Biomedical subjects
Publications and source records attributed to G A Johnston.
Acute generalized exanthematous pustulosis (AGEP) is identified by several characteristic features. We present a patient showing AGEP associated with azathioprine hypersensitivity. To our knowledge, this is the first reported case of this association.
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BACKGROUND: In 1989 we demonstrated that 71% of children referred to our paediatric dermatology clinic with atopic dermatitis (AD) had been subject to dietary manipulation by their parents in order to manage their disease. We have re-examined our clinic population to determine whether the documented rise in the use of complementary therapy in children with skin disease has been accompanied by a rise in dietary manipulation. OBJECTIVES: To qualify and quantify the usage of dietary manipulation in children with AD in secondary care. METHODS: A face-to-face structured questionnaire study of 100 children with AD. RESULTS: The mean age of the children interviewed was 7.3 years (median 5.9, range 0.6-17.1) and ethnic origin was 59% white, 35% Indo-Asian, 3% Afro-Caribbean and 3% mixed race. Seventy-five per cent of patients (75 of 100) had tried some form of dietary exclusion; the most common foods omitted were dairy products in 48% (36 of 75), eggs in 27% (20 of 75) and cow's milk in 25% (19 of 75). Forty-one per cent of patients (41 of 100) had tried some form of dietary supplementation. The most common dietary supplement was evening primrose oil in 59% (24 of 41), of whom 13% (three of 24) felt this had helped their skin. Only 51% (38 of 75) had consulted a doctor or dietician before commencing any dietary change, but 39% (29 of 75) felt that their skin had improved as a result of this dietary manipulation. CONCLUSIONS: In comparison with our previous study, the proportion of patients excluding foods from their diet had increased from 71% to 75%. The proportion of these dietary changes that are unsupervised has remained the same, as have the food types avoided. The proportion of patients who report that unsupervised dietary manipulation is beneficial has increased from 10% to 39%.
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BACKGROUND: The use of 'complementary' or 'alternative' medicine continues to rise in patients with skin disease, especially in those with chronic, inflammatory dermatoses. OBJECTIVES: To qualify and quantify the usage of complementary medicine (CM) in children with atopic dermatitis (AD) in secondary care. METHODS: A face-to-face structured questionnaire study of 100 consecutive children with AD and their parent or guardian. RESULTS: The mean age of the children interviewed was 7.3 years (median age 6.0 years, range 0.6-17.1) and ethnic origin was 59% white, 35% Indian, 3% Afro-Caribbean and 3% mixed race. Forty-six of 100 patients (46%) had used, or were currently using, CM. Of the 54 patients who had not yet used CM, 17 of 54 (31%) said they intended to try this in the future. The most commonly used CM was Chinese herbal medicine by 20 of 46 patients (43% of those who had used CM), followed by herbal medicine (41%) and homeopathy (35%). Of 74 patients using CM, 26 (35%) felt their AD had improved while 39 of 74 (53%) reported that it had remained unchanged. Twenty-six of 46 (56%) CM users in this study would not recommend CM to other patients with AD. There was a strong association between the use of CM and ethnicity (P = 0.01). Half of the patients who had used CM (23 of 46) had used it on the recommendation of family or friends with skin disease, 17 of 46 (37%) from family or friends without skin disease and three of 46 (6%) each from health professionals or from the media or internet. Twenty-five of 46 (54%) of CM users did so because conventional treatment was not working, and eight of 46 (17%) because they were worried about the side-effects of conventional treatment. While 39 of 100 (39%) of all patients felt that CM was safer than conventional medicine, only 14 of 100 felt it was more efficacious. Fifty-one of 100 were happy to combine both types of treatment and 66 of 100 felt that CM should be available from the National Health Service. CONCLUSIONS: In a population of children with AD attending a teaching hospital clinic in Leicester, U.K., 63% use or intend to use CM. This use is associated with ethnicity.
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Considering the ever increasing popularity of tattoos, significant reactions remain unusual. Red pigments are the commonest cause of delayed tattoo reactions. Histology typically shows extensive lichenoid basal damage, well away from the dermal pigment. We report two cases of lichenoid reactions to red tattoo pigment and review the literature on the subject.
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A 25-day-old neonate developed an unusual eruption with bullae and marked systemic symptoms. Investigation for bacterial, viral, autoimmune and immunobullous causes did not reveal any identifiable trigger and histological examination was highly suggestive of bullous erythema multiforme. Pulmonary infiltrates were noted late in the course of the disease. Differential diagnoses included bullous impetigo, primary herpes simplex infection, immunobullous disease, neonatal lupus and erythema multiforme. This case illustrates the difficulties in diagnosing and managing an unwell child with bullae and emphasizes the need to exclude treatable underlying causes.
We report the case of a 77-year-old male who developed a florid photosensitive eruption while taking thiazide diuretics for heart failure. The lesions were lichenoid in appearance and this was confirmed histologically. The eruption cleared on withdrawal of the drug. Although thiazide-induced photosensitivity is a well-documented phenomenon, there have been no histologically proven cases of a lichenoid eruption in light exposed areas in the recent literature.
The pharmacological effects of the enantiomers of cis-3-aminocyclopentanecarboxylic acids ((+)- and (-)-CACP), the enantiomers of trans-3-aminocyclopentanecarboxylic acids ((+)- and (-)-TACP), and the enantiomers of 4-aminocyclopent-1-ene-1-carboxylic acids ((+)- and (-)-4-ACPCA) were studied on human homomeric rho(1) and rho(2) GABA(C) receptors expressed in Xenopus oocytes using two-electrode voltage clamp methods. These compounds are conformationally restricted analogues of gamma-aminobutyric acid (GABA) held in a five-membered ring. (+)-TACP (EC(50) (rho(1))=2.7+/-0.2 microM; EC(50) (rho(2))=1.45+/-0.22 microM), (+)-CACP (EC(50) (rho(1))=26.1+/-1.1 microM; EC(50) (rho(2))=20.1+/-2.1 microM) and (-)-CACP (EC(50) (rho(1))=78.5+/-3.5 microM; EC(50) (rho(2))=63.8+/-23.3 microM) were moderately potent partial agonists at rho(1) and rho(2) GABA(C) receptors, while (-)-TACP (100 microM inhibited 56% and 62% of the current produced by 1 microM GABA at rho(1) and rho(2) receptors, respectively) was a weak partial agonist with low intrinsic activity at these receptors. In contrast, (+)-4-ACPCA (K(i) (rho(1))=6.0+/-0.1 microM; K(i) (rho(2))=4.7+/-0.3 microM) did not activate GABA(C) rho(1) and rho(2) receptors but potently inhibited the action of GABA at these receptors, while (-)-4-ACPCA had little effect as either an agonist or an antagonist. The affinity order at both GABA(C) rho(1) and rho(2) receptors was (+)-TACP>(+)-4-ACPCA >> (+)-CACP>(-)-CACP >> (-)-TACP >> (-)-4-ACPCA. This study shows that the cyclopentane and cyclopentene analogues of GABA affect GABA(C) receptors in a unique manner, defining a preferred stereochemical orientation of the amine and carboxylic acid groups when binding to GABA(C) receptors. This is exemplified by the partial agonist, (+)-TACP, and the antagonist, (+)-4-ACPCA.
An elderly female patient developed blisters localised to her split-skin donor and graft sites. Despite repeated swabs, bacteriology and virology returned negative; multiple antibiotic courses did not improve her condition, which generalised within weeks. Histology and immunofluorescence confirmed a clinical diagnosis of bullous pemphigoid and her condition resolved rapidly after treatment with prednisolone. Bullous pemphigoid can be precipitated or exacerbated by surgery and the diagnosis should be considered when patients present with persistent localised or generalised blisters, especially when microbiological investigations are negative.
A series of 2-cyclohexylideneperhydro-4,7-methanoindene derivatives was synthesized as novel androgen receptor ligands. Asymmetric hydroboration of key intermediate 2 afforded single enantiomer alcohol derivatives (3aR)-3 and (3aS)-3 which could be further transformed to give 12 variously substituted keto alcohol target compounds. X-ray crystallography of the 4-bromobenzenesulfonyl ester (3aS)-13 was used to establish their absolute configuration. The binding of these compounds to the rat ventral prostate androgen receptor showed moderate affinity with IC(50) values of 1.2 microM and above but with substantial enantiomeric dependencies which varied in accordance to Pfieffer's rule. Surprisingly, the (3aS)-5alpha-alcohols displayed similar affinity to the (3aR)-5beta-alcohols, and molecular modeling suggested an alternative mode of binding for the (3aS) series. The three compounds with the best androgen receptor affinity were assayed in vivo for antiandrogenic and androgenic effects on sex accessory organ growth in castrated immature rats and were found to be ineffective.
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The effects of the enantiomers of (+/-)-CAMP and (+/-)-TAMP [(+/-)-cis- and (+/-)-trans-2-aminomethylcyclopropanecarboxylic acids, respectively], which are cyclopropane analogues of GABA, were tested on GABA(A) and GABA(C) receptors expressed in Xenopus laevis oocytes using two-electrode voltage clamp methods. (+)-CAMP was found to be a potent and full agonist at homooligomeric GABA(C) receptors (K:(D) approximately 40 microM: and I:(max) approximately 100% at rho(1); K:(D) approximately 17 microM: and I:(max) approximately 100% at rho(2)) but a very weak antagonist at alpha(1)beta(2)gamma(2L) GABA(A) receptors. In contrast, (-)-CAMP was a very weak antagonist at both alpha(1)beta(2)gamma(2L) GABA(A) receptors and homooligomeric GABA(C) receptors (IC(50) approximately 900 microM: at rho(1) and approximately 400 microM: at rho(2)). Furthermore, (+)-CAMP appears to be a superior agonist to the widely used GABA(C) receptor partial agonist cis-4-aminocrotonic acid (K:(D) approximately 74 microM: and I:(max) approximately 78% at rho(1); K:(D) approximately 70 microM: and I:(max) approximately 82% at rho(2)). (-)-TAMP was the most potent of the cyclopropane analogues on GABA(C) receptors (K:(D) approximately 9 microM: and I:(max) approximately 40% at rho(1); K:(D) approximately 3 microM: and I:(max) approximately 50-60% at rho(2)), but it was also a moderately potent GABA(A) receptor partial agonist (K:(D) approximately 50-60 microM: and I:(max) approximately 50% at alpha(1)beta(2)gamma(2L) GABA(A) receptors). (+)-TAMP was a less potent partial agonist at GABA(C) receptors (K:(D) approximately 60 microM: and I:(max) approximately 40% at rho(1); K:(D) approximately 30 microM: and I:(max) approximately 60% at rho(2)) and a weak partial agonist at alpha(1)beta(2)gamma(2L) GABA(A) receptors (K:(D) approximately 500 micro: and I:(max) approximately 50%). None of the isomers of (+/-)-CAMP and (+/-)-TAMP displayed any interaction with GABA transport at the concentrations tested. Molecular modeling based on the present results provided new insights into the chiral preferences for either agonism or antagonism at GABA(C) receptors.
1. The effects of the naturally occurring neurosteroid tetrahydrodeoxycorticosterone (THDOC) on GABAA receptor-mediated miniature, spontaneous and evoked IPSCs was tested using patch-clamp techniques in slices of hippocampus and cerebellum from rats at two developmental stages ( approximately 10 and approximately 20 days postnatal). The cells studied were hippocampal granule cells and cerebellar Purkinje and granule cells. 2. Most miniature GABAergic currents (mIPSCs) decayed with two exponentials and neurosteroids caused a approximately 4-fold increase in the decay time constant of the second exponential at the highest concentration used (2 microM). Similar effects were seen at high concentrations of THDOC (1-2 microM) in all cell groups tested. No effects were seen on amplitude or rise time of mIPSCs. 3. The effects of THDOC (1 microM) were shown to be stereoselective and rapidly reversible, indicating that the neurosteroid binds to the GABAA receptor, rather than acting genomically. 4. At concentrations of THDOC likely to occur physiologically (50-100 nM), the decay time of IPSCs was also enhanced (25-50 %) in all cerebellar cell groups tested. In contrast, at 100 nM THDOC, seven of 11 hippocampal granule cells were sensitive from the 10 day group but the 20 day hippocampal granule cells showed no significant enhancement in the presence of these lower concentrations of THDOC. 5. The differences in sensitivity of hippocampal and cerebellar cells to THDOC are compared to data reported in the literature on regional development of expression of different receptor subunits in the brain and it is suggested that the progressive relative insensitivity of the 20 day hippocampal cells may depend on increasing expression of the delta subunit of the GABAA receptor and possibly an increase in the alpha4 subunit.
3- and 4-(Aminomethyl)-2,6-difuorophenols were tested for activity against the three major classes of GABA receptors. 4-(Amninomethyl)-2,6difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 microM with a 95% Confidence Interval range of 75.2 microM to 75.8 microM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at alpha1beta2gamma2 GABA(A) and GABA(B) receptors.
Many abused substances have been found to possess anxiogenic-like or/and anxiolytic-like properties. Discrepancies about the effects of MDMA, one of the most popular recreational drugs in recent years, on anxiety have been seen in the literature, and almost all of the data in this respect were derived from retrospective studies. The present study was thus designed to examine the drug's actions by using an animal model of anxiety, the elevated plus-maze test in male mice. Intraperitoneal MDMA at 1 mg/kg was ineffective, at 4 mg/kg decreased the percent of open arm entries (p < 0.01), and increased enclosed entries (p < 0.05), at 12 mg/kg had no significant effect, and at 20 mg/kg induced an increase of percent of open time (p < 0.01). As control drugs, amphetamine (0.5-4 mg/kg, i.p.) produced a dose-dependent, anxiogenic-like effect and diazepam (1 mg/kg, i.p.) induced an anxiolytic-like effect in the test. The results indicate that MDMA has anxiogenic-like properties at lower doses and anxiolytic-like at higher doses. The effects of MDMA and amphetamine on the mouse's responses to the plus-maze are compared. These findings provide a possible explanation for the controversies over MDMA's effects on anxiety in the literature.