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Biomedical subjects

A Harris

Publications and source records attributed to A Harris.

At least 109 records · Page 6Linked to original sources

Regional differences in optic disc and retinal circulation.

PURPOSE: To determine regional differences in the circulation of the optic disc, the peripapillary choroid and the retinal vessels using the techniques of computerized image analysis and fluorescein angiography. METHODS: Ten young normal subjects were studied. Fluorescein angiography was performed with a scanning laser ophthalmoscope. The rate of filling of fluorescein or slope was measured in the four quadrants of the optic disc, the peripapillary choroid and the major retinal arteries and veins. A total of 125 points was measured from each image of the fluorescein angiograms for a total of 20 to 30 images. Retinal vessel width was measured using computerized image analysis. RESULTS: Comparison of the rates of filling of fluorescein or slopes showed significant differences from zero among the four quadrants of the optic disc (p= 0.01 to <0.02), of the peripapillary choroid (p=0.01 to <0.05) and among the major retinal arteries (p=0.01 to <0.02) and retinal veins (p=0.02 to <0.05). No significant differences were noted between the quadrants for retinal arterial width with the retinal veins only showing a significant difference between the inferior nasal and inferior temporal vein (p=0.02 to <0.05). CONCLUSION: Evaluation of the circulation of the optic disc, retina, and peripapillary choroid should take into account regional differences among these structures.

Adult↗

Adolescent-parent interactions in middle-class African American families: longitudinal change and contextual variations.

Family interactions were examined longitudinally over 2 years in 79 middle-class African American families with early adolescents. Mothers and adolescents (as well as fathers and adolescents and triads in 2-parent families) were videotaped discussing a conflict for 10 min. A macro-coding system (J. G. Smetana, J. Yau, A. Restrepo, & J. L. Braeges, 1991) was modified to be culturally sensitive to African American families. Interaction ratings were reduced, through principal-components analyses, into composite variables. After control for family income, mothers' communication in triadic interactions became less positive over time. Both mothers' and fathers' communication was more positive in dyadic than triadic interactions. In triadic interactions, mothers validated sons more than daughters, and in dyadic interactions with either parent, boys were more receptive to parents than were girls. Findings extend previous research on adolescent-parent relationships to African American families.

Adolescent↗

Optic nerve head blood flow measurements in non-arteritic anterior ischaemic optic neuropathy.

PURPOSE: To determine whether a decrease in blood flow, measured by the Heidelberg retiinal flowmeter, can characterise a disc at risk and predict the occurrence of non-arteritic anterior ischaemic optic neuropathy (NAION). METHODS: Blood flow, volume and velocity were measured in the optic nerve heads of 14 unaffected fellow eyes of patients with unilateral NAION, and compared with those of the affected eyes and of the eyes of 7 age-matched healthy controls. RESULTS: The affected eyes were found to differ from the unaffected eyes in all three haemodynamic parameters. Flow (measured in arbitrary units) is the most important parameter to be taken into consideration. Blood flow was significantly lower in affected than in unaffected eyes (upper rim, p < 0.05; lower rim, p < 0.025). It was also significantly lower in the unaffected eyes than in the healthy control eyes (p < 0.005, upper and lower rims), and in the affected eyes than in the control eyes (p < 0.00005, upper and lower rims). CONCLUSION: Decreased blood flow in the optic nerve head may indicate a risk for NAION and be considered a characteristic of the disc at risk.

Aged↗

The macrophage - a novel system to deliver gene therapy to pathological hypoxia.

The use of activated macrophages in the treatment of cancer has been largely ineffectual. By 'arming' these cells with the ability to express a therapeutic gene we demonstrate significant advances in the efficacy of this approach. We have used a hypoxia-regulated adenoviral vector to transduce human macrophages with either a reporter or a therapeutic gene encoding human cytochrome P4502B6 (CYP2B6). Infiltration of transduced macrophages into a tumour spheroid results in induction of gene expression. We demonstrate significant tumour cell killing only in the presence of cyclophosphamide via activation by P4502B6 and show that this can be further targeted to tumours through hypoxia regulated gene expression. Gene Therapy (2000) 7, 255-262.

Adenoviridae↗

Benign anastomotic stricture following transthoracic subtotal oesophagectomy and stapled oesophago-gastrostomy: risk factors and management

AIMS: Benign anastomotic stricture (BAS) is a common cause of dysphagia following oesophagectomy. The aim of this study was to assess the incidence of BAS, identify risk factors for its development and evaluate the results of postoperative endoscopic dilatation. METHODS: A consecutive series of 234 patients undergoing oesophagectomy with a stapled intrathoracic oesophagogastric anastomosis (Autosuture CEEA gun) between April 1990 and April 1999 were studied. BAS was defined as dysphagia with anastomotic narrowing (XQ200 endoscope) and no suspicion of recurrence. Statistical analysis was by the chi2 and Mann-Whitney U tests. RESULTS: The postoperative mortality rate was 5 per cent (12 of 234) and the anastomotic leak rate 3 per cent (six of 234). One-third of patients (70 of 222) who survived surgery re-presented with dysphagia; 5 per cent (11 of 222) were found to have proven local recurrence and 27 per cent (59 of 222) BAS. The median time to development of BAS was 92 (range 24-210) days. BAS formation was significantly related to the size of the staple gun employed: 21 mm, 80 per cent (eight of ten); 25 mm, 32 per cent (25 of 78); 28 mm, 23 per cent (19 of 81); 31 mm, 19 per cent (seven of 37) and 34 mm, 0 per cent (none of five) (chi2 = 18.3, 4 d.f., P < 0.01). All patients underwent radiographically controlled endoscopic dilatation with no complications. Recurrent BAS occurred in over half of these patients (32 of 59), who had a median of 2 (range 2-17) recurrences all resolving within 532 (mean interval 68) days. Recurrent BAS formation was also significantly related to the size of the staple gun employed (chi2 = 11.6, 4 d.f., P < 0.05). Following the introduction of the Autosuture 'tilt-top' device in July 1995 the median size of gun used rose from 25 to 28 mm with an overall decrease in the incidence of BAS from 33 to 21 per cent (chi2 = 4.0, 1 d.f., P < 0.05). All patients with anastomotic leaks survived and none subsequently developed BAS. Similarly, no association was found between the development of BAS and the anastomotic site (measured from incisors), tumour subtype, resection margin length, sex, age or preoperative cardiorespiratory status. CONCLUSIONS: Staple gun size is an important risk factor for BAS formation and 'tilt-top' devices enable the use of a larger head with a subsequently lower incidence of BAS. Endoscopic dilatation is an effective treatment for BAS which rarely recurs and always resolves within 18 months.

Journal Article↗

Dermatitis following systemic prednisolone: patch testing with prednisolone eye drops.

Although positive reactions to topical corticosteroids can occur in over 1% of a patch-test population, systemic reactions to oral corticosteroids are uncommon. A 45-year-old woman who gave a clear history of the generalization of a cutaneous eruption following oral prednisolone was positive on patch testing using prednisolone eye drops.

Administration, Oral↗

Platelet-derived endothelial cell growth factor expression and angiogenesis in cervical intraepithelial neoplasia and squamous cell carcinoma of the cervix.

Growth and metastatic spread of invasive carcinoma depends on angiogenesis, the formation of new blood vessels. Platelet-derived endothelial cell growth factor (PD-ECGF) is an angiogenic growth factor for a number of solid tumors, including lung, bladder, colorectal, and renal cell cancer. Cervical intraepithelial neoplasia (CIN) is the precursor to squamous cell cervical carcinoma (SCC). Mean vessel density (MVD) increases from normal cervical tissue, through low- and high-grade CIN to SCC. We evaluated PD-ECGF immunoreactivity and correlated its expression with MVD in normal, premalignant, and malignant cervical tissue. PD-ECGF expression was assessed visually within the epithelial tissues and scored on the extent and intensity of staining. MVD was calculated by counting the number of vessels positive for von Willebrand factor per unit area subtending normal or CIN epithelium or within tumor hotspots for SCC. Cytoplasmic and/or nuclear PD-ECGF immunoreactivity was seen in normal epithelium. PD-ECGF expression significantly increased with histologic grade from normal, through low- and high-grade CIN, to SCC (P < .02). A progressive significant increase in the microvessel density was also seen, ranging from a mean of 28 vessels for normal tissue to 57 for SCC (P < .0005). No correlation was found between PD-ECGF expression and MVD (P = .45). We conclude that PD-ECGF expression and MVD increase as the cervix transforms from a normal to a malignant phenotype. PD-ECGF is thymidine phosphorylase, a key enzyme in the activation of fluoropyrimidines, including 5-fluorouracil. Evaluation of PD-ECGF thymidine phosphorylase expression may be important in designing future chemotherapeutic trials in cervical cancer.

Carcinoma, Squamous Cell↗

Endothelin-1-mediated retinal artery vasospasm and the rabbit electroretinogram.

Electroretinogram (ERG) changes invariably accompany the selective interruption of the retinal circulation that occurs in human central retinal artery occlusion. Since arteriolar ligation or ocular hypertension in the rabbit eye is occasionally used to model human central retinal artery occlusion, we conducted the present study to determine whether selective interruption of the retinal circulation of the rabbit eye alters retinal function as measured by the ERG. The vasoconstrictor, endothelin-1, was injected into the vitreous of rabbits' eyes to induce complete vasospasm and selective interruption of the retinal circulation. This procedure was compared to vascular ligation of the ophthalmic and ciliary arteries in which both the retinal and choroidal circulations were interrupted. A total of 8 rabbits was studied. Circulation was monitored angiographically in half of the eyes, and retinal function was monitored by the ERG in the remaining eyes. Endothelin-1 obliterated retinal arteriolar blood flow without affecting choroidal blood flow for at least 1 hr. Although ERG a-wave amplitude showed a small decline over 2 hr, b-wave and oscillatory potential amplitudes (measures of inner retinal function) showed no loss over this period. In contrast, ligation of the ophthalmic and ciliary arteries produced complete obliteration of both retinal arteriolar and choroidal blood flow and complete loss of the ERG after 2 min. Endothelin-1 induces acute, selective interruption of retinal arteriolar blood flow which has no significant physiologic effect on inner retinal function of the rabbit as monitored by the ERG. The avascular rabbit retina appears to be a poor choice for modeling human retinal artery occlusion.

Animals↗

Randomized, placebo-controlled pilot study of divalproex sodium in the treatment of acute exacerbations of chronic schizophrenia.

Experimental and clinical data suggest that GABA-ergic drugs such as valproate may have a potential role in the treatment of schizophrenia. The authors designed a 21-day prospective, double-blind, randomized, placebo-controlled pilot study of divalproex sodium as add-on treatment to haloperidol in 12 hospitalized patients with acute exacerbations of chronic schizophrenia. All patients received haloperidol 10 mg/day for 3 days and 15 mg/day for the remaining 18 days. In addition, five patients were randomly assigned to receive divalproex augmentation and seven to receive placebo. The divalproex dose was adjusted to a target serum concentration of 75 microg/mL for 2 weeks; placebo replaced divalproex during the third and last weeks to determine any carryover effect. Psychiatric rating scales were administered at baseline and on days 7, 14, and 21. Although the placebo group improved with haloperidol treatment, the divalproex group demonstrated greater improvement. On day 21, the divalproex group had greater improvement from baseline on the Clinical Global Impression Scale (p < or = 0.04), Brief Psychiatric Rating Scale (p < or = 0.13), and Schedule for Assessment of Negative Symptoms scores (p < or = 0.007). After divalproex withdrawal on day 15, a carryover effect was observed during week 3. The authors concluded that the addition of divalproex sodium to standard antipsychotic drugs may prove effective in relieving the symptoms of acute schizophrenia. Future studies may benefit from the design of this pilot study. However, it is premature to apply this augmentation strategy in the clinical setting just yet because of the small sample size and the likely heterogeneity of the disorder.

Acute Disease↗

Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glaucoma.

PURPOSE: To investigate the relationship between the effect of carbon dioxide (CO2) inhalation or oral nilvadipine, a calcium-channel blocker, on orbital blood flow in patients with normal-tension glaucoma, as determined by color Doppler imaging. PATIENTS AND METHODS: Sixteen patients with normal-tension glaucoma (mean age, 55.6+/-9.8 years; male:female ratio, 3:13) underwent color Doppler imaging to measure the resistance index, and peak systolic and end-diastolic blood flow velocities of the ophthalmic artery, central retinal artery, and nasal and temporal short posterior ciliary arteries. Measurements were taken before and during CO2 supplementation sufficient to increase the end-tidal CO2 partial pressure by 10%. The color Doppler imaging measurements were repeated after 2 to 4 weeks of treatment with 2 mg oral nilvadipine, and comparisons were made between the effects of the two treatments. RESULTS: Both CO2 inhalation and nilvadipine treatment significantly reduced the resistance index in the central retinal artery, nasal short posterior ciliary artery, and temporal short posterior ciliary artery. There was a significant correlation between the effects of the two treatments on the difference in the resistance indexes of the ophthalmic artery and central retinal artery, but not on those of the nasal or temporal short posterior ciliary artery. CONCLUSIONS: Both CO2 inhalation and oral nilvadipine significantly reduce the resistance index measured by color Doppler imaging in orbital vessels. The effect of oral nilvadipine might be predicted by CO2 inhalation in patients with normal-tension glaucoma.

Administration, Inhalation↗

Risk management in practice: how are we managing?

Aims to identify awareness of and involvement in risk assessments, training, incident reporting, information giving and consenting in an acute health care context. Explores how nurse managers perceived risk management as a concept and if they saw advanced neonatal nurse practitioners having a role to play in this activity. The method used was a postal survey of 62 nurse managers or clinical specialists responsible for neonatal nursing care services within NHS Trusts in the UK. Results show that while the nurse managers studies understood the definition of risk management in general, they were more vague about certain aspects of that definition. The nurse managers appeared to be passive in their dissemination and taking forward of risk management strategies, rather than proactively "promoting and helping them forward" as may be expected in facilitative managerial behaviour. Concludes that the challenges of clinical governance demand more proactive approaches to effect and demonstrate change, and support ongoing clinical quality improvements.

Attitude of Health Personnel↗

Do sex and hormonal status influence choroidal circulation?

AIMS: To investigate the relation between pulse amplitude (PA), pulsatile ocular blood flow (POBF), and sex and hormonal status. METHODS: Measurements of POBF and PA were obtained by ocular blood flow tonography in 76 healthy subjects: 32 males and 44 females (age range 17-77 years). Females were divided into two age groups: group 1 (premenopausal) 17-42 years, and group 2 (post-menopausal) 55 years old and over. Two groups of age matched males served as controls. RESULTS: Premenopausal females demonstrated a significantly higher rate of POBF and PA than age matched males and post-menopausal females. CONCLUSION: Sex and hormonal status were shown to influence choroidal circulation.

Adolescent↗

Altitudinal visual field asymmetry is coupled with altered retinal circulation in patients with normal pressure glaucoma.

AIM: To compare the effect of altitudinal asymmetric glaucomatous damage on retinal microcirculation in patients with normal pressure glaucoma (NPG). METHODS: In a prospective cross sectional study patients with NPG (washed out for antiglaucomatous therapy) and altitudinal asymmetric perimetric findings between the superior and inferior hemisphere (Humphrey 24-2) (n=18) were included and compared with 20 NPG patients with symmetrical field defects and 18 healthy subjects. Fluorescein angiograms were performed using a scanning laser ophthalmoscope. Using digital image analysis, arteriovenous passage time (AVP) and vessel diameters were assessed for comparison of corresponding affected and less affected temporal arcades. RESULTS: Both affected and less affected hemispheres showed significantly prolonged AVP times (p<0.001) when compared with healthy subject data. In hemispheres with more severe glaucomatous field loss the AVP times were significantly (p=0.04) prolonged compared with the less affected hemisphere (AVP affected 3.1 (SD 7) seconds v AVP less affected 2.61 (1.4) seconds). There was no asymmetry effect on arterial and venous diameter measurements. CONCLUSION: Altitudinal visual field defects are linked together with circulatory deficits of the retinal tissue. The attenuated circulation seems to be a considerable factor in the natural course of glaucomatous optic neuropathy.

Cross-Sectional Studies↗

Ovine male genital duct epithelial cells differentiate in vitro and express functional CFTR and ENaC.

To investigate the biology of the male genital duct epithelium, we have established cell cultures from the ovine vas deferens and epididymis epithelium. These cells develop tight junctions, high transepithelial electrical resistance, and a lumen-negative transepithelial potential difference as a sign of active transepithelial ion transport. In epididymis cultures the equivalent short-circuit current (I(sc)) averaged 20.8+/-0.7 microA/cm(2) (n = 150) and was partially inhibited by apical application of amiloride with an inhibitor concentration of 0.64 microM. In vas deferens cultures, I(sc) averaged 14.4+/-1.1 microA/cm(2) (n = 18) and was also inhibited by apical application of amiloride with a half-maximal inhibitor concentration (K(i)) of 0.68 microM. The remaining amiloride-insensitive I(sc) component in epididymis and vas deferens cells was partially inhibited by apical application of the Cl(-) channel blocker diphenylamine-2-carboxylic acid (1 mM). It was largely dependent on extracellular Cl(-) and, to a lesser extent, on extracellular HCO(-)(3). It was further stimulated by basolateral application of forskolin (10(-5) M), which increased I(sc) by 3.1+/-0.3 microA/cm(2) (n = 65) in epididymis and 0.9+/-0.1 microA/cm(2) (n = 11) in vas deferens. These findings suggest that cultured ovine vas deferens and epididymis cells absorb Na(+) via amiloride-sensitive epithelial Na(+) channels (ENaC) and secrete Cl(-) and HCO(-)(3) via apical cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels. This interpretation is supported by RT-PCR data showing that vas deferens and epididymis cells express CFTR and ENaC mRNA.

Amiloride↗

Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids.

Not all asthma can be adequately controlled, despite the use of high-dose inhaled corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in the pathogenesis of asthma, we hypothesized that the leukotriene receptor antagonist zafirlukast, in combination with high-doses of inhaled corticosteroids, might be efficacious in severe asthma. In a double-blind, parallel group study, 368 chronic adult asthmatic patients treated with inhaled corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of asthma symptoms during the run in period of the study, were randomly assigned to receive additional treatment with a high dose of zafirlukast (80 mg twice daily) (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p < 0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2 to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids, zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk of an asthma exacerbation, suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids.

Administration, Inhalation↗