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Biomedical subjects

J P Douglas

Publications and source records attributed to J P Douglas.

14 recordsLinked to original sources
PubMed2001

Transthyretin values correlate with mucosal recovery in patients with coeliac disease taking a gluten free diet.

AIMS: To assess changes in indicators of nutrition and iron deficiency as possible non-invasive markers of mucosal recovery in patients with coeliac disease on a gluten free diet. METHODS: Concentrations of transthyretin, retinol binding protein, soluble transferrin receptor, IgA anti-gliadin, and IgA anti-transglutaminase, and titres of IgA anti-endomysial antibody were measured in 36 newly diagnosed adult patients with coeliac disease and duodenal villous atrophy before (T0) and after one year (T1) on a gluten free diet. Duodenal biopsies taken at T0 and T1 were compared and graded as no improvement (no change in initial grade of villous atrophy) or improvement. RESULTS: Twenty two patients showed histological improvement and 14 showed no improvement. Transthyretin values increased in all patients with mucosal improvement and decreased in all patients showing no improvement. However, transthyretin values did not correlate with the degree of villous atrophy at T0 and T1 when assessed separately. Changes in retinol binding protein and soluble transferrin receptor values did not correlate with mucosal improvement. Coeliac disease associated antibodies (to gliadin, endomysium, and transglutaminase) decreased in most patients between T0 and T1, irrespective of mucosal recovery. CONCLUSIONS: Serial but not single measurements of transthyretin may be used as a non-invasive test to monitor mucosal recovery and therefore reduce the need for, or frequency of, follow up biopsies in treated patients with coeliac disease.

Adult↗
PubMed2000

Evaluation of the clinical utility of cerebrospinal fluid (CSF) indices of inflammatory markers in multiple sclerosis.

OBJECTIVES: Accumulating evidence indicates significant heterogeneity in MS and soluble (s) adhesion molecules are postulated as markers of disease activity. We sought to evaluate intrathecal production of these and other molecules across the clinical spectrum of MS. METHODS: CSF indices of IgG, sICAM-1, sVCAM-1, sE-selectin and sCD30 were calculated in 17 primary progressive (PPMS) patients, 15 secondary progressive patients (SPMS), 28 relapsing-remitting patients in relapse (RRMSR) and 14 RRMS patients in remission (RRMSNR) using commercially available ELISA kits. Patients had not received any immunomodulating therapy within the previous 6 months. MS patients were compared with 44 patients with non-inflammatory neurological diseases (NINDs). RESULTS: The most sensitive CSF index at a 90% level of specificity was for IgG which had 93% sensitivity in RRMSR and 92% sensitivity in RRMSNR. Corresponding sensitivity in PPMS and SPMS was 71% and 73% respectively. None of the other indices had sensitivity >50% apart from sVCAM-1 (64% in RRMSR and 52% RRMSNR) and sCD30 (53% in PPMS). CONCLUSIONS: Unsurprisingly the strongest association in MS was with the intrathecal production of IgG. Similar results in PPMS and SPMS may reflect comparable rates of progression in these 2 groups. Of the other molecules only intrathecal sVCAM-1 production is significantly associated with MS and only in relapsing-remitting disease.

Biomarkers↗
PubMed1999

Serum soluble adhesion molecules in multiple sclerosis: raised sVCAM-1, sICAM-1 and sE-selectin in primary progressive disease.

Leucocyte invasion into the central nervous system in multiple sclerosis (MS) is complex, involving T-cell/endothelium interaction dependent upon initial adhesion mediated by molecules such as E-selectin, L-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-(VCAM-1). Circulating levels of these can be measured by sensitive enzyme-linked immunoassay (ELISA) techniques. To assess whether serum concentrations of soluble adhesion molecules vary across the spectrum of patients with relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP) MS, we measured circulating levels of soluble (s)E-selectin, sL-selectin, sICAM-1 and sVCAM-1 in serum obtained from 78 PPMS patients, 71 patients with RRMS, 65 patients with SPMS and 66 patients with other neurological disease using commercially available ELISA systems. Levels of serum sVCAM-1 were significantly elevated in PPMS compared with RRMS in remission (P = 0.0001) and in relapse (P = 0.0001), whilst sICAM-1 was significantly elevated in PPMS compared with all other MS groups (vs SPMS, P = 0.006; vs RRMS in relapse, P = 0.003; vs RRMS in remission, P = 0.0001). Serum sE-selectin levels were significantly higher in PPMS compared with all other groups except inflammatory neurological disease (IND) [vs SPMS, P = 0.029; vs RRMS in relapse, P = 0.002; vs RRMS in remission, P = 0.001; vs non-inflammatory neurological disease (NIND), P = 0.002; vs IND, P = 0.076]. In PPMS there was no correlation between levels of any adhesion molecule and disability or disease duration. These results provide evidence for significant immunological heterogeneity in MS and suggest that different leucocyte/endothelial cell interactions may be active in various MS subgroups. It also challenges the hypothesis that PPMS is a less inflammatory form of the disease.

Adult↗
PubMed1999

Multiple evanescent white dot syndrome in older patients.

PURPOSE: To report two patients in their seventh decade who exhibited findings consistent with multiple evanescent white dot syndrome. METHODS: Case reports of two patients referred for evaluation of decreased vision, visual field loss, and retinal white spots. RESULTS: A 60-year-old man and a 67-year-old woman had photopsia, visual field loss, and decreased central visual acuity. Examination disclosed numerous white retinal spots, ranging from 50 to 400 microm, with eventual foveal granularity. Visual field testing showed an enlarged blind spot and peripheral field defects. Fluorescein angiography, electroretinography, and electrooculography results were consistent with multiple evanescent white dot syndrome. Eventually, the retinal lesions resolved in both patients and baseline visual acuity was recovered. CONCLUSION: A diagnosis of multiple evanescent white dot syndrome should be considered in patients with retinal findings typical of multiple evanescent white dot syndrome, regardless of age.

Aged↗
PubMed1998

Raised CSF levels of soluble adhesion molecules across the clinical spectrum of multiple sclerosis.

Endothelial activation is considered an important step in multiple sclerosis (MS) lesion formation, elevated cerebrospinal fluid (CSF) and serum levels of certain adhesion molecules being associated with varying stages of disease activity and clinical course. CSF and serum sVCAM-1, sICAM-1, sE-selectin and sL-selectin were measured by ELISA in 16 primary progressive (PPMS), 16 secondary progressive (SPMS) and 43 relapsing-remitting MS patients (RRMS) and compared with 20 inflammatory (IND) and 46 non-inflammatory neurological disease (NIND) controls. CSF sVCAM-1 and sICAM-1 were increased in all MS groups vs. NIND with no significant differences between the MS groups. CSF sE-selectin (p = 0.007) and the sE-selectin index (p = 0.01) were elevated in PPMS vs. RRMS in relapse, whilst serum sE-selectin was significantly raised in PPMS compared to RRMS in remission (p = 0.005), RRMS in relapse (p = 0.004), NIND (p = 0.03) and IND (p = 0.05). Adhesion molecule levels in both progressive MS groups were similar. These results provide evidence for a distinct inflammatory component in PPMS and for immunological heterogeneity between the clinical subgroups of MS.

E-Selectin↗
PubMed1998

Laser-induced chorioretinal venous anastomosis for nonischemic central retinal vein occlusion: evaluation of the complications and their risk factors.

PURPOSE: To evaluate the complications of laser-induced chorioretinal venous anastomosis in nonischemic central retinal vein occlusion (CRVO) and to identify the associated risks. METHODS: A retrospective consecutive series of 91 eyes (91 patients) with nonischemic CRVO with a mean +/- SD duration of 15.0 +/- 15.2 weeks (range, 3 to 72 weeks )and corrected visual acuity reduced to 20/100 or less because of perfused macular edema were reviewed. All eyes had one or more anastomotic attempts using argon laser (combined with Nd-YAG laser in 46 eyes) and a minimum of 12 months of follow-up. RESULTS: Successful chorioretinal venous anastomoses were created in 49 eyes (54%). Eighteen eyes (20%) had neovascular complications. These consisted of intravitreal, intraretinal, and subretinal neovascular membranes and were significantly associated with retinal ischemia (P < .001). There was avascular fibrous tissue proliferation at the anastomotic site in eight eyes (9%), and it was not associated with retinal ischemia (P = .727). No eye developed further capillary nonperfusion once an anastomosis became functional. A chorioretinal venous anastomosis was associated with improved vision (P < .001); 84% of eyes had an average +/- SD improvement of 4.3 +/- 3.8 lines (range, 2 to 20 lines), with the remaining 16% having no improvement or reduced vision. CONCLUSION: The major vision-threatening complication of laser-induced chorioretinal venous anastomosis for nonischemic CRVO is neovascular membranes occurring at the anastomotic site; these are associated with retinal ischemia. Prompt laser photocoagulation to areas of retinal ischemia that develop after the anastomotic attempt has been made may reduce the risk and severity of this complication.

Adult↗
PubMed1998

Elevated serum and CSF levels of soluble CD30 during clinical remission in multiple sclerosis.

OBJECTIVE: To ascertain the presence of the Th2 response in MS patients by evaluating the level of soluble (s) CD30 across the clinical spectrum of MS and during relapse and remission. BACKGROUND: MS is considered a T-cell-mediated disorder with the immune attack dominated by a Thl cytokine response. Elevated levels of sCD30 have been associated with CD4+ cells that secrete Th2-type cytokines. METHODS: Levels of sCD30 were determined in the serum and CSF of patients with primary progressive MS, secondary progressive MS, relapsing-remitting MS (RRMS), both in relapse and remission, and in patients with other inflammatory neurologic disease (IND) and noninflammatory neurologic disease (NIND). None of the patients were on immunomodulatory treatment. RESULTS: Higher serum levels of sCD30 were detected in all MS subgroups and IND patients compared with NIND patients. RRMS patients in remission had significantly higher levels than those in relapse (median, 45.7 U/mL versus 18.3 U/mL; p = 0.04). Significantly higher CSF levels were also found in all groups, except those with RRMS in relapse compared with NIND patients. Again, RRMS patients in remission had higher CSF sCD30 levels compared with those in relapse (median, 4.0 U/mL versus 3.0 U/mL; p = 0.08). CONCLUSIONS: Serum and CSF levels of sCD30 are increased in MS, particularly during remission. The results provide additional evidence for the presence of a Th2 response and indicate that sCD30 may be of value as a marker of lesion resolution.

Biomarkers↗
PubMed1997

Effect of low to moderate levels of smoking and alcohol consumption on serum immunoglobulin concentrations.

AIM: To determine the effect of low to moderate levels of smoking and alcohol consumption on immunoglobulin concentrations. METHODS: Serum samples from 1787 subjects with approximately equal numbers in each five year group from 15 to 64 years were obtained from a large random population survey in Northern Ireland. Details were available on each subject concerning the number of units of alcohol consumed per week and the number of cigarettes smoked per day. IgG, IgM, and IgA concentrations were measured by laser nephelometry on all serum samples. RESULTS: Low to moderate consumption of alcohol was associated with a decrease in IgG and IgM median concentrations in contrast to an increase in IgA median concentrations. The decrease in IgM and especially IgG median concentrations appeared to be related to the smoking habits of the subjects. Alcohol consumption alone was associated with increased IgA median concentrations whereas cigarette smoking alone was associated with reduced IgG median concentrations. CONCLUSION: Low levels of alcohol consumption and cigarette smoking influence IgG, IgM, and IgA serum concentrations. This should be borne in mind when selecting subjects for use in research and clinical settings.

Adolescent↗
PubMed1996

Serum and cerebrospinal fluid levels of soluble adhesion molecules in multiple sclerosis: predominant intrathecal release of vascular cell adhesion molecule-1.

Activated cerebral vascular endothelial cells express leukocyte, vascular cell, and intracellular adhesion molecules (E-selectin, VCAM-1 and ICAM-1) which facilitate leukocyte adhesion to endothelium and migration into inflammatory lesions. Paired serum and cerebrospinal fluid (CSF) levels of soluble (s) E-selectin, sVCAM-1 and sICAM-1 were determined by ELISA in patients with clinically definite MS in relapse, and patients with other inflammatory (IND) and non-inflammatory neurological disease (NIND). CSF levels of sVCAM-1 and sICAM-1 were significantly increased in MS patients compared to IND and NIND patients. Elevation of CSF sVCAM-1 in MS patients was the most marked finding (P = 0.0001) and an increased sVCAM-1 index indicated that this was due to intrathecal release of sVCAM-1. There were no differences in serum and CSF sE-selectin levels between the study groups. Measurement of the sVCAM-1 index may provide a marker of disease activity in patients with clinically definite MS.

Biomarkers↗
PubMed1996

Evaluation of formulae for CSF IgG synthesis using data obtained from two methods: importance of receiver operator characteristic curve analysis.

AIMS: To determine the clinical performance of three cerebrospinal fluid (CSF) IgG synthesis formulae using data obtained from two quantitation methods. METHODS: Receiver operator characteristic (ROC) analysis and decision index plots were used to compare a rate nephelometric (RN) and a rocket immunoelectrophoretic (RIEP) method for quantitating albumin and IgG for use in CSF IgG synthesis formulae. Further analysis was used to determine the most clinically accurate of these formulae for a diagnosis of multiple sclerosis with regard to technical accuracy and cost effectiveness. RESULTS: Values for albumin and IgG determined by RN gave better sensitivities and specificities than the RIEP method when applied to all three formulae; however, when the 95% confidence limits were considered, the difference was not significant. Using the RN method with an agreed "rule in" threshold value of 90% specificity, the IgG index gave the best clinical performance. CONCLUSION: ROC curve analysis and decision index plots provide valuable tools in assessing and comparing the clinical performance of new and existing laboratory assays.

Albumins↗
PubMed1986

The effect of pilocarpine on the visual field in normals.

Despite generalized consensus that pilocarpine-induced miosis results in some degree of visual field constriction, studies describing the predictability of this occurrence, as well as the nature of the field defects that may be seen, have not been undertaken. We studied 20 normal subjects, ranging in age from 24 to 57 years. Baseline refraction, pupillary measurements, and visual fields were performed in both eyes on a standardized Goldmann perimeter with the I-2e, I-3e, and I-4e test objects. Pilocarpine 2% was then instilled into the study eye and the field repeated at 30 and 120 minutes. An IBM PC computer program, designed by the authors, was used to calculate the area contained within each isopter. The probability of visual field constriction at 30 and 120 minutes after instillation of pilocarpine was found to be significant, especially with pupillary diameters of 2 mm or less. The I-2e isopter was most sensitive to miosis. Visual field constriction persisted with correction of ciliary spasm induced myopia, suggesting that miosis, especially when marked, can independently alter the visual field. The clinician, then, should make every effort to control visual field testing conditions in glaucoma patients on miotics to allow reliable serial comparisons.

Adult↗
PubMed1985

Extraocular muscle size comparison using standardized A-scan echography and computerized tomography scan measurements.

In many clinical situations, the standard for evaluating extraocular muscle (EOM) size, particularly in thyroid ophthalmopathy, has been use of the computerized tomography (CT) scanner. The impression is generally reported as "enlarged or normal EOMs." If the report of "normal EOM" on CT scan weighs heavily against the diagnosis of thyroid eye disease, how does this qualitative assessment compare with the diagnostic modality of ultrasound? The technique of standardized A-scan measurement of extraocular muscles has been extremely accurate. In this paper, standardized A-scan measurements and CT scan estimates of EOMs are compared in a series of ten patients with a clinical diagnosis of Graves' disease. Three of ten patients displayed enlarged EOMs by CT interpretations; seven of ten patients were categorized as consistent with Graves' disease by correlation with current ultrasonographic criteria for muscle enlargement, asymmetry, and high irregularity of tissue reflectivity.

Exophthalmos↗
PubMedDate not supplied

Giant papillary conjunctivitis associated with rigid gas permeable contact lenses.

Giant papillary conjunctivitis (GPC) is an external ocular inflammatory disorder associated with contact lens wear. GPC seems to occur less frequently with hard than with soft contact lens wear. The management of soft contact lens related GPC has included refitting with hard lenses, specifically the newer rigid gas permeable (RGP) lenses. We retrospectively studied 14 RGP lens wearers in whom GPC developed. Three patients had had GPC associated with soft contact lens wear and had been fitted with RGP lenses in an effort to restore contact lens tolerance. The interval of time between the initiation of RGP lens wear and the onset of GPC was inversely related to the lens oxygen transmissibility (DK value). Ophthalmologists should be aware of the association between GPC and rigid gas permeable lens wear.

Adolescent↗