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B J Harrison

Publications and source records attributed to B J Harrison.

At least 19 recordsLinked to original sources
PubMed2004

Evidence for synergistic modulation of early information processing by nicotinic and muscarinic receptors in humans.

Impairments in early information processing are a hallmark feature of diverse neuropsychiatric disorders including schizophrenia and Alzheimer's disease (AD). Several lines of evidence implicate a dysfunction of the cholinergic system in these disorders, particularly in AD where there is known degeneration in major cholinergic pathways. Inspection time (IT), a measure of early visual information processing speed, has been shown to be sensitive to cholinergic manipulation. The current study employed the IT task to (1) examine the independent roles of nicotinic and muscarinic receptors in modulating information processing and (2) investigate the interaction of nicotinic and muscarinic receptor systems in modulating information processing. Twelve healthy participants completed a randomized, double-blind, placebo-controlled study under four drug conditions; (1) placebo, (2) mecamylamine (15 mg; oral), (3) scopolamine (0.4 mg, s.c.), (4) mecamylamine (15 mg) + scopolamine (0.4 mg). IT measures were examined at baseline and 2.5 h post drug administration. Selective blockade of nicotinic receptors with mecamylamine did not significantly impair IT, whereas selective blockade of muscarinic receptors with scopolamine produced a significant but small impairment in IT. Combined blockade of both receptor types with scopolamine and mecamylamine produced a large impairment in IT performance. The results indicate that both nicotinic and muscarinic receptors are involved in modulating IT, and that the two systems may function synergistically to modulate early visual information processing. These findings suggest that functional abnormalities in both nicotinic and muscarinic systems may underlie deficits in early visual information processing seen in disorders such as Alzheimer's disease and schizophrenia.

Adult↗
PubMed2003

Influence of disease-modifying therapy on radiographic outcome in inflammatory polyarthritis at five years: results from a large observational inception study.

OBJECTIVE: To determine the effect of early treatment with disease-modifying antirheumatic drugs (DMARDs) in reducing radiographic progression over a 5-year period in patients with new-onset inflammatory polyarthritis. METHODS: Three hundred thirty-five consecutive patients with paired radiographs obtained 1 year and 5 years after enrollment in a population-based arthritis register were studied. Logistic regression was used to model differences in baseline factors associated with the start of DMARDs. The time from symptom onset to first use of DMARDs was stratified to represent 4 groups: no DMARD use, <6 months, 6-12 months, and >12 months. Radiographs of the hands and feet were scored using the Larsen method. Progression in the Larsen score was evaluated as a 5-year score adjusted for the first film score. Negative binomial regression was used to compare Larsen score progression for each of the 3 treatment groups with that for patients not receiving DMARDs. Results were then adjusted for severity, based on propensity modeling. RESULTS: Patients who received treatment had more radiographic progression than did patients who were untreated. Coefficients (95% confidence intervals), expressed as a multiple of the Larsen score in DMARD-treated patients compared with untreated patients, were as follows: 1.6 (1.1-2.3) for <6 months, 2.4 (1.5-3.6) for 6-12 months, and 2.0 (1.4-2.8) for >12 months. As expected, patients receiving treatment had more severe disease at baseline. Using the propensity score as a method of adjusting for disease severity, the influence of treatment on outcome became attenuated as follows: 1.1 (0.8-1.7) for <6 months, 1.6 (1.0-2.6) for 6-12 months, and 1.5 (1.0-2.2) for >12 months. This effect was also seen in the crude Larsen score at year 5. CONCLUSION: In this observational study, DMARD treatment was a marker not only of worse disease at presentation but also of the radiographic state and radiographic progression at 5 years. After adjustments were made for baseline disease severity, earlier therapy was shown to have a beneficial effect on outcome.

Adult↗
PubMed2003

Overexpression of type 2 iodothyronine deiodinase in follicular carcinoma as a cause of low circulating free thyroxine levels.

Thyroid function is normally undisturbed in patients with thyroid carcinoma. We have identified three patients with large or widely metastatic follicular thyroid carcinoma who had a persistently increased ratio of serum T(3) to T(4) in the absence of autonomous production of T(3) by the tumor. To investigate the possibility of tumor-mediated T(4) to T(3) conversion, we assayed types 1 and 2 iodothyronine selenodeiodinase (D1 and D2) activity in a 965-g follicular thyroid carcinoma resected from one of these patients. The V(max) for D2 was 8-fold higher than in normal human thyroid tissue. Resection of this tumor, leaving the left thyroid lobe intact, normalized the serum T(3) to T(4) ratio. In two other patients, treatment with sufficient levothyroxine to suppress TSH was associated with a high normal T(3) and a subnormal free T(4) index. In one, concomitant administration of the D1 inhibitors, propylthiouracil and propranolol, did not decrease the elevated serum T(3) to T(4) ratio. These data illustrate that increased T(4) to T(3) conversion in follicular thyroid carcinomas, probably by D2, can cause a significant perturbation in peripheral thyroid hormone concentrations.

Adenocarcinoma, Follicular↗
PubMed2002

Rheumatoid factor is the major predictor of increasing severity of radiographic erosions in rheumatoid arthritis: results from the Norfolk Arthritis Register Study, a large inception cohort.

OBJECTIVE: To identify the relative contributions of clinical and laboratory variables, determined at baseline, in predicting the deterioration of radiographic damage 5 years after presentation in patients with inflammatory polyarthritis. METHODS: Data from 439 subjects who sought primary care for inflammatory polyarthritis were analyzed. All subjects had paired radiographs, of which the first was obtained within 24 months of presentation and the second at 5 years after presentation. The contribution of baseline clinical and laboratory variables in predicting the degree of radiologic severity as judged by the Larsen score was assessed at both time points. Additionally, the role of these factors in predicting change after adjustment for baseline severity was also measured. RESULTS: By 5 years, 49% of subjects had evidence of erosions. The median Larsen score on the first film was 2 (interquartile range [IQR] 0-10) and the median score on the followup film was 7 (IQR 1-25). These corresponded to a median deterioration of 3 (IQR 0-14) in all subjects, whereas those subjects with evidence of erosions at first film showed a median deterioration of 15 (IQR 6-29) on followup. The rheumatoid factor (RF) status, C-reactive protein levels, the presence of nodules, and number of swollen joints at baseline were all predictive of radiographic severity at first film. Not surprisingly, the baseline radiographic score was a predictor of severity of deterioration. However, after adjusting for baseline severity, a high titer of RF (>1:160) was also an independent predictor of deterioration over 5 years: individuals with an initial RF at that level had a progression in their Larsen score that was 2.3 times (95% confidence interval 1.7-3.2) higher than that in the RF-negative individuals. Apart from this, only age had an independent effect, after adjusting for baseline severity, in predicting increasing radiographic joint damage. CONCLUSION: High-titer RF is an important variable in predicting continuing severity of radiographic damage during the first 5 years after presentation with inflammatory polyarthritis.

Adult↗
PubMed2002

Erosions in inflammatory polyarthritis are symmetrical regardless of rheumatoid factor status: results from a primary care-based inception cohort of patients.

BACKGROUND AND AIMS: Symmetry is considered an important criterion for the differentiation of rheumatoid arthritis (RA) from other forms of inflammatory polyarthritis (IP), particularly those that are seronegative. Because of the inclusion of symmetry in the diagnostic and classification process, however, its true occurrence in RA cannot be assessed. As a surrogate, peripheral inflammatory arthropathies associated with rheumatoid factor production may be more likely to be symmetrical. We examined the degree of symmetry of erosions in an unselected cohort of patients with IP and tested the hypothesis that the presence of rheumatoid factor (RF) is associated with greater symmetry. METHODS: All patients registered with The Norfolk Arthritis Register (NOAR; a UK primary-care based cohort of patients with IP with annual follow-up) and who had radiographs performed at the fifth anniversary from notification were included in the analysis. Radiographs of the hands and feet were read using the Larsen method; a score of 2 or more in any particular joint indicated an erosion. Log-linear modelling was used to determine the symmetry of erosions between right and left for the following joint groups: wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints. Log-linear modelling was also used to determine the influence of RF on symmetry. RESULTS: Five hundred and thirty-seven patients contributed to the analysis. The median time to performing radiographs was 69 months (interquartile range 65.5-74.8) from the onset of symptoms. A total of 212 (39%) patients had erosive disease. Overall, IP was found to be a symmetrical disease. Despite there being more erosions in RF-positive patients, there was no greater excess of symmetry in RF-positive compared with RF-negative patients. CONCLUSION: Radiographically, IP is a symmetrical disease irrespective of RF status. The use of symmetry as an important feature in identifying subgroups of patients with IP, such as RA, is challenged.

Arthritis, Rheumatoid↗
PubMed2002

Assessing periarticular bone mineral density in patients with early psoriatic arthritis or rheumatoid arthritis.

BACKGROUND: Periarticular osteoporosis is an early finding in the hands of patients with rheumatoid arthritis (RA), due to release of bone resorbing cytokines from the inflamed synovium. There has been disagreement as to whether periarticular bone loss occurs in psoriatic arthritis (PsA). Bone mineral density (BMD) can now be measured accurately using dual energy x ray absorptiometry (DEXA). Recently, DEXA has been used to measure periarticular BMD at predefined regions of interest (ROIs) around the joints. OBJECTIVES: Firstly, to compare periarticular BMD around the finger joints of patients with early RA or PsA. Secondly, to determine whether periarticular bone loss is related to joint inflammation and radiological erosions in RA and PsA. METHODS: Seventeen patients with RA and 15 with PsA were recruited, all with disease duration of less than five years. All finger joints were examined by one person for swelling, or tenderness, or both. Hand radiographs were scored for the presence of erosions. Periarticular BMD was measured at 10 predetermined ROIs using a Hologic QDA-4500A fan-beam densitometer. RESULTS: Patients with PsA were less likely to be positive for rheumatoid factor (RF) (13% v 94%) and more likely to be men (60% v 23%) than patients with RA. There were no other clinical differences between patients with RA or PsA. Patients with RA had significantly lower BMD at each of the ROIs than those with PsA (p<0.05). However, these differences disappeared after adjusting for age and sex. Among patients with RA, those with a higher total number of swollen and/or tender hand joints had significantly lower periarticular BMD at the metocarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. No such association was found for patients with PsA. CONCLUSIONS: In early disease, periarticular bone loss occurred both in patients with RA and those with PsA. Among patients with RA, periarticular osteoporosis was related to measures of joint inflammation. There was no association between joint inflammation and periarticular bone loss in patients with PsA, which lends support to the hypothesis that the primary site of inflammation in PsA is extrasynovial.

Absorptiometry, Photon↗
PubMed2002

The incidence of thyroid abnormalities in adults irradiated for lymphoma.

The aim of the study was to investigate the incidence of thyroid abnormalities in neck irradiated lymphoma patients. Of the 298 patients who had irradiation to the neck for lymphoma between 1966-1988, 174 were found to be alive and free of disease. These patients were invited to participate in the study. From the 174, 93 were able to participate (group 1). Two control groups were recruited; both were sex and aged matched. One group (group 2) consisted of lymphoma patients who were treated with chemotherapy (n=39) or irradiation to areas other than the neck (n=16). The other group (group 3) consisting of healthy volunteers (n=35) recruited from hospital staff and minor surgery attendees, had never had lymphoma or radiotherapy. All participants were required to complete a past medical history and thyroid symptom questionnaire, had blood taken for assays of thyroid stimulating hormone (TSH), thyroglobulin antibodies, thyroid peroxidase antibodies, sodium iodide symporter antibodies and TSH receptor antibodies and underwent ultrasound and clinical examination of the neck. A significant percentage of patients who had been irradiated in the neck had abnormalities on ultrasound, compared to groups 2 and 3 (77% vs 42% vs 24%). Abnormal TSH levels were found to be significantly more common in neck irradiated patients compared to the other groups (50% vs 9% vs 5%). There is a clear difference between neck irradiated patients and control groups. The importance of screening irradiated patients for thyroid abnormalities is re-emphasised.

Adult↗
PubMed2001

The association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis.

OBJECTIVE: Cigarette smoking is known to increase rheumatoid factor (RF) and nodule formation in patients with rheumatoid arthritis (RA). In this study, we examined the influence of smoking on disease outcome at 3 years among patients newly presenting with inflammatory polyarthritis (IP). METHODS: We studied 486 patients with IP who were referred to the Norfolk Arthritis Register, of whom 323 (67%) satisfied the American College of Rheumatology 1987 criteria for RA. Smoking status was assessed at baseline. Disease outcome was assessed at 3 years, using measures of joint inflammation, functional disability, and radiologic damage. The influence of smoking on disease outcome was explored using logistic regression techniques, with patients who had never smoked as the referent group. Results are expressed as odds ratios (ORs), with their 95% confidence intervals (95% CIs). RESULTS: Current smokers were significantly more likely to be RF positive at baseline (47%) than were ex-smokers (34%) and never smokers (31%). After 3 years, rheumatoid nodules were significantly more common in smokers (13%) compared with ex-smokers/never smokers (4%), a relationship which persisted after adjusting for age and sex (OR 4.07, 95% CI 1.38-12). In contrast, after adjusting for age and sex, current smokers had significantly fewer swollen joints (OR 0.61, 95% CI 0.37-0.98). However, smoking status had no influence on the development of erosions or functional disability. CONCLUSION: Despite smokers being more likely to develop nodules and to be RF positive, current smokers did not have higher levels of radiologic damage, and had fewer swollen joints. We hypothesize that this could be due to either the effect of cigarette smoking on the inflammatory response or other factors (e.g., reduced physical activity in smokers) which may limit joint inflammation and damage.

Adolescent↗
PubMed2001

Male breast neoplasia in association with selective serotonin re-uptake inhibitor therapy: a report of three cases.

Male breast cancer is a rare condition with very poorly understood risk factors. We report three cases of men with malignant and pre-malignant breast disease who had all been prescribed selective serotonin re-uptake inhibitors (SSRIs) for depression. Concerns about an association between this group of drugs and breast cancer in women have been previously raised and experimental evidence has suggested that these drugs could influence regulation of cellular proliferation acting through internal cellular messengers. Risk factors for the development of breast cancer are likely to be multifactorial, possibly more so in women given the complex physiological changes that occur in the female breast. Whilst the cases we report are anecdotal and other risk factors may be present, we suggest that assessment of any possible contribution that SSRI therapy may make to the development of breast neoplasia may be more easily assessed in a male population.

Aged↗
PubMed2001

The seductive lure of creative compensation.

In today's booming economy, the experienced development professional is being asked to take a more active role in the management of the organization. Not only is the development professional required to raise money in the traditional sense, but she is also being asked to create programs that will raise money in cyberspace, develop e-commerce ventures and product lines.

Administrative Personnel↗
PubMed2001

Are you running out of time?

In a perfect world we would all have a written daily plan of action that would be inviolate. Every task, every action, every conversation would be precisely timed to move us toward our ultimate personal goals. No one would trespass on our sacred schedule. But this is most definitely not a perfect world.

Appointments and Schedules↗
PubMed2001

Carolyn Farb: first lady of philanthropy.

From cancer and medical research, children's and women's issues, to arts, education, and culture, Carolyn Farb's skill as a volunteer fund raiser has been fine-tuned to equal that of the best professional fund raisers in the country. She has made chairing successful charitable events an art form and unselfish life's occupation.

Awards and Prizes↗
PubMed2001

Tainted money?

Explore the source record for details and available documents.

Ethics, Institutional↗
PubMed2000

Vasoactive and proliferative effects of parathyroid hormone and parathyroid hormone-related peptide on human vascular smooth muscle.

BACKGROUND: Hyperparathyroidism is associated with an increased incidence of hypertension and cardiovascular disease. Experiments in rats suggest that this results from desensitization of the normally inhibitory effects of parathyroid hormone-related peptide (PTHrP) on vascular smooth muscle cells (VSMCs) by previous exposure to parathyroid hormone (PTH). METHODS: Isometric tension in vitro was measured in segments of vessels obtained at neck surgery from six normotensive patients with hyperparathyroidism and 12 eucalcaemic controls undergoing thyroid surgery. Vessels were precontracted with noradrenaline to allow the vasodilatory effects of PTH and PTHrP to be observed. Human VSMCs were cultured in 0.5, 5 and 15 per cent serum with or without PTH (10(-11) to 10(-7) nmol l-(1)) and proliferation was assessed by cell counts after 14 days. RESULTS: Vasodilatation of arterial segments produced by both PTH 20 nmol l(-1) and PTHrP 100 nmol l(-1) did not differ significantly between control and hyperparathyroidism groups (P > 0.08, Mann-Whitney U test). Vasodilatation by PTHrP was not reduced by preincubation of vessels in vitro with PTH 50 nmol l(-1) for 1 h (P > 0.36, Wilcoxon test). No effects of PTH on serum-induced proliferation of human VSMCs were observed. CONCLUSION: These data imply that homologous desensitization to PTHrP is not implicated in the pathogenesis of vascular disease in patients with hyperparathyroidism.

Aged↗