1.Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia.
Mathias K FEHR ; Marc BAUMANN ; Michael MUELLER ; Daniel FINK ; Siegfried HEINZL ; Patrick IMESCH ; Konstantin DEDES
Journal of Gynecologic Oncology 2013;24(3):236-241
OBJECTIVE: The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS: Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION: Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.
Biopsy
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Colposcopy
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Disease Progression
;
Electronics
;
Electrons
;
Female
;
Follow-Up Studies
;
Humans
;
Immunosuppression
;
Logistic Models
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Multivariate Analysis
;
Odds Ratio
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Recurrence
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Risk Factors
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Smoke
;
Smoking
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Smoking Cessation
;
Vagina
;
Vulva
2.Seasonality in human semen quality of smokers and non-smokers: effect of temperature.
Robert KÜNZLE ; Michael D MUELLER ; Alexander W HUBER ; Heinz DRESCHER ; Nick A BERSINGER
Asian Journal of Andrology 2004;6(3):243-247
AIMTo analyse the possible effect of seasonal variation on semen parameters.
METHODSThe participants consisted of 1,688 men attending the andrology laboratory between 1991 and 1997 for reduced fertility in the couple. Semen analysis was performed according to the WHO manual. The 84 individual months of the study period were each assigned to one of the three groups according to the average monthly outside temperature; Group A (temperature < 4.4 degrees C), Group B (4.4 degrees C - 13.3 degrees C) and Group C (>13.3 degrees C).
RESULTSWhen comparing the different sperm parameters, the morphology was significantly better in Group C. However, when the smokers were analysed separately, this difference disappeared and significant seasonal variations were found in sperm density, total sperm count, motility and total motile sperm; they were deteriorated in the warmer season. In non-smokers, no such negative effect of increased temperature was observed.
CONCLUSIONSperm quality is influenced by seasonal factors. Increased environmental temperature, (maybe also light exposure) has an additional negative effect on the spermatogenesis in smokers, leading to reduced sperm quality in men with borderline fertility.
Adult ; Fertility ; drug effects ; physiology ; Humans ; Male ; Reference Values ; Seasons ; Semen ; physiology ; Smoking ; physiopathology ; Sperm Count ; Sperm Motility ; Switzerland ; Temperature
3.Multidetector CT Urography in Imaging of the Urinary Tract in Patients with Hematuria.
Michael M MAHER ; Mannudeep K KALRA ; Stefania RIZZO ; Peter R MUELLER ; Sanjay SAINI
Korean Journal of Radiology 2004;5(1):1-10
This review article comprehensively discusses multidetector CT urography protocols and their role in imaging of the urinary tract in patients with hematuria.
Hematuria/etiology/*radiography
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Human
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Incidental Findings
;
Sensitivity and Specificity
;
Tomography, X-Ray Computed/*methods/standards
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Urinary Tract/abnormalities
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Urography/methods/standards
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Urologic Diseases/complications/congenital/radiography
4.TGF-β Signalling is Suppressed under Pro-Hypertrophic Conditions in MSC Chondrogenesis Due to TGF-β Receptor Downregulation
Christian G PFEIFER ; Alexandra KARL ; Maximilian KERSCHBAUM ; Arne BERNER ; Siegmund LANG ; Rupert SCHUPFNER ; Matthias KOCH ; Peter ANGELE ; Michael NERLICH ; Michael B MUELLER
International Journal of Stem Cells 2019;12(1):139-150
BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) become hypertrophic in long term despite chondrogenic differentiation following the pathway of growth plate chondrocytes. This terminal differentiation leads to phenotypically unstable cartilage and was mirrored in vitro by addition of hypertrophy inducing medium. We investigated how intrinsic TGF-β signaling is altered in pro-hypertrophic conditions. METHODS AND RESULTS: Human bone marrow derived MSC were chondrogenically differentiated in 3D culture. At day 14 medium conditions were changed to 1. pro-hypertrophic by addition of T3 and withdrawal of TGF-β and dexamethasone 2. pro-hypertrophic by addition of BMP 4 and withdrawal of TGF-β and dexamethasone and 3. kept in prochondrogenic medium conditions. All groups were treated with and without TGFβ-type-1-receptor inhibitor SB431542 from day 14 on. Aggregates were harvested for histo- and immunohistological analysis at d14 and d28, for gene expression analysis (rt-PCR) on d1, d3, d7, d14, d17, d21 and d28 and for Western blot analysis on d21 and d28. Induction of hypertrophy was achieved in the pro-hypertrophic groups while expression of TGFβ-type-1- and 2-receptor and Sox 9 were significantly downregulated compared to pro-chondrogenic conditions. Western blotting showed reduced phosphorylation of Smad 2 and 3 in hypertrophic samples, reduced TGF-β-1 receptor proteins and reduced SOX 9. Addition of SB431542 did not initiate hypertrophy under pro-chondrogenic conditions, but was capable of enhancing hypertrophy when applied simultaneously with BMP-4. CONCLUSIONS: Our results suggest that the enhancement of hypertrophy in this model is a result of both activation of pro-hypertrophic BMP signaling and reduction of anti-hypertrophic TGFβ signaling.
Blotting, Western
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Bone Marrow
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Cartilage
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Chondrocytes
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Chondrogenesis
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Dexamethasone
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Down-Regulation
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Gene Expression
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Growth Plate
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Humans
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Hypertrophy
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In Vitro Techniques
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Mesenchymal Stromal Cells
;
Phosphorylation
5.Techniques, Clinical Applications and Limitations of 3D Reconstruction in CT of the Abdomen.
Michael M MAHER ; Mannudeep K KALRA ; Dushyant V SAHANI ; James J PERUMPILLICHIRA ; Stephania RIZZO ; Sanjay SAINI ; Peter R MUELLER
Korean Journal of Radiology 2004;5(1):55-67
Enhanced z-axis coverage with thin overlapping slices in breath-hold acquisitions with multidetector CT (MDCT) has considerably enhanced the quality of multiplanar 3D reconstruction. This pictorial essay describes the improvements in 3D reconstruction and technical aspects of 3D reconstruction and rendering techniques available for abdominal imaging. Clinical applications of 3D imaging in abdomen including liver, pancreaticobiliary system, urinary and gastrointestinal tracts and imaging before and after transplantation are discussed. In addition, this article briefly discusses the disadvantages of thin-slice acquisitions including increasing numbers of transverse images, which must be reviewed by the radiologist.
Adult
;
Aged
;
Biliary Tract/radiography
;
Female
;
Gastrointestinal Tract/radiography
;
Human
;
Image Processing, Computer-Assisted/*methods
;
Imaging, Three-Dimensional
;
Liver/radiography
;
Liver Transplantation/radiography
;
Male
;
Middle Aged
;
Pancreas/radiography
;
Radiography, Abdominal/*methods
;
Tomography, X-Ray Computed/*methods
;
Urography/methods
6.Gigantic Genomes Provide Empirical Tests of Transposable Element Dynamics Models
Wang JIE ; W.Itgen MICHAEL ; Wang HUIJU ; Gong YUZHOU ; Jiang JIANPING ; Li JIATANG ; Sun CHENG ; K.Sessions STANLEY ; Mueller Lockridge RACHEL
Genomics, Proteomics & Bioinformatics 2021;19(1):123-139
Transposable elements (TEs) are a major determinant of eukaryotic genome size. The collective properties of a genomic TE community reveal the history of TE/host evolutionary dynamics and impact present-day host structure and function, from genome to organism levels. In rare cases, TE community/genome size has greatly expanded in animals, associated with increased cell size and changes to anatomy and physiology. Here, we characterize the TE landscape of the genome and transcriptome in an amphibian with a giant genome—the caecilian Ichthyophis bannanicus, which we show has a genome size of 12.2 Gb. Amphibians are an important model sys-tem because the clade includes independent cases of genomic gigantism. The I. bannanicus genome differs compositionally from other giant amphibian genomes, but shares a low rate of ectopic recombination-mediated deletion. We examine TE activity using expression and divergence plots;TEs account for 15%of somatic transcription, and most superfamilies appear active. We quantify TE diversity in the caecilian, as well as other vertebrates with a range of genome sizes, using diver-sity indices commonly applied in community ecology. We synthesize previous models that integrate TE abundance, diversity, and activity, and test whether the caecilian meets model predictions for genomes with high TE abundance. We propose thorough, consistent characterization of TEs to strengthen future comparative analyses. Such analyses will ultimately be required to reveal whether the divergent TE assemblages found across convergent gigantic genomes reflect fundamental shared features of TE/host genome evolutionary dynamics.
7.Etiology, 3-Month Functional Outcome and Recurrent Events in Non-Traumatic Intracerebral Hemorrhage
Martina B. GOELDLIN ; Achim MUELLER ; Bernhard M. SIEPEN ; Madlaine MUELLER ; Davide STRAMBO ; Patrik MICHEL ; Michael SCHAERER ; Carlo W. CEREDA ; Giovanni BIANCO ; Florian LINDHEIMER ; Christian BERGER ; Friedrich MEDLIN ; Roland BACKHAUS ; Nils PETERS ; Susanne RENAUD ; Loraine FISCH ; Julien NIEDERHAEUSER ; Emmanuel CARRERA ; Elisabeth DIRREN ; Christophe BONVIN ; Rolf STURZENEGGER ; Timo KAHLES ; Krassen NEDELTCHEV ; Georg KAEGI ; Jochen VEHOFF ; Biljana RODIC ; Manuel BOLOGNESE ; Ludwig SCHELOSKY ; Stephan SALMEN ; Marie-Luise MONO ; Alexandros A. POLYMERIS ; Stefan T. ENGELTER ; Philippe LYRER ; Susanne WEGENER ; Andreas R. LUFT ; Werner Z’GRAGGEN ; David BERVINI ; Bastian VOLBERS ; Tomas DOBROCKY ; Johannes KAESMACHER ; Pasquale MORDASINI ; Thomas R. MEINEL ; Marcel ARNOLD ; Javier FANDINO ; Leo H. BONATI ; Urs FISCHER ; David J. SEIFFGE ;
Journal of Stroke 2022;24(2):266-277
Background:
and Purpose Knowledge about different etiologies of non-traumatic intracerebral hemorrhage (ICH) and their outcomes is scarce.
Methods:
We assessed prevalence of pre-specified ICH etiologies and their association with outcomes in consecutive ICH patients enrolled in the prospective Swiss Stroke Registry (2014 to 2019). Results We included 2,650 patients (mean±standard deviation age 72±14 years, 46.5% female, median National Institutes of Health Stroke Scale 8 [interquartile range, 3 to 15]). Etiology was as follows: hypertension, 1,238 (46.7%); unknown, 566 (21.4%); antithrombotic therapy, 227 (8.6%); cerebral amyloid angiopathy (CAA), 217 (8.2%); macrovascular cause, 128 (4.8%); other determined etiology, 274 patients (10.3%). At 3 months, 880 patients (33.2%) were functionally independent and 664 had died (25.1%). ICH due to hypertension had a higher odds of functional independence (adjusted odds ratio [aOR], 1.33; 95% confidence interval [CI], 1.00 to 1.77; P=0.05) and lower mortality (aOR, 0.64; 95% CI, 0.47 to 0.86; P=0.003). ICH due to antithrombotic therapy had higher mortality (aOR, 1.62; 95% CI, 1.01 to 2.61; P=0.045). Within 3 months, 4.2% of patients had cerebrovascular events. The rate of ischemic stroke was higher than that of recurrent ICH in all etiologies but CAA and unknown etiology. CAA had high odds of recurrent ICH (aOR, 3.38; 95% CI, 1.48 to 7.69; P=0.004) while the odds was lower in ICH due to hypertension (aOR, 0.42; 95% CI, 0.19 to 0.93; P=0.031).
Conclusions
Although hypertension is the leading etiology of ICH, other etiologies are frequent. One-third of ICH patients are functionally independent at 3 months. Except for patients with presumed CAA, the risk of ischemic stroke within 3 months of ICH was higher than the risk of recurrent hemorrhage.