[Acrokeratosis paraneoplastica Bazex 6 years prior to diagnosis of gastric cancer]. / Acrokeratosis paraneoplastica Bazex 6 Jahre vor Diagnose eines Magenkarzinoms.

BACKGROUND: Bazex's syndrome is a rare paraneoplasia that is usually associated with cancer. DIAGNOSIS: Characteristic for the disease are diffuse, psoriasis-like, acral erythema, distal hyperkeratosis and onychodystrophy. Differential diagnoses comprise psoriasis, eczema and tinea. CASE REPORT: We present the case of a 73-year-old man with acral hyperkeratosis, onychodystrophy, and diffuse palmar erythema. Gastric carcinoma was diagnosed by gastroscopy. After a gastrectomy was performed, regression of the skin lesions that the patient had been suffering from for more than 6 years was observed, confirming the diagnosis of Bazex's syndrome.

[Sequential digital dermatoscopic imaging. How much time is required per patient?]. / Sequenziell digitale Dermatoskopie. Wie groß ist der Zeitaufwand pro Patient?

BACKGROUND: Melanoma screening is possible using the naked eye, a loupe, a dermatoscope or a sequential digital dermatoscopic imaging (SDDI) device. The latter provides photodocumentation and makes it possible to assess changes over time. One potential disadvantage of this method has been felt to be in the time expenditure per patient. OBJECTIVES: Objective was to prospectively assess the time required for routine melanoma screening, using a SDDI device. MATERIALS AND METHODS: All patients screened for melanoma using a SDDI system (Mole Max2) in a private dermatology practice during 1 year were included prospectively. The time needed per patient was measured. Suspicious lesions were excised and histologically evaluated. The number needed to treat (NNT) was calculated. Excisions performed exclusively due to cosmetic reasons were not included. RESULTS: 381 patients with 10,356 melanocytic lesions were documented using SDDI and clinically assessed (mean: 27.18 melanocytic lesions per patient; min:1, max:110). Mean time consumption per lesion was 15.4 s. (min:3, max:57) and per patient about 7 min. 98 suspicious lesions were excised, among them13 melanomas; yielding a NNT of 7.54. CONCLUSIONS: SDDI can be easily integrated into the daily routine; a variety of systems are available. The time required is reasonable, about 7 min per patient and about 15 s per lesion. The quality of the evaluation is operator-dependent; it can be evaluated by determining the NNT. A major advantage of this diagnostic procedure is the photodocumentation which makes it possible to assess potential progression of a melanocytic lesion.

Specific immunotherapy normalizes tryptophan concentrations in patients with allergic rhinitis.

BACKGROUND/AIMS: An immune shift towards Th2-type immunity seems to be critical in the pathogenesis of allergic asthma and rhinitis. In a previous study, we found higher serum tryptophan concentrations in patients with seasonal tree or grass pollen rhinoconjunctivitis who underwent specific immunotherapy (SCIT) than in controls, and those with the highest levels at baseline responded less well to SCIT. In the present study, we examined whether 'booster immunotherapy' after cessation of SCIT had any influence on tryptophan metabolism during follow-up. METHODS: Serum concentrations of tryptophan, kynurenine and neopterin were assayed in 19 patients (mean age: 26.2 years; 6 females) allergic to grass and/or tree pollen before and after they had received a booster immunotherapy with 4 injections of an allergoid vaccine (Pollinex Quattro; Bencard Vienna, Austria) over 8 ± 3 months outside the pollen season. RESULTS: Serum tryptophan and kynurenine concentrations decreased after booster immunotherapy (mean ± SD, before immunotherapy: 81.1 ± 14.2 µmol/l, after immunotherapy: 61.4 ± 20.9 µmol/l and before immunotherapy: 2.25 ± 0.44, after immunotherapy: 1.69 ± 0.70 µmol/l, respectively; both p < 0.01); this was especially true in those responders who also tended to have lower baseline kynurenine concentrations as compared with nonresponders (p = 0.05). Finally, a correlation between changes in tryptophan metabolism and neopterin concentrations was observed after immunotherapy. CONCLUSIONS: The decrease in tryptophan and kynurenine concentrations following booster immunotherapy in hay fever patients strengthens the hypothesis that tryptophan metabolism might be involved in the course of allergic responses. However, it is still unclear whether the abnormal tryptophan metabolism in pollinosis patients is related to indoleamine 2,3-dioxygenase and/or to a specific cytokine background.

A case of dog-related human seminal plasma allergy.

Allergy to human seminal plasma (HSP) is rare. It presents with a variety of symptoms, ranging from localized changes to generalized reactions or even anaphylactic shock. Symptoms typically start within minutes to one hour after exposure. Diagnosis is based on history, evidence of specific IgE antibodies and skin prick testing (SPT). A 25-year-old Caucasian woman presented with eyelid swelling, generalized urticaria and dyspnea immediately after unprotected coitus with her partner. No symptoms occurred when barrier contraception was used. SPTand IgE testing (ImmunoCAP) demonstrated sensitization to HSP and dog dander. The patient's self-designed desensitization protocol, consisting of H1 blocker premedication followed by unprotected sexual intercourse, ameliorated her systemic reactions gradually and reduced the frequency of emergency hospital visits. She had a known allergy to male but not female dogs, and was highly sensitized to dog allergen Can f 5, a protein homologous to human prostate-specific antigen (PSA), suggesting a possible link to her HSP allergy.

High serum tryptophan concentration in pollinosis patients is associated with unresponsiveness to pollen extract therapy.

BACKGROUND/AIMS: The immunologic background of allergic asthma and rhinitis includes a preponderance of Th2-type immunity. In parallel, Th1-type immune response is suppressed by Th2-type cytokines. As a consequence, biochemical pathways triggered by Th1-type cytokine interferon-gamma, such as tryptophan degradation by indoleamine 2,3-dioxygenase and neopterin production, might be altered. We examined whether they are related to the outcome of hyposensitization therapy in atopic patients. METHODS: In serum specimens of 44 atopic patients (18 women, 26 men) before any specific immunotherapy, tryptophan and kynurenine concentrations were measured by HPLC, and the kynurenine to tryptophan ratio (kyn/trp) was calculated. Neopterin concentrations were measured by ELISA. Results were compared with concentrations in 38 serum specimens from healthy blood donors and with the outcome of specific subcutaneous immunotherapy in atopics: on clinical grounds, 27 patients were classified as responders, and 17 patients as non-responders. RESULTS: Serum tryptophan concentrations were higher in atopics (84.3 +/- 24.4 microM) than in blood donors (57.9 +/- 7.46 microM; p < 0.001), kynurenine and kyn/trp were not different between the 2 groups. All of the neopterin concentrations measured in patients were <8.7 nM, the upper limit of the normal. Non-responders to subcutaneous immunotherapy had significantly higher tryptophan concentrations (95.7 +/- 27.0 microM) than responders (77.1 +/- 19.9 microM; p = 0.01). No other marker concentrations differed between the groups. CONCLUSIONS: The measurement of serum tryptophan may present an option to predict the outcome of pollen extract therapy. Higher tryptophan levels may result from lower indoleamine 2,3-dioxygenase activity in atopics. However, this possible relationship needs to be confirmed in further studies.

Absence of contact sensitization to Aloe vera (L.) Burm. f.

Aloe vera has been used as a cosmetic and medical remedy since ancient times and has gained increasing popularity in recent years. Despite its widespread use, reports of allergic reactions are rare. We patch tested 702 consecutive patients with an oily extract from the leaves, Aloe pulvis from the entire plant and concentrated Aloe vera gel. A specially designed questionnaire was used for the use of Aloe vera, reasons and location of application, adverse reactions, occupation, hobbies and atopy. None of the subjects showed any reaction to one of the preparations. 2 components of the plant have to be distinguished: the bark of the leaves contains anthrachinones with pro-peristaltic and potential antibiotic and anticancer properties. Constraints have been imposed due to their considerable toxic potential. Today, mostly the Aloe gel from the center of the leaves is processed. It almost exclusively consists of carbohydrates to which also many medical effects have been attributed. Carbohydrates are not likely to induce contact sensitization, which might explain the outcome of our study. However, this does not justify unrestrained promotion of Aloe products, as scientific studies investigating the claims on its constitutional effects are few in number, and the majority of them have been unable to diminish the intuitive scepticism against miracle cures, like Aloe seems to be.

Specific sensitization to the common housefly (Musca domestica) not related to insect panallergy.

BACKGROUND: Allergy to houseflies is rare. We report a case of respiratory allergy from occupational exposure to houseflies in a farmer. CASE REPORT: A 30 year-old female farmer with a long-standing history of grass pollen allergy observed for 2 years rhino-conjunctivitis and mild asthma when entering livestock stables and barns. Allergy retesting revealed sensitization to various pollens but not to animal danders. Houseflies (Musca domestica) occurring on the farm in great quantity were suspected by the farmer herself as the causative agent. RESULTS: Skin prick testing with housefly was positive in the patient and negative in four controls. Experimental radioallergosorbant test was class 3 positive. Sensitization to house dust mite, storage mites and cockroach was not detectable. Western blots with housefly extracts revealed immunoglobulin E (IgE)-binding to bands of 70, 50, and approximately 16 kDa. Tropomyosin in the housefly extract (35 kDa) was recognized by a tropomyosin reference serum but not by the patient. In enzyme-linked immunosorbent assay (ELISA) inhibition assays using housefly as the solid phase, IgE-binding of the patient was inhibited by 75% by M. domestica and by 44% by the closely related lesser housefly (Fannia canicularis), but not by extracts from blowfly (Lucilia spp.), fruit fly (Drosophila spp.), horsefly (Haematopota pluvialis) and mosquito (Culex pipiens). The IgE-binding of the tropomyosin control serum was inhibited by 60-80% by all species. CONCLUSIONS: In accordance with previous reports, this case demonstrates that respiratory sensitization to insects may be highly specific. According to ELISA inhibition, cross-sensitization in the present case was restricted to species of the family of true flies (Muscidae).

Spina bifida as an independent risk factor for sensitization to latex.

PURPOSE: Patients with spina bifida are at a high risk for having an immediate type allergy to latex products. The number of surgical interventions, atopy and catheterization are well known responsible factors, whereas the condition of spina bifida per se has not been established as an independent risk factor. MATERIALS AND METHODS: A total of 131 patients with a shunted hydrocephalus (48 with spina bifida and 83 of other origin) were investigated for sensitization to latex by skin prick tests and determination of specific IgE. We hypothesized that the diagnosis of spina bifida will increase the risk for latex sensitization while considering potential confounding factors. Thus, we performed a multiple logistic regression analysis to determine independent risk factors. RESULTS: Whereas 56.3% (27/48) of children with spina bifida proved sensitized against latex, this result was the case in only 16.9% (14/83) with another cause of hydrocephalus (p <0.001). The mean number of surgical interventions was 6.2 for patients with no latex sensitization and 9.3 for those with sensitization (p = 0.02). Of patient sensitized to latex 43.9% had a history of atopy compared to 15.5% of those not sensitized (p = 0.02). Sensitized and nonsensitized patients were comparable regarding gender and catheterization. In a multiple logistic regression analysis the cause of the hydrocephalus (odds ratio 6.76 for spina bifida), atopy (odds ratio 3.37) and the number of surgical interventions (odds ratio 1.14 per operation) were identified as independent risk factors. CONCLUSIONS: The increased risk of latex sensitization in patients with spina bifida seems to be disease associated. Possible explanations for this finding may be genetic, antigen mediated, early latex exposure and immunological reasons.

The Arabidopsis sex1 mutant is defective in the R1 protein, a general regulator of starch degradation in plants, and not in the chloroplast hexose transporter.

Starch is the major storage carbohydrate in higher plants and of considerable importance for the human diet and for numerous technical applications. In addition, starch can be accumulated transiently in chloroplasts as a temporary deposit of carbohydrates during ongoing photosynthesis. This transitory starch has to be mobilized during the subsequent dark period. Mutants defective in starch mobilization are characterized by high starch contents in leaves after prolonged periods of darkness and therefore are termed starch excess (sex) mutants. Here we describe the molecular characterization of the Arabidopsis sex1 mutant that has been proposed to be defective in the export of glucose resulting from hydrolytic starch breakdown. The mutated gene in sex1 was cloned using a map-based cloning approach. By complementation of the mutant, immunological analysis, and analysis of starch phosphorylation, we show that sex1 is defective in the Arabidopsis homolog of the R1 protein and not in the hexose transporter. We propose that the SEX1 protein (R1) functions as an overall regulator of starch mobilization by controlling the phosphate content of starch.

Molecular characterisation of a new mutant allele of the plastid phosphoglucomutase in Arabidopsis, and complementation of the mutant with the wild-type cDNA.

Screening of transposon-associated mutants of Arabidopsis thaliana for altered starch metabolism resulted in the isolation of a mutant that did not accumulate starch in any tissue or at any developmental stage (starch-free mutant, stf1). Allelism tests with known mutants showed that stf1 represents a new mutant allele of the plastid isoform of the enzyme phosphoglucomutase (PGMp). The mutation was mapped to chromosome 5. An Arabidopsis EST that showed significant homology to the cytosolic isoform of phosphoglucomutase (PGM) from maize was able to complement the mutant phenotype. The Arabidopsis EST was transcribed and translated in vitro and the protein product was efficiently imported into isolated chloroplasts and processed to its mature form. The lack of starch biosynthesis in stf1 is accompanied by the accumulation of soluble sugars. The rate of CO2 assimilation measured in individual leaves was substantially diminished only under conditions of high CO2 and low O2. Remarkably, stf1 exhibits an increase rather than a decrease in total leaf PGM activity, suggesting an induction of the cytosolic isoform(s) in the mutant. The substrate for PGM, glucose 6-phosphate, accumulated in stf1 during the day, resulting in 10-fold higher content than in the wild type at the end of the photoperiod.

Identification, purification, and molecular cloning of a putative plastidic glucose translocator.

During photosynthesis, part of the fixed carbon is directed into the synthesis of transitory starch, which serves as an intermediate carbon storage facility in chloroplasts. This transitory starch is mobilized during the night. Increasing evidence indicates that the main route of starch breakdown proceeds by way of hydrolytic enzymes and results in glucose formation. This pathway requires a glucose translocator to mediate the export of glucose from the chloroplasts. We have reexamined the kinetic properties of the plastidic glucose translocator and, using a differential labeling procedure, have identified the glucose translocator as a component of the inner envelope membrane. Peptide sequence information derived from this protein was used to isolate cDNA clones encoding a putative plastidic glucose translocator from spinach, potato, tobacco, Arabidopsis, and maize. We also present the molecular characterization of a candidate for a hexose transporter of the plastid envelope membrane. This transporter, initially characterized more than 20 years ago, is closely related to the mammalian glucose transporter GLUT family and differs from all other plant hexose transporters that have been characterized to date.

Vulval and vaginal adenosis.

Vaginal adenosis is defined by the presence of metaplastic cervical or endometrial epithelium within the vaginal wall, thought to be derived from persistent Müllerian (synonymous with paramesonephric) epithelium islets in postembryonic life. Spontaneous vaginal adenosis appears to be a fairly common (present in about 10% of adult women) but mostly insignificant coincidental finding. In women prenatally exposed to diethylstilboestrol (DES), vaginal adenosis may arise in up to 90% and is associated with a high risk of vaginal carcinoma. Since the withdrawal of DES from the market, vaginal adenosis has virtually disappeared from the medical literature. A case of vaginal adenosis is presented in a middle-aged woman who had not been prenatally exposed to DES. The lesions differed from the spontaneous type by their sudden appearance, their extent and their pronounced subjective symptoms. It is speculated that protracted oral contraceptive intake may have played a causative role.

Leg ulcers associated with long-term hydroxyurea therapy.

Hydroxyurea is commonly used in the treatment of various hematologic disorders, e.g., chronic myelogenous leukemia (CML), polycythemia vera, and occasionally, at lower doses, for severe psoriasis vulgaris. Cutaneous side effects such as alopecia, diffuse hyperpigmentation, poikiloderma, atrophy of the skin, or nail changes occur, especially with long-term treatment. Painful leg ulcers in association with hydroxyurea have only rarely been reported. We describe 2 patients who developed spontaneous painful leg ulcers during long-term hydroxyurea therapy for a myeloproliferative disorder; these ulcers healed only after hydroxyurea was withdrawn.

Intravenous immunoglobulin treatment in therapy-resistant epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita is an uncommon autoimmune bullous disease of the skin and mucous membranes. It is chronic, disabling, and difficult to treat. We describe a case of severe epidermolysis bullosa acquisita of 7 years' duration that had been treated with azathioprine, corticosteroids, chlorambucil, plasma exchanges, cyclophosphamide, cyclosporine, and colchicine without any lasting effect. Seven cycles of treatment were administered with immunoglobulin given intravenously at a low dose, 40 mg/kg body weight daily for 5 days. The patient was free of disease for 10 months after the initiation of therapy. We suggest that low-dose regimens of immunoglobulins may be as effective in this disease as the high-dose regimens suggested in the literature, and at much lower cost.

Lack of association between atopy and the Ile181Leu variant of the beta-subunit of the high-affinity immunoglobulin E receptor.

A previous study has reported a strong association of a variant (Ile181Leu) of the beta-subunit of the high-affinity IgE receptor (Fc epsilon RI-beta) with allergic asthma bronchiale in a random patient sample. Based on their results the authors concluded that Fc epsilon RI-beta may be the maternally inherited, atopy-causing locus. We have investigated 40 unrelated atopic patients, 30 with allergic asthma and 10 with atopic dermatitis or allergic rhinoconjunctivitis along with some of their relatives for the presence of Ile181Leu by nucleic acid sequence analysis and/or hybridization with mutation-specific oligonucleotide probes. None of the probands showed this mutation suggesting that its association with atopy may be restricted to certain populations or occur at lower frequency than reported.

Werner syndrome: studies in an affected family reveal a cellular phenotype of unaffected siblings.

Werner syndrome is an inherited disease with symptoms of presenescence. The primary defect site either on the protein or at the DNA level is not known, nor is it possible to identify a heterozygous phenotype. On the basis of cellular peculiarities expressed in the homozygotes-lifespan reduction of cells in culture, length of population doubling time and chromosomal instability-we searched for a 'Werner-like' phenotype in otherwise phenotypically unaffected siblings. We established primary fibroblasts from eight members of a Tyrolean family, two of whom had been diagnosed as typical Werner syndrome, as well as from unrelated healthy young and old volunteers. Determination of the lifespan of each strain and studies on population doubling time and chromosomal instability revealed similar cellular characteristics in all family members, albeit to a lesser extent with the siblings than with the homozygotes when compared to age-matched controls. These features, also apparent in cultivated fibroblasts from old but healthy controls, appear to be indicative of Werner syndrome when expressed in young or middle aged persons. The possible identification of otherwise clinically healthy gene carriers of Werner syndrome is of utmost importance for genetic counselling and medical surveillance for this disorder.