Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer.

BACKGROUND: Cancer vaccines employing DC in their capacity as APC have been tolerated well and have shown some efficacy in clinical studies. IL-12, a cytokine critical for type 1 T-helper (Th1) lymphocyte and cytotoxic T-lymphocyte (CTL) differentiation, when released from a DC-based cancer vaccine, may support the generation of a cellular T-cell response. METHODS: We applied tumor cell lysate plus keyhole limpet hemocyanin (KLH)-loaded and 48-h lipopolysaccharide (LPS) plus IFN-gamma-stimulated fully mature DC, which do not release IL-12, subcutaneously to eight patients, and maximally 6-h stimulated semi-mature (sm) DC, which are potent producers of IL-12, subcutaneously (n=6) or intranodally (n=8) as a cancer vaccine to patients suffering from advanced solid pediatric malignancies. RESULTS: No serious adverse events were observed following application of IL-12-releasing smDC. Following immunization the majority of patients responded positively to KLH in a delayed-type hypersensitivity (DTH) test. In addition, three of six intranodally treated patients responded to the tumor Ag in the DTH test. DISCUSSION: We conclude that treatment with a DC-based cancer vaccine enabled to release the immune regulatory cytokine IL-12 is safe and feasible and has the potential to induce a cellular immune response in pediatric cancer patients.

Efficacy, chemistry and pharmacology of chinese herbal medicine for allergic rhinitis.

An extensive literature search identified six randomized controlled clinical trials in which the efficacy of Chinese herbal medicine had been investigated for the treatment of allergic rhinitis. Although four of these trials had methodological flaws, the therapeutic outcomes of all six have been reviewed. One of two trials considered to be of high quality was concerned with the treatment of seasonal allergic rhinitis and the other with perennial allergic rhinitis. It is considered that all six studies demonstrated various degrees of alleviation of the symptoms of allergic rhinitis. No serious side effects were reported in any of the trials. A number of the herbs in the Chinese herbal formulae used in the trials, and/or their constituent compounds have been reported to possess anti-allergic, anti-inflammatory or immune modulation activity. Such actions include inhibition of the release or action of mast cell mediators such as histamine, inhibition of inflammation induced by chemical agents, and modulation of serum IgE levels or of lymphocyte and/or macrophage activity. An aqueous, unresolved extract of the herbal formula used in one of the six trials has been reported to exhibit a range of pharmacological actions relevant to the treatment of allergic rhinitis. Essential oils, lignans, flavonoids and saponins are chemical classes that are frequently represented in individual herbs of the six Chinese herbal formulae used in the trials. The chemical structures characterising these classes of compound and the pharmacological actions of these and other constituents of the herbs, relevant to allergic rhinitis, have been reviewed.

The effects of Eleutherococcus senticosus and Panax ginseng on steroidal hormone indices of stress and lymphocyte subset numbers in endurance athletes.

A clinical trial was undertaken to investigate the effects of Eleutherococcus senticosus (ES) and Panax ginseng (PG) on competitive club-level endurance athletes engaged in their normal in-season training. Participants were matched for training stress and received a 33% ethanolic extract (8 mL/day) containing either ES, PG (equivalent to 4 g and 2 g/day of dried root, respectively), or a placebo. A pre-test and post-test were used to evaluate the effects of six weeks of supplementation on cortisol, testosterone, and testosterone to cortisol ratio (TCR) as well as circulating numbers of total T-cells, T-helper cells (CD4), T-suppressor cells (CD8), CD4 to CD8 ratio, natural killer cells, and B lymphocytes. None of the immune system variables changed significantly nor showed any clear trend from pre to post test in any of the treatment groups. No significant change in testosterone, cortisol or TCR was observed in the PG group. In the ES group, however, TCR decreased by 28.7% from 0.0464 to 0.0331 (P=0.03). The main contribution to this decrease appeared to be a non-significant (P= 0.07) 31% trend towards increased cortisol rather than a very small non-significant (P = 0.36) 7% decrease in the calculated mean for testosterone. This result suggested that contrary to initial expectation, ES increased rather than decreased hormonal indices of stress, which may be consistent with animal research suggesting a threshold of stress below which ES increases the stress response and above which ES decreases the stress response.

Panax ginseng and Eleutherococcus senticosus may exaggerate an already existing biphasic response to stress via inhibition of enzymes which limit the binding of stress hormones to their receptors.

A mechanism of action for Panax ginseng (PG) and Eleutherococcus senticosus (ES) is proposed which explains how they could produce the paradoxical effect of sometimes increasing and sometimes decreasing the stress response. The mechanism suggests that this biphasic effect results from increased occupancy of positive and negative feedback stress hormone receptors by their natural ligands due to inhibition of specific enzymes which function to limit receptor occupancy. Specifically, it is suggested that PG inhibits 11-beta hydroxysteroid dehydrogenase one and ES inhibits catechol- O -methyl transferase, both of which reside in close proximity to stress hormone receptors and catalyse the degradation of stress hormones into inactive compounds. In addition, it is suggested that the increased energy said to result from PG and ES may be a consequence of their increasing the occupancy of stress hormone receptors which function to redistribute the body's energy reserves from regeneration to activity.

[Communicative and social behavior of speech disordered children]. / Untersuchung zum kommunikativen und sozialen Verhalten sprachbehinderter Kinder.

The spheres covering behaviour disorders, social behaviour and communicative behaviour of speech impaired pupils which until now have been analyzed on a more theoretical level, ought to be studied using psychometric testing procedures and an esperimental observational situation in order to gain base data with which to set up a concrete catalogue of aims (learning program) based on the deficits thereby obtained. The study took place at the special school in Esslinger-Berkheim (Baden-Wurttemberg). By taking into account relevant specialized literature and the results of other studies, the following general hypotheses were advanced, namely, that the communication of speech handicapped children is troubled in respect of its content and relation, and that their social behaviour shows more egoistic than cooperative features. In order to determine social motivations and attitudes, we used Muller's "Social Motivation Test" (SMT) and Jorger's "Group test for the social attitude" (S-E-T). Due to the inconsistency between the attitudes measured by means of psychometric methods and the sbusequent free and genuine behaviour, an observational situation was developed during which the pupils, either in pairs or in groups of four and using puppets, took turns in thinking up a story, discussing the plot, roles, etc. and finally putting on the play. The whole was then analyzed by means of tape recordings and film shots, the interaction of the communicating partners being analyzed and categorized in two separate assessment stages: communicative behaviour and social behaviour. The pragmatic axioms of P. Watzlawick, the communication researcher, functioned as theoretical background. Flanders's linear time diagram was used as assessment system. Communicative and social learning aims were prepared in accordance with confirming hypotheses to enable a "preliminary area" for the practical work in (special) education to be defined. In addition, a rough outline was made of the conditional areas pertaining to social and communicative education of the speech impaired for the purpose of carrying out a systematic change.

Redox chemistry of green tea polyphenols: therapeutic benefits in neurodegenerative diseases.

Evidence for the medicinal and health benefits of polyphenols in green tea for the prevention of chronic diseases such as heart disease, various types of cancer and neurodegenerative diseases is advancing. Their in vivo effectiveness and molecular mechanisms are difficult to elucidate and remain a challenging task. We review the redox responsiveness and amyloid protein perturbation biophysical properties of the major green tea polyphenol constituent (-)- epigallocatechin-3-gallate [EGCG].

Chinese herbs for dementia diseases.

In the last twenty years a considerable body of information has accumulated on the chemical constituents of Chinese herbs and their therapeutic potential. Our evaluation/systematic review [1, 2] of well-designed, randomized double blind controlled trials on Chinese herbal medicines beneficial for the improvement of cognitive function revealed a range of either single herbs or herbal mixtures that provided neuroprotective benefits. Oxidative stress may directly initiate neurodegeneration and herbal antioxidant neuroprotection is considered as a preventative and therapeutic approach. We encountered Acoris gramineus rhizome (AGR), Panax ginseng, Polygala tenuifolia and Poria cocos as the four most frequently used herbs as single/herbal mixtures that were associated with positive cognitive enhancing outcomes. This review focuses on the evidence of their medicinal effects attributed to those constituents present in relatively high concentration.

[Plaque-like dermal fibromatosis]. / Die plaqueförmige dermale Fibromatose.

Plaquelike dermal fibromatosis with a preference for the periaxillary region is described in 22 women, 1 man and 2 boys before puberty. The lesions grew slowly but relentlessly and measured up to 5 cm in diameter. No recurrences after excision have occurred to date. Histologically there is bandlike proliferation throughout the stratum reticulare consisting of well-differentiated, highly cellular fibrous tissue.

[Histological diagnosis of inflammatory skin diseases. Use of a simple algorithm and modern diagnostic methods]. / Histologische Diagnostik entzündlicher Hauterkrankungen. Verwendung eines einfachen Algorithmus und moderner Methoden.

The histological diagnosis of inflammatory skin diseases on a day-to-day routine basis poses the difficult task to characterise a dynamic clinical process by histomorphological analysis of one single lesion. Very complex algorithms which are meant to lead to the correct diagnosis are difficult to use. To facilitate the process and reduce the number of algorithms the following method is proposed: 1. Histological examination under low power Definition of lesions altered by scratching 2. Localisation of the significant pathological alterations as follows: Changes in epidermis and dermis Blister formation Changes in dermis/subcutis without characteristic changes in the epidermis Changes mainly in the subcutis 3. Closer examination using a simple algorithm and planning of further investigations following defined criteria: In the case of changes in epidermis and dermis definition of spongiotic, psoriasiform or lichenoid dermatitis (Abb. 1). In the case of blister formation definition of the blister following the given algorithm (Abb. 1). In the case of changes in dermis/subcutis without characteristic changes in the epidermis after exclusion of vasculitis and lymphoma definition of the main pattern as lymphocytic, neutrophilic, eosinophilic, lymphoplasmocytic or granulomatous and following the given algorithm (Abb. 2). In the case of changes mainly in the subcutis after exclusion of vasculitis and lymphoma definition of the main pattern of panniculitis as septal or/and lobular (Abb. 2). Exclusion of PAS positive microorganisms and checking if the general pattern fits into infectious correlation. Use of clinicopathological correlation.

Propagation analysis of self-convergent beam width and characterization of hard-edge diffracted beams.

For a laser beam diffracted by a hard-edge aperture, propagation of the beam width, defined by the second-order moment of its irradiance distribution truncated according to the self-convergent-width criterion, obeys the familiar hyperbolic law. It is demonstrated numerically that, with the self-convergent-width approach, the beam-propagation parameters for three beam types (Gaussian, Hermite-Gaussian, and flattened Gaussian) diffracted by hard-edge apertures can be determined with the second-moment-based procedure that is recommended by the present draft standard only for unapertured laser beams.

Pseudomalignant erosion in hyperplastic gastric polyps.

Six cases of hyperplastic gastric polyps are described that, in the region of the eroded head, revealed strikingly atypical mesenchymal cells. These disseminated cells with marked nuclear pleomorphism and also atypical mitotic figures, undergoing direct transition to typical granulation tissue, are considered to be particularly activated mesenchymal cells. In a single case in which only excisional biopsy was performed, these cells were found to persist over a lengthy period, while in endoscopic-biopsy follow-ups of the polypectomized cases, these cells were subsequently no longer detectable. In four of the cases, the polyp was located in the region of the cardia, so that a traumatic factor may possibly be considered as having some causal relevance. In particular when biopsy excisions are performed, the differential diagnosis of this polyp with its endoscopic and histologic appearance of a tumor-like lesion, from epithelial and mesenchymal malignancies, as also from neural tumors, can be difficult.

Algebraic approach to characterizing paraxial optical systems.

The paraxial propagation formalism for ABCD systems is reviewed and written in terms of quantum mechanics. This formalism shows that the propagation based on the Collins integral can be generalized so that, in addition, the problem of beam quality degradation that is due to aberrations can be treated in a natural way. Moreover, because this formalism is well elaborated and reduces the problem of propagation to simple algebraic calculations, it seems to be less complicated than other approaches. This can be demonstrated with an easy and unitary derivation of several results, which were obtained with different approaches, in each case matched to the specific problem. It is first shown how the canonical decomposition of arbitrary (also complex) ABCD matrices introduced by Siegman [Lasers, 2nd ed. (Oxford U. Press, London, 1986)] can be used to establish the group structure of geometric optics on the space of optical wave functions. This result is then used to derive the propagation law for arbitrary moments in eneral ABCD systems. Finally a proper generalization to nonparaxial propagation operators that allows us to treat arbitrary aberration effects with respect to their influence on beam quality degradation is presented.

Carcinomatous metastases to the colon simulating Crohn's disease.

Multifocal lymphatic and hematogeneous metastatic infiltration of the colon by anaplastic carcinoma is described. The radiological and endoscopic examinations gave reason to believe that the patient was suffering from Crohn's disease. Only deep biopsy revealed the correct diagnosis. Clinical and pathological problems arising in the diagnosis are discussed.

[Telangiectatic anastomoses polyp of the stomach]. / Teleangiektatischer Anastomosenpolyp des Magens.

Teleangiectatic polyps (TP) of the stomach arise from granulation OFFsue mostly in elderly people in the area of gastrojejunostomy decades after surgery. During endoscopy usually polyps of a size up to 2 cm can be found with a diffuse erosion of the surface and bleeding immediately upon being touched; this may cause the clinical symptomatology of acute gastric bleeding or chronic anemia as a consequence of blood loss. TP has to be differentiated in the first line from gastric carcinoma. Therapy is difficult especially in patients with big polyps because of the bleeding tendency, 5 case reports of TP are given.

[Pigmented Paget's disease and pigmented breast cancer metastasis. Clinical and histologic simulation of malignant melanoma of the breast]. / Pigmentierter Morbus Paget und pigmentierte Mammakarzinommetastase. Klinische und histologische Nachahmer maligner Melanome der Brust.

Pigmented epidermotropic breast carcinoma has to be included in the differential diagnosis of pigmented lesions of the breast. Two rare cases of pigmented Paget's disease and pigmented metastatic breast carcinoma are presented, which mimicked malignant melanoma in both clinical and histological criteria.

[Drug induced esophageal ulcers]. / Das medikamentös bedingte Osophagusulkus.

Drug induced esophageal ulcers are more frequent than supposed. Four ulcerative lesions of the esophagus, two after ingestion of doxycycline-hydrochloride, one after metacycline-hydrochloride, and one after emeproniumbromide were detected at the department of Internal Medicine of a medium-sized standard-hospital during the last six years. Symptoms develop suddenly after taking the drug with minimum fluid, usually before going to bed. Retrosternal burning, odynophagia and dysphagia are pathognomonic features. The cause of ulceration is discussed to be a matter of the drug remaining in the esophagus and of its local cytolytic and corrosive effect. Cytomegalo and herpes-simplex-infections can be excluded as etiologic factor of such ulcers. The clinical diagnosis is verified by endoscopy only.