In vitro expression of the first capsule gene of Streptococcus pneumoniae, cpsA, is associated with serotype-specific colonization prevalence and invasiveness

The polysaccharide capsule protects Streptococcus pneumoniae from phagocytosis during invasive infection, but inhibits adherence. Serotypes vary in their tendency to colonize the nasopharynx or cause invasive infection, and differences in capsule expression may play a role. Expression of the first gene of the capsule operon, cpsA, during in vitro growth of 43 clinical isolates representing 14 common pneumococcal serotypes was compared using quantitative RT-PCR. Serotypes associated with invasive infection (1, 4, 5, 7F, 8 and 14) expressed an average of twofold (P=0.0003) more cpsA than serotypes associated with nasopharyngeal colonization (6A, 6B, 9V, 15, 18C, 19F, 23F and 33). There was no difference in cpsA expression in response to growth under environmental oxygen or anaerobic conditions between the invasive and colonizing transparent strains tested: oxygen concentration did not affect cpsA expression in either the invasive or the colonizing transparent strains. Expression of cpsA at OD(600) 0.6 tended to be greater in strains with a longer lag phase during in vitro growth (P=0.07). Therefore, cpsA expression under ambient oxygen concentrations correlates with serotype-specific invasiveness and is inversely associated with the prevalence of serotype-specific carriage.

[TGF-beta1 as a pathophysiological factor in fracture healing]

AIM: TGF-beta1 is an important local and systemic regulatory molecule during fracture healing. Various authors have shown differences in the systemic levels of TGF-beta1 over the time taken for bone healing in distraction osteogenesis and osteotomies. Previous studies have shown characteristic differences in the physiological levels of growth factors between normal fracture healing and delayed fracture union. The aim of the present study was to evaluate possible differences in sera levels of patients with normal and delayed union fracture healing. METHODS: Patients with long bone shaft fractures were recruited prospectively. Peripheral blood samples were collected over a period of 1 year using a standardized time schedule. At the end of the individual's investigation period, TGF-beta1 levels were determined. To achieve a homogeneous collective of patients, only those with a maximum of two fractures were included in the study. After matching for four criteria, we compared patients with normal fracture healing to patients with delayed unions. The fact of delayed union was accepted in case of failed consolidation 4 months after trauma. RESULTS: During a prospective study period of 1 year, 15 patients with normal fracture healing could be compared to 15 patients suffering from delayed union. By determining the absolute sera levels we found a typical increase of TGF-beta1 up to 2 weeks after fracture in both groups, with a subsequent decrease up to the sixth week after fracture. However, a decline in serum concentration occurred earlier in patients with delayed union, causing significantly lower TGF-beta1 levels in the non-union group 4 weeks after trauma (P=0.00006). CONCLUSION: Even with a relatively small number of patients, we could show a significant difference in serum concentrations of TGF-beta1 between the investigated groups. If these results can be verified within a larger collective, TGF-beta1 could be used as a predictive cytokine for delayed fracture healing.

[Autonomic neuropathy in somatization disorders]

AIM: We conducted a study to investigate whether patients with somatization disorder show abnormal values in autonomic testing, especially in the central baroreceptor sensitivity. PATIENTS AND METHODS: Seventy-one patients were included. All had a diagnosis of somatization disorder (ICD-10, F45.0). Psychometric testing was performed by means of validated questionnaires (STAI, STAXI, FPI, GBB, ADS, SOMS, SCL-90-R). Autonomic regulation was analyzed by international standards using frequency spectral calculation by fast Fourier transformation. Thereby 3 different groups were detected: 12 patients with a baroreceptor sensitivity (BRS) of less than 3.0 ms/mm Hg, 20 patients with normal BRS (> 9.0 ms/mm Hg), and an in-between group (n = 39) with intermediate BRS. Controlling for age, a covariance analysis was calculated. RESULTS: The two extreme groups showed no difference in psychometric testing. However, significant differences were discernible in spectral values of mid-frequency-band (p < 0.05) in a covariance analysis with age as covariate. Equally the 24 h blood pressure determination showed significantly higher values for the group with BRS < 3.0 ms/mm Hg (p < 0.05 to 0.001). CONCLUSIONS: In a high percentage (17 %) of patients diagnosed to have somatization disorder autonomic dysregulation becomes apparent and is accompanied by increased blood pressure. Therefore it doesn't seem accurate to overlook concomitant organic lesions in somatization disorders despite patients lacking overtly clinical signs but suffering from various unspecific symptoms.

Similarities in the Subgingival Microbiota Assessed by a Curet Sampling Method at Sites With Chronic Periodontitis

Background: The goal of this study was to determine whether site-specific differences in the subgingival microbiota could be detected by the checkerboard method in subjects with periodontitis. Methods: Subjects with at least six periodontal pockets with a probing depth (PD) between 5 and 7 mm were enrolled in the study. Subgingival plaque samples were collected with sterile curets by a single-stroke procedure at six selected periodontal sites from 161 subjects (966 subgingival sites). Subgingival bacterial samples were assayed with the checkerboard DNA-DNA hybridization method identifying 37 species. Results: Probing depths of 5, 6, and 7 mm were found at 50% (n = 483), 34% (n = 328), and 16% (n = 155) of sites, respectively. Statistical analysis failed to demonstrate differences in the sum of bacterial counts by tooth type (P = 0.18) or specific location of the sample (P = 0.78). With the exceptions of Campylobacter gracilis (P <0.001) and Actinomyces naeslundii (P <0.001), analysis by general linear model multivariate regression failed to identify subject or sample location factors as explanatory to microbiologic results. A trend of difference in bacterial load by tooth type was found for Prevotella nigrescens (P <0.01). At a cutoff level of >/=1.0 x 10(5), Porphyromonas gingivalis and Tannerella forsythia (previously T. forsythensis) were present at 48.0% to 56.3% and 46.0% to 51.2% of sampled sites, respectively. Conclusions: Given the similarities in the clinical evidence of periodontitis, the presence and levels of 37 species commonly studied in periodontitis are similar, with no differences between molar, premolar, and incisor/cuspid subgingival sites. This may facilitate microbiologic sampling strategies in subjects during periodontal therapy.

Displaced premolars in panoramic radiography: fact or fallacy?

OBJECTIVE: To test the null hypothesis that there is no difference between premolar position visualized on panoramic radiographs (PRs) and lateral headfilms (LHs). MATERIALS AND METHODS: The prevalence of differences in the direction of crown angulation between PR and LH was assessed. Furthermore, brass wire markers with different sagittal and transverse angulations were placed in a dry skull. With the markers in place, LHs and PRs were taken. RESULTS: A difference in the direction of crown angulation of unerupted second premolars between PR and LH occurred in 19.5% of patients. The reason for the angulation differences is a buccolingual orientation of the tooth, which appears as a mesiodistal angulation on the PR. CONCLUSION: The null hypothesis was rejected since in one-fifth of the patients premolar projection differs between the panoramic radiograph and the lateral headfilm.

Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas

BACKGROUND: The aim was to assess the clinical relevance of the World Health Organization and tumour node metastasis (TNM) classifications in patients with pancreatic neuroendocrine tumours (pNETs). METHODS: Prospectively collected data from 118 consecutive patients with a pNET receiving surgical intervention were analysed. RESULTS: Forty-one patients had well differentiated neuroendocrine tumours, 64 had well differentiated neuroendocrine carcinomas and 13 had poorly differentiated neuroendocrine carcinomas. Five-year survival rates were 95, 44 and 0 per cent respectively (P < 0.001). There was no difference in survival after R0 and R1/R2 resections in patients with neuroendocrine carcinomas (P = 0.905). In those with well differentiated neuroendocrine carcinomas, any resection and having a clinically non-functional tumour significantly increased survival (P = 0.003 and P = 0.037 respectively). The TNM stage was I in 37 patients, II in 15 patients, III in 32 patients and IV in 34 patients. There were significant differences in 5-year survival between stage I and II (88 and 85 per cent respectively) and stage III and IV (31 and 42 per cent respectively) (P = 0.010). CONCLUSION: Both classifications accurately reflect the clinical outcome of patients with pNET. The resection status may not be critical for long-term survival in patients with pNET.

Ear acupuncture points in neonates

OBJECTIVE: The aim of this study was to determine the presence and absence of acupuncture ear points in healthy neonates. DESIGN: This was a prospective observational study performed at a university teaching hospital. Subjects: The subjects were healthy neonates. We compared male and female neonates, right and left lobe, term and preterm deliveries, and cesarean sections versus vaginal deliveries. Examinations took place on the fifth day after delivery and were performed by a neuronal pen (SVESA 1070, SVESA GmbH, Munich, Germany). An integrated optical signal detected the ear points that were assigned to the Chinese ear map. MAIN OUTCOME MEASURES: This study looked at the presence and absence of acupuncture ear points in neonates. RESULTS: There were 27 male neonates and 23 female neonates. In 66% of neonates, no points at all were found. We detected 0-4 points on the right lobe and 0-2 points on the left lobe. The psychovegetative rim was the most common point in 26% of all children. No psychic points were detected. No significant differences were found between right and left ear lobes, male and female neonates, or term and preterm deliveries with respect to numbers of points or access of points. Moreover, there were no differences among modes of delivery. CONCLUSIONS: Some ear points in healthy neonates are detectable and not dependent on side of the ear lobe. Females had significantly more acupuncture points. There was an extremely significant difference in the group with 2 active earpoints between cesarean and vaginally delivered neonates. The most important point was the psychovegetative rim and the absence of psychic points in favor of the organ points. Possibly, ear points in neonates could be used for diagnostic and therapeutic options in neonates in the future.

Routine procedures in NICUs: factors influencing pain assessment and ranking by pain intensity

BACKGROUND: Pain associated with routine procedures in NICUs is often inadequately managed. Barriers to more appropriate pain management are nurses' and physicians' knowledge and the challenges of collaborative decision-making. Few studies describe the differing perceptions of procedural pain intensity among nurses and physicians in NICUs which could complicate common decision-making. This study set out to explore the factors influencing pain intensity assessment and to gain insight into a possible pain intensity classification of routine procedures in the NICU. METHOD: A survey was conducted among 431 neonatal health care professionals from 4 tertiary level NICUs. Each routine procedure was assessed on a 10-point visual analogue scale (VAS) assuming absence of analgesia. RESULTS: Multiple ANCOVA models showed that nurses rated 19 of the 27 procedures as significantly more painful than did physicians (p<0.05). We found no differences in pain assessment based on professional experience, gender or age. Of the 27 procedures listed, 70% were rated as painful and 44% were judged very painful. Ranking and classification of the pain intensity of routine procedures were drawn up. The general ranking of the median across all procedures shows that "insertion of a thoracic drain" is assessed as the most painful procedure. CONCLUSIONS: The majority of routine procedures in an NICU are considered to be painful. Nurses generally rate procedures as more painful than do physicians. This difference in assessment deserves exploration in regard to its impact on collaborative decision-making in neonate pain management.

Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury

INTRODUCTION: Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO2 by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO2 response to INO. METHODS: After animal ethics committee approval, pigs were anesthetized and exposed to 2 hours of endotoxin infusion. Levels of cytokines, prostanoid, leucotriene and endothelin-1 (ET-1) were sampled prior to endotoxin exposure and hourly thereafter. All animals were exposed to 40 ppm INO: 28 animals were exposed at either 4 hours or 6 hours and a subgroup of nine animals was exposed both at 4 hours and 6 hours after onset of endotoxin infusion. RESULTS: Based on the response to INO, the animals were retrospectively placed into a responder group (increase in PaO2 > or = 20%) or a nonresponder group. All mediators increased with endotoxin infusion although no significant differences were seen between responders and nonresponders. There was a mean difference in ET-1, however, with lower levels in the nonresponder group than in the responder group, 0.1 pg/ml versus 3.0 pg/ml. Moreover, five animals in the group exposed twice to INO switched from responder to nonresponder and had decreased ET-1 levels (3.0 (2.5 to 7.5) pg/ml versus 0.1 (0.1 to 2.1) pg/ml, P < 0.05). The pulmonary artery pressure and ET-1 level were higher in future responders to INO. CONCLUSIONS: ET-1 may therefore be involved in mediating the response to INO.

Entropy and bispectral index for assessment of sedation, analgesia and the effects of unpleasant stimuli in critically ill patients: an observational study

INTRODUCTION: Sedative and analgesic drugs are frequently used in critically ill patients. Their overuse may prolong mechanical ventilation and length of stay in the intensive care unit. Guidelines recommend use of sedation protocols that include sedation scores and trials of sedation cessation to minimize drug use. We evaluated processed electroencephalography (response and state entropy and bispectral index) as an adjunct to monitoring effects of commonly used sedative and analgesic drugs and intratracheal suctioning. METHODS: Electrodes for monitoring bispectral index and entropy were placed on the foreheads of 44 critically ill patients requiring mechanical ventilation and who previously had no brain dysfunction. Sedation was targeted individually using the Ramsay Sedation Scale, recorded every 2 hours or more frequently. Use of and indications for sedative and analgesic drugs and intratracheal suctioning were recorded manually and using a camera. At the end of the study, processed electroencephalographical and haemodynamic variables collected before and after each drug application and tracheal suctioning were analyzed. Ramsay score was used for comparison with processed electroencephalography when assessed within 15 minutes of an intervention. RESULTS: The indications for boli of sedative drugs exhibited statistically significant, albeit clinically irrelevant, differences in terms of their association with processed electroencephalographical parameters. Electroencephalographical variables decreased significantly after bolus, but a specific pattern in electroencephalographical variables before drug administration was not identified. The same was true for opiate administration. At both 30 minutes and 2 minutes before intratracheal suctioning, there was no difference in electroencephalographical or clinical signs in patients who had or had not received drugs 10 minutes before suctioning. Among patients who received drugs, electroencephalographical parameters returned to baseline more rapidly. In those cases in which Ramsay score was assessed before the event, processed electroencephalography exhibited high variation. CONCLUSIONS: Unpleasant or painful stimuli and sedative and analgesic drugs are associated with significant changes in processed electroencephalographical parameters. However, clinical indications for drug administration were not reflected by these electroencephalographical parameters, and barely by sedation level before drug administration or tracheal suction. This precludes incorporation of entropy and bispectral index as target variables for sedation and analgesia protocols in critically ill patients.

Analysis of in-cylinder pressure transducer data quality utilizing a SIDI turbocharged engine

In-cylinder pressure transducers have been used for decades to record combustion pressure inside a running engine. However, due to the extreme operating environment, transducer design and installation must be considered in order to minimize measurement error. One such error is caused by thermal shock, where the pressure transducer experiences a high heat flux that can distort the pressure transducer diaphragm and also change the crystal sensitivity. This research focused on investigating the effects of thermal shock on in-cylinder pressure transducer data quality using a 2.0L, four-cylinder, spark-ignited, direct-injected, turbo-charged GM engine. Cylinder four was modified with five ports to accommodate pressure transducers of different manufacturers. They included an AVL GH14D, an AVL GH15D, a Kistler 6125C, and a Kistler 6054AR. The GH14D, GH15D, and 6054AR were M5 size transducers. The 6125C was a larger, 6.2mm transducer. Note that both of the AVL pressure transducers utilized a PH03 flame arrestor. Sweeps of ignition timing (spark sweep), engine speed, and engine load were performed to study the effects of thermal shock on each pressure transducer. The project consisted of two distinct phases which included experimental engine testing as well as simulation using a commercially available software package. A comparison was performed to characterize the quality of the data between the actual cylinder pressure and the simulated results. This comparison was valuable because the simulation results did not include thermal shock effects. All three sets of tests showed the peak cylinder pressure was basically unaffected by thermal shock. Comparison of the experimental data with the simulated results showed very good correlation. The spark sweep was performed at 1300 RPM and 3.3 bar NMEP and showed that the differences between the simulated results (no thermal shock) and the experimental data for the indicated mean effective pressure (IMEP) and the pumping mean effective pressure (PMEP) were significantly less than the published accuracies. All transducers had an IMEP percent difference less than 0.038% and less than 0.32% for PMEP. Kistler and AVL publish that the accuracy of their pressure transducers are within plus or minus 1% for the IMEP (AVL 2011; Kistler 2011). In addition, the difference in average exhaust absolute pressure between the simulated results and experimental data was the greatest for the two Kistler pressure transducers. The location and lack of flame arrestor are believed to be the cause of the increased error. For the engine speed sweep, the torque output was held constant at 203 Nm (150 ft-lbf) from 1500 to 4000 RPM. The difference in IMEP was less than 0.01% and the PMEP was less than 1%, except for the AVL GH14D which was 5% and the AVL GH15DK which was 2.25%. A noticeable error in PMEP appeared as the load increased during the engine speed sweeps, as expected. The load sweep was conducted at 2000 RPM over a range of NMEP from 1.1 to 14 bar. The difference in IMEP values were less 0.08% while the PMEP values were below 1% except for the AVL GH14D which was 1.8% and the AVL GH15DK which was at 1.25%. In-cylinder pressure transducer data quality was effectively analyzed using a combination of experimental data and simulation results. Several criteria can be used to investigate the impact of thermal shock on data quality as well as determine the best location and thermal protection for various transducers.

Lung volume reduction surgery versus conservative treatment in severe emphysema

Lung volume reduction surgery (LVRS) has been proposed for patients with severe emphysema to improve dyspnoea and pulmonary function. It is unknown, however, whether prognosis and pulmonary function in these patients can be improved compared to conservative treatment. The effect of LVRS and conservative therapy were compared prospectively in 57 patients with emphysema, who fulfilled the standard criteria for LVRS. The patients were divided into two groups according to their own decision. Patients in group 1 (n=29, eight females, mean+/-SEM 58.8+/-1.7 yrs, forced expiratory volume in one second (FEV1) 27.6+/-1.3% of the predicted value) underwent LVRS. Patients in group 2 (n=28, five females, 58.5+/-1.8 yrs, FEV1 30.8+/-1.4% pred) preferred to postpone LVRS. There were no significant differences in lung function between the two groups at baseline; however, there was a tendency towards better functional status in the control group. The control group had a better modified Medical Research Council (MMRC) dyspnea score (3.1+/-0.15 versus 3.5+/-0.1, p<0.04). Model-based comparisons were used to estimate the differences between the two groups over 18 months. Significant improvements were observed in the LVRS group compared to the control group in FEV1, total lung capacity (TLC), Residual volume (RV), MMRC dyspnea score and 6-min walking distance on all follow up visits. The estimated difference in FEV1 was 33% (95% confidence interval 13-58%; p>0.0001), in TLC 12.9% (7.9-18.8%; p>0.0001), in RV 60.9% 32.6-89.2%; p>0.0001), in 6-min walking distance 230 m (138-322 m; p<0.002) and in MMRC dyspnoea score 1.17 (0.79-1.55; p<0.0001). In conclusion, lung volume reduction surgery is more effective than conservative treatment for the improvement of dyspnoea, lung function and exercise capacity in selected patients with severe emphysema.

OCT4 expression in human non-small cell lung cancer: implications for therapeutic intervention

Here we investigate the expression of OCT4 human lung adenocarcinoma and bronchioloalveolar carcinoma (BAC) tumor biopsies and tumor-derived primary cell cultures. OCT4 has been detected in several human tumors suggesting a potentially critical role in tumorigenesis. We assessed the presence of OCT4 in clinical tumor samples of both adenocarcinoma and BAC at the cellular and transcriptional levels, respectively. Furthermore, we evaluated tumor-derived cell cultures for potential differences in OCT4 expression. Immunohistochemical analysis depicted OCT4 in 2 of 8 adenocarcinoma tumor samples and 3 of 5 BAC tumor samples, with no apparent difference in the degree of expression among the sections examined. These results were validated by transcript analysis. Flow cytometric assessment of 11 adenocarcinoma-derived cell cultures and 3 BAC-derived cell cultures revealed significantly higher OCT4 expression in adenocarcinoma tumors compared to their normal counterparts. This, however, was not observed in the BAC cultures. Comparative studies of OCT4 in adenocarcinoma and BAC tumor cell cultures demonstrated a dramatically higher expression in the former. The expression of OCT4 may represent a specific and effective target for therapeutic intervention in adenocarcinoma and BAC. In addition, the aberrant expression and distribution of OCT4 may indicate important parameters concerning the differences between adenocarcinoma and BAC.

Biolimus-eluting biodegradable polymer versus sirolimus-eluting permanent polymer stent performance in long lesions: results from the LEADERS multicentre trial substudy

AIMS: Lesion length remains a predictor of target lesion revascularisation and results of long lesion stenting remain poor. Sirolimus-eluting stents have been shown to perform better than paclitaxel eluting stents in long lesions. In this substudy of the LEADERS trial, we compared the performance of biolimus biodegradable polymer (BES) and sirolimus permanent polymer stents (SES) in long lesions. METHODS AND RESULTS: A total of 1,707 'all-comer' patients were randomly allocated to treatment with BES and SES. A stratified analysis of angiographic and clinical outcomes at nine months and one year, respectively was performed for vessels with lesion length <20 mm versus >20 mm (as measured by quantitative angiography).Of 1,707 patients, 592 BES patients with 831 lesions and 619 SES patients with 876 lesions had only short lesions treated. One hundred and fifty-three BES patients with 166 lesions and 151 SES patients with 162 lesions had long lesions. There were no significant differences in baseline clinical characteristics, except for higher number of patients with long lesions presenting with acute myocardial infarction in both stent groups. Long lesions tended to have lower MLD and greater percent diameter stenosis at baseline than short lesions. Late loss was greater for long lesions than short lesions. There was no statistically significant difference in late loss between BES and SES stents (0.32+/-0.69 vs 0.24+/-0.57, p=0.59). Binary in-segment restenosis was present in 23.2% versus 13.1% of long lesions treated with BES and SES, respectively (p=0.042). In patients with long lesions, the overall MACE rate was similar for BES and SES (17% vs 14.6%; p=0.62). There was a trend towards higher overall TLR rate with BES (12.4 % vs 6.0%; HR=2.06; p=0.07) and clinically driven TLR (10.5% vs 5.3%: HR 1.94; p=0.13). Rates of definite stent thrombosis were 3.3% in the long lesion group and 1.3-1.7 % in the short lesion group. CONCLUSIONS: BES and SES appear similar with respect to MACE in long lesions in this "all-comer" patient population. However, long lesions tended to have a higher rate of binary in-segment restenosis and TLR following BES than SES treatment.

Effect of animal species and age on plate-induced vascular damage in cortical bone

Plates used for fracture fixation produce vascular injury to the underlying cortical bone. During the recovery of the blood supply, temporary osteoporosis is observed as a result of Haversian remodeling of the necrotic bone. This process temporarily reduces the strength of the bone. We tackled the postulate that quantitative differences exist between animal species, and in different bones within the same species, due to variations in the relative importance of the endosteal and periosteal blood supplies. Using implants scaled to the size of the bone, we found comparable cortical vascular damage in the sheep and in the dog, and in the tibia and femur of each animal. We observed a significant reduction in cortical vascular damage using plates that had a smaller contact area with the underlying bone. No significant difference in cortical vascular damage was noted in animals of different ages.