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Biomedical subjects

J N Matthews

Publications and source records attributed to J N Matthews.

At least 55 records · Page 3Linked to original sources

Pain after subcutaneous injection of recombinant human erythropoietin: does Emla cream help?

Recombinant human erythropoietin (rHuEpo) is used to correct anaemia in dialysis patients. Subcutaneous administration of rHuEpo may be associated with pain at the injection site. This study assessed the pain of subcutaneous infiltration of two different preparations of rHuEpo, alpha and beta, and the value of a local anaesthetic (Emla) cream, in reducing the pain of infiltration. Forty-eight haemodialysis patients were enrolled into a double-blind, placebo-controlled, paired-comparison study. Pain was assessed using a visual analogue scale, a verbal descriptive scale and a direct comparison between paired treatments. Subcutaneous injection of rHuEpo alpha was more painful than rHuEpo beta (P < 0.001); using placebo cream 42% of patients described the pain of rHuEpo alpha as severe or very severe, whereas none of the patients found rHuEpo beta so painful. Application of Emla for at least 2 h prior to injection resulted in a significant reduction in the pain of both preparations, but was unable to reduce the pain of rHuEpo alpha to that of rHuEpo beta. Subcutaneous injection of rHuEpo alpha is more painful than rHuEpo beta, even after application of Emla. Although the discomfort of rHuEpo beta is graded as very mild by most adult patients the use of Emla is associated with a significant reduction in discomfort, which may be of benefit to paediatric patients.

Adult↗

Statistical aspects of the design and analysis of studies to compare haemodialysis membranes.

Some aspects of the statistical design and analysis of short-term studies of haemodialysis membranes are reviewed. The potential benefits of crossover studies comparing more than two treatments are emphasized. Designs based on Latin squares are advocated and the importance of avoiding carryover effects by ensuring adequate time between successive treatments is stressed. Studies of this type will usually record data serially within each period, so appropriate graphical techniques and the use of summary measures for the analysis of this type of data are considered. An example of the analysis of a study, using MINITAB, is included. Some issues of sample size estimation are discussed, and finally some more advanced designs and methods of analysis are briefly considered.

Humans↗

Clinical comparison of high-flux cellulose acetate and synthetic membranes.

Solute transport and alterations in complement and clotting induced by a new high-flux cellulose acetate membrane (CA-HF800-E, Diaphan) were compared with those for cellulose triacetate (CTA) and polysulphone in a cross-over clinical study. The membranes are similar in their small-molecule removal. Serum beta 2-microglobulin decreased with all membranes but the decrease was independent of membrane type. Associated with beta 2-microglobulin removal was a protein loss which averaged 2636 mg for Diaphan, 4937 mg for CTA, and 2500 mg for polysulphone. Albumin presence in the dialysate was less than the limit of detection (5 mg/l) but for each of the membranes, occasional readings above the limit of detection were noted. C3a generation for Diaphan is comparable with that for CTA and polysulphone, but differed for C5a and neutropenia. A highly significant correlation of the area under the concentration time curve of the two complement components was noted for the cellulose based membranes (r = 0.875, P = 0.0002 for Diaphan, r = 0.823, P = 0.006 for CTA) this relationship was less marked for polysulphone (r = 0.396, P = 0.29). Induction of clotting characterized by the thrombin-antithrombin III (TAT) complex were similar for the three membranes, as were changes in platelet counts. Our findings indicate that while it is possible to modify cellulose to produce a membrane whose solute transport and biocompatibility is similar to synthetic membranes such as polysulphone, the structural modifications induce considerable differences in the amount of protein lost.

Adult↗

A refinement to the analysis of serial data using summary measures.

A widely used method for the analysis of data collected serially over time is to reduce the data on each subject to a single summary that reflects some salient aspect of the response. The summaries from all subjects are then analysed using appropriate univariate methods. In some cases it may be unreasonable to suppose that summaries in a group share a common distribution. A weighted analysis may be preferable, with data from each subject used to determine the weights. This approach is explored in the context of an analysis of data on foetal distress during labour.

Bayes Theorem↗

Age and gender influence the severity of thyroid-associated ophthalmopathy: a study of 101 patients attending a combined thyroid-eye clinic.

BACKGROUND: The pathogenesis of thyroid-associated ophthalmopathy is thought to be autoimmune, although environmental and genetic factors are also considered to be important. As the morbidity of thyroid-associated ophthalmopathy is considerable and treatment often unsatisfactory, there a need to identify possible predisposing factors. OBJECTIVE: The study was undertaken in order to ascertain the relationship between age, gender and severity of thyroid-associated ophthalmopathy. PATIENTS: One hundred and one consecutive patients with thyroid-associated ophthalmopathy who presented over a period of 5 years to a combined thyroid-eye clinic. METHODS: Patients were assessed by grading their inflammatory signs and degree of diplopia, and by measurement of exophthalmos, palpebral aperture, differential intraocular pressure, and visual acuity. On the basis of the above an ophthalmopathy index was devised to grade the overall severity of eye disease. RESULTS: The mean age was 49.2 years (SD 13.4), the female-to-male ratio was 4.05, and mean ophthalmopathy index 6.49 (SD 3.3). Optic nerve compression was present in 9.9% of patients. There was a positive relationship between age and ophthalmopathy index (P < 0.001); after correcting for age, males had an average ophthalmopathy index 41% greater than that of females. CONCLUSION: There is an association between severity of thyroid-associated ophthalmopathy and (i) advancing age and (ii) female-to-male ratio, which has not been previously described. Patients over the age of 60 (particularly males) with Graves' disease appear to be at risk of developing severe eye disease.

Age Factors↗

Ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring (ABPM) in adults is proving to be useful. The aim of this study was to determine if ABPM is accurate in the lower blood pressure range encountered in children and, equally important, whether it is acceptable to children. Thirty one children, between the ages of 6 and 18 years, were assessed using an ambulatory blood pressure monitor that uses an auscultatory method. Blood pressure was measured in the contralateral arm with a mercury sphygmomanometer and an oscillometric device at the beginning and end of the study for comparison. Over a blood pressure range of 90-130 mm Hg systolic and 40-80 mm Hg diastolic, a close agreement was found with the sphygmomanometer; the limits of agreement (+/- 2 SD) were 11.6 mm Hg for systolic blood pressure and 13.6 mm Hg for diastolic blood pressure. The bias was less than 1.0 mm Hg. The ambulatory device was worn by all patients for at least 16 hours with an average of 52 recordings per patient. The majority found the device comfortable to wear and were not woken from sleep.

Adolescent↗

An application of the truncated Poisson distribution to immunogold assay.

An example of the use of the truncated Poisson distribution in an immunogold assay of dystrophin, a gene product of importance in the study of muscular dystrophies, is presented. The practical benefit of using minimum variance unbiased estimators of relevant functions of the parameter of the distribution is considered.

Analysis of Variance↗

Delayed type hypersensitivity is abnormal in patients with lichen planus.

Lichen planus is characterized by the histological features of a cell-mediated attack on the epidermis. To see whether there is any defect in cutaneous immunity in non-lesional skin, we measured the response to a contact sensitizer in 17 patients with lichen planus and 27 control subjects. Sensitization was induced with 30 micrograms dinitrochlorobenzene applied to the thigh. The subjects were challenged 4 weeks later with three doses of dinitrochlorobenzene (8.8, 12.5 and 17.7 micrograms), and responses were quantified with calipers as the change in skinfold thickness at 48 h. Patients with lichen planus were significantly less responsive with smaller reactions at all challenge doses. These abnormalities suggest that the skin is abnormal in areas unaffected by the rash, and raise the possibility that there may be a primary defect in the cutaneous immune system in lichen planus.

Female↗

Quantifying anti-inflammatory agents' potency by measurement of response to dinitrochlorobenzene challenge.

Classical assays of topical corticosteroid potency based on the induction of vasoconstriction are unsatisfactory for a number of reasons. These include the doubtful relevance of vasoconstriction to immune inflammation, and more importantly, the inability to compare non-steroidal agents with corticosteroids. Here we describe a simple assay in which the inhibitory effect of agents upon delayed type hypersensitivity response to dinitrochlorobenzene can be quantified by measurements of reaction as skinfold thickness with Harpenden callipers. Using this system we have confirmed the greater potency of clobetasol propionate (Dermovate) compared with betamethasone valerate (Betnovate), but the evidence for an inhibitory effect of topical cyclosporin (10% cream) compared with base on this response is less convincing.

Administration, Topical↗

Cellulose-based haemodialysis membranes: biocompatibility and functional performance compared.

Regenerated cellulose membranes are widely used in the treatment of renal failure. The presence of hydroxyl (OH) groups on the membrane surface plays an important role in initiating complement activation and also influences thrombogenicity. The OH groups may be masked or reduced by alteration of the manufacturing process of the membrane. We have undertaken a clinical study of four cellulose-based membranes (Cuprophan, Hemophan, cellulose acetate, and cellulose triacetate) in which the hydroxyl groups of the membrane have been replaced and the magnitude of replacement has varied from less than 1% to greater than 80%, to assess the role that these modifications play in functional performance, biocompatibility (neutropenia, leukocyte activation, anaphylatoxin generation, and hypoxaemia). Our findings indicate that there does not appear to be a straightforward correlation between the numbers of hydroxyl groups replaced and modification of biocompatibility, suggesting that not all hydroxyl groups behave in a similar way.

Cellulose↗

Centiles for adult head circumference.

Reference range for head circumference on the Tanner charts do not go beyond age 16. In this study the head circumference and heights of 354 adults in two British centres were measured. The centile charts constructed from these measurements show that adult head circumference is related to height. The mean head circumference of a male of average height is above the 97th centile for a 16 year old on the Tanner charts. The paediatric charts are therefore inappropriate for use in adult males.

Adolescent↗

Estimation of reference ranges from normal samples.

Reference ranges are very widely used in medicine, and are typically computed as mean plus or minus two standard deviations. However, their precise statistical basis is rarely discussed, and is open to different interpretations. They are sometimes calculated using the Student t distribution and satisfy the condition that the expected coverage of the reference population is some nominal value such as 95 percent or 99 per cent. A case is made for using reference ranges which are based on estimating symmetric centiles of the underlying normal distribution, and appropriate formulae are given. The simplest such estimator, the sample mean plus or minus the normal-based number of sample standard deviations, is shown to have both theoretical and practical advantages.

Normal Distribution↗

Oral cyclosporin inhibits the expression of contact hypersensitivity in man.

The expression of delayed contact hypersensitivity was studied in 6 patients with chronic contact dermatitis treated with cyclosporin A (CsA) 5 mg/Kg/day. Quantitative patch test challenge was used to establish individual dose-response curves and threshold concentration to certain allergens in the European Standard Battery. In all 6 patients, responses were reduced over the whole range of allergen concentrations, and in the 5 in whom the threshold for expression of contact hypersensitivity could be determined, the threshold was raised by CsA therapy. In addition, the clinical manifestations of allergic contact dermatitis underwent complete resolution within 2-3 weeks of CsA therapy. It was concluded that CsA inhibits expression of delayed contact hypersensitivity reactions in human skin.

Administration, Oral↗

The action spectrum between 320 and 400 nm for clearance of psoriasis by psoralen photochemotherapy.

We have compared the effectiveness of oral 8-methoxypsoralen photochemotherapy (PUVA) using ultraviolet fluorescent lamps with peak emission at either 325, 352 or 370 nm in the treatment of 24 patients with psoriasis. The forearms of each patient were treated three times weekly with two of the three lamps. The erythemal sensitivity of each patient was tested before the first treatment to ensure that equally erythemal doses of radiation were given from each of the lamps. A side-to-side comparison was used to assess response to treatment at weekly intervals for the 6 weeks of the trial. The lamp with peak emission at 325 nm was shown to be significantly superior to either of the other lamps in terms of response assessed at weekly intervals, and time to clearance of psoriasis. An action spectrum, constructed from the median doses required for clearance of psoriasis using each of the lamps, showed that the effectiveness of the radiation decreased exponentially with increasing wavelength throughout the UVA waveband, such that radiation at 320 nm was an order of magnitude more effective than at 360 nm. This suggests that lamps with peak emission around 325 nm will be more effective than those conventionally used in PUVA units with a peak emission at 352 nm. Lamps with peak emission around 325 nm are also highly effective in the treatment of psoriasis with phototherapy alone. Thus a single treatment unit containing these lamps could be used either for PUVA or ultraviolet phototherapy of psoriasis, avoiding duplication or irradiation equipment.

Adolescent↗

Corrections in counting paired nuclei labelled with bromodeoxyuridine in tissue sections.

Bromodeoxyuridine is finding increasing use as an alternative to, or in conjunction with, tritiated thymidine for labelling nuclei in DNA synthesis. Precise identification of labelled nuclei is possible, even when there is considerable overlap between neighbouring nuclei. In the sparsely labelled renal cortex of the normal male mouse, 'flash labelling' with bromodeoxyuridine shows single labelled nuclei at 1 h. At 24, 48 and 72 h after injection of bromodeoxyuridine, some labelled cells are seen to lie adjacent and such labelled pairs are presumed to be the result of cell division. Single labelled nuclei at 24, 48 and 72 h might indicate arrest in DNA synthesis or a prolonged G2 period, but it is important to recognize that a correction must be made for paired labelled nuclei in which one member is out of the plane of section. The factors involved in making such a correction are discussed and a correction table calculated. In the normal male mouse renal cortex, we show that nearly all cells labelled at 1 h had divided by 72 h.

Animals↗