Recurrent ischemic colitis in a patient with leiden factor V mutation and systemic lupus erythematous with antiphospholipid syndrome

Ischemic colitis results from insufficient blood supply to the large intestine and is often associated with hypercoagulable states. The condition comprises a wide range presenting with mild to fulminant forms. Diagnosis remains difficult because these patients may present with non-specific abdominal symptoms. We report a 51- year-old female patient with known Leiden factor V mutation as well as systemic lupus erythematous along with antiphospholipid syndrome suffering from recurrent ischemic colitis. At admission, the patient complained about abdominal pain, diarrhea and rectal bleeding lasting for 24 hours. Laboratory tests showed an increased C-reactive protein (29.5 mg/dl), while the performed abdominal CT-scan revealed only a dilatation of the descending colon along with a thickening of the bowel wall. Laparotomy was performed showing an ischemic colon and massive peritonitis. Histological examination proved the suspected ischemic colitis. Consecutively, an anti-coagulation therapy with coumarin and aspirin 100 was initiated. Up to the time point of a follow up examination no further ischemic events had occurred. This case illustrates well the non-specific clinical presentation of ischemic colitis. A high index of suspicion, recognition of risk factors and a history of non-specific abdominal symptoms should alert the clinicians to the possibility of ischemic disease. Early diagnosis and initiation of anticoagulation therapy or surgical intervention in case of peritonitis are the major goals of therapy.

The immediate and sustained effects of volume challenge on regional blood flows in pigs

BACKGROUND: The postoperative assessment of volume status is not straightforward because of concomitant changes in intravascular volume and vascular tone. Hypovolemia and blood flow redistribution may compromise the perfusion of the intraabdominal organs. We investigated the effects of a volume challenge in different intra- and extraabdominal vascular beds. METHODS: Twelve pigs were studied 6 h after major intraabdominal surgery under general anesthesia when clinically normovolemic. Volume challenges consisted of 200 mL rapidly infused 6% hydroxyethyl starch. Systemic (continuous thermodilution) and regional (ultrasound Doppler) flows in carotid, renal, celiac trunk, hepatic, and superior mesenteric arteries and the portal vein were continuously measured. The acute and sustained effects of the challenge were compared with baseline. RESULTS: Volume challenge produced a sustained increase of 22% +/- 15% in cardiac output (P < 0.001). Blood flow increased by 10% +/- 9% in the renal artery, by 22% +/- 15% in the carotid artery, by 26% +/- 15% in the superior mesenteric artery, and by 31% +/- 20% in the portal vein (all P < 0.001). Blood flow increases in the celiac trunk (8% +/- 13%) and the hepatic artery (7% +/- 19%) were not significant. Increases in regional blood flow occurred early and were sustained. Mean arterial and central venous blood pressures increased early and decreased later (all P < 0.05). CONCLUSIONS: A volume challenge in clinically euvolemic postoperative animals was associated with a sustained increase in blood flow to all vascular beds, although the increase in the celiac trunk and the hepatic artery was very modest and did not reach statistical significance. Whether improved postoperative organ perfusion is accompanied by a lower complication rate should be evaluated in further studies.

[Effects of tobacco use on systemic health: relevant information for dentistry (II)--part 2: cardiovascular diseases and public health issues]

This is the sixth and concluding part of a series of publications from the Swiss task force named "Smoking - Intervention in the private dental office" on the topic "tobacco use and dental medicine". The focus of this review is the effects of smoking for the development of atherosclerosis as pathohistological correlate for acute coronary syndrome (ACS), arterial occlusive disease, and cerebrovascular diseases (stroke). Additionally, a causal relationship between tobacco use and an increased rate for complications during pregnancy and child birth will be discussed. Next to causal therapy of local and systemic diseases in general, an emphasis must be given to tobacco use prevention and cessation. Finally, important public health issues concerning smoking and tobacco use will be demonstrated, and options to improve the current situation will be presented.

Testing the GlaaS algorithm for dose measurements on low- and high-energy photon beams using an amorphous silicon portal imager

The GLAaS algorithm for pretreatment intensity modulation radiation therapy absolute dose verification based on the use of amorphous silicon detectors, as described in Nicolini et al. [G. Nicolini, A. Fogliata, E. Vanetti, A. Clivio, and L. Cozzi, Med. Phys. 33, 2839-2851 (2006)], was tested under a variety of experimental conditions to investigate its robustness, the possibility of using it in different clinics and its performance. GLAaS was therefore tested on a low-energy Varian Clinac (6 MV) equipped with an amorphous silicon Portal Vision PV-aS500 with electronic readout IAS2 and on a high-energy Clinac (6 and 15 MV) equipped with a PV-aS1000 and IAS3 electronics. Tests were performed for three calibration conditions: A: adding buildup on the top of the cassette such that SDD-SSD = d(max) and comparing measurements with corresponding doses computed at d(max), B: without adding any buildup on the top of the cassette and considering only the intrinsic water-equivalent thickness of the electronic portal imaging devices device (0.8 cm), and C: without adding any buildup on the top of the cassette but comparing measurements against doses computed at d(max). This procedure is similar to that usually applied when in vivo dosimetry is performed with solid state diodes without sufficient buildup material. Quantitatively, the gamma index (gamma), as described by Low et al. [D. A. Low, W. B. Harms, S. Mutic, and J. A. Purdy, Med. Phys. 25, 656-660 (1998)], was assessed. The gamma index was computed for a distance to agreement (DTA) of 3 mm. The dose difference deltaD was considered as 2%, 3%, and 4%. As a measure of the quality of results, the fraction of field area with gamma larger than 1 (%FA) was scored. Results over a set of 50 test samples (including fields from head and neck, breast, prostate, anal canal, and brain cases) and from the long-term routine usage, demonstrated the robustness and stability of GLAaS. In general, the mean values of %FA remain below 3% for deltaD equal or larger than 3%, while they are slightly larger for deltaD = 2% with %FA in the range from 3% to 8%. Since its introduction in routine practice, 1453 fields have been verified with GLAaS at the authors' institute (6 MV beam). Using a DTA of 3 mm and a deltaD of 4% the authors obtained %FA = 0.9 +/- 1.1 for the entire data set while, stratifying according to the dose calculation algorithm, they observed: %FA = 0.7 +/- 0.9 for fields computed with the analytical anisotropic algorithm and %FA = 2.4 +/- 1.3 for pencil-beam based fields with a statistically significant difference between the two groups. If data are stratified according to field splitting, they observed %FA = 0.8 +/- 1.0 for split fields and 1.0 +/- 1.2 for nonsplit fields without any significant difference.

Systemic analysis of microarray data sets towards identifying genes regulating root development

Nitrogen and water are essential for plant growth and development. In this study, we designed experiments to produce gene expression data of poplar roots under nitrogen starvation and water deprivation conditions. We found low concentration of nitrogen led first to increased root elongation followed by lateral root proliferation and eventually increased root biomass. To identify genes regulating root growth and development under nitrogen starvation and water deprivation, we designed a series of data analysis procedures, through which, we have successfully identified biologically important genes. Differentially Expressed Genes (DEGs) analysis identified the genes that are differentially expressed under nitrogen starvation or drought. Protein domain enrichment analysis identified enriched themes (in same domains) that are highly interactive during the treatment. Gene Ontology (GO) enrichment analysis allowed us to identify biological process changed during nitrogen starvation. Based on the above analyses, we examined the local Gene Regulatory Network (GRN) and identified a number of transcription factors. After testing, one of them is a high hierarchically ranked transcription factor that affects root growth under nitrogen starvation. It is very tedious and time-consuming to analyze gene expression data. To avoid doing analysis manually, we attempt to automate a computational pipeline that now can be used for identification of DEGs and protein domain analysis in a single run. It is implemented in scripts of Perl and R.

[Unusual pulmonary presentation of systemic Langerhans cell histiocytosis]

An 80-year-old nonsmoking man was referred to our hospital with bilateral perihilar pulmonary opacities. He had a history of epilepsy, sclerosing cholangitis, cutaneous lesions previously diagnosed as localised Langerhans cell histiocytosis. Symptoms included dry cough and dyspnea. Chest CT showed bilateral perihilar alveolar consolidation with bronchiectasis. Histological examination of a lung biopsy showed typical features of Langerhans cell granulomatosis. Investigations revealed anterior and posterior hypopituitarism. An important improvement occurred with corticosteroid and vinblastine treatment.

Integrin alphavbeta6 is a marker of the progression of biliary and portal liver fibrosis and a novel target for antifibrotic therapies

BACKGROUND/AIMS: The integrin alphavbeta6 promotes proliferation of specialized epithelia and acts as a receptor for the activation of latent TGFbeta1. We studied alphavbeta6 expression in experimental and human liver fibrosis and the potential of its pharmacological inhibition for treatment of hepatic fibrosis. METHODS: alphavbeta6 expression was studied by quantitative PCR and immunohistochemistry in rats with cirrhosis due to bile duct ligation (BDL), administration of thioacetamide (TAA), in Mdr2(Abcb4)(-/-) mice with spontaneous biliary fibrosis, and in livers of patients with chronic hepatitis C (n=79) and end-stage liver disease due to various etiologies (n=18). The effect of a selective alphavbeta6 inhibitor was evaluated in Mdr2(Abcb4)(-/-) mice with ongoing fibrogenesis. RESULTS: Integrin beta6 mRNA increased with fibrosis stage in hepatitis C and was upregulated between 25- and 100-fold in TAA- and BDL-induced cirrhosis, in Mdr2(Abcb4)(-/-) mice and in human end-stage liver disease. alphavbeta6 protein was absent in normal livers and expressed de novo on (activated) bile duct epithelia and transitional hepatocytes. A single dose of the alphavbeta6 inhibitor injected into Mdr2(Abcb4)(-/-) mice significantly induced profibrolytic matrix metalloproteinases (MMP)-8 and -9 after 3 h, with a corresponding increase in extracellular matrix-degrading activities. In parallel profibrogenic transcripts (procollagen alpha1(I), TGFbeta2, and MMP-2) showed a trend of downregulation. CONCLUSIONS: (1) Integrin alphavbeta6 is induced de novo in rodent and human liver fibrosis, where it is expressed on activated bile duct epithelia and (transitional) hepatocytes during fibrosis progression. (2) In vivo a single dose of a small molecule alphavbeta6 inhibitor induced antifibrogenic and profibrolytic genes and activities, suggesting alphavbeta6 is a unique target for treatment of liver fibrosis.

Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults

BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

[Cerebral vasculitis]

Cerebral vasculitis is a rare disease with a potentially harmful or even fatal outcome that often affects young adults. Primary autoimmune mediated disease can be distinguished from secondary vasculitis associated to infectious disorders, connective tissue diseases, malignancies or toxic drug effects. Pathomechanisms lead to destruction of the vessel wall and consecutive hemorrhagic or ischemic brain lesions. Beyond these mechanisms direct autoimmune mediated neurotoxicity is postulated. Clinical presentation is highly variable with potentially fluctuating signs and symptoms. Besides multifocal deficits from disseminated CNS involvement, diffuse encephalopathy or psychosis may result from diffuse CNS affection. For systemic vasculitis with CNS involvement, affection of joints, skin and organs may facilitate the diagnostic evaluation. CNS affection in systemic diseases is highly variable and may even precede systemic manifestation. The diagnostic work-up includes clinical evaluation, analysis of autoantibodies, MRI, digital subtraction angiography and biopsy of the affected tissue in doubtful cases. Standard therapy are corticosteroids often combined with immunosuppressants such as azathioprine, methotrexate or mycophenolate mofetil in chronic disease or cyclophosphamid in acute disorder. When therapy can be initiated timely, prognosis of cerebral vasculitis is usually favourable.

[Systemic ANCA-associated vasculitis--diagnosis and therapy]

ANCA-associated vasculitis represents a group of small-vessel vasculitides, including Wegener's granulomatosis, microscopic polyangiitis and the Churg-Strauss-syndrome. These diseases affect mainly small arteries, venules and capillaries, showing a lack of immunocomplex formation on immunohistology, the so-called "pauci-immune" vasculitis. Nevertheless, Anti-Neutrophil Cytoplasmatic Autoantibodies (ANCA's) are pathogenic for this type of disease. In spite of important advances in technical diagnostic tools, careful medical history and clinical examinations often give the clues for the correct diagnosis. Recent collaborative therapeutic studies have lead to therapeutic schemas that are much more adapted to the individual disease state. Besides the acute and sometimes life-threatening form of ANCA-vasculitis, chronic disease and relapses become more important in clinical practice. Thus, therapeutic efficacy must be outweighed against long-term toxicity to make the right choice for therapeutic intervention in ANCA-associated vasculitis.

Treatment of portal vein thrombosis by thrombectomy and regional thrombolysis

BACKGROUND. Portal vein thrombosis is a rare disorder. The prognosis of both the acute and the chronic forms is determined by the resulting acute or chronic portal hypertension. The therapeutic approach of choice is controversial. METHODS. A case of etiologically unclear thrombosis of the portal vein system in a young man is reported, which was treated successfully by means of portal vein thrombectomy combined with intraoperative and postoperative thrombolysis with recombinant tissue plasminogen activator (rTPA). RESULTS. Initial thrombectomy established sufficient venous return. However, rethrombosis of the portal vein occurred 2 days later. In a second operation rethrombectomy was followed by intraoperative regional application of rTPA, which was continued after operation during a period of 48 hours through a catheter inserted in a mesenteric vein. Patency of the portal system was confirmed 1 week after the procedure. The 1-year follow-up reconfirmed this result (through indirect portography and Doppler sonography). The patient received the anticoagulant phenprocoumon. CONCLUSIONS. The combination of surgical thrombectomy and regional thrombolysis with rTPA could offer a feasible therapeutic option for selected patients with acute prehepatic portal vein thrombosis.

The systemic angiogenic response during bone healing

INTRODUCTION: Angiogenesis is known to be a critical and closely regulated step during bone formation and fracture healing driven by a complex interaction of various cytokines. Delays in bone healing or even nonunion might therefore be associated with altered concentrations of specific angiogenic factors. These alterations might in turn be reflected by changes in serum concentrations. METHOD: To determine physiological time courses of angiogenic cytokines during fracture healing as well as possible changes associated with failed consolidation, we prospectively collected serum samples from patients who had sustained surgical treatment for a long bone fracture. Fifteen patients without fracture healing 4 months after surgery (nonunion group) were matched to a collective of 15 patients with successful healing (union group). Serum concentrations of angiogenin (ANG), angiopoietin 2 (Ang-2), basic fibroblast growth factor (bFGF), platelet derived growth factor AB (PDGF-AB), pleiotrophin (PTN) and vascular endothelial growth factor (VEGF) were measured using enzyme linked immunosorbent assays over a period of 24 weeks. RESULTS: Compared to reference values of healthy uninjured controls serum concentrations of VEGF, bFGF and PDGF were increased in both groups. Peak concentrations of these cytokines were reached during early fracture healing. Serum concentrations of bFGF and PDGF-AB were significantly higher in the union group at 2 and 4 weeks after the injury when compared to the nonunion group. Serum concentrations of ANG and Ang-2 declined steadily from the first measurement in normal healing fractures, while no significant changes over time could be detected for serum concentrations of these factures in nonunion patients. PTN serum levels increased asymptotically over the entire investigation in timely fracture healing while no such increase could be detected during delayed healing. CONCLUSION: We conclude that fracture healing in human subjects is accompanied by distinct changes in systemic levels of specific angiogenic factors. Significant alterations of these physiologic changes in patients developing a fracture nonunion over time could be detected as early as 2 (bFGF) and 4 weeks (PDGF-AB) after initial trauma surgery.

Systemic conditions and treatments as risks for implant therapy

PURPOSE: To evaluate whether systemic diseases with/without systemic medication increase the risk of implant failure and therefore diminish success and survival rates of dental implants. MATERIALS AND METHODS: A MEDLINE search was undertaken to find human studies reporting implant survival in subjects treated with osseointegrated dental implants who were diagnosed with at least one of 12 systemic diseases. RESULTS: For most conditions, no studies comparing patients with and without the condition in a controlled setting were found. For most systemic diseases there are only case reports or case series demonstrating that implant placement, integration, and function are possible in affected patients. For diabetes, heterogeneity of the material and the method of reporting data precluded a formal meta-analysis. No unequivocal tendency for subjects with diabetes to have higher failure rates emerged. The data from papers reporting on osteoporotic patients were also heterogeneous. The evidence for an association between osteoporosis and implant failure was low. Nevertheless, some reports now tend to focus on the medication used in osteoporotic patients, with oral bisphosphonates considered a potential risk factor for osteonecrosis of the jaws, rather than osteoporosis as a risk factor for implant success and survival on its own. CONCLUSIONS: The level of evidence indicative of absolute and relative contraindications for implant therapy due to systemic diseases is low. Studies comparing patients with and without the condition in a controlled setting are sparse. Especially for patients with manifest osteoporosis under an oral regime of bisphosphonates, prospective controlled studies are urgently needed.