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Biomedical subjects

J N Matthews

Publications and source records attributed to J N Matthews.

At least 73 records · Page 4Linked to original sources

'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↗

Low-dose exposure to antigen induces sub-clinical sensitization.

We examined the effects of a small initial sensitizing dose of antigen (dinitrochlorobenzene, DNCB) on the subsequent response to a second, defined sensitizing stimulus. The second stimulus was actually the regimen of four doses of DNCB (3.125, 6.25, 12.5, and 25 micrograms) normally used as the elicitation challenge. In two separate experiments 13 and 18 control subjects received an initial 'challenge' with the four doses to induce sensitivity, and 4 weeks later their responses were determined with a second, elicitation challenge. Two groups of 12 and 15 experimental subjects received an initial dose predicted to induce clinically detectable sensitivity in 50% or 25%, respectively. Four weeks later, their responsiveness was determined with quantitative challenge and the subjects who gave no response received a further challenge 4 weeks later. Their responses, compared with those from the control subjects, were augmented, indicating that sub-clinical priming of the immune system had indeed occurred.

Analysis of Variance↗

Ultrasound measurement of renal size in newborn infants.

Renal measurements were made by ultrasonography in 560 healthy newborn infants. Three dependent variables (kidney length, kidney depth, and kidney area) were measured, together with three independent variables (birth weight, head circumference, and gestational age). The SD of the measurement inconsistency was 0.13 cm for length, 0.078 cm for depth, and 0.32 cm2 for area; the percentages of total variance caused by measurement inconsistency were 7.9, 9.5, and 7.5, respectively. There was a significant difference between right and left kidneys in length and depth for each independent variable. The left kidney increased more in length and less in depth than the right so that the areas remained similar as the scale of variable increased. Kidney depth and area in boys were significantly larger than in girls, both dimensions increasing at equal rates. Centile charts for each dependent variable by each independent variable were constructed by a non-parametric method.

Birth Weight↗

Late perfusion. A simple remedy for renal allograft primary nonfunction.

Primary nonfunction in renal allografts makes the diagnosis of allograft dysfunction more difficult and may effect long-term graft survival. The prevention of primary nonfunction by a reperfusion technique has been assessed in a prospective analysis of 145 consecutive renal transplants performed in a single center. All kidneys were retrieved using an in situ perfusion method, and all but 13 recipients received a standardized immunosuppressive protocol with cyclosporine. The first 106 transplants were performed without the benefit of any additional perfusion, and the incidence of primary nonfunction was 57.5% in these patients. The last 39 kidneys received additional perfusion with kidney perfusion fluid immediately prior to implantation (late perfusion). In the latter group, the incidence of primary nonfunction was 30.8% (P = 0.007). Using logistic regression analysis, only three factors were found to be associated with primary nonfunction: immunosuppression with cyclosporine (P = 0.01), a second warm ischemia time of greater than 35 min (P = 0.002), and late perfusion (P = 0.003). In this study, the use of late perfusion alone has reduced the incidence of primary nonfunction by almost one half. The technique is simple, safe, inexpensive, and effective. Its routine use is now advocated in all renal transplants.

Cyclosporins↗

Contact sensitivity to dinitrochlorobenzene is impaired in atopic subjects. Controversy revisited.

If there is a primary dysfunction of the immune system in atopic eczema it might be reflected in altered capacity to generate delayed-type hypersensitivity. Therefore, the dose-response relationships for contact sensitization were determined for 22 patients (10 men) with minimal atopic eczema and compared with those from 27 nonatopic, healthy control subjects (12 men). Sensitization was induced with 30 micrograms of dinitrochlorobenzene applied to the thigh. Four weeks later the subjects were challenged with three doses of dinitrochlorobenzene (8.8, 12.5, and 17.7 micrograms), and responses were quantified with calipers as change in skinfold thickness at 48 hours. Atopic patients were significantly less responsive with smaller reactions at all challenge doses and a flatter challenge dose-response curve than that for control subjects. Thus, proper quantitative comparisons have shown that subjects with minimal atopic eczema do not mount a normal contact hypersensitivity response. However, it is not clear whether this is a consequence of the atopic state per se or is related to the presence of even a minor degree of eczema.

Adolescent↗

Quantification of epidermal growth factor in human breast cyst fluids: correlation with dehydroepiandrosterone-sulphate and electrolyte concentrations.

Epidermal growth factor (EGF), dehydroepiandrosterone (DHA)-sulphate and [Na+] and [K+] were assayed in 78 cyst fluids from patients with a palpable breast cyst. Epidermal growth factor was detected in all but 2 cysts, the mean value +/- SEM being 506.2 +/- 39.3 ng/ml, with a range of 0-1,599 ng/ml. When the cyst fluids were sub-divided according to their [Na+]:[K+] ratio, group A cyst fluids ( [Na+]:[K+] less than 3) had a significantly higher (p less than 0.001) level of EGF than group B cyst fluids ([Na+]:[K+] greater than 3). Furthermore, the relationship between EGF and [Na+] and [K+] and between EGF and DHA-sulphate seemed to differ between the 2 cyst types and each cyst type was therefore analyzed separately.

Aged↗

Sex differences in susceptibility to development of contact hypersensitivity to dinitrochlorobenzene (DNCB).

We have investigated the differences between the sexes in the development of contact sensitivity induced by dinitrochlorobenzene (DNCB). Ten male and 12 female subjects were sensitized with DNCB (30 micrograms applied on a 1 cm patch test disc) and challenged 1 month later with doses of 8.8, 12.5, 17.7 and 25 micrograms. The responses were measured after 48 h as increase in skinfold thickness with Harpenden callipers. Females showed a larger response at all challenge doses studied, and the slope of the log-dose response curve was significantly steeper in females. We conclude that there are significant differences in delayed type hypersensitivity between males and females.

Adult↗

Do education groups help diabetics and their parents?

The importance of education in the management of diabetes is recognised but has rarely been assessed in children. In a longitudinal controlled study we have examined the effect of a programme of education on the knowledge, diet, and concentration of glycated haemoglobin A1c in a group of diabetics. The programme took the form of two packages of education each consisting of four weekly meetings, in which small groups of parents and older children were led in a discussion of different aspects of diabetes. Only one of the 119 families who began the study failed to complete it. Family knowledge about diabetes improved as a result of the programme, although this was poorly retained in the fathers. A trend to improvement in several aspects of diet was noted but did not reach significance. A significant fall in glycated haemoglobin A1c was apparent seven months after the education in children aged 11 years and over. Those whose initial control was poor improved most. We conclude that such meetings should be considered as a useful adjunct to regular diabetic clinics.

Adolescent↗

Antigenic stimulation during ultraviolet therapy in man does not result in immunological tolerance.

People receiving therapy with either 8-methoxypsoralen plus long wavelength ultraviolet radiation (PUVA) or medium wavelength ultraviolet radiation (UVB) have been studied to see whether their unresponsiveness to the contact sensitizer dinitrochlorobenzene (DNCB) is a form of immunological tolerance. It was confirmed that both PUVA and UVB therapy impair sensitization by DNCB:4/13 PUVA-treated and 9/29 UVB-treated psoriatic subjects became sensitized by a dose of DNCB which sensitizes 100% of untreated patients. Subjects unsuccessfully sensitized during PUVA therapy could subsequently be sensitized perfectly normally. Subjects unsuccessfully sensitized during UVB therapy showed slight impairment of subsequent sensitization which was not statistically significant, and which was probably a persistent effect of UVB exposure. In conclusion, the temporary unresponsiveness seen in human subjects exposed to antigens during PUVA or UVB therapy is not due to immunological tolerance.

Antigens↗

Theoretical approach to active dispersal and colonization of houses by Triatoma infestans.

Dispersive flight by Triatoma infestans was modelled by assuming either unidirectional flight in a straight line, or that flight followed a pattern of 'random walk' analogous to two-dimensional Brownian motion. Parameter estimates for the models were derived from previous fieldwork in Argentina and Brazil. Calculated probabilities of houses becoming infested over a 1 year period were compared with actual changes of house infestation in a small farming community in central Brazil. It was found that infestation could be explained partly by the dispersive flight of the bugs according to the distances between houses, and partly by the predisposition of houses to infestation by virtue of their construction, since houses with cracked mud walls were particularly susceptible to infestation. Infested houses lying more than 200 m from uninfested houses appeared to make an almost negligible contribution to infestation of the uninfested houses. This suggests that buffer zones of this size around treated areas could help to minimize the risk of reinfestation after treatment.

Animals↗

Ultrasound screening of newborn urinary tract.

A non-invasive method to screen newborn babies for ureteric reflux might allow the possibility of appropriate action to prevent reflux nephropathy. We have tested the sensitivity of ultrasound screening of the urinary tract. 1061 unselected newborn infants born during 1986 were examined by ultrasound and the findings were recorded on videotape. Babies with dilated renal collecting systems underwent further investigations (micturating cystourethrography, intravenous urography, or radioisotope study). With these methods, 11 children were found to have renal disorders. A postal follow-up survey was carried out when the children were 3 years old. 657 (62%) families responded. We searched for non-responders among children born in 1986 who had subsequently had a renal radioisotope investigation: 5 non-responders were found among these children. Of the total, 24 children had had a urinary-tract infection: 3 more children with ureteric reflux were found; their neonatal ultrasound scans had suggested no abnormality. Thus, more than half the children of this cohort in whom hydronephrosis or ureteric reflux developed had only slight dilatation (less than 5 mm) on the neonatal scan. On review of the original videotapes there was no difference in internal dimension between left and right kidneys: the internal dimension was 5 mm or less in both kidneys in 96.3% of babies and 4 mm or less in 93.3%. Routine renal ultrasound scanning of newborn babies is of no value in detecting those who may have ureteric reflux: the number of other renal abnormalities likely to be detected is small.

Female↗