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Biomedical subjects

J Holmes

Publications and source records attributed to J Holmes.

At least 19 recordsLinked to original sources
PubMed2006

Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'?

Hypophosphatemia is a common complication of kidney transplantation. Tertiary hyperparathyroidism has long been thought to be the etiology, but hypophosphatemia can occur despite low parathyroid hormone (PTH) levels and can persist after high PTH levels normalize. Furthermore, even in the setting of normal allograft function, hypophosphatemia, and hyperparathyroidism, calcitriol levels remain inappropriately low following transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor-23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed a prospective, longitudinal study of 27 living donor transplant recipients to test the hypotheses that excessive FGF-23 accounts for hypophosphatemia and decreased calcitriol levels following kidney transplantation. Hypophosphatemia <2.5 mg/dl developed in 85% of subjects, including one who had previously undergone parathyroidectomy; 37% developed phosphate < or =1.5 mg/dl. The mean pre-transplant FGF-23 level was 1,218+/-542 RU/ml. Within the first week following transplantation, mean levels decreased to 557+/-579 RU/ml, which were still above normal. FGF-23 was independently associated with serum phosphate (P < 0.01), urinary excretion of phosphate (P < 0.01), and calcitriol levels (P < 0.01); PTH was not independently associated with any of these parameters. We calculated area under the curve for FGF-23 and PTH between the pre- and first post-transplant levels as a summary measure of early exposure to these phosphaturic hormones. An area under the FGF-23 curve greater than the median was associated with a relative risk of developing hypophosphatemia < or =1.5 mg/dl of 5.3 (P = 0.02) compared with lower levels. Increased area under the PTH curve was not associated with greater risk of hypophosphatemia. Excessive FGF-23 exposure in the early post-transplant period appears to be more strongly associated with post-transplant hypophosphatemia than PTH.

Adult↗
PubMed2006

Missing the point.

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Dental Caries↗
PubMed2005

Botulinum toxin type B: a new therapy for axillary hyperhidrosis.

UNLABELLED: Primary axillary hyperhidrosis is a disorder affecting mainly adolescents with significant adverse effects on quality of life. No ideal treatment exists, although recent data has demonstrated Botulinum toxin type A (Botox) as a treatment option. However, antibody formation may lead to loss of clinical benefit over time. Botulinum toxin type B (Neurobloc) has recently been introduced and may induce less immunogenic response. OBJECTIVE: To investigate the efficacy of Neurobloc for axillary hyperhidrosis. METHOD: Thirteen patients (22 axillae) were recruited to the study. The hyperhidrotic area was defined using the iodine-starch test then measured and photographed. 5000 MU of Neurobloc was administered subdermally. Patients were reviewed at 4, 8 and 12 weeks to assess outcome objectively (hyperhidrotic area measurements and photographs) and subjectively (sweat production and patient satisfaction). RESULTS: There was a significant reduction in hyperhidrotic area at follow-up compared to baseline. Mean percentage reduction in hyperhidrotic area was 84, 87 and 81% at 4, 8 and 12 weeks (p=0.001, paired t test). Patient satisfaction was 100% throughout. Subjective mean percentage reduction in sweat production was 98, 96 and 90 at 4, 8 and 12 weeks. Side effects were minimal. CONCLUSION: Neurobloc is an effective treatment for axillary hyperhidrosis.

Adult↗
PubMed2004

What drives quality of life in multiple sclerosis?

BACKGROUND: Extensive use of the EDSS measure of disease severity by clinicians, and the EQ-5D measure of quality of life by healthcare decision-makers, may not adequately reflect patient perceptions of the range and impact of their symptoms. AIM: To investigate the perceptions of MS patients in relation to specific symptoms and their general health-related quality of life. DESIGN: Questionnaire-based surveys. METHODS: Two consecutive postal surveys were sent to people whose contact details were on the database of the MS Trust. The first was sent to all 8,614. Of 3,403 respondents, 1992 agreed to participate in a second survey. RESULTS: In the first survey (response rate 40%), 1993 respondents (88%) reported moderate or severe fatigue; of 266 receiving disease-modifying therapy, 109 (41%) felt it improved their fatigue. In the second (response rate 78%), mean EQ-5D Index and z scores on the related quality of life deficit were significantly lower for respondents with relapsing or progressive disease than for those with benign disease. In the former groups (total n=1178), over 90% reported problems with mobility and usual activities, and over 80% reported problems with pain. The lowest mean SF-36 scores were for role-physical, physical functioning and vitality, vitality being higher in respondents receiving beta interferon vs. those who were not (p <0.0001). Vitality was highly correlated with social functioning (0.58), general health (0.51) and mental health (0.50). DISCUSSION: Fatigue can profoundly disrupt the occupational and social functioning of MS patients, but is not directly captured in either the EDSS or the EQ-5D. Further investigation of the patient-perceived benefits of disease-modifying therapy, particularly in relation to symptoms of fatigue, may be valuable.

Activities of Daily Living↗
PubMed2004

Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes.

Lateral ventricular enlargement has been reported in chronic fatigue syndrome, while cerebral neurospectroscopy has recently indicated that essential fatty acid treatment may be of value in this condition. An essential fatty acid supplement rich in eicosapentaenoic acid (EPA) was therefore given daily to a female patient with a 6-year history of unremitting symptoms of chronic fatigue syndrome. Cerebral magnetic resonance scanning was carried out at baseline and 16 weeks later. The EPA-rich essential fatty acid supplementation led to a marked clinical improvement in her symptoms of chronic fatigue syndrome, starting within 6-8 weeks. Accurate quantification of the lateral ventricular volumes in the baseline and 16-week follow-up registered images of high-resolution magnetic resonance imaging structural scans showed that the treatment was accompanied by a marked reduction in the lateral ventricular volume during this period, from 28,940-23,660 mm3.

Adult↗
PubMed2003

The Multi-Source Interference Task: validation study with fMRI in individual subjects.

Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but group-averaging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (P < 1.7 x 10(-4)) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312 +/- 61 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology.

Adult↗
PubMed2003

Clinical reversal of root caries using ozone, double-blind, randomised, controlled 18-month trial.

OBJECTIVE: To assess the effect of an ozone delivery system, combined with the daily use of a remineralising patient kit, on the clinical severity of non-cavitated leathery primary root carious lesions (PRCL's), in an older population group. DESIGN: A total of 89 subjects, (age range 60-82, mean +/- SD, 70.8 +/- 6 years), each with two leathery PRCL's, were recruited. The two lesions in each subject were randomly assigned for treatment with ozone or air, in a double-blind design, in a general dental practice. Subjects were recalled at three, six, 12 and 18 months. Lesions were clinically recorded at each visit as soft, leathery or hard, scored with a validated root caries severity index. RESULTS: There were no observed adverse events. After three months, in the ozone-treated group, 61 PRCL's (69%) had become hard and none had deteriorated, whilst in the control group, four PRCL's (4%) had become worse (p<0.01). At the six-month recall, in the ozone group, seven PRCL's (8%) remained leathery, the remaining 82 (92%) PRCL's had become hard, whilst in the control group, 10 PRCL's had become worse (11%) and one had become hard (p<0.01). At 12 and 18 months, 87 Subjects attended. In the ozone group at 12 months, two PRCL's remained leathery, compared to 85 (98%) that had hardened, whilst in the control group 21 (24%) of the PRCL's had progressed from leathery to soft, i.e. became worse, 65 PRCL's (75%) were still leathery, and one remained hard (p<0.01). At 18 months, 87 (100%) of ozone-treated PRCL's had arrested, whilst in the control group, 32 lesions (37%) of the PRCL's had worsened from leathery to soft (p<0.01), 54 (62%) PRCL's remained leathery and only one of the control PRCL's had reversed (p<0.01). CONCLUSIONS: Leathery non-cavitated primary root caries can be arrested non-operatively with ozone and remineralising products. This treatment regime is an effective alternative to conventional "drilling and filling".

Aged↗
PubMed2001

Susceptibility genes for a trait measure of attention deficit hyperactivity disorder: a pilot study in a non-clinical sample of twins.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder, and molecular genetic studies are underway, with most researchers focusing on identifying susceptibility genes in clinical samples with ADHD. An alternative approach is to search for quantitative trait loci underlying the trait measure of ADHD in non-clinical samples. Positive findings of association of the dopamine transporter DAT1 480 bp allele (allele 10) and the DRD4 7 repeat allele with clinical ADHD have been previously reported. In this pilot study, we examined these polymorphisms in a selected population-based sample of twins (50 high scoring pairs, 42 low scoring pairs). There was a trend for an increase in the frequency of the dopamine receptor DRD4 7 repeat allele in the high-scoring concordant monozygotic twins (odds ratio=1.4). Although this result was not statistically significant, the frequency of the 7 repeat allele was similar to that reported for our clinic sample of ADHD patients drawn from the same geographical area. There was a non-significant trend for an increased frequency of the DAT1 allele 10 (odds ratio=1.3). These results suggest that a molecular genetic study based on a questionnaire-derived measure of ADHD in a non-clinical sample is feasible and the results appear to be comparable with those from studies of clinical cases. However, sample size and power are key issues to consider when using this approach.

Adolescent↗
PubMed2001

No association between CHRNA7 microsatellite markers and attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable, common psychiatric disorder of childhood that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system may be functionally significant in ADHD. First, nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, smokers, and nonsmokers. Second, ADHD is a significant risk factor for early initiation of cigarette smoking in children and maternal cigarette smoking appears to be a risk factor for ADHD. Finally, animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems and locomotor activity. The nicotinic system has previously been studied in schizophrenia where the neuronal nicotinic acetylcholine receptor alpha 7 subunit gene (CHRNA7) has been implicated in decreased P50 inhibition and attentional disturbances in patients with schizophrenia and in many of their nonschizophrenic relatives. Three known microsatellite markers (D15S165, D15S1043, and D15S1360) near the nicotinic acetylcholine alpha 7 receptor gene, CHRNA7, were studied in 206 ADHD parent-proband trios of children aged 5-16 with ADHD according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ < 70) were excluded from the study. Markers D15S165 and D15S1360 were in linkage disequilibrium. The extended Transmission Disequilibrium Test analyses demonstrated no evidence that variation at the microsatellite markers D15S1360, D15S1043, and D15S165 influences susceptibility to ADHD. However, it remains possible that the CHRNA7 gene and other nicotinic system genes may be involved in conferring susceptibility to ADHD.

Adolescent↗
PubMed2001

Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable childhood-onset psychiatric condition characterized by developmentally inappropriate inattention, hyperactivity, and impulsiveness. The pathophysiology of ADHD is currently unknown. However, the therapeutic effects of stimulant medication together with findings from animal and neuroimaging studies as well as from several molecular genetic studies of the dopamine receptor D4 gene and dopamine transporter gene have implicated involvement of the dopaminergic system. To test the dopaminergic hypothesis further, we have looked for association between ADHD and alleles of seven dopamine-related candidate genes using a family-based association approach in a sample of 150 children diagnosed with ADHD. We tested polymorphisms in genes encoding three dopamine receptors (DRD3, DRD4, and DRD5) and four dopamine-relevant enzymes: tyrosine hydroxylase [tyrosine hydroxylase (TH)], dopamine beta hydroxylase (DbetaH), catechol-O-methyltransferase (COMT), and monoamine oxidase A (MAOA). We were unable to detect a significant association with any of the polymorphisms genotyped, although there was a trend for preferential transmission of the DRD5 148 bp marker allele and the MAOA 122 bp marker allele. We conclude that none of the alleles we have tested makes a major contribution to ADHD, although much larger samples are required to exclude small effects.

Adolescent↗
PubMed2001

Psychiatric illness and mortality after hip fracture.

People with dementia or delirium have increased mortality in the 6 months after hip fracture, but depression might take longer to have an effect. We assessed the psychiatric status of 731 participants with hip fracture and analysed the effect of psychiatric illness on mortality during the next 2 years. We found that dementia, delirium, and depression all increased the risk of mortality (p<0.0001, p<0.0001, and p=0.0359, respectively), and that mortality differed significantly between hospitals (p=0.0003). We suggest that psychiatric interventions should be asssessed in hip-fracture patients with adequate follow up of outcome measures.

Aged↗
PubMed2001

The behavior of oxygen as a collision-induced dissociation target gas.

The unusual and unique ability of O2 as target gas in kV collision-induced dissociations, to enhance a specific fragmentation of a mass selected ion, has been examined in detail. The affected dissociations studied were the loss of CH3* from CH3CH+X (X = OH, CH3, NH2, SH); CH3* and C1* loss from CH3C+(C1)CH3; C2H5* loss from CH3CH2CH+X (X = OH and NH2); H* loss from +CH2OH and +CH2NH2; O loss from 1,2-, 1,3-, and 1,4-C6H4(NO2)2+*; CH3NO+*; C6HsNO2+*; C5H5NO+* (pyridine N-oxide); 3- and 4-CH3C5H4NO+*. A general explanation of the phenomena, which was semiquantitatively tested in the present work, can be summarized as follows: the ion - O2 encounter excites the target molecules to their 3sigma(g)- state which resonantly return this energy to electronic state(s) in the ion. The excited ion now contains a sharp excess of a narrow range of internal energies, thus significantly and only enhancing fragmentations whose activation energies lie within this small energy manifold.

Journal Article↗
PubMed2001

Modeling emotion and behavior in animated personas to facilitate human behavior change: the case of the HEART-SENSE game.

The goal of this research is to determine whether a computer based training game (HEART-SENSE) can improve recognition of heart attack symptoms and shift behavioral issues so as to reduce pre-hospitalization delay in seeking treatment. Since treatment delay correlates with adverse outcomes, this research could reduce myocardial infarction mortality and morbidity. In Phase I we created and evaluated a prototype virtual village in which users encounter and help convince synthetic personas to deal appropriately with a variety of heart attack scenarios and delay issues. Innovations made here are: (1) a design for a generic simulator package for promoting health behavior shifts, and (2) algorithms for animated pedagogical agents to reason about how their emotional state ties to patient condition and user progress. Initial results show that users of the game exhibit a significant shift in intention to call 9-1-1 and avoid delay, that multi-media versions of the game foster vividness and memory retention as well as a better understanding of both symptoms and of the need to manage time during a heart attack event. Also, results provide insight into areas where emotive pedagogical agents help and hinder user performance. Finally, we conclude with next steps that will help improve the game and the field of pedagogical agents and tools for simulated worlds for healthcare education and promotion.

Algorithms↗
PubMed2001

Platelet activation and function after trauma.

BACKGROUND: Abnormal hemostasis is associated with many of the complications of trauma-associated morbidity and mortality. Platelets are integral in the maintenance of hemostasis. METHODS: Samples were obtained from 100 trauma patients on arrival at the emergency room (initial time) and at 24, 48, and 72 hours later. Samples were also obtained from 10 healthy controls at the same time intervals. Using flow cytometry, three parameters were used to measure platelet activation: platelet microparticles, expression of P-selectin (CD62P), and expression of the activated conformation of glycoprotein IIb-IIIa (PAC-1 binding). Platelet function was measured using a platelet function analyzer (PFA-100, Dade International Inc., Miami, FL). RESULTS: One hundred trauma patients were enrolled. The average age was 40 years, 75% were men, and 84% had blunt injuries. The mean Injury Severity Score was 22.3 +/- 10.9 (mean +/- SD) and the average Glasgow Coma Scale score was 11 +/- 4. All three platelet activation parameters were increased in trauma patients versus controls for all time periods (p < 0.001). Trauma patients had a trend toward a shorter initial collagen/epinephrine closure time versus controls (p = 0.096). Compared with the 24-, 48-, and 72-hour time intervals, initial collagen/epinephrine closure times were shortened (p < 0.001, p < 0.001, and p < 0.001). Platelet function returned to normal reference ranges within 24 hours but platelet activation parameters remained elevated at least 72 hours after initial trauma. In contrast, when trauma patients with and without brain injury were compared, brain injury patients had increased platelet activation but decreased platelet function (increased collagen/epinephrine closure times). In addition, there was a significant prolongation in collagen/epinephrine closure times for the 24-, 48-, and 72-hour time points in nonsurviving patients versus survivors. There was no association between platelet activation and function and other adverse outcomes including pulmonary embolism, deep venous thrombosis, and disseminated intravascular coagulation. CONCLUSION: Severe injury usually results in increased platelet activation and function. However, the combination of increased platelet activation with decreased function was associated with increased mortality.

Adult↗
PubMed2000

Untied

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Journal Article↗
PubMed2000

A series of outbreaks of food poisoning?

A series of independently occurring episodes which were notified individually as 'food poisoning' were, after investigation, linked to a common source water supply.

Caliciviridae Infections↗