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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1997

Responsiveness of human immunodeficiency virus type 1-infected Kenyan women with or without prior pneumococcal disease to pneumococcal vaccine.

In East Africa, Streptococcus pneumoniae is a common and serious, but potentially preventable, human immunodeficiency virus type 1 (HIV-1)-associated pathogen. For 54 HIV-1-infected women, baseline levels of capsule-specific antibody to 2 of 4 pneumococcal serotypes were lower than levels in 15 seronegative women (P < .05). After immunization, specific antibody to all 4 serotypes increased in HIV-1-infected and -uninfected women (P < .05). Convalescent levels for 2 of 4 serotypes were greater in seronegative women, but the levels were not different between HIV-1-infected women with (n = 21) or without (n = 33) prior invasive pneumococcal disease. The baseline functional activity to kill S. pneumoniae type 14 was lower in HIV-1-infected than -uninfected women but also rose significantly in all groups after immunization. It is concluded that HIV-1 infection in Kenyan women is associated with decreased levels of natural antibody to selected pneumococcal capsular serotypes, but the vaccine is immunogenic in these patients who are at high risk of invasive pneumococcal disease.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Naltrexone as an adjunctive treatment for older patients with alcohol dependence.

The authors examined the efficacy of naltrexone as an adjunctive treatment for alcohol dependence in older adults. Forty-four veterans over 50 years of age were enrolled in a 12-week, double-blind, placebo-controlled efficacy study of naltrexone (the equivalent of 50 mg per day). There were no differences in the frequency of any self-reported adverse effects or in liver enzyme values between the placebo- and naltrexone-treated groups. There were no differences between the treatment groups in the number of subjects remaining abstinent or in the number of subjects who relapsed. However, all placebo-treated subjects relapsed after sampling alcohol, whereas only three of six naltrexone-treated subjects met relapse criteria after alcohol exposure (P = 0.024). The authors conclude that naltrexone was well tolerated and efficacious in preventing relapse in subjects who drank.

Aged↗
PubMed1997

The UPDRS scale as a means of identifying extrapyramidal signs in patients suffering from dementia with Lewy bodies.

The study aimed to evaluate the merits of the Unified Parkinson's Disease Rating Scale (UPDRS) in the assessment of parkinsonism in patients suffering from Dementia with Lewy Bodies (DLB). Parkinsonian symptoms were assessed in 73 dementia patients using the UPDRS and staged using the Hoehn & Yahr system. A staging of 1 or greater was taken to indicate significant parkinsonism. DLB (n=42) was diagnosed using the McKeith et al. criteria, Alzheimer's disease (n=30) was diagnosed using the NINCDS ADRDA criteria. The inability of some patients to comply with some of the more complicated tasks meant that the full UPDRS assessment could only be completed in 35 (83%) of the DLB patients, 23 (66%) of whom had significant parkinsonism. Patients with parkinsonism were significantly younger than those without. A Principal Components Analysis derived a sub-scale including the items tremor at rest, action tremor, bradykinesia, facial expression and rigidity. These items had a specificity of 100% and a sensitivity of 85% for significant parkinsonism using a cut-off of 7/8. The brief scale had several advantages over the complete UPDRS. Unlike the full scale it was independent of the severity of cognitive impairment and the 5 key items could be assessed in 41 (98%) of the DLB patients. Autopsies have been completed on 31 patients, with a specificity of greater than 90% for the operationalized clinical diagnosis of DLB. It is suggested that a 5 item subscale of the UPDRS provides a reliable and generally applicable instrument for the assessment of parkinsonism in DLB patients.

Aged↗
PubMed1997

Fucosidosis: genetic and biochemical analysis of eight cases.

The molecular basis of the deficiency of alpha-L-fucosidase has been investigated in eight patients who had been diagnosed clinically and enzymatically as suffering from the autosomal recessive lysosomal storage disease fucosidosis. None of the patients had a deletion or gross alteration of the alpha-L-fucosidase gene (FUCA1). Single strand conformation polymorphism (SSCP) analysis followed by direct sequencing of amplified exons and flanking regions identified putative disease causing mutations in six of the patients, who had severe forms of the disease and very low residual alpha-L-fucosidase activity and protein. They were a 10 bp deletion in exon 1 (E113fs), a 1 bp deletion at position -2 of intron 2 (S216fs), a g-->a transition at IVS5+1, point mutations W183X and N329Y in exons 3 and 6, respectively, and a compound allele consisting of a point mutation in the signal peptide in exon 1, P5R, and a 1 bp insertion in exon 6 (Y330fs). One patient in whom an SSCP change was not detected had residual alpha-L-fucosidase activity and cross reacting protein in the heterozygous range and normal metabolism of metabolites containing fucose in his fibroblasts, consistent with the low activity polymorphism. The eighth patient, who had a partial deficiency of alpha-L-fucosidase in her fibroblasts and leucocytes at a young age but normal alpha-L-fucosidase activity and protein at a later age, was homozygous for the common Q281R polymorphism in exon 5. She had no other sequence changes and Kivlin (Peters plus) syndrome has subsequently been diagnosed. The basis of her transient deficiency of alpha-L-fucosidase is not known. The detection of five novel mutations in six severely affected patients confirms the genetic heterogeneity in fucosidosis.

Adult↗
PubMed1997

Tolerability of naltrexone in treating older, alcohol-dependent patients.

The authors conducted an interim analysis of the tolerability of naltrexone among older, alcohol-dependent adults. Thirty-six subjects over 50 years old were enrolled in a 12-week, double blind, placebo-controlled efficacy study of naltrexone. Sixteen subjects received naltrexone and were compared with the placebo group for the development of adverse effects. Self-reported adverse effects did not differ in frequency or duration between the placebo and naltrexone groups. There were no significant differences in laboratory values between the two groups. Naltrexone was well tolerated with no clinically significant adverse effects. However, the efficacy of naltrexone has yet to be determined in this age group.

Age Factors↗
PubMed1997

Does hippocampal atrophy on MRI predict cognitive decline? A prospective follow-up study.

OBJECTIVES: To investigate whether the presence of hippocampal atrophy (HCA) on MRI in Alzheimer's disease (AD) leads to a more rapid decline in cognitive function. To investigate whether cognitively unimpaired controls and depressed subjects with HCA are at higher risk than those without HCA of developing dementia. DESIGN: A prospective follow-up of subjects from a previously reported MRI study. SETTING: Melbourne, Australia. PARTICIPANTS: Five controls with HCA and five age-matched controls without HCA, seven depressed subjects with HCA and seven without HCA, and 12 subjects with clinically diagnosed probable AD with HCA and 12 without HCA were studied. They were followed up at approximately 2 years with repeat cognitive testing, blind to initial diagnosis and MRI result. MEASURES: HCA was rated by two radiologists blind to cognitive test score results. Cognitive assessment was by the Cambridge Cognitive Examination (CAMCOG). RESULTS: No significant differences in rate of cognitive decline, mortality or progression to dementia were found between subjects with or without HCA. CONCLUSIONS: HCA was not found to be a predictor of subsequent cognitive decline in this series.

Aged↗
PubMed1996

Collecting morbidity data in general practice: the Somerset morbidity project.

OBJECTIVE: To collect a valid, complete, continuous, and representative database of morbidity presenting to primary care and to use the data to help commission services on the basis of local need and effectiveness. SETTING: Computerised general practices in Somerset. METHODS: Participating general practices were selected to be representative of the district health authority population for general practice and population characteristics. All conditions presented at face to face consultations were assigned a Read code and episode type and the data were regularly validated. Data were sent by modem from the practices via a third party to the health authority each week. MAIN OUTCOME MEASURES: Proportion of consultations coded and accuracy of coding. RESULTS: 11 practices agreed to participate. Validations for completeness during April 1994 to March 1995 revealed that 96.4% of the records were coded; 94% of the 1090 records validated had appropriate episode types and 87% appropriate Read codes. The results have been used to help formulate the health authority's purchasing plans and have enabled a change in the local contracts for surgery for glue ear. CONCLUSIONS: The project has shown the feasibility of establishing a network of practices recording and reporting the morbidity seen in primary care. Early indications are that the data can be useful in evidence based purchasing.

Adolescent↗
PubMed1996

Childhood social circumstances and psychosocial and behavioural factors as determinants of plasma fibrinogen.

BACKGROUND: High plasma fibrinogen concentration is associated with an increased risk of coronary heart disease. We have investigated associations between plasma fibrinogen and factors operating in childhood and in adulthood, including the psychosocial characteristics. METHODS: In a cross-sectional study of Civil Servants in London, UK, 2095 men and 1202 women aged 45-55 years provided blood samples for fibrinogen measurement at the time of the Whitehall II study baseline. The participants completed a questionnaire on demographic characteristics, education, employment grade, parents' occupation, health behaviours, and work characteristics. FINDINGS: Measures of childhood environment (adult height, father's social class, and participant's education) were inversely associated with adult plasma fibrinogen concentration in both sexes. Lower socioeconomic status (as shown by employment grade) was associated with higher fibrinogen concentrations, with differences from top to bottom grade of 0.22 g/L (95% Cl 0.13-0.31) in men and 0.37 g/L (0.18-0.56) in women (p<0.0001, both sexes). This association was not accounted for by measures of childhood circumstances. Control over work, assessed by personnel managers, was inversely related to fibrinogen in both sexes, and a similar relation was seen for self-rated control over work among men but not women. Men in the bottom third of the distribution for self-rated and externally assessed control over work had higher fibrinogen concentrations than those in the top third for both measures (difference 0.16 g//L [0.07-0.26]; p<0.001.) There was no difference between these extremes among women (0.02 g/L [0.16 to 0.19]). Current smokers had higher fibrinogen concentrations than non-smokers, and moderate alcohol consumers had lower concentrations than those who drank occasionally or never. INTERPRETATION: Although our study was cross-sectional, it provides evidence that adult fibrinogen concentration is determined by factors operating throughout life. Fibrinogen may be a marker of the biological pathways that mediate the inverse socioeconomic gradient in coronary disease.

Adult↗
PubMed1996

Evaluating primary care interventions for incontinence.

Regular urinary incontinence affects one in six adult women. However, for the majority, good continence services are difficult to access and few primary care-based assessment and treatment facilities are available. A large randomised trial of assessment and treatment in primary care using a trained nurse was conducted in Somerset in 1990. This report summarises the methods and results of the initial study and reports the four-year follow-up results. The results show that 70 percent of women will gain long lasting benefit. This model of service provision will also benefit secondary care specialist services by ensuring that patients are appropriately managed in primary care before any possible referral.

Adult↗
PubMed1996

Crisis in emergency.

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Emergency Service, Hospital↗
PubMed1996

The effect of minocycline in rat models of inflammatory arthritis: correlation of arthritis suppression with enhanced T cell calcium flux.

Adjuvant and collagen arthritis in the rat are widely accepted T-cell-dependent counterparts of rheumatoid arthritis and were used to examine the antiinflammatory properties of minocycline. Administration of oral minocycline, a semisynthetic tetracycline, significantly decreased (P < 0.01) the incidence of arthritis in both models. In vivo exposure to minocycline also significantly increased the percentage of splenocytes exhibiting a rise in free intracellular calcium concentration ([Ca2+]i) following concanavalin A stimulation (P < 0.05 in adjuvant and P < 0.01 in collagen). This enhancement was mitogen dose-dependent and supported exclusively by extracellular Ca2+. Resting [Ca2+]i levels were unaffected by minocycline and predominantly the CD4+ subset was involved. No changes were observed in weight, IgG antibodies to collagen, synoviocyte release of collagenase and prostaglandin E2, acute inflammation in an air-pouch system, or cell surface expression of activation markers (interleukin-2 and transferrin receptors) by splenocytes or lymph node cells. As a controlled [Ca2+]i rise is a critical event in normal T cell activation, minocycline's antiarthritic profile in vivo may relate to perturbed Ca2+ influx during T cell activation, an alteration that could promote the development of clinical tolerance to otherwise arthritogenic stimuli.

Animals↗
PubMed1996

Adventitial remodeling after coronary arterial injury.

BACKGROUND: Intraluminal thrombus formation and medial smooth muscle (SM) cell proliferation are recognized responses of the arterial system to injury. In contrast to these well-characterized processes during vascular repair, changes involving the adventitia have been largely neglected in previous studies. Hence, the goal of this investigation was to assess the response of the adventitia to coronary arterial injury. METHODS AND RESULTS: Adventitial changes in porcine coronary arteries subjected to medial injury were characterized by immunohistochemistry, histochemistry, and microscopic morphometry. The rapid development of a hypercellular response in the adventitia was evident 3 days after balloon-induced medial injury. Cell proliferation, as assessed by proliferating cell nuclear antigen immunostaining, reached the maximum level in the adventitia at 3 days, whereas at 14 and 28 days, the number of replicating cells reverted toward the baseline. The proliferating activity in the adventitia exceeded that seen in the media at all times after injury. To further define the changes in the phenotype of adventitial cells, the expression of three cytoskeletal proteins (vimentin, alpha-SM actin, and desmin) was characterized. Fibroblasts in normal adventitia expressed vimentin but no alpha-SM actin or desmin. After injury, these cells acquired characteristics of myofibroblasts expressing alpha-SM actin, which peaked at 7 and 14 days. Desmin expression was patchy in the adventitia, as opposed to its homogeneous distribution in medial SM cells. The modulation of fibroblast phenotype was transient, inasmuch as alpha-SM actin immunostaining declined at 28 days after injury, when dense, collagen-rich scar was evident within the adventitia. The above-described changes involving hypercellularity of the adventitia, myofibroblast formation, and fibrosis were associated with a significant focal adventitial thickening at 3, 7, 14, and 28 days after injury (P < .01 versus uninjured coronary arteries). CONCLUSIONS: This study demonstrates the involvement of the adventitia in the vascular repair process after medial injury. The hypercellularity of the adventitial layer, proliferation of fibroblasts, and modulation of their phenotype to myofibroblasts are associated with the development of the thickened adventitia. It is postulated that these phenomena affect vascular remodeling and may provide an important insight into the mechanisms of vascular disorders.

Actins↗
PubMed1996

Hepatitis C in human immunodeficiency virus-coinfected patients: increased variability in the hypervariable envelope coding domain.

Patients coinfected with the hepatitis C virus (HCV) and the human immunodeficiency virus (HIV) were studied with regard to nucleotide sequence variability in the E2/NS1 first hypervariable region of the HCV genome. The nucleotide variability within individual patients was compared to patients infected only with HCV. The proportion of predicted synonymous and nonsynonymous amino acid changes, and the relationship to putative high-antigenicity sites, were evaluated in the hypervariable envelope domain. Ninety-one clones from 10 patients with HCV/HIV coinfection were sequenced, following polymerase chain reaction (PCR) amplification of the hypervariable region. The control HCV group included 53 clones from 7 patients. Sequence analysis encompassed the region coding for amino acids 384 to 414. Consensus sequences from each patient were used as the internal standard for nonsynonymous amino acid codon variability. Cumulative proportional comparison at each amino acid site revealed increased variability in HCV RNA from patients with HCV/HIV coinfection versus HCV alone (P < .05). The greatest variability was observed at amino acids 386, 397, 400, 402, 405, 407, and 414, with >l0 percent clonal variation at these sites. Jameson-Wolf plots were used to predict putative high-antigenicity domains. Nonsynonymous clonal variation resulted in alteration of putative antigenic sites within the hypervariable region. All clones had at least one high-probability site. Clones with unique predicted antigenic domains were observed more frequently in HIV/HCV coinfected patients, and, independent of viral titer, were consistent with increased sequence variability. These data suggest an accumulation of envelope variants in the HCV/HIV coinfected patients, which could be related to ineffective viral clearance, and may help explain prior reports of interferon (IFN) resistance in this patient group.

Adult↗
PubMed1996

The relationship between plasma potassium, muscle membrane excitability and force following quadriceps fatigue.

To examine the simultaneous changes in plasma [K+], muscle excitability and force during fatigue, ten male adults (mean age = 22 +/- 0.5 years) held an isometric contraction of their right quadriceps muscle at an intensity of 30% maximum voluntary contraction (MVC) for 3 min. Femoral venous and brachial arterial [K+] were determined from serial samples drawn before, during, and for 15 min following the 3-min contraction. Each blood sample was synchronized with a maximal stimulation of the right femoral nerve to evoke a twitch and compound muscle action potential (M-wave). Immediately post-exercise, twitch torque was only 42% of baseline and femoral venous plasma [K+] had increased significantly from 4.02 +/- 0.08 mmol/l to 5.9 +/- 0.22 mmol/l. Femoral venous plasma lactate rose to a peak level of 10.0 +/- 0.8 mmol/l at 1 min post exercise. The recovery of the twitch torque was exponentially related to the recovery of femoral venous plasma [K+] (r2 = 0.93, P < 0.01). There was no evidence for any loss of muscle membrane excitability during the period of increased extracellular [K+], in fact, the M-waves tended to be potentiated in the early phases of the recovery period. These results suggest that muscle membrane excitability is maintained in spite of increased extracellular [K+] following fatigue induced by a sustained submaximal quadriceps contraction. However, the strong relationship between twitch torque and femoral venous plasma [K+] suggests that K+ may be exerting its effect distal to surface membrane action potential propagation, most likely in the T-tubular region.

Adult↗
PubMed1996

Connexin 35: a gap-junctional protein expressed preferentially in the skate retina.

We have used low stringency hybridization to clone a novel connexin from a skate retinal cDNA library. A rat connexin 32 clone was used to isolate a single partial clone that was subsequently used to isolate seven more overlapping clones of the same cDNA. Two clones containing the entire open reading frame have a consensus sequence of 1456 bp and predict a protein of 302 amino acids length and molecular mass of 35,044 daltons, referred to as connexin 35 or Cx35. Southern blot analysis suggests that the cloned sequence lies in a single gene with one intron. Polymerase chain reaction amplification from genomic DNA and partial sequencing of this intron showed that it was approximately 950 bp in length, and located within the coding region 71 bp after the translation start site. Hydropathy analysis of the predicted protein and alignments with previously cloned connexins indicate that Cx35 has a long cytoplasmic loop and a relatively short carboxyl terminal tail. Multiple sequence alignments show that Cx35 has similarities to both alpha and beta groups of connexins and suggests that its origins may be near the divergence point for the two groups. Consensus sequences consistent with sites for phosphorylation by protein kinase C and by cAMP - or cGMP -dependent protein kinase were identified. Two transcripts were detected in Northern blot analysis: a 1.95-kb primary transcript and a 4.6-kb minor transcript. In RNA samples from 10 tissues, transcripts were detected only in the retina.

Amino Acid Sequence↗
PubMed1996

A magnetic resonance imaging study of white matter lesions in depression and Alzheimer's disease.

BACKGROUND: White matter changes, as revealed by magnetic resonance imaging (MRI), may occur in depression and Alzheimer's disease. METHOD: T2-weighted MRI scans were performed in 39 control subjects, 61 subjects with NINCDS/ADRDA Alzheimer's disease and 60 subjects with DSM-III-R major depression. Deep white matter lesions (DWML) and periventricular lesions (PVL) were rated on a standard 0-3 scale by two radiologists blind to clinical diagnosis. RESULTS: After controlling for differences in vascular risk factors and current blood pressure, DWML were significantly more common in depressed subjects and PVL in Alzheimer's disease subjects compared to controls. DWML were most common in those presenting in late life with their first ever depression and 50% of such subjects had severe (grade 3) DWML. CONCLUSION: An association between DWML and depression and PVL and Alzheimer's disease is supported. The increase with DWML that occurs with ageing may predispose some elderly subjects to depression.

Aged↗