Chronic Gastro-Duodenal Ulcerative Disease and the Death of Father Stephan Schätzl from Viechtwang (Austria).

Stephan Schätzl was the parish priest of Viechtwang, Upper Austria. He lived in the aftermath of the Peace of Augsburg in a period of schism between Roman Catholics and Lutherans. His portrait, depicted only 6 days before his demise in 1590, shows that he had extreme ante mortem cachexia. Documentary sources detailed his life and ill-health and it is proposed that he had chronic gastro-duodenal ulcerative disease which ultimately led his to death.

Hydroxy-chloroquine to treat COVID-19 - infected patients: Some lessons from medical anthropology and history of medicine.

It is certainly too early to take stock of Professor Raoult's intuitions, and moreover, that is not the aim of this short article. Nevertheless, experience has shown that in times of unprecedented health crises, prescriptions often turn out to be adventurous, especially when it comes to a new virus. The collective imagination around a remedy often takes the place of a guarantee or, on the contrary, a safeguard. Here, the authors question the implementation of hydroxy-chloroquine treatment in the context of the COVID-19 pandemic. How was his prescription discussed in this context of crisis? What lesson can we learn from medical anthropology and the history of medicine, by witnessing other epidemics and atypical or unconventional substances or behaviors of practitioners?

Il est certainement trop tôt pour faire le point sur les intuitions du professeur Raoult, et ce n'est d'ailleurs pas le but de ce court article. Néanmoins, l'expérience a montré qu'en période de crise sanitaire sans précédent, les prescriptions se révèlent souvent aventureuses, surtout lorsqu'il s'agit d'un nouveau virus. L'imagination collective autour d'un remède se substitue souvent à une garantie ou, au contraire, à une sauvegarde. Ici, les auteurs s'interrogent sur la mise en œuvre du traitement à l'hydroxy-chloroquine dans le contexte de la pandémie de la COVID-19. Comment sa prescription a-t-elle été discutée dans ce contexte de crise ? Quelle leçon pouvons-nous tirer de l'anthropologie médicale et de l'histoire de la médecine, en étant témoins d'autres épidémies et de substances ou comportements atypiques ou non conventionnels des praticiens ?

Disc cell therapy with bone-marrow-derived autologous mesenchymal stromal cells in a large porcine disc degeneration model.

PURPOSE: Disc regeneration through matrix-assisted autologous mesenchymal stromal cell therapy seems promising against disc degeneration with convincing results in small animal models. Whether these positive results can be transferred to larger animal models or humans is unclear. METHODS: Fibrin matrix-assisted autologous bone-marrow-derived mesenchymal stromal cell therapy was compared to acellular fibrin matrix therapy in a porcine in vivo model. First, disc degeneration was induced by annular puncture and partial nucleotomy with a large 16G-needle, and 12 weeks later, disc therapy was performed in a second surgery with a thinner 26G needle. Seventy-two lumbar discs from 12 aged adult pigs were evaluated by histology, micro-CT, and gene expression analysis 13 and 24 weeks after nucleotomy and 1 and 12 weeks after treatment, respectively. RESULTS: Radiologic disc height was not significantly different in both treatment groups. In the semi-quantitative histologic degeneration score, significant disc degeneration was still evident 1 week after treatment both in the mesenchymal stromal cell group and in the acellular fibrin matrix group. 12 weeks after treatment, degeneration was, however, not further increased and mesenchymal-stromal-cell-treated discs showed significantly less disc degeneration in the annulus fibrosus (p = 0.02), whereas reduction in the nucleus pulposus did not reach statistical significance. Cell treatment compared to matrix alone found less Col1 gene expression as a marker for fibrosis and more expression of the trophic factor BMP2 in the nucleus pulposus, whereas the inflammation marker IL1ß was reduced in the annulus fibrosus. CONCLUSIONS: Disc treatment with fibrin matrix-assisted autologous mesenchymal stromal cells reduced degenerative findings compared to acellular fibrin matrix alone. Regenerative changes, however, were not significant for all parameters showing limitations in a large biomechanically demanding model with aged discs. These slides can be retrieved under Electronic Supplementary Material.

[HPV infection in oral, pharyngeal and laryngeal papillomas]. / HPV-Infektion in oralen, pharyngealen und laryngealen Papillomen.

BACKGROUND: HPV infections play a major role in the pathogenesis of squamous cell carcinomas of the head and neck. Regarding benign papillomas, the role of HPV is still uncertain. MATERIALS AND METHODS: To clarify this issue, 100 exophytic papillomas of the oral cavity, pharynx and larynx were subjected to histopathological and molecular pathological examination. Excision biopsies were taken from 62 male and 38 female patients with an age range of 18 to 87 years. Biopsies were tested for p16 expression by immunohistochemistry and analyzed for HPV subtypes 6/11 (low-risk), 16/18 and 31/33/53 (high-risk) by chromogenic in situ hybridization. RESULTS: HPV infections were verified molecularly in 34 % of biopsies; in all cases with the low-risk HPV subtypes 6/11. Only one case showed infection with both 6/11 and 31/33/53 subtypes, but not subtype 16/18; whereas expression of p16 was found in 67 %. The rate of positive molecular verification of HPV infection (in situ hybridization) was highest in the laryngeal lesions with 61.1 %, followed by the oral cavity with 52.9 %, and lowest in pharyngeal lesions (21.5 %). Recurrent papillomas were seen in 18 cases (18 %), of which 14 were molecularly positive for HPV (in situ hybridization). A correlation between inflammatory infiltration and HPV infection could be verified in 82 %. CONCLUSION: Our data demonstrate an important role of HPV infection for the development of benign papillomas of the head and neck region. Furthermore, there is a positive correlation between HPV infection and recurrent papillomas. Therefore, a molecular morphological HPV analysis of papillomas could provide important prognostic data.

Dynamic Virus-Bacterium Interactions in a Porcine Precision-Cut Lung Slice Coinfection Model: Swine Influenza Virus Paves the Way for Streptococcus suis Infection in a Two-Step Process.

Swine influenza virus (SIV) and Streptococcus suis are common pathogens of the respiratory tract in pigs, with both being associated with pneumonia. The interactions of both pathogens and their contribution to copathogenesis are only poorly understood. In the present study, we established a porcine precision-cut lung slice (PCLS) coinfection model and analyzed the effects of a primary SIV infection on secondary infection by S. suis at different time points. We found that SIV promoted adherence, colonization, and invasion of S. suis in a two-step process. First, in the initial stages, these effects were dependent on bacterial encapsulation, as shown by selective adherence of encapsulated, but not unencapsulated, S. suis to SIV-infected cells. Second, at a later stage of infection, SIV promoted S. suis adherence and invasion of deeper tissues by damaging ciliated epithelial cells. This effect was seen with a highly virulent SIV subtype H3N2 strain but not with a low-virulence subtype H1N1 strain, and it was independent of the bacterial capsule, since an unencapsulated S. suis mutant behaved in a way similar to that of the encapsulated wild-type strain. In conclusion, the PCLS coinfection model established here revealed novel insights into the dynamic interactions between SIV and S. suis during infection of the respiratory tract. It showed that at least two different mechanisms contribute to the beneficial effects of SIV for S. suis, including capsule-mediated bacterial attachment to SIV-infected cells and capsule-independent effects involving virus-mediated damage of ciliated epithelial cells.

Unusual spinal tuberculosis in an Avar Age skeleton (Csongrád-Felgyo, Ürmös-tanya, Hungary): A morphological and biomolecular study.

The paleopathological analysis of a well-preserved young adult female skeleton from the AD 7-8th century (Avar Age) in Hungary revealed multiple lytic lesions in all of the thoracic and lumbar vertebral bodies. The lesions were characterized by smooth marginal zones and space-occupying mass appearance. The considerable loss of spongy bone in the thoracolumbar vertebrae resulted in angular deformity and fusion, characteristic of the healing stage of TB. Osteolytic lesions were also observed on the vertebral processes, ribs and sternum. On the endocranial surface, abnormal blood vessel impressions were revealed, indicating some kind of meningitis. The X-ray and CT analysis of the affected bones detected abnormal structures and cystic zones of destruction. The lesions were however not always bordered by areas of increased density, which is typical in cystic TB. Vertebral remains were also subjected to biomolecular analysis in two different laboratories, which attested the presence of Mycobacterium tuberculosis complex (MTBC) DNA and supported the paleopathological diagnosis of TB. Spoligotyping analysis confirmed the presence of MTBC DNA and more specifically an infection caused by bacteria belonging to the M. tuberculosis lineage. This case study provides new data for the paleoepidemiology of TB in this geographical area and historical period, and draws attention to the great variability of TB lesions in the human skeleton.

Loss of notochordal cell phenotype in 3D-cell cultures: implications for disc physiology and disc repair.

INTRODUCTION: Embryonic notochordal disc nucleus cells (NC) have been identified to protect disc tissue against disc degeneration but in human beings NC phenotype gets lost with aging and the pathophysiological mechanisms are poorly understood. NC may stimulate other cells via soluble factors, and NC-conditioned medium can be used to stimulate matrix production of other disc cells and mesenchymal stem cells and thus may be of special interest for biological disc repair. As this stimulatory effect is associated with the NC phenotype, we investigated how cell morphology and gene-expression of the NC phenotype changes with time in 3D-cell culture. MATERIALS AND METHODS: NC and inner annulus chondrocyte-like cells (CLC) from immature pigtails (freshly isolated cells/tissue, 3D-alginate beads, 3D-clusters) were cultured for up to 16 days under normoxia and hypoxia. Protein-expression was analysed by immunohistology and gene-expression analysis was carried out on freshly isolated cells and cultured cells. Cell morphology and proliferation were analysed by two-photon-laser-microscopy. RESULTS: Two-photon-laser-microscopy showed a homogenous and small CLC population in the inner annulus, which differed from the large vacuole-containing NC in the nucleus. Immunohistology found 93 % KRT8 positive cells in the nucleus and intracellular and pericellular Col2, IL6, and IL12 staining while CLC were KRT8 negative. Freshly isolated NC showed significantly higher KRT8 and CAIII but lower Col2 gene-expression than CLC. NC in 3D-cultures demonstrated significant size reduction and loss of vacuoles with culture time, all indicating a loss of the characteristic NC morphology. Hypoxia reduced the rate of decrease in NC size and vacuoles. Gene-expression of KRT8 and CAIII in NC fell significantly early in culture while Col2 did not decrease significantly within the culture period. In CLC, KRT8 and CAIII gene-expression was low and did not change noticeably in culture, whereas Col2 expression fell with time in culture. CONCLUSIONS: 3D-culture caused a rapid loss of NC phenotype towards a CLC phenotype with disappearance of vacuoles, reduced cell size, increased proliferation, and gene-expression changes. These findings may be related to NC nutritional demands and support the latest hypothesis of NC maturation into CLC opposing the idea that NC get lost in human discs by cell death or apoptosis to be replaced by CLC from the inner annulus.

[Adenocarcinoma of the stomach and neuroendocrine carcinoma of the colon in a 45-year-old male patient suffering from common variable immunodeficiency (CVID) and ulcerative colitis]. / Adenokarzinom des Magens und neuroendokrines Kolonkarzinom bei einem 45-jährigen Patienten mit Common Variable Immunodeficiency (CVID) und Colitis ulcerosa.

Common variable immunodeficiency (CVID) is the most common primary antibody deficient syndrome in adults. Among the broad spectrum of clinical manifestations are recurrent infections, allergies, autoimmune, tumour, pulmonary, liver and gastrointestinal diseases. Here we report the case of a 45-year-old male patient, who has been suffering from ulcerative colitis - likewise recognised as a CVID-associated disease - for many years. He was admitted to our clinic with a rapid progressive reduction of his general condition and a loss of weight. Diagnostic work-up revealed adenocarcinoma of the stomach as well as an undifferentiated neuroendocrine carinoma of the colorectum at the rectosigmoidal junction. Curative resection of the distal stomach and proctolcolectomy were performed. To date, the pathogenesis of the association of many diseases with CVID is still ambiguous. Yet, there is no doubt about the significantly higher incidence of e.g., inflammatory bowel disease or gastric cancer in patients with CVID. Our case highlights that in patients with CVID and obscure deterioration of their general health condition a careful search for especially malignant complications is mandatory although to date there are no precise recommendations for screening.

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model.

INTRODUCTION: Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light (UVL) directly used after injection may be useful. Therefore, this study evaluates a new HA/collagen hydrogel matrix with in situ polymerization after implantation in an established porcine nucleotomy model. MATERIALS AND METHODS: 12 mature minipigs were used. A total of 60 lumbar discs were analyzed. 36 discs underwent partial nucleotomy with a 16G biopsy needle. Of those, 24 discs received matrix (porcine nucleus pulposus collagenous scaffold component and chemically modified HA) which was in situ polymerized using UVL immediately after transplantation. 12 nucleotomized discs and 24 non-nucleotomized discs served as controls. After 24 weeks, animals were killed. X-rays, MRIs, histology, and gene expression analysis were done. RESULTS: Disc height was reduced equally after sole nucleotomy and nucleotomy with HA treatment and in MRIs signal intensity decreased. For both nucleotomy groups, the nucleus histo-degeneration score showed a significant increase compared to controls. In histology, HA treatment resulted in more scarring and inflammation in the annulus. Gene expression of catabolic MMPs was up-regulated, whereas IFN-gamma, IL-6, and IL-1b were unchanged. CONCLUSION: Although nucleotomy and administration of the implant material did not cause generalized inflammation of the disc, localized annular damage with annulus inflammation and scarring resulted in detrimental degenerative disc changes. As a result, therapeutic strategies should strongly focus on the prevention of annular damage or techniques for annular repair to remain disc integrity.

Fatal dengue hemorrhagic fever imported into Germany.

Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador. Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.

Age-related changes in human cervical, thoracal and lumbar intervertebral disc exhibit a strong intra-individual correlation.

INTRODUCTION: Intervertebral disc (IVD) degeneration is characterized as a multifactorial disease, in which the hereditary background is thought to be of high importance. Accordingly, one would expect all spinal levels (lumbar/cervical/thoracal) to be affected by above-average disc degeneration in genetically predisposed individuals. The aim of this study, therefore, was to analyze the amount of degenerative changes in different spine levels in humans from different ages. MATERIALS AND METHODS: In detail, the presence, localization and abundance of histomorphological changes in the annulus fibrosus (AF) and nucleus pulposus (NP) in the cervical (C5/C6), thoracic (T2/T3) and lumbar (L2/L3) spine were investigated in complete autopsy IVD specimens (47 individuals) covering a complete age range (0-95 years). RESULTS: Results indicate that the highest degree of histo-degenerative changes were observed in the NP in all spine levels and showed an age-related expression pattern. With regard to the different spine levels, lumbar disc specimen showed significantly more degenerative changes compared to cervical and thoracic discs, whereas no statistical difference was observed between cervical and thoracic discs. In summary, highest grades of degeneration were observed in lumbar discs (especially in the NP). Intra-individual correlations between the degeneration score in the different levels showed a significant individual concordance. CONCLUSIONS: The intra-individual correlation of degenerative changes in all three examined spine regions further supports the notion that individual, i.e. genetic factors are strong predisposing factor for the development of age-related disc alterations.

Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1ß treated human intervertebral disc cells.

INTRODUCTION: Increased levels of proinflammatory cytokines seem to play a pivotal role in the development of back pain in a subpopulation of patients with degenerative intervertebral disc (IVD) disease. As current treatment options are mostly limited to surgical interventions or conservative treatment, anti-inflammatory substances might offer a novel, more target-orientated therapeutic approach. Triptolide (TPL), a natural substance found in the Chinese medicinal herb Tripterygium wilfordii Hook, has been demonstrated to possess anti-inflammatory effects in various cells, but no studies exist so far for the IVD. Therefore, the aim of this study was to determine the effects of TPL on human IVD cells by analyzing changes in gene expression and underlying molecular mechanisms. MATERIALS AND METHODS: In order to investigate the anti-inflammatory, anabolic and anti-catabolic effect of TPL, dose-dependency experiments (n = 5) and time course experiments (n = 5) were performed on IL-1ß prestimulated human IVD cells and changes in gene expression of IL-6/-8, TNF-α, PGE2S, MMP1/2/3/13, aggrecan and collagen-I/-II were analyzed by real-time RT-PCR. The molecular mechanisms underlying the effects observed upon TPL treatment were investigated by analyzing involvement of Toll-like receptors TLR2/4 (real-time RT-PCR, n = 5), NF-κB, MAP kinases p38, ERK and JNK (immunoblotting and immunocytochemistry, n = 4) as well as RNA polymerase II (immunoblotting, n = 3). RESULTS: Results showed that 50 nM TPL exhibited an anti-inflammatory, anti-catabolic and anabolic effect on the mRNA level for IL-6/-8, PGE2S, MMP1/2/3/13, aggrecan, collagen-II and TLR2/4, with most pronounced changes after 18 h for proinflammatory cytokines and MMPs or 30 h for TLRs and matrix proteins. However, we also observed an up-regulation of TNF-α at higher concentrations. The effects of TPL did not seem to be mediated via an inhibition of NF-κB or a decrease of RNA polymerase II levels, but TPL influenced activity of MAP kinases p38 and ERK (but not JNK) and expression of TLR2/4. CONCLUSIONS: In conclusion, TPL may possess promising potential for the treatment of inflammation-related discogenic back pain in vitro, but its analgetic effect will need to be confirmed in an appropriate in vivo animal model.

Eleonora of Toledo (1522-1562): Evidence for tuberculosis and leishmaniasis co-infection in Renaissance Italy.

Clinical reports for Eleonora of Toledo (1522-1562), the wife of Cosimo I de' Medici, imply that during her 28th year she developed pulmonary tuberculosis, which was complicated by an attack of pernicious malaria, killing her at age 40. Eleonora's autopsy indicated that she had severe lung lesions consistent with chronic pulmonary infection. To clarify her disease status, we performed paleomolecular investigations. Our results identified ancient DNA from the Mycobacterium tuberculosis complex (MTB), along with Leishmania infantum (VL). Our data are of particular interest since in Tuscany the endemic foci of L. infantum are widely distributed and overlapped with those of malaria prior to its eradication. Although we can only speculate about Eleonora's true state of health, this clear evidence of long-term co-infection with MTB and VL is of major medical and biological interest since the co-evolution of the two pathogens and host-pathogen interactions in co-infected individuals are still not fully understood.