ABSTRACT
BACKGROUND AND STUDY AIMS: The Integrated Pulmonary Index® (IPI) is a mathematically-determined factor based on parameters of capnography and pulse oximetry, which should enable sensitive detection of impaired respiratory function. Aim was to investigate whether an additional measurement of the IPI during sedation for interventional endoscopy, compared to standard monitoring alone, allows a reduction of sedation-related respiratory depression. PATIENTS AND METHODS: 170 patients with standard monitoring randomly underwent either a blinded recording of capnography (control group, n=87) or capnography, including automated IPI calculation (IPI group, n=83), during deep sedation with midazolam and propofol. The primary endpoint was the maximum decrease of oxygen saturation from the baseline level before sedation. Secondary endpoints: incidence of hypoxemia (SaO2<90%), other sedation-related complications (apnea rate, bradycardia, hypotension), patient cooperation and satisfaction (VAS). RESULTS: Mean propofol dose in the IPI group (245±61mg) was comparable to the control group (225±47mg). The average drop of the oxygen saturation in the IPI group (6.5±4.1%) was nearly identical to that of the control group (7.1±4.6%, p=0.44). Apnea episodes >15s was found in 46 patients of the control and 31 of the IPI group (p<0.05). Frequency of occurrence of a drop in pO2-saturation <90%, bradycardia <50/min or a drop of systolic pressure <90mmHg were not significantly different in both groups. Mechanical ventilation was not required in any case. Patient cooperation and satisfaction were assessed similar in both groups. CONCLUSION: A clinically appealing advantage of IPI-assessment during deep sedation with midazolam and propofol for interventional endoscopy could not be documented. However, IPI registration was more effective in reducing the incidence of apnea episodes.
Subject(s)
Capnography/methods , Endoscopy, Gastrointestinal , Hypnotics and Sedatives/administration & dosage , Midazolam/administration & dosage , Oximetry/methods , Propofol/administration & dosage , Adult , Aged , Aged, 80 and over , Apnea/etiology , Deep Sedation/methods , Female , Germany , Humans , Hypoxia/etiology , Male , Middle Aged , Oxygen/blood , Prospective StudiesABSTRACT
BACKGROUND AND STUDY AIMS: This was to determine whether intervention based on additional capnographic monitoring reduces the incidence of hypoxemia during midazolam and propofol sedation for endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Patients (American Society of Anesthesiologists [ASA] IââIV) scheduled for ERCP under midazolam and propofol sedation were randomly assigned to a control arm with standard monitoring or an interventional arm with additional capnographic monitoring. In both arms detection of apnea prompted withholding of propofol administration, stimulation of the patient, insertion of a nasopharyngeal tube, or further measures. The primary study end point was incidence of hypoxemia (oxygen saturation [Sao 2] below 90â%); secondary end points included occurrences of severe hypoxemia (Sao 2â≤â85â%), bradycardia, and hypotension, and sedation quality (patient cooperation and satisfaction). RESULTS: 242 patients were enrolled at three German endoscopy centers. Intention-to-treat analysis revealed no significant reduction in hypoxemia incidence in the capnography arm compared with the standard arm (38.0â% vs. 44.4â%, Pâ=â0.314). Apnea was more frequently detected in the capnography arm (64.5â% vs. 6.0â%, Pâ<â0.001). There were no differences regarding rates of bradycardia and hypotension. Per-protocol analysis showed lower incidence of hypoxemia in the capnography arm compared with the standard arm (31.5â% vs. 44.8â%, Pâ=â0.048). There was one death related to sedation in the standard arm. Sedation quality was similar in the two groups. CONCLUSION: Intention-to-treat analysis showed hypoxemia incidence was not significantly lower in the additional capnography arm compared with standard monitoring. Additional capnographic monitoring of ventilatory activity resulted in improved detection of apnea.
Subject(s)
Capnography , Cholangiopancreatography, Endoscopic Retrograde/methods , Conscious Sedation/adverse effects , Hypnotics and Sedatives/adverse effects , Hypoxia/prevention & control , Midazolam/adverse effects , Propofol/adverse effects , Adult , Aged , Aged, 80 and over , Conscious Sedation/methods , Female , Humans , Hypnotics and Sedatives/administration & dosage , Hypoxia/epidemiology , Hypoxia/etiology , Incidence , Intention to Treat Analysis , Male , Midazolam/administration & dosage , Middle Aged , Monitoring, Physiologic , Outcome and Process Assessment, Health Care , Propofol/administration & dosageABSTRACT
BACKGROUND & AIMS: The aim of our study was to search for highly up-regulated genes in primary malignant liver tumours and to analyse their expression at the mRNA- and protein level. METHODS: Using a random-based gene fishing approach (representational difference analysis coupled to array hybridisation) we identified 7 genes high abundantly expressed in hepatocellular carcinoma (HCC) as compared to non-neoplastic liver tissue, among them a gene fragment of the aldo-ketoreductase (AKR) superfamily. Full length cloning and sequencing of the gene fragment identified it as B10 gene of the AKR-family 1 (AKR1B10). For expression analysis on transcriptional level quantitative real-time RT-PCR was performed in 22 HCC and 22 non-neoplastic liver cirrhotic tissues. RESULTS: Our data demonstrate significantly higher expression levels of AKR1B10-mRNA in HCC compared to non-tumourous cirrhotic liver tissue (p<0.0001). To evaluate its protein expression in primary malignant liver tumours, we investigated tissue arrays of 210 HCC and 51 cholangiocarcinomas (CC) by immunohistochemistry, using a monoclonal antibody against AKR1B10. Protein staining of AKR1B10 was significantly increased in well and moderately differentiated tumours compared to corresponding non-neoplastic liver tissue (p=0.023). However, AKR1B10-staining decreased in advanced, low differentiated tumours with a significant inverse correlation between AKR1B10-staining and tumour proliferation, indicated by Ki67 (MIB-1) staining (r=-0.89, p=0.02). CONCLUSION: The over-expression of AKR1B10 in early stages of well and moderately differentiated tumours and its down-regulation in advanced tumour-stages with low grade of differentiation demonstrated that AKR1B10 may be a helpful marker for differentiation and proliferation of HCC and CC.
Subject(s)
Aldehyde Reductase/genetics , Biomarkers, Tumor/genetics , Liver Neoplasms/enzymology , Liver Neoplasms/genetics , Aldehyde Reductase/metabolism , Aldo-Keto Reductases , Base Sequence , Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Case-Control Studies , Cell Differentiation , Cell Proliferation , Cholangiocarcinoma/enzymology , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , DNA Primers/genetics , Gene Expression Profiling , Humans , Immunohistochemistry , Liver Cirrhosis/enzymology , Liver Cirrhosis/genetics , Liver Neoplasms/pathology , Neoplasm Staging , Oligonucleotide Array Sequence Analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA, Neoplasm/genetics , RNA, Neoplasm/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND AND GOALS: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant polyposis syndrome caused by STK11 germline mutations. PJS is associated with an increased risk of cancer. In our cohort, clinical and phenotypic parameters were correlated with genotypic findings and patients were prospectively followed by surveillance. STUDY: Thirty-one patients treated between 2000 and 2006, were evaluated. STK11 genotyping was performed and phenotypes of patients with truncating (TM) and nontruncating mutations (NTM) were compared. RESULTS: Median age at first symptoms was 11 years and complications occurred before the age of ten in 42% of patients. STK11 mutations were detected in 16 of 22 families (12 TM; four NTM). Patients with TM had more surgical gastrointestinal (GI) interventions (p = 0.021), and female patients in the TM group had an increased risk of undergoing gynecological surgery (p = 0.016). Also, there was a trend towards a higher polyp count (p = 0.11) and earlier age at first polypectomy (p = 0.13) in the TM group. Ten carcinomas were detected in six patients resulting in a cancer risk of 65% up to the age of 65 years. Patients with TM tended to develop more cancers (p = 0.10). Importantly, our surveillance strategy used detected 50% of cancers (n = 5) at an early potentially curable stage. CONCLUSIONS: Our study shows that almost half of PJ patients have complications early in life independent of mutational status. Patients with TM require more surgical GI interventions and tend to develop more polyps and cancers. Furthermore, close surveillance detects early stage cancers in patients. We propose that surveillance should be started as early as 8 years in all patients to avoid complications. Moreover, patients with TM may benefit from surveillance at shorter intervals.
Subject(s)
Colonic Neoplasms/complications , Colonic Neoplasms/surgery , Colonic Polyps/complications , Colonic Polyps/surgery , Mutation/genetics , Peutz-Jeghers Syndrome/complications , Peutz-Jeghers Syndrome/genetics , Adolescent , Adult , Age Distribution , Child , Child, Preschool , Colonic Neoplasms/epidemiology , Colonic Polyps/epidemiology , Female , Genetic Association Studies , Germany/epidemiology , Humans , Infant , Male , Middle Aged , Peutz-Jeghers Syndrome/epidemiology , Peutz-Jeghers Syndrome/surgery , Young AdultABSTRACT
SEN virus (SENV) has been tentatively linked to transfusion-associated non-A-E hepatitis. We investigated SENV's role in unexplained hepatitis in other settings. Polymerase chain reaction amplification was used to detect 2 SENV variants (SENV-D and SENV-H) in 1706 patients and control subjects. SENV was detected in 54 (22%) of 248 patients with acute or chronic non-A-E hepatitis, 9 (35%) of 26 patients with hepatitis-associated aplastic anemia, and 0 of 17 patients with cryptogenic acute liver failure, compared with 150 (24%) of 621 control subjects with liver disease and 76 (10%) of 794 healthy control subjects. When controlling for geographic region, the prevalence of SENV among case and control subjects was not significantly different. The severity of acute or chronic hepatitis A, B, or C was not influenced by coexisting SENV infection. No etiological role for SENV in the cause of cryptogenic hepatitis could be demonstrated.