Search PubMed⌕ Search

Biomedical subjects

D McLeod

Publications and source records attributed to D McLeod.

At least 91 records · Page 5Linked to original sources

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↗

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↗

Major depression and cardiac autonomic control.

We investigated autonomic control of heart rate in patients with major depression, melancholic type. Twenty-three depressed inpatients who were being treated with tricyclic antidepressants and 23 depressed patients who were taking no medications were compared with age- and sex-matched control groups on resting cardiac vagal tone and heart rate. In unmedicated depressed patients, cardiac vagal tone was comparable to that of control subjects, but heart rate was significantly higher. This increase in heart rate may have been due to sympathetic activation caused by anxiety, since the depressed patients were significantly more anxious than the control subjects. Medicated patients exhibited diminished cardiac vagal tone and higher heart rate than unmedicated patients and controls. This was probably due to the anticholinergic effects of the antidepressants. Our findings suggest that cardiac vagal tone is not lower than normal in patients with depression, melancholic type.

Adult↗

A general practice case-control study of delayed immunisation in under two year old children.

AIM: To identify social factors which characterise the household of children with delayed immunisation. METHOD: The study was done in 15 general practices in the Wellington city region with a case-control design where preschool children who were not up to date (cases) for their immunisations were compared with children who were up to date (controls). RESULTS: There were 215 cases where immunisation was delayed among 3723 children at the time of audit in June 1996. Ethnic status was available from general practice records in 33% of cases and 40% of controls. There were more Maori and Pacific Island children among the cases compared to controls (39% versus 21%, odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.12-5.10, p = 0.022. CASE SAMPLE HOUSEHOLDS COMPARED WITH CONTROLS HAD: (1) more children in the households (mean 2.27 versus 1.98, p = 0.01); (2) more households with a female as the only adult (35% versus 24%, OR = 1.61, 95% CI 1.04-2.51, p = 0.034). There was no difference in the proportions of male only adults (0.02% versus 0.01%, p = 0.70); (3) more mothers who were under 30 years of age (38% versus 25%, OR = 1.61, 95% CI 1.04-2.51, p = 0.034); and more fathers under 30 years of age (20% versus 10%, OR = 2.16, 95% CI 0.97-4.84, p = 0.06); (4) fewer mothers who were up to date with their recorded cervical smear status (66% versus 83%, OR = 0.69, 95% CI 0.23-0.63, p < 0.001); (5) more parents with an active community services card (38% versus 25%, OR 1.82, 95% CI 1.17-2.82, p = 0.007); (6) fewer siblings being immunised (70% versus 94%, OR = 0.14, 95% CI 0.07-0.28, p < 0.001). CONCLUSION: There is a distinct group of New Zealand children for whom immunisation is delayed. Such children live in households which can be characterised by various social factors easily obtainable from general practice records. The identified households could be targeted for efficient preventive care by general practices.

Adult↗

Baby feeding: the thoughts behind the statistics.

AIM: To investigate attitudes towards baby feeding and to identify reasons why women stop breast feeding. METHOD: A series of six focus groups were held with thirty eight mothers with babies aged between 3 and 18 months, who had been breast and/or bottle fed. RESULTS: The discussions identified a number of significant themes. Decisions on baby feeding were made before birth. Women felt under considerable pressure to breast feed and felt guilty about bottle feeding. Information available about baby feeding was generally inconsistent, unrealistic and incomplete although all women were well informed about the benefits of breast feeding. Most women found breast feeding more difficult than anticipated and needed more help with common problems. A number of difficulties were identified with bottle feeding. Those women who enjoyed breast feeding were most likely to continue. The best support for breast feeding came from other mothers and supportive partners. Ceasing breast feeding was difficult for some women. CONCLUSION: Exploring mothers' attitudes to breast feeding highlighted the need for non judgemental attitudes to baby feeding and consistent information and support on both breast and bottle feeding. Duration of breast feeding is likely to be improved if problems can be addressed. A larger, more detailed prospective study would more accurately identify problem areas and suggest ways of solving them.

Attitude↗

How is quality of life in prostate cancer patients influenced by modern treatment? The Wallenberg Symposium.

OBJECTIVES: To identify complications of various forms of treatments for prostate cancer and their influence on patients' quality of life with the ultimate goal of suggesting a Quality of Life Questionnaire specific for prostate cancer for further validation. METHODS: The literature was screened for reports on the more common complications following various forms of therapy for prostate cancer. Frequencies were summarized. The scarce literature reporting on quality of life in prostate cancer was reviewed and conflicting data were discussed and reassessed. Suggested questionnaires used in other studies were critically scrutinized and the various questions recorded. RESULTS: Following radical surgery, impotence and incontinence were the most common complications reducing patients' quality of life. The literature was not uniform with regard to whether loss of sexual function was regarded as a worse complication than loss of urinary control. Following radiotherapy, intestinal problems and sexual dysfunction were the dominating side effects. Quality of life was best preserved in surveillance-only series. Following endocrine therapy, not only impotence and hot flushes were focused upon, but also mental dysfunction and intestinal dysfunction from nonsteroidal antiandrogens, additionally, the importance of effective palliation was highlighted. A Quality of Life Questionnaire should contain general domains relevant to cancer patients, cancer-specific questions, and prostate-cancer-specific questions. The latter group includes: worry for prostate cancer and its prognosis, bone/pelvic pain, lower urinary tract symptoms, urinary incontinence, urinary diversion, bowel function, sexual function, endocrine effects, and satisfaction with medical care for prostate cancer. CONCLUSIONS: A modern trial of prostate cancer treatment should be regarded as insufficient without including a validated Quality of Life Questionnaire.

Costs and Cost Analysis↗

Management of acute asthma: gaps between opinion and recorded action by general practitioners.

OBJECTIVE: To describe the mismatch between general practitioners' recorded actions and opinions in the management of acute asthma. DESIGN: A comparison between clinical record data and questionnaire data on the ideal management of acute asthma. SETTING: The after-hours medical centre (AMC)--a service run by nearly all general practitioners in the Wellington region of New Zealand. STUDY PARTICIPANTS: Sixty general practitioners working at the AMC, treating 266 patients with acute asthma over a two-month period. RESULTS: A mismatch of over 40 percent occurred for pulse rate, respiratory rate, peak expiratory flow rate, modification of inhaled bronchodilators, and steroids, the use of nebulised medication and oral steroids. Other mismatches of interest to participating general practitioners were the prescribing of antibiotics for asthma, the difference in clinical behaviour between adults and children and the use of verbal action plans in asthma management. There was no mismatch for the recording of wheeze on auscultation in children, increasing inhaled asthma relieving drugs in adults, not using X-rays, not injecting asthma drugs, and not referring to hospital for most acute asthma. CONCLUSION: The mismatches created "gaps" between opinion and action which had face validity to participating general practitioners. The findings indicate the need for implementation of guidelines and for more research to explain how the mismatches arise.

Acute Disease↗

Objective morphological assessment of macular hole surgery by scanning laser tomography.

AIM: To assess the morphological change in retinal topography using a scanning laser tomographer following macular hole surgery. To compare the results of scanning laser tomography with clinical evaluation and visual function assessment. METHODS: The sample for this pilot study comprised four eyes exhibiting different stages of macular hole formation preoperatively. Subjects were assessed preoperatively and at 1 and 3 months postoperatively. Each assessment included visual acuity, letter contrast sensitivity, clinical examination (including automated static perimetry), and scanning laser tomography. The Heidelberg retina tomograph (HRT) was used to acquire digitised scanning laser tomography images of the macula (10 degrees and 20 degrees fields). Surgery essentially comprised vitrectomy, peeling of the posterior hyaloid face, if still attached, and intraocular gas tamponade. The magnitude and significance of topographic change were determined postoperatively using the HRT topographic difference facility. RESULTS: Topographic difference analysis of the right and left eyes of case 1 showed a significant reduction in the height of the retina postoperatively. Topographic difference analysis of case 2 showed no significant change in topography. Topographic difference analysis of case 3 showed a significant increase in the height of the retina postoperatively. Scanning laser tomography agreed with clinical assessment based upon fundus biomicroscopy in three of the four eyes studied; the postoperative closure of the stage 2 macular hole (as noted by clinical assessment) proved to be too small to reach statistical significance. Scanning laser tomography agreed with the assessment of visual function in two eyes; the agreement between scanning laser tomography and visual function depends, in part, on the stage of development of the macular hole. CONCLUSION: Scanning laser tomography provides an objective evaluation of the outcome of macular hole surgery. Studies employing larger sample sizes are required to fully determine the clinical worth of the technique.

Adult↗

Intravitreal growth factors in proliferative diabetic retinopathy: correlation with neovascular activity and glycaemic management.

AIM: Many growth factors are implicated in proliferative diabetic retinopathy (PDR). It was decided to test the hypothesis that no one factor is predominant but that a regular profile of levels of different growth factors might be operating, and that the profile might differ according to whether or not insulin therapy was part of the patient's glycaemic management. The levels of several growth factors in vitrectomy samples were therefore determined from diabetic patients with tractional, non-haemorrhagic sequelae of PDR and these levels were correlated with (a) each other (growth factor profile), (b) neovascular activity, and (c) the method of glycaemic management (insulin treated (IT) or non-insulin treated (NIT)). METHODS: 72 samples of vitreous were obtained from either diabetic patients with PDR (n = 51) or non-diabetic (control) patients (n = 21). Levels of bFGF, IGF-I, EGF, and insulin were determined by radioimmunoassay; levels of TGF-beta 2 by ELISA; and levels of IGF-I binding protein by western ligand blotting. The data were analysed using appropriate statistics. RESULTS: There was no regular growth factor profile. bFGF levels were significantly greater in vitreous from NIT patients compared with IT patients and controls. The highest levels of bFGF were found in NIT patients with actively vascularised membranes. TGF-beta 2 levels were significantly greater in vitreous from IT patients compared with NIT patients and controls The highest levels of TGF-beta 2 were found in IT patients with actively vascularised membranes. IGF-I levels were significantly greater in diabetics (irrespective of insulin treatment) than non-diabetics and the highest levels of IGF-I were found in IT patients with actively vascularised membranes. A 34 kDa IGFBP was the predominant IGFBP identified in vitreous and was found to be elevated in diabetics patients. CONCLUSION: In PDR there is a correlation between intravitreal growth factor levels and both disease state (whether active or fibrotic) and method of glycaemic management.

Analysis of Variance↗

Retinal detachment following excimer laser.

AIM: To report the clinical presentation, surgical management, and outcome of retinal detachment following excimer laser. METHODS: Retrospective analysis of retinal detachments observed in 11 eyes of 10 myopic patients who had previously undergone photorefractive keratectomy (PRK) or phototherapeutic keratectomy (PTK) by excimer laser. RESULTS: Symptoms of visual loss in two eyes were initially attributed to corneal haze. In 10 of 11 eyes visualisation of the retinal detachment and causative break was possible despite mild corneal haze and optical aberrations caused by the refractive laser procedure. Retinal reattachment was achieved in all 11 eyes though one eye required four surgical interventions. CONCLUSION: This is the first published report to describe an association between retinal detachment and previous excimer laser treatment. The association would appear to reflect the predisposition of myopes to retinal detachment. Clinicians should be aware of potential retinal pathology in patients undergoing PRK.

Adult↗

Cell attachment to, and contraction of, the retina in vitro.

PURPOSE: To examine the behavior of fibroblasts and retinal pigment epithelial cells after attachment to the retinal surface in vitro to elucidate the pathobiology of the early stages of epiretinal membrane formation. METHODS: Human retinal pigment epithelial (HRPE) cells and bovine Tenon's capsule fibroblasts (BTFs) were seeded onto the surface of bovine retinal explants maintained in organ culture. The changes induced in the underlying retina, including contraction, were assessed during a period of up to 10 days. Immunohistochemistry was used to assess proliferation of the seeded cells and to determine deposition of extracellular matrix. RESULTS: Explants of bovine neuroretina were maintained in organ culture, with good morphologic preservation of the inner limiting lamina and inner retinal layers, for 7 to 10 days. The HRPE cells and the BTFs attached to the retinal surface and exerted tractional forces, producing partial- and full-thickness retinal folding. Contraction commenced within 24 hours of attachment of the cells and continued for several days, with most of the contraction occurring within the next 48 to 72 hours. The HRPE cells and BTFs were found to be equally contractile. Deposition of cellular fibronectin (but not collagen type I) was demonstrated. CONCLUSIONS: The contractile cellular membranes generated in this organ culture system exhibit many of the morphologic and functional features of epiretinal membranes found in the early stages of proliferative vitreoretinopathy.

Adult↗

The characteristics and outcomes for patients presenting with unintentional domestic injuries to general practice.

AIM: To describe domestic unintentional injuries in three large, computerised general practices in the Wellington area. METHOD: Details of all domestic injuries were recorded from Accident Compensation Corporation (ACC) forms. RESULTS: Initial consultations for domestic unintentional injuries counted for 29.4% of all injuries for which ACC forms were completed and represented 1.2% of all patient contacts. The very young and elderly presented more frequently with domestic unintentional injuries. The types of injury and the injury incident varied between age groups. Most (75%) of the injured patients were treated by the practices without referral. CONCLUSION: Most (96%) of the patients who presented with domestic unintentional injuries were registered patients of the practices. This relationship provides an important opportunity for general practitioners to advise patients about accident prevention. More research is needed to compare the presentation of domestic unintentional injuries in general practice and in hospitals with accidents in the community.

Accidental Falls↗

A simple organ culture model for assessing the effects of growth factors on corneal re-epithelialization.

The effects of growth factors on re-epithelialization of wounded human and bovine corneas were studied in a simple organ culture system. Excisional trephine and epithelial scrape wounds were created on bovine and human corneo-scleral rings in which the endothelial corneal concavity was then filled with an agar-collagen mixture. Organ culture was undertaken at 37 degrees C in a humidified 5% CO2 incubator with serum-free Medium 199 maintained at the level of the conjunctival epithelium. Rates of reepithelialization in response to addition of exogenous epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and transforming growth factor type beta 1 (TGF-beta 1) were assessed by image analysis. Corneal cultures could be maintained for up to 3 weeks without significant stromal oedema or keratocyte deterioration and with little loss of epithelial architecture. Following wounding the cornea reepithelialized in a similar fashion to that observed in vivo i.e. a lag phase followed by migration/proliferation and the reformation of an intact multilayered epithelium. EGF accelerated, basic FGF had no effect on, and TGF-beta 1 inhibited the rate of corneal re-epithelialization. Our organ culture model maintains corneal integrity and provides a practical system in which to study factors that modulate corneal reepithelialization following wounding.

Animals↗

Type VI collagen is present in human and bovine vitreous.

BACKGROUND: Heterotypic (mixed) collagen fibrils that contain collagen types II, IX and V/XI have previously been identified in vitreous gel. The purpose of this study was to determine whether vitreous gel also contains type VI collagen microfibrils, as they are widely distributed in other tissues where they may play an important structural role. METHODS: Bovine and human vitreous gel was analysed by rotary shadowing electron microscopy after bacterial collagenase digestion and gel filtration chromatography. Bovine vitreous was extracted in 4 M guanidine hydrochloride, and following isopycnic centrifugation fractions were analysed by western blotting. RESULTS: Type VI collagen microfibrils were identified by electron microscopy in human and bovine vitreous. Type VI collagen was identified by western blot analysis. CONCLUSION: Type VI collagen is present in vitreous and may participate in the structural assembly of the vitreous gel.

Animals↗