[Pityrosporumfolliculitis (malasseziafolliculitis)].
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Antifungal Agents↗
Biomedical subjects
S Meller
Publications and source records attributed to S Meller.
[Topical treatment of subacute-cutaneous lupus erythematosus with tacrolimus].
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Administration, Topical↗
[Current aspects of the therapy with topical calcineurin inhibitors].
Since their approval, topical calcineurin inhibitors have proven to be effective medications in the treatment of atopic eczema. On March 10, 2005, the Food and Drug Administration (FDA) followed the advice of the Pediatric Advisory Council and issued a "black box warning" for the use of Protopic (Tacrolimus) und Elidel (Pimecrolimus). This FDA alert has caused worldwide uncertainty among parents and patients. Several dermatological societies have issued critical position statements. This report reviews the existing information underlying the warning and places it into the context of current knowledge.
Administration, Topical↗
[Palmoplantar erythrodysesthesia after intravenous therapy with docetaxel].
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Adult↗
ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors.
ATP has recently emerged as an important proinflammatory mediator that has direct excitatory actions on sensory neurons through activation of ion channel-coupled P2X receptors. The purpose of the current work is to assess whether ATP alters the release of neuropeptides from sensory neurons and the receptors mediating this putative action. Exposing embryonic sensory neurons in culture to concentrations of ATP up to 300 microm did not increase the release of immunoreactive substance P or calcitonin gene-related peptide from sensory neurons. However, pre-exposing sensory neurons to 0.1 to 100 microm ATP prior to and throughout administration of 30 nM capsaicin resulted in a significant augmentation of release evoked by the vanilloid. This sensitizing action of ATP is blocked by suramin but not pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid and is mimicked by the P2Y receptor agonists, 2-2-chloroadenosine triphosphate and UTP, but not by 2-(methylthio)adenosine 5'-triphosphate or alpha,beta-methyleneadenosine 5'-diphosphate. This profile of drug actions suggests that the sensitizing actions of ATP are mediated by P2Y receptors. Pretreating sensory neurons with bisindolylmaleimide I, a selective protein kinase C (PKC) inhibitor, attenuates the augmentation of capsaicin-induced peptide release by ATP, further implicating P2Y receptors in the actions of ATP. Immunoblotting also indicates the presence of P2Y2-like immunoreactive substance in embryonic dorsal root ganglia neurons. Together, these data support the notion that ATP acts at P2Y receptors in sensory neurons in a PKC-dependent manner to augment their sensitivity to other stimuli.
Adenosine Triphosphate↗
[Contact dermatitis caused by spinach, hedge mustard and chives].
A 54-year-old female working as a vegetable farmer presented with painful pruritic skin lesions on both hands. Physical examination showed a hyperkeratotic fissured eczema. RAST, prick- and patch testing revealed type I and IV hypersensitivity to spinach, ruccola, and chives, so that a protein contact dermatitis was diagnosed.
Chive↗
[Drug-induced exanthema caused by pegylated interferon-alpha 2b].
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Administration, Oral↗
Haploidentical vs autologous hematopoietic stem cell transplantation in patients with acute leukemia beyond first remission.
This is a retrospective comparison of partially mismatched related donor transplantation (PMRDT) and autotransplantation (ABMT) in advanced acute leukemia. Patients underwent T-cell-depleted PMRDT (n=164) or ABMT (n=131) for acute myeloid leukemia (n=130) or acute lymphoblastic leukemia (n=165). Fewer PMRDT patients were in remission (29 vs 85%; P<0.0001). The 5-year cumulative incidence of transplant-related mortality (TRM) was 52% after PMRDT and 16% after ABMT (P<0.0001). The 5-year cumulative incidence of relapse was 32% after PMRDT and 54% after ABMT (P=0.006). The actuarial unadjusted 5-year disease-free survival (DFS) was 16% after PMRDT and 30% after ABMT. In Cox's regression analysis, PMRDT (P<0.0001) and age >15 years (P=0.002) were associated with higher TRM, active disease (P=0.0021), ABMT (P=0.0074) and male sex (P=0.011) with higher relapse, and age >15 years (P=0.0007) and PMRDT (P=0.047) with lower DFS. Amongst second remission patients, TRM was higher after PMRDT (P=0.0003), relapse was higher after ABMT (P=0.034), and 5-year DFS was comparable (32% ABMT and 25% PMRDT). ABMT, if feasible, may be preferable to PMRDT in advanced acute leukemia patients since lower relapse after PMRDT is offset by higher TRM. If an autograft is not feasible because of nonavailability of autologous cells or very advanced disease, PMRDT is a potential alternative.
Acute Disease↗
Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease.
Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.
Acute Disease↗
Allogeneic transplantation from HLA-matched sibling or partially HLA-mismatched related donors for primary refractory acute leukemia.
Allogeneic transplantation is successful in a minority of patients with primary refractory acute leukemia (PRAL). An HLA-matched sibling donor (MSD) is available only in 30-40% of the patients, whereas a partially mismatched related donor (PMRD) is available for most. We compared the outcome of 24 MSD (median age 24 years) and 19 PMRD (median age 34 years; P = 0.04) allograft recipients with PRAL. All MSD patients received non-T cell-depleted marrow whereas all PMRD patients received partially T cell-depleted marrow. All evaluable PMRD patients and 90% of the evaluable MSD patients attained CR. Six patients in each group with recurrent/persistent disease died. Ten PMRD (3-year probability 70%) and 14 MSD (3-year probability 63%) patients died of treatment-related causes. At the last follow-up, three PMRD (18-50 months; 3-year probability 14%) and four MSD (20-166 months; 3-year probability 20%) patients were alive and well. We conclude that allogeneic transplantation is a viable therapeutic option for PRAL. PMRD transplantation is a reasonable alternative in patients with no MSD, and results in similar outcome. In terms of identifying a donor and harvesting cells, a PMRD transplant is significantly quicker than an unrelated donor transplant - a point of great practical importance in the setting of failed induction chemotherapy where time is of the essence.
Acute Disease↗
Novel SNPs in the CD18 gene validate the association with MPO-ANCA+ vasculitis.
Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg-Strauss syndrome (CSS) are characterized by the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Anti-myeloperoxidase (MPO)-ANCA are a typical feature of MP and CSS, while anti-proteinase 3 (PRTN3)-ANCA are highly specific for WG. Several reports indicate that ANCA may directly contribute to pathological processes, ie, through an increase of adhesivity between polymorphonuclear (PMN) and endothelial cells (EC). PMN interact and endothelium interact via the adhesion cascade (AC). CD18 is a key molecule of the AC, as CD18 defects abrogate the adhesion of PMN and cause leukocyte adhesion deficiency, an immunodeficient trait. We have screened the entire coding and regulatory regions of the CD18 gene. Ten single nucleotide polymorphisms (SNP) were identified, four of them showing significant associations with MPO-ANCA(+) vasculitis. One of these SNP's was localized in an alternate transcription initiation site. This polymorphism may influence CD18 gene expression, resulting in dose-dependent increase in adhesion and consecutively facilitated degranulation and respiratory burst. In this manner the pro-adherent genotype may predispose to MPO-ANCA(+) vasculitis.
Antibodies, Antineutrophil Cytoplasmic↗
Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants.
Incidences of and risk factors for Streptococcus pneumoniae sepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P =.03) and chronic GVHD (10-year probability, 14% vs 4%; P =.002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127; P =.07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16; P =.04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk. (Blood. 2000;95:3683-3686)
Adolescent↗
The association of CD18 alleles with anti-myeloperoxidase subtypes of ANCA-associated systemic vasculitides.
Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg Strauss syndrome (CSS) are rare systemic autoimmune disorders. Common features are anti-neutrophil cytoplasmic antibodies (ANCA) in patient sera. Whereas WG patients show mainly anti-proteinase 3 ANCA, MP and CSS patients typically present anti-myeloperoxidase (MPO) ANCA. ANCA play an important role in the pathogenesis in the vessel wall by activating polymorphonuclear cells (PMN) and increased adhesivity between PMN and endothelial cells via adhesion molecules. Here we investigated major adhesion molecules as predisposition factors via common polymorphisms in or in the vicinity of the candidate genes ICAM-1, e-selectin, PLAUR, CD11b, and CD18. A restriction fragment-length polymorphism in exon 11 of the CD18 gene was associated with MPO-ANCA(+) systemic vasculitis. Our data indicate that a common variant of the CD18 gene confers increased risk for CSS and MP, supporting that genetic factors are involved in the etiology and pathogenesis of ANCA-associated systemic vasculitides.
Alleles↗
Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years.
As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.
Adolescent↗
Proteinase 3 gene polymorphisms and Wegener's granulomatosis.
BACKGROUND: Wegener's granulomatosis (WG) is a rare systemic autoimmune disease characterized by small-vessel vasculitis leading to organ damage and the presence of antineutrophil cytoplasmic autoantibodies (ANCAs). ANCAs were shown to be involved in the pathogenesis of the disease by increasing adhesion of polymorphonuclear cells (PMNs) to endothelial cells and through activation of primed PMN. The main autoantigen of ANCA in WG is proteinase 3 (PR3), a neutrophil- and monocyte-derived neutral serine protease. The association of WG with individuals continuously expressing a high level of PR3 on the surface of PMNs suggests that PR3 variants or altered regulation of PR3 expression might be directly involved in the pathogenesis of the disease. METHODS: We screened the entire coding and promoter sequences of the PR3 gene for polymorphisms by means of polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Allelic, genotypic, and haplotype frequencies were compared between 79 WG patients and a cohort of 129 healthy controls. RESULTS: Seven single-nucleotide polymorphisms (SNPs), one amino acid change (Val119Ile), one 84 bp insertion/deletion, and a microsatellite were identified. An association with WG could be demonstrated for the A-564G polymorphism in the PR3 promoter affecting a putative transcription factor-binding site. CONCLUSIONS: This study excludes certain PR3 epitope variants as autoantigenic stimuli in WG, since the Val119Ile polymorphism showed no differences between patients and controls. Overexpression of PR3, however, might predispose the patient to the development of autoimmune ANCA-associated vasculitis.
Alleles↗
Application of microdialysis for the determination of muscle and subcutaneous tissue concentrations after oral and topical ibuprofen administration.
BACKGROUND: The topical administration of non-steroidal antiinflammatory drugs (NSAIDs) is widely used for the treatment of soft tissue pain. However, it is not known whether effective tissue concentrations are reached with the topical route. OBJECTIVE: To evaluate and compare unbound muscle and subcutaneous tissue ibuprofen concentrations with use of microdialysis after topical and oral administration. METHODS: In a 2-way crossover design, 11 healthy volunteers received either 800 mg oral ibuprofen or 16 g of 5% ibuprofen gel applied onto the skin of the thigh (defined area, 17 x 19 cm). Microdialysis catheters were inserted into the medial vastus muscle (25 to 30 mm) and into the subcutaneous adipose layer of the thigh (4 to 5 mm). Dialysate was collected in 20-minute intervals up to 5 hours. RESULTS: Essentially all of the orally administered dose was recovered in urine as ibuprofen or metabolites during 24 hours, but only about 0.55% of the topically administered dose was recovered. The relative systemic bioavailability of ibuprofen gel, based on urine recovery data, was (mean +/- SD) 0.57%+/-0.30%. Mean values of the dialysate areas under the drug concentration-time curves after topical and oral administration were 731.2+/-605.0 and 176.6+/-122.9 ng x h x mL(-1) for subcutaneous tissue and 63.5+/-90.3 and 213.4+/-117.2 ng x h x mL(-1) for muscle, respectively. Muscle dialysate concentrations after topical administration varied considerably among the subjects. CONCLUSION: These results suggest that, if target tissue concentrations correlate directly with the degree of pain relief, patients with pain caused by dermal or subcutaneous tissue damage will have greater pain relief after topical administration of ibuprofen accompanied with less systemic side effects. In addition, a proportion of patients with muscle pain may also experience pain relief from topical ibuprofen.
Administration, Cutaneous↗
Three-dimensional computer vision for tooth restoration.
If a person with carious lesions needs or requests crowns or inlays, these dental fillings have to be manufactured for each tooth and each person individually. We survey computer vision techniques which can be used to automate this process. We introduce three particular applications which are concerned with the reconstruction of surface information. The first one aims at building up a database of normalized depth images of posterior teeth and at extracting characteristic features from these images. In the second application, a given occlusal surface of a posterior tooth with a prepared cavity is digitally reconstructed using an intact model tooth from a given database. The calculated surface data can then be used for automatic milling of a dental prosthesis, e.g. from a preshaped ceramic block. In the third application a hand-made provisoric wax inlay or crown can be digitally scanned by a laser sensor and copied three dimensionally into a different material such as ceramic. The results are converted to a format required by the computer-integrated manufacturing (CIM) system for automatic milling.
Adolescent↗
[Influence of the degree of carbohydrate metabolism imbalance in gestational diabetes on pregnancy and newborns condition].
UNLABELLED: The aim of our study was the evaluation of the correlation between carbohydrate metabolism imbalance at the moment of gestational diabetes mellitus (GDM) diagnosis and regulation of glycemia during pregnancy, pregnancy complications, time and mode of delivery and conditions of the newborns. MATERIAL: 231 women with GDM delivered in our hospital between 1993-1996 were investigated. This population was divided into 6 groups, according to glycemia levels. METHOD: The term of diagnosis of the GDM, medical treatment (diet or diet and insulin), the degree of metabolic regulation archived, mode and time of delivery, as well as state of newborns were analysed. RESULTS: In groups I and VI we noticed the greatest percentage of patients treated with insulin (68%, 67%), versus 26% in group II and 17% in group III. In group VI in all cases treated with insulin we begun this therapy shortly after marking GDM. Glycemia in 24 hrs period after GDM diagnosis in group I were 122.7 +/- 28.6 mg/dl, in group VI 112.0 +/- 23.6 mg/dl, while we noticed 90.3 +/- 15.6 mg/dl in group II and 87.7 +/- 15.9 mg/dl in group III. Blood glucose level < 100 mg/dl in first determination of 24 hrs profiles we noticed in 5% in group I, 2% in group VI while 20% in group II and 51% in group III. Average levels of glycemia in last 24 hrs profiles before delivery in group I were 93.0 +/- 15.8 mg/dl, in group VI 96.2 +/- 21.1 mg/dl while 87.8 +/- 13.5 mg/dl in group II and 86.8 +/- 14.1 mg/dl in group III. Blood glucose level < 100 mg/dl of daily profile before the end of pregnancy was discovered in 8% in group I, 47% in group III. The greatest amount of complications (pregnancy induced hypertension and imminent premature delivery) was diagnosed in group VI-75% and in group III-55%. Surgical delivery took place in group I in 50%, in group V in 46%, in group VI in 67% while 17% in group II, 35% in group III and 30% in group IV. Macrosomy of newborns (> 4000 g) was diagnosed in group I in 36% in group V in 23% and in group VI in 42% while 9%, 6% and 15% in groups, II, III and IV respectively. The condition of newborns in the 1st minute of life was determined as good (8-10 points in Apgar scale) in significant percentage, in 87%, 75%, 70% in groups II, III, IV while only 59%, 62%, 58% in groups I, V, VI respectively. CONCLUSION: Serious intensification of carbohydrates metabolism disorders at the moment of diagnosing GDM, such as fasting glycemia > 140 mg/dl and the result after 2 hours > 200 mg/dl in 75 g OGTT more often requires insulin treating connect with numerous difficulties both in pregnancy monitoring and also has inadventageous influence on obstetrics outcomes-increasing percentage of surgery deliveries and macrosomies, that change the condition of newborns for worse.
Adult↗