Determinants of glomerular volume in different cortical zones of the human kidney

Enlarged glomerular size is a feature of focal segmental glomerulosclerosis, obesity-related glomerulopathy, diabetic nephropathy, and hypertension. The distribution of glomerular volumes within different cortical zones and glomerular volume alterations with age and obesity may contribute to understanding the evolution of these diseases. We analyzed the distributions of volumes of individual glomeruli in the superficial, middle, and juxtamedullary cortex of normal human kidneys using the disector/Cavalieri method. Volumes (V-glom) of 720 nonsclerotic glomeruli (30 per kidney, 10 per zone) were estimated in autopsy kidneys of 24 American men, 12 aged 20 to 30 yr and 12 aged 51 to 69 yr. Black and white individuals were represented equally. The range of individual V-glom within subjects varied from two- to eight-fold. There were no significant zonal differences in V-glom in the young or those with body surface area (BSA) <= 2.11 m(2). In contrast, superficial glomeruli in the older age group, in those with BSA > 2.11 m(2), and in white subjects were significantly larger than juxtamedullary glomeruli. Black subjects tended toward larger V-glom than white subjects, and this difference was significant and most marked in the juxtamedullary zone and independent of age, BSA, and glomerular number. There is a wide range in individual V-glom in adults. BSA, race, and age independently influence V-glom different zones of the renal cortex. These findings might reflect processes of aging and susceptibility factors to renal disease.

Evidence-based medicine is affordable: The cost-effectiveness of current compared with optimal treatment in rheumatoid and osteoarthritis

Objective. To determine the cost-effectiveness of averting the burden of disease. We used secondary population data and metaanalyses of various government-funded services and interventions to investigate the costs and benefits of various levels of treatment for rheumatoid arthritis (RA) and osteoarthritis (OA) in adults using a burden of disease framework. Method. Population burden was calculated for both diseases in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented cut-rent evidence-based guidelines, and the direct treatment cost-effectiveness ratio in dollars per YLD averted for both treatment levels. Results. The majority of people with arthritis sought medical treatment. Current treatment for RA averted 26% of the burden, with a cost-effectiveness ratio of $19,000 per YLD averted. Optimal, evidence-based treatment would avert 48% of the burden. with a cost-effectiveness ratio of $12,000 per YLD averted. Current treatment of OA in Australia averted 27% of the burden, with a cost-effectiveness ratio of $25,000 per YLD averted. Optimal, evidence-based treatment would avert 39% of the burden, with an unchanged cost-effectiveness ratio of $25,000 per YLD averted. Conclusion. While the precise dollar costs in each country will differ, the relativities at this level of coverage should remain the same. There is no evidence that closing the gap between evidence and practice would result in a drop in efficiency.

Carbamyl phosphate synthase deficiency: Diagnosed during pregnancy in a 41-year-old

Carbamyl phosphate synthase deficiency (CPS) is a rare urea cycle defect. We present a case of a 41-year-old woman diagnosed with CPS deficiency during pregnancy. She is the oldest CPS-deficient patient, at diagnosis, reported to date and the first to be diagnosed during pregnancy. This case highlights the need for consideration of inborn errors of metabolism in adults presenting with unusual neurological and psychiatric conditions. Crown Copyright (c) 2006 Published by Elsevier Ltd. All rights reserved.

The number, morphology, and distribution of retinal ganglion cells and optic axons in the Australian lungfish Neoceratodus forsteri (Krefft 1870)

Australian lungfish Neoceratodus forsteri may be the closest living relative to the first tetrapods and yet little is known about their retinal ganglion cells. This study reveals that lungfish possess a heterogeneous population of ganglion cells distributed in a horizontal streak across the retinal meridian, which is formed early in development and maintained through to adult stages. The number and complement of both ganglion cells and a population of putative amacrine cells within the ganglion cell layer are examined using retrograde labelling from the optic nerve and transmission electron-microscopic analysis of axons within the optic nerve. At least four types of retinal ganglion cells are present and lie predominantly within a thin ganglion cell layer, although two subpopulations are identified, one within the inner plexiform and the other within the inner nuclear layer. A subpopulation of retinal ganglion cells comprising up to 7% or the total population are significantly larger (> 400 mu m(2)) and are characterized as giant or alpha-like cells. Up to 44% of cells within the retinal ganglion cell layer represent a population of presumed amacrine cells. The optic nerve is heavily fasciculated and the proportion of myelinated axons increases with body length from 17% in subadults to 74% in adults. Spatial resolving power, based on ganglion cell spacing, is low (1.6-1.9 cycles deg(-1), n = 2) and does not significantly increase with growth. This represents the first detailed study of retinal ganglion cells in sarcopterygian fish, and reveals that, despite variation amongst animal groups, trends in ganglion cell density distribution and characteristics of cell types were defined early in vertebrate evolution.

Estimating cause-specfic mortality from community- and facility-based data sources in the United Republic of Tanzania: options and implications for mortality burden estimates

Objective To compare mortality burden estimates based on direct measurement of levels and causes in communities with indirect estimates based on combining health facility cause-specific mortality structures with community measurement of mortality levels. Methods. Data from sentinel vital registration (SVR) with verbal autopsy (VA) were used to determine the cause-specific mortality burden at the community level in two areas of the United Republic of Tanzania. Proportional cause-specific mortality structures from health facilities were applied to counts of deaths obtained by SVR to produce modelled estimates. The burden was expressed in years of life lost. Findings. A total of 2884 deaths were recorded from health facilities and 2167 recorded from SVR/VAs. In the perinatal and neonatal age group cause-specific mortality rates were dominated by perinatal conditions and stillbirths in both the community and the facility data. The modelled estimates for chronic causes were very similar to those from SVR/VA. Acute febrile illnesses were coded more specifically in the facility data than in the VA. Injuries were more prevalent in the SVR/VA data than in that from the facilities. Conclusion. In this setting, improved International classification of diseases and health related problems, tenth revision (ICD-10) coding practices and applying facility-based cause structures to counts of deaths from communities, derived from SVR, appears to produce reasonable estimates of the cause-specific mortality burden in those aged 5 years and older determined directly from VA. For the perinatal and neonatal age group, VA appears to be required. Use of this approach in a nationally representative sample of facilities may produce reliable national estimates of the cause-specific mortality burden for leading causes of death in adults.