Appearance of specific antibody-bearing cells in human bronchial mucosa after local immunization with bacterial vaccine.

The immune response to local in vivo inhalation of a lysed bacteria vaccine was assessed in surgical specimens of main-stem bronchi from patients who had undergone pneumectomy for cancer. The patient population included 22 subjects; 11 of these received the aerosol vaccine twice a day for 10 days prior to surgery, while the remaining 11 patients were used as controls and were not immunized. The submucous glands of immunized subjects showed significantly more cells than did those of the controls, i.e., 62 +/- 8 versus 37 +/- 7, respectively (P less than 0.05). The following five antigens were chosen for study by fluorescence assay: Streptococcus pneumoniae types II and III, Haemophilus influenzae, Streptococcus sp. strain D19, and Klebsiella pneumoniae. An immunization-dependent correlation was found between immunoglobulin A, immunoglobulin A-bearing cells, and specific antibody-bearing cells on the one hand and three of the five antigens (S. pneumoniae types II and III and Streptococcus sp. strain D19) on the other hand. This is the first time that a relationship has been established between bacterial immunization of the lower respiratory tract and local immunoglobulin production in humans.     

Human melanoma progression in skin reconstructs : biological significance of bFGF

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.     

Reinfektionsversuche an Lymnaea stagnalis mit Isthmiophora melis (Trematoda,Echinostomatidae) durch Miracidienexposition nach vorausgegangener Redienimplantation

Zusammenfassung Die natürliche intramolluskäre Entwicklung des Darmegels Isthmiophora melis verläuft über zwei morphologisch distinkte Redienformen: Auf zwei Generationen makropharyngeater Redien (Mutterredien) folgen nur noch Generationen mikropharyngeater Redien (Tochterredien) sowie Cercarien. Die Bildung von Mutterredien unterbleibt in Schnecken, die nur durch Implantation von Tochterredien experimentell infiziert wurden. Werden Schnecken nacheinander beiden Infektionsmodi unterworfen, der Tochterredienimplantation und der Miracidienexposition, so läßt sich aus dem Vorhandensein oder Fehlen von Mutterredien ablesen, welche der Infektionen von Erfolg war.Mittels dieser Methode wurde geprüft, ob Isthmiophora-parasitierte Lymnaea-Individuen gegen homologen Miracidienbefall resistent sind. Sie erwiesen sich als nicht resistent gegen Reinfektion, und zwar auch dann, wenn sie bereits in die Phase des Cercarienausstoßes eingetreten waren.

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Experimental re-infection of Lymnaea stagnalis with Isthmiophora melis (trematoda, echinostomatidae) by exposition to miracidia after implantation of rediae

Summary The natural intramolluscular development of the intestinal fluke Isthmiophora melis takes place in two morphologically distinct forms of rediae: Two generations of macropharyngeate rediae (mother rediae) are followed only by generations of micropharyngeate rediae (daughter rediae) and cercariae. Mother rediae are not produced in snails infected by implantation of daughter rediae only. If snails are subjected to the implantation of daughter rediae and exposed to miracidiae successsively, the presence, or absence, of mother rediae indicates which of the infections has been successful.This method of investigation was used in order to ascertain whether Lymnaea individuals parasitized by Isthmiophora are resistant against invading miracidia of homologous species. They proved not resistant against re-infection, even if they had already entered the stage of shedding cercariae.

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Ermöglicht durch Beihilfen der Deutschen Forschungsgemeinschaft.     

A New Care Model Reduces Polypharmacy and Potentially Inappropriate Medications in Long-Term Care

ObjectivesAssess the impact of a new pharmaceutical care model on (1) polypharmacy and (2) potentially inappropriate medication (PIM) use in long-term care facilities (LTCFs).DesignPragmatic quasi-experimental study with a control group. This multifaceted model enables pharmacists and nurses to increase their professional autonomy by enforcing laws designed to expand their scope of practice. It also involves a strategic reorganization of care, interdisciplinary training, and systematic medication reviews.Setting and ParticipantsTwo LTCFs exposed to the model (409 residents) were compared to 2 control LTCFs (282 residents) in Quebec, Canada. All individuals were aged 65 years or older and residing in included LTCFs.MeasuresPolypharmacy (≥10 medications) and PIM (2015 Beers criteria) were analyzed throughout 12 months between March 2017 and June 2018. Groups were compared before and after implementation using repeated measures mixed Poisson or logistic regression models, adjusting for potential confounding variables.ResultsOver 12 months, for regular medications, polypharmacy decreased from 42% to 20% (exposed group) and from 50% to 41% (control group) [difference in differences (DID): 13%, P < .001]. Mean number of PIMs also decreased from 0.79 to 0.56 (exposed group) and from 1.08 to 0.90 (control group) (DID: 0.05, P = .002).Conclusions and ImplicationsCompared with usual care, this multifaceted model reduced the probability of receiving ≥10 medications and the mean number of PIMs. Greater professional autonomy, reorganization of care, training, and medication review can optimize pharmaceutical care. As the role of pharmacists is expanding in many countries, this model shows what could be achieved with increased professional autonomy of pharmacists and nurses in LTCFs.     

Primary intracerebral plasma cell granuloma: a light, immunocytochemical, and ultrastructural study of one case

A case of primary intracerebral plasma cell granuloma without meningeal attachment is presented. Histologically, the lesion showed two different patterns. At the center, it displayed the features of a benign fibrous histiocytoma. At the periphery, a mixture of polyclonal plasma cells, lymphocytes, and "epithelial-like" cells was observed. Electron microscopy and immunocytochemistry confirmed the histiocytic nature of the "epithelial-like cells." The differential diagnosis and histogenesis of such a lesion are discussed.     

Flupirtine-induced liver injury—Seven cases from the Berlin Case–control Surveillance Study and review of the German spontaneous adverse drug reaction reporting database

Purpose

The hepatotoxic potential of the analgesic flupirtine has attracted increased attention over the past years. Recently, risk minimisation measures such as maximum treatment duration of 2 weeks have been requested by the European Medicines Agency (EMA). This study was conducted to further elucidate the clinical pattern of flupirtine-induced liver injury (FILI).

Methods

Seven FILI patients were ascertained in all Berlin hospitals in the Berlin Case–control Surveillance Study (FAKOS) between 2002 and 2011. Furthermore, we reviewed the severe cases of flupirtine-associated hepatotoxicity included in the adverse drug reaction database of the Federal Institute for Drugs and Medical Devices (BfArM) in Germany from between 1991 and 2012.

Results

All seven FILI patients of FAKOS were hospitalised. Six of them were female, mean age was 55 years, and the most common symptoms were fatigue and jaundice. Three patients developed acute liver failure (ALF). Discontinuation of flupirtine invariably led to clinical and laboratory improvement. Review of the BfArM cases (n?=?248) showed female sex predominance and high prevalence of jaundice and ALF. Time to onset of symptoms was less than 2 weeks in 9 % of the patients with respective data.

Conclusions

Our results corroborate previous findings on FILI’s clinical pattern and on its potentially severe course. Although the hepatotoxic risk might be higher after the first 2 weeks of treatment, earlier onset of severe FILI cannot be ruled out. Postauthorisation safety studies are needed to evaluate EMA’s risk minimisation measures and to quantify flupirtine’s risk according to its duration of use.     

Standards der histo- pathologischen Diagnose maligner Melanome Empfehlungen der Arbeitsgruppe des Zentralregisters Malignes Melanom der Deutschen Dermatologischen Gesellschaft

Zusammenfassung Die Begutachtung melanozyt?rer Tumoren repr?sentiert einen der wichtigsten und vordringlichsten Aspekte der Routinediagnostik in der Dermatohistopathologie. Für die Diagnosestellung eines malignen Melanoms oder eines differentialdiagnostisch in Frage kommenden melanozyt?ren N?vus sind einheitliche und reproduzierbare histologische Kriterien zu fordern. Die prognostisch relevanten und für das therapeutische Vorgehen wichtigen Tumorparameter müssen bei malignen Melanomen im histopathologischen Befundbericht vollst?ndig und einheitlich erfa?t werden. Die Empfehlungen der Arbeitsgruppe zur histopathologischen Diagnostik bei malignen Melanomen sind nachfolgend zusammengefa?t. Eingegangen am 28. Februar 1997 Angenommen am 9. Mai 1997