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J W Bainbridge

Publications and source records attributed to J W Bainbridge.

10 recordsLinked to original sources
PubMed2001

Gene replacement therapy in the retinal degeneration slow (rds) mouse: the effect on retinal degeneration following partial transduction of the retina.

The retinal degeneration slow (rds or Prph2(Rd2/Rd2)) mouse, a model of recessive retinitis pigmentosa, lacks a functional gene encoding peripherin 2. This membrane glycoprotein is required for the formation of photoreceptor outer segment discs. The striking feature of the rds mouse is the complete failure to develop outer segments. We have previously examined the short-term effect of gene replacement therapy using an adeno-associated (AAV) vector and demonstrated induction of outer segments and improvement of photoreceptor function. Here we have extended our analysis and have demonstrated that the potential for ultrastructural improvement is dependent upon the age at which animals are treated, but the effect of a single injection on photoreceptor ultrastructure may be long-term. However, there was no significant effect on photoreceptor cell loss, irrespective of the date of administration, despite the improvements in morphology and function. Our investigation excluded procedure-related damage, vector toxicity and immune responses as major factors which might counteract the benefits of photoreceptor restoration, but suggested that transgene over-expression is of significance. These findings suggest that successful gene therapy in patients with photoreceptor defects may ultimately depend upon intervention in early stages of disease and upon accurate control of transgene expression.

Animals↗
PubMed2001

In vivo gene transfer to the mouse eye using an HIV-based lentiviral vector; efficient long-term transduction of corneal endothelium and retinal pigment epithelium.

We have evaluated the transduction profiles of an HIV-based lentiviral vector delivered regionally to ocular tissues in vivo. Following subretinal injection, a green fluorescent protein (GFP) reporter gene was efficiently and stably expressed in retinal pigment epithelial (RPE) cells. Limited transduction of adjacent photoreceptors occurred in newborn mice, but was inefficient in adult animals. Injection of the vector into the anterior chamber resulted in efficient and stable transduction of corneal endothelial cells. Efficient in vivo gene transfer into cells of the corneal endothelium and retinal pigment epithelium by lentiviral vectors may therefore offer a valuable approach to the treatment of disorders of the cornea and outer retina.

Animals↗
PubMed2000

Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy.

The gene Prph2 encodes a photoreceptor-specific membrane glycoprotein, peripherin-2 (also known as peripherin/rds), which is inserted into the rims of photoreceptor outer segment discs in a complex with rom-1 (ref. 2). The complex is necessary for the stabilization of the discs, which are renewed constantly throughout life, and which contain the visual pigments necessary for photon capture. Mutations in Prph2 have been shown to result in a variety of photoreceptor dystrophies, including autosomal dominant retinitis pigmentosa and macular dystrophy. A common feature of these diseases is the loss of photoreceptor function, also seen in the retinal degeneration slow (rds or Prph2 Rd2/Rd2) mouse, which is homozygous for a null mutation in Prph2. It is characterized by a complete failure to develop photoreceptor discs and outer segments, downregulation of rhodopsin and apoptotic loss of photoreceptor cells. The electroretinograms (ERGs) of Prph2Rd2/Rd2 mice have greatly diminished a-wave and b-wave amplitudes, which decline to virtually undetectable concentrations by two months. Subretinal injection of recombinant adeno-associated virus (AAV) encoding a Prph2 transgene results in stable generation of outer segment structures and formation of new stacks of discs containing both perpherin-2 and rhodopsin, which in many cases are morphologically similar to normal outer segments. Moreover, the re-establishment of the structural integrity of the photoreceptor layer also results in electrophysiological correction. These studies demonstrate for the first time that a complex ultrastructural cell defect can be corrected both morphologically and functionally by in vivo gene transfer.

Animals↗
PubMed2000

Decreased visual acuity in patients with cytomegalovirus retinitis and AIDS.

PURPOSE: To investigate the causes of decreased visual acuity in patients with cytomegalovirus (CMV) retinitis in the acquired immunodeficiency syndrome (AIDS). METHODS: All human immunodeficiency virus (HIV)-positive patients seen in two ophthalmology units over a 15 month period from September 1996 were included in this retrospective study. A detailed ophthalmic examination was performed on all patients and in addition those with CMV retinitis underwent serial fundus photography. Decreased visual acuity was defined as a best corrected visual acuity < or = 6/12. CMV and retroviral treatment, CD4+ count and HIV viral load were also documented for each patient. RESULTS: Of 110 patients seen over the 15 month period, 26 (41 eyes) had a diagnosis of CMV retinitis. Twelve patients (16 eyes) with CMV retinitis had decreased visual acuity. The decreased visual acuity in 7 eyes was initially due to the CMV retinitis involving the macula and the optic nerve. Retinal detachment was responsible in 2 eyes and optic nerve atrophy in 1 eye. In 6 eyes (4 patients) the decreased visual acuity was due to a maculopathy--cystoid macular oedema and/or an epiretinal membrane in the presence of an inactive zone 2 or 3 CMV retinitis--with all these patients exhibiting a vitritis of varying grade. The decreased visual acuity in the maculopathy subgroup was irreversible in all except 1 eye, and 2 eyes in this category later developed a cataract. CONCLUSION: In this series, CMV-retinitis-'related' maculopathy was a major (38%) cause of decreased visual acuity, occurring in the absence of zone 1 retinitis and despite inactive peripheral CMV retinitis. A varying degree of vitritis was an associated feature in all these patients. This study therefore highlights maculopathy as an important and previously unrecognised significant cause of visual morbidity in CMV retinitis.

AIDS-Related Opportunistic Infections↗
PubMed1999

Ocular complications of intravenous cidofovir for cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To describe the frequency of anterior uveitis and ocular hypotony in cidofovir-treated patients with acquired immune deficiency syndrome (AIDS)-related cytomegalovirus (CMV) retinitis. METHODS: A retrospective review was performed of all patients with AIDS-related CMV retinitis during a 12-month period. The CMV retinitis activity, concurrent illnesses and medications, and CD4+ lymphocyte count were recorded in addition to the degree of anterior chamber inflammation and intraocular pressure at each visit. The frequency of uveitis and ocular hypotony in cidofovir-treated patients was determined and the possible influence of other ocular and systemic factors considered. RESULTS: Eight of 9 patients on cidofovir developed anterior uveitis. The cellular anterior chamber activity resolved with topical corticosteroid administration in all eyes with uveitis but significant flare persisted despite topical steroids in 3 patients. Posterior synechiae responded poorly to topical mydriatic therapy, resulting in inadequate mydriasis which significantly limited the fundal view. One patient developed a visually significant unilateral hypotonous maculopathy. CONCLUSIONS: Patients treated with intravenous cidofovir for AIDS-related CMV retinitis are at significant risk of ocular adverse effects. Prompt treatment with topical corticosteroids and mydriatics may control uveitis and in some cases cidofovir treatment may be cautiously continued. In the event of ocular hypotony cidofovir should be discontinued in favour of an alternative anti-cytomegaloviral agent.

AIDS-Related Opportunistic Infections↗
PubMed1998

Is eye padding routinely necessary after uncomplicated phacoemulsification?

PURPOSE: To investigate the value of eye padding following uncomplicated phacoemulsification under peribulbar anaesthesia. METHODS: A prospective randomised controlled study was conducted to compare the effect of a conventional eye pad and shield with that of a clear eye shield applied without a pad in 83 patients undergoing routine phacoemulsification under peribulbar anaesthesia without lid block. The primary outcome measures were corneal fluorescein staining, discomfort, diplopia and mobility. RESULTS: Moderate or severe corneal fluorescein staining on the first post-operative day was significantly more common in the pad and shield group (39%) than in the clear shield group (19%) (p < 0.01). There was no significant difference in post-operative pain as measured either by visual analogue scale or by categorical pain scale. Forty per cent of the clear shield group reported transient post-operative diplopia during the immediate post-operative period compared with 7% of the pad and shield group (p < 0.001). There was no significant difference in reported mobility between the two groups. CONCLUSIONS: Following phacoemulsification under peribulbar anaesthesia, the use of a gauze eye pad is associated with greater corneal fluorescein staining than a clear plastic shield without pad and offers no reduction in discomfort. A clear shield protects the globe against direct trauma, is associated with reduced moderate to severe corneal staining and facilitates vision in the early post-operative period. Transient diplopia reported by some patients given a clear shield is not disabling and would not be expected to occur in patients with one seeing eye. The use of a clear shield alone is a safe alternative to eye padding and offers important advantages in patients with one seeing eye.

Aged↗
PubMed1998

A prospective controlled study of a 10/0 absorbable polyglactin suture for corneal incision phacoemulsification.

PURPOSE: To evaluate the performance of a 10/0 monofilament absorbable polyglactin suture for temporal 5.2 mm corneal incision phacoemulsification. METHODS: A prospective randomised controlled study of 49 patients undergoing phacoemulsification with a sutured temporal 5.2 mm corneal section was conducted to compare the refractive results and complications of a 10/0 monofilament absorbable polyglactin suture with 10/0 nylon. RESULTS: Thirty-eight patients completed the study. There was no significant difference in induced astigmatism between the two groups. All absorbable sutures were intact at 1 week. Six weeks post-operatively the absorbable suture was still intact in 1 (6%) patient, present but broken in 4 (24%) and completely absent in 12 (70%) patients. All polyglactin sutures had been completely absorbed by 12 weeks. Absorption of the polyglactin sutures was associated with mild localised corneal haze in 3(18%) cases (p = 0.055). One of the 18 patients (6%) in the polyglactin suture group presented with iris prolapse associated with knot failure 1 week post-operatively. There was no significant difference in foreign body symptoms between the two groups. CONCLUSIONS: 10/0 polyglactin sutures maintain adequate tensile strength during the immediate post-operative period for small incision surgery and are associated with minimal induction of astigmatism. Their subsequent absorption obviates the need for routine suture removal. Suture absorption is well tolerated although in some cases a mild degree of local tissue reaction raises concern about possible mechanisms of absorption. The risk of knot failure may be reduced by an alternative suture tying technique. 10/0 monofilament polyglactin is an attractive option when a suture is required during small incision cataract surgery.

Absorption↗
PubMed1998

Intraocular lens implants and risk of endophthalmitis.

AIM: To investigate the possible association between the use of three piece foldable silicone polypropylene (SPP) intraocular lenses (IOLs) and an increased risk of postoperative endophthalmitis. METHODS: A retrospective analysis was conducted of all cases of postoperative endophthalmitis following phacoemulsification surgery in a single unit over a 3 year period. The incidence of postoperative endophthalmitis in eyes with SPP IOLs was compared with the incidence in eyes with single piece polymethylmethacrylate (PMMA) IOLs. RESULTS: 772 cataract extractions by phacoemulsification were performed. One (0.16%) of the 622 patients with PMMA IOLs developed endophthalmitis. Excluding one patient who had aplastic anaemia, five (3.33%) of 150 patients with SPP IOLs developed endophthalmitis. The relative risk for postoperative endophthalmitis associated with the use of the SPP IOL compared with the PMMA IOL was 20.1 (p = 0.015). CONCLUSION: This study adds further evidence to the concept that SPP IOLs can be a significant risk factor in the development of postoperative endophthamitis.

Aged↗
PubMed1990

AIDS education in rural Uganda--a way forward.

A survey of acquired immunodeficiency syndrome (AIDS)-related knowledge and attitudes was conducted during July and August 1988 in rural SW Uganda. The aim was to assess the impact of Uganda's AIDS education programme and to consider how future programmes could be more effectively implemented. Four hundred and seventy-six individuals aged 12-45 years were selected by a quota method, to form a sample stratified by age and sex. Mass AIDS education has successfully raised levels of knowledge but misconceptions persist. However, it has failed, firstly, to stress the urgency of AIDS as a personal issue, and secondly, to change negative attitudes toward people with AIDS: 57% would avoid or stigmatise an individual with AIDS. Unexpectedly, findings show that a correlation exists (P less than 0.05) between high levels of 'correct' beliefs and negative attitudes toward people with AIDS. To achieve future behavioural and attitude changes, possible ways forward for Ugandan AIDS education include involvement of HIV carriers in education, small-scale targetted approaches developed by active participation of the target group and through role playing of people with AIDS.

Acquired Immunodeficiency Syndrome↗