15 research outputs found
Diagnostic Dilemma in a Patient with Jaundice: How to Differentiate between Autoimmune Pancreatitis, Primary Sclerosing Cholangitis and Pancreas Carcinoma
A 68-year-old male patient was referred to our institution in May 2011 for a suspected tumor in the pancreatic head with consecutive jaundice. Using magnetic resonance imaging, further differentiation between chronic inflammation and a malignant process was not possible with certainty. Apart from cholestasis, laboratory studies showed increased values for CA 19-9 to 532 U/ml (normal <37 U/ml) and hypergammaglobulinemia (immunoglobulin G, IgG) of 19.3% (normal 8.0–15.8%) with an elevation of the IgG4 subtype to 2,350 mg/l (normal 52–1,250 mg/l). Endoscopic retrograde cholangiopancreatography revealed a prominent stenosis of the distal ductus hepaticus communis caused by pancreatic head swelling and also a bihilar stenosis of the main hepatic bile ducts. Cytology demonstrated inflammatory cells without evidence of malignancy. Under suspicion of autoimmune pancreatitis with IgG4-associated cholangitis, immunosuppressive therapy with steroids and azathioprine was started. Follow-up endoscopic retrograde cholangiopancreatography after 3 months displayed regressive development of the diverse stenoses. Jaundice had disappeared and blood values had returned to normal ranges. Moreover, no tumor of the pancreatic head was present in the magnetic resonance control images. Due to clinical and radiological similarities but a consecutive completely different prognosis and therapy, it is of fundamental importance to differentiate between pancreatic cancer and autoimmune pancreatitis. Especially, determination of serum IgG4 levels and associated bile duct lesions induced by inflammation should clarify the diagnosis of autoimmune pancreatitis and legitimate immunosuppressive therapy
Evaluation of left and right ventricular parameters by electron-beam computed tomography in patients with passive epicardial constraint
GesamtdissertationDie chronische Herzinsuffizienz gehört zu den weltweit häufigsten Erkrankungen
mit steigender Inzidenz. Trotz optimaler medikamentöser Therapie ist die
Lebenserwartung von Patienten mit manifester Herzinsuffizienz verkĂĽrzt.
Pathophysiologisch fĂĽhrt eine systolische Dysfunktion des Myokards
unterschiedlicher Genese über eine Erhöhung der ventrikulären Wandspannung zu
einer Aktivierung von neuroendokrinen Anpassungsmechanismen, die kurzfristig
fĂĽr eine Stabilisierung der Myokardfunktion sorgen, jedoch langfristig die
Progression der Herzinsuffizienz herbeifĂĽhren. Das Ziel dieser Arbeit ist eine
neue Therapieoption, die passive Kardiomyoplastie (CorCap, Cardiac Support
Device, kurz: CSD; Acorn Cardiovascular Inc., St. Paul, MN) mit radiologischen
Verfahren zu evaluieren. Während dieser Operation wird dem Patienten ein
elastisches Polyesternetz um das Herz implantiert, mit dem Zweck, dem
Remodeling-Effekt sowie dem Anstieg der Wandspannung entgegenzuwirken und
damit den weiteren Fortschritt der Erkrankung zu limitieren. In den dieser
Arbeit vorliegenden Studien wurden Patienten mit einer dilatativen
Kardiomyopathie (DCMP) vor und mindestens zu einem Zeitpunkt nach der
Implantation des HerzunterstĂĽtzungssystems mittels
Elektronenstrahlcomputertomographie (EBCT) untersucht. Bestimmt wurden die
links- und rechtsventrikulären Ventrikelvolumina sowie die Ejektionsfraktion
und Myokarddicke. Des Weiteren wurden die regionale Wandkinetik und die
Ventrikelgeometrie ermittelt. Der Vorteil der EBCT besteht in kurzen
Bildakquisitionszeiten und der Möglichkeit, Patienten mit metallischen
Implantaten zu untersuchen. AuĂźerdem fĂĽhren die im Vergleich zur
Magnetresonanztomographie kĂĽrzeren Untersuchungszeiten und die offenere Bauart
des EBCT zu einer höheren Akzeptanz durch die Patienten. Die Messungen mittels
EBCT zeigten postoperativ eine signifikante Abnahme der links- und
rechtsventrikulären Volumina mit gleichzeitiger Zunahme der Ejektionsfraktion
sowie einer Verbesserung der regionalen Kontraktilität. Die ermittelten
FĂĽllungskurven zeigten keinen hinreichenden Anhalt fĂĽr die Entwicklung einer
konstriktiven Physiologie nach der Netzimplantation. Zusammenfassend lässt
sich sagen, dass die passive Kardiomyoplastie zu einer kurz- und
mittelfristigen Normalisierung morphologischer und funktioneller Parameter
beider Ventrikel fĂĽhrt. Ob dieses Verfahren eine alternative Therapieoption
bei Patienten mit DCMP darstellt und auch zu einer erhöhten
Ăśberlebenswahrscheinlichkeit fĂĽhrt, muss die Auswertung doppeltverblindeter
Langzeitstudien im Vergleich zu etablierten Behandlungsmethoden zeigen.Congestive heart failure is one of the most common diseases worldwide with
increasing incidence. Although drug therapy is quite effective, the mortality
of patients with progressive heart failure is still high. The loss of systolic
myocardial function leads to an increase of wall stress and to an activation
of the neuroendocrine system with a long term progression. The aim of the
study is the radiological evaluation of a new surgical technique, the cardiac
support device (CorCap, Cardiac Support Device; Acorn Cardiovascular Inc., St.
Paul, MN). The key goal of this surgical procedure is reduction of the wall
stress and reversion of the remodelling effect due to the biocompatible
compliant mesh graft which is wrapped around the ventricles. Patients with
dilated cardiomyopathy are referred to electron beam computer tomography
(EBCT) before surgery and twice after the mesh graft implantation. Analysed
parameters are volumes of the left and right ventricles, ejection fraction and
the myocardial wall thickening. The advantage of EBCT lies in the short
acquisition time per CT section as well as the possibility to examine patients
with contraindications for MRI. The analysis indicates a significant decrease
of left and right ventricular volumes after surgery with simultaneous increase
of ejection fraction and regional contractility. Ventricular filling shows no
evidence of constriction. In summary, the cardiac support device leads to a
short and mid term normalization of functional parameters in both ventricles
although it is still unclear whether the new therapy is associated with an
increase in survival
S100A9 is a Biliary Protein Marker of Disease Activity in Primary Sclerosing Cholangitis
<div><h3>Background and Aims</h3><p>Bile analysis has the potential to serve as a surrogate marker for inflammatory and neoplastic disorders of the biliary epithelium and may provide insight into biliary pathophysiology and possible diagnostic markers. We aimed to identify biliary protein markers of patients with primary sclerosing cholangitis (PSC) by a proteomic approach.</p> <h3>Methods</h3><p>Bile duct-derived bile samples were collected from PSC patients (n = 45) or patients with choledocholithiasis (n = 24, the control group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to analyse the proteins, 2-D-gel patterns were compared by densitometry, and brush cytology specimens were analysed by RT-PCR.</p> <h3>Results</h3><p>A reference bile-duct bile proteome was established in the control group without signs of inflammation or maligancy comprising a total of 379 non-redundant biliary proteins; 21% were of unknown function and 24% had been previously described in serum. In PSC patients, the biliary S100A9 expression was elevated 95-fold (p<0.005), serum protein expression was decreased, and pancreatic enzyme expression was unchanged compared to controls. The S100A9 expression was 2-fold higher in PSC patients with high disease activity than in those with low activity (p<0.05). The brush cytology specimens from the PSC patients with high disease activity showed marked inflammatory activity and leukocyte infiltration compared to the patients with low activity, which correlated with S100A9 mRNA expression (p<0.05).</p> <h3>Conclusions</h3><p>The bile-duct bile proteome is complex and its analysis might enhance the understanding of cholestatic liver disease. Biliary S100A9 levels may be a useful marker for PSC activity, and its implication in inflammation and carcinogenesis warrants further investigation.</p> </div
Correlation between biliary proteins and disease activity in PSC patients.
<p>Bile from PSC patients showed a marked increase in biliary protein content. (<b>A</b>) Box plots of the protein concentration per volume show a marked increase for the PSC patients. If the PSC patients were classified based on disease activity, either by endoscopic findings (<b>C</b>) or by Mayo Risk score (<b>E</b>), the corresponding biliary protein concentrations showed significantly greater concentrations in the patients with high PSC activity than in those with low activity. If the bile samples were normalised by the bile-acid content, the results were similar (<b>B,</b> controls versus all the PSC patients; <b>D,</b> PSC patients classified by endoscopic findings; <b>F,</b> PSC patients classified by Mayo Risk Score). Box plots of the protein concentration normalised by the BA concentration. (control = 24, PSC = 45, low MRS = 25, intermediate MRS = 20; low endoscopic = 26; high endoscopy activity = 19; ns = not significant; *p<0.05; **p<0.005).</p
Radiofrequency Ablation of Metastases from Renal Cell Carcinoma: Technique, Complications, and Midterm Outcome
Identification of S100A9 as a marker of disease activity.
<p>The protein patterns among the PSC and choledocholithiasis (control) patients were compared. Intensities of 25 spots uniquely identified by mass spectrometry were measured using densitometry. The spot resembling S100A9 was markedly upregulated in the PSC patients with high activity (<b>B</b>) compared to those with low activity (<b>A</b>). Circled spots: haemoglobin (red), S100A9 (yellow), serum proteins (black), pancreatic enzymes (green), and others (blue). An evaluation of the relative amount of S100A9 in the spots demonstrated a clear upregulation of S100A9 in the PSC patients (<b>C</b>). Subgroup analyses of the PSC patients performed according to disease activity revealed a distinct increase in S100A9 in the PSC patients with high disease activity relative to those with low disease activity (<b>D</b>). The PSC patients were also stratified by their Mayo risk scores. (n: control = 6; PSC = 18; low MRS = 13; intermediate MRS = 5; low endoscopic = 12; high endoscopic = 6). The total S100 levels were significantly elevated in the PSC patients PSC (<b>F</b>) (*p<0.05; **p<0.005). The RT-PCR analyses of the brush cytology samples demonstrated marked upregulation of S100A9 expression (n = 8, 4 in the low activity group and 4 in the high activity group; p<0.05) (<b>G</b>).The brush cytology from the patients with unclear strictures demonstrated corresponding cytological findings. The cytology from a patient with low disease activity showed regular epithelial cells (arrowheads) (<b>H</b>), whereas the cytology from a patient with high disease activity showed leukocyte infiltrate (arrows) and altered epithelial cells (<b>I</b>).</p
Patient characteristics.
<p>MRS Mayo risk score; PSC low and high activities refer to the endoscopic finding.</p
A Frequent <em>PNPLA3</em> Variant Is a Sex Specific Disease Modifier in PSC Patients with Bile Duct Stenosis
<div><p>Background & Aims</p><p>Primary sclerosing cholangitis predominantly affects males and is an important indication for liver transplantation. The rs738409 variant (I148M) of the <i>PNPLA3</i> gene is associated with alcoholic and non-alcoholic liver disease and we evaluated its impact on the disease course of PSC.</p> <p>Methods</p><p>The I148M polymorphism was genotyped in 121 German PSC patients of a long-term prospective cohort and 347 Norwegian PSC patients.</p> <p>Results</p><p>In the prospective German cohort, actuarial survival free of liver transplantation was significantly reduced for I148M carriers (p = 0.011) compared to wildtype patients. This effect was restricted to patients with severe disease, as defined by development of dominant stenosis (DS) requiring endoscopic intervention. DS patients showed markedly decreased survival (p = 0.004) when carrying the I148M variant (I148M: mean 13.8 years; 95% confidence interval: 11.6–16.0 vs. wildtype: mean 18.6 years; 95% confidence interval: 16.3–20.9) while there was no impact on survival in patients without a DS (p = 0.87). In line with previous observations of sex specific effects of the I148M polymorphism, the effect on survival was further restricted to male patients (mean survival 11.9 years; 95% confidence interval: 10.0–14.0 in I148M carriers vs. 18.8 years; 95% confidence interval: 16.2–21.5 in wildtype; p<0.001) while female patients were unaffected by the polymorphism (p = 0.65). These sex specific findings were validated in the Norwegian cohort (p = 0.013).</p> <p>Conclusions</p><p>In male PSC patients with severe disease with bile duct stenosis requiring intervention, the common I148M variant of the <i>PNPLA3</i> gene is a risk factor for reduced survival.</p> </div
Bile purification and identification of biliary proteins.
<p>(<b>A</b>) Comparison of serum (S), plasma (P), and bile duct-derived bile proteins (B) from two choledocholithiasis patients demonstrates many similar expressed proteins; however, the protein composition differs between the serum and bile samples. (<b>B</b>) Albumin and IgG depletion and purification for the crude bile duct-derived bile samples. The purification of the bile samples was monitored using 1-D silver stained gels, and the crude bile samples (Lane 1) were compared to the precipitated samples depleted of albumin and IgG. The arrow indicates the marked reduction in albumin. (<b>C</b>) A mixture of bile samples was separated by 1-D Gel electrophoresis, cut into the depicted slices and analysed by mass spectrometry. The 301 identified proteins with a Mascot score >100 were classified according to reported subcellular localisation (<b>D</b>), the biological processes in which they are involved (<b>E</b>) and the pathways the majority of proteins are involved (<b>F</b>).</p
2-D SDS-PAGE analysis of purified bile.
<p>2-D gels of biliary proteins. pH range of the first-dimension isoelectric focusing gel is shown at the bottom, and the sizes of the molecular mass standards (in kDa) for the second dimension are indicated on the left. The proteins corresponding to the spots on the gels (circled in blue) were identified by mass spectrometry. (<b>A</b>) 500 µg of protein was separated on a gradient from pH 3–11 (non-linear). To identify less abundant proteins, (<b>B</b>), 1 mg of protein was separated; more prominent spots were excluded, and the less prominent spots were identified by mass spectrometry.</p