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Biomedical subjects

I J Constable

Publications and source records attributed to I J Constable.

At least 145 records · Page 8Linked to original sources

Clinical results of hydrogel lens implantation.

Polymethylmethacrylate has proven to be a useful intraocular lens (IOL) implant material and remains the most widely used material for the fabrication of IOLs. Complications, however, from IOL implantation still occur. A hydrogel lens has been designed for posterior chamber placement. A clinical study from August 1983 to June 1985 was undertaken to determine the safety and efficacy of this new lens manufactured from 38% poly HEMA. The noninflammatory postoperative complications were limited to lens decentration and opacification of the lens capsule. Three cases of posterior capsule opacification required YAG laser capsulotomy. Laser capsulotomy is feasible and the lens appeared to be more resistant to damage from the YAG laser than polymethylmethacrylate lenses. In general, the material appeared to be well tolerated and there have been no cases of persistent iritis or clinically detectable cystoid macular edema. If the visual acuity outcome by age decade for all patients irrespective of follow-up time is considered, 92% of patients achieved 20/40 or better corrected visual acuity.

Aged↗

Mass screening of the optic disc for glaucoma: a follow-up study.

Because of the high false positive and negative rates for detection of suspects when screening for glaucoma by tonometry, we screened 12 156 subjects over the age of 40 years or with a stated family history of glaucoma by examining the optic discs. This was followed by Schiotz tonometry. Eight hundred and twelve (6.7%) suspects were referred to their primary physician for investigation by an ophthalmologists. A database program was used to send out follow-up letters to both suspects and ophthalmologists. Three hundred and seventy-nine replies were received from ophthalmologists: 100 (26.4%) of these suspects had ocular hypertension and 68 (17.9%) had glaucoma. Of these 68, 60 (15.8%) had chronic simple glaucoma, five (1.3%) had secondary open-angle glaucoma, and three (0.79%) had primary closed-angle glaucoma. The prevalence of all types of glaucoma in this group for which follow-up was obtained was at least 0.56% of the total number screened. Assuming that the prevalence was similar for the group for whom no replies were obtained, the prevalence of glaucoma in this population is approximately 1.19%. Screening by optic disc examination is therefore likely to detect most cases of glaucoma.

Aged↗

Trachoma: 1985 update in Western Australia.

Aboriginal preschool and school children were surveyed in the Eastern Goldfields Region and the Eastern Kimberley Region of Western Australia between 1979 and 1985. Statistics from these surveys show that there has been an apparent change in pattern of follicular trachoma since the National Trachoma and Eye Health Programme in some of the communities. The prevalence of follicular trachoma in the 0 to 9 year old age groups had declined from 26.4% in 1977 to 8.8% in 1984/1985 in the Eastern Goldfields and Red Centre combined (0.10 greater than p greater than 0.05). The prevalence reduction occurred in areas where there have been improvements in school hygiene and housing. The prevalence of cicatricial trachoma has also apparently declined from 65% in 1977 to 39% in 1985 in the Red Centre, from 39% in 1977 in the Eastern Goldfields to 21.7% in 1985, and from 58% in 1977 to 24.9% in 1985 in the Eastern Kimberley, Communities at risk were identified and recommendations made for frequency of continued screening, depending on age, distribution and location.

Adolescent↗

Prevalence of diabetic complications in relation to risk factors.

The prevalence of diabetic complications is reported from a cross-sectional study of rural diabetic subjects in Western Australia. Logistic-regression analysis has been used to discover potential risk factors associated with each complication. A distinction has been made between time-related variables (age, age at diagnosis, duration of diabetes) and other risk variables. We have attempted to identify the major time-related risk variables for each complication and then examined the effect of other risk variables after accounting for the major time-related variables. The important time-related variables were found to be duration of diabetes for retinopathy, age for macrovascular disease, duration and age at diagnosis of diabetes for sensory neuropathy, and age for renal impairment. When matched on these important time-related variables, the overall prevalences of complications for insulin-dependent (IDDM) compared with non-insulin-dependent (NIDDM) diabetic patients were essentially the same. An exception is renal impairment, for which IDDM patients had a higher prevalence than did NIDDM patients of the same age. After allowing for time-related variables, the analysis also demonstrates positive independent associations between diabetic control (glycosylated hemoglobin) and retinopathy and between diabetic control and macrovascular disease. Plasma cholesterol (positively) and high-density lipoprotein cholesterol (negatively) were related independently to both macrovascular disease and renal impairment. Very few differences in the risk-factor profiles for complications were found for IDDM compared with NIDDM patients after allowing for time-related variables.

Age Factors↗

Diabetes in part-aborigines of Western Australia.

One thousand, two hundred and eighteen diabetic subjects living in and around country towns of Western Australia were screened for complications of diabetes. This population included 134 subjects of Aboriginal descent, who were compared with the Caucasoids taking part. In the Aboriginal group there was a greater proportion of Type 2 (non-insulin-dependent) diabetic patients, a relative female preponderance (69% compared with 51%) and a tendency to present at an earlier age of onset than their Caucasoid counterparts. Diabetic complications were at least as common in the Aboriginal group as in the Caucasoid patients. Indeed, retinopathy within 10 years of onset of diabetes was more common in the Aborigines. Peripheral neuropathy was more prevalent in Aborigines treated by diet alone or oral hypoglycaemic agents than in Caucasoids. A much greater prevalence of proteinuria was an additional feature of the Aboriginal subgroup (29% versus 4%).

Adult↗

Vitreous haemorrhage after cataract extraction.

One hundred eyes undergoing intracapsular cataract extraction and 100 undergoing extracapsular extraction were examined prospectively within one week postoperatively and again at 6-10 weeks postoperatively. Indirect ophthalmoscopy showed vitreous haemorrhage in 36% of the intracapsular group and 13% of the extracapsular group. Vitreous haemorrhage was significantly related to the occurrence of operative hyphaema (p less than 0.01) but not to iridectomy (p greater than 0.05). In the intracapsular group the use of chymotrypsin significantly reduced the incidence of vitreous haemorrhage (p less than 0.01). Three different types of vitreous haemorrhage were identified--streaks, diffuse haze, and beads in the vitreous base. Wound haemorrhage and operative hyphaema account for most cases, but it is suggested that zonular traction may be responsible for the bead haemorrhages and also for the retinal haemorrhages reported by other authors. Although no difference in visual result or incidence of cystoid macular oedema was observed in this study, a relationship to the vitreoretinal pathology of aphakia is suggested.

Adolescent↗

Taxol for the treatment of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) results in retinal detachment and visual impairment due to fibroblastic proliferation in the vitreous and subsequent cellular contraction. The authors have used an in vitro model for PVR to evaluate the action of the antineoplastic drug, taxol, on chorioretinal fibroblast proliferation and contractility. Dose response curves obtained show taxol to be a potent inhibitor of both cellular events. Fifty percent inhibition of contraction and proliferation occurred at 2 X 10(-8)M and 3 X 10(-9)M, respectively. On the basis of this pharmacodynamic data, three dosage regimes were chosen to evaluate possible prevention of PVR in an animal model based on the intravitreal injection of cultured fibroblasts. These animals trials show that a single intravitreal dose of either 35 micrograms or 0.5 microgram taxol significantly reduces incidence and extent of PVR. The average grade of vitreoretinal traction at 28 days for 35 micrograms taxol and 250,000 cells was 0.4 (control 1.8); for 35 micrograms taxol and 700,000 cells, 1.0 (control 2.2); and for 0.5 microgram taxol and 250,000 cells, 1.0 (control 2.3). Delayed optic nerve damage was noted with the highest dose used, but a good therapeutic margin may exist. Long-term clinical histopathologic and electrophysiologic studies will be required. The authors conclude from these preliminary studies that taxol holds definite promise for the relief of traction retinal detachment and PVR.

Alkaloids↗

Corneal endothelial loss with new intraocular lenses.

When we compared the effect of a hydrogel intraocular lens on the corneal endothelium of rabbits to the damage produced by uncoated methylmethacrylate intraocular lenses and methylmethacrylate lenses coated with sodium hyaluronate or methylcellulose, we found that the endothelial damage produced by the hydrogel lenses in a standard 0.25 mm2 of contact was 3.6%. This value was not significantly different from that for the control corneas (0.4%). Uncoated methylmethacrylate lenses caused 62% endothelial loss but coating them with sodium hyaluronate or methylcellulose reduced the loss to 27% and 57% respectively. The results suggested that a hydrogel intraocular lens produces minimal endothelial damage and that coating a methylmethacrylate lens with sodium hyaluronate or methylcellulose does not provide reliable endothelial protection.

Animals↗

Clinical macrovascular disease in Caucasoid diabetic subjects: logistic regression analysis of risk variables.

A cross-sectional study of 1084 Caucasoid diabetic subjects in rural Western Australia revealed a high rate of clinical macrovascular disease (46%), including coronary heart disease (13%), stroke (8%), and peripheral vascular disease (38%). Age was the major time-related variable for total macrovascular disease and for peripheral vascular disease, with identical prevalence rates in Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes when age was taken into account. In 179 Type 1 diabetic subjects, logistic regression analysis showed no associated risk factors other than age. In 905 Type 2 diabetic subjects the independent risk factors for total macrovascular disease, identified by a forward step-wise selection procedure, were age as the major contributor, with plasma creatinine levels and plasma glucose levels (all p less than 0.001), high-density lipoprotein cholesterol levels, serum total cholesterol levels, and the (supine-erect) systolic blood pressure difference (all p less than 0.05). There were no direct associations with percentage desirable weight, cigarette smoking or male sex. Type 2 diabetic subjects demonstrated a very strong negative association between high-density lipoprotein cholesterol levels and coronary heart disease, and significant associations were found also between plasma glucose levels and coronary heart disease (p less than 0.01), and glycosylated haemoglobin levels and peripheral vascular disease (p less than 0.001).

Adolescent↗

Assessing the risk of diabetic retinopathy.

We used multiple logistic regression to analyze cross-sectional data on 1,006 patients with diabetes mellitus who were examined in a rural diabetic screening program. The factors found to have independent and significant associations with the presence of retinopathy were duration of diabetes, albuminuria, serum creatinine, glycosylated hemoglobin, and plasma glucose levels, blood pressure, and percentage of desirable weight. By comparing the contribution of each significant factor to the deviance from the regression models, we estimated the relative importance of each. Duration of diabetes was by far the most important predictive factor. The logistic model provided a good fit to the observed prevalence rates in various risk groups but was less satisfactory for predicting the presence or absence of retinopathy in individual patients. The discovery of presently unknown risk factors may improve this situation.

Adolescent↗

Effect of cyclic AMP on cellular contractility and DNA synthesis in chorioretinal fibroblasts maintained in collagen matrices.

Dibutyryl cyclic AMP (db-cAMP), theophylline and forskolin were found to be potent inhibitors of DNA synthesis and cell contractility in chorioretinal fibroblasts maintained in 3-dimensional collagen matrices. Dose-response curves were constructed for the inhibitory action of these agents on both cellular parameters and their interrelationship examined by regression analysis. The results obtained indicate that these parameters were equally inhibited by cAMP with the exception of high concentrations of db-cAMP (greater than 10(-3) M) where a greater effect on DNA synthesis than cell contractility was observed which was attributed to additional inhibition of DNA synthesis by db-cAMP degradation products. It is proposed from the present results and those of other investigators that cAMP regulates non-transformed fibroblast proliferation and contraction through a common regulatory mechanism possibly involving cAMP-dependent protein kinases and calcium ions.

Animals↗

Catecholamines in aqueous humour of glaucoma patients.

Aqueous humour catecholamine concentrations were assayed in open angle glaucoma, and cataract patients during surgery, under general anaesthesia. Plasma catecholamines were measured at the same time. Aqueous humour noradrenaline is apparently reduced by pretreatment with adrenaline, timolol and pilocarpine. (Noradrenaline concentrations were 0.599 +/- 0.239 ng/ml in glaucoma, and 0.970 +/- 0.445 ng/ml in cataract patients.) Dopamine was found in two of six cataract patients (0.123 and 0.318 ng/ml), and in all the glaucoma group (0.221 +/- 0.170 ng/ml). Plasma noradrenaline concentration was probably increased in glaucoma, when compared to the cataract patients. These results confirm our findings in the non-human primate, and suggest that adrenaline may act, at least in part, by causing denervation or inhibition of noradrenaline release in the anterior segment of the eye, and probably by release of dopamine into the aqueous humour. The unexplained and new finding of dopamine in the aqueous humour may have some bearing on the action of dopaminergic drugs for the treatment of glaucoma. Future treatment of ocular hypertension may rely more on sympathetic denervation than on conventional adrenergic therapy.

Adrenergic Agonists↗

Aqueous humor catecholamines.

The catecholamines norepinephrine, (NE) epinephrine (E) and dopamine (DA) were detected for the first time in the aqueous humor of humans under general anesthesia and monkeys under ketamine. The catecholamine levels in aqueous humor of 9 humans were assayed. NE was 0.796 +/- 0.457 ng./ml., E ranged between 0 and 0.132 ng./ml. in 4 out of 9 subjects, and DA was found in 2 of the 9 eyes. (0. 123ng ./ml. and 0. 318ng ./ml..) Plasma levels were measured in 8 of the human subjects at the time of aqueous sampling -NE was 0.311 +/- 0.171, E ranged between 0 and 0.097 (4 out of 8 subjects) and DA was detected in one subject- 0.037 ng./ml.. Monkey aqueous levels were NE:2.843 +/- 0.668 and DA:0.462 +/- 0.177 ng./ml., with an intact iris. (N = 8 eyes.) NE was 0.497 +/- 0.049, and DA 0.426 +/- 0.218 ng./ml. after total iridectomy. (N = 4 eyes) E was not detected in the monkey under these conditions. Whilst NE may be produced in part by the iris, DA levels were not affected by iridectomy. This implies that DA may be produced by structures unrelated to sympathetic nerve endings of the iris in the anterior segment of the non-human primate eye, perhaps by diffusion from the ciliary body or retina. Ketamine is known to inhibit catecholamine uptake, which may explain the high levels measured in the monkey. Human aqueous catecholamine levels measured under anesthesia may be affected by a variety of the drugs used. It is postulated that dopaminergic neurones and associated receptors may be present in the anterior segment of the eye. This may explain the presence of aqueous humor dopamine and the effects of dopaminergic drugs on intraocular pressure.

Adult↗

Iron-binding proteins in vitreous humour.

The soluble protein composition of Macaque monkey vitreous humour was studied in order to understand its iron-binding properties. The protein content of vitreous humour was 217 micrograms/ml +/- 4.6%, 40% of which was serum albumin and 30% an iron-binding protein of hydrodynamic properties identical to that of transferrin or lactoferrin. Relative to serum, the vitreous humour contained a 13-fold excess of this protein(s). Isoelectric focusing, iron-binding and immunoelectrophoretic studies indicated that both vitreous humour and aqueous humour contained lactoferrin as well as serum transferrin. The iron-binding capacity of these proteins in vitreous humour was equivalent to the mass of haemoglobin iron contained in at least 570000 monkey erythrocytes. It was concluded that the intraocular lactoferrin originated from within the eye. These iron-binding proteins may play a protective role in ocular disturbances such as vitreous haemorrhage, iron foreign body toxicity and infection.

Animals↗

Draining pus from the cornea.

Thirteen patients with varying grades of suppurative keratitis were studied with regard to their response to keratoplasty. In all patients there was a rapid improvement in symptoms and signs. In eight of the 13 there was restoration at least of previous function: one patient lost all vision due to secondary closed-angle glaucoma, because he refused further surgery. Corneal graft opacification occurred in three eyes; one other became partially opaque; whilst in a fourth, the lamellar graft remained clear while the original autograft failed. At last follow-up, all eyes were normotensive and free of symptoms. Keratoplasty should assume an important part of the management of suppurative keratitis, from both theoretical and practical considerations.

Adult↗

Progress in continual eye pressure monitoring.

Observations of intraocular pressure (IOP) variations in response to CO2, adrenaline, speech and compression of the neck veins were documented by continual monitoring of IOP by radiotelemetry. Carbon dioxide increased IOP in the supine, but not in the erect, conscious subject. Adrenaline 2% caused a rapid short-lived painful increase in IOP, followed by a profound decrease. This was due to an increase in facility of outflow and was associated with paralysis of the sympathetic supply to the iris. Speech caused a small rise in IOP which was reversed by rest in silence. Compression of the neck veins caused a variable increase in IOP. These physiological variations in IOP may contribute to the errors of tonometry.

Carbon Dioxide↗

The value of rational biopsy. Tissue culture of chorioretinal biopsies.

Although tissue biopsies for diagnosis have been an integral part of the development of many medical areas, progress has been restricted in the case of chorioretinal disease because of the inherent risks involved in such surgery. The recent advances in microsurgery of the eye, and in vitreoretinal surgery in particular, have provided the impetus to develop a safe technique for retinal biopsy and to look for diagnostic and therapeutic indications.

Animals↗