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1.
J Dairy Sci ; 102(4): 3204-3215, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30799107

ABSTRACT

Female fertility has a major role in dairy production and affects the profitability of dairy cattle. The genetic progress obtained by traditional selection can be slow because of the low heritability of classical fertility traits. Endocrine fertility traits based on progesterone concentration in milk have higher heritability and more directly reflect the cow's own reproductive physiology. The aim of our study was to identify genomic regions for 7 endocrine fertility traits in dairy cows by performing a genome-wide association study with 54,000 SNP. The next step was to fine-map targeted genomic regions with significant SNP using imputed sequences to identify potential candidate genes associated with the normal and atypical progesterone profiles. The association between a SNP and a phenotype was assessed by a single SNP analysis, using a linear mixed model that included a random polygenic effect. Phenotypes and genotypes were available for 1,126 primiparous and multiparous Holstein-Friesian cows from research herds in Ireland, the Netherlands, Sweden, and the United Kingdom. In total, 44 significant SNP associated with 7 endocrine fertility traits were identified on Bos taurus autosome (BTA) 1-4, 6, 8-9, 11-12, 14-17, 19, 21-24, and 29. Three chromosomes, BTA8, BTA17, and BTA23, were imputed from 54,000 SNP genotypes to the whole-genome sequence level with Beagle version 4.1. The fine-mapping identified several significant associations with delayed cyclicity, cessation of cyclicity, commencement of luteal activity, and inter-ovulatory interval. These associations may contribute to an index of markers for genetic improvement of fertility. Several potential candidate genes reported to affect reproduction were also identified in the targeted genomic regions. However, due to high linkage disequilibrium, it was not possible to identify putative causal genes or polymorphisms for any of the regions.


Subject(s)
Cattle/genetics , Fertility , Genome-Wide Association Study/veterinary , Milk/chemistry , Progesterone/analysis , Animals , Cattle/blood , Chromosomes , Corpus Luteum/physiology , Dairying , Female , Genome , Genotype , Lactation , Linear Models , Linkage Disequilibrium , Phenotype , Reproduction
2.
Inj Prev ; 22(2): 153-60, 2016 Apr.
Article in English | MEDLINE | ID: mdl-25392367

ABSTRACT

BACKGROUND: Programme evaluations conducted alongside randomised controlled trials (RCTs) have potential to enhance understanding of trial outcomes. This paper describes a multi-level programme evaluation to be conducted alongside an RCT of a falls prevention programme (RESPOND). OBJECTIVES: (1) To conduct a process evaluation in order to identify the degree of implementation fidelity and associated barriers and facilitators. (2) To evaluate the primary intended impact of the programme: participation in fall prevention strategies and the factors influencing participation. (3) To identify the factors influencing RESPOND RCT outcomes: falls, fall injuries and emergency department (ED) re-presentations. METHODS/DESIGN: 528 community-dwelling adults aged 60-90 years presenting to two EDs with a fall will be recruited and randomly assigned to the intervention or standard care group. All RESPOND participants and RESPOND clinicians will be included in the evaluation. A mixed methods design will be used and a programme logic model will frame the evaluation. Data will be sourced from interviews, focus groups, questionnaires, clinician case notes, recruitment records, participant-completed calendars, hospital administrative datasets and audio-recordings of intervention contacts. Quantitative data will be analysed via descriptive and inferential statistics and qualitative data will be interpreted using thematic analysis. DISCUSSION: The RESPOND programme evaluation will provide information about contextual and influencing factors related to the RESPOND RCT outcomes. The results will assist researchers, clinicians and policy makers regarding decisions about future falls prevention interventions. Insights gained may be applicable to a range of chronic conditions where similar preventive intervention approaches are indicated. TRIAL REGISTRATION NUMBER: This programme evaluation is linked to the RESPOND RCT which is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).


Subject(s)
Accidental Falls/prevention & control , Community Health Services/organization & administration , Emergency Service, Hospital , Preventive Health Services , Wounds and Injuries/prevention & control , Accidental Falls/statistics & numerical data , Aged , Aged, 80 and over , Australia/epidemiology , Clinical Protocols , Emergency Service, Hospital/statistics & numerical data , Environment Design , Female , Hospitalization , Humans , Male , Preventive Health Services/organization & administration , Program Evaluation , Risk Assessment , Surveys and Questionnaires , Wounds and Injuries/epidemiology
3.
Inj Prev ; 21(1): e1, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24958769

ABSTRACT

INTRODUCTION: Participation in falls prevention activities by older people following presentation to the emergency department (ED) with a fall is suboptimal. This randomised controlled trial (RCT) will test the RESPOND programme, an intervention designed to improve older persons' participation in falls prevention activities through delivery of patient-centred education and behaviour change strategies. DESIGN AND SETTING: A RCT at two tertiary referral EDs in Melbourne and Perth, Australia. PARTICIPANTS: 528 community-dwelling people aged 60-90 years presenting to the ED with a fall and discharged home will be recruited. People who require an interpreter or hands-on assistance to walk; live in residential aged care or >50 km from the trial hospital; have terminal illness, cognitive impairment, documented aggressive behaviour or a history of psychosis; are receiving palliative care or are unable to use a telephone will be excluded. METHODS: Participants will be randomly allocated to the RESPOND intervention or standard care control group. RESPOND incorporates (1) a home-based risk factor assessment; (2) education, coaching, goal setting and follow-up telephone support for management of one or more of four risk factors with evidence of effective interventions and (3) healthcare provider communication and community linkage delivered over 6 months. Primary outcomes are falls and fall injuries per person-year. DISCUSSION: RESPOND builds on prior falls prevention learnings and aims to help individuals make guided decisions about how they will manage their falls risk. Patient-centred models have been successfully trialled in chronic and cardiovascular disease; however, evidence to support this approach in falls prevention is limited. TRIAL REGISTRATION NUMBER: The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614000336684).


Subject(s)
Accidental Falls/prevention & control , Community Health Services/organization & administration , Emergency Service, Hospital/statistics & numerical data , Preventive Health Services/organization & administration , Wounds and Injuries/prevention & control , Accidental Falls/statistics & numerical data , Aged , Aged, 80 and over , Clinical Protocols , Environment Design , Female , Hospitalization , Humans , Male , Middle Aged , Patient Discharge , Program Evaluation , Risk Assessment , Risk Factors , Western Australia/epidemiology , Wounds and Injuries/epidemiology
4.
J Dairy Sci ; 97(11): 7230-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25151875

ABSTRACT

The objective of this study was to quantify the genetic variation in normal and atypical progesterone profiles and investigate if this information could be useful in an improved genetic evaluation for fertility for dairy cows. The phenotypes derived from normal profiles included cycle length traits, including commencement of luteal activity (C-LA), interluteal interval, luteal phase length. and interovulatory interval. In total, 44,977 progesterone test-day records were available from 1,612 lactations on 1,122 primiparous and multiparous Holstein-Friesian cows from Ireland, the Netherlands, Sweden, and the United Kingdom. The atypical progesterone profiles studied were delayed cyclicity, prolonged luteal phase, and cessation of cyclicity. Variance components for the atypical progesterone profiles were estimated using a sire linear mixed model, whereas an animal linear mixed model was used to estimate variance components for the cycle length traits. Heritability was moderate for delayed cyclicity (0.24 ± 0.05) and C-LA (0.18 ± 0.04) but low for prolonged luteal phase (0.02 ± 0.04), luteal phase length (0.08 ± 0.05), interluteal interval (0.08 ± 0.14), and interovulatory interval (0.03 ± 0.04). No genetic variation was detected for cessation of cyclicity. Commencement of luteal activity, luteal phase length, and interovulatory interval were moderately to strongly genetically correlated with days from calving to first service (0.35 ± 0.12, 0.25 ± 0.14, and 0.76 ± 0.24, respectively). Delayed cyclicity and C-LA are traits that can be important in both genetic evaluations and management of fertility to detect (earlier) cows at risk of compromised fertility. Delayed cyclicity and C-LA were both strongly genetically correlated with milk yield in early lactation (0.57 ± 0.14 and 0.45 ± 0.09, respectively), which may imply deterioration in these traits with selection for greater milk yield without cognizance of other traits.


Subject(s)
Cattle/genetics , Cattle/metabolism , Genetic Variation , Progesterone/metabolism , Animals , Estrous Cycle/genetics , Estrous Cycle/physiology , Europe , Female , Fertility/genetics , Genetic Testing , Lactation/genetics , Linear Models , Parity , Pregnancy
5.
Br J Ophthalmol ; 94(11): 1427-31, 2010 Nov.
Article in English | MEDLINE | ID: mdl-19850584

ABSTRACT

AIM: To review the evidence for the presence of lower levels of psychosocial well-being in working-age adults with visual impairment and for interventions to improve such levels of psychosocial well-being. METHODS: Systematic review of quantitative studies published in English from 2001 to July 2008 that measured depression/mental health, anxiety, quality of life, social functioning or social support. RESULTS: Included were 29 studies that measured one or more outcomes (N = 52). Working-age adults with visual impairment were significantly more likely to report lower levels of mental health (mean difference = 14.51/100), social functioning (MD = 11.55/100) and quality of life. Studies regarding the prevalence of depressive symptoms produced inconsistent results but had methodological limitations. CONCLUSIONS: Future research is required into the prevalence of loneliness, anxiety and depression in adults with visual impairment, and to evaluate the effectiveness of interventions for improving psychosocial well-being such as counselling, peer support and employment programmes.


Subject(s)
Anxiety/etiology , Depressive Disorder/etiology , Vision Disorders/psychology , Adult , Forecasting , Humans , Interpersonal Relations , Mental Health , Quality of Life , Social Adjustment , Social Support
6.
Clin Exp Rheumatol ; 24(6): 636-42, 2006.
Article in English | MEDLINE | ID: mdl-17207378

ABSTRACT

OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c microsatellite markers with 1) the clinical disease activity and 2) the induction of remissions in patients with early rheumatoid arthritis (RA) treated with two treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis Combination therapy) trial of two years, 195 patients with recent-onset RA were randomly assigned to receive either a combination (COMBI) (sulphasalazine, methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE) (initially sulphasalazine with or without prednisolone) disease modifying antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1 typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS: At baseline the 28 joint disease activity scores (DAS28) of the patients positive for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the other patients. In the SINGLE patients the DAS28 improved comparably in patients with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the TNFb1-positive COMBI patients (n = 22) improved significantly more than that of the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1% (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8% (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1- patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively. CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more favourably to COMBI treatment than the patients without this microsatellite allele. The finding may be of clinical relevance for the choice of DMARDs in early RA.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Lymphotoxin-alpha/genetics , Lymphotoxin-beta/genetics , Microsatellite Repeats , Polymorphism, Genetic/genetics , Tumor Necrosis Factor-alpha/genetics , Adolescent , Adult , Aged , Alleles , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/pathology , Drug Therapy, Combination , Female , HLA-DR Antigens/metabolism , Humans , Hydroxychloroquine/therapeutic use , Male , Methotrexate/therapeutic use , Middle Aged , Prednisolone/therapeutic use , Prognosis , Remission Induction , Sulfasalazine/therapeutic use , Treatment Outcome , Tumor Necrosis Factors
7.
Ann Rheum Dis ; 63(11): 1406-12, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15479890

ABSTRACT

OBJECTIVES: To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients. METHODS: 322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes. RESULTS: The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes. CONCLUSIONS: When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.


Subject(s)
Arthritis, Rheumatoid/genetics , Genes, MHC Class II , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Arthritis, Rheumatoid/immunology , Case-Control Studies , Chi-Square Distribution , Female , Finland , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Male , Models, Genetic , Risk
8.
Equine Vet J Suppl ; (34): 17-21, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12405653

ABSTRACT

Studies of the effect of varying dietary carbohydrate compositions on exercise metabolism of horses are scarce. In the present study, the starch and sugar proportions were altered in the diet to 4 Standardbred horses. In a crossover experiment, the horses were offered a hay and oat diet, where the oats were substituted for barley syrup (BS) at 4 levels (BS 0, 0.5, 1.0 and 1.5 kg). Each diet was consumed for 21 days and both an incremental treadmill exercise test (IE) and a 40 min submaximal exercise test (SE) were performed. During the IE there was a significant (P<0.05) increase in mean VO2 on BS 1.5 and at the highest speed respiratory exchange ratio (RER) was significantly lower on BS 1.0 and 1.5. During the SE, RER and HR were significantly higher on BS 1.0 and 1.5. There were no significant effects of diets on plasma levels of glucose, lactate and insulin. Following the SE there was a significant decrease in the muscle glycogen content on BS 0, which was not observed in the other diets. In addition, there was a numerical decrease in the glycogen utilisation with increasing proportions of sugar in the diet. In conclusion, this study indicates that horses on diets with a high sugar inclusion respond with an increased heart rate during exercise of lower intensities; and that the response in VO2 and RER may differ depending on the exercise intensity. In addition, glycogen utilisation during submaximal exercise was lowered when daily sugar intake was increased. However, further investigation is needed to evaluate whether this strategy of feeding could be beneficial for exercising horses competing over endurance distances.


Subject(s)
Animal Nutritional Physiological Phenomena , Dietary Carbohydrates/administration & dosage , Horses/metabolism , Physical Conditioning, Animal/physiology , Starch/administration & dosage , Animal Feed , Animals , Cross-Over Studies , Dietary Carbohydrates/metabolism , Exercise Test/veterinary , Glycogen/analysis , Hordeum , Horses/physiology , Male , Muscle, Skeletal/metabolism , Oxygen Consumption
9.
Equine Vet J ; 34(2): 133-42, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11902756

ABSTRACT

In the present study, the main objective was to study factors affecting postexercise voluntary water intake in horses. Four Standardbred horses (mean +/- s.e. bwt 500 +/- 8 kg) were used to study water intake and effects of altering hydration status before an incremental exercise test (INCR) and a 40 min constant velocity exercise test (CONST) on a treadmill. Exercise was performed during normohydration (N), after dehydration for 24 h (DEH) and after hyperhydration with 12 l water 30 min before exercise (HH). DEH resulted in a bodyweight loss of 3% and there were signs of some fluid uptake prior to exercise in both HH trials. By the end of the INCR, the calculated change in plasma volume (PVcalc) was -13 +/- 1, -21 +/- 1 and -11 +/- 3% in the N, DEH and HH trials, respectively. During the highest exercise velocities a hypotonic shift of fluid was seen in all INCR trials. There was a greater accumulation of plasma lactate (pLA) in HH-than in N-INCR, probably caused by the extra weight to be carried. CONST induced a similar fluid loss (3%) in all trials, but the decrease in PVcalc at the end of exercise was significantly smaller in HH (-7 +/- 2%) than in N (-14 +/- 1%) and DEH (-19 +/- 2%). In DEH-INCR and DEH-CONST, plasma sodium concentration (pNa) was higher than in N until drinking water was offered 1 h postexercise. In the presence of both an increased pNa and a decrease in PVcalc when dehydrated, the horses drank immediately when offered water postexercise. In N-CONST, there was a significant decrease in calculated PVcalc (-10 +/- 2%) but no increase in pNa when water was given and in this trial the horses rehydrated less rapidly. Plasma aldosterone concentration (PAC) had increased to the same magnitude in all trials after about 10 min, irrespective of type of exercise or hydration status. It was concluded that when both an osmotic and hypovolemic thirst stimulus was present, the horses rehydrated more rapidly postexercise.


Subject(s)
Drinking , Exercise Test/veterinary , Fluid Shifts/physiology , Horses/physiology , Water-Electrolyte Balance/physiology , Animals , Blood Volume/physiology , Blood Volume/veterinary , Body Weight , Dehydration/blood , Dehydration/veterinary , Female , Fluid Therapy/veterinary , Horses/blood , Lactic Acid/blood , Male , Time Factors
10.
J Psychol ; 135(3): 269-76, 2001 May.
Article in English | MEDLINE | ID: mdl-11577969

ABSTRACT

Sixty-seven college students rated a counselor on expertness, trustworthiness, and attractiveness based on reading 1 of 2 randomly assigned session transcripts. The desire to choose the depicted counselor was also measured. In both transcripts, the counselor self-disclosed his or her use of prayer. A single-client statement varied across the 2 transcripts such that one contained a congruent counselor self-disclosure (counselor disclosure after client disclosure) and the other included an incongruent self-disclosure (counselor disclosure without client disclosure). A potential covariate, religiosity, was examined but did not draw significant variance. Participants in the congruent group reported a more favorable total perception, a higher attractiveness perception, and a greater desire to choose the counselor than did participants in the incongruent group. Limitations and implications for future research are discussed.


Subject(s)
Counseling , Perception , Professional Competence , Adolescent , Adult , Humans , Random Allocation , Religion , Self Disclosure
11.
Scand J Plast Reconstr Surg Hand Surg ; 35(3): 239-46, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11680392

ABSTRACT

Defects 10 mm long were created in long bone in the diaphysis of both radii of 18 rabbits (test and control side). On the test side, ingrowth of bone marrow into the defects was hindered or delayed by: plugging the opening of the cut bone ends with gutta-percha points (n = 7); plugging with Gelfoam (n = 6); or by removing the bone marrow by flushing with saline (n = 5). The defects on both test and control side were covered with an expanded polytetrafluoroethylene membrane, shaped as a tube. Healing was followed with radiographs for four to five months, after which the animals were killed and ground sections of the areas of the defects were prepared for histological examination. On the control side, nine of 18 animals had complete osseous bridging of the defect, and a small transverse non-mineralised zone remained in the centre of the healed defect in the other animals. This zone consisted of loose connective and cartilagenous tissue as well as connective tissue obviously derived from the outside of the membrane. By preventing or delaying the ingrowth of bone marrow we retarded the regeneration of mineralised bone, particularly in the gutta-percha and flushed bone marrow groups. The principle of guided tissue regeneration may be used to achieve regeneration of extensive long-bone defects. Any attempts to delay or prevent bone marrow ingrowth into the defects did retard regeneration of segmental long-bone defects.


Subject(s)
Bone Marrow/physiology , Bone Regeneration , Radius/physiology , Animals , Male , Rabbits , Wound Healing/physiology
12.
Physiol Behav ; 73(1-2): 1-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11399288

ABSTRACT

This study investigated three methods of water supply on drinking preference and behavior in six Standardbred geldings (2-9 years, 505+/-9 kg). The water sources were buckets (B), pressure valve (PV), and float valve (FV) bowls. In an initial drinking preference test, PV was tested at three flow rates: 3, 8, and 16 l/min (PV3, PV8, and PV16), and FV at 3 l/min (FV3). Water intake was measured in l and presented as the percentage of the total daily water intake from each of two simultaneously presented alternatives. The intake from PV8 was greater than from both PV3 (72+/-11% vs. 28+/-11%) and PV16 (90+/-4% vs. 10+/-4%). All horses showed a strong preference for B, 98+/-1% of the intake compared to 2+/-1% from PV8. Individual variation in the data gave no significant difference in preference between the two automatic bowls. In the second part of the study, drinking behavior and fluid balance were investigated when the horses drank from FV3, PV8, and B for 7 consecutive days in a changeover design. Despite a tendency for an increase in total daily drinking time from FV3, the daily water intake was significantly lower (43+/-3 ml/kg) than from PV8 (54+/-2 ml/kg) and B (58+/-3 ml/kg). Daily net water gain [intake-(fecal+urinary output)] was only 0.5+/-3 ml/kg with FV3, resulting in a negative fluid balance if insensible losses are included. These results show that the water supply method can affect both drinking behavior and fluid balance in the horse.


Subject(s)
Drinking Behavior/physiology , Horses/physiology , Water Supply , Water-Electrolyte Balance/physiology , Animals , Choice Behavior/physiology , Male , Thirst/physiology
13.
Ann Rheum Dis ; 60(4): 413-5, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11247876

ABSTRACT

OBJECTIVE: To determine whether there are genetic differences between female and male patients with familial rheumatoid arthritis (RA). METHODS: 45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB1*04 subtypes and associations of DRB1*04 haplotypes with DQB1*0301 or DQB1*0302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules. RESULTS: HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044). CONCLUSION: The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases.


Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease , Sex Factors , Adult , Age of Onset , Alleles , Arthritis, Rheumatoid/blood , Female , HLA-DR Antigens/genetics , Haplotypes , Humans , Male , Middle Aged , Polymerase Chain Reaction , Rheumatoid Factor/blood , Statistics, Nonparametric
14.
Ann Rheum Dis ; 59(3): 173-7, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10700424

ABSTRACT

OBJECTIVE: To search for possible immunogenetic differencies between the patients with familial and non-familial rheumatoid arthritis (RA). METHODS: The study compared 129 familial RA patients with 217 non-familial patients for the frequencies of HLA-DR antigens including DR4 subtypes, DR4-DQB1*0301 and DR4-DQB1*0302 haplotypes and HLA-B27 antigen as well as the age of disease onset and existence of rheumatoid factor or joint erosions. RESULTS: Two major differences between familial and non-familial groups were found: firstly, familial RA patients had increased frequency of HLA-DR4 as compared with the non-familial RA group (68.2 v. 54.8%; p = 0.019). Secondly, the mean age at onset of RA was significantly lower in the familial than in the sporadic RA patients (42.0 v. 46.5 years; p = 0.0020) and the difference still remained when the DR4 positive and negative subgroups were compared separately. CONCLUSION: These results confirm the more prominent association with HLA-DR4 in familial than in the non-familial cases and suggest that accumulation of HLA risk genes may, at least partly, explain the familial occurrence of the disease. Other susceptibility genes may also be concentrated in multiplex case families as suggested by an earlier age at the onset of RA in both HLA-DR4 positive and negative familial patients.


Subject(s)
Arthritis, Rheumatoid/genetics , HLA-DR4 Antigen/blood , Adolescent , Adult , Age of Onset , Arthritis, Rheumatoid/immunology , Biomarkers/blood , Female , Genetic Predisposition to Disease , HLA-DR Antigens/blood , Humans , Male , Middle Aged
15.
Clin Oral Implants Res ; 11(2): 99-106, 2000 Apr.
Article in English | MEDLINE | ID: mdl-11168200

ABSTRACT

The aim of the present study was to evaluate if early access to the endosteal bone compartment by removal of the outer cortical bone plate will enhance bone augmentation in a secluded space. Two titanium cylinders were placed on the skull of each of 8 rabbits. Each cylinder was placed into a circular slit, secured to the skull bone via two mini-screws and supplied with a titanium lid. On the test side, the outer plate of the cortical bone, demarcated by the slit, was removed. The subsequent bleeding resulted in blood fill of the cylinders to various degrees. On the control side, the corfical bone plate was left intact and no bleeding was observed at the time of the placement of the titanium lids. After 3 months, the animals were sacrificed to obtain histology and histomorphometry. No differences in the total amount of augmented bone tissue, in relation to the total experimental area (75.5% +/- 10.9% at the test sites and 71.2% +/- 13.5% at the control sites) or of the augmented mineralized bone tissue in relation to the total amount of augmented bone tissue, was revealed (17.8% +/- 3.0% and 16.0% +/- 4.9% respectively). There was no difference in the morphological appearance of the augmented bone between test and control sites and there were no obvious similarities in the appearance between the newly formed bone tissue and the donor bone. The augmented bone consisted of slender bone trabeculae, distributed in abundant marrow spaces. A conspicuous finding was that the bone trabeculae tended to climb along the inner walls of the titanium cylinder. It is concluded that decortication of the calvarial bone in the rabbit does not result in more bone formation beyond the skeletal envelope after a healing period of 3 months compared to no removal of the cortical bone plate inside a secluded experimental area.


Subject(s)
Bone Transplantation/physiology , Bone and Bones/physiology , Implants, Experimental , Osteogenesis/physiology , Animals , Bone Transplantation/methods , Female , Periosteum/physiology , Rabbits , Skull/surgery , Statistics, Nonparametric , Titanium
16.
Neurology ; 52(8): 1668-72, 1999 May 12.
Article in English | MEDLINE | ID: mdl-10331697

ABSTRACT

OBJECTIVE: To determine whether N-acetylaspartate (NAA) is reduced in patients with Salla disease, a neurodegenerative disorder. BACKGROUND: 1H MRS allows the brain metabolism to be studied noninvasively in vivo. N-acetyl (NA) is composed primarily of NAA, which is regarded as a neuronal marker. The NA signal in 1H MRS is reduced in several neurodegenerative disorders. Increased NA signal has thus far only been found in Canavan's disease as a result of NAA accumulation in the brain tissue. In Salla disease, an autosomal recessive free sialic acid storage disorder, N-acetylneuraminic acid (NANA), accumulates in lysosomes of brain tissue. METHODS: The authors studied eight patients with Salla disease (age range, 6 to 44 years) and eight age-matched healthy volunteers using quantitative 1H MRS. The spectra were obtained from two selected 8-cm3 volumes of interest localized in the basal ganglia and in the parietal white matter using conventional 1.5-T MRI equipment. The spectral resonance lines of NA groups, creatine and phosphocreatine (Cr), and choline-containing compounds (Cho) were analyzed quantitatively. All MR images were evaluated to verify the state of myelination. RESULTS: 1H MRS from parietal white matter revealed 34% higher NA and 47% higher Cr concentrations, and a 35% lower Cho concentration in the patients with Salla disease compared with the age-matched control subjects. The patients had a 22% higher water content in their parietal white matter, whereas in the basal ganglia the water concentrations did not differ significantly. In the patients' basal ganglia the Cr concentration was 53% higher. CONCLUSIONS: NAA is considered to be a neuronal marker that, except for Canavan's disease, has been found or assumed to be either stable or reduced. However, in Salla disease the high NA signal may have a contribution from accumulated lysosomal NANA, which offsets the possible loss of NAA. The high Cr is in line with the increased glucose uptake found in our earlier 2-fluoro-2-deoxy-D-glucose-PET study, reflecting increased energy demand. It is worth noting that in a conventional 1H MRS ratio-based analysis these underlying abnormalities would have remained undetected. Our study thus emphasizes the importance of a quantitative assessment of metabolite concentrations in 1H MRS for detecting altered brain metabolism.


Subject(s)
Brain/metabolism , Lysosomal Storage Diseases/metabolism , Magnetic Resonance Spectroscopy/methods , Adolescent , Adult , Brain/pathology , Child , Humans , Lysosomal Storage Diseases/pathology , Magnetic Resonance Imaging , Protons
17.
Equine Vet J Suppl ; (30): 398-403, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10659289

ABSTRACT

The aim of this investigation was to study sweat production during exercise at 2 ambient temperatures (20 degrees C and 35 degrees C) and the concurrent localisation of carbonic anhydrase (CA) in the sweat gland. Horses develop alkalosis during prolonged exercise and the sweat contains HCO3-. Carbonic anhydrase is therefore of interest since it catalyses the reaction CO2 + H2O<-->HCO3- + H+. Four standardbred trotters performed an exercise test. Skin biopsies were taken from the neck, and sweat rate, blood and skin temperatures were measured. There was a close relationship between sweat rate, temperatures and work intensity at 20 degrees C. Temperatures and sweat rate were higher at 35 degrees C and did not fall when the work intensity dropped. A significant decrease in the sweat gland cell area was found after exercise at 35 degrees C with an accompanying decrease of vesicles. Strong CA activity was present at the luminal cell membrane and weaker basolaterally. The staining intensity increased after exercise. We suggest that CA might be of importance for counteracting the alkalosis developed after exercise by delivering HCO3- for generation of the alkaline pH in sweat.


Subject(s)
Carbonic Anhydrases/analysis , Horses/physiology , Physical Conditioning, Animal , Sweat Glands/enzymology , Sweating/physiology , Animals , Body Temperature , Climate , Heart , Weight Loss
18.
Clin Implant Dent Relat Res ; 1(1): 41-8, 1999.
Article in English | MEDLINE | ID: mdl-11359310

ABSTRACT

BACKGROUND: By using the guided tissue regeneration concept it is possible to augment bone, beyond the skeletal envelope, provided certain biologic, surgical, and barrier-related demands are met. Among barrier-related factors of importance are the surface properties. PURPOSE: The aim of this study was to evaluate whether different surface roughness of the barrier wall influences the amount and morphology of augmented bone in a secluded space, using a titanium cylinder as barrier device placed on the rabbit skull. MATERIALS AND METHODS: Cylinders of commercially pure titanium were fabricated by machining, using a turning tool. The inner cylinder wall was either left untreated or grit-blasted with titanium dioxide to increase surface roughness. The topographic profile of the inner surface of two cylinders (1 turned and 1 grit-blasted) was measured in vitro to achieve a numeric characterization of each type of surface topography. Two cylinders, one with grit-blasted and one with turned inner walls, were surgically placed and secured to the skull bone of each of eight rabbits. The plate of the cortical bone, facing the experimental area framed by the cylinder wall was removed, and care was taken to ensure total blood fill of the cylinders. After 3 months, the animals were sacrificed to obtain histology for histomorphometry. RESULTS: The relative volume of augmented tissue in the grit-blasted cylinders (77.9 +/- 10.5%) did not differ significantly from that in the turned cylinders (73.4 +/- 5.5%, p = .118), neither did the volume of mineralized bone (20.1 +/- 8.2% vs. 22.1 +/- 7.2%, p = .064). The trabecular density of the augmented bone was higher close to the walls of both the turned and the grit-blasted cylinders compared to the overall trabecular density within the cylinders, but no significant difference between the two groups. However, the area of mineralized bone in direct contact with the inner surface of the titanium cylinder was significantly larger in the grit-blasted (33.9 +/- 13.3%) compared to the turned cylinders (12.0 +/- 8.5%, p = .01). CONCLUSIONS: The use of titanium barriers with a grit-blasted inner surface compared to barriers with a turned surface resulted in the formation of similar amounts of bone beyond the skeletal envelope of the rabbit skull. However, a larger area of augmented mineralized bone was found in direct contact with the inner surface of the grit-blasted cylinders.


Subject(s)
Bone Regeneration , Guided Tissue Regeneration/instrumentation , Implants, Experimental , Animals , Female , Rabbits , Skull/surgery , Statistics, Nonparametric , Surface Properties , Titanium
19.
Gynecol Obstet Invest ; 46(4): 220-4, 1998.
Article in English | MEDLINE | ID: mdl-9813438

ABSTRACT

The parameters regulating the fluidity of myometrial and placental phospholipids include double bonds, fatty acid chain lenght and the cholesterol/phospholipid ratio. The transformation of these parameters was studied during pregnancy and labor. Myometrial and placental tissue samples were collected from 24 patients: 6 were nonpregnant, 6 early-pregnant, 6 late-pregnant not in labor and 6 in labor. After butanol extraction, tissue cholesterol and lipid phosphorus were determined. Proton NMR spectroscopy of the phospholipids was performed at 500 MHz. The myometrial cholesterol/phospholipid ratio was slightly elevated in pregnant patients not in labor. The uterine muscle of the nonpregnant patients contained more CH=CH groups in the phospholipids than that of the late-pregnant patients. There were 29 more double bonds in placental than in uterine tissue per 100 fatty acid molecules. The average fatty acid chain length varied from 14.0 to 18.8. The placenta has longer fatty acid chains than the uterine smooth muscle. The myometrial carbon chain was shortened on the average by 1.4 and the placental by 1.0 carbon atoms, when the patient went into clinical labor. These findings suggest fluidity changes in myometrial and placental phospholipids during human pregnancy and labor.


Subject(s)
Muscle, Smooth/chemistry , Myometrium/chemistry , Phospholipids/analysis , Placenta/chemistry , Adult , Butanols , Cholesterol/analysis , Fatty Acids/analysis , Fatty Acids/chemistry , Female , Humans , Labor, Obstetric/physiology , Magnetic Resonance Spectroscopy , Membrane Fluidity , Phospholipids/chemistry , Pregnancy
20.
Am J Vet Res ; 59(4): 489-94, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9563636

ABSTRACT

OBJECTIVE: To investigate effects of hydration status and exercise intensity on plasma atrial natriuretic peptide (ANP) concentration in exercising horses. ANIMALS: 4 trained Standardbreds. PROCEDURE: Horses performed a 40-minute exercise test at 65 to 70% maximal heart rate (HRmax; no incline) and a 12-minute test at approximately 90% HRmax (3.5 degrees incline). The 40-minute test was performed with ad libitum access to drinking water (normohydration), after water had been withheld for 24 hours (dehydration), and 30 minutes after 12 L of water at body temperature had been given via nasogastric tube (hyperhydration). The 12-minute test was only performed with normohydrated horses. RESULTS: Plasma ANP concentration was higher toward the end of exercise during hyperhydration than during the other 2 hydration states, and the area under the plasma ANP concentration curve was significantly greater during hyperhydration than during dehydration. The maximal plasma ANP value induced during the 12-minute test was similar to that of the 40-minute test. After the 12-minute test, plasma ANP concentration did not decrease during the first 30 minutes of recovery, whereas after the 40-minute test, plasma ANP concentration decreased by approximately 30% during the same period. CONCLUSIONS: Hydration status can affect plasma ANP concentration in horses during submaximal exercise. Maximal plasma ANP concentration was similar at the 2 exercise intensities studied, but the postexercise return to baseline values differed. CLINICAL RELEVANCE: Changes in hydration status can cause alterations in plasma concentration of ANP, one of the hormones involved in the control of cardiovascular functions during exercise.


Subject(s)
Atrial Natriuretic Factor/blood , Horses/physiology , Physical Conditioning, Animal/physiology , Physical Exertion/physiology , Water-Electrolyte Balance/physiology , Animals , Blood Proteins/metabolism , Female , Heart Rate , Male , Respiration , Time Factors
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