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Biomedical subjects

D McLeod

Publications and source records attributed to D McLeod.

At least 19 recordsLinked to original sources
PubMed1999

Influence of age on the parasympatholytic property of tricyclic antidepressants.

Clinical evidence indicates that parasympatholytic effects of tricyclic antidepressants increase with age. The aim of the present study was to determine the possible physiological reason for this phenomenon. Subjects included 23 patients (14 female) with major depression, melancholic type, and 23 age- and sex-matched healthy control subjects. Cardiac vagal tone was measured at rest using both spectral analysis and a time domain beat-to-beat method. Results of the spectral and time domain methods for the estimation of vagal tone used in this study were highly correlated in control subjects as well as in medicated depressed subjects. Both patients and control subjects showed an age-related decline in cardiac vagal tone. Tricyclic antidepressants decreased vagal tone significantly by 25-49% depending on age (20-60 years), although the age difference was not significant. The greater effect of tricyclic antidepressants on parasympathetic activity typically seen in older age groups may reflect the fact that predrug levels of vagal tone are already low in older patients. Measurement of vagal tone prior to drug administration may therefore be of prognostic value for anticholinergic side effects.

Adult↗
PubMed1999

Management of day-surgery patients with cataract attending a peripheral ophthalmic clinic.

PURPOSE: To compare two organisational models of management for patients with cataract referred to a peripheral ophthalmic clinic who underwent day-surgery at a main eye hospital. METHOD: Patients were randomised into two groups. The experimental group (n = 25) received pre-operative assessment by a trained ophthalmic nurse at the peripheral clinic immediately following diagnosis of cataract and diary-booking for surgery. The control group (n = 24) received a separate appointment for pre-operative assessment at the main hospital. For all patients, the first review appointment (3 or 5 days post-operatively) and all subsequent review was at the peripheral clinic. Outcome measures included: visual acuity, subjective visual function (VF-14), anxiety and depression (HADS), semi-structured interviews to ascertain patient satisfaction, and a cost-benefit analysis. RESULTS: There were no significant differences at any time between the experimental and control groups with respect to visual acuity, subjective visual function or anxiety and depression. The experimental model was found to be more cost-effective and provided a less fragmented means of care delivery. The majority of patients in both groups expressed satisfaction with their care but, overall, the experimental model was preferred. CONCLUSIONS: Nurse-led pre-operative assessment of patients with cataract at a peripheral ophthalmic clinic is safe, cost-effective and is preferred by patients.

Aged↗
PubMed1999

Planning and managing research into day-surgery for cataract.

Between 1995 and 1997, a randomized controlled study, funded by the Department of Health, was carried out into the management of patients with cataract attending a peripheral ophthalmic clinic and who had been assessed as suitable for day-surgery. The research took place in a clinical setting and it was accepted from the outset that, while such studies have the power to give information about the real clinical world, this also means that the research is potentially at the mercy of events within that world. The purpose of this paper is to report how the study was set up and integrated into the clinic. First, a literature review was undertaken in order to focus the aims of the study more clearly. Second, drawing on principles of action research, clinical and research staff worked together to implement the study. This strategy allowed a flexible approach to the research which enabled problems to be handled as they arose.

Ambulatory Surgical Procedures↗
PubMed1999

Three dimensional analysis of microaneurysms in the human diabetic retina.

The retinal vasculature of postmortem normal human and diabetic eyes was studied using an immunohistochemical technique in conjunction with confocal laser scanning microscopy. The technique, which stained for von Willebrand factor, allowed both large areas of the retinal vasculature to be visualised and abnormalities to be studied in detail without disturbing the tissue architecture. Only one microaneurysm, defined as any focal capillary dilation, was observed in 10 normal eyes but numerous microaneurysms were seen in 4 out of 5 diabetic retinas; counts varied between 0 and 26 per 0.41 mm2 sample area. Microaneurysms were classified into 3 categories according to morphology: saccular, fusiform and focal bulges. Most were saccular, these having no preferred orientation. The majority of microaneurysms were associated with just 2 vessels suggesting they were unlikely to develop at vascular junctions. The majority were observed to originate from the inner nuclear layer and were therefore in the deeper part of the inner retinal capillary plexus. Variation in the staining of microaneurysms may correlate with endothelial dysfunction seen clinically as dye leakage during fluorescein angiography.

Aged↗
PubMed1999

Coats' disease of the retina (unilateral retinal telangiectasis) caused by somatic mutation in the NDP gene: a role for norrin in retinal angiogenesis.

Coats' disease is characterized by abnormal retinal vascular development (so-called 'retinal telangiectasis') which results in massive intraretinal and subretinal lipid accumulation (exudative retinal detachment). The classical form of Coats' disease is almost invariably isolated, unilateral and seen in males. A female with a unilateral variant of Coats' disease gave birth to a son affected by Norrie disease. Both carried a missense mutation within the NDP gene on chromosome Xp11.2. Subsequently analysis of the retinas of nine enucleated eyes from males with Coats' disease demonstrated in one a somatic mutation in the NDP gene which was not present within non-retinal tissue. We suggest that Coats' telangiectasis is secondary to somatic mutation in the NDP gene which results in a deficiency of norrin (the protein product of the NDP gene) within the developing retina. This supports recent observations that the protein is critical for normal retinal vasculogenesis.

Amino Acid Substitution↗
PubMed1999

Immunolocalisation of the VEGF receptors FLT-1, KDR, and FLT-4 in diabetic retinopathy.

AIM: To determine the spatial and temporal changes in the staining pattern of the VEGF receptors FLT-1, KDR, and the putative receptor FLT-4 during the pathogenesis of diabetic retinopathy. METHODS: Immunohistochemical localisation of VEGF receptors, using antibodies against FLT-1, FLT-4, and KDR, was carried out on specimens of normal human retina (n = 10), diabetic retinas (a) with no overt retinopathy (n = 12), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n = 5), (c) with active proliferative retinopathy (n = 6), and (d) with no residual proliferative retinopathy after scatter photocoagulation therapy (n = 14), and surgically excised diabetic fibrovascular membranes (n = 11). The degree and pattern of immunostaining was recorded. RESULTS: FLT-1 staining was apparent in the retinas from both non-diabetic and diabetic retinas; weak to moderate staining was generally confined to the inner nuclear layer, the ganglion cell layer, and the retinal vessels during all stages of the disease process. Staining of the retinal vessels was raised in diabetic tissue compared with non-diabetic tissue. The preretinal vessels of the diabetic subjects stained moderately to intensely for FLT-1. In contrast with FLT-1 staining minimal immunostaining for KDR was demonstrated in the non-diabetic eyes and the unlasered eyes; however, weak staining for KDR was observed in the inner nuclear layer and the ganglion cell layer of the unlasered eyes with diabetic changes. In those retinas with preretinal neovascularisation KDR immunoreactivity was moderate to intense in the intra- and preretinal vessels. However, in the excised membranes, where the vessels may have been in a quiescent state, the levels of KDR were weak to moderate. After apparently successful laser treatment KDR staining was reduced in the intraretinal vessels. Minimal FLT-4 staining was observed throughout normal eyes while weak to moderate FLT-4 staining was generally confined to the inner nuclear layer and the ganglion cell layer of the unlasered diabetic eyes. Weak to moderate levels of FLT-4 staining were observed in the intraretinal vessels except after apparently successful laser treatment where reduced levels of staining were observed. Weak to moderate staining was observed in the preretinal vessels. CONCLUSIONS: This study supports a role for FLT-1, KDR, and possibly FLT-4 in the pathogenesis of diabetic retinopathy; however, their specific roles in the progression of the disease may differ.

Aged↗
PubMed1999

Growth factor staining patterns in the pig retina following retinal laser photocoagulation.

AIM: To identify changes in growth factor expression in miniature pig retinas following retinal laser photocoagulation. METHODS: Pigs were sacrificed at different times (15 minutes to 42 days) post-laser and the retinas were immunolabelled for basic fibroblast growth factor, insulin-like growth factor I, transforming growth factor beta, epidermal growth factor, transforming growth factor alpha, platelet derived growth factor, vascular endothelial growth factor, and epidermal growth factor receptor. Total mRNA levels were also determined. RESULTS: With the exception of vascular endothelial growth factor, immunoreactivity for all other growth factors studied and epidermal growth factor receptor was observed throughout normal non-lasered control retina, generally being high in the retinal pigment epithelium and low in the neural retina. Changes in growth factor expression following laser photocoagulation were observed only in burn areas and changes were mainly confined to the retinal pigment epithelium and outer nuclear layer. The immunoreactivity within retinal pigment epithelial cells in burn areas was either absent or decreased following laser treatment but returned to normal by 21 days. The immunoreactivity was increased within the outer nuclear layer of burn areas during the healing process but returned to normal by 42 days. Vascular endothelial growth factor immunoreactivity was weak/absent in the normal retina and remained unchanged following laser photocoagulation. Change of total mRNA levels in burn areas during time post-laser was confined to retinal pigment epithelial cells, being low immediately following photocoagulation and returning to normal by 42 days. CONCLUSIONS: These results demonstrate a temporal alteration in growth factor expression and transcriptional activity in the retina following laser photocoagulation.

Animals↗
PubMed1999

Effects of hyaluronan lyase, hyaluronidase, and chondroitin ABC lyase on mammalian vitreous gel.

PURPOSE: To determine the effects of enzymes on mammalian vitreous gel and to thus infer the structural roles of hyaluronan and chondroitin sulfate in the gel. METHODS: The wet weights of bovine vitreous gels were compared before and after incubation with Streptomyces hyaluronan lyase, chondroitin ABC lyase, testicular hyaluronidase, or buffer alone. The extent of hyaluronan depolymerization was determined by chromatography and that of chondroitin sulfate depolymerization by western blot analysis. RESULTS: After digestion with Streptomyces hyaluronan lyase (30 U/gel), the gel wet weight was the same as that of controls (incubated with buffer alone) despite 94% of the hyaluronan having been depolymerized; when digested with 100 U/gel, the gel wet weight decreased (to 57% of original wet weight versus 86% for controls, P = < 0.001) and hyaluronan was completely depolymerized. Chondroitin ABC lyase digestion (0.2 U/gel) resulted in a slight reduction in gel wet weight (90% versus 96%, P = < 0.001) and depolymerization of 88% of the hyaluronan; the presence of fully digested chondroitin sulfate chains was established. Digestions with 100 and 500 U/gel of testicular hyaluronidase resulted in a decrease (P = < 0.001, both cases) in gel wet weight (53% versus 82%, 100 U/gel; 57%, versus 86%, 500 U/gel) with 75% and 97% hyaluronan depolymerization, respectively. CONCLUSIONS: Depolymerization of all vitreous hyaluronan and of chondroitin sulfate resulted in gel wet weight reduction but not gel destruction. Digestion with 30 U/gel of Streptomyces hyaluronan lyase revealed a small pool (6%) of relatively enzyme-resistant hyaluronan that specifically contributed toward maintaining gel wet weight.

Animals↗
PubMed1998

What do general practitioners do when patients present with symptoms indicative of urinary tract infections?

AIM: The primary aim of the study was to examine whether the results of laboratory investigations of midstream urine samples from patients with suspected urinary tract infection influenced management by general practitioners. METHOD: Eleven general practitioners in the Network participated in the study by recording treatment and outcomes for consecutive patients with symptoms of urinary tract infection. RESULTS: Data from 216 patients were included in the study. Dipsticks were used to test the urine of 98 patients (45%) and midstream urine samples were sent to the laboratory for 176 patients (82%). Antibiotics were prescribed for 176 patients (82%). Antibiotics were prescribed for 95% of patients with symptoms of dysuria, frequency and urgency. Where the laboratory results showed infection there was no change in treatment after the general practitioners received the results for 75 patients (85%). Among those patients where the laboratory reported no infection there was no change in treatment after the general practitioner received the results for 53 patients (87%). CONCLUSIONS: The results of laboratory investigation of midstream urine samples did not change the treatment provided for the majority of patients in the study.

Adolescent↗
PubMed1998

The cost of childhood immunisation in general practice.

AIM: To estimate the cost, to general practices in the Wellington Immunisation Network, of the audit process of recalling and immunising children according to the New Zealand Immunisation Schedule. METHOD: Practices recorded all clinical and clerical time spent on immunisation as well as the materials used throughout one audit cycle. Staff time and materials were costed directly. Practice overheads were apportioned to immunisation according to the actual time spent on each of the tasks relating to immunisation relative to the total staff hours at the practice. RESULTS: The average cost of immunising a child who attended a non-capitated practice after a single reminder or recall was $15.15. The cost to the practice after taking the practice nurse subsidy and GMS into account was $8.51. The cost of immunising children who were not immunised at the first recall increased in proportion to the number of recall reminders. The annual average cost of immunisation to practices in the study exceeded the revenue obtained from the Immunisation Benefit. CONCLUSION: Overall, given the frequency of recall reminders, there was a net cost to practices for childhood immunisation after deducting the current immunisation benefit rate of $9.78 excluding GST. Thus, the practices in this study made a "loss" in carrying out childhood immunisations.

Child, Preschool↗
PubMed1998

Short-wavelength sensitive visual field loss in patients with clinically significant diabetic macular oedema.

The aim of the study was to compare the sensitivity of short-wavelength and conventional automated static threshold perimetry for the psychophysical detection of abnormality in patients with clinically significant diabetic macular oedema. The sample comprised 24 patients with clinically significant diabetic macular oedema (mean age 59.75 years, range 45-75 years). One eye of each patient was selected. Exclusion criteria included the presence of lenticular opacity. The sensitivity of the macular visual field of each patient was determined with programme 10-2 of the Humphrey Field Analyser on two occasions, using both short-wavelength and conventional stimulus parameters; the results of the second session were analysed to minimise learning effects. A pointwise horizontal hemifield asymmetry analysis was derived for short-wavelength perimetry (thereby negating the influence of pre-receptoral absorption); the pointwise pattern deviation probability plot was analysed for conventional perimetry. Abnormality was defined as 3 or more contiguous stimulus locations with negative asymmetries (short-wavelength) or reduced sensitivity values (conventional) that resulted in a statistical probability level of p less than 0.05. The fields of 8 patients were abnormal as assessed by conventional perimetry while all were classified as abnormal using short-wavelength perimetry. In the 8 patients who exhibited both abnormal conventional and abnormal short-wavelength perimetry results, the extent of field loss was generally greater using short-wavelength perimetry. The position of the localised field loss (i.e. as distinct from field loss that was generalised across the visual field) assessed by short-wavelength perimetry corresponded with the clinical mapping of the area of diabetic macular oedema but the extent of this loss was generally greater than that suggested by clinical assessment. Short-wavelength automated perimetry offers improved sensitivity for the psychophysical detection of clinically significant diabetic macular oedema.

Aged↗
PubMed1998

Influence of laser photocoagulation for clinically significant diabetic macular oedema (DMO) on short-wavelength and conventional automated perimetry.

The aim of the study was to determine the effect of laser photocoagulation for clinically significant diabetic macular oedema (DMO) on macular visual function as assessed by conventional and short-wavelength automated static threshold perimetry. The sample comprised 24 patients who required laser photocoagulation for clinically significant DMO (mean age 59.75 years, range 45-75 years). One eye of each patient was selected for the study. Patients underwent conventional and short-wavelength perimetry using programme 10-2 of the Humphrey Field Analyser on two separate occasions prior to treatment and subsequently within 1 week of, and at 1, 2, 4 and 12 weeks after, treatment. The pointwise pattern deviation plot was analysed for conventional perimetry and a pointwise horizontal and vertical hemifield asymmetry analysis was derived for short-wavelength perimetry (thereby negating the influence of pre-receptoral absorption). The extent of sensitivity loss was determined by counting the number of stimulus locations with statistical probability levels of p less than 0.05. Group mean log minimum angle of resolution (logMAR) visual acuity was largely unchanged over the course of the study. Conventional perimetry showed an increase in the group mean number of abnormal contiguous stimulus locations from 2.4 (SD 4.3, range 0-14) immediately prior to treatment, to 12.4 (SD 7.8, range 0-30) within 1 week of treatment; at 3 months post-treatment, the group mean number of abnormal contiguous stimulus locations was 8.1 (SD 6.5, range 0-20). A similar but less pronounced change was found for short-wavelength perimetry. The spatial position of the post-treatment localised sensitivity loss corresponded with the area of retinal photocoagulation. Despite proven benefit in the stabilisation of visual acuity, laser photocoagulation for clinically significant DMO invariably results in a localised loss of perimetric sensitivity within 10 degrees eccentricity of the fovea. Evidence for the value of laser therapy for clinically significant DMO must be re-examined.

Aged↗
PubMed1998

The large chondroitin sulphate proteoglycan versican in mammalian vitreous.

Hyaluronan is a major component of the vitreous gel. Hyaluronan-binding macromolecules, including the aggregating proteoglycans, have been shown to perform an important role in maintaining the structural integrity of a number of tissues. However, there have not previously been any biochemical data to establish the presence of these types of macromolecules in vitreous. Bovine vitreous gel was solubilized (apart from a residual collagenous pellet) in 4 M guanidine hydrochloride and after dialysis into phosphate buffered saline analyzed by gel filtration chromatography with in-line measurement of refractive index and multi-angle laser light scattering. The concentration of hyaluronan in whole vitreous was found to be 0.57 mg/ml. The average molecular weight of the hyaluronan was found to be 170,000 (after isolation of the vitreous hyaluronan by isopycnic centrifugation in 0.5 M guanidine hydrochloride and papain digestion). Following Superose 12 gel filtration chromatography of the Streptomyces hyaluronan lyase digested vitreous extract, a pool of material was identified at or near the void volume of the column, and this material was shown to contain sulphated proteoglycans. Analysis of fractions following Superose 12 gel filtration chromatography by Western blotting showed that this pool of material contained the chondroitin sulphate proteoglycans versican and type IX collagen. Link protein was also identified in vitreous extracts by Western blotting. In whole vitreous, the concentration of versican was found to be 21.4+/-2.8 microg/ml and of link protein 0.62+/-0.07 microg/ml. Versican and link protein were thus present in approximately 1:1 molar ratios, but hyaluronan was present in a molar excess of 150 times. Therefore, aggregating proteoglycans are present in vitreous but, assuming that they bind to hyaluronan in-vivo, their overall density along the hyaluronan is much lower than that found in other tissues.

Animals↗
PubMed1998

Scanning laser tomography Z profile signal width as an objective index of macular retinal thickening.

AIMS: (i) To evaluate the relation between retinal thickness and the Z profile signal width of a scanning laser tomographer in selected patients exhibiting clinically manifest and circumscribed macular retinal thickening; (ii) to compare the Z profile signal width values of a group of age similar normal subjects with those of the patients with macular retinal thickening; and (iii) to present the methodology underlying the Z profile signal width derivation. METHODS: Three patients with the following conditions were selected: widespread diabetic macular oedema; localised diabetic macular oedema; and macular hole. The patients were selected because they exhibited clinically manifest and circumscribed macular retinal thickening. Patients underwent fundus photography and a clinical examination which included fundus biomicroscopy. Fourteen age similar normal subjects were also assessed. The Heidelberg retina tomograph (HRT) was utilised to acquire seven topographic images of each macula. Z profile signal width data were analysed using custom software. Signal width was measured at 50% of the maximum intensity. RESULTS: For each patient with macular retinal thickening, Z profile signal width analysis (after normalisation to reduce the influence of variation in reflectance intensity between successive images) revealed a significant (p < 0.0001) localised increase of signal width which agreed with the HRT topographic analysis of retinal height, and also the clinical assessment of retinal thickness. The mean normalised Z profile signal width for the normal subjects (assessed over the whole image) ranged from 0.278 (SD 0.039) to 0.444 (0.063); these values compared with those obtained from patients in areas of macular retinal thickening of 0.761 (0.224) to 0.953 (0.194). Z profile signal width test-retest data for the patient with localised diabetic macular oedema were plus or minus 0.159 which compared with a mean signal width value of 0.761. CONCLUSION: The evidence of this study, based upon three selected patients with macular retinal thickening and 14 normal subjects, would suggest that Z profile signal width analysis offers a non-invasive, objective, topographic, and reproducible index of macular retinal thickening. Studies employing larger sample sizes are required to determine the true clinical worth of the technique.

Aged↗
PubMed1998

VEGF localisation in diabetic retinopathy.

AIM: To determine the staining pattern of vascular endothelial growth factor (VEGF) at different stages of diabetic retinopathy (including post-laser photocoagulation) and to compare staining in excised fibrovascular and fibrocellular (non-diabetic) preretinal membranes. METHODS: Immunohistochemical localisation of VEGF, using antibodies raised against VEGF165 and VEGF121,165,189, was carried out on specimens of normal human retina (n = 15), diabetic retinas ((a) with no overt retinopathy (n = 19), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n = 6), (c) with active proliferative retinopathy (n = 6), (d) with no residual proliferative retinopathy after photocoagulation therapy (n = 15)), excised diabetic fibrovascular membranes (n = 19), and non-diabetic fibrocellular membranes (n = 7). The degree and pattern of immunostaining was recorded. RESULTS: In general, VEGF was absent from the majority of normal retinas. VEGF staining was apparent in most diabetic tissues but the staining pattern was dependent on both the specificity of the antibody used and the category of tissue. Staining with the VEGF165 antibody was generally confined to endothelial cells adn perivascular regions while the VEGF121,165,189 antibody was also associated with extravascular components of the inner retina. Intensity of immunostaining of diabetic eyes was dependent on the severity of retinopathy being least in diabetics with no overt retinopathy and greatest in retinas with proliferative retinopathy. Interestingly, the intensity of immunostaining in diabetic retinas which had undergone laser surgery for proliferative retinopathy was reduced to basal levels. Moderate to intense immunostaining was observed in all fibrovascular and fibrocellular membranes examined. CONCLUSIONS: This study supports a circumstantial role for VEGF in the pathogenesis of both the preclinical and proliferative stages of diabetic retinopathy.

Adult↗
PubMed1998

Increased expression of placenta growth factor in proliferative diabetic retinopathy.

Proliferative diabetic retinopathy is thought to be mediated by the hypoxic regulation of angiogenic growth factors, in particular the vascular endothelial growth factor (VEGF) family. The aim of this study was to determine if placental growth factor (PIGF), a recently identified member of the VEGF family, was expressed in diabetic eyes undergoing preretinal neovascularization. Rabbit anti-PIGF antiserum was raised using a 20-amino acid N-terminal sequence to PIGF and did not cross react with VEGF165. Immunohistochemistry was performed on specimens of normal retina (n = 8), diabetic retina in the absence (n = 7) and presence (n = 4) of proliferative retinopathy, scatter laser-treated diabetic retina (n = 7), excised fibrovascular preretinal membranes (n = 12), and nondiabetic fibrocellular epiretinal (n = 7) membranes. PIGF levels were also determined in vitrectomy specimens from patients with either proliferative diabetic retinopathy or macular hole. PIGF immunoreactivity was intensely localized to the endothelial and perivascular regions of newly formed blood vessels of excised fibrovascular preretinal membranes. Intense localization of PIGF protein was also observed in superficial retinal vessels in diabetic retinae adjacent to neovascular preretinal membranes. Localization of PIGF was weak or absent in diabetic retinae that showed no evidence of neovascular proliferation. PIGF protein was also absent in normal retinae, in diabetic retinae that had received extensive treatment with scatter laser photocoagulation, and in nonvascularized epiretinal membranes. PIGF was present in all diabetic vitreous samples (mean 103 pg/ml) but nondetectable in control samples. These results strongly implicate a role for PIGF in the pathogenesis of proliferative diabetic retinopathy.

Adult↗