2) testing and multiple logistic regression analysis. A*03, B*27, and Cw*01 occurred more frequently in those with viral clearance (39.5%, 14%, and 9.3%, respectively) compared with those with chronic infection (19.1%, 2.1%, and 1.4%, respectively; P < or = .005). B*08 occurred more often in those with chronic infection compared with viral clearance (39.7% vs. 19.8%; P =.002). In combination with previously reported class II allele associations, over 75% that successfully eliminate HCV carry either A*03, DRB1*0101, or *0401, compared with only 37% of those with chronic infection (P <.0001). The haplotypes A*03-B*07-DRB1*15-DQB1*0602 and A*02-B*27-Cw*01-DRB1*0101-DQB1*0501 are associated with viral clearance (P =.004 and.01, respectively). By multiple logistic regression analysis, the alleles A*03, B*27, DRB1*0101, *0401, and *15 are associated with viral clearance, and B*27 has the strongest association (odds ratio [OR] 7.99). The haplotype A*01-B*08-Cw*07-DRB1*03011-DQB1*0201 is associated with chronic infection (P =.002), being independent for DQB1*0201 (OR 0.27). In conclusion, certain class I alleles are associated with outcome in this homogeneous cohort. More significantly, either HLA-A*03, -DRB1*0101, or -*0401 are carried by an overwhelming majority of those subjects who successfully clear HCV.

Adverse effects with PUVA and UVB phototherapy.

PUVA and UVB phototherapy are very effective and popular treatments for a variety of dermatological problems. This article gives an overview of the possible acute and chronic adverse effects of these therapies.

Barriers to breast cancer screening: an integrative review.

Breast cancer has been increasing at an alarming rate and is considered to be of epidemic proportions in the United States, with current estimates indicating that 1 in 8 women will develop breast cancer during their lifetimes, according to Breast Cancer Facts and Figures, 1997, by the American Cancer Society [ACS]. In spite of the advances in technology to improve early diagnosis and an increased emphasis on education to promote awareness of early detection, 46,000 women die annually. A significant number of these losses could be prevented through risk reduction measures, yet many women do not practice breast self-exam (BSE) or receive adequate clinical screening. The purpose of this integrative review is to provide an analysis of the barriers to breast cancer screening with recommendations for future research. The studies will be categorized using the three modalities for breast cancer screening, mammography, clinical breast exam (CBE) and BSE. Demographic variables that impede breast cancer screening will be integrated into each section. The evidence is clear that in spite of breast cancer screening guidelines, increased awareness and access to mammography screening, women in the United States are not being screened adequately. Recommendations for future research will be included.

Dual actions of isthmic input to tectal neurons in a reptile, Gekko gekko.

We analyzed postsynaptic potentials and dye-labeled morphology of tectal neurons responding to electrical stimulation of the optic nerve and of the nucleus isthmi in a reptile, Gekko gekko, in order to compare with previously reported interactions between the optic tectum and the nucleus isthmi in amphibians and birds. The results indicate that isthmic stimulation exerts inhibitory and excitatory actions on tectal cells, similar to dual isthmotectal actions in amphibians. It appears that dual actions of the isthmotectal pathway in amphibians and reptiles are shared by two subdivisions of the nucleus isthmi in birds. The morphology of tectal cells responding to isthmic stimulation is generally similar to that of tectoisthmic projecting neurons, but they differ particularly in that some tectoisthmic cells bear numerous varicosities whereas cells receiving isthmic afferents do not. Thus, it is likely that at least some tectoisthmic cells may not be in the population of tectal cells that can be affected by isthmic stimulation. Forty-four percent of injections resulted in dye-coupled labeling, suggesting extensive electrical connections between tectal cells in reptiles.