Milk fat globule membrane is a protein-lipid complex that may strengthen the gut barrier. The main objective of this study was to assess the ability of a membrane-rich milk fat diet to promote the ...integrity of the gut barrier and to decrease systemic inflammation in lipopolysaccharide (LPS)-challenged mice. Animals were randomly assigned to one of 2 American Institute of Nutrition (AIN)-76A formulations differing only in fat source: control diet (corn oil) and milk fat diet (anhydrous milk fat with 10% milk fat globule membrane). Each diet contained 12% calories from fat. Mice were fed diets for 5 wk, then injected with vehicle or LPS (10mg/kg of BW) and gavaged with dextran-fluorescein to assess gut barrier integrity. Serum was assayed for fluorescence 24h after gavage, and 16 serum cytokines were measured to assess the inflammatory response. Gut permeability was 1.8-fold higher in LPS-challenged mice fed the control diet compared with the milk fat diet. Furthermore, mice fed the milk fat diet and injected with LPS had lower serum levels of IL-6, IL-10, IL-17, monocyte chemotactic protein (MCP)-1, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and IL-3 compared with LPS-injected mice fed the control diet. The results indicate that the membrane-rich milk fat diet decreases the inflammatory response to a systemic LPS challenge compared with corn oil, and the effect coincides with decreased gut permeability.
Abstract The goal of this study was to evaluate the role of both the % of dietary, 18-carbon PUFA (2.5%, 5% and 10%) and the n-6:n-3 ratio (1:1, 10:1 and 20:1) on the acute inflammatory response. ...Mice were fed diets for 8 weeks and injected intraperitoneally with LPS to induce acute inflammation. After 24 h mice were sacrificed and plasma cytokines measured. Diets significantly affected the erythrocyte PUFA composition and the effect of PUFA ratio was more prominent than of PUFA concentration. The % dietary PUFA affected feed efficiency ( p <0.05) and there was a PUFA×ratio interaction with body fat ( p <0.01). In mice fed high %kcal from PUFA, those given a low n-6:n-3 ratio had more body fat than those fed a high ratio. Of the twelve cytokines measured, eleven were significantly affected by the % PUFA ( p <0.05), whereas five were affected by the ratio ( p <0.05). For seven cytokines, there was a significant PUFA×ratio interaction according to a two way ANOVA ( p <0.05). These data indicate that dietary polyunsaturated fatty acids can affect LPS induced-inflammation.
Background
MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women.
Methods
...Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value.
Results
In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a “buffet” of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice.
Conclusion
New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed.
Main Messages
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MRI evolves as a third lung imaging modality, combining morphological and functional information.
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It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients.
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In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT.
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In interstitial lung disease, it serves for research, but the clinical value remains to be proven.
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New users are advised to make themselves familiar with the particular advantages and limitations.
Several endoscopic antireflux therapies have been marketed, but long-term data on their objective and clinical efficacy are sparse. This report presents prospective 1-year follow-up results, ...including technical, clinical, and functional success rates, for the first of these treatments to be developed, endoscopic gastroplication (EGP).
A total of 43 EGP procedures were carried out in 38 patients with gastroesophageal reflux disease (GERD). Two or three EndoCinch gastroplications were constructed at the level of the gastric cardia in each patient; five patients were treated twice within 6 - 12 months. Each endoscopic suture joined two gastric folds to each other as a double fold, known as a "gastroplication", in order to narrow the esophagogastric junction. Postprocedure data after 2 months and after 1 year were compared with preoperative data, focusing on symptoms, medication requirements, endoscopic findings, and pH-metry results.
In contrast to the findings at 2 months (which showed that 72 % of the sutures were present and that there was a reduction in the percentage of time when the esophageal pH was < 4 from 15.4 % to 8.7 %), the results 1 year after EGP were considered to indicate failure of the treatment in all 38 patients because none of them still had all of the initially placed gastroplications in situ (90 % of gastroplications were lost). The percentage of patients who did not require proton pump inhibitor medication decreased from 52 % at 2 months to only 20 % at 1 year and even more patients had evidence of reflux esophagitis at 1 year (56 %) than had initially demonstrated signs of this (41 %).
EGP has some short-term beneficial effects on clinical symptoms and pH-metry. However, mainly due to the loss of the endoscopically placed sutures, these effects were not maintained at the 1-year follow-up. EGP cannot therefore be recommended for routine clinical use. Better endoscopic methods need to be developed, and they should be adequately tested before being marketed.
Background: Advanced and incurable Klatskin tumors of Bismuth-type III and IV cause obstructive jaundice. Palliation of patients with Klatskin tumors is usually carried out by bilateral endoscopic ...stent placement. Endoscopic retrograde cholangiography (ERC) in such patients is associated with a comparatively high morbidity and mortality mainly due to postprocedure bacterial cholangitis. To reduce ERC-related complications the outcome of replacing ERC with magnetic resonance cholangiopancreatography (MRCP) was investigated. Subsequently, unilateral contrast injection and stent placement were performed, thus avoiding bilateral contrast injection and stent insertion. Methods: Patients thought to have a Klatskin tumor underwent clinical evaluation, laboratory, and noninvasive imaging studies before ERC. Patients were enrolled in this feasibility study if investigators agreed with the clinical diagnosis of an advanced and incurable Klatskin tumor. MRCP images were used to determine the predominate ductal drainage for the liver segments thus directing stent placement. Based on these findings, unilateral ERC and subsequent unilateral stent placement were performed. Antibiotics were not given before ERC. Amsterdam-type stents (10F) were placed and replaced routinely at 2 months. In cases of earlier occlusion, the stents were replaced immediately. Results: Thirty-five patients underwent MRCP, ERC, and unilateral stent deployment. Two further patients enrolled after MRCP were withdrawn because ERC could not be carried out. In 35 patients with unilateral stents bilirubin levels decreased (18.9 ± 6.3 mg/dL to 3.2 ± 2.3 mg/dL) and jaundice resolved in 86%. After first stent deployment, post-ERC bacterial cholangitis occurred in 6% (2 of 35) of patients. Conclusions: This new method of MRCP-guided endoscopic unilateral stent placement could reduce ERC-related complications caused by initial stent deployment.The results of this study justify a randomized prospective comparative trial. (Gastrointest Endosc 2001;53:40-6.)
The clinical importance of magnetic resonance cholangiopancreatography (MRCP) as a noninvasive diagnostic modality for investigation of the biliary tree and pancreatic duct system is under debate. ...Using endoscopic retrograde cholangiopancreatography (ERCP) as the gold standard, this study determined in a prospective, blinded fashion the sensitivity and further statistic values of MRCP findings for evaluation of the biliary and pancreatic tract.
Seventy-eight patients referred for ERCP were studied prospectively with MRCP and ERCP during a 12-month period. All images were interpreted on a blinded basis by two radiologists. Any dilations, strictures, and intraductal abnormalities were recorded and correlated with the clinical diagnoses.
MRCP images of diagnostic quality were obtained in 76 of the 78 patients (97%). Magnetic resonance cholangiography (MRC) showed sensitivities (and positive predictive values) of 71% (62%) for recognition of normal bile ducts, 83% (91%) for recognition of dilation, 85% (100%) for recognition of strictures, 77% (91%) for correct stricture location, and 80% (100%) for diagnosing bile duct calculi. In addition, the sensitivity of MRC in classifying benign and malignant strictures was 50% and 80%, respectively. The statistical values (sensitivity and positive predictive value) for magnetic resonance pancreatography findings were determined for the recognition of normal pancreatic ducts (33% and 50%), recognition of dilation (62% and 100%), recognition of strictures (76% and 87%) and correct location (66% and 100%), diagnosis of benign strictures (87% and 87%) and malignant strictures (60% and 75%), and for diagnosing pancreatic duct stones (60% and 100%).
MRCP is capable of providing diagnostic information equivalent to ERCP in many patients, and should be applied whenever established techniques provide no results, or inadequate results.
Endoscopic retrograde cholangiopancreatography (ERCP) is an established modality for the diagnosis and treatment of pancreaticobiliary disorders. In contrast to ERCP in patients who have not ...undergone gastrectomy, ERCP in patients with a Billroth II gastrojejunostomy or a Roux-en-Y anastomosis is considerably more difficult. It was nevertheless considered that ERCP might be possible in most patients with gastrectomies, and this hypothesis was tested.
A total of 2256 patients were admitted to our hospital for ERCP from 1990 to 1994. Of these, 65 (3%) had gastrojejunostomies, either with Billroth II reconstructions or with the Roux-en-Y procedure. ERCP was always performed with a conventional side-viewing endoscope.
We examined the 65 patients with gastrojejunostomies. Of these, 91% had Billroth II anastomoses and 9% had received Roux-en-Y reconstructions. We successfully reached the papilla of Vater with the endoscope in 92% of the patients with Billroth II gastrojejunostomies (54 of 59), but in only 33% of the patients with Roux-en-Y reconstructions (two of six). In 8% of the cases of Billroth II anastomosis, it was not possible to advance the endoscope into the duodenal stump, due to intestinal stenoses (5%) or excessive intestinal length (3%). Failure in case of regular Billroth II anatomy occurred only in patients who had not received Braun enteroenterostomies. Failure also occurred in 67% of the Roux-en-Y gastrojejunostomy cases due to excessive intestinal length.
Most patients with Billroth II gastrojejunostomy (92% of those in the present study) and some patients with Roux-en-Y anastomosis (33% of those in the present study) can be investigated by ERCP and endoscopically treated in cases of pancreaticobiliary disorder. Braun enteroenterostomy has no negative impact on the endoscopic access to the papilla of Vater in patients with Billroth II gastrojejunostomy. Surgical reconstruction of the gastrointestinal tract to perform gastrojejunostomy should also take endoscopic requirements into account. In view of both the potential postoperative complications and endoscopic requirements, the jejunojejunostomy should be placed nearer to the gastrojejunostomy than 60 cm, and the afferent loop should be as short as possible.
The goal of this study was to define the regulation of nitric oxide release by coronary microvessels from the failing and nonfailing human heart and to determine the role of local kinin production in ...the elaboration of nitric oxide by human coronary microvascular endothelium.
Ten hearts from humans with end-stage heart failure and two hearts from patients without heart failure were harvested at the time of orthotopic cardiac transplantation. Microvessels were sieved and the production of nitrite was determined by the Griess reaction. Microvessels were incubated in the presence of agonists for nitric oxide production (acetylcholine and bradykinin), which caused dose-dependent increases in nitrite, a response that was blocked by NG-nitro-L-arginine methyl ester and receptor-specific antagonists (atropine and HOE 140, respectively). In addition, the production of nitrite by microvessels from the failing heart appeared to be less than that produced by microvessels from the nonfailing heart. Incubation with norepinephrine or the alpha2-adrenergic agonist BHT 920 also caused dose-dependent increases in nitrite production, which were blocked by the B2-receptor antagonist HOE 140. This implicated local kinin synthesis as an intermediate step in the production of nitric oxide in response to alpha2-adrenoceptor stimulation. The production of nitric oxide was also prevented by the addition of serine protease inhibitors, which blocked the action of local kallikrein, again suggesting a role for local kinin synthesis.
Our results indicate that nitric oxide is produced by human coronary microvessels, that nitric oxide production may be reduced but certainly not increased in microvessels from the failing human heart, and that there is active local kinin generation in these blood vessels.
Surgical resection provides the only chance of cure for patients suffering from hilar cholangiocarcinoma. Although appropriate procedures are not agreed upon, an increase in radicality has been ...observed during the past 20 years.
The literature as well as our own experience after 133 resections of hilar cholangiocarcinomas were reviewed.
Tumor-free margins represent the most important prognostic parameter. Hilar resections as least radical resective procedure will generate rates of formally curative resections of less than 50%. Even after these formally curative resections, long-term survival cannot be achieved. Only additional liver resections will increase the number of long-term survivors to significant figures. In our series, the best 5-year survival rate of 72% was achieved after right trisegmentectomy with concomitant resection of the portal vein bifurcation.
Right trisegmentectomy and combined portal vein resection represent the best way to comply with basic rules of surgical oncology for hilar cholangiocarcinoma. This procedure will provide the most pronounced benefit among various types of liver resection, whereas local resections of the extrahepatic bile duct must be considered as an oncologically inefficient procedure.
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