Zur pathologischen Anatomie der Torula-Meningoencephalitis

Es werden 4 Fälle von Torula-Meningoencephalitis beschrieben. Die histologische Untersuchung ergab, daß, entgegen der bisher herrschenden Lehrmeinung, gliöse Reaktionen am Hirngewebe beobachtet werden können. Wird die Pia-Glia-Membran des Virchow-Robin schen Raumes von den Erregern durchdrungen, so kommt es zur Bildung von Monstregliazellen, unter Umständen auch zur Wucherung mikrogliöser Elemente. Bezüglich der Prozeßausbreitung im Nervensystem ist festzustellen, daß diese vorwiegend nach dem Prinzip der Fortleitung von den Meningen her erfolgt. Indessen muß zur Erklärung isolierter Herdchen in den tieferen Hirnbezirken auch eine hämatogene Metastasierung angenommen werden.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41753/1/415_2004_Article_BF00217990.pd

Macular hole surgery: an analysis of risk factors for the anatomical outcome with special emphasis on the experience of the surgeon

Purpose: The aim of this study was to evaluate risk factors for the anatomical and functional outcomes of macular hole (MH) surgery with special emphasis on the experience of the surgeon. Methods: A total of 225 surgeries on idiopathic MHs (IMHs) performed by 6 surgeons with a mean follow-up period of 20.5 months were reviewed in this retrospective study. Outcome parameters focused on IMH closure, complications and visual acuity improvement. The results of MH surgeries performed by experienced surgeons were compared to those of surgeons in training. Results: The average MH size was 381 µm (standard deviation [SD]=168). Brilliant blue G (BBG) for internal limiting membrane (ILM) staining was used in 109 (48%) eyes and indocyanine green (ICG) in 116 (52%) eyes. As endotamponade, 20% SF6 was used in 38 (17%) cases, 16% C2F6 in 33 (15%) cases and 16% C3F8 in 154 (68%) cases. IMH closure was achieved in 194 eyes (86%). Mean preoperative visual acuity was 0.84 logarithm of the minimum angle of resolution (log MAR; SD=0.29, range: 0.3–1.5); surgery led to a mean improvement of 0.40 (SD=0.37) log MAR. Although the MH closure rate was the same using BBG or ICG for ILM peeling, visual acuity improvement was better in eyes peeled with BBG compared to eyes peeled with ICG (log MAR: BBG: 0.38 [95% CI: 0.32, 0.44] vs ICG: 0.48 [95% CI: 0.42, 0.54], P=0.029). Surgeons with previous experience in vitreoretinal surgery of ≥6 years achieved better visual outcomes compared to surgeons with 0–3 years of experience, regardless of the MH size, preoperative visual acuity, time to follow-up or dye used for ILM peeling (0–3 years [0.27, ∆log MAR] vs ≥6 years [0.43, ∆log MAR], P=0.009). Conclusion: Our results indicate that vitrectomy with ILM peeling performed by non-experienced surgeons is a safe procedure leading to good anatomical and functional results. Very experienced surgeons may achieve even better functional outcomes

Analysis of long-term mortality after total body irradiation-based and melphalan-based chemotherapy conditioning for acute myeloid leukemia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment option for selected patients with acute myeloid leukemia. Yet, the influence of total body irradiation (TBI)-based conditioning as compared to non-TBI-based conditioning on long-term mortality is unclear. We retrospectively evaluated outcomes after TBI-based (n = 91) and non-TBI-based conditioning (melphalan-based, n = 248) for 1st allo-HSCT patients transplanted at the University Hospital Regensburg between 1999 and 2020. TBI was performed with an average dose rate of 4 cGy/min. Median follow-up was 8.3 years (interquartile range, 4.8–12.9 years). Cumulative incidence rates of 5-year non-relapse mortality (NRM) were 17% (95% confidence interval, CI, 10–25) and 33% (95% CI, 27–40) after TBI- and non-TBI-based conditioning (P < 0.001). Five-year cumulative incidences of relapse (CIR) were 42% (95% CI, 32–52) and 29% (95% CI, 23–35) after TBI- and non-TBI-based conditioning (P = 0.030). The 5-year OS was 54% (95% CI, 43–64) and 55% (95% CI, 48–62) after TBI- and non-TBI-based conditioning. Both groups had similar 100-day acute graft-versus-host disease (aGVHD, 43% vs. 40%) and 5-year chronic GVHD (34% vs. 36%). The multivariable regression models found no associations of TBI with the outcomes NRM, CIR, PFS, OS, aGVHD, and cGVHD. TBI was no risk factor for NRM, even including mortality caused by secondary malignancies. NRM was influenced by patient age, advanced disease status, and the use of female donors for male recipients. TBI- and non-TBI-based conditioning appear to be equally effective and tolerable for AML patients eligible for 1st allo-HSCT

Development of a human mitochondrial oligonucleotide microarray (h-MitoArray) and gene expression analysis of fibroblast cell lines from 13 patients with isolated F1Fo ATP synthase deficiency

<p>Abstract</p> <p>Background</p> <p>To strengthen research and differential diagnostics of mitochondrial disorders, we constructed and validated an oligonucleotide microarray (h-MitoArray) allowing expression analysis of 1632 human genes involved in mitochondrial biology, cell cycle regulation, signal transduction and apoptosis. Using h-MitoArray we analyzed gene expression profiles in 9 control and 13 fibroblast cell lines from patients with F₁F_oATP synthase deficiency consisting of 2 patients with mt9205ΔTA microdeletion and a genetically heterogeneous group of 11 patients with not yet characterized nuclear defects. Analysing gene expression profiles, we attempted to classify patients into expected defect specific subgroups, and subsequently reveal group specific compensatory changes, identify potential phenotype causing pathways and define candidate disease causing genes.</p> <p>Results</p> <p>Molecular studies, in combination with unsupervised clustering methods, defined three subgroups of patient cell lines – M group with mtDNA mutation and N1 and N2 groups with nuclear defect. Comparison of expression profiles and functional annotation, gene enrichment and pathway analyses of differentially expressed genes revealed in the M group a transcription profile suggestive of synchronized suppression of mitochondrial biogenesis and G1/S arrest. The N1 group showed elevated expression of complex I and reduced expression of complexes III, V, and V-type ATP synthase subunit genes, reduced expression of genes involved in phosphorylation dependent signaling along MAPK, Jak-STAT, JNK, and p38 MAP kinase pathways, signs of activated apoptosis and oxidative stress resembling phenotype of premature senescent fibroblasts. No specific functionally meaningful changes, except of signs of activated apoptosis, were detected in the N2 group. Evaluation of individual gene expression profiles confirmed already known <it>ATP6/ATP8 </it>defect in patients from the M group and indicated several candidate disease causing genes for nuclear defects.</p> <p>Conclusion</p> <p>Our analysis showed that deficiency in the ATP synthase protein complex amount is generally accompanied by only minor changes in expression of ATP synthase related genes. It also suggested that the site (mtDNA vs nuclear DNA) and the severity (ATP synthase content) of the underlying defect have diverse effects on cellular gene expression phenotypes, which warrants further investigation of cell cycle regulatory and signal transduction pathways in other OXPHOS disorders and related pharmacological models.</p

Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr