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Biomedical subjects

J M Gibson

Publications and source records attributed to J M Gibson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Progestins abrogate estrogen-induced changes in the insulin-like growth factor axis.

OBJECTIVE: We sought to investigate the effect of oral progestins on estrogen-mediated changes in the insulin-like growth factor axis in the peripheral circulation. STUDY DESIGN: Oral conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, desogestrel, or norethindrone was given in a randomized triple-crossover fashion to 10 healthy postmenopausal women, and the effects on the insulin-like growth factor axis were determined. RESULTS: Baseline circulating insulin-like growth factor I levels were significantly reduced by conjugated equine estrogen (359 +/- 54 vs 225 +/- 44 ng/mL; P =.0001). This effect was reversed by progestins (medroxyprogesterone acetate, 254 +/- 44 ng/mL; desogestrel, 266 +/- 50 ng/mL; norethindrone, 286 +/- 48 ng/mL; F = 12.2; P =.0015). Free insulin-like growth factor I was reduced by conjugated equine estrogen (1.00 +/- 0.15 ng/mL vs 2.10 +/- 0.39 ng/mL; P =.004), but addition of progestogens had no further effect. Insulin-like growth factor II and insulin levels were unaffected by conjugated equine estrogen or progestins. Plasma insulin-like growth factor binding protein 1 concentration increased significantly from baseline with conjugated equine estrogen alone (44.1 +/- 6.0 vs 154 +/- 30 microg/L; P =.003). This rise was opposed by progestins of increasing androgenicity (medroxyprogesterone acetate, 130 +/- 26 microg/L; desogestrel, 100 +/- 16 microg/L; norethindrone, 78.0 +/- 12 microg/L; F = 12.5; P =.0015). Insulin-like growth factor binding protein 3 levels fell with conjugated equine estrogen, and this was reversed by progestins (conjugated equine estrogen, 2.17 +/- 0.13 mg/L; vs norethindrone and conjugated equine estrogen, 2.41 +/- 0.12 mg/L; F = 7.6; P =.01). Insulin-like growth factor binding protein 4 levels increased with conjugated equine estrogen with or without progestins, whereas insulin-like growth factor binding protein 2 levels were unchanged. CONCLUSIONS: Coadministration of androgenic progestins abrogates estrogen-related changes in circulating insulin-like growth factor I, insulin-like growth factor binding protein 1, and insulin-like growth factor binding protein 3. Such hormone replacement therapy-induced changes may have significant consequences for the development of cardiovascular disease and osteoporosis and implications for the use of insulin-like growth factor I in monitoring growth hormone replacement.

Cross-Over Studies↗
PubMed2000

Non-convulsive status epilepticus: a treatable cause of confusion in pituitary apoplexy.

Confusion occurring in pituitary apoplexy is well described. We describe a case of pituitary apoplexy associated with confusion, occurring as a result of non-convulsive status epilepticus. Electroencephalography should be performed in pituitary apoplexy associated with confusion if this treatable and potentially serious complication is not to be missed.

Adenoma↗
PubMed2000

Plasma VEGF and soluble VEGF receptor FLT-1 in proliferative retinopathy: relationship to endothelial dysfunction and laser treatment.

PURPOSE: To study plasma levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), its soluble receptor (sFlt-1) and von Willebrand factor (vWf, an index of endothelial damage or dysfunction) in patients with proliferative retinopathy and corresponding changes in plasma levels after pan-retinal photocoagulation (PRP). METHODS: Eighteen patients (10 men; age, 57+/-16 years, mean +/- SD) with proliferative retinopathy secondary to diabetes (n = 13) and ischemic retinal vein occlusion (n = 5) with no previous PRP therapy were studied. Blood samples were obtained before and at 4 months after the last PRP session. Baseline (prelaser) plasma levels of VEGF, sFlt-1, and vWf (all by ELISA) were compared with levels in 16 diabetic patients with background retinopathy ("hospital controls"), and 18 healthy, age- and sex-matched "healthy controls." RESULTS: Patients with proliferative retinopathy had significantly raised plasma VEGF when compared with both control groups (P = 0.001). Patients with proliferative retinopathy and hospital controls had significantly raised plasma vWf levels when compared with healthy controls (P = 0.012). There was no difference in sFlt-1 levels between patients and controls (P = 0.162). After PRP, there was a significant reduction in plasma VEGF levels at 4 months' follow-up (P < 0.001), but no significant changes in plasma sFlt-1 or vWf levels. Patients with complete resolution of neovascularization had a trend toward lower median VEGF levels (80 versus 150 pg/ml, P = 0.062), but vWf levels (P = 0.50) and sFlt-1 (P = 0.479) were not statistically different. Baseline VEGF and sFlt-1 levels were significantly correlated (Spearman r = 0.505, P = 0.032) but after PRP at 4 months' follow-up, this was no longer significant (r = -0.269, P = 0.28). CONCLUSIONS: In this pilot study, patients with proliferative retinopathy demonstrate elevated peripheral markers of angiogenesis and endothelial dysfunction, suggesting a role for these processes in the pathogenesis of this condition. A fall in levels of VEGF after successful laser treatment may provide an opportunity for monitoring disease progression or relapse via a blood sample.

Diabetes Complications↗
PubMed1999

Modification of plasma insulin-like growth factors and binding proteins during oral contraceptive use and the normal menstrual cycle.

OBJECTIVE: Sex steroid regulation of the insulin-like growth factor axis is a subject of contention. We examined the effect of combined oral contraceptives and investigated the cyclic variations in the insulin-like growth factor axis. STUDY DESIGN: Fasting blood samples were taken from 9 women receiving oral contraceptives, 10 women receiving no medication, and 10 male subjects. RESULTS: In women receiving oral contraceptives, insulin-like growth factor binding protein 1 remained highly phosphorylated and levels were acutely increased by sex steroid treatment (305 +/- 110 microg/L on day 14 of the cycle [medication phase] vs 118 +/- 70 microg/L during the medication-free period, P <.03). In women receiving no medication, insulin-like growth factor binding protein 1 levels were significantly lower (69 +/- 50 microg/L on day 14 of the menstrual cycle, P <.001) and varied cyclically, with a rise in the late-secretory phase that coincided with the appearance of nonphosphorylated and less phosphorylated insulin-like growth factor binding protein 1 isoforms. Compared with those in untreated women and in men, insulin-like growth factor I levels were decreased in women receiving oral contraceptives (405 +/- 104 ng/mL in untreated women and 330 +/- 28 ng/mL in men vs 287 +/- 73 ng/mL in women receiving oral contraceptives, P <.004). Oral contraceptive use had no effect on insulin-like growth factor II levels, and neither insulin-like growth factor I nor insulin-like growth factor II showed cyclic variation. CONCLUSION: The bioavailability of insulin-like growth factor I is reduced in users of oral contraceptives. This may contribute to the metabolic changes observed in such subjects.

Adult↗
PubMed1999

Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNA(Leu) A to G mutation.

OBJECTIVE: To study the association of retinal disease and the syndrome of maternally inherited diabetes and deafness caused by an A to G mutation in the tRNA leucine gene at base pair 3243 (A3243G) of the mitochondrial genome. DESIGN: Observational study of a genetically defined subject group. PARTICIPANTS: Thirteen subjects with the mitochondrial DNA A3243G mutation from seven different pedigrees with maternally inherited diabetes and deafness. INTERVENTION: Assessment of visual symptoms and visual acuity, dilated indirect ophthalmoscopy, retinal photography, and retinal electrophysiology. MAIN OUTCOME MEASURES: Loss of vision, funduscopic evidence of pigmentary retinal disease or diabetic retinopathy, and electrophysiologic evidence of defective functioning of the retinal pigment epithelium/photoreceptor complex. RESULTS: Funduscopic examination revealed abnormalities of retinal pigmentation in ten subjects (77%). Defects included speckled and patchy hyperpigmentation at the posterior pole of the fundus, particularly in the macular area, and varying degrees of loss of retinal pigmentation. Three subjects (23%) had visual symptoms, which included night blindness, visual loss, and photophobia. Electrophysiologic studies revealed impaired electro-oculogram responses in four of nine subjects with defects of retinal pigmentation (44%), two of whom also had much reduced scotopic and, to a lesser extent, flicker electroretinogram b wave potentials. Two subjects had diabetic retinopathy, including one with retinal depigmentation and impaired electro-oculogram activity. Both subjects with diabetic retinopathy had unilateral reduced electroretinogram responses, especially oscillatory potentials. CONCLUSIONS: Abnormalities of retinal pigmentation are common in subjects with maternally inherited diabetes and deafness caused by the mitochondrial DNA A3243G mutation. Visual symptoms, in particular loss of visual acuity, appear to be infrequent. The combination of deficits in the electro-oculogram and scotopic and flicker electroretinograms suggests that the retinal dystrophy includes defective functioning of retinal pigment epithelial cells and of both rod and cone photoreceptors. The pigmentary retinopathy does not prevent diabetic retinopathy; a single subject had funduscopic and electrophysiologic evidence of both diseases. Current evidence suggests that the mitochondrial DNA A3243G mutation accounts for 0.5% to 2.8% of diabetes. Most ophthalmic and diabetic clinics are therefore likely to contain such patients, who may benefit from identification of the genetic defect causing their disease and from genetic counseling.

Adenine↗
PubMed1999

Sorsby's fundus dystrophy: a case report of 24 years follow-up with electrodiagnostic tests and indocyanine green angiography.

PURPOSE: Five families with dominantly inherited macular dystrophy were originally described by Sorsby et al. in 1949. Key features include early bilateral central visual loss secondary to either choroidal neovascularisation or central geographical atrophy and late progressive chorioretinal atrophy. We report a member of one of the original families who has been studied with a series of investigations over a long time, providing important information on differences in the phenotype and natural history of a rare genetically determined macular dystrophy. METHODS: The patient has been followed up for the last 24 years, from asymptomatic to full manifestation of Sorsby's fundus dystrophy. Series of fundus photographs, colour vision, dark adaptation and electrodiagnostic tests were performed. The disease was also studied with fundus fluorescein angiography and indocyanine green angiography. RESULTS: Unlike her other family members, who were reported in other studies as all having rapid loss of vision secondary to disciform macular disease, our patient has a unique clinical course in that she has a progressive bilateral central and generalised chorioretinal atrophy with a well-preserved minute central island of fovea. Nyctalopia was her early and only symptom. There was evidence of central scotoma, tritanopia and mild abnormality in dark adaptation. Rod function was affected earlier and to a larger degree than cone function. CONCLUSIONS: The overall features suggest phenotypic variability within a family in this autosomal dominant macular dystrophy. The findings from indocyanine green angiography and a consecutive series of electrodiagnostic tests in this condition support the theory of partial choroidal hypoperfusion and an interesting progressive rod-cone dystrophy as part of the pathophysiology.

Adult↗
PubMed1999

Phosphorylated insulin-like growth factor binding protein 1 is increased in pregnant diabetic subjects.

During pregnancy, IGFs and their binding proteins (IGFBPs) are important for the growth of fetal and maternal tissues. IGFBP-1 normally circulates as a single, highly phosphorylated species (hpIGFBP-1). However, in pregnancy there are lesser phosphorylated isoforms (lpIGFBP-1) with decreased affinity for IGF-I, allowing for increased IGF bioavailability. Because regulation of IGFBP-1 is abnormal in type 1 diabetes, we examined the impact of this on IGFBP-1 and its phosphorylation status in diabetic pregnancy. We assessed IGFBP-1 in relation to birth weight, maternal weight gain, duration of diabetes, glycemic control, and the presence or absence of retinopathy in 44 diabetic and 11 nondiabetic subjects. We found that in type 1 diabetic patients there was a significant negative relationship between hpIGFBP-1 and birth weight (r = -0.42, P < 0.01) and between the ratio of hpIGFBP-1 to lpIGFBP-1 and birth weight (r = -0.38, P = 0.02) by week 18 of gestation. Multiple regression analysis confirmed that hpIGFBP-1 was the best single predictor of birth weight (R2 = 0.3, P = 0.001) in diabetic subjects using models including other parameters known to influence fetal size. In contrast to hpIGFBP-1 levels, lpIGFBP-1 levels were not associated with birth weight, but were significantly related to initial maternal BMI and maternal weight throughout gestation in diabetic subjects (r = -0.57, P < 0.001). hpIGFBP-1 levels were positively related to duration of diabetes (r = 0.38, P < 0.01). Diabetic subjects had significantly higher hpIGFBP-1 and lpIGFBP-1 levels than nondiabetic subjects (hpIGFBP-1: 215 +/- 21 vs. 108 +/- 13 microg/l, P = 0.01; lpIGFBP-1: 139 +/- 12 vs. 66 +/- 5 microg/l, P < 0.001), but the ratio of hpIGFBP-1 to lpIGFBP-1 was similar in both groups (2.1 +/- 0.3 [diabetic] vs. 1.7 +/- 0.2 [nondiabetic], NS). In summary, maternal IGFBP-1 levels were higher in diabetic than in normal pregnancies. Diabetic subjects with prolonged duration of diabetes and retinopathy had higher total IGFBP-1 levels than those with shorter disease duration. Thus hpIGFBP-1 in diabetic pregnancy is positively related to the duration of diabetes and inversely related to fetal growth, with lpIGFBP-1 being related to maternal weight and BMI. The ratio of hpIGFBP-1 to lpIGFBP-1 may be a more robust indicator of fetal outcome, since it was consistent between diabetic and nondiabetic subjects. Measurement of the different phosphorylated isoforms of IGFBP-1 may increase the usefulness of IGFBP-1 as a predictor of fetal growth in both normal and diabetic pregnancy.

Adult↗
PubMed1999

How to drastically reduce priming in word stem completion--and still present the words.

This paper describes a series of experiments in which we demonstrated that "dysphonemic" word stems, which are likely not pronounced in isolation as they are within a word (e.g., MUS in MUSHROOM or LEG in LEGEND), showed less priming than did "phonemic stems" (e.g., MUS in MUSTARD or LEG in LEGACY). Furthermore, words with either dysphonemic or phonemic three-letter stems gave rise to equivalent levels of priming when test cues were four-letter stems (LEGE) or word fragments (L_G_ND). Moreover, the difference between phonemic and dysphonemic stems persisted when nonpresented completion rates were matched. A final cued-recall experiment revealed that performance was greater for phonemic stems than for dysphonemic stems and that this difference was greater for older participants than for younger ones. These results are not readily accounted for by extant theoretical approaches and point to important methodological issues regarding stem completion.

Adult↗
PubMed1998

Sintering and oxidation using a novel ultrahigh vacuum transmission electron microscope with in situ magnetron sputtering.

The synthesis and processing of materials is often highly sensitive to the presence of trace contaminants and a number of technologically important materials demand the clean conditions associated with an ultrahigh vacuum environment. With increasing interest in understanding materials phenomena occurring on smaller and smaller length scales, the transmission electron microscope is finding increasing application in the characterization of new materials and processes. The need for ex situ sample preparation prior to analysis can raise questions regarding the validity of the data, however, due to contamination and the introduction of microstructural artifacts. In this paper we discuss the application of the ultrahigh vacuum transmission electron microscope to in situ studies of materials synthesis. To illustrate the capabilities of the electron microscope in this context, we present two case studies: the synthesis and subsequent sintering of supported copper nanoparticles, and the initial stages of the growth of Cu2O on clean (001) Cu. We describe the novel aspects of the instrumentation used, the methods of sample preparation, and our application of the plan-view imaging technique to in situ investigations.

Copper↗
PubMed1998

Pupillary dilatation and driving in diabetic patients.

Diabetic patients routinely have their pupils dilated for fundoscopy as part of the annual review. To assess the ability of diabetic patients to drive after pupillary dilatation we studied 61 diabetic patients (18 IDDM, 43 NIDDM), mean age 54.98 years, before and 1 h after pupillary dilatation with 1% tropicamide. Binocular visual acuity (BVA) and contrast sensitivity were checked without glare, with glare, and with glare and sunglasses. Glare was introduced using a 60 W bulb in all 61 patients and with a 500 W bulb in 37 of these patients. Prior to dilatation all 61 patients had a BVA of 6/9 or better. A significant reduction in BVA was found post-dilatation (p = 0.005) and 4 out of the 61 patients (6.56%) had a post-dilatation BVA of less than 6/9. The 60 W glare source caused a significant reduction in BVA pre-dilatation (p < 0.05), but not the 500 W glare. With glare, post-dilatation BVA reduced further, resulting in 6 and 7 patients having a BVA of less than 6/9 with the 60 W and 500 W glare source, respectively. The addition of sunglasses with glare did not improve the BVA. No patient with a BVA of 6/5 pre-dilatation reduced to less than 6/9 post-dilatation. No significant change in contrast sensitivity was found in any of the test conditions. We conclude that patients who meet the visual legal requirements to drive (BVA < or = 6/9) prior to dilatation may not fulfil them post-dilatation. This has important clinical implications and the time course of the phenomenon requires exploration. Meanwhile, patients need to be warned not to drive after pupillary dilatation when they attend for annual fundoscopic examination, certainly for at least two hours.

Adult↗
PubMed1998

Pain and powerlessness: the experience of living with peripheral vascular disease.

Peripheral vascular disease (PVD) is a widespread condition, the most common manifestation being a gradual occlusion of the arteries of the legs due to atheroma, which results in symptoms of ischaemia such as intermittent claudication or rest pain, ulceration and gangrene. Treatment of the condition is palliative and reconstructive, and aims to salvage the limb, restore mobility and function, and relieve pain. It usually involves attempts to revascularize the affected limb, either by surgical procedures such as bypass grafting, or by percutaneous transluminal angioplasty or thrombolysis. In some cases, it may be necessary to amputate the limb or part of it. Despite the chronicity of PVD, little is known about the ways in which individuals with vascular disease cope with their condition and about the effect it has on their life. In this context the aims of this study were to explore the lived experience of peripheral vascular disease, in order to identify key themes and categories, using a phenomenological grounded theory approach. A sample of nine individuals was drawn from patients who had had vascular bypass surgery within the past 18 months. Data were collected using audiotaped one-to-one interviews and the researcher's field notes, and were validated with a group of experienced vascular nurses. Transcripts were analysed using open and axial coding techniques, and major and minor categories were identified and related to other data collected. It appeared that vascular patients experienced powerlessness in relation to the direct effects of their condition and in relation to its treatment modalities. The findings suggested that the 'acute' style of management of PVD often led to unrealistic expectations on the patient's part, which gave rise to the experience of powerlessness. The implications of these findings for the management of patients with PVD are discussed.

Activities of Daily Living↗
PubMed1998

Using the Delphi technique to identify the content and context of nurses' continuing professional development needs.

In order to identify and prioritize the development needs of medical and surgical nurses, their possible approaches to learning, and the contextual factors influencing their professional development, a Delphi survey was carried out using a panel of 28 participants. Current development needs included skills in essential clinical care, specialist nursing, changing roles, patient care management, research and practice development. Although there was ambivalence about changing nurses' clinical roles, participants expected roles to diversify in the future. The need for responsiveness to change was emphasized, as was the need to maintain current areas of expertise. Professional development activity could take many forms, but fostering an organizational climate in which development was inherent in everyday working practices was felt to be as valuable as formal course attendance. Restricting factors included lack of time, resources, support and recognition. The survey has enabled professional and practice development activities to be prioritized locally, and the method used could be readily applied to other settings.

Attitude of Health Personnel↗
PubMed1998

New developments in retinal drusen.

Retinal drusen are an important manifestation of age-related maculopathy, and increase with ageing. Recent studies have shown that gentle laser photocoagulation can lead to resolution of soft drusen and may lessen the high risk of development of choroidal neovascularisation in these cases. Laser induced regression of retinal drusen appears to be a safe technique, but no long term results are yet available. Retinal drusen may also occur as a dominantly inherited disorder and current evidence suggests that these represent more than one disorder. Misclassification of retinal drusen as retinal exudates is an important cause of false positive referral in diabetic retinopathy screening programmes.

Aged↗