Effectiveness, safety and impact of guselkumab on sexuality and perceived stigmatization in patients with psoriasis in routine clinical practice: Week 28 results from the prospective German multicentre G-EPOSS study.

BACKGROUND: G-EPOSS is a prospective, non-interventional, German multicentre study of patients with moderate-to-severe plaque psoriasis receiving guselkumab, a therapeutic monoclonal antibody targeting interleukin-23, in a real-world setting. OBJECTIVES: The objective of the study was to evaluate the effectiveness and safety of guselkumab, including its impact on skin, health-related quality of life (HRQoL), sexuality, and perceived stigmatization. METHODS: Patients (≥18 years old) received guselkumab per routine clinical practice. The primary endpoint was the proportion of patients achieving absolute Psoriasis Area and Severity Index (PASI) ≤ 3 at Week (W)28. Secondary endpoint assessments over 28 weeks included the Nail Psoriasis Severity Index (NAPSI), anogenital Physician's Global Assessment (aPGA), and Dermatology Life Quality Index (DLQI). Sexuality and perceived stigmatization were assessed by patients using the Relationship and Sexuality Scale (RSS) and Perceived Stigmatization Questionnaire (PSQ), respectively. RESULTS: Overall, 293 patients were included in the evaluable set population. Mean age and disease duration were 45.6 and 17.6 years, respectively. At baseline, mean PASI, aPGA and DLQI scores were 15.3, 2.7 and 11.3, respectively. In total, 25.9% of patients had received a prior biologic. Overall, 83.0% of patients achieved PASI ≤ 3, and 56.2%/35.1% achieved PASI ≤ 1/PASI = 0, respectively, at W28. Among those with NAPSI ≥ 1 and aPGA ≥ 1 at baseline, NAPSI = 0 and aPGA = 0 were achieved by 39.2% and 61.1% of patients, respectively, and 61.4% of patients achieved DLQI 0-1 at W28. Improvements were observed over 28 weeks across individual items of the DLQI, RSS and PSQ, indicating improved HRQoL and sex life, and decreased perceived stigmatization. Based on DLQI Question (Q)9, 53.6% of patients experienced sexual difficulties at baseline, which decreased to 12.1% at W28. DLQI Q9 responses were consistent with RSS item responses, highlighting DLQI Q9 as a sentinel for sexual impairment. CONCLUSIONS: Guselkumab improved overall skin symptoms and HRQoL in patients with psoriasis and decreased sexual impairment and perceived stigmatization. No new safety signals were observed. STUDY CODE: CNTO1959PSO4008.

Propofol-induced mitochondrial and contractile dysfunction of the rat ventricular myocardium.

Propofol is a short-acting hypnotic agent used in human medicine for sedation and general anesthesia. Its administration can be associated with serious cardiovascular side-effects that include decrease in arterial blood pressure and cardiac output. The aim of the present study was to evaluate propofol effects on mitochondrial respiration, myocardial contractility and electrophysiology in the same samples isolated from the heart ventricles of adult rats. Mitochondrial oxygen consumption was measured in permeabilized samples dissected from free walls of both ventricles using high-resolution respirometry. State LEAK was determined with malate and glutamate. Active respiration was induced by ADP (state PI) and further by succinate, a Complex II substrate (PI+II). Rotenone was injected to measure state PII. Antimycin A, a Complex III inhibitor was used to determine residual oxygen consumption (ROX). N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride and ascorbate were injected simultaneously for respirometric assay of cytochrome c oxidase activity (CIV). Isometric contractions and membrane potentials were determined on multicellular preparations isolated from right and left ventricles. Propofol concentrations used ranged from 0.005 to 0.5 mmol/l. All respiratory parameters were significantly higher in the left control ventricles compared to the right ones. Propofol significantly decreased Complex I activity at concentration 0.025 mmol/l and papillary muscle contraction force at 0.1 mmol/l. Propofol did not affect action potential duration at any concentration studied. Our study suggests that mechanisms contributing to the impaired myocardial contraction during propofol anesthesia might include also mitochondrial dysfunction manifested by compromised activity of the respiratory Complex I.

[Tropical and travel-related dermatomycoses : Part 2: cutaneous infections due to yeasts, moulds, and dimorphic fungi]. / Tropen- und Reise-assoziierte Dermatomykosen : Teil 2: Kutane Infektionen durch Hefepilze, Schimmelpilze und dimorphe Pilze.

Besides dermatophytoses, a broad range of cutaneous infections due to yeasts and moulds may occur in subtropical and tropical countries where they can affect travellers. Not to be forgotten are endemic occurring dimorphic or biphasic fungi in countries with hot climate, which cause systemic and secondary cutaneous infections in immunosuppressed and immunocompetent people. In the tropics, the prevalence of pityriasis versicolor, caused by the lipophilic yeast Malassezia spp., is about 30-40 %, in distinct areas even 50 %. Increased hyperhidrosis under tropical conditions and simultaneously humidity congestion have to be considered as significant disposing factors for pityriasis versicolor. In tropical countries, therefore, an exacerbation of a preexisting pityriasis versicolor in travellers is not rare. Today, mostly genital yeast infections due to the new species Candida africana can be found worldwide. Due to migration from Africa this yeast pathogen has reached Germany and Europe. Eumycetomas due to mould fungi are rarely diagnosed in Europe. These deep cutaneous mould infections are only found in immigrants from African countries. The therapy of eumycetoma is protracted and often not successful. Cutaneous cryptococcoses due to the yeast species Cryptococcus neoformans and Cryptococcus gattii occur worldwide; however, they are found more frequently in the tropics. Immunosuppressed patients, especially those with HIV/AIDS, are affected by cryptococcoses. Furthermore, Cryptococcus gattii also causes infections in immunocompetent hosts in Central Africa, Australia, California, and Central America.Rarely found are infections due to dimorphic fungi after travel to countries where these fungal pathogens are endemic. In individual cases, cutaneous or lymphogenic transferred sporotrichosis due to Sporothrix schenkii can occur. Furthermore, scarcely known is secondary cutaneous coccidioidomycosis due to Coccidioides immitis after travelling to desert-like endemic regions in southwestern states of the United States and in Latin America, where primary respiratory infection due to this biphasic fungus can be acquired. The antifungal agent itraconazole is the treatment of choice for sporotrichosis and coccidioidomycosis. Talaromyces marneffei-until recently known as Penicillium marneffei-is only found in Southeastern Asia. Mycosis due to this dimorphic fungus has to be considered as an AIDS-defining opportunistic infection. After hematogeneous spread, Talaromyces marneffei affects the skin and mucous membranes of the mouth. Amphotericin B and itraconazole can be used for therapy.

[Tropical and travel-related dermatomycoses: Part 1: Dermatophytoses]. / Tropen- und Reise-assoziierte Dermatomykosen : Teil 1: Dermatophytosen.

Today, tropical and travel-related dermatomycoses must be increasingly anticipated to present in dermatological offices and clinics. Skin infections due to dermatophytes or other fungi may occur after a journey in countries with a high prevalence for the respective causative fungal pathogen, e.g., tinea corporis due to Trichophyton soudanense. Otherwise, more frequently, single infections and even localized outbreaks due to "exotic" or "imported" pathogens of dermatophytoses occur. These epidemics are observed in childcare facilities in Germany and in other European countries. Source of infection are immigrants from Africa and sometimes from Asian countries. Furthermore, African children, and sometimes also adults, are often only asymptomatic carriers of such anthropophilic dermatophytes. Outbreaks of dermatophyte infections with one and more affected children and also adult staff and teachers due to Trichophyton violaceum or Microsporum audouinii in kindergartens and schools are not a rarity these days. Further tropical and travel-associated dermatophytes are Trichophyton tonsurans, Trichophyton schoenleinii, and Trichophyton concentricum. Tinea capitis should be treated in a species-specific manner. Griseofulvin is the treatment of choice for infections due to Microsporum species. In contrast, tinea capitis due to Trichophyton species has to be treated by terbinafine, however, because the agent is not approved for children in Germany, only after receiving written consent of parents. Alternatives are fluconazole and itraconazole. Onset and aggravation of tinea pedis during travel has its origin in a preexisting neglected fungal infection of the feet. In the tropics, exacerbations and secondary bacterial complications of tinea pedis develop under distinctly promoting conditions.

[Possibilities and limits for treating psoriasis with biologics. Case reports]. / Möglichkeiten und Grenzen der Psoriasistherapie mit Biologics: Fallbeispiele.

The availability of biologics for the therapy of psoriasis has radically changed the options for systemic therapy of this disease. Their use is often coupled with a variety of restrictions--as a rule they are to be used as a 'last-line' therapy. The status of previous systemic therapy as a basic requirement for the use of biologics is analyzed and simultaneously, the possibilities of the physician to use the indication spectrum of biologics for the benefit of the patient are demonstrated by case reports.

Identification of a 27 kDa protein in patients with anaphylactic reactions to mango.

Mango fruit has become increasingly popular in recent years. We report on 2 patients who developed anaphylactic reactions after the ingestion of fresh mango. Allergy to mango was confirmed by a positive skin prick test result and positive cellular allergen stimulation test results. Neither of the patients had detectable mango-specific immunoglobulin (Ig) E levels. Results were validated by sodium dodecyl sulfate polyacrylamide gel electrophoresis immunoblotting and analyzed using Quantiscan.We identified 2 major allergens with a molecular weight of 27 kDa in both patients, in addition to a 15 kDa allergen in 1 patient and a 32 kDa allergen in the other. Currently available IgE systems seem to be lacking these mango allergens and as such are probably unsuitable for diagnosing type 1 sensitization to mango. Skin prick testing with fresh mango fruit therefore seems to be a much more reliable test method for clinical practice.

Ellobius lutescens: sex determination and sex chromosome.

The mole vole Ellobius lutescens is an interesting animal, not only concerning its sex determination mechanism without the Y-chromosomal Sry gene, that triggers sex determination in nearly all other mammalian species, but also regarding the karyotype with an odd number of chromosomes, being identical in male and female animals. The odd chromosome represents the X chromosome, and therefore, even males do not have a Y chromosome. We present an overview of a search for candidate genes of male sex determination in the mole vole Ellobius lutescens. A singular X raises questions about the need for X chromosome inactivation in female cells. We present preliminary data that support a hypothesis that the E. lutescens Xist gene may be degenerated and thus non-functional.

[Mycosis fungoides and B-cell chronic lymphocytic leukemia: an extremely rare coincidence]. / Mycosis fungoides und chronisch lymphatische B-zell-leukämie: eine äusserst seltene koinzidenz.

The simultaneous appearance of mycosis fungoides (MF) and B-cell chronic lymphocytic leukemia (B-CLL) in the same patient is extremely rare. Only seven cases have been described in literature. A 72-year-old patient was diagnosed with coincident MF, stage Ib, and B-CLL, Binet stage A. Hypotheses on simultaneous occurrence of B- and T-cell malignancies as well as a new therapeutic option are discussed.

Molecular genetics of colorectal motility disorders.

In the last years, several genes have been identified which are involved in the development and differentiation of the enteric nervous system (ENS). Among the congenital intestinal innervation disorders described (aganglionosis, hypoganglionosis, heterotopic ganglia, intestinal neuronal dysplasia), up to now Hirschsprung's disease (HSCR) has been linked to mutational defects in these genes. GDNF and its co-receptor RET are the genes with the most mitogene potency on precursor cells of the ENS. The endothelin system (EDNRB/EDN3) also plays a key role in the development of the ENS by preventing its premature differentiation. Our own studies could show that, whereas a homozygous mutation of EDNRB causes long-segment HSCR, a heterozygous EDNRB deficiency leads to alterations of the ENS resembling the histopathology observed in intestinal neuronal dysplasia. Modern molecular genetic technologies combined with a subtle phenotypic assessment of the ENS will allow investigators to identify other genes within the complex signalling cascade required for the formation of the ENS. The recognition that intestinal innervation disorders are, at least in part, a multigenetic disease should provide support for consequent genetic screening in these patients.

Abnormalities of the enteric nervous system in heterozygous endothelin B receptor deficient (spotting lethal) rats resembling intestinal neuronal dysplasia.

BACKGROUND: A homozygous mutation of the endothelin B receptor (EDNRB) gene in spotting lethal (sl/sl) rats leads to Hirschsprung's disease (HSCR) with long segmented aganglionosis. However, the effects on the development of the enteric nervous system (ENS) promoted by a heterozygous mutation of the EDNRB gene are not known. The present study aimed to describe and morphometrically assess the phenotypic abnormalities of the ENS in heterozygous (+/sl) EDNRB deficient rats in comparison with homozygous (sl/sl) EDNRB deficient and wild-type (+/+) rats. METHODS: The distal small intestine, caecum, and colon were obtained from sl/sl, +/sl, and +/+ rats. To demonstrate the three dimensional organisation of the ENS, the intestinal wall was microdissected into wholemounts and incubated against the pan-neuronal marker protein gene product 9.5. Assessment of the ENS included morphometric quantification of ganglionic size and density, the number of nerve cells per ganglia, and the diameter of nerve fibre strands within both the myenteric and submucous plexus. RESULTS: Sl/sl rats were characterised by complete aganglionosis resembling the same histopathological features observed in patients with HSCR. +/sl rats revealed more subtle abnormalities of the ENS: the submucous plexus was characterised by a significantly increased ganglionic size and density, and the presence of hypertrophied nerve fibre strands. Morphometric evaluation of the myenteric plexus did not show statistically significant differences between +/sl and +/+ rats. CONCLUSIONS: In contrast with sl/sl rats, +/sl rats display non-aganglionated malformations of the ENS. Interestingly, these innervational abnormalities resemble the histopathological criteria for intestinal neuronal dysplasia (IND). Although IND has been described in several intestinal motility disorders, the concept of a clearly defined clinical-histopathological entity is still controversially discussed. The present findings support the concept of IND based on clearly defined morphological criteria suggesting a genetic link, and thus may provide a model for human IND. Furthermore, the data underline the critical role of the "gene dose" for the phenotypic effects promoted by the EDNRB/EDN3 system and confirm that the development of the ENS is not an "all or none" phenomenon.

Emergency contraception: pediatricians' knowledge, attitudes, and opinions.

UNLABELLED: Emergency contraception (EC) is the use of a method of contraception after unprotected intercourse to prevent unintended pregnancy. Although first described over 20 years ago, physician awareness of EC has been limited and many feel uncomfortable prescribing it. OBJECTIVE: To assess the knowledge, attitudes, and opinions of practicing pediatricians regarding the use of EC in adolescents. METHODS: An anonymous questionnaire was mailed to all 954 active members of New York Chapter 2, District II of the American Academy of Pediatrics. The questionnaire assessed basic knowledge, attitudes, and opinions regarding EC in adolescents. Data were analyzed by physician age, gender, year completed residency, and practice type. RESULTS: Two hundred thirty-three practicing pediatricians (24.4%) completed the survey. Of the respondents, 23.7% had been asked to prescribe EC to an adolescent and 49% of these cases involved a rape victim. Only 16.7% of pediatricians routinely counsel adolescent patients about the availability of EC, with female pediatricians more likely to do so. Most respondents (72.9%) were unable to identify any of the Food and Drug Administration-approved methods of EC. Only 27.9% correctly identified the timing for its initiation and only 31.6% of respondents felt comfortable prescribing EC. Inexperience with use was cited as the primary reason for not prescribing EC by 70% of respondents. Twelve percent cited moral or religious reasons and 17% were concerned about teratogenic effects. There were no differences in comfort level based on age, gender, or practice type. Twenty-two percent of respondents believed that providing EC encourages adolescent risk-taking behavior and 52.4% would restrict the number of times they would dispense EC to an individual patient. A minority of respondents (17%) believed that adolescents should have EC available at home to use if necessary and only 19.6% believed that EC should be available without a prescription. The vast majority (87.5%) were interested in learning more about EC. CONCLUSIONS: Despite the safety and efficacy of EC, the low rate of use is of concern. Pediatricians are being confronted with the decision to prescribe EC but do not feel comfortable prescribing it because of inadequate training in its use. Practicing pediatricians are aware of their lack of experience and are interested in improving their knowledge base.

Risk factors for pelvic inflammatory disease in inner-city adolescents.

OBJECTIVE: To determine risk factors associated with pelvic inflammatory disease (PID) among inner-city adolescents. STUDY DESIGN: A case-control study was performed from 1994 to 1997 in an inner-city hospital. METHODS: Seventy-one adolescent girls diagnosed with PID and 52 sexually active adolescents girls without PID participated in a confidential face-to-face interview using a questionnaire about risk behaviors. Established criteria were used for the diagnosis of PID. Data were analyzed using t tests, chi-square tests, and stepwise logistic regression. RESULTS: Persons with PID were significantly more likely to show younger age at first intercourse, older sex partners, involvement with a child protection agency, prior suicide attempt(s), consumption of alcohol before last sex, and a current Chlamydia trachomatis infection. There were no significant differences between the two groups regarding number of lifetime sex partners, condom use, rape, syphilis, prior PID, hepatitis B, hepatitis C, or HIV infection. CONCLUSIONS: Not previously noted in the literature are the association of PID with older sex partners, prior involvement in a child protection agency, and a prior suicide attempt. Confirming prior studies are the association of PID with earlier age at first sex, alcohol use, and C trachomatis infection.

Firesetting.

Firesetting results in a significant loss of life and property in the U.S. Child and adolescent firesetting accounts for a large percent of all firesetting occurrences. This article reviews the etiology and prevalence of firesetting in adolescence, presents case studies, and discusses approaches to management, therapy, and prognosis of adolescent firesetters.

[Severe course of ornithosis and its intensive care and diagnostic problems--a case report]. / Schwerer Verlauf einer Ornithose und ihre intensivmedizinische und diagnostische Problematik--eine Kasuistik.

Ornithosis is still a life-threatening illness unless diagnosed early and adequately treated with antibiotics. Diagnosis, however, is difficult because often no direct contact with birds is obvious. We report on the course of a severe case of ornithosis in a 45-year-old man who had no previous health problems. Infection with Chlamydia psittaci probably occurred by inhaling of contaminated dust produced by flocks of wild pigeons. A special feature of the case is that commonly used serological tests (complement fixation reaction, CFR; ELISA) failed to yield clear results. Since propagation of Chlamydia psittaci requires special biological laboratory containment facility no. 3, we were able to detect the pathogen in faeces, blood, and urine using the direct immunofluorescence antibody technique (DIFT) and a modified peroxidase antiperoxidase technique (PAP). A lot of Chlamydia psittaci was found. These results were verified by electron microscopy. As a result, the treatment could be quickly adjusted to the application of doxycyclin, which led to a rapid improvement in the patient's condition. This direct detection of Chlamydia psittaci by DIFT, the PAP technique or electron microscopy, also in faeces, blood and urine specimens, represents a useful addition to the usual microbiological methods for the diagnosis of this pathogen.

School attendance, health-risk behaviors, and self-esteem in adolescents applying for working papers.

Since health-risk behaviors are often encountered in clusters among adolescents, it was hypothesized that adolescents with poor school attendance would be associated with more health-risk behaviors (e.g., substance use, violence) than those who attend school regularly. This study assessed the relationship between poor school attendance and health-risk behaviors, and described health-risk behaviors and self-esteem among adolescents seeking employment. In this cross-sectional study, school attendance (poor vs. regular attendance) was related to health-risk behaviors by asking 122 subjects seen at a New York City Working Papers Clinic to complete both a 72-item questionnaire about their health-risk behaviors and the 58-item Coopersmith Self-Esteem School Form Inventory. Chi-square and Fisher's Exact Tests were performed. The poor and regular attenders of school differed significantly in only 5 out of 44 items pertaining to health-risk behaviors. Self-esteem measures for the two groups did not differ from one another or from national norms. In this sample, depression "in general" (global) and "at home," but not "at school," were associated significantly with suicidal thoughts/attempts and serious past life events (e.g. family conflict, sexual abuse). There were no significant associations between depression or self-esteem and illicit substance or alcohol use. We found few associations between poor school attendance and health-risk behaviors in this sample of employment-seeking adolescents. The poor and regular attenders of school were similar in most aspects of their health-risk behaviors and self-esteem.

A survey on the occurrence of Fusarium mycotoxins in Bavarian cereals from the 1987 harvest.

Bavarian cereals and wheat flour from the 1987 harvest were analysed for nivalenol (NIV) and deoxynivalenol (DON) using high performance liquid chromatography (HPLC) and for T-2 toxin and zearalenone (ZEA) by enzyme-linked-immunosorbent assay (ELISA). The study included 190 field samples of wheat, barley, rye and oat with visibly damaged ears, 45 samples of wheat intended for feed production and two series of wheat flour (type 550) and whole wheat flour collected in October 1987 and June 1988. The field samples examined showed a high DON contamination of wheat (87%) with an average of 3.96 mg/kg and a maximum of 43.8 mg/kg. Mean levels between 0.33 mg/kg and 0.27 mg/kg DON could be detected in barley, rye and oat. Of the wheat samples, 58% contained ZEA with a maximum of 1.560 mg/kg. The highest levels of ZEA were detected in samples which also showed high concentrations of DON. The NIV and T-2 toxin levels were comparatively low. Thirty percent of the samples showed NIV concentrations between 0.04 mg/kg and 0.29 mg/kg and 38% contained between 0.005 and 0.60 mg/kg of T-2. In the wheat samples for feed production, only DON was detected with an average of 0.190 mg/kg and a maximum of 0.75 mg/kg. The highest DON levels (0.58 mg/kg) from October 1987 were found in the wheat flour samples which were lower than the highest DON concentration (3.24 mg/kg) detected in the samples collected during June 1988. This fact was probably due to a substantial amount of non-contaminated wheat from 1986. The toxin concentrations in the whole wheat flour were not higher than in the type 550 flour.(ABSTRACT TRUNCATED AT 250 WORDS)

Monomeric serum calcitonin and bone turnover during anticonvulsant treatment and in congenital hypothyroidism.

Decreased basal and calcium-stimulated calcitonin serum levels have been found in children with congenital hypothyroidism and in those receiving anticonvulsant drugs. The purpose of our investigation was to confirm these results using a new technique for calcitonin measurement and to study the effect on bone turnover. Calcitonin serum levels were measured with two different antibodies before and after a low-dose Ca infusion in patients receiving phenytoin, primidone, carbamazepine, or valproate and in patients with congenital hypothyroidism receiving L-thyroxine. In comparison with control values, basal and Ca-stimulated extractable calcitonin, representing the monomeric and biologically active form of the hormone, were moderately decreased in patients with epilepsy receiving phenytoin and primidone, and severely decreased in patients with hypothyroidism. Ca and bone metabolism were normal, except for an elevated renal threshold for phosphate (indicating phosphate conservation) in patients receiving phenytoin and primidone, and increased fasting urinary excretion of Ca and hydroxyproline (indicating increased bone resorption) in patients with hypothyroidism. The secretory capacity of the C cells for monomeric calcitonin is decreased in children receiving treatment with some, but not all, anticonvulsant drugs, and lacking in patients with hypothyroidism. Patients with calcitonin deficiency may be prone to osteopenia if the tendency to increased osteoclastic activity is aggravated by secondary hyperparathyroidism in patients with epilepsy receiving phenytoin and primidone or by inappropriate thyroid replacement therapy in patients with hypothyroidism.