PubMed Health⌕ Search

Biomedical subjects

H Stege

Publications and source records attributed to H Stege.

At least 19 recordsLinked to original sources

VETSTAT-the Danish system for surveillance of the veterinary use of drugs for production animals.

The Danish Ministry of Food, Agriculture and Fisheries funds a monitoring system based on drug usage information collected at the herd level: VETSTAT. VETSTAT is constructed as a relational database and data originates from three sources: pharmacies, veterinarians and feed mills. All administration of drugs for use in animal production is reported on a monthly basis. Pharmacies provided 95% of the total weight antimicrobial compounds used in Denmark in 2001. More than 80% of the antimicrobial compounds reported by pharmacies were sold on prescription to end-users (owners) and included information on animal species, age-group and diagnostic grouping; >90% of the total amount of antimicrobials sold on prescription was used for pigs. In 2001, sales of 96,500 kg of antimicrobials were reported.

Animal Feed↗

[Acyclovir-resistant herpes exulcerans et persistens. Type II].

Immunocompromised patients are developing in an increasing frequency acyclovir-resistant herpes simplex infections. Different treatment options need to be evaluated considering the possible side effects in regard to the patients' immunocompromised status. A 73-year-old woman with B-cell lymphatic leukemia with a secondary antibody deficiency syndrome and anemia suffered for one year with perianal ulcerations caused by acyclovir-resistant herpes simplex infection Type II. Based on previous reports about successful treatment of acyclovir-resistant herpes simplex infections with foscarnet, cidofovir or vidarabine and considering the different side effects of these drugs as well as the underlying diseases of the patient, we treated her with foscarnet intravenously. After 3 months the ulcers showed a nearly complete remission.

Acyclovir↗

Successful treatment of solar urticaria by extracorporeal photochemotherapy (photopheresis)--a case report.

UNLABELLED: Solar urticaria is characterized by erythema and whealing immediately after exposure to ultraviolet radiation and/or visible light. We report about a patient with severe solar urticaria, who was highly sensitive to both UVA radiation and visible light with a Minimal Urticaria Dose (MUD) of 7 J/cm2 UVA. Management of this patient was extremely difficult because standard treatment with oral antihistamines, hardening with UVA, UVB, visible light or oral PUVA and even oral cyclosporin A were completely ineffective. We therefore decided to perform extracorporeal photochemotherapy (photopheresis, ECP). After nine treatment cycles with photopheresis the MUD increased from 7 J/cm2 UVA before treatment to 22 J/cm2 UVA. This hardening effect was associated with a significant decrease of the frequency and severity of whealing and the accompanying symptoms (pain, fatigue, pruritus). CONCLUSION: Photopheresis might be of some benefit in selected patients with otherwise intractable solar urticaria.

Humans↗

Effect of xenogenic repair enzymes on photoimmunology and photocarcinogenesis.

Exposure to ultraviolet B (UVB) radiation leads to an increased generation of UVB-induced skin damage in humans. The most important UVB-induced side effects are UVB-induced immunosuppression and photocarcinogenesis and there is a large body of evidence that cyclobutane pyrimidine dimers (CPD) induced by UVB radiation play a pivotal role in both processes. The topical application of DNA repair enzymes is a new innovative strategy to reduce the amount of CPDs in human skin. Two different methods have recently been established. The use of T4 endonuclease V was of clinical efficacy in protecting patients with a nucleotide excision repair defect from premalignant and malignant skin lesions. Application of photolyase, a xenogenic enzyme which has been found in different organisms is also capable of removing UVB-induced CPD from normal human skin cells in vivo and appears to be more effective than T4 endonuclease V in damage removal. Photolyase encapsulated in liposomes may have in the near future a broad use as an active ingredient in modern skin care products.

Animals↗

Risk factors for intestinal pathogens in Danish finishing pig herds.

The objective of this investigation was to identify risk factors for infection with the intestinal bacteria: Lawsonia intracellularis, Brachyspira hyodysenteriae, Serpulina intermedia, Brachyspira innocens, Brachyspira pilosicoli and swine-pathogenic Escherichia coli (serogroups O138, O139, O141 and O149) in Danish finishing pig herds.A total of 79 herds was randomly selected and visited during 1998. From each herd, 20 faecal samples were collected from individual pigs weighing 30-50 kg. In total, 1580 faecal samples were collected and examined by polymerase chain reaction (L. intracellularis) or culture (all other agents). Information on feed and management procedures was collected by filling in questionnaires at the herd visits. The questionnaires included information on 29 dichotomous variables and three continuous variables. Variables with P<0.25 in a preliminary screening (chi2- or t-test) were selected for the statistical modelling. Our conclusions, based on the results of multifactorial logistic regression (cut-off: P=0.05), were the following: 1. Consistent batch production was associated with reduced prevalences of L. intracellularis and weakly -haemolytic spirochetes (S. intermedia, B. innocens, B. pilosicoli) (OR's=0.43 and 0.06, respectively). 2. Home-mixed (and/or non-pelleted) feed was associated with reduced prevalences of L. intracellularis and weakly -haemolytic spirochetes (OR's=0.6 and 0.4, respectively). 3. Providing straw to finishers was associated with a reduced prevalence of weakly -haemolytic spirochetes (OR=0.28-0.32). 4. Not using antimicrobial growth promoters for piglets was associated with an increased prevalence of S. intermedia (OR=11.11). 5. Rare occurrence of post-weaning diarrhoea (as opposed to common) was associated with an increased prevalence of weakly -haemolytic spirochetes (OR=8.3-13.7).

Animals↗

Data-quality issues and alternative variable-screening methods in a questionnaire-based study on subclinical Salmonella enterica infection in Danish pig herds.

Our aim was to determine risk factors for subclinical Salmonella enterica infection in Danish finishing-pig herds. In this paper, the evaluation, combining and initial reduction of variables is presented, along with assessment of the hypotheses in the preliminary statistical testing. The first group of herds was selected at random with no former knowledge of S. enterica infection. Both the herd prevalence and the within-herd prevalence among these herds turned out to be low; hence, some additional herds were selected from The Danish Salmonella Control program, based on their high seroprevalence. This resulted in a hybrid case-"control" design of the study and therefore, five different methods of categorising the data were used to ensure that variables were not wrongfully excluded as a result of using an improper design. Our questionnaire focused on management, infection-limiting precautions and feed and feeding procedures. To establish the prevalence of S. enterica infection within herds at the time of the visit, 50 blood samples from each herd were collected and serologically examined. The reliability of each variable from the questionnaire was assessed and it was decided which variables should be selected, disregarded, combined with other variables and/or recoded. In the simple statistical testing (2x2 tables, cut-off: P=0.25) herds were defined as subclinically S. enterica infected if the within-herd proportion of individual pigs with OD%>10 was more than 20%. The results included questionnaires from 96 randomly selected and 39 high-seroprevalence herds and 6814 blood samples. The initial 95 variables originally included in the questionnaires were reduced to 21 by critical check, combination, recoding and preliminary screening. We failed to demonstrate "herd size" as a risk factor for subclinical S. enterica infection in pig herds.

Analysis of Variance↗

Prevalence of intestinal pathogens in Danish finishing pig herds.

Our aim was to determine the prevalence of the intestinal bacteria: Lawsonia intracellularis, Brachyspira hyodysenteriae, Serpulina intermedia, Brachyspira innocens, Brachyspira pilosicoli, pathogenic Escherichia coli (serogroups O138, O139, O141 and O149) and Salmonella enterica in Danish finishing pig herds. A total of 79 herds was randomly selected and visited during 1998. From each herd, 20 faecal samples were collected from individual pigs weighing 30-50kg. Furthermore, 10 pooled pen samples were collected and examined for S. enterica. In total, 1580 faecal samples and 790 pen samples were collected and examined by polymerase chain reaction (PCR) or culture. L. intracellularis was found in 74 herds (93.7%), B. hyodysenteriae in two herds (2.5%), S. intermedia in 10 herds (12. 7%), B. innocens in 27 herds (34.2%), B. pilosicoli in 15 herds (19. 0%), pathogenic E. coli in 19 herds (24.1%) and S. enterica in eight herds (10.1%). The within-herd prevalences of L. intracellularis and B. hyodysenteriae were 25-30%; the within-herd prevalences of the other agents were 5-10%. Three herds (4%) were not infected with any of the bacteria and 25 herds (32%) were only infected with L. intracellularis.

Animals↗

Prevalence of subclinical Salmonella enterica infection in Danish finishing pig herds.

Our aim was to determine the Salmonella enterica prevalence in 96 randomly selected Danish pig herds, based on serological examination of blood samples and bacteriological examination of faecal samples (collected simultaneously from the same pens). For comparison, 39 high-seroprevalence herds were included in the study. The representativeness of the selected herds was assessed, based on descriptive statistics of herd size and type. Totals of 1330 pen samples and 6814 blood samples were examined.The results from the meat-juice screening in the Danish S. enterica Control Programme were available for 3372 meat-juice samples from 91 of the 96 randomly selected herds and 1195 meat-juice samples from 37 of the 39 high-seroprevalence herds. Of the 96 randomly selected herds, 23 herds had no positive pen samples (out of 10), no positive blood samples (out of 50) and no positive meat-juice samples (out of approximately 30-40 samples in 6 months). Ten herds had one or more positive meat-juice samples but were otherwise negative. S. Typhimurium was isolated from 30 of the 39 high-seroprevalence herds. Our conclusions were: (1) The within-herd seroprevalence among the 96 randomly selected Danish pig herds was low (average within-herd seroprevalence=2%, maximum=32%). (2) Among the 39 high-seroprevalence herds (recently assigned level 3 in the S. enterica Control Programme), S. enterica was isolated from 77% of the herds when 10 pen samples were examined bacteriologically. (3) Seropositivity tended to be related to the presence of S. Typhimurium.

Animals↗

Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin.

Ultraviolet-B (UVB) (290-320 nm) radiation-induced cyclobutane pyrimidine dimers within the DNA of epidermal cells are detrimental to human health by causing mutations and immunosuppressive effects that presumably contribute to photocarcinogenesis. Conventional photoprotection by sunscreens is exclusively prophylactic in nature and of no value once DNA damage has occurred. In this paper, we have therefore assessed whether it is possible to repair UVB radiation-induced DNA damage through topical application of the DNA-repair enzyme photolyase, derived from Anacystis nidulans, that specifically converts cyclobutane dimers into their original DNA structure after exposure to photoreactivating light. When a dose of UVB radiation sufficient to induce erythema was administered to the skin of healthy subjects, significant numbers of dimers were formed within epidermal cells. Topical application of photolyase-containing liposomes to UVB-irradiated skin and subsequent exposure to photoreactivating light decreased the number of UVB radiation-induced dimers by 40-45%. No reduction was observed if the liposomes were not filled with photolyase or if photoreactivating exposure preceded the application of filled liposomes. The UVB dose administered resulted in suppression of intercellular adhesion molecule-1 (ICAM-1), a molecule required for immunity and inflammatory events in the epidermis. In addition, in subjects hypersensitive to nickel sulfate, elicitation of the hypersensitivity reaction in irradiated skin areas was prevented. Photolyase-induced dimer repair completely prevented these UVB radiation-induced immunosuppressive effects as well as erythema and sunburn-cell formation. These studies demonstrate that topical application of photolyase is effective in dimer reversal and thereby leads to immunoprotection.

Adult↗

Inhibition of intercellular adhesio nmolecule-1 (ICAM-1) expression in ultraviolet B-irradiated human antigen-presenting cells is restored after repair of cyclobutane pyrimidine dimers.

The present study assessed the molecular mechanism underlying ultraviolet (UV) B radiation-induced inhibition of the expression of the adhesion molecule ICAM-1 in human antigen-presenting cells (APC). UVB radiation-induced inhibition of ICAM-I expression in human peripheral blood monocytes was associated with the generation of cyclobutane pyrimidine dimers (CPD). CPD were reduced by 60% after treatment with liposomal packed photolyase, an enzyme which removes CPD after absorption of photoreactivating light. Although incomplete, reduction of CPD was associated with complete restoration of ICAM-1 expression at the mRNA and protein level. Neither reduction of CPD level nor restoration of ICAM-1 expression were observed, if monocytes were treated with empty liposomes, or if they were irradiated with photoreactivating light prior to application of photolyase. DNA damage might also induce soluble mediators capable of autocrine inhibition of ICAM-1 expression. UVB irradiation of monocytes did not induce IL-10 production, but resulted in release of prostaglandin (PG) E2. Treatment of unirradiated monocytes with PGE2 completely inhibited ICAM-1 expression, thus mimicking the UVB effect. Inhibition of monocytic PGE2 production by indomethacin, however, did not restore ICAM-1 expression. These results suggest that formation of CPD is necessary and sufficient for UVB radiation-induced inhibition of ICAM-1 expression. In contrast, PGE2 might serve a paracrine role in UVB radiation-induced immunosuppression.

Antigen-Presenting Cells↗

Evaluation of the capacity of sunscreens to photoprotect lupus erythematosus patients by employing the photoprovocation test.

Although sunscreens are widely used to photoprotect patients with photosensitive lupus erythematosus (LE), standardized controlled studies that can prove their efficacy for this indication have been lacking. Therefore, in the present study, the capacity of three different, commercially available sunscreens to prevent the development of skin lesions that have been induced in LE patients under standardized, reproducible conditions by employing a provocative phototest was assessed. In a double blind, intraindividual comparative study, 11 patients with LE were photoprovoked according to a standard protocol. All patients developed LE-specific skin lesions upon photoprovocation with a combination of UVA plus UVB radiation. Each of the sunscreens tested prevented the development of skin lesions in this assay, but to various extents. Suncreen A (UVB: Octocrylene; UVA: Mexoryl SX, Mexoryl XL, Parsol 1789; TiO2) was by far the most effective by protecting in 11/11 patients. This protective capacity was corroborated by studies in which strong ICAM-1 mRNA expression was found in unprotected test areas, but not in sunscreen A pretreated sites. In contrast to sunscreen A, sunscreen B (UVB: Eusolex 6300, Parsol MCX, Uvinul T150, Neohelipan; UVA: Parsol 1789; TiO2) protected in 5 patients and sunscreen C (Eusolex 6300, Parsol MCX, Uvinul T150; UVA: Parsol 1789; TiO2) in 3 out of 11 patients. These studies indicate that the use of sunscreens is beneficial to LE patients because it can prevent the development of UV radiation-induced skin lesions. Effective protection, however, might vary considerably between different sunscreens.

Adult↗

Neurotrophin-4 production by human epidermal keratinocytes: increased expression in atopic dermatitis.

Chronic inflammatory conditions of human skin, such as prurigo lesions of atopic dermatitis, are characterized clinically by intense pruritus and histologically by increased innervation. Regulation of skin innervation is thought to depend on neurotrophic factors. In this study, human skin cells were identified as a source of neurotrophins. Cultured keratinocytes expressed neurotrophin-4, whereas dermal fibroblasts expressed neurotrophin-3. In vitro stimulation with interferon-gamma, a marker cytokine for atopic eczema, induced keratinocyte neurotrophin-4 production, which was able to support growth of a neuroglioblastoma-derived cell line. In vivo, immunohistochemistry of human skin for neurotrophins showed neurotrophin-4 staining in the epidermal layer and neurotrophin-3 staining in the dermal compartment. Neurotrophin-4 but not neurotrophin-3 expression was markedly increased in interferon-gamma-injected skin. Prurigo lesions of atopic dermatitis skin were characterized by intense epidermal staining for neurotrophin-4, suggesting a pathophysiologic role for this neurotrophin in the increased innervation characteristic for these skin lesions. This study demonstrates differential expression and regulation of neurotrophins in human skin. It also identifies keratinocyte-derived neurotrophin-4 as a possible link between the immune and the nerve system of human skin.

Antibodies↗

Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma.

BACKGROUND: The results of a recent study suggested that ultraviolet A1 radiation (UVA1R; 340-400 nm) phototherapy for atopic dermatitis works through induction of apoptosis in skin-infiltrating helper T cells, indicating the possibility that other helper T cell-mediated skin diseases may respond to UVA1R as well. OBJECTIVE: The purpose of this open pilot study was to assess the therapeutic effectiveness of UVA1 phototherapy for cutaneous T-cell lymphoma (CTCL). METHODS: UVA1 phototherapy was used as monotherapy in patients (n = 3) with histologically proven CTCL (stages IA and IB). For daily whole body UVA1 irradiations, either a high-dose (n = 2; 130 J/cm2 UVA1 per exposure) or medium-dose (n = 1; 60 J/cm2 UVA1) regimen was used. Therapeutic effectiveness was assessed clinically and histologically. RESULTS: In each of the 3 patients, skin lesions began to resolve after only a few UVA1 radiation exposures. Complete clearance was observed between 16 and 20 exposures, regardless of whether the high- or medium-dose regimen had been employed. CONCLUSION: These studies suggest that patients with CTCL stages IA and IB can be treated effectively with UVA1 phototherapy.

Aged↗

Effect of topical tazarotene in the treatment of congenital ichthyoses.

The clinical efficacy and tolerability of the topical receptor-selective retinoid tazarotene in the treatment of congenital ichthyoses was investigated. Twelve consecutive patients with different forms of congenital ichthyosis were enrolled in an open, non-randomized, intraindividually controlled, half-side pilot study. Diagnoses were X-linked recessive ichthyosis, non-erythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant ichthyosis vulgaris and ichthyosis bullosa of Siemens (IBS). Tazarotene 0.05% gel was applied unilaterally daily on a defined body area measuring 10% of the body surface area. The contralateral side was treated with an ointment containing 10% urea. After 14 days, application frequency was reduced to three times a week, and stopped after another 2 weeks. The follow-up period was 3 months. Reduction in scaling and roughness was used to assess the clinical response in the tazarotene-treated area compared with the control area. Clinical and laboratory assessments were performed every 14 days during the trial. Unilateral improvement in favour of the tazarotene-treated side was observed in nine of 12 patients (75%). Four patients (33%) achieved an excellent response and four (33%) achieved a good response. No therapeutic effect was seen in patients with IBS. The remission persisted during the reduction phase and after discontinuation for up to 2 months. Local irritation in three patients was the only side-effect detectable. Short-term topical application of tazarotene 0.05% gel is a very effective and well-tolerated treatment modality in different forms of congenital ichthyoses and may be an alternative to systemic retinoid therapy.

Administration, Cutaneous↗

Successful monotherapy of severe and intractable atopic dermatitis by photopheresis.

BACKGROUND: Patients with chronic atopic dermatitis can become unresponsive to standard immunosuppressive therapy and thus pose a serious therapeutic problem. OBJECTIVE: Our purpose was to evaluate the therapeutic effectiveness of photopheresis in the management of patients with severe and intractable atopic dermatitis. METHODS: Photopheresis was used as monotherapy in patients (n = 3) who previously did not respond to treatment with glucocorticosteroids, cyclosporine, phototherapy, or photochemotherapy. Patients were treated at 2-week intervals (total number of treatments = 10). RESULTS: In all patients, photopheresis induced clinical improvement and reduction of elevated serum levels of eosinophil cationic protein and total IgE. Prolongation of the intervals between treatments from 2 to 4 weeks caused worsening in one patient, whereas shortening of treatment-free intervals improved both clinical and laboratory findings. CONCLUSION: These studies indicate that photopheresis may be used as monotherapy for the treatment of patients with severe atopic dermatitis that has become intractable to standard therapeutic modalities.

Adult↗