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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 163 records · Page 9Linked to original sources
PubMed1999

Effect of acute intraocular pressure changes on short posterior ciliary artery haemodynamics.

BACKGROUND/AIMS: Vascular insufficiency due to abnormal autoregulation has been proposed as a major factor in the development of glaucoma. The anterior optic nerve is primarily perfused by the short posterior ciliary arteries. The autoregulatory capacity of these vessels in response to acutely elevated intraocular pressure (IOP) was examined in normal human subjects. METHODS: Colour Doppler imaging was performed on the short posterior ciliary arteries of 10 normal subjects at baseline and during four incremental IOP elevations. Using a scleral suction cup placed temporally, IOP was elevated to approximately 25, 30, 40, and 50 mm Hg. Additional measurements were performed immediately after pressure release. Systolic and diastolic flow velocities were measured and Pourcelot's resistivity index was calculated. RESULTS: Systolic and diastolic flow velocities decreased linearly with each incremental increase in IOP (p < 0.001). Pourcelot's resistivity index increased linearly with each incremental increase in IOP (p < 0.001). Changes in end diastolic velocity, peak systolic velocity, and Pourcelot's resistivity index were linearly related to changes in IOP. CONCLUSION: The normal healthy eye is not able to autoregulate to maintain PCA blood flow velocities in response to acute large elevations in IOP.

Adult↗
PubMed1999

Peripapillary retinal blood flow in normal tension glaucoma.

AIMS: To determine if normal tension glaucoma (NTG) patients differ from age matched controls in blood flow to the peripapillary retina, as measured with confocal scanning laser Doppler flowmetry (cSLDF; "Heidelberg retinal flowmetry"). METHODS: 12 NTG patients and 12 age matched controls were compared using (a) 10 x 10 pixel boxes (the instrument default sample size), taken from the nasal and temporal peripapillary retina, (b) the average from two of these boxes, and (c) every qualifying pixel within the peripapillary retina. RESULTS: Patients and controls did not differ in blood flow measured using the default sample from a single 10 x 10 pixel box, placed in either the temporal or nasal peripapillary retina, or expressed as the average from these two boxes. However, in histograms using every pixel from the peripapillary retina, NTG patients displayed significantly higher percentages of minimal flow pixels (defined as less than one arbitrary unit of flow: 30% v 19%, p < 0.01), and significantly lower flow in the 25th, 50th, and 75th percentile flow pixel (each p < 0.05) than did age matched controls. CONCLUSION: NTG is characterised by reduced blood flow in the peripapillary retina, a result suggesting that blood flow deficits accompany, and perhaps may contribute to, disease development in these patients.

Blood Flow Velocity↗
PubMed1999

Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change.

BACKGROUND/AIMS: Autoregulation of blood flow during posture change is important to ensure consistent organ circulation. The purpose of this study was to compare the change in retrobulbar ocular blood flow in glaucoma patients with normal subjects during supine and upright posture. METHODS: 20 open angle glaucoma patients and 20 normal subjects, similar in age and sex distribution, were evaluated. Blood pressure, intraocular pressure, and retrobulbar blood velocity were tested after 30 minutes of sitting and again after 30 minutes of lying. Retrobulbar haemodynamic measures of peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were obtained in the ophthalmic and central retinal arteries using colour Doppler imaging (CDI). RESULTS: When changing from the upright to supine posture, normal subjects demonstrated a significant increase in OA EDV (p = 0.016) and significant decrease in OA RI (p = 0.0006) and CRA RI (p = 0.016). Glaucoma patients demonstrated similar changes in OA measures of EDV (p = 0.02) and RI (p = 0.04), but no change in CRA measures. CONCLUSION: Glaucoma patients exhibit faulty autoregulation of central retinal artery blood flow during posture change.

Blood Flow Velocity↗
PubMed1999

ELISA is the superior method for detecting antineutrophil cytoplasmic antibodies in the diagnosis of systemic necrotising vasculitis.

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) have been used as a diagnostic marker for systemic necrotising vasculitis, a disease classification which includes Wegener granulomatosis, microscopic and classic polyarteritis nodosa, and Churg Strauss disease. OBJECTIVE: To compare the diagnostic value of the two methods for detecting these antibodies--immunofluorescence and enzyme linked immunosorbent assay (ELISA)--with respect to biopsy proven active systemic necrotising vasculitis in a clinically relevant population. METHODS: A prospective study to ascertain the patient's diagnosis at the time of each of the 466 requests for ANCA received at one laboratory over a nine month period, and allocate each to one of five diagnostic groups: active and inactive biopsy proven systemic necrotising vasculitis, suspected systemic necrotising vasculitis, low probability systemic necrotising vasculitis, and not systemic necrotising vasculitis. RESULTS: ELISA was superior to immunofluorescence in the diagnosis of systemic necrotising vasculitis because it was less likely to detect other diseases. This was reflected in its specificity of 97% and positive predictive value of 73%, compared with 90% and only 50% for immunofluorescence (p = 0.0006 and p = 0.013, respectively). ELISA had a negative predictive value of 98% which was not significantly different to immunofluorescence. ELISA was technically superior. CONCLUSIONS: ELISA is the superior method of ANCA detection in the diagnosis of systemic necrotising vasculitis and should be used in conjunction with a compatible clinical picture and histological evidence.

Adolescent↗
PubMed1999

Mucin gene expression during differentiation of human airway epithelia in vitro. Muc4 and muc5b are strongly induced.

Mucus hypersecretion is characteristic of chronic airway diseases. However, regulatory mechanisms are poorly understood. Human airway epithelial cells grown on permeable supports at the air-liquid interface (ALI) develop a mucociliary morphology resembling that found in vivo. Such cultures provide a model for studying secretory cell lineage, differentiation, and function, and may provide insight regarding events leading to mucus hypersecretion. The mucin gene expression profile of well-differentiated human airway epithelial cells in culture has not yet been established. We compared expression of all the currently described mucin genes in poorly differentiated (conventional cultures on plastic) and well-differentiated (ALI) human nasal and bronchial epithelial cells. Differentiation-dependent upregulation of MUC3, MUC5AC, MUC5B, and MUC6 messenger RNA (mRNA) was demonstrated using reverse transcriptase-polymerase chain reaction (RT-PCR). Northern blot analysis showed a similar increase for MUC4 and demonstrated that induction of MUC4 and MUC5B expression depended on retinoic acid. MUC1, MUC2, MUC7, and MUC8 mRNAs were also detected by RT-PCR, but these genes did not appear to be strongly regulated as a function of differentiation. Mucin gene expression was similar in bronchial and nasal cells. Thus, mucociliary differentiation of human airway epithelia in vitro entails upregulation of several mucin genes.

Cell Differentiation↗
PubMed1999

Expression of the MUC 6 mucin gene in development of the human kidney and male genital ducts.

The MUC 6 mucin cDNA was isolated from a human stomach cDNA library and has been shown to be expressed in a number of other tissues in the gastrointestinal tract, including the gallbladder, pancreas, and parts of the ileum and colon. Here we establish that MUC 6 is expressed transiently in the nephrogenic zone of the kidney in the early mid-trimester of development. MUC 6 transcripts were detected in the epithelium of ureteric buds at 13 weeks and at lower levels from 17 to 23 weeks of gestation. Traces of MUC 6 mRNA were seen in the collecting ducts but not elsewhere in the developing kidney, and MUC 6 glycoprotein was detected in the epithelium of ureteric buds and collecting ducts. MUC 6 transcripts were absent from adult kidney. This pattern of expression of MUC 6 in the developing kidney suggests a role in epithelial organogenesis. MUC 6 transcripts were also present at low levels in mid-trimester epididymal epithelium.

Epididymis↗
PubMed1999

Brightness alters Heidelberg retinal flowmeter measurements in an in vitro model.

PURPOSE: The Heidelberg Retinal Flowmeter (HRF), a laser Doppler flowmetry device, has captured interest as a research and clinical tool for measurement of ocular blood flow. Concerns remain about the range and accuracy of the values that it reports. METHODS: An in vitro blood-flow model was constructed to provide well-controlled laminar flow through a glass capillary for assessment by HRF. A change in material behind the glass capillary was used to simulate changing brightness conditions between eyes. RESULTS: Velocities reported by the HRF correlated linearly to true velocities below 8.8 mm/sec. Beyond 8.8 mm/sec, HRF readings fluctuated randomly. True velocity and HRF reported velocities were highly correlated, with r = 0.967 (P < 0.001) from 0.0 mm/sec to 2.7 mm/sec mean velocity using a light background, and r = 0.900 (P < 0.001) from 2.7 mm/sec to 8.8 mm/sec using a darker background. However, a large change in the y-intercept occurred in the calibration curve with the background change. CONCLUSIONS: The HRF may report velocities inaccurately because of varying brightness in the fundus. In the present experiment, a darker background produced an overreporting of velocities. An offset, possibly introduced by a noise correction routine, apparently contributed to the inaccuracies of the HRF measurements. Such offsets vary with local and global brightness. Therefore, HRF measurements may be error prone when comparing eyes. When used to track perfusion in a single eye over time, meaningful comparison may be possible if meticulous care is taken to align vessels and intensity controls to achieve a similar level of noise correction between measurements.

Blood Flow Velocity↗
PubMed1999

Effects of long-term hypotensive therapy with nonselective beta-blockers on ocular hemodynamics in primary open-angle glaucoma.

PURPOSE: Vascular factors have been implicated in the progression of glaucoma, but the impact of long-term beta blocker therapy on ocular circulation remains largely undefined. The purpose of this study was to prospectively evaluate the level of retrobulbar blood flow in patients with primary open-angle glaucoma (POAG) before and during long-term treatment with a nonselective topical beta blocker, and to compare these measures with those in untreated control subjects. METHODS: Twelve control subjects and 12 patients with POAG were tested for intraocular pressure (IOP), heart rate, blood pressure, contrast sensitivity, visual field sensitivity, and retrobulbar flow velocity as measured by color Doppler imaging (CDI). Patients were evaluated after 4 weeks of drug washout and again after 3 and 6 months of treatment with a nonselective beta blocking agent. Control subjects were tested once. RESULTS: At baseline, patients with POAG had significantly higher IOP than normal controls; CDI measures of the central retinal artery (CRA) and short posterior ciliary artery (SPCA) in the patients were significantly different from those in control subjects. In the patients, treatment resulted in a significant reduction in IOP and in CRA and SPCA resistance index. CONCLUSION: Untreated patients with POAG have altered circulation in the CRA and SPCA compared with subjects of similar age and gender. These measures recover significantly during topical beta blocker therapy. The relationship of the pretreatment deficit and posttreatment recovery of CDI blood flow measures to the progression and therapeutic impediment of glaucomatous optic nerve deterioration remains to be determined.

Adrenergic beta-Antagonists↗
PubMed1999

Mechanism of exercise-induced ocular hypotension.

PURPOSE: Although acute dynamic exercise reduces intraocular pressure (IOP), the factors that provoke this response remain ill-defined. To determine whether changes in colloid osmotic pressure (COP) cause the IOP changes during exercise, standardized exercise was performed after dehydration and hydration with isosmotic fluid. METHODS: Progressive cycle ergometer exercise to volitional exhaustion was performed after 4 hours' dehydration, and after hydration with 946 ml isosmotic liquid (345 mOsM). In each experiment, venous blood taken before and immediately after exercise was analyzed for hematocrit, plasma protein concentration, total plasma osmolality, and plasma COP. RESULTS: Exercise in both experiments significantly reduced IOP and elevated COP (each P < 0.01). Dehydration, compared with hydration, also significantly reduced IOP and elevated COP, when measured before and after exercise (P < 0.05). The correlation of mean IOP with mean COP, over the entire range created by varying exercise and hydration statuses, was statistically significant (r = -0.99; P < 0.001). In contrast, other indexes of hydration status, including hematocrit, total plasma osmolality, and plasma protein concentration, failed to change as IOP changed and failed to correlate with IOP, on either a group or individual basis, in conditions of varying levels of exercise and hydration. CONCLUSIONS: Acute dynamic exercise and isosmotic fluid ingestion each seem to change IOP through changes in COP.

Blood Proteins↗
PubMed1999

Regulation of intraocular pressure after water drinking.

PURPOSE: Acute oral water loading transiently elevates intraocular pressure (IOP) via mechanisms that remain unexplained. We tested the possibilities that water drinking might elevate IOP by creating a blood-aqueous osmotic gradient, or that it might instead alter active ion pumping and the formation of aqueous humor. METHODS: In the first series, 16 young, healthy individuals were studied during dehydration and for 1 hour after rehydration (14 mL H2O/kg body weight). Hematocrit, total plasma osmolality, and plasma colloid osmotic pressure were determined simultaneously with measurements of IOP. In a second series (N = 16), rehydration occurred after pretreatment with either placebo or a topical carbonic anhydrase inhibitor (1 drop 2% dorzolamide in each eye, 12 and 2 hours before oral water loading). RESULTS: In both series, mean IOP increased significantly 15 minutes after water ingestion and remained elevated above baseline for 45 minutes. In contrast, colloid osmotic pressure and hematocrit were unaltered by water drinking, and neither these variables nor total plasma osmolality correlated with IOP. In the second series, pretreatment with dorzolamide reduced baseline IOP, but failed to alter the magnitude or time course of IOP elevations induced by water drinking. CONCLUSION: Because water drinking failed to create a blood-ocular osmotic pressure gradient, neither vitreous hydration nor increased aqueous ultrafiltration can explain increases in IOP after acute hydration. Because the increase in ocular tension apparently also is independent of active bicarbonate pumping, factors affecting aqueous drainage must explain the water drinking effect.

Aqueous Humor↗
PubMed1999

Dyspepsia and Helicobacter pylori: test, treat or investigate?

The annual prevalence of dyspepsia in the UK is about 25%. Dyspepsia is one of the most common reasons for a patient to visit a primary care physician (PCP), accounting for between 3 and 4% of all PCP consultations. Antisecretory drugs prescribed by PCPs to relieve dyspepsia consume over 7% of the annual UK National Health Service drugs budget. In patients < 45 years old and in the absence of sinister symptoms (weight loss, anorexia or gastrointestinal blood loss) or treatment with non-steroidal anti-inflammatory drugs, three conditions account for the majority of cases of dyspepsia, namely functional (non-ulcer) dyspepsia (up to 60%), gastroesophageal reflux (5-15%) and peptic ulcer disease (15-25%). The discovery of Helicobacter pylori and its association with peptic ulcer disease led to a reevaluation of the management strategies used for dyspepsia. It became possible, using non-invasive testing, to determine whether a patient with dyspepsia was colonized with H. pylori and if not, it made peptic ulcer disease most unlikely. There are four main strategies for the management of patients with dyspepsia: empiric treatment, 'test and treat', 'test and investigate', or simply 'investigate'. The advantages, disadvantages and possible outcomes using each of these strategies are discussed using an evidence-based approach.

Diagnosis, Differential↗
PubMed1999

In vivo analysis of DNase I hypersensitive sites in the human CFTR gene.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator gene (CFTR) shows a complex pattern of expression. The regulatory elements conferring tissue-specific and temporal regulation are thought to lie mainly outside the promoter region. Previously, we identified DNase I hypersensitive sites (DHS) that may contain regulatory elements associated with the CFTR gene at -79.5 and at -20.5 kb with respect to the ATG and at 10 kb into the first intron. MATERIALS AND METHODS: In order to evaluate these regulatory elements in vivo we examined these DHS in a human CFTR gene that was introduced on a yeast artificial chromosome (YAC) into transgenic mice. The 310 kb human CFTR YAC was shown to restore the pheno-type of CF-null mice and so is likely to contain most of the regulatory elements required for tissue-specific expression of CFTR. RESULTS: We found that the YAC does not include the -79.5 kb region. The DHS at -20.5 kb is present in the chromatin of most tissues of the transgenic mice, supporting its non-tissue-specific nature. The DHS in the first intron is present in a more restricted set of tissues in the mice, although its presence does not show complete concordance with CFTR expression. The intron I DHS may be important for the higher levels of expression found in human pancreatic ducts and in lung submucosal glands. CONCLUSION: These data support the in vivo importance of these regulatory elements.

Animals↗
PubMed1999

Regional differences in retinal vascular reactivity.

PURPOSE: Although glaucomatous visual field defects are more common in the superior field than in the inferior field, microaneurysms are more frequent in the superior than in the inferior retina in diabetic retinopathy. The authors hypothesized that differences in vascular hemodynamics in the two areas might contribute to these phenomena. METHODS: The blood flow response to hyperoxia and hypercapnia was evaluated in peripapillary retinal tissue superior and inferior to the optic nerve head using confocal scanning laser Doppler flowmetry. In 14 young, healthy persons, blood flow was measured while breathing room air and during isocapnic hyperoxia (100% O2 breathing) and isoxic hypercapnia (PCO2 increased 15% above baseline). Histograms were generated from pixel-by-pixel analysis of retinal portions of superior and inferior temporal quadrants of the entire image. RESULTS: Baseline blood flow in the inferior temporal quadrant was significantly greater than in the superior temporal quadrant (P < 0.05). However, the inferior region failed to increase in perfusion during hypercapnia and experienced significant mean blood flow reduction; flow reduction in the pixels at the 25th, 50th, 75th, and 90th percentile of flow; and an increased percentage of pixels without measurable flow, during hyperoxia (each P < 0.05). In contrast, in the superior temporal region, hyperoxia failed to reduce blood volume, velocity, or flow, whereas hypercapnia significantly increased mean flow; increased flow in the pixels at the 25th, 50th, 75th, and 90th percentile of flow; and reduced the percentage of pixels without measurable flow (each P < 0.05). CONCLUSIONS: The inferior temporal quadrant of the peripapillary retina is, in comparison with the superior temporas region, less responsive to vasodilation and more responsive to vasoconstriction. These differences could contribute to different susceptibility to visual field defect or vascular dysfunction in the superior and inferior retina.

Adolescent↗
PubMed1998

Homologue scanning mutagenesis of heregulin reveals receptor specific binding epitopes.

The EGF domain of heregulin has all the receptor binding characteristics of full-length heregulin and has strong homology to the ligands for erbB-1. Despite this, it does not bind erbB-1 but instead binds erbB-3 and erbB-4. The sequence similarity between HRG and the erbB-1 ligands suggest that a few residues are responsible for receptor binding specificity. To determine the sequences involved in receptor binding, we performed homologue scanning mutagenesis on the EGF domain of HRGalpha using sequences of TGFalpha or EGF. We found three sets of mutations in the N-terminal subdomain that were responsible for receptor binding specificity. Mutations in the C-terminal subdomain affected the binding affinity, but did appear to confer any specificity.

Adenocarcinoma↗
PubMed1998

Effects of oxaceprol on the microcirculation in ischemia/reperfusion injury.

Oxaceprol, an established drug for treatment of degenerative joint disease, has recently been shown in vitro to reduce leukocyte adhesion to cultured endothelial cells and leukocyte extravasation in vivo in an arthritis animal model. The aim of this study was to examine the effects of Oxaceprol on the microcirculation of striated skin muscle. In the dorsal skinfold chamber of the awake Syrian golden hamster I/R injury was induced by applying a 4-hour complete pressure ischemia. Prior to the ischemia, after 30 minutes, 2 hours and 24 hours of reperfusion the following parameters were assessed in a blinded study: macromolecular leakage, leukocyte rolling fraction, adherent leukocytes, and functional capillary density (FCD). Rhodamine 6G to stain leukocytes in-vivo and FITC Dextran (MW 150,000) was used as a plasma marker. 15 minutes prior to reperfusion the animals received either an i.v. bolus infusion of Oxaceprol (50mg/kg) or an equivalent volume of saline, which was followed by a 45-minute continuous infusion at the same dose. At the conclusion of the experiment samples were collected from the chamber tissue for histological quantification of leukocyte extravasation using an esterase stain. Oxaceprol treatment resulted in a significant decrease of postischemic leukocyte adherence after 0.5 h and 2h of reperfusion. The histological sections revealed a significant reduction in the number of extravasated leukocytes. There was a reduction of macromolecular leakage and treatment also resulted in a preservation of tissue perfusion, as was indicated by a significant increase in FCD in the treatment group compared to the ischemia group. In summary, Oxaceprol was able to protect the tissue from ischemia/reperfusion injury.

Animals↗
PubMed1998

Regulation of retinal and optic nerve blood flow.

Blood flow to the retina and optic nerve remains constant over a range of elevated intraocular pressure or mean arterial pressure, independent of sympathetic activation (pressure autoregulation). In addition, increased metabolic activity in these tissues proportionally increases blood flow (metabolic autoregulation). At constant metabolic rate, altered arterial oxygen content reciprocally alters blood flow, leaving total oxygen delivery constant, while blood flow rises and falls with the arterial carbon dioxide tension. These responses are similar to those of the cerebral circulation. However, while aging, atherosclerosis, arterial hypotension, and individual variation may profoundly alter blood flow regulation and predispose to the development of illness, these factors remain largely unexplored.

Animals↗