Non-professional identification of malignant melanoma: are wives more attentive?
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Adult↗
Biomedical subjects
P Kind
Publications and source records attributed to P Kind.
Assessing health-related quality-of-life in individuals with haemophilia.
The objectives of this study were to analyse current levels of health-related quality-of-life (HR-QoL) in individuals with severe haemophilia and to assess the scope for these levels to improve. To do this, 249 individuals with severe, moderate and mild haemophilia were asked to complete Medical Outcomes Study (MOS) Short-Form 36 (SF-36) and EuroQol (EQ-5D) questionnaires. Access was also gained to two appropriate normative data sets. The results from these questionnaires showed that HIV status, history of orthopaedic surgery and bleeding frequency in the previous calendar year were not strong predictors of HR-QoL for individuals with severe haemophilia. However, for the majority of scales, age was found to be a strong predictor of HR-QoL for this patient group. The results from the analysis also showed that compared to individuals with moderate/mild haemophilia and the UK male normative population, individuals with severe haemophilia generally recorded poorer levels of HR-QoL. These results suggest, therefore, that individuals with severe haemophilia have reduced levels of HR-QoL compared to individuals with moderate/mild haemophilia and the general population, irrespective of differences in age. The results also suggest that the scope for primary prophylaxis to increase HR-QoL in individuals with severe haemophilia is significant.
Adult↗
Transcriptional activation of endogenous retroviral sequences in human epidermal keratinocytes by UVB irradiation.
Ultraviolet radiation is a pathogenic factor in various diseases, e. g., autoimmune disorders such as lupus erythematosus. On the other hand, endogenous retroviruses are discussed as etiologic agents in lupus erythematosus. Therefore, we investigated the influence of ultraviolet irradiation on expression of human endogenous retroviral sequences and human endogenous retroviral sequence promoter-driven transcription of cellular genes using human epidermal keratinocytes as a model system. First, conserved sequences of endogenous retroviral pol genes were amplified from cellular mRNA by reverse transcriptase polymerase chain reaction with degenerate oligonucleotide primers. Polymerase chain reaction products were hybridized in a reverse dot blot hybridization assay to a representative number of distinct cloned human endogenous retroviral pol fragments. Using this method, we could show that irradiation with 30 mJ per cm2 ultraviolet B activates transcription of various endogenous retroviral pol sequences in primary epidermal keratinocytes as well as in a spontaneously immortalized keratinocyte cell line (HaCaT). Interestingly, some of these sequences were found to be closely related to pol sequences of human endogenous retroviral sequences which have been shown to be expressed in autoimmune patients. Analysis of human endogenous retroviral pol expression in vivo using skin biopsies of lupus erythematosus patients revealed similar activation patterns. In a second approach, ultraviolet B- induced chimeric transcripts were isolated which are initiated by human endogenous retroviral promoters and proceed into cellular sequences using a newly established modified differential display polymerase chain reaction technique. The activation of human endogenous retroviral sequence transcription by ultraviolet B may contribute to the pathogenesis of lupus erythematosus, where inappropriate antigenic presentation of ultraviolet B-induced viral and cellular proteins could stimulate autoantibody production.
Base Sequence↗
Problems of behaviour, reading and arithmetic: assessments of comorbidity using the Strengths and Difficulties Questionnaire.
BACKGROUND: Estimates of academic underachievement among school children vary widely, depending on the geographical location and on the criteria used to define attainment. AIM: To examine the relationship between behaviour problems and academic attainment in a large UK primary school. METHOD: A school population (364 children from Years 3 to 6 inclusive) were assessed on a range of cognitive ability tasks. These included standardised tests of reading, arithmetic and verbal and non-verbal intelligence. Under-achievement was assessed using different criteria. To assess behaviour, teachers completed the Strengths and Difficulties Questionnaire (Goodman, 1997) for each participating child. Finally, academic progress of a subset of children was assessed after one year. RESULTS: Indicated a significant relationship between behaviour and academic attainment; prosocial behaviour was positively correlated with reading and arithmetic, hyperactivity and conduct problems were negatively correlated. This association was especially strong in the children rated by the questionnaire as hyperactive, where around 1 in 5 had a specific reading deficit. However, there was no evidence to indicate that children with behaviour problems made less academic progress over a one-year period relative to their peers. CONCLUSION: The study highlights the importance of assessing both cognitive skills and behaviour, particularly when planning the educational management of children with reading difficulties.
Catchment Area, Health↗
Variations in population health status: results from a United Kingdom national questionnaire survey.
OBJECTIVE: To measure the health of a representative sample of the population of the United Kingdom by using the EuroQoL EQ-5D questionnaire. DESIGN: Stratified random sample representative of the general population aged 18 and over and living in the community. SETTING: United Kingdom. SUBJECTS: 3395 people resident in the United Kingdom. MAIN OUTCOME MEASURES: Average values for mobility, self care, usual activities, pain or discomfort, and anxiety or depression. RESULTS: One in three respondents reported problems with pain or discomfort. There were differences in the perception of health according to the respondent's age, social class, education, housing tenure, economic position, and smoking behaviour. CONCLUSIONS: The EQ-5D questionnaire is a practical way of measuring the health of a population and of detecting differences in subgroups of the population.
Adolescent↗
Further evidence that syringolymphoid hyperplasia with alopecia is a cutaneous T-cell lymphoma.
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Alopecia↗
Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.
BACKGROUND: Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis. OBSERVATIONS: After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group. CONCLUSIONS: There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.
Administration, Cutaneous↗
[In situ PCR and PCR in situ hybridization of paraffin-embedded tissue. New diagnostic possibilities in pathology].
In situ polymerase chain reaction (PCR) and PCR in situ hybridization are new diagnostic tools in dermatopathology. These techniques can combine the sensitivity of PCR with the advantage of in situ hybridization to localize specific cellular structures. With optical control of the PCR reaction product in these techniques, false-positive results due to contamination can be minimized. Several working protocols have been established which allow detection of DNA and RNA sequences in a rapid and reproducible manner. Two different methods have been established to detect the amplification product, the indirect PCR in situ hybridization (PCRisHyb), and the direct in situ PCR (isPCR). An easy and reproducible method for PCRisHyb and isPCR in formalin-fixed and paraffin-embedded tissue is described and the two techniques are compared. Using both isPCR and PCRisHyb, the amplification product can be visualized with an optimal morphological preservation of the tissue. Indirect PCRisHyb showed a slightly higher specificity whereas direct isPCR was the quicker, easier and less expensive method.
Chickenpox↗
Methodological and statistical issues of quality of life (QoL) and economic evaluation in cancer clinical trials: report of a workshop.
In recent years, quality of life (QoL) and economic evaluations have become increasingly important as additional outcome measures in cancer clinical trials. However, both fields of research are relatively new and in need of finding solutions to a substantial number of specific methodological problems. This paper reports on the proceedings of a symposium aimed at summarising and discussing some of the most contentious methodological and statistical issues in QoL and economic evaluations. In addition, possible solutions are indicated and the most pertinent areas of research are identified. Issues specific to QoL evaluations that are addressed include clinically meaningful changes in QoL scores; how to analyse QoL data and to handle missing and censored data and integration of length of life and QoL outcomes. Issues specific to economic evaluations are the advantages and disadvantages of various outcome measures; statistical methods to analyse economic data and choice of decision criteria and analytical perspective. How to perform QoL and economic evaluations in large and simple trials and whether the gap between QoL and utility measures can be bridged are also discussed.
Clinical Trials as Topic↗
Measuring health status in British patients with rheumatoid arthritis: reliability, validity and responsiveness of the short form 36-item health survey (SF-36).
The objective was to assess the performance of the SF-36 health survey (SF-36) in a sample of patients with rheumatoid arthritis (RA) stratified by functional class. The eight SF-36 subscales and the two summary scales (the physical and mental component scales) were assessed for test retest reliability, construct validity and responsiveness to self-reported change in health. In 233 patients with RA, the SF-36 scales were: reliable (intra-class correlation coefficients 0.76-0.93); correlated with American College of Rheumatology (ACR) core disease activity measures [Spearman r = -0.12 (erythrocyte sedimentation rate) to -0.89 (Modified Health Assessment Questionnaire)]; and responsive to improvements in health (standardized response means 0.27-0.9). The distribution of scores on four of the eight subscales (physical function, role limitations physical, role limitations emotional and social function) was clearly non-Gaussian. Very marked floor effects were noted with the physical function scale, and both ceiling and floor effects with the other three subscales. The two SF-36 physical and mental component summary scales are reliable, valid and responsive measures of health status in patients with RA. Six of the eight subscales meet standards required for comparing groups of patients, and the physical function and general health scales may be suitable for monitoring individuals. The two scales measuring role limitations have poor measurement characteristics. The SF-36 pain and physical function scales may be suitable for use as patient self-assessed measures of pain and physical function within the ACR core disease activity set.
Activities of Daily Living↗
Comparison of the MOS short form-12 (SF12) health status questionnaire with the SF36 in patients with rheumatoid arthritis.
OBJECTIVE: To compare the performance of the MOS SF12 health survey (SF12) with the SF36 in a sample of 233 patients with rheumatoid arthritis (RA) stratified by functional class. METHODS: The SF12 and SF36 physical and mental component summary scales (PCS and MCS) were compared for test retest reliability [intra-class correlation coefficient (RC) and repeatability], construct validity and responsiveness [standardized response mean (SRM)] to self-reported change in health. RESULTS: Overall, despite its brevity, the SF12 is comparable to the SF36 with only some loss of performance. The SF12-PCS is slightly less reliable (RC = 0.75) and responsive to improvements in health (SRM = 0.52) than the SF36-PCS (RC = 0.81; SRM = 0.61). The SF12-PCS correlates strongly with the SF36-PCS (R = 0.94), SF36 physical function subscale (R = 0.77) and modified Stanford Health Assessment Questionnaire (MHAQ) (R = 0.71), but only weakly with the SF36 mental health subscale (R = 0.22). SF12-PCS discriminated well between Steinbrocker functional classes; patients in functional classes 1-4, respectively, have SF12-PCS scores 1sigma, 2sigma, 2.4sigma and 2.7sigma below the population norm (ANOVA, F = 35.8, P < 0.000). The SF12-MCS is relatively unresponsive to reported improvement in RA (SRM = 0.31), but is reliable (RC = 0.71) and correlates well with the SF36-MCS (R = 0.71). SF12-MCS correlates more closely than the SF36-MCS with the SF36 mental health subscale (R = 0.86) and Hospital Anxiety and Depression (HAD) scale (R = 0.76). In ANOVA models, only the HAD (R2 = 57%) score contributes significantly to variance in SF12-MCS (F = 254.8; P < 0.000), but both the HAD (R2 = 24%) and MHAQ (R2 = 10%) scores contribute to variance in the SF36-MCS (F = 50.9; P < 0.000). Thus, the SF12-MCS has better construct validity for mental health than SF36-MCS in RA subjects. Missing responses to items were high amongst patients in functional class 4 (34%). CONCLUSION: The SF12 is a reliable, valid and responsive measure of health status in the majority of RA patients, and meets standards required for comparing groups of patients. Its application in the most severely disabled subjects is uncertain.
Adult↗
p16INK4a expression is frequently decreased and associated with 9p21 loss of heterozygosity in sporadic melanoma.
The product of the p16/INK4a/CDKN2/MTS1 tumor-suppressor gene acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein. p16 is inactivated in a wide range of human malignancies, including familial melanoma. However, its expression and function in sporadic melanoma has not been extensively investigated. We studied p16 expression in 62 archival melanomas and 30 archival nevi and lentigines by immunohistochemistry. Eighteen of 26 (69%) superficial spreading melanomas, 17 of 28 (61%) nodular melanomas, all of three lentigo maligna melanomas, and all of five melanoma metastases were found to harbor less than 10% p16-positive tumor cells. In contrast, only six of 24 (25%) nevi had less than 10% positive cells. No correlation between tumor thickness and loss of p16 expression was found. Using DNA from micro-dissected tumor and matched normal tissues, five of seven (71%) p16-negative melanoma cases had 9p21 loss of heterozygosity (LOH), and one of these 9p21 LOH cases had promoter region hypermethylation of the remaining p16 allele. These data demonstrate that partial or complete loss of p16 expression is prevalent in sporadic melanoma and is frequently associated with 9p21 LOH.
Chromosomes, Human, Pair 9↗
Kaposi's sarcoma in a patient with erythroblastopenia and thymoma: reactivation after topical corticosteroids.
We report a 69-year-old female with erythroblastopenia and thymoma who developed lesions of Kaposi's sarcoma (KS) after thymectomy, 2 months after the initiation of therapy with methylprednisolone. Control of mucocutaneous KS lesions was obtained with radiotherapy, interferon alfa-2b and withdrawal of systemic immunosuppressive therapy. Erosive oral lichen planus appeared later, and after therapy with topical corticosteroids a new lesion of KS developed that regressed after withdrawal of topical corticosteroids. The detection of HHV-8 only in lesional skin supports the hypothesis that this virus can trigger the development of KS lesions.
Administration, Topical↗
The influence of ill-health experience on the valuation of health.
Social valuations for health states are potentially useful both in clinical decision-making and in health-resource allocation, but there is some evidence that the experience of illness may affect such valuations. This article compares valuations of hypothetical health states obtained from a sample of chronically ill patients, with valuations obtained from a sample of relatively healthy individuals. The instrument used to obtain these values was the EuroQOL 5D questionnaire (EQ-5D). We found that the EQ-5D values of chronically ill patients differed significantly from the values obtained from healthier individuals, particularly in the case of the more severe health states. Healthy individuals assigned negative values to some hypothetical health states, indicating that they consider them to be worse than death, whereas chronically ill patients assigned positive values to all health states. These results raise difficult questions about whose values should count when health-status measures are incorporated in clinical and economic evaluation, and in particular when deciding upon the allocation of scarce resources.
Activities of Daily Living↗
Automated high-resolution polymerase chain reaction fragment analysis: a method for detecting T-cell receptor gamma-chain gene rearrangements in lymphoproliferative diseases.
Southern blot analysis and the polymerase chain reaction (PCR) are powerful tools for detecting clonal antigen receptor gene rearrangements. However, a number of limitations restrict the predictive value of the results obtained by these techniques as they are commonly used. We describe a new method, automated high-resolution PCR fragment analysis, that can partially overcome many of the limitations of analyzing the T-cell receptor (TCR) gamma-chain gene. Analysis of TCR-gamma is performed using PCR with four sets of primers, previously described by others, specific for all variable (V) and joining (J) regions of the TCR gamma-chain gene. In addition, the four V region primers are 5' end-labeled with a fluorescent compound, 5-carboxyfluorescein. After amplification, the labeled PCR products are separated with an automated sequencing system, ABI 373 (Applied Biosystems, Weiterstadt, Germany). With the help of the Gene-Scan software ABI 672 (Applied Biosystems) and fluorescent-labeled DNA length markers, the exact size of each peak can be displayed and analyzed. The resolution of this method allows separation of PCR products differing in length by as little as 1 bp. Semiquantitative estimation of specific clones also can be performed. Infiltrate-specific gene rearrangement patterns can be identified and recognized in different tissue specimens at the time of diagnosis or in subsequent biopsy specimens. We conclude that automated high-resolution PCR fragment analysis allows more accurate and convenient analysis of the TCR gamma-chain gene.
Automation↗
A family of activity-dependent neuronal cell-surface chondroitin sulfate proteoglycans in cat visual cortex.
Monoclonal antibody Cat-301 recognizes a chondroitin sulfate proteoglycan (CSPG) expressed on the extracellular surface of cell bodies and proximal dendrites of specific subsets of neurons in many areas of the mammalian CNS, including the cat visual cortex. The Cat-301 CSPG is first detected at the close of the critical period in development, a period during which the pattern of neuronal activity determines the mature synaptic circuitry and neuronal phenotype. In the cat visual cortex, dark-rearing from birth prolongs the duration of the critical period and attenuates the expression of the Cat-301 antigen, implicating the Cat-301 CSPG in the cellular mechanisms that terminate the period of synaptic plasticity. Because the Cat-301 antigen is expressed on only a limited subset of neurons, we have further examined the molecular heterogeneity among neuronal cell-surface CSPGs and have asked (1) whether other neuronal subsets carry distinct CSPGs and (2) whether the activity-dependent expression of the Cat-301 CSPG is a property generalizable to related cell-surface CSPGs. Here, we report two new monoclonal antibodies, Cat-315 and Cat-316, which together with Cat-301 define a family of at least seven related yet distinct CSPGs. These three antibodies define nonidentical subsets of neurons in the cat visual cortex. The expression of normal levels of these CSPGs is reduced by dark-rearing. Together, these data show that the family of cell-surface CSPGs is molecularly diverse, that different sets of neurons express distinct complements of cell-surface antigens, and that the regulation of CSPG expression by activity may be a general feature of neuronal cell-surface CSPGs.
Animals↗
Radiation lentigo. A distinct cutaneous lesion after accidental radiation exposure.
BACKGROUND: Accidental exposure of skin to ionizing radiation leads to long-term alterations such as fibrosis, keratosis, and teleangiectasias. Also, noncharacteristic hyperpigmentation and hypopigmentation may be noted. OBSERVATIONS: A distinct lesion is described on the calves of a white male survivor of the 1986 nuclear accident at Chernobyl, Ukraine. Several years after the accident at Chernobyl, characteristic pigmented macules developed in the areas of skin that had previously been exposed to ionizing radiation: there was a marked, sharply demarcated lentiginous hyperpigmentation of epidermal and basal keratinocytes and melanocytes, as well as an increase in the number of melanocytes. No cellular atypia was noted. CONCLUSIONS: This case demonstrates the potential of high single doses of ionizing radiation to induce pigmented lesions with similar clinical and histological features as they have been described after exposure to natural UV radiation or radiation from a tanning bed or sunlamp or after therapy with oral psoralen with long-wave UV-A radiation (PUVA), described as solar, tanning bed, and PUVA lentigines. The absence of cellular atypia may account for a favorable prognosis and enables clear distinction from more serious diagnoses such as lentigo maligna melanoma.
Humans↗