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1.
Article in English | MEDLINE | ID: mdl-32560418

ABSTRACT

State sanctioned violence aimed at Black individuals and communities is an issue that has pervaded American history and society since before the establishment of the United States. For Black males, anticipating and preparing for involuntary police contact, unfortunately, is an inevitable part of life. The purpose of this study is to examine the impact of reports of police abuse on mental health and perceived racial out-group perceptions and the protective role of religiosity among a nationally representative sample of Black American adolescent boys (Mage = 14.98). Linear multiple regression was used to determine the interactive effects of subjective religiosity and reported police abuse on Black American adolescent boys. Higher reports of subjective religiosity were associated with lower depressive symptomatology. Reports of police abuse were associated with lower public regard beliefs (belief that society views Black Americans less favorably). Results highlight the impact experiencing police abuse has on Black adolescent boys and we conclude with implications, areas for future research and intervention points.


Subject(s)
Black or African American , Mental Health , Police , Religion , Violence , Adolescent , Black or African American/psychology , Humans , Male , Mental Health/ethnology , United States
2.
J Anim Physiol Anim Nutr (Berl) ; 102(1): 297-307, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28276099

ABSTRACT

Currently, nutritional management is recommended when serum creatinine (Cr) exceeds 1.4 mg/dl in dogs with IRIS-Stage 2 chronic kidney disease (CKD) to slow progressive loss of kidney function, reduce clinical and biochemical consequences of CKD, and maintain adequate nutrition. It is unknown if dietary interventions benefit non-azotemic dogs at earlier stages. A prospective 12-month feeding trial was performed in client-owned dogs with IRIS-Stage 1 CKD (n = 36; 20 had persistently dilute urine with urine specific gravity (USG) <1.020 without identifiable non-renal cause; six had persistent proteinuria of renal origin with urine protein creatinine (UPC) ratio >0.5; 10 had both). Ease of transition to therapeutic renal food and effects on renal biomarkers and quality of life attributes were assessed. Dogs were transitioned over 1 week from grocery-branded foods to renal food. At 0, 3, 6, 9, and 12-months a questionnaire to assess owner's perception of their pet's acceptance of renal food and quality of life was completed. Renal biomarkers, including serum Cr, blood urea nitrogen (BUN), and symmetric dimethylarginine (SDMA), and USG and UPC ratio were measured. Of 36 dogs initially enrolled, 35 (97%) dogs were transitioned to therapeutic renal food. Dogs moderately or extremely liked the food 88% of the time, ate most or all of the food 84% of the time, and were moderately or extremely enthusiastic while eating 76% of the time. All renal biomarkers (Cr, BUN, and SDMA) were decreased (p ≤ .05) from baseline at 3-months, and remained decreased from baseline at 12-months in dogs completing the study (n = 20). Proteinuria was reduced in 12 of 16 dogs (p = .045) with proteinuria. Owners reported improvement in overall health and quality of life attributes, and hair and coat quality (all p < .01). In summary, dogs with IRIS-Stage 1 CKD readily transition to renal food. Decreasing serum biomarker concentrations and reduction in proteinuria suggest stabilized kidney function.


Subject(s)
Animal Feed , Dog Diseases/diet therapy , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/veterinary , Animals , Biomarkers , Dogs , Female , Longitudinal Studies , Male , Prospective Studies , Urinalysis/veterinary
3.
Bone Joint J ; 99-B(6): 724-731, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28566390

ABSTRACT

AIMS: The aim of this study was to evaluate the long-term clinical and radiographic outcomes of the Birmingham Interlocking Pelvic Osteotomy (BIPO). PATIENTS AND METHODS: In this prospective study, we report the mid- to long-term clinical outcomes of the first 100 consecutive patients (116 hips; 88 in women, 28 in men) undergoing BIPO, reflecting the surgeon's learning curve. Failure was defined as conversion to hip arthroplasty. The mean age at operation was 31 years (7 to 57). Three patients (three hips) were lost to follow-up. RESULTS: Survivorship was 76% at ten years and 57% at a mean of 17 years. Younger patients (< 20 years) had the best survivorship (20 hips at risk; 90% at 17 years; 95% confidence interval 65 to 97). Post-operative complications occurred after 12 operations (10.4%) over the duration of the study. Increasing patient age and hip arthritis grade were primary determinants of surgical failure. CONCLUSION: BIPO provides good to excellent survivorship in appropriately selected patients, with a relatively low rate of complications. Our results are comparable with other established methods of periacetabular osteotomy (PAO), such as the Bernese PAO, even during the surgeon's initial learning curve. Cite this article: Bone Joint J 2017;99-B:724-31.


Subject(s)
Bone Diseases, Developmental/surgery , Osteotomy/methods , Pelvic Bones/surgery , Adolescent , Adult , Arthroplasty, Replacement, Hip , Bone Diseases, Developmental/diagnostic imaging , Child , Female , Humans , Ilium/surgery , Kaplan-Meier Estimate , Male , Middle Aged , Osteotomy/adverse effects , Pelvic Bones/diagnostic imaging , Prospective Studies , Radiography , Retrospective Studies , Treatment Outcome , Young Adult
4.
J Nutr Health Aging ; 20(10): 1010-1023, 2016.
Article in English | MEDLINE | ID: mdl-27925141

ABSTRACT

OBJECTIVE: To determine the effects of feeding traditional and renal protective foods (RPF) supplemented with functional food bioactives on glomerular filtration rate (GFR), lean body percent (LB%), and selected circulating biomarker and metabolite concentrations in a geriatric dog model. DESIGN: Randomized block design and cross-sectional study. SETTING: Hill's Pet Nutrition, Inc. dog colony. PARTICIPANTS: Eighty-one geriatric dogs (mean age, 10.4; range, 7.9-14.2 years) and 30 mature-adult dogs (mean age, 5.0; range, 3.3-6.9 years). INTERVENTION: Geriatric dogs were fed one of three foods (n = 27 per group) for 6 months: a traditional RPF (control) that was energy dense and mildly protein-restricted, or control food supplemented with increasing amounts of functional food bioactives: fish oil, lipoic acid, fruits and vegetables, and higher quality protein sources [functional foods one (FF1) and two (FF2)]. Geriatric dogs were compared before and after the feeding trial with mature adult dogs. MEASUREMENTS: Renal function was assessed by GFR, LB% was determined by dual energy x-ray absorptiometry, and circulating biomarkers and metabolites were measured in blood. RESULTS: Before the feeding trial, GFR (+28.2%), LB% (+18.6%), and serum total protein (+10.0%) were higher in mature versus healthy geriatric dogs (all P<0.001). Geriatric dogs consuming all three foods increased (P<0.001) GFR over time; group averages ranged from 13.0-16.9%. Dogs fed the highest supplemented level of bioactives (FF2) had lower (P<0.001) symmetric dimethylarginine (SDMA) concentrations (-14.3%). Feeding functional foods did not alter body weight, but increased (P<0.001) serum protein concentration (+6.7%). CONCLUSION: Supplementation with functional food bioactives can temporarily reverse the age-associated decline in renal function and serum total protein.


Subject(s)
Aging/blood , Geriatric Assessment , Kidney/physiology , Absorptiometry, Photon , Aged , Animals , Arginine/analogs & derivatives , Arginine/blood , Biomarkers/blood , Body Weight , Carnitine/blood , Cross-Sectional Studies , Diet/veterinary , Dietary Proteins/administration & dosage , Dietary Proteins/blood , Dietary Supplements , Disease Models, Animal , Dogs , Female , Fish Oils/administration & dosage , Fish Oils/blood , Fruit , Glomerular Filtration Rate , Humans , Kidney/physiopathology , Male , Thioctic Acid/administration & dosage , Thioctic Acid/blood , Vegetables
5.
J Vet Intern Med ; 30(3): 794-802, 2016 May.
Article in English | MEDLINE | ID: mdl-27103204

ABSTRACT

BACKGROUND: Serum concentrations of symmetric dimethylarginine (SDMA) detected chronic kidney disease (CKD) in cats an average of 17.0 months before serum creatinine (Cr) concentrations increased above the reference interval. OBJECTIVES: To report on the utility of measuring serum SDMA concentrations in dogs for detection of CKD before diagnosis by measurement of serum Cr. ANIMALS: CKD dogs (n = 19) included those persistently azotemic for ≥3 months (n = 5), dogs that were azotemic at the time of death (n = 4), and nonazotemic dogs (n = 10). CKD dogs were compared with healthy control dogs (n = 20). METHODS: Retrospective study, whereby serum Cr concentrations were determined by enzymatic colorimetry and serum SDMA concentrations were determined by liquid chromatography-mass spectrometry in dogs with necropsy confirmed CKD. RESULTS: Serum SDMA increased before serum Cr in 17 of 19 dogs (mean, 9.8 months; range, 2.2-27.0 months). Duration of elevations in serum SDMA concentrations before the dog developed azotemia (N = 1) or before the dog died (N = 1) was not determined. Serum SDMA and Cr concentrations were linearly related (r = 0.84; P < .001). Serum SDMA (r = -0.80) and serum Cr (r = -0.89) concentrations were significantly related to glomerular filtration rate (both P < .001). CONCLUSION AND CLINICAL IMPORTANCE: Using serum SDMA as a biomarker for CKD allows earlier detection of kidney dysfunction in dogs than does measurement of serum Cr. Earlier detection might be desirable for initiating renoprotective interventions that slow progression of kidney disease.


Subject(s)
Arginine/analogs & derivatives , Creatinine/blood , Dog Diseases/blood , Renal Insufficiency, Chronic/veterinary , Animals , Arginine/blood , Azotemia/blood , Azotemia/veterinary , Biomarkers/blood , Dog Diseases/diagnosis , Dogs , Female , Glomerular Filtration Rate/veterinary , Male , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Retrospective Studies
7.
J Neuromuscul Dis ; 2(1): 93-97, 2015.
Article in English | MEDLINE | ID: mdl-28198710

ABSTRACT

Excessive daytime sleepiness (EDS) has not been investigated using objective tests in myasthenia gravis (MG). We investigated whether objective measurements of somnolence better detected abnormalities compared with sleepiness questionnaires in MG, and determine if MG patients have EDS. Eight patients with mild-to-moderate MG were recruited. Patients completed maintenance of wakefulness, overnight polysomnography, multiple sleep latency tests, Epworth Sleepiness Scale, and fatigue questionnaires. Seven patients demonstrated EDS on objective testing, while Epworth scores were abnormal in two, and the measures showed poor correlation. Our findings highlight that the ESS may be inadequate to diagnose EDS and lead to under-reporting of daytime somnolence in patients with MG.

8.
Vet J ; 202(3): 588-96, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25458884

ABSTRACT

The purpose of this study was to determine whether feeding cats reduced protein and phosphorus foods with added fish oil, L-carnitine, and medium-chain triglycerides (MCT) altered serum biomarkers of renal function. Thirty-two healthy cats, mean age 14.0 (8.3-19.6) years, were fed control food or one of two experimental foods for 6 months. All foods had similar concentrations of moisture, protein, and fat (approximately 8.0%, 26.5%, and 20.0%, respectively). Both experimental foods contained added fish oil (1.5%) and L-carnitine (500 mg/kg). Experimental-food 2 also contained increased MCT (10.5% from coconut oil), 1.5% added corn oil, and reduced animal fat. Glomerular filtration rate (GFR), serum biochemistries, renal function biomarkers including serum creatinine (sCr) and symmetrical dimethylarginine (SDMA), and plasma metabolomic profiles were measured at baseline, and at 1.5, 3, and 6 months. Body composition was determined by dual-energy X-ray absorptiometry. Although both experimental foods altered plasma fatty acids, carnitine and related metabolites, and lysophospholipid concentrations, there were no changes in renal function biomarkers. There was, however, a benefit in using SDMA versus sCr to assess renal function in older cats with less total lean mass. Compared with cats <12 years, those >15 years had lower total lean mass (P < 0.01), lower GFR (P = 0.04), and lower sCr concentrations (P < 0.01). However, SDMA concentrations (P < 0.01) were higher in older cats. This study shows that in cats, serum SDMA concentration is more highly correlated with GFR than sCr concentration, and, unlike sCr, which declines with age because of muscle wasting, SDMA increases as GFR declines with age.


Subject(s)
Arginine/analogs & derivatives , Body Composition/drug effects , Creatinine/blood , Diet/veterinary , Fatty Acids, Omega-3/metabolism , Kidney Function Tests/veterinary , Age Factors , Animal Feed/analysis , Animals , Arginine/blood , Biomarkers/blood , Blood Chemical Analysis/veterinary , Blood Proteins/metabolism , Body Mass Index , Cats , Cross-Sectional Studies , Diet, Protein-Restricted/veterinary , Fatty Acids, Omega-3/blood , Female , Glomerular Filtration Rate/veterinary , Male
9.
J Vet Intern Med ; 28(6): 1676-83, 2014.
Article in English | MEDLINE | ID: mdl-25231385

ABSTRACT

BACKGROUND: Symmetric dimethylarginine (SDMA) has been shown to be an accurate and precise biomarker for calculating estimated glomerular filtration rate (GFR) in humans, as well as a more sensitive biomarker than serum creatinine concentration (sCr) for assessing renal dysfunction. OBJECTIVES: The purpose of this retrospective study was to report on the utility of measuring serum SDMA concentrations in cats for detection of chronic kidney disease (CKD) before diagnosis by conventional measurement of sCr. ANIMALS: Chronic kidney disease cats (n = 21) included those persistently azotemic for ≥3 months (n = 15), nonazotemic cats with GFR >30% decreased from median GFR of normal cats (n = 4), and nonazotemic cats with calcium oxalate kidney stones (n = 2). Healthy geriatric cats (n = 21) were selected from the same colony. METHODS: Symmetric dimethylarginine concentrations (liquid chromatography-mass spectroscopy) and sCr (enzymatic colorimetry) were determined retrospectively from historical data or banked serum samples in azotemic cats or at the time GFR (iohexol clearance) was measured in nonazotemic cats. RESULTS: Serum SDMA (r = -0.79) and sCr (r = -0.77) concentrations were significantly correlated to GFR (both P < .0001). Symmetric dimethylarginine became increased before sCr in 17/21 cats (mean, 17.0 months; range, 1.5-48 months). Serum SDMA had higher sensitivity (100%) compared with sCr (17%), but lower specificity (91% versus 100%) and positive predictive value (86% versus 100%). CONCLUSION AND CLINICAL IMPORTANCE: Using serum SDMA as a biomarker for CKD allows earlier detection of CKD in cats compared with sCr, which may be desirable for initiating renoprotective interventions that slow progression of CKD.


Subject(s)
Arginine/analogs & derivatives , Cat Diseases/blood , Creatinine/blood , Renal Insufficiency, Chronic/veterinary , Animals , Arginine/blood , Biomarkers/blood , Cat Diseases/diagnosis , Cats , Female , Glomerular Filtration Rate/veterinary , Male , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Retrospective Studies
10.
Aliment Pharmacol Ther ; 38(3): 284-93, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23750909

ABSTRACT

BACKGROUND: The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry. AIM: To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features. METHODS: Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests. RESULTS: Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious. CONCLUSIONS: This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC.


Subject(s)
Colitis, Ulcerative/drug therapy , Gastrointestinal Agents/therapeutic use , Phosphorothioate Oligonucleotides/therapeutic use , Administration, Topical , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Enema , Female , Gastrointestinal Agents/administration & dosage , Humans , Intercellular Adhesion Molecule-1/drug effects , Male , Mesalamine/therapeutic use , Middle Aged , Phosphorothioate Oligonucleotides/administration & dosage , Treatment Outcome
11.
Hand Surg ; 17(1): 143-4, 2012.
Article in English | MEDLINE | ID: mdl-22351554

ABSTRACT

Four-corner fusion is an accepted surgical treatment for established SLAC and SNAC wrist. We describe a technique of bone grafting to be used in conjunction with any of the standard fusion techniques. A step by step, illustrated approach allows the easy placement of an autograft which is in contact with all surfaces of the bones involved in the fusion.


Subject(s)
Arthrodesis/methods , Bone Transplantation/methods , Carpal Bones/surgery , Wrist Joint/surgery , Humans
12.
Hand Surg ; 16(3): 301-5, 2011.
Article in English | MEDLINE | ID: mdl-22072464

ABSTRACT

Trapezio-metacarpal joint arthritis is common, affecting 7% of men and 15% of women. Numerous surgical techniques are described for this condition but it is not clear which is best. Eighty-six silicone trapezium replacements were assessed at an average of 46 months (six to 156 months) postoperatively for patient satisfaction, pain, key and power grip strength, range of motion, complications and disability with DASH score. Patient satisfaction was 92%. There was excellent pain reduction from 4.2 to 0.6 on a scale of 0 to 5. Strength was 72% and 84% of age-sex-matched normal data for key and power grips, respectively. The complication rate was low, with two cases of persistent pain. One resolved spontaneously, the other resolved following revision of the silicone implant. The average DASH score was 30. Silicone trapezium replacement is an effective operation that offers the patient good pain relief, strength and good function with few complications.


Subject(s)
Arthroplasty, Replacement/methods , Joint Prosthesis , Metacarpophalangeal Joint/surgery , Osteoarthritis/surgery , Patient Satisfaction , Trapezium Bone/surgery , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Metacarpophalangeal Joint/diagnostic imaging , Metacarpophalangeal Joint/physiopathology , Middle Aged , Osteoarthritis/diagnostic imaging , Osteoarthritis/physiopathology , Pain Measurement , Radiography , Range of Motion, Articular , Retrospective Studies , Time Factors , Trapezium Bone/diagnostic imaging , Treatment Outcome
13.
Tissue Antigens ; 77(1): 23-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20887385

ABSTRACT

Previous linkage studies have identified a region at 1p36 as the susceptibility locus (IBD7) of inflammatory bowel disease (IBD). The objective of this study was to investigate whether polymorphisms of caspase-9 (CASP9) gene and RUNX3 are associated with IBD susceptibility and clinical phenotypes. We studied 555 Crohn's disease (CD) and 651 ulcerative colitis (UC) patients recruited from a single UK center. A total of 964 healthy Caucasian subjects were recruited as controls from general practitioner well person clinics in Oxfordshire. Fourteen single nucleotide polymorphisms (SNPs) of CASP9 and 11 SNPs of RUNX3 were genotyped using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (homogenous MassEXTEND, hME, Sequenom™, Sequenom Inc., San Diego, CA). Linkage disequilibrium (LD) and haplotype association analysis were performed using 2ld and phase v2.0 software. No association of individual SNPs of CASP9 or RUNX3 with UC or CD was identified. The rs1052571 of CASP9 was associated with severe UC [P = 0.0034, odds ratio (OR) = 1.957, 95% confidence interval (CI) = 1.240-3.088]. Significant haplotype associations between CASP9 and IBD were identified, while no association of RUNX3 haplotypes with either UC or CD was found. Our findings suggested that CASP9 gene might be another IBD susceptibility gene.


Subject(s)
Caspase 9/genetics , Core Binding Factor Alpha 3 Subunit/genetics , Genetic Predisposition to Disease , Inflammatory Bowel Diseases/genetics , Adult , Female , Humans , Male , United Kingdom , White People/genetics
14.
J Vet Intern Med ; 24(5): 1020-6, 2010.
Article in English | MEDLINE | ID: mdl-20707845

ABSTRACT

BACKGROUND: Food supplemented with fish oil improves clinical signs and weight bearing in dogs with osteoarthritis (OA). OBJECTIVE: Determine whether increasing the amount of fish oil in food provides additional symptomatic improvements in OA. ANIMALS: One hundred and seventy-seven client-owned dogs with stable chronic OA of the hip or stifle. METHODS: Prospective, randomized clinical trial using pet dogs. Dogs were randomly assigned to receive the baseline therapeutic food (0.8% eicosopentanoic acid [EPA] + docosahexaenoic acid [DHA]) or experimental foods containing approximately 2- and 3-fold higher EPA+DHA concentrations. Both veterinarians and owners were blinded as to which food the dog received. On days 0, 21, 45, and 90, serum fatty acid concentrations were measured and veterinarians assessed the severity of 5 clinical signs of OA. At the end of the study (day 90), veterinarians scored overall arthritic condition and progression of arthritis based on their clinical signs and an owner interview. RESULTS: Serum concentrations of EPA and DHA rose in parallel with food concentrations. For 2 of 5 clinical signs (lameness and weight bearing) and for overall arthritic condition and progression of arthritis, there was a significant improvement between the baseline and 3X EPA+DHA foods (P=.04, .03, .001, .0008, respectively) but not between the baseline and the 2X EPA+DHA foods. CONCLUSIONS AND CLINICAL IMPORTANCE: Increasing the amount of fish oil beyond that in the baseline food results in dose-dependent increases in serum EPA and DHA concentrations and modest improvements in the clinical signs of OA in pet dogs.


Subject(s)
Dog Diseases/drug therapy , Fish Oils/administration & dosage , Fish Oils/therapeutic use , Osteoarthritis/veterinary , Animal Feed/analysis , Animals , Diet/veterinary , Dogs , Dose-Response Relationship, Drug , Fatty Acids/blood , Female , Lameness, Animal/drug therapy , Male , Osteoarthritis/drug therapy
15.
Tissue Antigens ; 76(1): 48-56, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20403135

ABSTRACT

The first Crohn's disease (CD) susceptibility gene identified was CARD15, which is a member of the emerging NOD-like receptor (NLR) family. These function as intracellular cystosolic pattern recognition receptors (PRRs) and play a central role in the innate immune response. We studied other members of the NLR family using a gene-wide haplotype tagging approach in a well-characterised collection of 547 CD patients and 465 controls. Four single nucleotide polymorphisms (SNPs) in NLRP3 had P values < 0.05 and are in high linkage disequilibrium (LD) with each other (r(2) > 0.90 for all four SNPs). rs4925648 and rs10925019 were the most strongly associated with CD susceptibility (P = 0.001, odds ratio (OR) 1.62, 95% CI 1.2-2.18; and P = 6.5 x 10(-4), OR 1.65, 95% CI 1.23-2.19, respectively). rs1363758 located in NLRP11 was associated with CD susceptibility [P = 0.002 (1.64, 1.19-2.25)], which was weakly confirmed in an independent case-cohort collection on joint analysis [P = 0.05, (1.28, 1-1.64)]. On sub-phenotype analysis, an interesting association between NLRP1 and skin extra-intestinal manifestations and colonic, inflammatory CD was identified. None of these results was replicated in the Wellcome Trust Case Control Consortium study and therefore need replication in a further large cohort.


Subject(s)
Crohn Disease/genetics , Nod Signaling Adaptor Proteins/genetics , Adolescent , Adult , Female , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Humans , Male , Phenotype , Polymorphism, Single Nucleotide
16.
J Food Prot ; 72(11): 2368-74, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19903402

ABSTRACT

Four real-time PCR assays that can be used with U.S.- and European Union-rendered materials to detect three ruminant species (bovine, caprine, and ovine) and a select set of avians (chicken, goose, and turkey) were developed. This method was evaluated against stringent acceptance criteria previously developed by the U.S. Food and Drug Administration, Center for Veterinary Medicine's Office of Research. Acceptance criteria for determining success used a statistical approach requiring a 90% probability of achieving the correct response, within a 95% confidence interval. A minimum detection level of 0.1% meat and bone meal (MBM) was required, consistent with the sensitivity of the validated PCR-based method currently used by the U.S. Food and Drug Administration as an aid in enforcement of the Agency's feed ban. PCR primer specificity was determined by using a panel of DNA samples derived from 16 different animal species. The method is able to detect 0.1% rendered material in complete feed in less than 1.5 h of total assay time, a significant improvement over the current method, which requires 7 to 8 h for completion. The real-time assay for the detection of animal material passed stringent acceptance criteria for sensitivity, selectivity, and specificity. The method also passed ruggedness, real-time platform, and second analyst trials. Two external laboratories participating in a peer-verification trial demonstrated 100% specificity in identifying bovine MBM, ovine MBM, or caprine meat meal, while exhibiting a 0.6% rate of false positives. These results demonstrated that this method was capable of being used by other laboratories.


Subject(s)
Animal Feed/analysis , Laboratories/standards , Minerals/analysis , Polymerase Chain Reaction/standards , Proteins/analysis , Animals , Biological Products/analysis , Cattle , Consumer Product Safety , Encephalopathy, Bovine Spongiform/prevention & control , Encephalopathy, Bovine Spongiform/transmission , Food Contamination/analysis , Goats , Humans , Polymerase Chain Reaction/methods , Reproducibility of Results , Sensitivity and Specificity , Sheep , Species Specificity
17.
Childs Nerv Syst ; 25(11): 1447-53, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19672605

ABSTRACT

OBJECTIVE: The objective of the study was to measure upper limb motor function in young adults with spina bifida meningomyelocele (SBM) and typically developing age peers. METHOD: Participants were 26 young adults with SBM, with a Verbal or Performance IQ score of at least 70 on the Wechsler scales, and 27 age- and gender-matched controls. Four upper limb motor function tasks were performed under four different visual and cognitive challenge conditions. Motor independence was assessed by questionnaire. RESULTS: Fewer SBM than control participants obtained perfect posture and rebound scores. The SBM group performed less accurately and was more disrupted by cognitive challenge than controls on limb dysmetria tasks. The SBM group was slower than controls on the diadochokinesis task. Adaptive motor independence was related to one upper limb motor task, arm posture, and upper rather than lower spinal lesions were associated with less motor independence. CONCLUSIONS: Young adults with SBM have significant limitations in upper limb function and are more disrupted by some challenges while performing upper limb motor tasks. Within the group of young adults with SBM, upper spinal lesions compromise motor independence more than lower spinal lesions.


Subject(s)
Arm , Hydrocephalus/complications , Meningomyelocele/complications , Motor Activity , Spinal Dysraphism/complications , Adolescent , Adult , Case-Control Studies , Cerebellar Ataxia , Female , Humans , Hydrocephalus/pathology , Male , Meningomyelocele/pathology , Neuropsychological Tests , Posture , Retrospective Studies , Spinal Cord/pathology , Spinal Dysraphism/pathology , Surveys and Questionnaires , Young Adult
18.
Tissue Antigens ; 74(4): 322-9, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19659809

ABSTRACT

Linkage in families and association in population case-control investigations have clearly shown that genes within the major histocompatibility complex region on chromosome 6p are relevant to the susceptibility and pathogenesis of ulcerative colitis (UC) and Crohn's disease. However, identifying the causative variants by fine mapping has not been conclusive. In this study using 58 single nucleotide polymorphisms (SNPs) with 616 UC cases, there was significant association with SNP rs2294881 of the (butyrophilin-like 2) BTNL2 gene with odds ratio (OR) = 2.80, confidence interval (CI) = 1.62-4.84 and P = 5.69 x 10(-4) (P(Bonferroni) = 3.3 x 10(-2)) and replication of SNP rs9268480. The missense SNP rs2076523 (K196E) showed novel association with a subset of UC cases with colectomy (n = 126), OR = 0.25, CI = 0.11-0.58 and P = 4.42 x 10(-4) (P(Bonferroni) = 2.56 x 10(-2)). These three associated variants within the BTNL2 gene were neither in linkage disequilibrium with each other nor correlated with the SNPs tagging the human leukocyte antigen (HLA)-DRB1*1502 and HLA-DRB1*0301 alleles.


Subject(s)
Colitis, Ulcerative/genetics , Haplotypes/genetics , Membrane Glycoproteins/genetics , Polymorphism, Single Nucleotide/genetics , Butyrophilins , Case-Control Studies , Cohort Studies , Colectomy , Colitis, Ulcerative/pathology , Colitis, Ulcerative/surgery , Female , Genome-Wide Association Study , Genotype , HLA-DR Antigens/classification , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Humans , Linkage Disequilibrium , Male , Polymerase Chain Reaction
19.
Mucosal Immunol ; 2(3): 220-31, 2009 May.
Article in English | MEDLINE | ID: mdl-19262505

ABSTRACT

The MEP1A gene, located on human chromosome 6p (mouse chromosome 17) in a susceptibility region for inflammatory bowel disease (IBD), encodes the alpha-subunit of metalloproteinase meprin A, which is expressed in the intestinal epithelium. This study shows a genetic association of MEP1A with IBD in a cohort of ulcerative colitis (UC) patients. There were four single-nucleotide polymorphisms in the coding region (P=0.0012-0.04), and one in the 3'-untranslated region (P=2 x 10(-7)) that displayed associations with UC. Moreover, meprin-alpha mRNA was decreased in inflamed mucosa of IBD patients. Meprin-alpha knockout mice exhibited a more severe intestinal injury and inflammation than their wild-type counterparts following oral administration of dextran sulfate sodium. Collectively, the data implicate MEP1A as a UC susceptibility gene and indicate that decreased meprin-alpha expression is associated with intestinal inflammation in IBD patients and in a mouse experimental model of IBD.


Subject(s)
Genetic Predisposition to Disease , Inflammatory Bowel Diseases/genetics , Metalloendopeptidases/genetics , Alleles , Animals , Colitis, Ulcerative/genetics , Colitis, Ulcerative/metabolism , Colitis, Ulcerative/pathology , Dextran Sulfate , Humans , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/metabolism , Inflammatory Bowel Diseases/pathology , Metalloendopeptidases/metabolism , Mice , Mice, Knockout , Polymorphism, Single Nucleotide , RNA, Messenger/metabolism
20.
Inflamm Bowel Dis ; 15(6): 823-8, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19145641

ABSTRACT

BACKGROUND: To determine the long-term outcome of patients admitted with acute severe colitis (ASC) who avoided colectomy on the index admission, a retrospective cohort study was performed. METHODS: Patients admitted for intensive treatment of ASC in 1992-1993 previously described for a predictive index of short-term outcome in severe ulcerative colitis (UC) were followed for a median 122 months (range 3-144). Complete responders (CR) to intensive therapy had <3 nonbloody stools/day on day 7 of the index admission; incomplete responders (IR) were all others who avoided colectomy on that admission. Main outcome measures were colectomy-free survival, time to colectomy, and duration of steroid-free remission. RESULTS: In all, 6/19 CR (32%) came to colectomy compared to 10/13 IR (P = 0.016; relative risk 3.33, 95% confidence interval [CI] 1.12-9.9). The median +/- interquartile range time to colectomy was 28 +/- 47 months (range 6-99) for CR who came to colectomy versus 7.5 +/- 32 (3-72) months for IR (P = 0.118). Among the IR, 7/13 came to colectomy within 12 months, and all within 6 years from the index admission. The longest period of steroid-free remission was 42 +/- 48 (0-120) months for CR, but 9 +/- 20 (1-35) months for IR (P = 0.011). CONCLUSIONS: One week after admission with ASC in the prebiologic era, IRs had a 50% chance of colectomy within a year and 70% within 5 years, despite cyclosporin and azathioprine where appropriate. The maximum duration of remission in CRs was almost 5 times longer than IRs. It is unknown whether biologics change the long-term outcome.


Subject(s)
Colectomy/statistics & numerical data , Colitis, Ulcerative , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Adult , Azathioprine/therapeutic use , Cohort Studies , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/surgery , Cost of Illness , Cyclosporine/therapeutic use , England/epidemiology , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Middle Aged , Predictive Value of Tests , Remission Induction , Retrospective Studies , Risk Factors , Severity of Illness Index , Steroids/therapeutic use , Time Factors
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