Adjusting for baseline: change or percentage change.
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Bias↗
Biomedical subjects
J N Matthews
Publications and source records attributed to J N Matthews.
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↗
An indirect calorimetry system for ventilator dependent very low birthweight infants.
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Calorimetry, Indirect↗
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↗
Predicting outcome after childhood hemolytic uremic syndrome.
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Child↗
'Irritants' increase the response to an allergen in allergic contact dermatitis.
We studied the effect of "irritants" on the response to an allergen in 15 patients. Dilutions of allergens were applied in duplicate, and 24 hours later they were removed and sodium lauryl sulfate (11 subjects) or anthralin (dithranol) (four subjects) was applied for a further 24 hours to one set of patches. Control dilutions of irritants alone were applied. Responses were measured objectively at 72 hours. The response to both allergen and irritant was greater than to either alone. Doses of allergen, which did not produce a response when applied alone, produced a response when an irritant was added. Irritants therefore increase the allergic contact dermatitis response and may explain the presence of contact dermatitis in patients with negative patch tests.
Allergens↗
Analysis of serial measurements in medical research.
In medical research data are often collected serially on subjects. The statistical analysis of such data is often inadequate in two ways: it may fail to settle clinically relevant questions and it may be statistically invalid. A commonly used method which compares groups at a series of time points, possibly with t tests, is flawed on both counts. There may, however, be a remedy, which takes the form of a two stage method that uses summary measures. In the first stage a suitable summary of the response in an individual, such as a rate of change or an area under a curve, is identified and calculated for each subject. In the second stage these summary measures are analysed by simple statistical techniques as though they were raw data. The method is statistically valid and likely to be more relevant to the study questions. If this method is borne in mind when the experiment is being planned it should promote studies with enough subjects and sufficient observations at critical times to enable useful conclusions to be drawn. Use of summary measures to analyse serial measurements, though not new, is potentially a useful and simple tool in medical research.
Animals↗
Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA.
Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C.
Alprostadil↗
Factorial designs for crossover clinical trials.
When measuring the joint effect of two factors it is advantageous to use a factorial design. If the application is suitable, efficiency may be further improved by using a crossover design. This paper presents a flexible method for amalgamating these two devices. Designs are constructed from smaller designs, known as bricks, generated cyclically from tabulated initial sequences. The bricks have known efficiencies for estimation of direct treatment main effects and interactions; the efficiencies can be simply combined to approximate the efficiencies of the whole design. This allows the user to build a design that is tailored to the particular objectives of the experiment. Three and four periods, and two factors with up to four levels are considered.
Antihypertensive Agents↗
Comparison of four methods of preoxygenation.
We studied four different techniques of preoxygenation in 20 healthy volunteers, by continuous analysis of respired gases. Three minutes of tidal breathing from a Magill breathing system or four vital capacity breaths from a non-rebreathing system were found to be equally effective, whereas four vital capacity breaths from a Magill breathing system were less effective. Maximal expiration before application of the face mask resulted in improved oxygenation when four vital capacity breaths were taken from a Magill system.
Adult↗
Inhibition of photosensitivity in erythropoietic protoporphyria with terfenadine.
The effect of terfenadine on the response to irradiation with blue light was measured in seven patients with erythropoietic protoporphyria. Terfenadine caused significant inhibition of the immediate flare reaction, but did not alter the erythemal response localized to the irradiation sites. Treatment with beta-carotene had no effect on the flare and erythemal responses. However, the flare reaction was still inhibited by terfenadine during treatment with beta-carotene. These results show that histamine release is involved in the mechanism of porphyrin photosensitivity. H1 receptor antagonists may be of use in the treatment of patients with erythropoietic protoporphyria.
Adolescent↗
The influence of area of application on sensitization by dinitrochlorobenzene.
We have investigated the effect on sensitization of altering the area of application of 2,4,dinitrochlorobenzene (DNCB) at a constant dose per unit area. We showed that, when an area of less than 1 cm2 is used, this area is critical in determining the degree of sensitization. This contrasts with previous work that showed, for larger areas, an alteration in the area of application had little effect on sensitization, whereas keeping the area constant and increasing the concentration of DNCB increased the degree of sensitization. We suggest that not only is the amount of antigen important in determining response, but also the distribution of the antigen as presented to the afferent limb of the immune system.
Dermatitis, Contact↗