Association of moderate alcohol use and binge drinking during pregnancy with neonatal health.

Background:  Heavy drinking and smoking during pregnancy are known to have a negative impact on the unborn child. However, the impact of low-to-moderate alcohol consumption and binge drinking has been debated recently. The aim of this study was to examine the relationship of moderate prenatal drinking and binge drinking with birthweight, being small for gestational age (SGA) at birth, preterm birth, and neonatal asphyxia. Methods:  Moderate alcohol drinking, binge drinking, and several possible confounders were assessed in 1,258 pregnant women; information on neonatal health was obtained at birth. Results:  Results indicate that 30.8% of the women drank at low levels (<2 glasses/wk), 7.9% drank moderately (2 to 4 glasses/wk), and 0.9% showed higher levels of drinking (≥5 glasses/wk); 4.7% reported binge drinking (defined as ≥3 glasses/occasion). 6.4% of the children were SGA (<10th percentile of birthweight adjusted for gestational age), 4.6% were preterm (<37th week of gestation), and 13.0% showed asphyxia (arterial cord pH <7.10 and/or arterial cord lactate >6.35 mmol and/or Apgar score <7 at 5 minutes). When controlling for maternal age, citizenship, occupational status, parity, smoking, use of prescription/over-the-counter drugs, illicit drug use, and child gender moderate drinking was related to lower birthweight (p < 0.01), and moderate drinking and binge drinking were associated with neonatal asphyxia at trend level (p = 0.06 and p = 0.09). Moderate drinking and binge drinking were not related to length of gestation. Conclusions:  In contrast to recent reviews in the field, our results assume that moderate drinking and binge drinking are risk factors for neonatal health.

Decreased glucose-induced thermogenesis after weight loss in obese subjects: a predisposing factor for relapse of obesity?

Glucose-induced thermogenesis (GIT) after a 100-g oral glucose load was measured by continuous indirect calorimetry in 32 nondiabetic and diabetic obese subjects and compared to 17 young and 13 middle aged control subjects. The obese subjects were divided into three groups: A (n = 12) normal glucose tolerance, B (n = 13) impaired glucose tolerance, and C (n = 7) diabetics, and were studied before and after a body weight loss ranging from 9.6 to 33.5 kg consecutive to a 4 to 6 months hypocaloric diet. GIT, measured over 3 h and expressed as percentage of the energy content of the load, was significantly reduced in obese groups A and C (6.2 +/- 0.6, and 3.8 +/- 0.7%, respectively) when compared to their age-matched control groups: 8.6 +/- 0.7 (young) and 5.8 +/- 0.3% (middle aged). Obese group B had a GIT of 6.1 +/- 0.6% which was lower than that of the young control group but not different from the middle-aged control group. After weight loss, GIT in the obese was further reduced in groups A and B than before weight loss: ie, 3.4 +/- 0.6 (p less than 0.001), 3.7 +/- 0.5 (p less than 0.01) respectively, whereas in group C, weight loss induced no further diminution in GIT (3.8 +/- 0.6%). These results support the concept of a thermogenic defect after glucose ingestion in obese individuals which is not the consequence of their excess body weight but may be one of the factors favoring the relapse of obesity after weight loss.

Molecular Analysis of the PTEN Gene in a Choroidal Schwannoma in the Context of a Hamartomatous Syndrome

Purpose: To investigate the molecular involvement of PTEN, a tumor suppressor gene, in a case of cellular pigmented choroidal Schwannoma in a patient with hamartomatous syndrome due to heterozygous PTEN germline mutation. Methods: Histopathological, immunohistochemical, and electron microscopy analyses were performed by standard procedures. Paraffin-embedded samples of normal and tumor eye tissues were collected and DNA was extracted. A 145 bp region flanking the heterozygous c.406T>C mutation in exon 5 of PTEN was amplified by PCR and sequenced. To evaluate the allelic status of PTEN in the tumor sample, we cloned different PCR products in E. coli using a TA cloning procedure. Results: Histopathology demonstrated a posterior choroidal mass measuring 1.3 x 1.6 x 1.4 cm. The tumor was composed by fascicles of spindle cells with wavy cytoplasm. No Verrocay bodies could be identified. Scattered histiocytes with clear cytoplasm were present. By immunohistochemistry, the cells were expressing S100 and focally Melan A proteins. Pericellular type IV collagen could be demonstrated. Interlacing cytoplasmic processes covered by thick basement membrane could be found by electron microscopy as well as few premelanosomes. Moderate PTEN expression by immunohistochemistry was identified in some cells. As expected, the germline mutation could be detected by DNA sequencing in both the paraffin-embedded normal and tumor eye tissues. Analysis of 33 E. coli colonies bearing clones from the tumor eye tissue DNA surprisingly revealed that most of them contained the PTEN wild-type allele (29 vs. 4, Fisher's test p-value = 0.002). Conclusions: This is the first reported case of choroidal cellular Schwannoma arising in the context of a PTEN hamartomatous syndrome. Allelic analysis of PTEN in the tumor suggests a statistically-significant partial loss of heterozygozity in favor of the wild-type allele. Our findings are in clear contrast with what is usually observed in cancer tissues, for which mutated alleles of tumor suppressor genes are usually brought to homozygosity. Similar results were previously reported in human non-Hodgkin's lymphomas, displaying an overexpression of the wild-type form of the tumor suppressor gene p53. We are in the process of investigating additional DNA derived from other fresh and paraffin-embedded tissues from the patient, in order to gain insights on the molecular bases of PTEN involvement in this rare choroidal Schwannoma.

Real-time, in vivo intracellular recordings of caterpillar-induced depolarization waves in sieve elements using aphid electrodes.

Plants propagate electrical signals in response to artificial wounding. However, little is known about the electrophysiological responses of the phloem to wounding, and whether natural damaging stimuli induce propagating electrical signals in this tissue. Here, we used living aphids and the direct current (DC) version of the electrical penetration graph (EPG) to detect changes in the membrane potential of Arabidopsis sieve elements (SEs) during caterpillar wounding. Feeding wounds in the lamina induced fast depolarization waves in the affected leaf, rising to maximum amplitude (c. 60 mV) within 2 s. Major damage to the midvein induced fast and slow depolarization waves in unwounded neighbor leaves, but only slow depolarization waves in non-neighbor leaves. The slow depolarization waves rose to maximum amplitude (c. 30 mV) within 14 s. Expression of a jasmonate-responsive gene was detected in leaves in which SEs displayed fast depolarization waves. No electrical signals were detected in SEs of unwounded neighbor leaves of plants with suppressed expression of GLR3.3 and GLR3.6. EPG applied as a novel approach to plant electrophysiology allows cell-specific, robust, real-time monitoring of early electrophysiological responses in plant cells to damage, and is potentially applicable to a broad range of plant-herbivore interactions.

Overall Burden of Healthcare-Associated Infections Among Surgical Patients: Results of a National Study.

OBJECTIVE:: To assess the overall burden of healthcare-associated infections (HAIs) in patients exposed and nonexposed to surgery. BACKGROUND:: Targeted HAI surveillance is common in healthcare institutions, but may underestimate the overall burden of disease. METHODS:: Prevalence study among patients hospitalized in 50 acute care hospitals participating in the Swiss Nosocomial Infection Prevalence surveillance program. RESULTS:: Of 8273 patients, 3377 (40.8%) had recent surgery. Overall, HAI was present in 358 (10.6%) patients exposed to surgery, but only in 206 (4.2%) of 4896 nonexposed (P < 0.001). Prevalence of surgical site infection (SSI) was 5.4%. Healthcare-associated infections prevalence excluding SSI was 6.5% in patients with surgery and 4.7% in those without (P < 0.0001). Patients exposed to surgery carried less intrinsic risk factors for infection (age >60 years, 55.6% vs 63.0%; American Society of Anesthesiologists score >3, 5.9% vs 9.3%; McCabe for rapidly fatal disease, 3.9% vs 6.6%; Charlson comorbidity index >2, 12.3% vs 20.9%, respectively; all P < 0.001) than those nonexposed, but more extrinsic risk factors (urinary catheters, 39.6% vs 14.1%; central venous catheters, 17.8% vs 7.1%; mechanical ventilation, 4.7% vs 1.3%; intensive care stay, 18.3% vs 8.8%, respectively; all P < 0.001). Exposure to surgery independently predicted an increased risk of HAI (odds ratio 2.43; 95% CI 2.0-3.0). CONCLUSIONS:: Despite a lower intrinsic risk, patients exposed to surgery carried more than twice the overall HAI burden than those nonexposed; almost half was accountable to SSI. Extending infection control efforts beyond SSI prevention in these patients might be rewarding, especially because of the extrinsic nature of risk factors.

Quantification of magmatic and hydrothermal processes in a peralkaline syenite-alkali granite complex based on textures, phase equilibria, and stable and radiogenic isotopes

The Puklen complex of the Mid-Proterozoic Gardar Province, South Greenland, consists of various silica-saturated to quartz-bearing syenites, which are intruded by a peralkaline granite. The primary mafic minerals in the syenites are augite +/- olivine + Fe-Ti oxide + amphibole. Ternary feldspar thermometry and phase equilibria among mafic silicates yield T = 950-750degreesC, a(SiO2) = 0.7-1 and an f(O2) of 1-3 log units below the fayalite-magnetite-quartz (FMQ) buffer at 1 kbar. In the granites, the primary mafic minerals are ilmenite and Li-bearing arfvedsonite, which crystallized at temperatures below 750degreesC and at f(O2) values around the FMQ buffer. In both rock types, a secondary post-magmatic assemblage overprints the primary magmatic phases. In syenites, primary Ca-bearing minerals are replaced by Na-rich minerals such as aegirine-augite and albite, resulting in the release of Ca. Accordingly, secondary minerals include ferro-actinolite, (calcite-siderite)(ss), titanite and andradite in equilibrium with the Na-rich minerals. Phase equilibria indicate that formation of these minerals took place over a long temperature interval from near-magmatic temperatures down to similar to300degreesC. In the course of this cooling, oxygen fugacity rose in most samples. For example, late-stage aegirine in granites formed at the expense of arfvedsonite at temperatures below 300degreesC and at an oxygen fugacity above the haematite-magnetite (HM) buffer. The calculated delta(18)O(melt) value for the syenites (+5.9 to +6.3parts per thousand) implies a mantle origin, whereas the inferred delta(18)O(melt) value of <+5.1parts per thousand for the granitic melts is significantly lower. Thus, the granites require an additional low-delta(18)O contaminant, which was not involved in the genesis of the syenites. Rb/Sr data for minerals of both rock types indicate open-system behaviour for Rb and Sr during post-magmatic metasomatism. Neodymium isotope compositions (epsilonNd(1170 Ma) = -3.8 to -6.4) of primary minerals in syenites are highly variable, and suggest that assimilation of crustal rocks occurred to variable extents. Homogeneous epsilon(Nd) values of -5.9 and -6.0 for magmatic amphibole in the granites lie within the range of the syenites. Because of the very similar neodymium isotopic compositions of magmatic and late- to post-magmatic minerals from the same syenite samples a principally closed-system behaviour during cooling is implied. In contrast, for the granites an externally derived fluid phase is required to explain the extremely low epsilon(Nd) values of about -10 and low delta(18)O between +2.0 and +0.5parts per thousand for late-stage aegirine, indicating an open system in the late-stage history. In this study we show that the combination of phase equilibria constraints with stable and radiogenic isotope data on mineral separates can provide much better constraints on magma evolution during emplacement and crystallization than conventional whole-rock studies.

Collaborative quality improvement to manage pain in acute care hospitals.

Objective. Collaborative quality improvement programs have been successfully used to manage chronic diseases in adults and acute lung complications in premature infants. Their effectiveness to improve pain management in acute care hospitals is currently unknown. The purpose of this study was to determine whether a collaborative quality improvement program implemented at hospital level could improve pain management and overall pain relief. Design.To assess the effectiveness of the program, we performed a before-after trial comparing patient's self-reported pain management and experience before and after program implementation. We included all adult patients hospitalized for more than 24 hours and discharged either to their home or to a nursing facility, between March 1, 2001 and March 31, 2001 (before program implementation) and between September 15, 2005 and October 15, 2005 (after program implementation). Setting.A teaching hospital of 2,096 beds in Geneva, Switzerland. Patients.All adult patients hospitalized for more than 24 hours and discharged between 1 to 31 March 2001 (before program) and 15 September to 15 October 2005 (after program implementation). Interventions.Implementation of a collaborative quality improvement program using multifaceted interventions (staff education, opinion leaders, patient education, audit, and feedback) to improve pain management at hospital level. Outcome Measures.Patient-reported pain experience, pain management, and overall hospital experience based on the Picker Patient Experience questionnaire, perceived health (SF-36 Health survey). Results.After implementation of the program only 2.3% of the patients reported having no pain relief during their hospital stay (vs 4.5% in 2001, P = 0.05). Among nonsurgical patients, improvements were observed for pain assessment (42.3% vs 27.9% of the patients had pain intensity measured with a visual analog scale, P = 0.012), pain management (staff did everything they could to help in 78.9% vs 67.9% of cases P = 0.003), and pain relief (70.4% vs 57.3% of patients reported full pain relief P = 0.008). In surgical patients, pain assessment also improved (53.7.3% vs 37.6%) as well as pain treatment. More patients received treatments to relieve pain regularly or intermittently after program implementation (95.1% vs 91.9% P = 0.046). Conclusion.Implementation of a collaborative quality improvement program at hospital level improved both pain management and pain relief in patients. Further studies are needed to determine the overall cost-effectiveness of such programs.

Short-term stability of testosterone and epitestosterone conjugates in urine samples: quantification by liquid chromatography-linear ion trap mass spectrometry.

A simple method using liquid chromatography-linear ion trap mass spectrometry for simultaneous determination of testosterone glucuronide (TG), testosterone sulfate (TS), epitestosterone glucuronide (EG) and epitestosterone sulfate (ES) in urine samples was developed. For validation purposes, a urine containing no detectable amount of TG, TS and EG was selected and fortified with steroid conjugate standards. Quantification was performed using deuterated testosterone conjugates to correct for ion suppression/enhancement during ESI. Assay validation was performed in terms of lower limit of detection (1-3ng/mL), recovery (89-101%), intraday precision (2.0-6.8%), interday precision (3.4-9.6%) and accuracy (101-103%). Application of the method to short-term stability testing of urine samples at temperature ranging from 4 to 37 degrees C during a time-storage of a week lead to the conclusion that addition of sodium azide (10mg/mL) is required for preservation of the analytes.

Loss of penicillin tolerance by inactivating the carbon catabolite repression determinant CcpA in Streptococcus gordonii.

OBJECTIVES: Antibiotic tolerance is a phenomenon allowing bacteria to withstand drug-induced killing. Here, we studied a penicillin-tolerant mutant of Streptococcus gordonii (Tol1), which was shown to be deregulated in the expression of the arginine deiminase operon (arc). arc was not directly responsible for tolerance, but is controlled by the global regulator CcpA. Therefore, we sought whether CcpA might be implicated in tolerance. METHODS: The ccpA gene was characterized and subsequently inactivated by PCR ligation mutagenesis in both the susceptible wild-type (WT) and Tol1. The minimal inhibitory concentration and time-kill curves for the strains were determined and the outcome of penicillin treatment in experimental endocarditis assessed. RESULTS: ccpA sequence and expression were similar between the WT and Tol1 strains. In killing assays, the WT lost 3.5 +/- 0.6 and 5.3 +/- 0.6 log(10) cfu/mL and Tol1 lost 0.4 +/- 0.2 and 1.4 +/- 0.9 log(10) cfu/mL after 24 and 48 h of penicillin exposure, respectively. Deletion of ccpA almost totally restored Tol1 kill susceptibility (loss of 2.5 +/- 0.7 and 4.9 +/- 0.7 log(10) cfu/mL at the same endpoints). In experimental endocarditis, penicillin treatment induced a significant reduction in vegetation bacterial densities between Tol1 (4.1 log(10) cfu/g) and Tol1DeltaccpA (2.4 log(10) cfu/g). Restitution of ccpA re-established the tolerant phenotype both in vitro and in vivo. CONCLUSIONS: CcpA, a global regulator of the carbon catabolite repression system, is implicated in penicillin tolerance both in vitro and in vivo. This links antibiotic survival to bacterial sugar metabolism. However, since ccpA sequence and expression were similar between the WT and Tol1 strains, other factors are probably involved in tolerance.

Nutritional influences on lipogenesis and thermogenesis after a carbohydrate meal.

In vivo lipogenesis and thermogenesis were studied for 24 h after ingestion of 500 g of carbohydrate (CHO) in subjects who had consumed either a high-fat, a mixed, or a high-CHO diet during the 3-6 days preceding the test. CHO oxidation and conversion to fat was significantly less in the high-fat diet group (222 +/- 5 g) than in the mixed (300 +/- 13 g) or high-CHO diet (331 +/- 7 g) groups, resulting in a greater glycogen storage in the high-fat (278 +/- 6 g) than in the other two groups (197 +/- 11 and 170 +/- 2 g). Net lipogenesis occurred sooner and lasted longer in the high-CHO group, amounting to 0.8 +/- 0.5, 3.4 +/- 0.6, and 9 +/- 1 g of lipid synthesized in the high-fat, mixed, and high-CHO groups, respectively. The thermic effect of the CHO load was 5.2 +/- 0.5% on the high-fat, 6.5 +/- 0.4% on the mixed diet, and 8.6 +/- 0.4% on the high-CHO diet. Significant relationships were demonstrated between the postabsorptive nonprotein respiratory quotient and net lipogenesis after the CHO load (r = 0.82) and between net lipogenesis and the increase in energy expenditure (r = 0.71). It is concluded that the antecedent diet influences the amount of net lipogenesis and the magnitude of thermogenesis after a large CHO test meal. However, lipogenesis remains too limited even after such large CHO intakes to cause an increase in the body's fat content.

Predictive accuracy of original and recalibrated Framingham risk score in the Swiss population.

OBJECTIVE: To compare the predictive accuracy of the original and recalibrated Framingham risk function on current morbidity from coronary heart disease (CHD) and mortality data from the Swiss population. METHODS: Data from the CoLaus study, a cross-sectional, population-based study conducted between 2003 and 2006 on 5,773 participants aged 35-74 without CHD were used to recalibrate the Framingham risk function. The predicted number of events from each risk function were compared with those issued from local MONICA incidence rates and official mortality data from Switzerland. RESULTS: With the original risk function, 57.3%, 21.2%, 16.4% and 5.1% of men and 94.9%, 3.8%, 1.2% and 0.1% of women were at very low (<6%), low (6-10%), intermediate (10-20%) and high (>20%) risk, respectively. With the recalibrated risk function, the corresponding values were 84.7%, 10.3%, 4.3% and 0.6% in men and 99.5%, 0.4%, 0.0% and 0.1% in women, respectively. The number of CHD events over 10 years predicted by the original Framingham risk function was 2-3 fold higher than predicted by mortality+case fatality or by MONICA incidence rates (men: 191 vs. 92 and 51 events, respectively). The recalibrated risk function provided more reasonable estimates, albeit slightly overestimated (92 events, 5-95th percentile: 26-223 events); sensitivity analyses showed that the magnitude of the overestimation was between 0.4 and 2.2 in men, and 0.7 and 3.3 in women. CONCLUSION: The recalibrated Framingham risk function provides a reasonable alternative to assess CHD risk in men, but not in women.

Mobilization of hemopoietic stem cells with high-dose methotrexate plus granulocyte-colony-stimulating factor in patients with primary central nervous system lymphoma.

BACKGROUND: High-dose therapy with autologous stem cell support after standard dose induction is a promising approach for therapy of primary central nervous system lymphoma (PCNSL). High-dose methotrexate (HD-MTX) is a standard drug for induction of PCNSL; however, data about the capacity of HD-MTX plus granulocyte-colony-stimulating factor (G-CSF) to mobilize hemopoietic progenitors are lacking. STUDY DESIGN AND METHODS: This investigation describes the data from stem cell mobilization and apheresis procedures after one or two cycles of HD-MTX for induction of PCNSL within the East German Study Group for Haematology and Oncology 053 trial. Eligible patients proceeded to high-dose busulfan/thiotepa after induction therapy and mobilization. RESULTS: Data were available from nine patients with a median age of 58 years. The maximal CD34+ cell count per microL of blood after the first course of HD-MTX was 13.89 (median). Determination was repeated in six patients after the second course with a significantly higher median CD34+ cell count of 33.69 per microL. Five patients required two apheresis procedures and in four patients a single procedure was sufficient. The total yield of CD34+ cells per kg of body weight harvested by one or two leukapheresis procedures was 6.60 x 10(6) (median; range, 2.68 x 10(6)-15.80 x 10(6)). The yield of CD34+ cells exceeded the commonly accepted lower threshold of 3 x 10(6) cells per kg of body weight in eight of nine cases. Even in the ninth, hemopoietic recovery after stem cell reinfusion was rapid and safe. CONCLUSION: HD-MTX plus G-CSF is a powerful combination for stem cell mobilization in patients with PCNSL and permits safe conduction of time-condensed and dose-intense protocols with high-dose therapy followed by stem cell reinfusion after HD-MTX induction.

Intraoperative cerebral perfusion in geriatric patients

Background: It is unknown whether cerebral perfusion in geriatric and younger patients under general anaesthesia differs. Methods: We compared 2 groups of patients undergoing elective major non-cardiac surgery under standardized general anaesthesia (thiopental, sevoflurane, fentanyl, atracurium). Group 1: 18-40 yrs (n = 20), Group 2: >65 yrs (n = 37). Cerebral perfusion was investigated with transcranial Doppler and near-infrared spectroscopy (NIRS). Arterial blood pressure was monitored continuously with a Finapres device. Mx, an index allowing continuous monitoring of cerebrovascular autoregulation based on the changes in mean arterial blood pressure (MAP) and cerebral blood flow velocity was calculated. Data are shown as mean } SD. Results: MAP (86 } 9.6 vs 79 } 10.9 mm Hg, p = 0.02), end-tidal concentration of sevoflurane (1.9 } 0.3 vs 1.6 } 0.3%, p <0.01), and the cerebral tissue oxygenation index measured by NIRS (72 } 4 vs 68 } 5%, p = 0.01), were significantly lower in Group 2. The end-tidal concentration of O2 was significantly higher in Group 2 (46 } 4 vs 48 } 4% p = 0.04). There were no significant differences between Group 1 and 2 for cerebral blood flow velocity (41 } 10 vs 43 } 18 cm/s), end tidal CO2 (4.7 } 0.3 vs 4.6 } 0.3 kPa) and cerebrovascular autoregulation (Mx 0.42 } 0.2 vs 0.48 } 0.2). In Group 1 35% and in Group 2 43% of the patients had an index of autoregulation suggesting disturbed cerebrovascular autoregulation (p = n.s.). Conclusions: In elderly patients under general anaesthesia with sevoflurane the cerebral tissue oxygenation index was significantly lower than in younger patients despite higher end-tidal oxygen concentrations. Our data suggest subtle differences in cerebral perfusion between geriatric and younger

Performance of noninvasive ventilation algorithms on ICU ventilators during pressure support: a clinical study.

To evaluate the impact of noninvasive ventilation (NIV) algorithms available on intensive care unit ventilators on the incidence of patient-ventilator asynchrony in patients receiving NIV for acute respiratory failure. Prospective multicenter randomized cross-over study. Intensive care units in three university hospitals. Patients consecutively admitted to the ICU and treated by NIV with an ICU ventilator were included. Airway pressure, flow and surface diaphragmatic electromyography were recorded continuously during two 30-min periods, with the NIV (NIV+) or without the NIV algorithm (NIV0). Asynchrony events, the asynchrony index (AI) and a specific asynchrony index influenced by leaks (AIleaks) were determined from tracing analysis. Sixty-five patients were included. With and without the NIV algorithm, respectively, auto-triggering was present in 14 (22%) and 10 (15%) patients, ineffective breaths in 15 (23%) and 5 (8%) (p = 0.004), late cycling in 11 (17%) and 5 (8%) (p = 0.003), premature cycling in 22 (34%) and 21 (32%), and double triggering in 3 (5%) and 6 (9%). The mean number of asynchronies influenced by leaks was significantly reduced by the NIV algorithm (p < 0.05). A significant correlation was found between the magnitude of leaks and AIleaks when the NIV algorithm was not activated (p = 0.03). The global AI remained unchanged, mainly because on some ventilators with the NIV algorithm premature cycling occurs. In acute respiratory failure, NIV algorithms provided by ICU ventilators can reduce the incidence of asynchronies because of leaks, thus confirming bench test results, but some of these algorithms can generate premature cycling.