A new formula for calculating standard liver volume for living donor liver transplantation without using body weight.

BACKGROUND & AIMS: The standard liver volume (SLV) is widely used in liver surgery, especially for living donor liver transplantation (LDLT). All the reported formulas for SLV use body surface area or body weight, which can be influenced strongly by the general condition of the patient. METHODS: We analyzed the liver volumes of 180 Japanese donor candidates and 160 Swiss patients with normal livers to develop a new formula. The dataset was randomly divided into two subsets, the test and validation sample, stratified by race. The new formula was validated using 50 LDLT recipients. RESULTS: Without using body weight-related variables, age, thoracic width measured using computed tomography, and race independently predicted the total liver volume (TLV). A new formula: 203.3-(3.61×age)+(58.7×thoracic width)-(463.7×race [1=Asian, 0=Caucasian]), most accurately predicted the TLV in the validation dataset as compared with any other formulas. The graft volume for LDLT was correlated with the postoperative prothrombin time, and the graft volume/SLV ratio calculated using the new formula was significantly better correlated with the postoperative prothrombin time than the graft volume/SLV ratio calculated using the other formulas or the graft volume/body weight ratio. CONCLUSIONS: The new formula derived using the age, thoracic width and race predicted both the TLV in the healthy patient group and the SLV in LDLT recipients more accurately than any other previously reported formulas.

Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study.

IMPORTANCE: Depression and obesity are 2 prevalent disorders that have been repeatedly shown to be associated. However, the mechanisms and temporal sequence underlying this association are poorly understood. OBJECTIVE: To determine whether the subtypes of major depressive disorder (MDD; melancholic, atypical, combined, or unspecified) are predictive of adiposity in terms of the incidence of obesity and changes in body mass index (calculated as weight in kilograms divided by height in meters squared), waist circumference, and fat mass. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study, CoLaus (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), with 5.5 years of follow-up included 3054 randomly selected residents (mean age, 49.7 years; 53.1% were women) of the city of Lausanne, Switzerland (according to the civil register), aged 35 to 66 years in 2003, who accepted the physical and psychiatric baseline and physical follow-up evaluations. EXPOSURES: Depression subtypes according to the DSM-IV. Diagnostic criteria at baseline and follow-up, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured Diagnostic Interview for Genetic Studies. MAIN OUTCOMES AND MEASURES: Changes in body mass index, waist circumference, and fat mass during the follow-up period, in percentage of the baseline value, and the incidence of obesity during the follow-up period among nonobese participants at baseline. Weight, height, waist circumference, and body fat (bioimpedance) were measured at baseline and follow-up by trained field interviewers. RESULTS: Only participants with the atypical subtype of MDD at baseline revealed a higher increase in adiposity during follow-up than participants without MDD. The associations between this MDD subtype and body mass index (β = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (β = 2.44; 95% CI, 0.21-4.66), and fat mass in men (β = 16.36; 95% CI, 4.81-27.92) remained significant after adjustments for a wide range of possible cofounding. CONCLUSIONS AND RELEVANCE: The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.

Composition of weight gain during the neonatal period and longitudinal growth follow-up in premature babies.

Changes in the rate of growth and adiposity index (Quetelet index), calculated as weight/(length)2, kg/m2, were monitored from birth to 3 years in 19 premature babies (post-conceptional age 31.2 +/- 2 weeks) who were subjected during rapid growth (16 +/- 4 g/kg.day) to initial metabolic balance studies in the first weeks of life. These studies showed that the rate of fat accretion in these infants (3.3 +/- 0.9 g/kg.day) was substantially greater than that observed in fetuses of the same gestational age (2 g/kg.day) but the adiposity index was lower (9.6 +/- 1 kg/m2) than intrauterine values (11 kg/m2). Since at 6 months of age (corrected for gestational age at birth) the adiposity index was close to normality (103% of standard), the greater rate of fat accretion in early life contributed to progressively restore total body fat in premature babies. It is concluded that despite substantial fat deposition during the first weeks of life, the future evolution of these premature babies is favourable as judged from the normalization of adiposity index within the first 2 years of life.

Aquaporin expression after thrombin preconditioning in ischemic mouse brain

Background: Aquaporin-4 (AQP4), a water channel, is induced early after stroke.The role of AQP4 in the development and resolution of oedema after stroke remainsdebated. The absence of AQP4 in KO-mice reduces the cytotoxic oedema formationbut in contrast aggravates the vasogenic edema. Thrombin at high dose is known toinduce an oedema and at a low dose (thrombin preconditioning, TPC), to inducetolerance to ischemia. We studied the expression of AQPs in ischemic mouse brainsafter TPC and correlation with oedema formation.Methods: For thrombin preconditioning (TPC), mice were injected intracerebroventricularlywith a low dose of thrombin (0.1U in 2?l), followed 24 hours laterby a 30 min transient middle cerebral occlusion (MCAo). AQP4 expression wasevaluated by immunohistochemistry 1h and 48h after ischemia and correlated withoedema formation in vehicle injected and TPC mice.Results: After TPC, oedema formation, assessed by hemispheric enlargement, wassignificantly attenuated at 1h (4.5 ± 2% vs 11.0 ± 5% in CTL, p<0.05, n=8),which was confirmed by wet weight/dry weight ratio (79.6 ± 0.3% vs 80.1 ± 0.1in ctl, p<0.05, n=0.05). At the same time-point, AQP4 expression was significantlyincreased in TPC mice, (148.9% of the control, P<0.05, n=6) in the ischemicstriatum. The oedema was still reduced at 48h after stroke onset in TPC mice. At48h, the level of expression for AQP4 was still higher for TPC animal although notreaching significance (NS). The lesion size was significantly reduced at 48h afterstroke in TPC mice (5.1 ± 1.6 vs 10.6 ± 1.8 mm2 in CTL, n=5).Discussion: The correlation between the early induction of AQP4 and the decreaseof oedema formation in TPC mice suggests that the induction of AQP4 preventsthe development of oedema.Funding: FNS #3100A0-108001, #3200 68306.02 & #3100A0-112484 and Swiss-Heart foundation.

Trends in self-reported prevalence and management of hypertension, dyslipidaemia and diabetes in adults in Switzerland, 1992-2007

Purpose: to assess the trends of self-reported prevalence of cardiovascular risk factors (CV RFs: hypertension, dyslipidaemia, diabetes) and their management for period 1992 to 2007 in the Swiss population. Methods: four National health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and controllevels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the targeted population. Multivariate analysis adjusted on age, sex, education, nationality and SMI was conducted using logistic regression. Results: prevalence of ail CV RFs increased between 1992 and 2007, see table. Although the self-reported prevalence of treatment among subjects with CV RFs increased, and this was confirmed by multivariate analysis: OR for hypocholesterolaemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of dyslipidaemic and 50% of diabetic subjects weren't treated. Conversely, an adequate control of CV RFs was reported by treated subjects, with an increase during the study period. This increase was confirmed by multivariate analysis (not shown). Conclusion: the self-reported prevalence of hypertension, dyslipidaemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.

Characterization and binding affinities of SmLANP: a new Schistosoma mansoni member of the ANP32 family of regulatory proteins.

Members of the leucine-rich repeat protein family are involved in diverse functions including protein phosphatase 2-inhibition, cell cycle regulation, gene regulation and signalling pathways. A novel Schistosoma mansoni gene, called SmLANP, presenting homology to various genes coding for proteins that belong to the super family of leucine-rich repeat proteins, was characterized here. SmLANP was 1184bp in length as determined from cDNA and genomic sequences and encoded a 296 amino acid open reading frame that spanning from 6 to 894bp. The predicted amino acid sequence had a calculated molecular weight of 32kDa. Analysis of the predicted sequence indicated the presence of 3 leucine-rich domains (LRR) located in the N-terminal region and an aspartic acid rich region in the C-terminal end. SmLANP transcript is expressed in all stages of the S. mansoni life cycle analyzed, exhibiting the highest expression level in males. The SmLANP protein was expressed in a GST expression system and antibodies raised in mice against the recombinant protein. By immunolocalization assay, using adult worms, it was shown that the protein is mainly present in the cell nucleus through the whole body and strongly expressed along the tegument cell body nuclei of adult worms. As members of this family are usually involved in protein-protein interaction, a yeast two hybrid assay was conducted to identify putative binding partners for SmLANP. Thirty-six possible partners were identified, and a protein ATP synthase subunit alpha was confirmed by pull down assays, as a binding partner of the SmLANP protein.

Origin of the relative afferent pupillary defect in optic tract lesions.

OBJECTIVE: To determine the percent decussation of pupil input fibers in humans and to explain the size and range of the log unit relative afferent pupillary defect (RAPD) in patients with optic tract lesions. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Five patients with a unilateral optic tract lesion. METHODS: The pupil response from light stimulation of the nasal hemifield, temporal hemifield, and full field of each eye of 5 patients with a unilateral optic tract lesion was recorded using computerized binocular infrared pupillography. Six stimulus light intensities, separated by 0.5-log unit steps, were used; 12 stimulus repetitions were given for each stimulus condition. MAIN OUTCOME MEASURES: For each stimulus condition, the pupil response of each eye was characterized by plotting the mean pupil contraction amplitude as a function of stimulus light intensity. The percentage of decussating afferent pupillomotor input fibers was calculated from the ratio of the maximal pupil contractions elicited from each eye. The RAPD was determined pupillographically from full-field stimulation to each eye. RESULTS: In all patients, the pupil response from the functioning temporal hemifield ipsilateral to the tract lesion was greater than that from the functioning contralateral nasal hemifield. This temporal-nasal asymmetry increased with increasing stimulus intensity and was similar in hemifield and full-field stimuli, eventually saturating at maximal light intensity. The log unit RAPD did not correlate with the estimated percentage of decussating pupil fibers, which ranged from 54% to 67%. CONCLUSIONS: In patients with a unilateral optic tract lesion, the pupillary responses from full-field stimulation to each eye are the same as comparing the functioning temporal field with the functioning nasal field. The percentage of decussating fibers is reflected in the ratio of the maximal pupil contraction amplitudes resulting from stimulus input between the two eyes. The RAPD that occurs in this setting reflects the difference in light sensitivity between the intact temporal and nasal hemifields. Its magnitude does not correlate with the difference in the number of crossed and uncrossed axons, but its sidedness contralateral to the side of the optic tract lesion is consistent with the greater percentage of decussating pupillomotor input.

Proinflammatory activity of cell-wall constituents from gram-positive bacteria.

Innate immunity reacts to conserved bacterial molecules. The outermost lipopolysaccharide (LPS) of Gram-negative organisms is highly inflammatory. It activates responsive cells via specific CD14 and toll-like receptor-4 (TLR4) surface receptor and co-receptors. Gram-positive bacteria do not contain LPS, but carry surface teichoic acids, lipoteichoic acids and peptidoglycan instead. Among these, the thick peptidoglycan is the most conserved. It also triggers cytokine release via CD14, but uses the TLR2 co-receptor instead of TLR4 used by LPS. Moreover, whole peptidoglycan is 1000-fold less active than LPS in a weight-to-weight ratio. This suggests either that it is not important for inflammation, or that only part of it is reactive while the rest acts as ballast. Biochemical dissection of Staphylococcus aureus and Streptococcus pneumoniae cell walls indicates that the second assumption is correct. Long, soluble peptidoglycan chains (approximately 125 kDa) are poorly active. Hydrolysing these chains to their minimal unit (2 sugars and a stem peptide) completely abrogates inflammation. Enzymatic dissection of the pneumococcal wall generated a mixture of highly active fragments, constituted of trimeric stem peptides, and poorly active fragments, constituted of simple monomers and dimers or highly polymerized structures. Hence, the optimal constraint for activation might be 3 cross-linked stem peptides. The importance of structural constraint was demonstrated in additional studies. For example, replacing the first L-alanine in the stem peptide with a D-alanine totally abrogated inflammation in experimental meningitis. Likewise, modifying the D-alanine decorations of lipoteichoic acids with L-alanine, or deacylating them from their diacylglycerol lipid anchor also decreased the inflammatory response. Thus, although considered as a broad-spectrum pattern-recognizing system, innate immunity can detect very subtle differences in Gram-positive walls. This high specificity underlines the importance of using well-characterized microbial material in investigating the system.

Hypoxia: unique myocardial morphology?

OBJECTIVE: The objective of this study was to investigate the effects of chronic and intermittent hypoxia on myocardial morphology. METHODS: Rats randomly divided into 3 groups (n = 14 per group) were exposed to room air (Fio(2) = 0.21), chronic hypoxia (Fio(2) = 0.10), and intermittent hypoxia (chronic hypoxia with 1 hour per day of room air) for 2 weeks. Weight, blood gas analysis, hematocrit, hemoglobin, red cells, and right and left ventricular pressures were measured. Hearts excised for morphologic examination were randomly divided into 2 groups (9 per group for gross morphologic measurements and 5 per group for histologic and morphometric analysis). The weight ratio of right to left ventricles plus interventricular septum, myocyte diameter, cross-sectional area, and free wall thickness in right and left ventricles were measured. RESULTS: Despite the same polycythemia, the right ventricle pressure (P <.05) and ratio of right to left ventricle pressures (P <.02) were higher after chronic hypoxia than intermittent hypoxia. The ratio of heart weight to total body weight and the ratio of right to left ventricles plus interventricular septum was higher (P <.01) in chronic and intermittent hypoxia than in normoxia. Myocyte diameter was not different between the right and left ventricles in normoxia, whereas right ventricle myocytes were larger than left ventricle myocytes in chronic hypoxia (P <.05) and intermittent hypoxia (P <.0005). There was marked dilatation of right ventricle size (P <.001) and marked reduction of left ventricle (P <.001) size in chronic and intermittent hypoxia compared with normoxia. The total ventricular area (right ventricle plus left ventricle area) remained the same in all groups. The wall thickness ratio in chronic hypoxia and intermittent hypoxia was increased (P <.001) compared with normoxia in the right ventricle but not in the left ventricle. CONCLUSIONS: Intermittent reoxygenation episodes do not induce a lesser ventricular hypertrophic response than observed with chronic hypoxia. The functional myocardial preconditioning consequence of intermittent reoxygenation is not supported by structural differences evident with the available techniques.

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults between 1992 and 2007

PURPOSE: to assess the trends of prevalence of self-reported cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia, diabetes) and their management for the period of 1992 to 2007 in Switzerland. METHODS: four health interview surveys conducted between 1992 and 2007 in representative samples of the Swiss population (63,782 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed after weighting. Weights were calculated by raking ratio such that the marginal distribution of the weighted totals conforms to the marginal distribution of the target population. Multivariate analysis was conducted using logistic regression. RESULTS: prevalence of all CV RFs increased between 1992 and 2007. Also, the prevalence of self-reported treatment among subjects with CV RFs increased, as confirmed by multivariate analysis: OR for hypolipidemic treatment relative to 1992: 0.64 [0.52-0.78]; 1.39 [1.18-1.65] and 2.00 [1.69-2.36] for 1997, 2002 and 2007, respectively. Still, in 2007, circa 40% of hypertensive, 60% of hypercholesterolemic and 50% of diabetic subjects weren't treated. On the other hand, there is an increase of the prevalence of controlled RFs as reported by treated subjects. This was confirmed by multivariate analysis 12.1 [12.0 - 12.2]; 4.16 [4.1 - 4.23] and 2.85 [2.79 - 2.90] for hypertension, hypercholesterolemia and diabetes, respectively, in 2007, relative to 1992. CONCLUSION: the prevalence of self-reported hypertension, hypercholesterolemia and diabetes increased between 1992 and 2007 in the Swiss population. Despite a good control of treated subjects, still a significant percentage of subjects with CV RFs are not treated.

Persistent spatial clusters of high body mass index in a Swiss urban population as revealed by the 5-year GeoCoLaus longitudinal study.

OBJECTIVE: Body mass index (BMI) may cluster in space among adults and be spatially dependent. Whether and how BMI clusters evolve over time in a population is currently unknown. We aimed to determine the spatial dependence of BMI and its 5-year evolution in a Swiss general adult urban population, taking into account the neighbourhood-level and individual-level characteristics. DESIGN: Cohort study. SETTING: Swiss general urban population. PARTICIPANTS: 6481 georeferenced individuals from the CoLaus cohort at baseline (age range 35-74 years, period=2003-2006) and 4460 at follow-up (period=2009-2012). OUTCOME MEASURES: Body weight and height were measured by trained healthcare professionals with participants standing without shoes in light indoor clothing. BMI was calculated as weight (kg) divided by height squared (m(2)). Participants were geocoded using their postal address (geographic coordinates of the place of residence). Getis-Ord Gi statistic was used to measure the spatial dependence of BMI values at baseline and its evolution at follow-up. RESULTS: BMI was not randomly distributed across the city. At baseline and at follow-up, significant clusters of high versus low BMIs were identified and remained stable during the two periods. These clusters were meaningfully attenuated after adjustment for neighbourhood-level income but not individual-level characteristics. Similar results were observed among participants who showed a significant weight gain. CONCLUSIONS: To the best of our knowledge, this is the first study to report longitudinal changes in BMI clusters in adults from a general population. Spatial clusters of high BMI persisted over a 5-year period and were mainly influenced by neighbourhood-level income.