A hierarchic approach for experimental investigations into the pathogenesis of acute pancreatitis

The complexity of pathogenesis and clinical observations of acute pancreatitis demands a simultaneous experimental investigation at various structural and functional levels. The induction of acute pancreatitis by transformation of a pancreatic edema after short-term pancreatic ischemia was used for studies on the contribution of an alteration of energy metabolism to pathogenesis. The experiments demonstrate that in 70 percent of the rats the pancreatic edema was transformed into acute pancreatitis by 20 min ischemia. This was checked by morphological and enzymic means. For studying the influence of short-term ischemia in the cellular metabolism of acinar cells, pancreatic exocrine cells have been isolated from normal pancreas or that altered by ischemia. These cells were morphologically characterized and their capacity of energy metabolism was quantified.     

Individual receptor profiling as a novel tool to support diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC)

Purpose

Dysregulation of neurotransmitter receptors may contribute to bladder overactivity (OAB) symptoms. To address the question whether specific receptor expression patterns are associated with bladder pain syndrome/interstitial cystitis (BPS/IC), we examined the expression of muscarinic, purinergic and histamine receptors in the detrusor.

Methods

Detrusor receptor expression was investigated in bladder biopsies of female BPS/IC patients (n?=?44; age 60.64?±?13.78, mean?±?SD) and carcinoma patients (n?=?11; age 58.91?±?12.72) undergoing cystectomy. Protein expression of muscarinic (M2, M3), purinergic (P2X1–3) and histamine receptors (H1, H2) was analysed by confocal immunofluorescence, and gene expression was quantified by real-time polymerase chain reaction (qPCR).

Results

M2, P2X1, P2X2 and H1 receptor immunoreactivity (-IR) was significantly enhanced in BPS/IC compared to the control group, while there was no difference for M3-, P2X3- and H2-IR. We calculated a score, which separated BPS/IC from control patients with an AUC of 89.46%, showing 84.09% sensitivity and 90.91% specificity. Patients had a 9.25 times enhanced calculated risk for BPS/IC. In addition, two patient subgroups (M2?>?M3 and M3?>?M2) were observed, which differed in associated purinergic and histamine receptor expression.

Conclusions

M2, P2X1, P2X2 and H1 were significantly upregulated in BPS/IC patients, and H2 was occasionally highly overexpressed. There was no significant correlation between receptor protein and gene expression, implying posttranslational mechanisms being responsible for the altered receptor expressions. On the basis of individual receptor profiles, upregulated receptors could be targeted by monotherapy or combination therapy with already approved receptor inhibitors, thereby promoting tailored therapy for patients suffering from BPS/IC-like symptoms.     

Visual motion responses in the posterior cingulate sulcus: a comparison to V5/MT and MST

Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.     

Aortic valve replacement for aortic regurgitation and stenosis, in patients with severe left ventricular dysfunction.

OBJECTIVE: Aortic valve replacement for aortic valve stenosis (AS) and regurgitation (AR) in patients with severe left ventricular (LV) dysfunction contains an increased risk. Few data are available on the outcome of such patients. METHODS: Fifty-five consecutive patients with severe LV dysfunction (ejection fraction, EF; <30%) and aortic valve replacement for AS (n=35) or AR (n=20) were investigated between 1994 and 2001. EF was 25+/-5%, mean transvalvular gradient 26+/-6mmHg (AS), aortic valve area 0.66+/-0.18cm(2) (AS), cardiac index (CI) 2.4+/-0.9l/min/m(2), enddiastolic LV diameter (LVEDD) 64+/-8mm and endsystolic LV diameters (LVESD) was 55+/-3mm. Ninety percent of patients were in New York Heart Association (NYHA) functional class III/IV at admission to the hospital. Concomitant coronary artery bypass grafts (CABG) were performed in 14 patients. Follow-up examinations including chest X-ray, echocardiography, exercise testing, were performed among survivors. RESULTS: The survival rates for AS were: 1-year 76%, 2-year 68.8%, 5-year 64.2%; for AR: 1-year 94.4%, 2-year 86.5%, 5-year 74.2%. NYHA functional class improved from 90% in class III/IV to 45 (AR group) and 24% (AS group) at follow-up (P<0.02). The LVEDD decreased to 54+/-8mm after 1 year. The EF improved to 38+/-4 (AR group) and 40+/-5% (AS group) at follow-up. CONCLUSIONS: Despite severe LV dysfunction, increased 1-year mortality especially in the AS group, aortic valve replacement was associated with improved functional status, symptoms and EF in both groups and in most patients. We, therefore, conclude that aortic valve replacement in patients with severe LV dysfunction can be performed with acceptable risk.     

Off-Pump Extraanatomic Bypass from the Ascending to the Descending Aorta for Re-Operation of Interrupted Aortic Arch in an Adolescent

Abstract   The appearance of re-stenosis after repair of an interrupted aortic arch may be a surgical challenge due to adhesions. Here, we describe an approach using off-pump coronary artery bypass grafting techniques to reach the descending aorta through a median sternotomy in a patient with aortic arch stenosis after conduit repair. The 17-year-old patient with diagnoses of interrupted aortic arch and ventricular septal defect presented after two previous operations (one left lateral thoracotomy and one median sternotomy) with a stenosed vascular graft between ascending and descending aorta. Surgery was done via re-sternotomy without cardio-pulmonary bypass. An extraanatomic graft was used to connect ascending and descending aorta. When performing the distal anastomosis, the heart was exposed using a standard suction device. This case demonstrates that the use of modern techniques may facilitate surgical approaches dramatically. In our opinion the above-described technique is the first choice for all patients requiring arch repair following multiple previous operations, performed via sternotomy and thoracotomy.     

Bichat guidelines for the clinical management of brucellosis and bioterrorism-related brucellosis

Interest in Brucella species as a biological weapon stems from the fact that airborne transmission of the agent is possible. It is highly contagious and enters through mucous membranes such as the conjunctiva, oropharynx, respiratory tract and skin abrasions. It has been estimated that 10-100 organisms only are sufficient to constitute an infectious aerosol dose for humans. Signs and symptoms are similar in patients whatever the route of transmission and are mostly non-specific. Symptoms of patients infected by aerosol are indistinguishable from those of patients infected by other routes. Regimens containing doxycycline plus streptomycin or doxycycline plus rifampin are effective for most forms of brucellosis. Isolation of patients is not necessary. Trimethoprim-sulfamethoxazole and fluoroquinolones also have good results against Brucella, but are associated with high relapse rates when used as monotherapy. The combination of ofloxacin plus rifampicin is associated with good results. Even if there is little evidence to support its utility for post-exposure prophylaxis, doxycycline plus rifampicin is recommended for 3 to 6 weeks.     

Electromagnetic navigation during flexible bronchoscopy

BACKGROUND: Flexible bronchoscopy is routinely utilized in the diagnosis and treatment of various lung diseases. Nondiagnostic bronchoscopy leads to more invasive interventions, such as transthoracic needle aspiration, mediastinoscopy or even thoracotomy. Electromagnetic navigation is a novel technology that facilitates approaching peripheral lung lesions, which are difficult to sample by conventional means. The navigation system involves creating an electromagnetic field around the chest and localizing an endoscopic tool using a microsensor overlaid upon previously acquired CT images. OBJECTIVES: To determine the practicality, accuracy and safety of real-time electromagnetic navigation, coupled with previously acquired 3D CT images, in locating artificially created peripheral lung lesions in a swine model. METHODS: Peripheral lung lesions were created in four swine models by insertion of a metal tube (1 x 10 mm) via a transthoracic approach. An electromagnetic field was created by placing the animal on an electromagnetic location board. A position sensor incorporated into the distal tip of a dedicated tool was used to navigate to the various target lesions. Information gathered in real time during bronchoscopy was presented on a monitor simultaneously by displaying previously acquired CT images. Upon reaching the target lesion, biopsies were performed and the functionality and safety of the superDimension/Bronchus System was observed and documented. RESULTS: The registration accuracy expressed by the fiducial target registration error, expressing both the registration quality and the stability of fiducial (registration) points, was 4.5 mm on average. No adverse effects, such as pneumothorax or internal bleeding, were encountered in any of the animals in this study. CONCLUSIONS: Real-time electromagnetic positioning technology coupled with previously acquired CT images is an accurate technology added to standard bronchoscopy to assist in reaching peripheral lung lesions and performing biopsies.     

Recruitment of DNA methyltransferase I to DNA repair sites

In mammalian cells, the replication of genetic and epigenetic information is directly coupled; however, little is known about the maintenance of epigenetic information in DNA repair. Using a laser microirradiation system to introduce DNA lesions at defined subnuclear sites, we tested whether the major DNA methyltransferase (Dnmt1) or one of the two de novo methyltransferases (Dnmt3a, Dnmt3b) are recruited to sites of DNA repair in vivo. Time lapse microscopy of microirradiated mammalian cells expressing GFP-tagged Dnmt1, Dnmt3a, or Dnmt3b1 together with red fluorescent protein-tagged proliferating cell nuclear antigen (PCNA) revealed that Dnmt1 and PCNA accumulate at DNA damage sites as early as 1 min after irradiation in S and non-S phase cells, whereas recruitment of Dnmt3a and Dnmt3b was not observed. Deletion analysis showed that Dnmt1 recruitment was mediated by the PCNA-binding domain. These data point to a direct role of Dnmt1 in the restoration of epigenetic information during DNA repair.     

Early clinical symptoms and therapy of haemorrhages in old age (author's transl)]

There is hardly a bleeding, where the extrinsic-and/or the intrinsic-system of the coagulation does not take part in. Haemorrhages represent a symptom only, and it is always to clear, if they are come from a local process of illness or from a general tendency of haemorrhage. There is point to the clinical differences of great bleeding (coagulopathy) and bleedings like points (the causes lie in the thrombocytes or in a vascular damage). The early clinical symptoms and the therapy of haemorrhages by the old human without the primary disturbance of the coagulate-system are discussed.