Antony R. Young

Bio: Antony R. Young is an academic researcher from King's College London. The author has contributed to research in topics: Human skin & Erythema. The author has an hindex of 55, co-authored 214 publications receiving 8432 citations. Previous affiliations of Antony R. Young include Guy's Hospital & University of London.

Chromophores in human skin

Abstract: Human skin, especially the epidermis, contains several major solar ultraviolet-radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid, amino acids, melanins and their precursors and metabolites. The lack of solubility of melanins prevents their absorption spectra being defined by routine techniques. Indirect spectroscopic methods show that their spectral properties depend on the stimulus for melanogenesis. The photochemical consequences of UVR absorption by some epidermal chromophores are relatively well understood whereas we lack a detailed understanding of the consequent photobiological and clinical responses. Skin action spectroscopy is not a reliable way of relating a photobiological outcome to a specific chromophore but is important for UVR hazard assessment. Exogenous chromophores may be administered to the skin in combination with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of sunburn and possibly skin cancer.

How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)

Abstract: Objectives. To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives.Methods. The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, Functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work.Results. A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0).Conclusions. Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.

Melanogenesis: A Photoprotective Response to DNA Damage?

Abstract: Exposure to ultra violet radiation (UVR) is associated with significant long-term deleterious effects such as skin cancer. A well-recognised short-term consequence of UVR is increased skin pigmentation. Pigmentation, whether constitutive or facultative, has widely been viewed as photoprotective, largely because darkly pigmented skin is at a lower risk of photocarcinogenesis than fair skin. Research is increasingly suggesting that the relationship between pigmentation and photoprotection may be far more complex than previously assumed. For example, photoprotection against erythema and DNA damage has been shown to be independent of level of induced pigmentation in human white skin types. Growing evidence now suggests that UVR induced DNA photodamage, and its repair is one of the signals that stimulates melanogenesis and studies suggest that repeated exposure in skin type IV results in faster DNA repair in comparison to skin type II. These findings suggest that tanning may be a measure of inducible DNA repair capacity, and it is this rather than pigment per se which results in the lower incidence skin cancer observed in darker skinned individuals. This evokes the notion that epidermal pigmentation may in fact be the mammalian equivalent of a bacterial SOS response. Skin colour is one of most conspicuous ways in which humans vary yet the function of melanin remains controversial. Greater understanding of the role of pigmentation in skin is vital if one is to be able to give accurate advice to the general public about both the population at risk of skin carcinogenesis and also public perceptions of a tan as being healthy.

Acute effects of UVR on human eyes and skin.

Abstract: Solar UVR ( approximately 295-400 nm) has acute clinical effects on the eyes and the skin. The only effect on the eye is inflammation of the cornea (photokeratitis), which is caused by UVB (and non-solar UVC) and resolves without long-term consequences within 48 h. The effects on the skin are more extensive and include sunburn (inflammation), tanning and immunosuppression for which UVB is mainly responsible. Tanning is modestly photoprotective against further acute UVR damage. Skin colour is also transiently changed by UVA-dependent immediate pigment darkening, the function of which is unknown. Skin type determines sensitivity to the acute and chronic effects of UVR on the skin. Some of the photochemical events that initiate acute effects are also related to skin cancer. Solar UVB is also responsible for the synthesis of vitamin D.

Vitamin D deficiency.

Abstract: admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Central sensitization: implications for the diagnosis and treatment of pain.

Abstract: Nociceptor inputs can trigger a prolonged but reversible increase in the excitability and synaptic efficacy of neurons in central nociceptive pathways, the phenomenon of central sensitization. Central sensitization manifests as pain hypersensitivity, particularly dynamic tactile allodynia, secondary punctate or pressure hyperalgesia, aftersensations, and enhanced temporal summation. It can be readily and rapidly elicited in human volunteers by diverse experimental noxious conditioning stimuli to skin, muscles or viscera, and in addition to producing pain hypersensitivity, results in secondary changes in brain activity that can be detected by electrophysiological or imaging techniques. Studies in clinical cohorts reveal changes in pain sensitivity that have been interpreted as revealing an important contribution of central sensitization to the pain phenotype in patients with fibromyalgia, osteoarthritis, musculoskeletal disorders with generalized pain hypersensitivity, headache, temporomandibular joint disorders, dental pain, neuropathic pain, visceral pain hypersensitivity disorders and post-surgical pain. The comorbidity of those pain hypersensitivity syndromes that present in the absence of inflammation or a neural lesion, their similar pattern of clinical presentation and response to centrally acting analgesics, may reflect a commonality of central sensitization to their pathophysiology. An important question that still needs to be determined is whether there are individuals with a higher inherited propensity for developing central sensitization than others, and if so, whether this conveys an increased risk in both developing conditions with pain hypersensitivity, and their chronification. Diagnostic criteria to establish the presence of central sensitization in patients will greatly assist the phenotyping of patients for choosing treatments that produce analgesia by normalizing hyperexcitable central neural activity. We have certainly come a long way since the first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity.

How does photodynamic therapy work

Abstract: Those readers already familiar with the field of photodynamic therapy (PDT)t will consider this title somewhat presumptuous since it implies that the answer to the posed question is known. Indeed, answers to many questions regarding PDT have been found over the past decade, but a comprehensive understanding of all mechanisms involved in PDT tumor destruction has not yet emerged. This paper will attempt to deal with this complex subject by giving a sequential account of the effects occurring during PDT tissue treatment on a cellular and tissue level. Photodynamic therapy is based on the dye-sensitized photooxidation of biological matter in the target tissue (Foote, 1990). This requires the presence of a dye (sensitizer) in the tissue to be treated. Although such sensitizers can be naturally occurring constituents of cells and tissues, in the case of PDT they are introduced into the organism as the first step of treatment. In the second step, the tissuelocalized sensitizer is exposed to light of wavelength appropriate for absorption by the sensitizer. Through various photophysical pathways, also involving molecular oxygen, oxygenated products harmful to cell function arise and eventual tissue destruction results. In keeping with the chronological nature of this review, the subject matter will be divided into the