PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-18 (18)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
1.  The role and utility of faecal markers in inflammatory bowel disease 
Crohn’s disease and ulcerative colitis are characterized by periods of symptomatic relapse and remission. Diagnosis and assessment of inflammatory bowel disease has so far been based on clinical evaluation, serum parameters, radiology and endoscopy. Faecal markers such as calprotectin or lactoferrin have emerged as new diagnostic tools to detect and monitor intestinal inflammation. This review focuses on their potential clinical applications and limitations in the management of inflammatory bowel disease.
doi:10.1177/1756283X14553384
PMCID: PMC4265086  PMID: 25553077
calprotectin; Crohn’s disease; inflammation; inflammatory bowel disease; lactoferrin; ulcerative colitis
2.  Infliximab in the Treatment of Crohn Disease and Type 1 Diabetes 
Diabetes Care  2013;36(7):e90-e91.
doi:10.2337/dc13-0199
PMCID: PMC3687309  PMID: 23801815
3.  Clinical and histopathological correlations of fecal calprotectin release in colorectal carcinoma 
AIM: To determine calprotectin release before and after colorectal cancer operation and compare it to tumor and histopathological parameters.
METHODS: The study was performed on patients with diagnosed colorectal cancer admitted for operation. Calprotectin was measured in a single stool sample before and three months after the operation using an enzyme-linked immunosorbent assay (ELISA). Calprotectin levels greater than or equal to 50 μg/g were considered positive. The compliance for collecting stool samples was assessed and the value of calprotectin was correlated to tumor and histopathological parameters of intra- and peri-tumoral inflammation. Surgical specimens were fixed in neutral buffered formalin and stained with hematoxylin and eosin. Staging was performed according to the Dukes classification system and the 7th edition tumor node metastasis classification system. Intra- and peri-tumoral inflammation was graded according to the Klintrup criteria. Immunohistochemical quantification was performed for MPO, CD45R0, TIA-1, CD3, CD4, CD8, CD57, and granzyme B. Statistical significance was measured using Wilcoxon signed rank test, Kruskal Wallis test and Spearman’s rank correlation coefficient as appropriate.
RESULTS: Between March 2009 and May 2011, 80 patients with colorectal cancer (46 men and 34 women, with mean age of 71 ± 11.7 years old) were enrolled in the study. Twenty-six patients had rectal carcinoma, 29 had left-side tumors, 23 had right-side tumors, and 2 had bilateral carcinoma. In total, 71.2% of the patients had increased levels of calprotectin before the operation (median 205 μg/g, range 50-2405 μg/g) and experienced a significant decrease three months after the operation (46 μg/g, range 10-384 μg/g, P < 0001). The compliance for collecting stool samples was 89.5%. Patients with T3 and T4 tumors had significantly higher values than those with T1 and T2 cancers (P = 0.022). For all other tumor parameters (N, M, G, L, V, Pn) and location, no significant difference in calprotectin concentration was found. Furthermore, the calprotectin levels and histological grading of both peri- and intra-tumoral inflammation was not correlated. Additional testing with specific markers for lymphocytes and neutrophils also revealed no statistically significant correlation.
CONCLUSION: Fecal calprotectin decreases significantly after colorectal cancer operation. Its value depends exclusively on the individual T-stage, but not on other tumor or histopathological parameters.
doi:10.3748/wjg.v20.i17.4994
PMCID: PMC4009532  PMID: 24803811
Calprotectin; Colorectal cancer; Inflammation; Tumor size; Granulocytes
4.  Diagnostic yield of endoscopy in patients with abdominal complaints: incremental value of faecal calprotectin on guidelines of appropriateness 
BMC Gastroenterology  2014;14:57.
Background
European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) criteria have been developed to increase diagnostic yield, but their predictive value is limited. We investigated the incremental diagnostic value of faecal calprotectin to EPAGE criteria.
Methods
In a post-hoc analysis of a prospective study, EPAGE criteria were applied to 298 of 575 (51.8%) patients who had undergone esophagogastroduodenoscopy (EGD), colonoscopy or both for abdominal complaints at the Division of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland. Faecal calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. Final endoscopic diagnoses were blinded to calprotectin values.
Results
Of 149 EGDs and 224 colonoscopies, 17.6% and 14.7% respectively were judged inappropriate by EPAGE criteria. Appropriate or uncertain indications revealed more endoscopic findings in both EGD (46.3% vs. 23.1%, P = 0.049) and colonoscopy (23.6% vs. 6.1%, P = 0.041) than inappropriate indications. Median calprotectin levels were higher (81.5 μg/g, interquartile range 26-175, vs. 10 μg/g, IQR 10–22, P < 0.001) and testing was more often positive (>50 μg/g) in patients with endoscopic findings, both in EGD (58.2% vs. 33.0%, P = 0.005) and in colonoscopy (57.3% vs. 7.4%, P < 0.001). The use of faecal calprotectin in addition to EPAGE criteria improved the risk reclassification of patients by endoscopic findings. The calculated net reclassification index was 37.8% (P = 0.002) for EGD and 110.9% (P <0.001) for colonoscopy, thus improving diagnostic yield to 56.8% and 70.2%, respectively.
Conclusions
The use of faecal calprotectin in addition to EPAGE criteria improved diagnostic yield in patients with abdominal complaints.
doi:10.1186/1471-230X-14-57
PMCID: PMC4021405  PMID: 24679065
Esophagogastroduodenoscopy; Colonoscopy; Appropriateness; Calprotectin; Diagnostic accuracy
5.  Green tea extract enhances parieto-frontal connectivity during working memory processing 
Psychopharmacology  2014;231(19):3879-3888.
Rationale
It has been proposed that green tea extract may have a beneficial impact on cognitive functioning, suggesting promising clinical implications. However, the neural mechanisms underlying this putative cognitive enhancing effect of green tea extract still remain unknown.
Objectives
This study investigates whether the intake of green tea extract modulates effective brain connectivity during working memory processing and whether connectivity parameters are related to task performance.
Material and methods
Using a double-blind, counterbalanced, within-subject design, 12 healthy volunteers received a milk whey-based soft drink containing 27.5 g of green tea extract or a milk whey-based soft drink without green tea as control substance while undergoing functional magnetic resonance imaging. Working memory effect on effective connectivity between frontal and parietal brain regions was evaluated using dynamic causal modeling.
Results
Green tea extract increased the working memory induced modulation of connectivity from the right superior parietal lobule to the middle frontal gyrus. Notably, the magnitude of green tea induced increase in parieto-frontal connectivity positively correlated with improvement in task performance.
Conclusions
Our findings provide first evidence for the putative beneficial effect of green tea on cognitive functioning, in particular, on working memory processing at the neural system level by suggesting changes in short-term plasticity of parieto-frontal brain connections. Modeling effective connectivity among frontal and parietal brain regions during working memory processing might help to assess the efficacy of green tea for the treatment of cognitive impairments in psychiatric disorders such as dementia.
doi:10.1007/s00213-014-3526-1
PMCID: PMC4159594  PMID: 24643507
Cognition; Working memory; Green tea extract; Brain activity; Effective connectivity; Dynamic causal modeling
6.  Glucose-Induced Glucagon-Like Peptide 1 Secretion Is Deficient in Patients with Non-Alcoholic Fatty Liver Disease 
PLoS ONE  2014;9(1):e87488.
Background & Aims
The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal peptide hormones regulating postprandial insulin release from pancreatic β-cells. GLP-1 agonism is a treatment strategy in Type 2 diabetes and is evaluated in Non-alcoholic fatty liver disease (NAFLD). However, the role of incretins in its pathophysiology is insufficiently understood. Studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism. We determined the secretion of incretins after oral glucose administration in non-diabetic NAFLD patients.
Methods
N = 52 patients (n = 16 NAFLD and n = 36 Non-alcoholic steatohepatitis (NASH) patients) and n = 50 matched healthy controls were included. Standardized oral glucose tolerance test was performed. Glucose, insulin, glucagon, GLP-1 and GIP plasma levels were measured sequentially for 120 minutes after glucose administration.
Results
Glucose induced GLP-1 secretion was significantly decreased in patients compared to controls (p<0.001). In contrast, GIP secretion was unchanged. There was no difference in GLP-1 and GIP secretion between NAFLD and NASH subgroups. All patients were insulin resistant, however HOMA2-IR was highest in the NASH subgroup. Fasting and glucose-induced insulin secretion was higher in NAFLD and NASH compared to controls, while the glucose lowering effect was diminished. Concomitantly, fasting glucagon secretion was significantly elevated in NAFLD and NASH.
Conclusions
Glucose-induced GLP-1 secretion is deficient in patients with NAFLD and NASH. GIP secretion is contrarily preserved. Insulin resistance, with hyperinsulinemia and hyperglucagonemia, is present in all patients, and is more severe in NASH compared to NAFLD. These pathophysiologic findings endorse the current evaluation of GLP-1 agonism for the treatment of NAFLD.
doi:10.1371/journal.pone.0087488
PMCID: PMC3906180  PMID: 24489924
7.  Measurement of calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count 
AIM: To evaluate the diagnostic capability of calprotectin in ascitic fluid for detecting a polymorphonuclear (PMN) cell count > 250/μL ascites.
METHODS: In this prospective observational study, a total of 130 ascites samples were analysed from 71 consecutive patients referred for paracentesis. Total and differential leukocyte cell counts were determined manually with a Neubauer chamber and gentian-violet stain. Calprotectin was measured in 1 mL ascetic fluid by enzyme-linked immunosorbent assay (ELISA) and a point-of-care (POC) lateral flow assay with the Quantum Blue® Reader (Bühlmann Laboratories). All measurements were carried out in a central laboratory by senior personnel blinded to patient history. A PMN count > 250/μL was the primary endpoint of the study. The diagnostic value of ascitic calprotectin measurement was assessed by comparing to the final diagnosis of each patient that had been adjudicated by investigators blinded to calprotectin values.
RESULTS: The PMN count was > 250/μL in 19 samples (14.6%) from 15 patients (21.1%) and varied widely among the study population (range 10-19 800/mL and 1-17 820/mL, respectively). Spontaneous bacterial peritonitis (SBP) was the final diagnosis in four patients (5.6%). All patients with PMN ≤ 250/μL had negative bacterial culture. PMN count was elevated in five patients with peritoneal carcinomatosis, three with lymphoma, one with neuroendocrine carcinoma, and two with secondary peritonitis due to abdominal perforation. PMN cell counts correlated with ascitic calprotectin values (Spearman’s rho; r = 0.457 for ELISA, r = 0.473 for POC). A considerable range of ascitic calprotectin concentrations was detected by ELISA [median 0.43 μg/mL, interquartile range (IQR) 0.23-1.23 (range 0.10-14.93)] and POC [median 0.38 μg/mL, IQR 0.38-0.56 (range 0.38-13.31)]. Ascitic calprotectin levels were higher in samples with PMN > 250/μL, by both ELISA [median (IQR) 2.48 μg/mL (1.61-3.65) vs 0.10 μg/mL (0.10-0.36), P < 0.001] and POC [2.78 μg/mL (2.05-5.37) vs 0.38 μg/mL (0.38-0.41), P < 0.001]. The area under the receiver operating characteristics curve for identifying an elevated PMN count was 0.977 (95%CI: 0.933 to 0.995) for ELISA and 0.982 (95%CI: 0.942 to 0.997) for POC (P = 0.246 vs ELISA). Using the optimal cut-off value for ELISA (0.63 μg/mL), ascitic calprotectin had 94.8% sensitivity, 89.2% specificity, positive and negative likelihood ratios of 8.76 and 0.06 respectively, positive and negative predictive values of 60.0% and 99.0% respectively, and 90.0% overall accuracy. Using the optimal cut-off value for POC (0.51 μg/mL), the respective values were 100.0%, 84.7%, 6.53, 0.00, 52.8%, 100% and 87.7%. Correlation between ELISA and POC was excellent (r = 0.873, P < 0.001). The mean ± SD of the difference was -0.11 ± 0.48 μg/mL with limits of agreement of + 0.8 μg/mL (95%CI: 0.69 to 0.98) and -1.1 μg/mL (95%CI: -1.19 to -0.91).
CONCLUSION: Ascitic calprotectin reliably predicts PMN count > 250/μL, which may prove useful in the diagnosis of SBP, especially with a readily available bedside testing device.
doi:10.3748/wjg.v19.i13.2028
PMCID: PMC3623979  PMID: 23599621
Calprotectin; Ascites; Liver cirrhosis; Spontaneous bacterial peritonitis; Polymorphonuclear cells
8.  Carbon dioxide accumulation during analgosedated colonoscopy: Comparison of propofol and midazolam 
AIM: To characterize the profiles of alveolar hypoventilation during colonoscopies performed under sedoanalgesia with a combination of alfentanil and either midazolam or propofol.
METHODS: Consecutive patients undergoing routine colonoscopy were randomly assigned to sedation with either propofol or midazolam in an open-labeled design using a titration scheme. All patients received 4 μg/kg per body weight alfentanil for analgesia and 3 L of supplemental oxygen. Oxygen saturation (SpO2) was measured by pulse oximetry (POX), and capnography (PcCO2) was continuously measured using a combined dedicated sensor at the ear lobe. Instances of apnea resulting in measures such as stimulation of the patient, a chin lift, a mask maneuver, or withholding of sedation were recorded. PcCO2 values (as a parameter of sedation-induced hypoventilation) were compared between groups at the following distinct time points: baseline, maximal rise, termination of the procedure and 5 min after termination of the procedure. The number of patients in both study groups who regained baseline PcCO2 values (± 1.5 mmHg) five minutes after the procedure was determined.
RESULTS: A total of 97 patients entered this study. The data from 14 patients were subsequently excluded for clinical procedure-related reasons or for technical problems. Therefore, 83 patients (mean age 62 ± 13 years) were successfully randomized to receive propofol (n = 42) or midazolam (n = 41) for sedation. Most of the patients were classified as American Society of Anesthesiologists (ASA) II [16 (38%) in the midazolam group and 15 (32%) in the propofol group] and ASA III [14 (33%) and 13 (32%) in the midazolam and propofol groups, respectively]. A mean dose of 5 (4-7) mg of IV midazolam and 131 (70-260) mg of IV propofol was used during the procedure in the corresponding study arms. The mean SpO2 at baseline (%) was 99 ± 1 for the midazolam group and 99 ± 1 for the propofol group. No cases of hypoxemia (SpO2 < 85%) or apnea were recorded. However, an increase in PcCO2 that indicated alveolar hypoventilation occurred in both groups after administration of the first drug and was not detected with pulse oximetry alone. The mean interval between the initiation of sedation and the time when the PcCO2 value increased to more than 2 mmHg was 2.8 ± 1.3 min for midazolam and 2.8 ± 1.1 min for propofol. The mean maximal rise was similar for both drugs: 8.6 ± 3.7 mmHg for midazolam and 7.4 ± 3.2 mmHg for propofol. Five minutes after the end of the procedure, the mean difference from the baseline values was significantly lower for the propofol treatment compared with midazolam (0.9 ± 3.0 mmHg vs 4.3 ± 3.7 mmHg, P = 0.0000169), and significantly more patients in the propofol group had regained their baseline value ± 1.5 mmHg (32 of 41 vs 12 of 42, P = 0.0004).
CONCLUSION: A significantly higher number of patients sedated with propofol had normalized PcCO2 values five minutes after sedation when compared with patients sedated with midazolam.
doi:10.3748/wjg.v18.i38.5389
PMCID: PMC3471107  PMID: 23082055
Colonoscopy; Deep sedation; Propofol; Hypoventilation; Blood gas monitoring; Transcutaneous
9.  Metabolic and Hormonal Changes After Laparoscopic Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: a Randomized, Prospective Trial 
Obesity Surgery  2012;22(5):740-748.
Background
The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood.
Methods
In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)).
Results
In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (p < 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (p < 0.012 vs. LRYGB).
Conclusions
Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms.
doi:10.1007/s11695-012-0622-3
PMCID: PMC3319900  PMID: 22354457
Metabolic surgery; Glycemic control; Laparoscopic Roux-en-Y gastric bypass; Laparoscopic sleeve gastrectomy; Gut hormones; Cholecystokinin (CCK); Ghrelin; Glucagon-like peptide 1 (GLP-1); Peptide YY (PYY)
10.  Value of fecal calprotectin in the evaluation of patients with abdominal discomfort: an observational study 
BMC Gastroenterology  2012;12:5.
Background
The evaluation of patients with abdominal discomfort is challenging and patient selection for endoscopy based on symptoms is not reliable. We evaluated the diagnostic value of fecal calprotectin in patients with abdominal discomfort.
Methods
In an observational study, 575 consecutive patients with abdominal discomfort referred for endoscopy to the Department of Gastroenterology & Hepatology at the University Hospital Basel in Switzerland, were enrolled in the study. Calprotectin was measured in stool samples collected within 24 hours before the investigation using an enzyme-linked immunosorbent assay. The presence of a clinically significant finding in the gastrointestinal tract was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.
Results
Median calprotectin levels were higher in patients with significant findings (N = 212, median 97 μg/g, IQR 43-185) than in patients without (N = 326, 10 μg/g, IQR 10-23, P < 0.001). The area under the receiver operating characteristics curve (AUC) to identify a significant finding was 0.877 (95% CI, 0.85-0.90). Using 50 μg/g as cut off yielded a sensitivity of 73% and a specificity of 93% with good positive and negative likelihood ratios (10.8 and 0.29, respectively). Fecal calprotectin was useful as a diagnostic parameter both for findings in the upper intestinal tract (AUC 0.730, 0.66-0.79) and for the colon (AUC 0.912, 0.88-0.94) with higher diagnostic precision for the latter (P < 0.001). In patients > 50 years, the diagnostic precision remained unchanged (AUC 0.889 vs. 0.832, P = 0.165).
Conclusion
In patients with abdominal discomfort, fecal calprotectin is a useful non-invasive marker to identify clinically significant findings of the gastrointestinal tract, irrespective of age.
doi:10.1186/1471-230X-12-5
PMCID: PMC3267677  PMID: 22233279
Gastroenterology; Endoscopy; Diagnosis; Biomarker
11.  Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1: a ‘first in man’ Phase I investigation 
AIMS
GS-101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate-1 (IRS-1). Inhibition of IRS-1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization. We aimed to investigate the safety, tolerability and bioavailability of GS-101 eye drops.
METHODS
This was a Phase I open-label study. The investigation was performed in two steps. Local ocular tolerability was first assessed with the application of one single low dose in one eye. After no signs of intolerance were observed in the subjects, the dose escalation phase of the study was initiated, and the remaining subjects received three times daily escalating doses of GS-101 in one eye for 14 days.
RESULTS
The 14 healthy volunteers tolerated well 14 days' continued use of escalating doses of GS-101 from 43 to 430 µg per day. Other than itching, experienced also in the control eye by one subject and determined to be unrelated to the study treatment, no signs of intolerance were observed.
CONCLUSIONS
The tolerability profile obtained from this study suggests that GS-101 is safe for human use. Further clinical evaluations in diseases related to abnormal angiogenesis are being targeted. In particular, the neovascularization-related orphan indications of corneal graft rejection, retinopathy of pre-maturity and neovascular glaucoma are currently under Phase II clinical investigation and are showing promising results.
doi:10.1111/j.1365-2125.2009.03450.x
PMCID: PMC2767278  PMID: 19694734
antiangiogenic; cornea; insulin receptor substrate-1; pathologic neovascularization
12.  Prevalence and risk factors of hepatitis B and C virus infections in an impoverished urban community in Dhaka, Bangladesh 
BMC Infectious Diseases  2010;10:208.
Background
Viral hepatitis is a serious global public health problem affecting billions of people globally, and both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are rapidly spreading in the developing countries including Bangladesh due to the lack of health education, poverty, illiteracy and lack of hepatitis B vaccination. Also there is lack of information on their prevalence among the general population. So, a population-based serological survey was conducted in Dhaka to determine the prevalence and risk factors of HBV and HCV infections.
Methods
Healthy individuals were selected for demographic and behavioural characteristics by stratified cluster sampling and blood tested for hepatitis B surface antigen (HBsAg), antibody to HBV core antigen (anti-HBc), and anti-HCV antibodies (anti-HCV).
Results
From June 2005-November 2006, 1997 participants were screened for HBsAg, anti-HBc and anti-HCV, 738 (37%) were males with mean (SD) age of 24 (14) years. HBV-seropositivity was documented in 582 (29%) participants: 14 (0.7%) were positive for HBsAg, 452 (22.6%) for anti-HBc and 116 (5.8%) for both HBsAg and anti-HBc. Four (0.2%) participants were positive for anti-HCV, and another five (0.3%) for both anti-HBc and anti-HCV. Ninety-six/246 (39%) family members residing at same households with HBsAg positive participants were also HBV-seropositive [74 (30.1%) for anti-HBc and 22 (8.9%) for both HBsAg and anti-HBc], which was significantly higher among family members (39%) than that of study participants (29%) (OR 1.56; p < 0.001). In bivariate analysis, HBV-seropositivity was significantly associated with married status (OR 2.27; p < 0.001), history of jaundice (OR 1.35; p = 0.009), surgical operations (OR 1.26; p = 0.04), needle-stick injuries (OR 2.09; p = 0.002), visiting unregistered health-care providers (OR 1.40; p = 0.008), receiving treatment for sexually transmitted diseases (STD) (OR 1.79; p = 0.001), animal bites (OR 1.73; p < 0.001); ear-nose-body piercing in females (OR 4.97; p < 0.001); circumcision (OR 3.21; p < 0.001), and visiting community barber for shaving in males (OR 3.77; p < 0.001). In logistic regression analysis, married status (OR 1.32; p = 0.04), surgical operations (OR 1.39; p = 0.02), animal bites (OR 1.43; p = 0.02), visiting unregistered health-care providers (OR 1.40; p = 0.01); and ear-nose-body piercing in females (OR 4.97; p < 0.001) were significantly associated with HBV-seropositivity.
Conclusions
The results indicate intermediate level of endemicity of HBV infection in Dhaka community, with much higher prevalence among family members of HBsAg positive individuals but low prevalence of HCV infections, clearly indicating need for universal hepatitis B vaccination. The use of disposable needles for ear-nose-body piercing need to be promoted through public awareness programmes as a preventive strategy.
doi:10.1186/1471-2334-10-208
PMCID: PMC2918606  PMID: 20630111
13.  Colon Capsule Endoscopy compared to Conventional Colonoscopy under routine screening conditions 
BMC Gastroenterology  2010;10:66.
Background
Colonoscopy (CSPY) for colorectal cancer screening has several limitations. Colon Capsule Endoscopy (PillCam Colon, CCE) was compared to CSPY under routine screening conditions.
Methods
We performed a prospective, single-center pilot study at a University Hospital. Data were obtained from November 2007 until May 2008. Patients underwent CCE on Day 1 and CSPY on Day 2. Outcomes were evaluated regarding sensitivity and specificity of polyp detection rate, with a significance level set at >5 mm.
Results
59 individuals were included in this study, the results were evaluable in 56 patients (males 34, females 22; median age 59). CCE was complete in 36 subjects. Polyp detection rate for significant polyps was 11% on CSPY and 27% on CCE.
6/56 (11%) patients had polyps on CSPY not detected on CCE (miss rate).
Overall sensitivity was 79% (95% confidence interval [CI], 61 to 90), specificity was 54% (95% CI, 35 to 70), positive predictive value (PPV) was 63% and negative predictive value (NPV) was 71%. Adjusted to significance of findings, sensitivity was 50% (95% CI, 19 to 81), specificity was 76% (95% CI, 63 to 86), PPV was 20% and NPV was 93%.
Conclusion
In comparison to the gold standard, the sensitivity of CCE for detection of relevant polyps is low, however, the high NPV supports its role as a possible screening tool.
Trial Registration
NCT00991003.
doi:10.1186/1471-230X-10-66
PMCID: PMC2905323  PMID: 20565828
14.  Single-Ascending-Dose Pharmacokinetics and Safety of the Novel Broad-Spectrum Antifungal Triazole BAL4815 after Intravenous Infusions (50, 100, and 200 Milligrams) and Oral Administrations (100, 200, and 400 Milligrams) of Its Prodrug, BAL8557, in Healthy Volunteers 
BAL8557 is the water-soluble prodrug of a novel antifungal triazole, BAL4815. BAL4815 is active against a broad spectrum of major opportunistic and pathogenic fungi, including strains that are resistant to other azoles. Cohorts of healthy male subjects received single-ascending oral (p.o.) doses of BAL8557 that were equivalent to 100, 200, or 400 mg of BAL4815 or single-ascending, 1-h constant-rate intravenous (i.v.) infusions of BAL8557 which were equivalent to 50, 100, or 200 mg of BAL4815. In each cohort, six subjects were randomly assigned to receive active drug and two subjects were assigned to receive the placebo. All doses were well tolerated, and no severe or serious adverse events occurred. Maximum plasma concentrations of BAL4815 were observed 1.5 to 3 h after p.o. drug intake or at the end of the 1-h infusion. After both routes of administration, values for maximum drug concentration observed in plasma and area under the concentration-time curve increased slightly more than proportionally to the administered dose. Mean elimination half-lives were particularly long (56 to 77 h after p.o. administration and 76 to 104 h after i.v. administration). The volume of distribution was large (155 to 292 liters after p.o. administration and 304 to 494 liters after i.v. administration) and systemic clearance was low (1.9 to 2.8 liter/h after p.o. administration and 2.8 to 5.0 liter/h after i.v. administration). Urinary recovery of BAL4815 was less than 0.4% of the infused dose. Based on the exposure data, oral bioavailability of BAL4815 is assumed to be very high. The pharmacokinetics of BAL4815 are well suited to maintaining concentrations of BAL4815 for a long period of time in the body and to enabling an effective treatment of systemic mycoses.
doi:10.1128/AAC.50.1.279-285.2006
PMCID: PMC1346775  PMID: 16377698
17.  Reply 
Gut  1991;32(11):1428-1429.
PMCID: PMC1379185
18.  Tolerability and safety of GS-101 eye drops, an antisense oligonucleotide to insulin receptor substrate-1: a ‘first in man’ Phase I investigation 
AIMS
GS-101 (GeneSignal, Epalinges, Switzerland) is an antisense oligonucleotide that inhibits the expression of the scaffold protein insulin receptor substrate-1 (IRS-1). Inhibition of IRS-1 results in the prevention of neovascular growth and was shown to prevent the angiogenic process in preclinical in vitro and in vivo experiments. There is therefore a strong therapeutic rational for targeting angiogenesis in pathological neovascularization. We aimed to investigate the safety, tolerability and bioavailability of GS-101 eye drops.
METHODS
This was a Phase I open-label study. The investigation was performed in two steps. Local ocular tolerability was first assessed with the application of one single low dose in one eye. After no signs of intolerance were observed in the subjects, the dose escalation phase of the study was initiated, and the remaining subjects received three times daily escalating doses of GS-101 in one eye for 14 days.
RESULTS
The 14 healthy volunteers tolerated well 14 days' continued use of escalating doses of GS-101 from 43 to 430 µg per day. Other than itching, experienced also in the control eye by one subject and determined to be unrelated to the study treatment, no signs of intolerance were observed.
CONCLUSIONS
The tolerability profile obtained from this study suggests that GS-101 is safe for human use. Further clinical evaluations in diseases related to abnormal angiogenesis are being targeted. In particular, the neovascularization-related orphan indications of corneal graft rejection, retinopathy of pre-maturity and neovascular glaucoma are currently under Phase II clinical investigation and are showing promising results.
doi:10.1111/j.1365-2125.2009.03450.x
PMCID: PMC2767278  PMID: 19694734
antiangiogenic; cornea; insulin receptor substrate-1; pathologic neovascularization

Results 1-18 (18)