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Biomedical subjects

P Lehmann

Publications and source records attributed to P Lehmann.

At least 73 records · Page 4Linked to original sources
PubMed1998

An integrated model for the differentiation of chemical-induced allergic and irritant skin reactions.

Contact and photocontact allergic as well as irritant and photoirritant skin reactions represent a major problem in clinical dermatology and during the development of new pharmaceuticals. Furthermore, there is a lack of in vitro and in vivo assays that provide a clear differentiation between allergic and irritant skin reactions. Here, we describe an integrated model to differentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose-response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed that irritants predominantly induced skin inflammation, which in turn stimulated draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin inflammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern whereas DI < 1 demonstrates an irritant potential of a chemical. Experiments with the contact allergen oxazolone, the photocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritant 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore, flow cytometric analysis of lymph node-derived T- and B-cell subpopulations revealed that contact sensitizer, but not irritant, induced the expression of CD69 on the surface of I-A+ cells. In conclusion, further studies with a broad range of irritants and allergens will be required to confirm general applicability.

Animals↗
PubMed1998

[Scabies--provoked bullous lichen planus in a child].

Lichen ruber planus is considered a T-cell mediated immunologic reaction with unclear pathogenesis. Drugs and infections (especially hepatitis B and C) are well-known provocation factors. After an infection with scabies a 13 year old boy developed a generalized lichen planus including bullous lesions. For the first time scabies is presented as a trigger for lichen planus. In childhood, lichen planus is characterized by atypical clinical features and sometimes a severe course.

Adolescent↗
PubMed1998

Kinetics of photosensitivity in bath-PUVA photochemotherapy.

BACKGROUND: Bath-PUVA is used to treat a variety of dermatoses. However, the kinetics of 8-methoxypsoralen during treatment are not completely clarified. OBJECTIVE: The purpose of this study was to investigate the intensity of the phototoxic response and the persistence of phototoxicity after bath-PUVA. METHODS: Twelve volunteers were exposed to UVA doses ranging from 0.5 to 40 J/cm2 from 10 to 240 minutes after bath-PUVA treatment. The resulting phototoxic response of the skin was determined. RESULTS: Irradiation 10 minutes after the psoralen bath led to the lowest assessed minimal phototoxic dose (MPD) of 1.42 J/cm2 (mean, SD +/- 0.29). Thereafter, the MPD increased significantly and sharply every hour. At 4 hours after the psoralen bath, UVA doses up to 40 J/cm2 failed to induce any phototoxic erythema (MPD). CONCLUSION: For optimal effects, UVA irradiation has to be administered immediately after the psoralen bath; no restrictive behavior is necessary after bath-PUVA treatment.

Adult↗
PubMed1998

The Maudsley Addiction Profile (MAP): a brief instrument for assessing treatment outcome.

AIM: To develop a brief, multi-dimensional instrument for assessing treatment outcome for people with drug and/or alcohol problems. The Maudsley Addiction Profile (MAP) is the first instrument to be developed in the United Kingdom for this purpose. DESIGN: Field testing with quota-recruitment of problem drug users and problem alcohol users in treatment with researcher and clinician-administered test-retest interviews. SETTING: Two community and two inpatient services at the Bethlem Royal and Maudsley Hospital, London. PARTICIPANTS: Subjects (160 drug users and 80 alcohol users) interviewed by eight interviews (four researchers and four clinicians), each of whom interviewed 30 subjects on two occasions. MEASURES: Sixty items across substance use, health risk, physical/psychological health and personal/social functioning domains. FINDINGS: Average completion time of the MAP was 12 minutes. The questionnaire was acceptable to a majority of subjects and performed well with both researcher and clinician interviewers. Internal reliability and feasible concurrent validity assessments of the scales and items were highly satisfactory. Test-retest reliability was good, average intraclass correlation coefficients across eight substances were 0.94 and 0.81 across health risk, health problems, relationship conflict, employment and crime measures. CONCLUSIONS: The MAP can serve as a core research instrument with additional outcome measures added as required. The collection of a set of reliable quantitative measures of problems among drug and alcohol users by research or treatment personnel for outcome evaluation purposes need not be time-consuming.

Adult↗
PubMed1998

Aberrant timing in epidermal expression of inducible nitric oxide synthase after UV irradiation in cutaneous lupus erythematosus.

Photosensitivity is a main criterion for the diagnosis of systemic lupus erythematosus (LE), and ultraviolet (UV) irradiation plays a key role in the pathogenesis of cutaneous LE. Patients with a tentative diagnosis of LE are routinely tested for skin lesion development after experimental UV irradiation, providing an ideal opportunity to evaluate early, preclinical events involved in the pathogenesis of LE. Several reports have shown expression of the cytokine-inducible nitric oxide synthase (iNOS) in autoimmune diseases. Therefore, we investigated the role of iNOS expression at mRNA and protein level in the pathogenesis of LE lesions. Skin biopsies from patients with different subtypes of LE were examined, and iNOS expression was found in six of 18 biopsies from cutaneous LE patients and two of three biopsies from systemic LE patients. In biopsies taken 4-20 d after UV irradiation, epidermal iNOS expression was seen in all patients (n = 10) after UVB and in four of 10 patients provoked by UVA. In healthy controls (n = 8) epidermal iNOS expression was detected 24 h after UV irradiation, persisting for another day before subsiding on day 3. In LE patients (n = 8) the exact reverse situation was seen: an iNOS-specific signal was undetectable in keratinocytes for 2 d after UV irradiation, but became positive on day 3 and persisted for up to 25 d in the evolving skin lesions. Our findings demonstrate a time-restricted, UV-induced iNOS expression in human skin; moreover, the results indicate that both the kinetics of iNOS induction as well as the time span of local iNOS expression may be critical to the development of cutaneous LE lesions.

Adult↗
PubMed1998

Economic burden of drug dependency. Social costs incurred by drug users at intake to the National Treatment Outcome Research Study.

BACKGROUND: The use of illegal drugs is seen as a major social problem. The social costs can be high. METHODS: Self-report data from interviews at intake to the National Treatment Outcome Research Study (NTORS) for 1075 drug users and cost data from various sources were used to estimate criminal behaviour and health and addiction service costs for a 12-month period. Multivariate statistical analysis was used to analyse cost variations. RESULTS: Total costs for one year for the drug users amounted to over 12 million Pounds, the majority attributable to self-reported criminal behaviour. Social costs were positively related to a variety of factors including instability in living circumstances, amount of heroin used and whether or not drugs were taken intravenously. CONCLUSIONS: The study clearly demonstrates the economic and social burden associated with heavy drug users and highlights the need for further investigations into the costs and benefits of policies that can reduce these social costs.

Age Factors↗
PubMed1998

Substance use, health and social problems of service users at 54 drug treatment agencies. Intake data from the National Treatment Outcome Research Study.

BACKGROUND: The National Treatment Outcome Research Study (NTORS) is the first large-scale, prospective, multi-site treatment outcome study of drug users in the UK. METHOD: Substance use, health and social problems of 1075 service users were assessed at intake to 54 agencies chosen to be representative of the main national drug treatment modalities. RESULTS: Heroin dependence was the most frequently reported problem often with poly-drug and alcohol problems. Most service users injected drugs and a quarter of the injectors shared injecting equipment. Poly-drug use and heavy drinking were more common among service users admitted to residential treatments. High criminality rates were reported. Psychological and physical health problems were common and many service users had prior contact with psychiatric and medical services. CONCLUSIONS: The range and severity of problems adversely affect individual users, their families, and present a challenge to addiction treatment services. These problems create costs for the health care, social service and criminal justice system responses.

Adolescent↗
PubMed1998

Dementia in people aged 65 years and older: a growing problem?

This study examines trends in death rates from dementias and neurodegenerative disorders in people aged 65 and over in England and Wales between 1979 and 1996. In total, there were 171,590 deaths from dementias and neurodegenerative disorders, with the number of deaths per year increasing from 3,021 in 1979 to 10,415 in 1996. Age-standardised death rates for all diagnoses combined increased from 39 to 96 per 100,000 for men and from 45 to 101 for women between 1979 and 1996. The most dramatic increase was seen in death rates from Alzheimer's disease which increased from less than 1 per 100,000 in 1979 to 19 for men and 21 for women in 1996.

Aged↗
PubMed1998

Preferential relative porphyrin enrichment in solar keratoses upon topical application of delta-aminolevulinic acid methylester.

Topically applied delta-aminolevulinic acid is used efficiently for the treatment of solar keratoses by photodynamic therapy. Recent animal studies suggest that porphyrin sensitization of epithelial tissue is improved by using esters rather than free delta-aminolevulinic acid. The present study examines porphyrin metabolite formation after topical application of delta-aminolevulinic acid or delta-amino-levulinic acid methylester in human solar keratoses versus adjacent normal skin. Level of total porphyrins, porphyrin metabolites and protein were measured in skin samples excised after 1 and 6 h. Higher levels of porphyrins were observed in solar keratoses than in normal skin with both substances. Maximum porphyrin levels were present in solar keratoses treated with delta-aminolevulinic acid for 6 h. However, the ratio of porphyrins in solar keratoses versus adjacent normal skin was higher with delta-aminolevulinic acid methylester. The pattern of porphyrins showed no significant difference between normal and afflicted skin, protoporphyrin being predominant. The results suggest that application of free delta-aminolevulinic acid may be more effective in sensitizing solar keratoses. However, treatment with delta-aminolevulinic acid methylester leads to a preferential enrichment of porphyrins within lesional skin.

Administration, Topical↗
PubMed1997

A local lymph node assay to analyse immunosuppressive effects of topically applied drugs.

Topical glucocorticosteroids represent the mainstay of antiinflammatory therapy in the treatment of inflammatory skin diseases. Their clinical use, however, is limited by local and systemic side-effects. Thus, in dermatopharmacology there is a large demand for alternative non-steroidal antiinflammatories. Other than transplantation models, most of the frequently used in vivo test systems for assessment of drug-induced immunosuppression measure changes in inflammatory skin responses by means of skin erythema and edema after challenge of sensitized animals. The aim of this study was to develop an alternative mouse model to detect and analyse immunosuppressive effects of topically applied drugs. On the basis of a modified local lymph node assay, we analysed effects of topical hydrocortisone, dexamethasone, mometasone furoate and FK506 (tacrolimus) during the induction phase of contact hypersensitivity. On 4 consecutive days, NMRI mice were treated on the dorsal surfaces of both ears with increasing concentrations of test compound. During the last 3 days, the mice received in addition the contact sensitizer, oxazolone (1%). On day 5, draining auricular lymph nodes were removed in order to assess lymph node cell counts and perform flow cytometric analysis of lymph node cell subpopulations (CD4+/CD25+, Ia+/CD69+, Ia+/B220+). All test compounds proved to exert significant immunosuppressive effects after topical application, but showed differences in their immunomodulatory potential. In conclusion, the local lymph node assay serves as an appropriate model to characterize immunosuppressive effects of topically applied drugs by measuring immunologically relevant end-points.

Administration, Topical↗
PubMed1997

[Vital long-term preservation of human gingiva in perfusion culture].

Perfusion culture offers the advantage of keeping gingiva alive for a long time as an stable explant according to cell biological parameters. To investigate the suitability of cultured human gingival explants for transplantations the biopsies were put into a newly developed perfusion chamber and cultured for at least 21 days. Gingiva explants were derived from healthy donors undergoing surgical removal of molar teeth. The tissue pieces were cultured without prior proteolytic desintegration or subculture. Immediately after excision a morphological and immunohistochemical analysis of the tissue was carried out and the distribution pattern of cytokeratin and vimentin was examined. Gingival explants cultured for 7, 14 and 21 days in serum-free keratinocyte growth medium in perfusion culture were analyzed in the same way. The morphology of the cultured explant (21 days) was well preserved from stratum basale up to stratum corneum. As proved by immunohistochemical incubation with antibodies to CK 5/6, CK 14 and CK 19, a tissue-specific cytokeratin (CK) expression pattern was maintained during the whole perfusion period. After 7 days of culture vimentin was synthesized in the fibroblast layer and was found in small quantities in each layer of the epithelium. In contrast to conventional cultures, where dissociation of the tissue and a subculture interruption is usually needed for long-term culture, this is not necessary for perfusion cultured tissue. The use of perfusion-cultured gingival explants as autogenous transplants is investigated herein.

Gingiva↗