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Biomedical subjects

J M Gibson

Publications and source records attributed to J M Gibson.

At least 73 records · Page 4Linked to original sources

Focus of nursing in critical and acute care settings: prevention or cure?

The fluidity of the boundaries of critical and acute care can lead to challenges for nurses working on acute general wards when caring for post-critical care patients and for those in whom a critical care situation arises during a period of acute care. The development and use of critical care skills pose special difficulties for acute care nurses, because of the acuteness and infrequency of such incidents and the diversity of skills the nurses need to possess. Nonetheless, critical care is an important component of an acute ward nurse's repertoire, particularly in relation to preventing episodes of critical illness. It might be expected that the increased provision of high dependency units and the formation of postoperative care teams would relieve some of this pressure, but such developments are, in fact, more likely to create an increase in overall patient acuity. They may, in addition, lead to an over-reliance on the use of such facilities and must be implemented carefully in order to bridge, rather than widen, the gap between acute and critical care. Critical care is used in this paper as a global term, to encompass all settings where patients are usually more highly dependent and critically ill than patients on general wards. It includes intensive therapy, high-dependency, coronary care and other specialist critical care units.

Activities of Daily Living↗

Prevalence of age-related maculopathy at two points in time in an elderly British population.

UNLABELLED: As the demography of Western society changes, the population prevalence of diseases such as age-related macular degeneration (AMD) is expected to rise. Despite this, there remains a paucity of quality data concerning the population prevalence of AMD, the commonest cause of blindness in the elderly. PURPOSE: To report the prevalence of AMD at two points in time in an elderly population. METHOD: A geographically defined random population sample of elderly people was defined in 1980, and studied in 1982-4. In 1990, a cohort of survivors was identified. Participants underwent full ophthalmic examination with fundus photography using the same camera on each occasion. Photographs were randomly encoded and graded by two independent masked observers using the Wisconsin Age-related Maculopathy Grading System. Disagreements were resolved by consensus. RESULTS: Eighty-eight survivors participated in the follow-up examinations. Of these, 82 subjects had gradable retinal photographs for both examination points in at least one eye. There were 158 pairs of images (initial and subsequent) available for analysis. The mean age was 80 years (range 77-90 years) at the initial examination, and 87 years (range 84-97 years) at the subsequent examination; 70.7% of subjects were female. Prevalence rates for the initial examination were: drusen 72.8%, drusen confluence 37.3%, degeneration of the retinal pigment epithelium (RPE) 51.3%, increased pigment 22.2%, exudative AMD 1.9% and geographic atrophy 1.9%. Rates at second examination were: drusen 62.7% drusen confluence 41.8%, RPE degeneration 72.8%, increased pigment 16.5%, exudative AMD 3.8% and geographic atrophy 3.2%. CONCLUSION: This 'double' prevalence study provides detailed data on AMD lesions at two points in time in a population-based group of elderly people.

Age Distribution↗

Seven year follow-up of age-related maculopathy in an elderly British population.

UNLABELLED: Despite age-related macular degeneration (AMD) being the commonest cause of blindness amongst the elderly in Western society, the incidence of new lesions is poorly documented and the natural history of existing disease remains ill understood. PURPOSE: To document in an elderly population the incidence of new AMD lesions and the progression of pre-existing AMD over time. METHOD: Baseline ophthalmic examinations were performed on a geographically defined random population sample of elderly people in 1982-4, and retinal photographs taken. The present study re-examined and re-photographed survivors after approximately 7 years using the same fundus camera. Photographs were randomly encoded, and independently graded for AMD features by two masked observers using the Wisconsin AMD grading system. Disagreements were resolved by review to reach a consensus. RESULTS: Eighty-two of the 88 participating survivors had photographs of gradable quality on both occasions in at least one eye. Mean age at follow-up was 87 years (range 84-97 years) and 70.7% of subjects were female. Paired photographs were available on 158 eyes, and showed important differences in drusen type, drusen area and characteristics of the retinal pigment epithelium (RPE) between initial and subsequent examinations. The 7 year incidence (and regression) of lesions was: drusen 30.6% (20.0%), RPE degeneration 54.5% (8.8%), increased pigment 11.6% (64.7%), subretinal haemorrhage 1.3%, subretinal scar/fibrin 1.3% and geographic study 1.3%. CONCLUSION: These unique population-based results provide new insight into the natural history of AMD in an elderly population.

Aged↗

Purification and characterization of the insulin-like growth factor-binding protein-1 phosphoform found in normal plasma.

Our previous work has shown that, in the normal circulation, insulin-like growth factor-binding protein-1 (IGFBP-1) is present as a single highly phosphorylated species. In this study, we have purified this previously uncharacterized isoform of IGFBP-1 to determine its ligand-binding affinity and the potential significance of highly phosphorylated IGFBP-I. Immunoaffinity chromatography was used to isolate IGFBP-1 from normal human plasma and from human hepatoma (Hep G2) cell medium as an alternative source of the IGFBP-1 phosphoform in the circulation. The affinity of this highly phosphorylated IGFBP-1 was compared with that of nonphosphorylated IGFBP-1 and recombinant human (rh) IGFBP-3 by equilibrium binding to IGF-II and IGF-II. Anion exchange (IEX) HPLC, nondenaturing electrophoresis, alkaline phosphatase treatment, and ligand-binding studies indicated that the highly phosphorylated IGFBP-1 from HepG2 cells was comparable with IGFBP-1 from plasma. In binding to IGF-I, the plasma phosphoform of IGFBP-1 was found to have a higher affinity (2.3 +/- 1.1 x 10(10) M-1) than nonphosphorylated IGFBP-1 (2.5 +/- 1.7 x 10(9) M-1, P < 0.002). However, when binding to IGF-II, phosphorylation had no affect on the affinity of IGFBP-1 (3.6 +/- 2 x 10(9) M-1 vs. 1.8 +/- 3 x 10(9) M-1, P not significant). Therefore, in the circulation, IGF-I has a considerably higher affinity than IGF-II for IGFBP-1 (P < 0.02). The affinity of phosphorylated IGFBP-1 from plasma (2.3 +/- 1.1 x 10(10) M-1) also was significantly higher than the affinity of IGFBP-3 for IGF-I (5.6 +/- 4.2 x 10(9) M-1, P < 0.005). These data suggest that the highly phosphorylated IGFBP-1 in the normal circulation will preferentially bind IGF-I rather than IGF-II, whereas in pregnancy, the affinity of IGFBP-1 for IGF-I will be reduced because of the appearance of non- and lesser-phosphorylated forms. This lends support to the theory that changes in IGFBP-1 phosphorylation may influence the modulatory effects of IGFBP-1 on IGF bioavailability.

Chromatography, High Pressure Liquid↗

Transgenic white clover. Studies with the auxin-responsive promoter, GH3, in root gravitropism and lateral root development.

We report improved method for white clover (Trifolium repens) transformation using Agrobacterium tumefaciens. High efficiencies of transgenic plant production were achieved using cotyledons of imbibed mature seed. Transgenic plants were recovered routinely from over 50% of treated cotyledons. The bar gene and phosphinothricin selection was shown to be a more effective selection system than nptII (kanamycin selection) or aadA (spectinomycin selection). White clover was transformed with the soybean auxin responsive promoter, GH3, fused to the GUS gene (beta-glucuronidase) to study the involvement of auxin in root development. Analysis of 12 independent transgenic plants showed that the location and pattern of GUS expression was consistent but the levels of expression varied. The level of GH3:GUS expression in untreated plants was enhanced specifically by auxin-treatment but the pattern of expression was not altered. Expression of the GH3:GUS fusion was not enhanced by other phytohormones. A consistent GUS expression pattern was evident in untreated plants presumably in response to endogenous auxin or to differences in auxin sensitivity in various clover tissues. In untreated plants, the pattern of GH3:GUS expression was consistent with physiological responses which are regarded as being auxin-mediated. For the first time it is shown that localised spots of GH3:GUS activity occurred in root cortical tissue opposite the sites where lateral roots subsequently were initiated. Newly formed lateral roots grew towards and through these islands of GH3:GUS expression, implying the importance of auxin in controlling lateral root development. Similarly, it is demonstrated for the first time that gravistimulated roots developed a rapid (within 1 h) induction of GH3:GUS activity in tissues on the non-elongating side of the responding root and this induction occurred concurrently with root curvature. These transgenic plants could be useful tools in determining the physiological and biochemical changes that occur during auxin-mediated responses.

Agrobacterium tumefaciens↗

Reduced insulin-like growth factor binding protein-1 (IGFBP-1) levels correlate with increased cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM).

IGF-I and -II levels are altered in patients with atherogenic lipid profiles and may contribute to the development of macrovascular disease in NIDDM. We examined cardiovascular risk factors, IGF-I, IGF-II and IGFBP-1 in 74 NIDDM patients analysed as a whole group and according to treatment type. IGF-I was not significantly associated with cardiovascular risk factors but IGF-II levels correlated positively with total and LDL cholesterol most markedly in the diet treated group (0.72, p < 0.01 and 0.76, p < 0.01 respectively). In the whole group reduced IGFBP-1 levels were significantly associated with factors known to increase cardiovascular risk: i.e. low HDL cholesterol (0.31, p < 0.01) and elevated blood pressure (-0.35, p < 0.01), BMI (-0.37, p < 0.01), insulin (-0.29, p < 0.01) and proinsulin (-0.24, p < 0.01). In the treatment groups IGFBP-1 was lower in patients on diet alone (n = 11, 42.6 +/- 11.6 mu g/l) and sulphonylurea +/- insulin (n = 39, 53.2 +/- 7.6 mu g/l) relative to insulin treatment (n = 24, 103.0 +/- 19, 7 mu g/l, p < 0.05). The lower levels of IGFBP-1 were not due to a significant change in phosphorylation status from the highly phosphorylated circulating form since lesser and non-phosphorylated variants were undetectable in 53/74 patients. Multiple regression analysis revealed the best predictors of IGFBP-1 were BMI and MAP (R2 = 0.2. p < 0.001) and for blood pressure, IGFBP-1 and age (R2 = 0.47, p < 0.001). These findings indicate that in NIDDM patients low IGFBP-1 levels are associated with multiple factors predisposing to atherogenesis.

Blood Pressure↗

Hypertensive retinopathy: a review of existing classification systems and a suggestion for a simplified grading system.

With the advent of sophisticated ophthalmological investigations and a better understanding of the pathophysiology and clinical or prognostic correlates of the fundal lesions in hypertension, the limitations of early classification schemes using simple ophthalmoscopic appearances are increasingly apparent. This review describes the existing classification systems for hypertensive retinopathy and their limitations, as well as the pathophysiological effects of hypertension on the retinal vasculature. A new and simpler grading system for hypertensive retinopathy is proposed, dividing the features according to prognosis into two categories of non-malignant vs malignant hypertension. Such a simpler, updated system for our medical practice has been long overdue.

Humans↗

Fibrinogen, cholesterol and smoking as risk factors for non-arteritic anterior ischaemic optic neuropathy.

Non-arteritic anterior ischaemic optic neuropathy (AION) is thought to be due to occlusion of the posterior ciliary circulation. Raised lipid and fibrinogen concentrations are recognised risk factors for vessel occlusion in cardiovascular disease and stroke but, although suspected as risk factors in non-arteritic AION, they have not been studied in this condition. We therefore performed a case-control study on 41 patients with non-arteritic AION, looking at these and other atherosclerotic risk factors. The odds ratio of cholesterol being > 6.5 mmol/l in non-arteritic AION was 2.7 (95% confidence interval 1.09 to 6.65; p < 0.05) and of fibrinogen being > 3.6 g/l was 5 (2.66 to 9.39; p < 0.05). Smoking was also found to be significantly associated with non-arteritic AION, the odds ratio being 16 (3.23 to 79.23; p < 0.001). These were the only risk factors found to be significantly associated with non-arteritic AION. This raises the possibility that appropriate medical management of these factors could be given to prevent recurrence in the fellow eye.

Aged↗

Hormonal regulation of circulating insulin-like growth factor-binding protein-1 phosphorylation status.

Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) normally circulates as a single, highly phosphorylated species. However, IGFBP-1 phosphorylation status can be altered, such as in pregnancy where non- and lesser phosphorylated isoforms are also present. We have examined how hormonal regulators of circulating IGFBP-1 influence its phosphorylation status and, hence, its ability to modulate IGF activity. In response to insulin-induced hypoglycemia (0.2 U/kg, iv), an increase in the highly phosphorylated isoform was observed after 5 h [16 (range, 11.5-35.5) to 77 (range, 63-250) microgram/L; 4.8-fold increase; P = 0.009], but no non- or lesser phosphorylated variants could be detected. Glucagon (1 mg, sc), increased IGFBP-1 from 27 (range, 13-36.5) to 112 (range, 100.5-129) micrograms/L (4.1-fold increase; P = 0.009) after 90 min despite preceding insulin concentrations of more than 500 pmol/L, but again the IGFBP-1 remained in the highly phosphorylated form. Regulation of IGFBP-1 phosphorylation by sex steroids was studied by comparing women receiving a combined oral contraceptive with women on no medication. Although plasma IGFBP-1 levels were significantly elevated in the treatment group [120 (range, 97.5-237.5) vs. 52 (range, 38-70) micrograms/L; P < 0.004], there was no difference in the form of IGFBP-1 present. The acute effect of somatostatin (500 micrograms/h) on IGFBP-1 phosphorylation status was also studied. Somatostatin only increased the phosphoform characteristic of normal subjects; the appearance of non- or lesser phosphorylated variants was not induced. The effect of rhIGF-I (80 or 120 micrograms, sc) on plasma IGFBP-1 was studied in three subjects with Laron's syndrome. A transient increase in the highly phosphorylated isoform of IGFBP-1 was noted; there was no rise in the non- and lesser phosphorylated isoforms also found in the plasma of Laron's syndrome subjects. These data suggest that only the highly phosphorylated species of IGFBP-1 is under hormonal control; regulation of the non- and lesser phosphorylated variants remains to be determined.

Adult↗

Choice of treatment affects plasma levels of insulin-like growth factor-binding protein-1 in noninsulin-dependent diabetes mellitus.

Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) modulates the metabolic and mitogenic effects of IGFs. Although IGFBP-1 levels are abnormally high in insulin-dependent diabetes (IDDM), relatively little is known in NIDDM; conflicting data have suggested both high and low levels. We investigated whether treatment modifies IGFBP-1 levels in two groups of NIDDM patients. Study 1 examined fasting concentrations in groups of patients with NIDDM, comparable except for treatment type (sulfonylurea, n = 23; once daily insulin, n = 15; sulfonylurea plus once daily insulin, n = 14; multiple insulin injections, n = 9) and 25 nondiabetic subjects. In sulfonylurea-treated patients there were markedly reduced plasma IGFBP-1 concentrations (median, interquartile range in parentheses): control, 61.0 (36-96) micrograms/L; sulfonylureas alone, 31.5 (21-61) micrograms/L (P < 0.01); and sulfonylureas plus insulin, 31.5 (9-53) micrograms/L (P < 0.01). Once daily insulin was associated with values similar to those in the control group [62.0 (27-103) micrograms/L; P = NS], whereas IGFBP-1 levels were higher with multiple insulin injection therapy [156.0 (71-184) micrograms/L; P < 0.05]. Proinsulin levels were higher in sulfonylurea-treated patients, but there was no significant correlation between IGFBP-1 and proinsulin within any individual group. Study 2 examined the effects of treatment on the dynamics of IGFBP-1 levels between 0800-1900 h. In control subjects (n = 8), levels fell from 0800 h (mean +/- SEM, 22.4 +/- 5.2 micrograms/L) to 1000 h (14 +/- 5.2 micrograms/L), followed by a rise, more rapid after food, to a peak at 1240 h (20.6 +/- 3.7 micrograms/L). Levels then declined until 1500 h (10.7 +/- 2.9 micrograms/L), with a further postprandial peak at 1840 h (23.1 +/- 3.2 micrograms/L). Sulfonylurea therapy (n = 6) resulted in a complete loss of this pattern, with a marked fall in IGFBP-1 from 0800 h (22 +/- 2.7 micrograms/L) to less than 7 micrograms/L for the remainder of the study (area under the curve, 1150-1400 h, P < 0.001 vs. control). By contrast, in metformin-treated patients (n = 7), neither IGFBP-1 levels nor postprandial peaks were significantly different from those in the control group. Our findings suggest that in patients with NIDDM, the regulation of IGFBP-1 is markedly influenced by the choice of treatment.

Carrier Proteins↗

Tests that are robust against variance heterogeneity in k x 2 designs with unequal cell frequencies.

Heterogeneity of variance produces serious bias in conventional analysis of variance tests of significance when cell frequencies are unequal. Welch in 1938 and 1947 proposed an adjusted t test for the difference between two means when cell frequencies and population variances are both unequal. This article describes two ways to use the Welch t to evaluate the significance of the main effect for two treatments across k levels of a concomitant factor in a two-way design. Monte Carlo results document the bias in conventional analysis of variance tests and the stable and appropriately conservative results from applications of the Welch t to evaluation of treatment effects in the two-way design.

Analysis of Variance↗

Power of a test that is robust against variance heterogeneity.

Welch (1947) proposed an adjusted t test that can be used to correct the serious bias in Type I error protection that is otherwise present when both sample sizes and variances are unequal. The implications of the Welch adjustment for power of tests for the difference between two treatments across k levels of a concomitant factor are evaluated in this article for k x 2 designs with unequal sample sizes and unequal variances. Analyses confirm that, although Type I error is uniformly controlled, power of the Welch test of significance for the main effect of treatments remains rather seriously dependent on direction of the correlation between unequal variances and unequal sample sizes. Nevertheless, considering the fact that analysis of variance is not an acceptable option in such cases, the Welch t test appears to have an important role to play in the analysis of experimental data.

Analysis of Variance↗

Friendly societies.

Readers will probably be aware of the two friendly societies associated with the dental profession, the Dentists' Provident Society Ltd. and the Dentists' and General Mutual Benefit Society, which offer permanent sickness cover to their members. They may not be aware, however, that these societies are part of a wider movement which at one time offered almost the only available protection for the worker against the expenses of sickness and death.

History, 17th Century↗

Visual acuity and pupillary reactions after peribulbar anaesthesia.

The effect of peribulbar anaesthesia on optic nerve function in 20 patients, before and after cataract surgery, was measured. All the patients had decreased visual acuity. Five (25%) had no perception of light. Seventeen (85%) developed a relative afferent pupil defect (RAPD). No patients saw the operating instruments. Seven (35%) had improved visual acuity immediately postoperatively. Patients should be warned that they may lose vision completely on being given a peribulbar anaesthetic; however their vision will improve, but not necessarily immediately, postoperatively. Examination for an RAPD is a good method of providing reassurance that the operating instruments will not be seen.

Aged↗