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Biomedical subjects

R E Schopf

Publications and source records attributed to R E Schopf.

At least 19 recordsLinked to original sources
PubMed2001

[Neurotrophic ulcer as late sequela of trigeminal nerve excision].

A patient is presented with trophic ulcerations in the area innervated by the trigeminal nerve occurring 17 years after alcohol injection into the trigeminal ganglion and 16 years after excision of the trigeminal nerve. The mean period from time of trigeminal nerve injury to onset of the ulcer usually varies from several weeks to 1 or 2 years as reported in the literature. Our case demonstrates a late manifestation of the trigeminal trophic syndrome.

Aged↗
PubMed2001

IDEC-114 (IDEC).

IDEC is developing a PRIMATIZED-anti-B7 antibody (IDEC-114) for the treatment of autoimmune and inflammatory diseases, such as psoriasis and rheumatoid arthritis. It is currently undergoing phase II trials in patients with psoriasis [395813]. A randomized, blind, placebo-controlled, multiple-dose phase II study was initiated in January 2001 to evaluate the potential clinical activity and safety of IDEC-114 in patients with moderate-to-severe psoriasis [395813]. The antibody targets the B7 antigen on the surface of antigen-presenting cells that normally interact with T-cells to initiate an immune response. Antibodies directed at B7 may be useful in preventing unwanted immune responses in autoimmune diseases such as systemic lupus erythematosus, idiopathic thrombocytopenic purpura as well as transplant rejection [178382], [178929]. PRIMATIZED antibodies, genetically engineered from cynomolgus macaque monkey and human components, are structurally indistinguishable from human antibodies. They may, therefore, be less likely to cause adverse reactions in humans, making them potentially suited for long-term, chronic treatment [244805]. IDEC has signed an antibody humanization patent licensing agreement with Protein Design Labs [240591]. IDEC is also collaborating with Mitsubishi-Tokyo (formerly Mitsubishi Kasei) on the development of this antibody [178382].

Adjuvants, Immunologic↗
PubMed2000

Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism.

Genes encoded on chromosome 6 within the major histocompatibility complex region are thought to play an important role in the pathogenesis of psoriasis. A potential candidate gene is tumor necrosis factor alpha. The tumor necrosis factor alpha promoter contains several polymorphisms including two G-->A transitions at position -308 and -238, which are the most common in Caucasian populations. The TNF238.2 (-238A) allele has been strongly associated with psoriasis. We have investigated the effect of the -238 and -308 variants on transcription of the tumor necrosis factor alpha gene in luciferase reporter gene assays. In addition, peripheral blood mononuclear cells of 47 patients with psoriasis and 43 controls were stimulated with different antigens and mitogens (streptococcal sonicate and superantigen, lipopolysaccharide, phorbol-12-myristate, phytohemagglutinin, CD3 antibodies) and tumor necrosis factor alpha production was measured in supernatants by enzyme-linked immunosorbent assay. The psoriasis-associated tumor necrosis factor alpha promoter allele TNF238.2 showed a significantly decreased transcriptional activity. Peripheral blood mononuclear cells carrying this allele produced significantly less tumor necrosis factor alpha after stimulation with T cell mitogens and streptococcal antigens in comparison to controls. The promoter allele TNF238.2 seems to influence tumor necrosis factor alpha production; a possible role in the pathogenesis of psoriasis has to be further evaluated.

Adult↗
PubMed2000

Asphyxiation by laryngeal edema in patients with hereditary angioedema.

OBJECTIVE: To describe the occurrence of fatal laryngeal edema in patients with hereditary angioedema due to C1 esterase inhibitor deficiency. PATIENTS AND METHODS: We describe 6 patients from various regions of Germany who died from laryngeal edema within the last 10 years. Furthermore, we conducted a retrospective survey of 58 patients with hereditary angioedema, originating from 46 affected families. The data were obtained from the attending physicians and from the patients' relatives. RESULTS: Among the 6 reported patients, aged 9 to 78 years, hereditary angioedema had been diagnosed in 3 and was undiagnosed in 3. None of them had an emergency cricothyrotomy or received C1 inhibitor concentrate. The interval between onset of the laryngeal edema and asphyxiation was 20 minutes in a 9-year-old boy, and in the other patients, the interval was 1 to 14 hours (mean for all, 7 hours). The retrospective survey of 58 patients with hereditary angioedema revealed 23 deaths by asphyxiation (40%). The average age of all 29 patients at the time of asphyxiation was 39 years. CONCLUSION: Laryngeal edema in hereditary angioedema may be fatal. Most of the patients asphyxiated between their 20th and 50th years of life, but asphyxiation can occur even in children. The possibility that the first episode of laryngeal edema may be fatal must be emphasized to the relatives, and attending physicians must have a high degree of awareness.

Adolescent↗
PubMed1999

Pimecrolimus (Novartis).

Pimecrolimus, an ascomycin macrolactam derivative, is an inhibitor of T-cell and mast cell activation under development by Novartis for the potential treatment of psoriasis and allergic dermatitis. Novartis is developing both topical and oral formulations of the compound. By December 1998, the topical form of the compound was in phase III trials and the oral form was in phase II trials. Phase III trials were initiated in July 1999 for the treatment of atopic dermatitis. In December 1998, Warburg Dillon Read predicted sales of SFr 30 million in 2000 rising to SFr 184 million in 2002. In March 1999, Credit Suisse First Boston predicted sales of 10 million USD in 2001 rising to 90 million USD in 2003.

Journal Article↗
PubMed1998

[Pyostomatitis vegetans and Crohn's disease. A specific association of 2 diseases].

HISTORY AND CLINICAL FINDINGS: A 27-year-old man was referred to the dermatological out-patient clinic because of inflammatory changes in the oral mucosa of unknown cause. 5 months earlier he had been diagnosed as having Crohn's disease of the terminal ileum. On both sides of the buccal mucosa there were rough erythematous vegetations and disseminated miliary abscesses, which extended to the labial gingiva and the soft palate. Further physical examination was unremarkable. INVESTIGATIONS: Several inflammatory parameters were increased: C-reactive protein 100 mg/l, erythrocyte sedimentation rate 55/88 mm, eosinophilic cationic protein 35.8 ng/ml (normal range 2.3-16 ng/ml). White cell count was normal (7,25/nl), with a lymphocytopenia of 11.9%. There was no eosinophilia. Haemoglobin was reduced to 11.6 g/dl and the platelets raised to 526/nl. Smears of the oral mucosa showed no fungal, viral or bacterial infection. Biopsy revealed leucocytic microabscesses in the epithelium, granulation tissue and flat ulcerations with adjoining superficial necrotic zones. DIAGNOSIS, TREATMENT AND COURSE: The clinical and histological picture as well as the association with Crohn's disease (CD) suggested pyostomatitis vegetans (PV). The PV was treated with disinfectant mouth washes which improved the subjective findings. Budesonide was given for CD. CONCLUSION: PV is a rare and usually isolated condition, but it can also occur in association with a chronic gastrointestinal disease such as ulcerative colitis and Crohn's disease. The diagnosis of PV indicates a thorough gastroenterological investigation.

Adult↗
PubMed1998

Ascomycin macrolactam derivative SDZ ASM 981 inhibits the release of granule-associated mediators and of newly synthesized cytokines in RBL 2H3 mast cells in an immunophilin-dependent manner.

Mast cells play an important role in the pathological development of many inflammatory and allergic diseases and inhibition of mast cell activation is a potential target for therapeutic intervention. Therefore, the effect of the novel ascomycin macrolactam derivative SDZ ASM 981 on Fc epsilonRI-mediated activation of rat basophilic leukemia (RBL) cells, as a model for mast cell activation, was investigated. First, the ability to inhibit different mast cell immunophilins in vitro was tested. Using recombinant macrophilin-12 (FKBP-12), inhibition of rotamase activity with an IC50 of approximately 6 nM was observed. The rotamase activity of cyclophilin A (18 kDa) was not affected. Secondly, the effect of SDZ ASM 981 on Fc epsilonRI-mediated mast cell activation was investigated in the RBL cell model. SDZ ASM 981 inhibited exocytosis of preformed mediators (e.g. serotonin) with an IC50 of approximately 30 nM. Transcription and release of newly synthesized mediators (e.g. TNF-alpha) was inhibited with an IC50 of approximately 100 nM. The inhibitory effect of SDZ ASM 981 was antagonized by rapamycin. We conclude that SDZ ASM 981 is a potent inhibitor of Fc epsilonRI-mediated activation of mast cells in vitro. The mechanism of action involves formation of (calcineurin) inhibitory complexes with macrophilins. We suggest that this inhibitory action on mast cells might contribute to the antiinflammatory effect of SDZ ASM 981 observed in vivo (e.g. in aptopic dermatitis and psoriasis).

Amino Acid Isomerases↗
PubMed1998

Conversion of psoriasis patients from the conventional formulation of cyclosporin A to a new microemulsion formulation: a randomized, open, multicentre assessment of safety and tolerability.

OBJECTIVE: To assess the safety, tolerability and efficacy of a new cyclosporin A (CyA) microemulsion formulation, Sandimmun Neoral (Neoral), in patients with severe psoriasis that was stable on CyA administered as Sandimmun (SIM). METHODS: In this 24-week, open, randomized, prospective, multicentre trial, 28 patients continued on the same dosage of SIM, while 30 converted to Neoral at 2.5 mg/kg/day or a dosage equivalent to their pre-conversion SIM dosage. During the study, dosages could be adjusted to maintain efficacy, because of adverse events or after disease stabilization. The maximum permitted dosage for either formulation was 5.0 mg/kg/day. Primary efficacy criteria were change in Psoriasis Area and Severity Index (PASI) from baseline and time to relapse. RESULTS: The dosage was increased to maintain efficacy in 22 patients (Neoral 13; SIM 9) and 20 dose reductions for safety were required (Neoral 14, SIM 6). In both groups, PASI scores remained stable throughout and relapses were primarily a result of dosage reduction after disease stabilization. No significant difference was found between groups in the proportion of patients remaining relapse-free. Adverse events were recorded in 20 patients receiving Neoral and 14 receiving SIM. Most drug-related events were of mild or moderate severity and reflected the known CyA side-effect profile. Dose titration guidelines ensured that mean blood pressure and serum creatinine concentrations remained stable in both groups. CONCLUSIONS: If the guidelines for CyA use are followed and the Neoral dosage does not exceed 5 mg/kg/day, conversion of stable patients with severe psoriasis from SIM to Neoral should present no clinically relevant safety or tolerability problems and efficacy of treatment is maintained.

Adolescent↗
PubMed1998

Eosinophils, pruritus and psoriasis: effects of treatment with etretinate or cyclosporin-A.

BACKGROUND: The antipsoriatic drugs cyclosporin A (CyA) and etretinate have been found to influence proinflammatory eosinophilic leukocytes and pruritus. AIM: We compared the number of blood eosinophils, concentration of serum eosinophil cationic protein (ECP), and pruritus in patients with psoriasis treated with either CyA or etretinate. STUDY DESIGN: Patients with psoriasis vulgaris were randomly assigned to treatment for 10 weeks with either CyA (n = 21) or etretinate (n = 10). The psoriasis area-and-severity index (PASI-score) and pruritus (according to a 0-3 scale) served as clinical parameters, the blood esosinophil counts (Coulter Counter) and the serum ECP (RIA, Pharmacia) as laboratory parameters. RESULTS: After CyA treatment the PASI-score amounted to 24 +/- 4%, after etretinate to 56 +/- 6% of the initial values (mean +/- SEM). One week after CyA treatment, esosinophils dropped from 190 +/- 21 to 137 +/- 16/microliter (P = 0.038, Wilcoxon test), after 10 weeks to 127 +/- 18/microliter (P = 0.006). By contrast, under etretinate blood eosinophil counts only changed marginally. Before treatment, ECP concentrations of 15.71 +/- 1.30 (CyA) and 15.3 +/- 5.53 micrograms/l (etretinate) were measured (normal range 3-16 micrograms/l), ECP remained constant under both CyA and etretinate or tended to increase after 10 weeks; about 50% of the patients exhibited elevated ECP concentrations. Pruritus diminished more with CyA than etretinate therapy. PASI-scores and pruritus were directly proportional. OUTCOME: We conclude that treatment of psoriasis with CyA leads to a rapid drop of blood eosinophils and that the activation state of eosinophils does not decrease after antipsoriatic treatment. Pruritus in psoriasis is coupled to disease severity. The underlying antipsoriatic mechanisms of CyA may be linked to lowering the number of blood eosinophils.

Blood Proteins↗
PubMed1997

A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis.

Tumor necrosis factor-alpha is considered to be one of the important mediators in the pathogenesis of psoriasis. A strong association of juvenile onset psoriasis with the major histocompatibility complex encoded HLA-Cw6 antigen has been reported but it is unclear whether Cw6 itself or a closely linked gene is involved in the pathogenesis. This study has focused on the association of promoter polymorphisms of the major histocompatibility complex encoded tumor necrosis factor-alpha gene with psoriasis and psoriatic arthritis. Tumor necrosis factor-alpha promoter polymorphisms were sought by sequence-specific oligonucleotide hybridization and by direct sequencing in Caucasian patients with juvenile onset psoriasis and with psoriatic arthritis and in healthy controls. A mutation at position -238 of the tumor necrosis factor-alpha promoter was present in 23 of 60 patients (38%; p < 0.0001; p[corr] < 0.008) with juvenile onset psoriasis and in 20 of 62 patients (32%; p < 0.0003; p[corr] < 0.03) with psoriatic arthritis, compared with seven of 99 (7%) Caucasian controls. There was a marked increase of homozygotes for this mutation in the psoriasis group. Another mutation at position -308 was found in similar proportions of patients and controls. Our study shows a strong association of the tumor necrosis factor-alpha promoter polymorphism at position -238 with psoriasis and psoriatic arthritis. Our findings suggest that this promoter polymorphism itself or a gene in linkage disequilibrium with tumor necrosis factor-alpha predispose to the development of psoriasis.

Adult↗
PubMed1996

TAP-polymorphisms in juvenile onset psoriasis and psoriatic arthritis.

Juvenile onset psoriasis is strongly associated with the HLA-class I genes Cw6 and B57 whereas patients with psoriatic arthritis show an increased frequency of HLA-B27. It is unclear whether additional major histocompatibility genes also increase disease susceptibility. The TAP genes (transporter associated with antigen processing) encode two membrane-spanning proteins that translocate antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 60 patients with juvenile onset psoriasis, 63 psoriatic arthritis patients, and 101 caucasoid controls revealed an increase of the TAP1*0101 allele in the psoriasis group, that could not be explained by linkage to other investigated HLA genes. There were no differences for TAP2 alleles.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

German randomized double-blind multicentre comparison of terbinafine and itraconazole for the treatment of toenail tinea infection.

One-hundred and ninety-five patients with toenail tinea unguium were recruited to a multicentre double-blind clinical trial. Patients were given 250 mg terbinafine or 200 mg itraconazole daily for 12 weeks, with follow-up for a further 40 weeks. At the end of the study, mycological cure rates were 81% (70/86 assessed) for terbinafine and 63% (53/84 assessed) for itraconazole (two-tailed, P < 0.01). The length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (two-tailed, P < 0.05). Patient self-assessment also favoured terbinafine, with 65% evaluating it as good to very good, compared with 58% for itraconazole. Before treatment the terbinafine group had a mean of 6.7 and the itraconazole group 6.3 affected nails per patient. Total cure was achieved in 69% of terbinafine and 61% of itraconazole affected nails. We conclude that terbinafine is more effective than itraconazole in the treatment of toenail tinea infection.

Adult↗
PubMed1996

Ethanol enhances the mitogen-driven lymphocyte proliferation in patients with psoriasis.

Ethanol has been reported to exacerbate psoriasis. Since immunological mechanisms are considered to be important for the pathogenesis of psoriasis, we compared the effects of ethanol on lymphocyte proliferation in 15 healthy control individuals and 15 patients with psoriasis. We employed the spontaneous and phytohemagglutin in (PHA)-induced uptake of 3H-TdR to measure lymphocyte proliferation. Ethanol was added to cultures at concentrations ranging from 0.5 to 0.0005% (vol./vol.). We found that both spontaneous and PHA-driven lymphocyte proliferations were significantly lower in patients with psoriasis (P < 0.002). Spontaneous blastogenesis in both controls and patients remained stable under ethanol. In controls, ethanol suppressed the PHA-driven lymphocyte proliferation in a dose-dependent fashion. By contrast, in patients with psoriasis ethanol significantly increased lymphocyte proliferation by 2-3 times (p < 0.002). Our data indicate that in psoriasis the lower lymphocyte transformation is abnormally enhanced by minimal doses of ethanol.

Adult↗
PubMed1995

Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group.

OBJECTIVE: To compare the efficacy and tolerability of terbinafine and itraconazole in the treatment of toenail tinea unguium. DESIGN: Multicentre, double blind, parallel group study. SETTING: 17 university hospitals, one army hospital, and five dermatology practices. PATIENTS: 195 patients with clinically suspected toenail tinea and growth of dermatophytes in baseline culture; data on 86 patients in the terbinafine group and 84 patients in the itraconazole group were fully evaluated for efficacy. INTERVENTIONS: Daily dose of 250 mg terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40 weeks. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and clinical improvement (length and area of unaffected nail) at week 52 or at discontinuation of treatment. RESULTS: At the end of the study mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of 84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of 86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (2P < 0.05). CONCLUSION: Terbinafine is more effective than itraconazole in the treatment of toenail tinea infection.

Adult↗
PubMed1995

[Gianotti-Crosti syndrome in Epstein-Barr virus infection].

Gianotti-Crosti syndrome, a relatively rare, distinctive eruption occurring after hepatitis B infection, is characterized by a lichenoid papular exanthema, usually localized on the face, limbs, and buttocks. Hepatitis B antigenaemia is associated with Gianotti-Crosti syndrome only in some cases. Recent reports indicate that a variety of infectious agents are associated with Gianotti-Crosti syndrome. This is a report of 2 1/2-year-old girl with Gianotti-Crosti syndrome and concurrent primary Epstein-Barr virus infection without evidence of hepatitis B infection.

Acrodermatitis↗
PubMed1995

Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis.

Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400 mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P < or = 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P < or = 0.01) and the 400-mg groups (P < or = 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose-dependent, and appeared to be similar to those seen with cyclosporin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗