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Biomedical subjects

M Wilkins

Publications and source records attributed to M Wilkins.

At least 19 recordsLinked to original sources

Hardness and ultrasonic characteristics of the human crystalline lens.

PURPOSE: To evaluate the relationship between hardness of the human crystalline lens and its acoustic characteristics. SETTING: St. George's Hospital Medical School, University of London, London, United Kingdom. METHODS: Cataractous lenses from patients who had extracapsular cataract surgery were studied for hardness and ultrasonic characteristics. Lens hardness was assessed with an automated guillotine. Ultrasound velocity and attenuation were measured with a scanning acoustic macroscope using the pulse transmission reflection method. RESULTS: Thirty-seven lenses from 37 patients (mean age 75.5 years) were evaluated. Lens hardness was associated with ultrasound attenuation (r = 0.65, P <.0001) and attenuation frequency gradient (r = 0.67, P <.0001). The correlation of hardness with mean ultrasound velocity was not significant (r = 0.22, P =.2). CONCLUSIONS: The attenuation of ultrasound waves by the human crystalline lens correlated with its hardness. Ultrasonography can be used to evaluate lens hardness.

Aged↗

Prediction and assessment of the effects of mixtures of four xenoestrogens.

The assessment of mixture effects of estrogenic agents is regarded as an issue of high priority by many governmental agencies and expert decision-making bodies all over the world. However, the few mixture studies published so far have suffered from conceptual and experimental problems and are considered to be inconclusive. Here, we report the results of assessments of two-, three- and four-component mixtures of o,p'-DDT, genistein, 4-nonylphenol, and 4-n-octylphenol, all compounds with well-documented estrogenic activity. Extensive concentration-response analyses with the single agents were carried out using a recombinant yeast screen (yeast estrogen screen, YES). Based on the activity of the single agents in the YES assay we calculated predictions of entire concentration-response curves for mixtures of our chosen test agents assuming additive combination effects. For this purpose we employed the models of concentration addition and independent action, both well-established models for the calculation of mixture effects. Experimental concentration-response analyses revealed good agreement between predicted and observed mixture effects in all cases. Our results show that the combined effect of o,p'-DDT, genistein, 4-nonylphenol, and 4-n-octylphenol in the YES assay does not deviate from expected additivity. We consider both reference models as useful tools for the assessment of combination effects of multiple mixtures of xenoestrogens.

DDT↗

Effects of pectin on diarrhea in critically ill tube-fed patients receiving antibiotics.

BACKGROUND: Anaerobic colonic flora are necessary for the fermentation of fiber into short-chain fatty acids and constitute the bulk of fecal mass. Lack of dietary fiber in most enteral feedings, compounded by antibiotic therapy, suppresses normal colonic metabolism, resulting in diarrhea. Pectin, a water-soluble fiber, stimulates epithelial growth in the colon and thus reduces diarrhea. METHODS: Forty-four critically ill patients receiving enteral nutrition and antibiotic therapy were randomized to receive fiber-containing or fiber-free tube feedings and pectin or placebo. Data on frequency, consistency, and volume of fecal output; energy (caloric) intake; and administration of specific medications were collected for 9 days. Diarrhea was defined as 2 or more days with scores of 12 or higher on the Hart and Dobb diarrhea scale. RESULTS: Subjects in the 4 groups did not differ significantly in age, sex, severity of illness, or energy intake. Twelve subjects (27.3%) experienced diarrhea. Significantly fewer subjects in the fiber-free/placebo and fiber/pectin groups experienced diarrhea than did subjects in the fiber/placebo group (P = .02). On the basis of repeated-measures analysis of variance of daily mean scores, the severity of diarrhea did not differ significantly among the study groups over time (P = .16). CONCLUSIONS: The reduced rate of diarrhea found in this study may be related to the stringent definition of diarrhea used. The therapeutic dose of pectin for reducing diarrhea needs further exploration. The trend was toward less diarrhea in the fiber/pectin group, but the study needs to be replicated with a larger sample.

Adult↗

Understanding and controlling the scarring response: the contribution of histology and microscopy.

In response to injury, the body usually initiates a full and swift wound healing response resulting in reconstructed, repaired tissue. In certain instances, due to a variety of factors, this may not happen, an example being chronic granulating venous leg ulcers. At the other extreme, the wound may heal excessively, producing disabling hypertrophic scarring such as can occur following large, deep burn injuries. Our group is interested in the surgical treatment of the eye disease glaucoma. As will be explained, the successful surgical treatment of this disease depends on a reduced scarring response at the end of wound healing. The purpose of this article is to give an overview of our microscopic and histological experimental work which has furthered our understanding of tissue repair, particularly the scarring response and its potential modification for successful glaucoma surgery.

Antimetabolites↗

Calcium waves and oscillations driven by an intercellular gradient of inositol (1,4,5)-trisphosphate.

In response to a local mechanical stimulus, mixed glial cells initially exhibit a propagating intercellular Ca2+ wave. Subsequently, cells within a zone, at a specific distance from the stimulated cell, display asynchronous intracellular Ca2+ oscillations. The experimental hypothesis that the initial Ca2+ wave could be mediated by the passive diffusion of inositol (1,4,5)-trisphosphate (IP3) from the stimulated cell has been verified by model simulations. Further simulations with the same model also show that Ca2+ oscillations can only occur within model cells when the IP3 concentration is within a specific range. Thus, this passive diffusion model predicts (a) that the IP3 concentration gradient established in the cells following mechanical stimulation will initiate Ca2+ oscillations in cells in a specific zone along this gradient and (b) that different Ca2+ oscillatory patterns will occur within a specified oscillatory zone. Both of these predictions have been confirmed by experimental data. The failure of experimentally observed Ca2+ oscillations to approach synchrony or entrain indicates a low intercellular calcium permeability of about 0.1 micron/s, and further suggests that Ca2+ does not appear to act as a significant messenger in the initiation of these intercellular Ca2+ waves or oscillations. In conclusion a passive diffusion of IP3, but not Ca2+, through gap junctions remains the preferred hypothesis for the mechanism underlying mechanically-stimulated intercellular calcium waves and Ca2+ oscillations.

Binding Sites↗

Intercellular spiral waves of calcium.

Intercellular calcium waves have been observed in a large number of cell types, and are known to result from a variety of stimuli, including mechanical or hormonal stimulation. Recently, spiral intercellular waves of calcium have been observed in slices of hippocampal tissue. We use an existing model to study the properties of spiral intercellular calcium waves. Although intercellular spiral waves are well known in the context of cardiac muscle, due to the small value of the calcium diffusion coefficient intercellular calcium waves have fundamentally different properties. We show that homogenisation techniques give a good estimate for the plane wave speed, but do not describe spiral behaviour well. Using an expression for the effective diffusion coefficient we estimate the intercellular calcium permeability in liver. For the bistable equation, we derive an analytic estimate for the value of the intercellular permeability at which wave propagation fails. In the calcium wave model, we show numerically that the spiral period is first a decreasing, then an increasing, function of the intercellular permeability. We hypothesise that this is because the curvature of the spiral core is unimportant at low permeability, the period being approximately set instead by the speed of a plane wave along a line of coupled cells in one dimension.

Animals↗

Immunosensors: electrochemical sensing and other engineering approaches.

This article overviews the engineering approaches and the recent trends in the development of alternative immunoassay systems. A brief description of the main principles and limitations of conventional immunoassay is given. Immunosensing approaches overcoming these limitations are discussed. Alternatives to traditional immunoassay systems are discussed in terms of the enhancement of immunointeraction processes and in terms of the various detection principles. Applications of flow-injection techniques to the development of immunosensing systems are presented. Immunosensors are categorized based on the detection principle employed, as immunoelectrodes (electrochemical immunosensors), piezoelectric immunosensors, or as sensors based on optical detection of the immunointeraction. The discussion focuses on electrochemical immunosensors. In conclusion, the engineering issues involved in immunosensor development are outlined and trends towards practical applications are discussed.

Animals↗

The effectiveness of the routine clinic visit in the follow-up of breast cancer patients: analysis of a defined patient cohort.

The study aimed to identify the proportion of patients with relapse or a contralateral breast tumour who are diagnosed as a consequence of regular follow-up in a specialist breast clinic after breast conserving surgery and radiotherapy for early breast cancer. A retrospective review was undertaken of 490 consecutive patients entered into a randomized clinical trial of radiotherapy fractionation at a single institution. As part of the trial, patients were reviewed in a multidisciplinary breast clinic 3-monthly for the first 3 years, 6-monthly between 3 and 5 years and annually thereafter, with biennial mammography. For this study, information was retrieved from hospital records to ascertain: (a) whether patients were symptomatic at the time of relapse or contralateral breast tumour; and (b) whether they presented at a scheduled appointment or brought their appointment dates forward. The subsequent management of patients with relapse was reviewed to determine whether or not this may have been influenced favourably by a policy of regular follow-up. Twenty-one (44%) of the 48 patients with locoregional relapse were asymptomatic. Of these, 17 were detected by clinical examination (that is, directly as a result of a routine clinic attendance), while four were detected by routine mammography. Ten of the 17 patients diagnosed by clinical examination had successful surgery for locoregional relapse and all have remained disease free. Five of 17 developed distant metastases within 6 months and two others had skin nodules on the breast excised. Only three of the 67 patients with distant relapses were asymptomatic. Two of the 11 patients with contralateral breast tumours were asymptomatic and were diagnosed on routine mammography. The benefits and cost-effectiveness of less rigid approaches to follow-up of breast cancer patients needs to be evaluated in large prospective randomized trials.

Adult↗

Visual recovery under glare conditions following laser capsulotomy.

The purpose of this study was to look at the changes in Snellen visual acuity and contrast sensitivity under standard and glare conditions before and after Nd:YAG laser capsulotomy. Contrast sensitivity was measured with a Pelli-Robson chart; a Brightness Acuity Tester was used as a glare source. Seventeen pseudophakic patients with no other ocular disease underwent a capsulotomy. Under standard conditions, 7 showed an improvement in visual acuity and 15 showed an improvement in contrast sensitivity. Under glare conditions, 10 patients showed an improvement in visual acuity and all 17 showed an improvement in contrast sensitivity. The improvement in average contrast sensitivity was greater under glare (0.330) than under standard conditions (0.210; p = 0.01). Contrast sensitivity measurement, particularly under glare conditions, provides additional information in the assessment of pseudophakes with opaque posterior capsules.

Aged↗

Renal response to candoxatrilat in patients with heart failure.

OBJECTIVES: Our primary objective was to compare the effects of three different doses of candoxatrilat with the effects of placebo on urinary volume in patients with moderately severe heart failure. The effects of candoxatrilat on urinary composition, neuroendocrine indexes and renal hemodynamic function were also studied. BACKGROUND: Candoxatrilat, a neutral endopeptidase inhibitor, reduces degradation of atrial natriuretic peptide and provokes diuresis in patients with mild heart failure, but the renal effects have not been studied in patients with moderately severe heart failure in a placebo-controlled study. METHODS: In a double-blind crossover trial, the effects of intravenous boluses of saline vehicle (placebo) and 50, 100 and 200 mg of candoxatrilat were compared on separate days in 12 patients with heart failure. Urinary output and composition were measured for 8 h. Renal blood flow and glomerular filtration rate were determined by radionuclide techniques. Blood was withdrawn for the measurement of hormones before and 3 h after dosing. RESULTS: All doses of candoxatrilat increased urinary volume (e.g., [mean +/- SEM] 263 +/- 53 to 490 +/- 82 ml for saline solution and the 200-mg dose, respectively, p < 0.01) and sodium content (14 +/- 4 to 37 +/- 11 mmol, p < 0.001) in the 1st 4 h after dosing. Plasma atrial natriuretic peptide increased (140 +/- 26 to 279 +/- 37 pg/ml, p < 0.01), whereas aldosterone decreased (178 +/- 41 to 125 +/- 35 pg/ml, p < 0.01), and renin activity was unchanged (10 +/- 2 to 12 +/- 3 ng/ml per h). CONCLUSIONS: Candoxatrilat given acutely causes diuresis, even in patients with moderately severe heart failure.

Aged↗

A randomized cross-over study of the efficacy of codeine phosphate versus Ispaghulahusk in patients with gynaecological cancer experiencing diarrhoea during pelvic radiotherapy.

Diarrhoea is the commonest acute complication during radiotherapy treatment to the pelvis. Codeine phosphate and a low residue diet is the standard therapy for radiation-induced diarrhoea at The Royal Marsden NHS Trust. The hypothesis put forward was that Ispaghulahusk and codeine phosphate were equally effective in the treatment of diarrhoea during radiotherapy. Participants in the study were female patients who had experienced change of bowel habit whilst receiving radiotherapy for their gynaecological cancer. Quantitative data was collected from patient diaries and treatment flow-sheets. Ten patients were randomized into the trial, five to codeine phosphate, and five to Ispaghulahusk. Continuing the trial was questioned after 10 patients had been treated. All five patients in the codeine phosphate arm received adequate control, while the five patients allocated to the Ispaghulahusk arm were all crossed-over to codeine phosphate with resolution of their diarrhoea. The results show that Ispaghulahusk, whilst not totally ineffective at controlling diarrhoea, was significantly less effective than codeine phosphate. Our conclusion is that there is insufficient reason to change to a less effective and less palatable preparation for the control of radiation-induced diarrhoea.

Codeine↗

Evaluation of the short-term impact of counseling in general practice.

This paper describes the findings of a randomised controlled trial of the short-term impact of counseling in the general practice setting. Compared with patients who received usual advice from their general practitioner for acute problems such as relationship difficulties, anxiety and depression, those who received counseling from qualified counselors working within the primary health care context showed greater improvement in psychological health as measured by the General Health Questionnaire. Significantly fewer of those counselled were prescribed anti-depressant drugs by the general practitioners in the study, or were referred to psychiatrists or clinical psychologists for care. In addition those patients who attended sessions with the practice counselor were more likely to report that they were satisfied with their treatment and more expressed feelings of well-being.

Adult↗

Iron overload in multiply transfused patients who are HIV seropositive.

AIMS: To assess histologically the amount of iron deposited in liver biopsy specimens from HIV positive patients; and to perform estimations of liver iron on tissue from patients with an increase in parenchymal stainable iron. To correlate the amount of blood transfused and the degree of iron overload. METHODS: Liver biopsy specimens (n = 120) from 109 HIV positive patients, 74 of whom had AIDS, were examined retrospectively and the amount of iron, as visualised with Perls's stain, was graded. Fibrosis was assessed using connective tissue stains. Estimations of liver iron were performed on tissue retrieved from paraffin wax blocks in cases with histological grade 3 or 4 iron overload. The amount of blood transfused before liver biopsy was determined from the notes for each patient. RESULTS: Fifteen of the 120 liver biopsy specimens had significantly increased amounts of iron in their hepatocytes, as assessed histologically, and this was confirmed in seven cases by measurement of liver iron. There was a close correlation between the amount of blood transfused and the degree of iron overload. In the initial biopsy specimens only one case showed portal tract expansion. Three of the five patients who had repeat biopsies, however, showed progressive fibrosis. CONCLUSION: Multiply transfused HIV positive patients may develop clinically important iron overload and are at risk of developing progressive fibrosis. Superimposed liver disease, especially viral hepatitis, in these high risk patients may exacerbate the effects of the iron overload.

Adult↗

Selective alpha 1-adrenoreceptor blockers in the treatment of hypertension: should we be using them more?

It has become apparent in recent years that in the treatment of essential hypertension, reduction of blood pressure alone is not sufficient to reduce significantly the morbidity and mortality from ischaemic heart disease. Since the emergence of a multifactorial approach to the prevention of cardiovascular disease, the potential interaction between antihypertensive therapy and metabolic factors, such as control of blood glucose and lipid levels, has become an important consideration. Abnormal function of the sympathetic nervous system may contribute to both the initiation, or maintenance, of hypertension and the associated metabolic disturbances. The new generation of selective alpha 1-adrenoreceptor blockers, besides lowering blood pressure, appear to have favourable effects on lipid and glucose metabolism. The use of these drugs and their place in the treatment of hypertension are discussed.

Adrenergic alpha-Antagonists↗