BACKGROUND: Early photorefractive keratectomy ablations were of limited diameter and depth to maintain the integrity of the globe and to minimise postoperative haze. This study evaluated the effects of deeper, larger diameter wounds on refractive stability and corneal haze, and investigated the effects of ablation profile on wound healing and visual performance. METHODS: One hundred patients undergoing -3.00D and -6.00D corrections were randomised to receive 5 mm, 6 mm, or multizone treatments. The multizone treatment was 6 mm in diameter, but only the depth of the 5 mm treatment. Outcome was measured by Snellen visual acuity, residual refractive error, objective techniques for haze and halos, pupil diameter, subjective night vision, and requirement for retreatment. RESULTS: Overall, the results of 6 mm treatments were superior to those of 5 mm and multizone treatments: they had a smaller hyperopic shift (p < 0.01), a more predictable (p < 0.001) and stable refractive outcome, less haze (p < 0.05), smaller halos (p < 0.05), fewer subjective night vision problems, and fewer patients required retreatment. CONCLUSIONS: Analysis of these data and a literature review of corneal wound healing demonstrated that the improved outcome associated with the 6 mm beam did not relate to the depth of ablation. The factor with greatest apparent influence on the development of haze and regression was the slope of the wound surface over the entire area of the ablation. Tapering the wound edge provided no additional benefit, and contributed to night vision problems. It is, therefore, recommended that small diameter or multizone treatments should not be used in low and moderate myopia.

Adult↗

PubMed1996

In vivo human lens epithelial cell proliferation on the anterior surface of PMMA intraocular lenses.

AIMS: To study in vivo human lens epithelial cell proliferation on the anterior surface of PMMA implants and its interaction with postoperative blood-aqueous barrier breakdown in eyes undergoing cataract surgery. METHODS: A prospective study was carried out on three consecutive patient cohorts undergoing cataract surgery with intraocular lens implantation using three different surgical techniques which produce different anatomical relations between the implant and lens capsule. Specular microscopy of the anterior implant surface was used to document the natural history, topography, and density of lens epithelial cells and the laser flare and cell meter were used to measure postoperative blood-aqueous barrier breakdown. RESULTS: All groups showed lens epithelial cell proliferation onto the anterior surface of PMMA implants. This was initiated by and restricted to the region of anterior capsule-implant contact and decreased with the onset of anterior capsular opacification. Significant correlation was found in all groups between lens epithelial cell proliferation and postoperative blood-aqueous barrier breakdown. CONCLUSIONS: Human lens epithelial cell behaviour on PMMA surfaces in vivo differs from that seen in culture studies. Humoral factors in the aqueous, biomaterial properties of the implant, and its anatomical relations with the anterior and posterior lens capsule influence lens epithelial cell behaviour in vivo.

Analysis of Variance↗

PubMed1996

Ulcerative colitis complicated by renal cell carcinoma: a series of three patients.

Three patients are described in whom renal cell carcinoma was diagnosed between seven months and 14 years after the onset of ulcerative colitis. All three had required treatment with corticosteroids and azathioprine, as well as maintenance therapy with 5-aminosalicylate derivatives, for chronic active colitis. One patient had coexisting polymyalgia rheumatica; one had primary biliary cirrhosis. It is uncertain whether this association, which has not previously been described, has pathogenetic importance or has arisen simply by chance. Genetic predisposition or the effect of drug treatment, particularly immunosuppression, may be pertinent to the co-occurrence of these diseases.

Carcinoma, Renal Cell↗

PubMed1996

Drug and alcohol problems among individuals with severe mental illness in south London.

BACKGROUND: High rates of comorbid alcohol and drug disorders have previously been found among individuals with severe mental illnesses such as schizophrenia and bipolar affective disorders. Clinical and social outcomes have been reported to be worse in this group and service costs greater than in individuals with severe mental illness only. These 'dual diagnosis' patients have mainly been investigated in the USA, and there has been very little research in Europe, where patterns of substance abuse may be different. METHOD: All patients with psychotic illnesses who had any contact with the mental health services in a geographically defined sector in South London over a specified period were studied. Individuals with problems related to alcohol or drugs were identified using standardised interviews with subjects and their keyworkers. Data on psychiatric service use during the previous 2 years were also obtained. RESULTS: One hundred and seventy-one subjects with psychotic illnesses were interviewed (response rate: 78.4%). The one-year prevalence rate for any substance problem was 36.3% (95% CI = 29.1-43.5), for alcohol problems it was 31.6% (95% CI = 24.6-38.5), and for drug problems 15.8% (95% CI = 10.3-21.3). Young male subjects were at higher risk of having substance problems. Patients with substance problems had spent almost twice as many days in hospital as those without such problems over the previous two years (difference = 26.3 days, 95% CI = 3.8-48.7). CONCLUSIONS: The prevalence of substance problems among people suffering from severe mental disorders is high, and seems to be associated with greater use of in-patient services. This is a significant clinical problem, with cost implications. Further investigation is needed for adequate service provision.

Adolescent↗

PubMed1996

Angiographic abnormalities of experimental autoimmune uveoretinitis.

PURPOSE: Experimental autoimmune uveoretinitis (EAU) is an invaluable animal model for studying inflammatory eye disease in humans. Indocyanine green (ICG) is a fluorescent dye that can be used to image both retinal and choroidal vessels. This study was performed to examined the retinal and choroidal vascular abnormalities of a rat model of EAU using ICG and fluorescein as the contrast media to assess the suitability of this model for studying ICG angiographic abnormalities in inflammatory eye disease in humans. METHODS: Twenty-six black-hooded Lister rats were inoculated with bovine retinal S-antigen plus adjuvant with or without Bordetella pertussis antigen. Fluorescein and ICG angiograms were performed at different stages of clinical disease with a scanning laser ophthalmoscope. RESULTS: EAU was more severe and primarily choroidal disease in rats given Bordetella pertussis, but no animals showed evidence of dye leakage from large choroidal vessels. There was frank leakage of indocyanine green from retinal vessels. Leakage of both fluorescein and ICG retinal vessels largely correlated with disease activity. Retinal pigment epithelial lesions either corresponded to areas of hypofluorescence on the ICG angiogram alone or were represented by areas of ICG hyperfluorescence that had overlying areas of fluorescein leakage from retinal capillaries. CONCLUSIONS: This study has demonstrated the vascular abnormalities of this model of EAU using ICG and fluorescein as the contrast media. The suitability of this method for studying ICG angiographic abnormalities in inflammatory eye disease in humans is encouraging.

Animals↗

PubMed1996

A new non-contact corneal aesthesiometer (NCCA).

A novel method for testing the corneal nerve function, through non-invasive measurement of corneal sensitivity, is presented. The method of using a controlled pulse of air to stimulate the corneal surface is described. Technical information of the aesthesiometer's construction is given. Examples of the ability of the instrument to accurately locate the corneal sensitivity threshold using either a method of constant stimuli, or a method of limits, is described for 14 normal, non-lens wearing eyes. Measurements are made in millibars of air pressure required. Mean normal values found were 0.342 +/- 0.068 millibars. Discussion is made of the instrument's mode of action, its advantages over other invasive instruments, and potential clinical application.

Adult↗

PubMed1996

Eusol: the plastic surgeon's choice?

Many products are currently promoted for use on wounds. Edinburgh University Solution of Lime (Eusol) has recently received adverse publicity regarding its use in wound management. One hundred and twenty-four consultant plastic surgeons were surveyed regarding their use of Eusol. Ninety-five replies were obtained (77%); of those who replied, 78 (82%) still use Eusol, while nine out of 17 who do not are prevented from using it as they are unable to obtain necessary supplies. In plastic surgery, Eusol is still being used by plastic surgeons in specific situations.

Anti-Infective Agents↗

PubMed1996

Excimer laser phototherapeutic keratectomy for recurrent erosions: a clinical study.

BACKGROUND AND OBJECTIVE: Recurrent corneal erosion is a common corneal disease. It may be difficult to treat, with a number of patients suffering persistent symptoms despite having had conventional therapy. The aim of this study was to evaluate the usefulness of the excimer laser for the treatment of recurrent corneal erosions. PATIENTS AND METHODS: The authors studied 31 eyes of 24 patients who underwent excimer laser phototherapeutic keratectomy (PTK) for recurrent corneal erosion. Three eyes were treated during an acute episode of recurrent erosion. The remaining eyes were treated during a symptom-free interval. The affected area of epithelium was removed and a 25 pulse ablation was performed to Bowman's membrane. RESULTS: In 30 eyes there was a marked improvement in symptoms postoperatively, with no recurrences. However, 1 eye had one recurrent episode 2 weeks after PTK. Postoperatively, refraction and corneal topography were unaltered in all cases. CONCLUSIONS: Excimer laser PTK appears to be a safe and promising procedure for cases of recurrent corneal erosion refractory to medical treatment.

Adult↗

PubMed1996

The importance of the corneal epithelium in excimer-laser photorefractive keratectomy.

To evaluate the importance of the epithelium for postoperative regression we undertook excimer-laser photoreactive keratectomy (PRK) in six rabbits. After the epithelium had been removed mechanically, two rabbits underwent a -3.0 D procedure; two rabbits, a -6.0 D procedure; and two rabbits, a -9.0 D procedure. Refraction was monitored pre- and postoperatively using streak retinoscopy. Rabbits were killed at 3 weeks after PRK and the thickness of the corneal epithelium in the centre of the ablation zone and in an untreated area just outside the treatment zone was measured using light microscopy. At the time of killing, no stromal haze was visible on slit-lamp biomicroscopy. In all rabbits the thickness of the corneal epithelium over the untreated area was between 31.4 and 36.7 microns. In contrast, the thickness of the epithelium in the centre of the ablation zone in rabbits treated with a -3.0 D procedure was only slightly increased, and retinoscopy showed a change in refraction of around 3 D. All other rabbits showed a significant increase in epithelial thickness, whereas the amount of thickness correlated with the amount of myopic regression. One rabbit in the -6.0 D group showed an increase in epithelial thickness of 18.4 microns and a myopic regression of 1.5 D. In both rabbits in the -9.0 D group the amount of corneal tissue removed by the laser was nearly completely substituted by epithelial hyperplasia. Postoperative retinoscopy showed nearly the same refraction as had been obtained preoperatively. In summary, the postoperative control of epithelial thickness seems to be an important factor for the success of excimer-laser PRK and, in particular, for high degrees of myopia.

Animals↗

PubMed1995

Improved cationic lipid formulations for in vivo gene therapy.

The problem of assessing in vivo activity of gene delivery systems is complex. The reporter gene must be carefully chosen depending on the application. Plasmids with strong promoters, enhancers and other elements that optimize transcription and translation should be employed, such as the CMVint and pCIS-CAT constructs. Formulation aspects of cationic lipid-DNA complexes are being studied in several laboratories, and the physical properties and molecular organization of the complexes are being elucidated. Likewise, studies on the mechanism of DNA delivery with cationic lipids are accumulating which support the basic concept that the complexes fuse with biological membranes leading to the entry of intact DNA into the cytoplasm. Naked plasmid DNA administered by various routes is expressed at significant levels in vivo. This observation is not restricted to skeletal and heart muscle, but has been observed in lung, dermis, and in undefined tissues following intravenous administration. Most of the widely available cationic lipids, including Lipofectin, Lipofectamine and DC-cholesterol have a very poor ability to enhance DNA expression above the baseline naked DNA level, at least in lung. In this report we have revealed a novel cationic lipid, DLRIE, which can significantly enhance CAT expression in mouse lung by 25-fold above the naked DNA level. Other compounds are currently being evaluated which can enhance the naked DNA expression even higher. Plasmid vector improvements have led to further increase in in vivo lung expression, so that the net improvement is > 5,000-fold. Results of this nature are advancing the pharmaceutical gene therapy opportunities for synthetic cationic lipid based gene delivery systems.

Animals↗

PubMed1995

Analysis of consensus sequence patterns in Giardia cytoskeleton gene promoters.

Protein-coding genes in the ancient eukaryote Giardia lamblia lack typical promoter consensus elements. We have analysed the immediate 5' flanking sequences of seven genes of related function (structural cytoskeleton proteins) to identify shared DNA motifs that might have a role in transcription initiation. Transcription start sites for five genes have been determined previously. Genomic mapping and mRNA primer extension experiments demonstrate additionally that the genes for beta-giardin and median body protein are (i) present as single copies in the genome, (ii) transcribed with very short 5' leader sequences. Two search algorithms designed to extract conserved motifs from either aligned or non-aligned sequences independently discovered three sites constituting a common pattern in all seven promoters. Sites were optimally aligned using weight matrix building trials to achieve the maximum 'information content'. Profiling the information content of best alignments defines the extent of the homologies as: a 9 bp box (initiator) at the start site and upstream 18 and 6 bp boxes. The initiator is the most highly conserved element and contains a universal Py-A-Pu motif at which transcription starts. We show that the best matrices can be combined in a search pattern that correctly locates transcription start sites in genomic DNA sequences.

Algorithms↗

PubMed1995

Purification and characterization of recombinant cystic fibrosis transmembrane conductance regulator from Chinese hamster ovary and insect cells.

We have developed procedures to purify highly functional recombinant cystic fibrosis transmembrane conductance regulator (CFTR) from Chinese hamster ovary (CHO) cells to high homogeneity. Purification of CHO-CFTR was achieved using a combination of alkali stripping, alpha-lysophosphatidylcholine extraction, DEAE ion-exchange, and immunoaffinity chromatography. Insect CFTR from Sf9 cells was purified using a modification of the method of Bear et al. (Bear, C. E., Li, C., Kartner, N., Bridges, R. J., Jensen, T. J., Ramjeesingh, M. and Riordan, J. R. (1992) Cell 68, 809-818), which included extraction with sodium dodecyl sulfate, hydroxyapatite, and gel filtration chromatography. Characterization of the properties of purified CFTR from both cell sources using a variety of electrophysiological and biochemical assays indicated that they were very similar. Both the purified CHO-CFTR and Sf9-CFTR when reconstituted into planar lipid bilayers exhibited a low pS, chloride-selective ion channel activity that was protein kinase A- and ATP-dependent. Both the purified CHO-CFTR and Sf9-CFTR were able to interact specifically with the nucleotide photoanalogue 8-N3-[alpha-32P]ATP with half-maximal binding at 25 and 50 microM, respectively. These values compare well with those reported for 8-N3-[alpha-32P]ATP binding to CFTR in its native membrane form. Thus CFTR from either insect or CHO cells can be purified to high homogeneity with retention of many of the biochemical and electrophysiological characteristics of the protein associated in its native plasma membrane form. The availability of these reagents will facilitate further investigation and study of the structure and function of CFTR and its interactions with cellular proteins.

Adenosine Triphosphate↗