Autosomal dominant polycystic kidney disease in Toronto

Autosomal dominant polycystic kidney disease in Toronto. This study describes the Toronto, Ontario experience with autosomal dominant polycystic kidney disease (ADPKD). Patients were divided into three groups: Group 1, 19 families studied with genetic markers; Group 2, 80 pre-dialysis ADPKD patients followed by Toronto nephrologists in whom the incidence of non-renal complications and the mean age of onset of symptomatology is documented; Group 3, 4,449 individuals who entered end-stage renal failure (ESRF) in the Toronto region between the years 1981 and 1992, 320 with ADPKD and 4129 with other diseases. In this third group age of onset of ESRF, frequency, age and cause of death is compared between ADPKD and non-ADPKD. ADPKD caused by a gene different from that linked to chromosome 16 short-arm probes occurred at a frequency of between 8 and 17%. Incidence of hepatic cysts in ADPKD was similar to that of previous series, other organ involvement was underdiagnosed without deliberate screening, and incidence of symptomatic intracranial aneurysm was 1.25%. A 5% excess of patients with ADPKD died of cerebro-vascular accident. Years of survival after ESRF measured by life table analysis was significantly greater for ADPKD patients than for non-ADPKD patients. A high frequency of death due to infection still exists in ADPKD despite the reduction of invasive procedures in diagnosis and treatment, and despite the presumably improved recent methods of managing infection. The average age of onset of ESRF has been delayed by over six years, and average age of death of ADPKD patients at 63.9 years-old by 12.4 years since 1960

Deuterium oxide elimination kinetics for estimation of body water mass and flux: Developments for a thrifty, rapid and noninvasive method in dairy goats

International audienc

Phénotypage fin de la composition corporelle : calibration et comparaison directe de huit méthodes chez la chèvre laitière

International audienceEight methods were compared to estimate dairy goat body composition, by calibrating against chemical composition measured post-mortem. The methods tested on 20 Alpine goats were body condition score (BCS), 3D imaging assessment of BCS or whole body scan, ultrasound, computer tomography (CT), adipose cell diameter, deuterium oxide dilution space (D2OS) and bioelectrical impedance spectroscopy. Regressions were tested between predictive variates and empty body composition. The best equations for estimation of lipid mass included body weight combined with i) perirenal adipose tissue mass and cell diameter (R² = 0.95), ii) volume of fatty tissues measured by CT (R² = 0.92), or iii) D2OS (R² = 0.91). The best equations for estimation of protein mass combined body weight with D2OS (R² = 0.97) or sternal BCS (R² = 0.95). Whole body 3D imaging method and ultrasound measurements were not satisfactory estimators of body composition (R² ≤ 0.40).Huit méthodes ont été comparées pour phénotyper la composition corporelle chez 20 chèvres laitières : la note d’état corporel (NEC), l’imagerie 3D pour estimer la NEC et reconstituer le corps entier, l’échographie, la tomodensitométrie (CT), le diamètre des adipocytes, l’espace de diffusion de l’eau deutérée (EDD2O) et l’impédancemétrie. Les différentes variables issues des méthodes testées ont été incluses dans des régressions linéaires pour déterminer la composition chimique du corps vide mesurée après abattage. Les équations les plus précises pour l’estimation de la masse de lipides combinent le poids vif et i) le poids total et le diamètre des adipocytes du tissu adipeux périrénal (R² = 0,95), ii) le volume des tissus gras mesuré par CT (R² = 0,92) ou iii) l’EDD2O (R² = 0,91). Les meilleures équations d’estimation de la masse de protéines incluent le poids vif et l’EDD2O (R² = 0,97) ou la NEC sternale (R² = 0,95). L’imagerie 3D corps entier et les mesures échographiques ne semblent pas être de bons estimateurs de la composition corporelle (R² ≤ 0.40)

Meta-analysis of Plasmodium falciparumvar Signatures Contributing to Severe Malaria in African Children and Indian Adults

P. falciparum malaria can cause multiple disease complications that differ by patient age. Previous studies have attempted to address the roles of parasite adhesion and biomass in disease severity; however, these studies have been limited to single geographical sites, and there is limited understanding of how parasite adhesion and biomass interact to influence disease manifestations. In this meta-analysis, we compared parasite disease determinants in African children and Indian adults. This study demonstrates that parasite biomass and specific subsets of var genes are independently associated with detrimental outcomes in both childhood and adult malaria. We also explored how parasite var adhesion types and biomass play different roles in the development of specific severe malaria pathologies, including childhood cerebral malaria and multiorgan complications in adults. This work represents the largest study to date of the role of both var adhesion types and biomass in severe malaria.The clinical presentation of severe Plasmodium falciparum malaria differs between children and adults, but the mechanistic basis for this remains unclear. Contributing factors to disease severity include total parasite biomass and the diverse cytoadhesive properties mediated by the polymorphic var gene parasite ligand family displayed on infected erythrocytes. To explore these factors, we performed a multicohort analysis of the contribution of var expression and parasite biomass to severe malaria in two previously published pediatric cohorts in Tanzania and Malawi and an adult cohort in India. Machine learning analysis revealed independent and complementary roles for var adhesion types and parasite biomass in adult and pediatric severe malaria and showed that similar var profiles, including upregulation of group A and DC8 var, predict severe malaria in adults and children. Among adults, patients with multiorgan complications presented infections with significantly higher parasite biomass without significant differences in var adhesion types. Conversely, pediatric patients with specific complications showed distinct var signatures. Cerebral malaria patients showed broadly increased expression of var genes, in particular group A and DC8 var, while children with severe malaria anemia were classified based on high transcription of DC8 var only. This study represents the first large multisite meta-analysis of var expression, and it demonstrates the presence of common var profiles in severe malaria patients of different ages across distant geographical sites, as well as syndrome-specific disease signatures. The complex associations between parasite biomass, var adhesion type, and clinical presentation revealed here represent the most comprehensive picture so far of the relationship between cytoadhesion, parasite load, and clinical syndrome