RESUMO
Acne vulgaris (acne) is a common inflammatory disorder of the cutaneous pilo-sebaceous unit. Here we perform a genome-wide association analysis in the United Kingdom, comparing severe cases of acne (n=1,893) with controls (n=5,132). In a second stage, we genotype putative-associated loci in a further 2,063 acne cases and 1,970 controls. We identify three genome-wide significant associations: 11q13.1 (rs478304, Pcombined=3.23 × 10(-11), odds ratio (OR) = 1.20), 5q11.2 (rs38055, P(combined) = 4.58 × 10(-9), OR = 1.17) and 1q41 (rs1159268, P(combined) = 4.08 × 10(-8), OR = 1.17). All three loci contain genes linked to the TGFß cell signalling pathway, namely OVOL1, FST and TGFB2. Transcripts of OVOL1 and TFGB2 have decreased expression in affected compared with normal skin. Collectively, these data support a key role for dysregulation of TGFß-mediated signalling in susceptibility to acne.
Assuntos
Acne Vulgar/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Adulto , Estudos de Casos e Controles , Proteínas de Ligação a DNA/genética , Feminino , Folistatina/genética , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta2/genética , Adulto JovemRESUMO
Previous studies have indicated that volatile compounds specific to bladder cancer may exist in urine headspace, raising the possibility that headspace analysis could be used for diagnosis of this particular cancer. In this paper, we evaluate the use of a commercially available gas sensor array coupled with a specifically designed pattern recognition algorithm for this purpose. The best diagnostic performance that we were able to obtain with independent test data provided by healthy volunteers and bladder cancer patients was 70% overall accuracy (70% sensitivity and 70% specificity). When the data of patients suffering from other non-cancerous urological diseases were added to those of the healthy controls, the classification accuracy fell to 65% with 60% sensitivity and 67% specificity. While this is not sufficient for a diagnostic test, it is significantly better than random chance, leading us to conclude that there is useful information in the urine headspace but that a more informative analytical technique, such as mass spectrometry, is required if this is to be exploited fully.
Assuntos
Biomarcadores Tumorais/urina , Carcinoma de Células de Transição/urina , Gases/urina , Urinálise/instrumentação , Neoplasias da Bexiga Urinária/urina , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
In a previous canine study, we demonstrated that volatile organic compounds specific to bladder cancer are present in urine headspace, subsequently showing that up to 70% of tumours can be correctly classified using an electronic nose. This study aimed to evaluate the sensitivity and specificity which can be achieved by a group of four trained dogs. In a series of 30 double-blind test runs, each consisting of one bladder cancer urine sample placed alongside six controls, the highest sensitivity achieved by the best performing dog was 73% (95% CI 55-86%), with the group as a whole correctly identifying the cancer samples 64% (95% CI 55-73%) of the time. Specificity of the dogs individually ranged from 92% (95% CI 82-97%) for urine samples obtained from healthy, young volunteers down to 56% (95% CI 42-68%) for those taken from older patients with non-cancerous urological disease. Odds ratio comparisons confirmed a significant decrease in performance as the extent of urine dipstick abnormality and/or pathology amongst the control population increased. Importantly, however, statistical analysis indicated that covariates such as smoking, gender and age, as well as blood, protein and /or leucocytes in the urine did not significantly alter the odds of response to the cancer samples. Our results provide further evidence that volatile biomarkers for bladder cancer exist in urine headspace, and that these have the potential to be exploited for diagnosis.
Assuntos
Biomarcadores Tumorais/urina , Neoplasias da Bexiga Urinária/diagnóstico , Compostos Orgânicos Voláteis/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/urina , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Olfato , Neoplasias da Bexiga Urinária/urinaRESUMO
Intense itch and urge to scratch are the major symptoms of many chronic skin ailments, which are increasingly common. Vicious itch-scratch cycles are readily established and may diminish quality of life for those afflicted. We investigated peripheral and central processing of two types of itch sensation elicited by skin-prick tests of histamine and allergen solutions. Itch-related skin blood flow changes were measured by laser Doppler in 14 subjects responsive to type I allergens and 14 nonatopic subjects. In addition, this study examined central processing of both types of itch using functional magnetic resonance imaging (fMRI). Itch perception and blood flow changes were significantly greater when itch was induced by allergens compared with histamine. Both types of itch correlated significantly with activity in the genual anterior cingulate, striatum, and thalamus. Moreover, itch elicited by allergens activated orbitofrontal, supplementary motor, and posterior parietal areas. Histamine-induced itch also significantly correlated with activation in the insula bilaterally. The identification of limbic and ventral prefrontal activation in two types of itch processing likely reflects the subjects' desire to relieve the itch sensation by scratching, and these regions have been repeatedly associated with motivation processing. A dysfunction of the striato-thalamo-orbitofrontal circuit is believed to underlie the failure to regulate motivational drive in disorders associated with strong urges, e.g., addiction and obsessive compulsive disorder. The patterns of itch-induced activation reported here may help explain why chronic itch sufferers frequently self-harm through uncontrollable itch-scratch cycles.
Assuntos
Encéfalo/fisiologia , Motivação , Nociceptores/fisiopatologia , Prurido/fisiopatologia , Pele/fisiopatologia , Volição/fisiologia , Adulto , Alérgenos/efeitos adversos , Encéfalo/anatomia & histologia , Feminino , Mãos/inervação , Mãos/fisiologia , Histamina/efeitos adversos , Humanos , Hiperemia/induzido quimicamente , Hiperemia/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Rede Nervosa/anatomia & histologia , Rede Nervosa/fisiologia , Inibição Neural/fisiologia , Nociceptores/efeitos dos fármacos , Medição da Dor/métodos , Prurido/induzido quimicamente , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Pele/irrigação sanguínea , Pele/inervaçãoRESUMO
Dermatologic diseases encompass a broad category of pathologic situations. Infection remains a significant aspect of the pathology faced in patient encounters, and it is natural to expect that anti-infectives play a major element in the armamentarium utilized by dermatologists. Aside from the treatment of the classic bacterial and fungal infections, there are now new uses for antiviral agents to help suppress recurrent disease, such as herpes simplex. There is also the novel approach of using anti-infectives, or agents that have been thought to have antimicrobial activity, to treat inflammatory diseases. This review describes anti-infectives, beginning with common antibiotics used to treat bacterial infections. The discussion will then cover the current use of antivirals. Finally, the description of antifungals will be separated, starting with the oral agents and ending with the topical antimycotics. The use of anti-infectives in tropical dermatology has been purposefully left out, and perhaps should be the subject of a separate review. Cutaneous bacterial infections consist chiefly of those microorganisms that colonize the skin, such as species of staphylococcus and streptococcus. Propionibacterium acnes and certain other anaerobes can be involved in folliculitis, pyodermas and in chronic conditions such as hidradenitis suppurativa.
Assuntos
Anti-Infecciosos/uso terapêutico , Dermatologia/métodos , Dermatopatias Infecciosas/tratamento farmacológico , Anti-Infecciosos/farmacologia , HumanosRESUMO
OBJECTIVE: To determine whether dogs can be trained to identify people with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. DESIGN: Experimental, "proof of principle" study in which six dogs were trained to discriminate between urine from patients with bladder cancer and urine from diseased and healthy controls and then evaluated in tests requiring the selection of one bladder cancer urine sample from six controls. PARTICIPANTS: 36 male and female patients (age range 48-90 years) presenting with new or recurrent transitional cell carcinoma of the bladder (27 samples used for training; 9 used for formal testing); 108 male and female controls (diseased and healthy, age range 18-85 years--54 samples used in training; 54 used for testing). MAIN OUTCOME MEASURE: Mean proportion of successes per dog achieved during evaluation, compared with an expected value of 1 in 7 (14%). RESULTS: Taken as a group, the dogs correctly selected urine from patients with bladder cancer on 22 out of 54 occasions. This gave a mean success rate of 41% (95% confidence intervals 23% to 58% under assumptions of normality, 26% to 52% using bootstrap methods), compared with 14% expected by chance alone. Multivariate analysis suggested that the dogs' capacity to recognise a characteristic bladder cancer odour was independent of other chemical aspects of the urine detectable by urinalysis. CONCLUSIONS: Dogs can be trained to distinguish patients with bladder cancer on the basis of urine odour more successfully than would be expected by chance alone. This suggests that tumour related volatile compounds are present in urine, imparting a characteristic odour signature distinct from those associated with secondary effects of the tumour, such as bleeding, inflammation, and infection.
Assuntos
Carcinoma de Células de Transição/diagnóstico , Cães/fisiologia , Olfato/fisiologia , Neoplasias da Bexiga Urinária/diagnóstico , Urina/fisiologia , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Ensino/métodosRESUMO
A multicentre, randomized, double-blind, crossover study was designed to investigate the effects of prednisone on allergic and irritant patch test reactions. 24 subjects with known allergy to nickel were recruited and patch tested with a nickel sulfate dilution series in aqueous solution, 5% nickel sulfate in petrolatum and 2 dilution series of the irritants nonanoic acid and sodium lauryl sulfate. The subjects were tested x2, both during treatment with prednisone 20 mg oral daily and during placebo treatment. The total number of positive nickel patch test reactions decreased significantly in patients during prednisone treatment. The threshold concentration to elicit a patch test reaction increased and the overall degree of reactivity to nickel sulfate shifted towards weaker reactions. The effect of prednisone treatment on the response to irritants was divergent with both increased and decreased numbers of reactions, although there were no statistically significant differences compared with placebo. It is concluded that oral treatment with prednisone suppresses patch test reactivity to nickel, but not to the irritants tested.