Knee osteoarthritis patients with severe nocturnal pain have altered proximal tibial subchondral bone mineral density.

OBJECTIVE: Our objective was to investigate relationships between proximal tibial subchondral bone mineral density (BMD) and nocturnal pain in patients with knee osteoarthritis (OA). METHODS: The preoperative knee of 42 patients booked for knee arthroplasty was scanned using quantitative computed tomography (QCT). Pain was measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and participants were categorized into three groups: 'no pain', 'moderate pain', and 'severe pain' while lying down at night. We used depth-specific image processing to assess tibial subchondral BMD at normalized depths of 0-2.5 mm, 2.5-5.0 mm and 5-10 mm relative to the subchondral surface. Regional analyses of each medial and lateral plateau included total BMD and maximum BMD within a 10 mm diameter core or 'focal spot'. The association between WOMAC pain scores and BMD measurements was assessed using Spearman's rank correlation. Regional BMD was compared pairwise between pain and no pain groups using multivariate analysis of covariance using age, sex, and BMI as covariates and Bonferroni adjustment for multiple comparisons. RESULTS: Lateral focal BMD at the 2.5-5 mm depth was related to nocturnal pain (ρ = 0.388, P = 0.011). The lateral focal BMD was 33% higher in participants with 'severe pain' than participants with 'no pain' at 2.5-5 mm depth (P = 0.028) and 32% higher at 5-10 mm depth (P = 0.049). There were no BMD differences at 0-2.5 mm from the subchondral surface. CONCLUSION: This study suggests that local subchondral bone density may have a role in elucidating OA-related pain pathogenesis.

Regional depth-specific subchondral bone density measures in osteoarthritic and normal patellae: in vivo precision and preliminary comparisons.

SUMMARY: Computed tomography-based depth-specific image processing is able to precisely identify regional differences between healthy patellae and patellae with osteoarthritis. INTRODUCTION: This study aims to assess the precision errors and potential differences in regional, depth-specific subchondral bone mineral density (BMD) in normal and osteoarthritic (OA) human patellae in vivo using CT-based density analyses. METHODS: Fourteen participants (2 men and 12 women; mean age, 51.4; SD, 11.8 years) were scanned using clinical quantitative CT (QCT) three times over 2 days. Participants were categorized as either normal (n = 7) or exhibiting radiographic OA (n = 7). Average subchondral BMD was assessed at three depths relative to the subchondral surface. Regional BMD analysis included: total lateral facet BMD, total medial facet BMD, and superior/middle/inferior BMD of lateral and medial facets at normalized depths of 0-2.5, 2.5-5, and 5-7.5 mm from the subchondral surface. We assessed precision using root mean square coefficients of variation (CV%). We evaluated differences between OA and normal BMD by (1) calculating percentage differences between the groups (in relation to normal BMD) (2) relating percentage differences to respective CV% errors and (3) determining effect sizes using Cohen's d. RESULTS: Root mean square CV% precision errors ranged from 1.1 to 5.9 %. Percentage differences between OA and normal BMD varied from -1.6 to -30.1 % (BMD lower in OA patellae). In relation to precision errors, percentage differences were, on average, 5.5× greater than CV% errors. Cohen's d effect sizes ranged from -1.7 to -0.1. Largest differences were noted at depths of 2.5-5 and 5-7.5 mm from the subchondral surface. CONCLUSIONS: Patellar subchondral BMD measures were precise (average CV%, ≤3 %). This region- and depth-specific CT-based imaging tool characterized regional standardized BMD differences between normal and OA patellae in vivo.

Nutrition research in the military.

Military research performed in an operational environment involves mission-specific considerations. The Institute of Naval Medicine was tasked in 2008 by the Surgeon General to investigate the nutritional status of deployed British military personnel, and how this might affect body composition, physical fitness and operational capability. This paper briefly describes the logistic and technical issues specific to military research that were encountered by the study team, how these issues were overcome and how this research has influenced military practice.

Deployed antimicrobial stewardship: an audit of antimicrobial use at Role 3.

INTRODUCTION: Infections due to multidrug-resistant organisms are increasingly prevalent, and antimicrobial stewardship has become a priority for many healthcare organisations, including the Defence Medical Services. In military environments, infectious diseases remain a significant burden, and infections complicating the care of modern complex combat injuries are well recognised. A focus on infection prevention and control in the deployed environment is essential, and an important element of this is an antimicrobial formulary and stewardship programme. This audit analyses antimicrobial prescribing practices by military clinicians in patients admitted to UK/US Role 3 medical treatment facility in Camp Bastion, Afghanistan, relative to the UK published guidance. METHODS: Retrospective case note review of all in-patient admissions during two time periods (October 2011 and October 2012). Notes were independently reviewed by an infection specialist not involved in the management of the patients. RESULTS: 475 case notes were reviewed, of which 250 received antimicrobials. Coalition forces represented the most common patient group (131/250), with battle injury the most frequent indication (139/250) for antimicrobial prescription, followed by disease (100/250). A total of 302 antimicrobials were prescribed, with co-amoxiclav being the most frequently used antibiotic in 74% (185/250) of patients. 84.8% (212/250) were prescribed antimicrobials in line with the antimicrobial formulary. In battle injury, 93.5% (130/139) of antimicrobial prescriptions were in line with the formulary compared with 73.9% (82/111) in disease and non-battle injury patients. CONCLUSIONS: Maintaining a strong infection control effort in the deployed setting, even in a stabilised operational environment, is difficult, but our data show good compliance to the antimicrobial formulary superior to that reported in civilian hospitals. To improve this, further innovative strategies are required, combined with a continued focus on infection control basics across the full spectrum of care.

Synthesis and characterization of SIRT6 protein coated magnetic beads: identification of a novel inhibitor of SIRT6 deacetylase from medicinal plant extracts.

SIRT6 is a histone deacetylase that has been proposed as a potential therapeutic target for metabolic disorders and the prevention of age-associated diseases. Thus, the identification of compounds that modulate SIRT6 activity could be of great therapeutic importance. The aim of this study was to develop a screening method for the identification of novel modulators of SIRT6 from a natural plant extract. We immobilized SIRT6 onto the surface of magnetic beads, and assessed SIRT6 enzymatic activity on synthetic acetylated histone tails (H3K9Ac) by measuring products of the deacetylation process. The SIRT6 coated magnetic beads were then suspended in fenugreek seed extract (Trigonella foenum-graecum) as a bait to identify active ligands that suppress SIRT6 activity. While the entire extract also inhibited SIRT6 activity in a cell-based assay, the inhibitory effect of two flavonoids from this extract, quercetin and vitexin, was only detected in vitro. This is the first report on the use of protein-coated magnetic beads for the identification of an active ligand from a botanical matrix, and it sets the basis for the de novo identification of SIRT6 modulators from complex biological mixtures.

The effect of a patellar brace on three-dimensional patellar kinematics in patients with lateral patellofemoral osteoarthritis.

OBJECTIVE: Patellar bracing is a mechanical treatment strategy for patellofemoral osteoarthritis (OA) that aims to unload the lateral compartment of the joint by translating the patella medially. Our objective was to determine whether a patellar brace can correct patellar kinematics in patients with patellofemoral OA. DESIGN: We assessed the effect of a patellar brace on three-dimensional patellar kinematics (flexion, spin and tilt; proximal, lateral and anterior translation) at sequential, static knee postures, using a validated magnetic resonance imaging (MRI)-based method, in 19 patients with radiographic lateral patellofemoral OA. Differences in kinematics between unbraced and braced conditions were assessed in the unloaded and loaded knee (15% bodyweight load) using hierarchical linear random-effects models. Random slope and quadratic terms were included in the model when significant (P<0.05). RESULTS: Bracing with load caused the patellae to translate 0.46 mm medially (P<0.001), tilt 1.17° medially (P<0.001), spin 0.62° externally (P=0.012) and translate 1.09 mm distally (P<0.001) and 0.47 mm anteriorly (P<0.001) over the range of knee flexion angles studied. Bracing also caused the patellae to extend in early angles of knee flexion (P<0.001). The brace caused similar trends for the unloaded condition, though magnitudes of the changes varied. CONCLUSION: Bracing changed patellar kinematics, but these changes did not appear large enough to be clinically meaningful because no reduction in pain was observed in the parent study.

Influence of lifetime hip joint force on the risk of self-reported hip osteoarthritis: a community-based cohort study.

OBJECTIVE: To investigate the influence of cumulative lifetime hip joint force on the risk of self-reported medically-diagnosed hip osteoarthritis (OA). DESIGN: Prospective cohort. SETTING: General population. PARTICIPANTS: Members of Canadian Association of Retired Persons, community-dwelling. MAIN OUTCOME: Health-professional diagnosed hip OA, self-reported. METHODS: Exposure data on lifetime physical activity type (occupational, household, sport) and dose (frequency, intensity, duration) was collected in 2005. Subjects were ranked in terms of a 'cumulative peak force index' (CFPI), a measure of lifetime mechanical hip joint force. Multivariable survival analyses were performed to obtain adjusted effects for mean lifetime exposure and during 5-year age periods. RESULTS: Of 2918 subjects aged 45-85, 176 (6.03%) developed hip OA during the 2-year follow up (43 men, 133 women). The highest quintile of mean lifetime hip CPFI (HR 2.32; 95% CI 1.31-4.12), and high hip force in three age periods (35-39, 40-44, 45-49) were independently associated with hip OA. Previous hip injury was an approximate five-fold risk for development of hip OA across all models. In analysis by activity domain (occupation, sport, household), there was a trend (non-significant) for the highest quintile of occupational force, but not sport or household, to be associated with hip OA. CONCLUSIONS: A newly proposed measure of lifetime mechanical hip force was used to estimate the risk of self-reported, medically-diagnosed hip OA. While there are important limitations, this prospective study suggests that lifelong physical activity is generally safe. Very high levels of lifetime force from all domains combined, and in particular from occupational forces, may be important in the etiology of hip OA.

Video playback demonstrates episodic personality in the gloomy octopus.

Coleoid cephalopods, including octopuses, cuttlefish and squid, rely mainly on visual signals when interacting with conspecifics, predators and prey. Presenting visual stimuli, such as models, photographs, mirrors and live conspecifics, can thus provide insight into cephalopod behaviour. These methods, however, have limitations - mirrors and live animals lack experimental control, whereas models and photographs sacrifice motion-based information. Video playback addresses these issues by presenting controlled, moving and realistic stimuli but, to date, video playback has not been used successfully with any cephalopod. Here, we developed a video playback technique for the gloomy octopus (Octopus tetricus) that incorporated recent advances in video technology. We then used this technique to test for personality, which we defined as behavioural differences between individuals that are consistent over time and across ecologically important contexts. We captured wild octopuses and tested them on 3 separate days over a 10 day period. On each test day, subjects were presented with videos of a food item, a novel object and a conspecific. These represented a foraging, novel and threatening context, respectively. A fourth video without a moving stimulus controlled for the playback monitor itself and potential artifacts associated with video playback. Experimental stimuli evoked unambiguous and biologically appropriate responses from the subjects. Furthermore, individuals' responses to the three experimental contexts were highly correlated within a given test day. However, within a given context, individuals behaved inconsistently across the 3 test days. The reordering of ranks suggests that rather than fulfilling the criteria for personality, gloomy octopus show temporal discontinuities, and hence display episodic personality.

Computed tomography topographic mapping of subchondral density (CT-TOMASD) in osteoarthritic and normal knees: methodological development and preliminary findings.

OBJECTIVES: To develop a precise imaging tool which measures three-dimensional (3D) subchondral bone mineral density (BMD), and investigate its ability to distinguish subchondral bone properties in osteoarthritic and normal cadaveric tibiae. METHODS: We developed a novel imaging tool [Computed tomography topographic mapping of subchondral density (CT-TOMASD)], which employs a surface projection image processing technique to map 3D subchondral BMD measured in relation to depth from the joint surface. Sixteen intact cadaver knees from 10 donors (8M:2F; age: 77.8+/-7.4) were scanned using quantitative computed tomography (QCT). Projections of average BMD to normalized depths of 2.5mm and 5.0mm were acquired, with regional analyses including: (1) medial and lateral BMD, (2) anterior/central/posterior compartmental BMD, (3) max BMD contained within a 10mm diameter 'core', and (4) medial:lateral BMD ratio. Precision was assessed using coefficients of variation (CV%). Osteoarthritis (OA) severity was assessed by examination of computed tomography (CT) and fluoroscopic radiographic images, and categorized using modified Kellgren-Lawrence (mKL) scoring. RESULTS: Precision errors for CT-TOMASD BMD measures were focused around 1.5%, reaching a maximum CV% of 3.5%. OA was identified in eight compartments of six knees. Substantial qualitative and quantitative differences were observed between the OA and normal knees, with the medial:lateral BMD ratio and peak core regional analyses demonstrating differences greater than 4.7 standard deviations (SDs) when compared with normals. Preliminary results revealed effect sizes ranging from 1.6 to 4.3 between OA and normal knees. CONCLUSIONS: CT-TOMASD offers precise 3D measures of subchondral BMD. Preliminary results demonstrate large qualitative and quantitative differences and large effect sizes between OA and normal knees. This method has the potential to identify and quantify changes in subchondral BMD associated with OA disease progression.

Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro.

Human hepatoma cells mimic the acute phase response after treatment with monocyte-conditioned medium. Levels of secreted fibrinogen, alpha-1 acid glycoprotein, C-reactive protein, haptoglobin, and the third component of complement were elevated compared with control levels after 48 h of incubation with conditioned supernatant medium from an enriched fraction of normal peripheral monocytes. Albumin levels declined and alpha-1 antitrypsin remained unchanged. Levels of specific mRNA were measured by hybridization to slot blots and Northern blots and changed in correspondence with protein alterations. Interleukin-1 and tumor necrosis factor stimulated the third component of complement, but did not elevate any other member of the acute phase group and were therefore only partially active in this system. The identification of an in vitro model of the human acute phase response will permit analysis of the molecular basis for coordinate regulation of this group of facultative genes.

Impaired energy homeostasis in C/EBP alpha knockout mice.

Mice homozygous for the targeted deletion of the c/ebp alpha gene, which expresses the CCAAT/enhancer-binding protein alpha (C/EBP alpha), did not store hepatic glycogen and died from hypoglycemia within 8 hours after birth. In these mutant mice, the amounts of glycogen synthase messenger RNA were 50 to 70 percent of normal and the transcriptional induction of the genes for two gluconeogenic enzymes, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, was delayed. The hepatocytes and adipocytes of the mutant mice failed to accumulate lipid and the expression of the gene for uncoupling protein, the defining marker of brown adipose tissue, was reduced. This study demonstrates that C/EBP alpha is critical for the establishment and maintenance of energy homeostasis in neonates.

Deformation and recovery of cartilage in the intact hip under physiological loads using 7T MRI.

UNLABELLED: Accurate measurement of cartilage deformation in loaded cadaver hip joints could be a valuable tool to answer clinically relevant research questions. MRI is a promising tool, but its use requires an understanding of cartilage deformation and recovery properties in the intact hip. Our objective was to answer the following questions: (1) How long does it take for hip cartilage to reach a deformed steady-state thickness distribution under simulated physiological load, and how much does the cartilage deform? (2) How long does it take for hip cartilage to return to the original cartilage thickness distribution once the load is removed? METHODS: Five human hip specimens were axially loaded to 1980N in a 7T MR scanner and scanned every 15min throughout loading. One specimen was scanned every hour throughout recovery from load. One repeatability specimen was loaded and scanned every day for 4 days. Hip cartilage was segmented as a single unit and thickness was measured radially. RESULTS: The hip cartilage reached a steady-state thickness distribution after 225min of load, and 16.5h of recovery. Mean strain after 225min of load was 30.9%. The repeatability specimen showed an average day-to-day change in mean cartilage thickness of 0.10mm over 4 days of data collection. The amount of deformation (0.96mm) was far greater than the image resolution (0.11mm) and error due to repeatability (0.10mm). CONCLUSION: Using an ex vivo model, this method has potential for assessing changes in hip cartilage strain due to injury or surgical intervention.

Consistency of patellar spin, tilt and lateral translation side-to-side and over a 1 year period in healthy young males.

The purpose of this study was to determine the consistency and symmetry of in vivo measures of patellar spin, tilt, and medial/lateral translation in healthy knees. Patellofemoral joint kinematics were measured bilaterally through a range of loaded knee flexion in 10 active males (aged 19.0 (0.57) years) at baseline, 6, and 12 months using a validated magnetic resonance imaging method. Effects due to time and limb were determined using ANOVA. Variation over 12 months and from side-to-side was summarized as the average of the mean absolute deviations of the measures at 1 degrees increments of knee flexion for corresponding loading cycles for each knee. The measures did not differ over time (p>0.52) or side-to-side (p>0.17). The mean intrasubject variability over the three time points was < or = 1.17 (0.3) degrees for spin and tilt and < or = 0.83 (0.61) mm for lateral translation. The mean intrasubject variability between limbs was 2.14 (1.29) degrees for spin, 0.46 (1.96) degrees for tilt and 1.29 (1.28)mm for lateral translation. The consistency of measures of normal patellar motion over a 1 year period supports application of this methodology to evaluate changes in patellar motion in longitudinal studies involving patient populations.

Intraoperative vs. weightbearing patellar kinematics in total knee arthroplasty: a cadaveric study.

BACKGROUND: During knee replacement surgery, surgeons optimize intraoperative patellar tracking with the aim of optimizing postoperative tracking. This link has not been investigated to date. Our research questions were: (1) How well do patellar kinematics correlate between passive and weightbearing flexion across numerous changes in component placement? (2) How do the kinematics differ between the two loading configurations? METHODS: Eight cadaveric knee joints with modified knee components that allowed 11 different femoral, tibial and patellar placements were tested in two experimental rigs simulating intraoperative and weightbearing dynamic flexion. Baseline placement had all components in neutral position. Pearson correlation coefficients were calculated for absolute baseline kinematics and for relative kinematics due to changes in component position (i.e., the 10 altered positions vs. baseline). FINDINGS: Correlations between intraoperative and weightbearing rigs for absolute baseline kinematics were unpredictable, ranging from poor to excellent (mean 0.56 for tilt and mean 0.50 for shift). Correlations between rigs for changes in tilt and shift, i.e. relative kinematics, were strong (>0.8) or very strong (>0.9), with the exception of shift in early flexion (0.54). Differences in relative kinematics, which averaged 2.2 degrees in tilt (standard deviation 1.8 degrees ) and 1.6mm in shift (standard deviation 1.7mm), were notably smaller and less variable than differences in absolute kinematics, which averaged 4.2 degrees in tilt (standard deviation 3.6 degrees ) and 4.3mm in shift (standard deviation 3.9mm). INTERPRETATION: The results of this study suggest that, while absolute kinematics may differ between conditions, if a surgeon adjusts a component position to improve patellar kinematics intraoperatively, the effects of such a geometric change will likely carry through to the postoperative joint.

Determinants of patellar tracking in total knee arthroplasty.

BACKGROUND: Optimizing patellar tracking in total knee arthroplasty is a surgical priority. Despite this, a comparison of the effects of different component placements on patellar tracking is not available; the biomechanical impact of the patellar resection angle has not been studied; and the similarity between intraoperative and postoperative effects, fundamental to improving patellar tracking, is unknown. Our objective was to compare the impact of the major controllable femoral, tibial and patellar component positions on patellar kinematics during both passive and loaded flexion. METHODS: We tested eight cadaveric knee specimens in two rigs, simulating intraoperative and weightbearing flexion. Optoelectronic marker arrays were attached to the femur, tibia and patella to record kinematics throughout the range of motion. We modified posterior-stabilized fixed-bearing knee components to allow for five types of variations in component placement in addition to the neutral position: femoral component rotation, tibial component rotation, patellar resection angle, patellar component medialization and additional patellar thickness, for a total of 11 individual variations. FINDINGS: The major determinants of patellar tilt and shift were patellar component medialization, patellar resection angle and femoral component rotation. The relative order of these variables depended on the structure (bone or component), kinematic parameter (tilt or shift) and flexion angle (early or late flexion). Effects of component changes were consistent between the intraoperative and weightbearing rigs. INTERPRETATION: To improve patellar tracking, and thereby the clinical outcome, surgeons should focus on patellar component medialization, patellar resection angle and femoral component rotation. These have been linked with anterior knee pain as well. Neither tibial component rotation nor patellar thickness should be adjusted to improve patellar tracking.

Enhanced case management can be delivered for patients with EVD in Africa: Experience from a UK military Ebola treatment centre in Sierra Leone.

BACKGROUND: Limited data exist describing supportive care management, laboratory abnormalities and outcomes in patients with Ebola virus disease (EVD) in West Africa. We report data which constitute the first description of the provision of enhanced EVD case management protocols in a West African setting. METHODS: Demographic, clinical and laboratory data were collected by retrospective review of clinical and laboratory records of patients with confirmed EVD admitted between 5 November 2014 and 30 June 2015. RESULTS: A total of 44 EVD patients were admitted (median age 37 years (range 17-63), 32/44 healthcare workers), and excluding those evacuated, the case fatality rate was 49% (95% CI 33%-65%). No pregnant women were admitted. At admission 9/44 had stage 1 disease (fever and constitutional symptoms only), 12/44 had stage 2 disease (presence of diarrhoea and/or vomiting) and 23/44 had stage 3 disease (presence of diarrhoea and/or vomiting with organ failure), with case fatality rates of 11% (95% CI 1%-58%), 27% (95% CI 6%-61%), and 70% (95% CI 47%-87%) respectively (p = 0.009). Haemorrhage occurred in 17/41 (41%) patients. The majority (21/40) of patients had hypokalaemia with hyperkalaemia occurring in 12/40 patients. Acute kidney injury (AKI) occurred in 20/40 patients, with 14/20 (70%, 95% CI 46%-88%) dying, compared to 5/20 (25%, 95% CI 9%-49%) dying who did not have AKI (p = 0.01). Ebola virus (EBOV) PCR cycle threshold value at baseline was mean 20.3 (SD 4.3) in fatal cases and 24.8 (SD 5.5) in survivors (p = 0.007). Mean national early warning score (NEWS) at admission was 5.5 (SD 4.4) in fatal cases and 3.0 (SD 1.9) in survivors (p = 0.02). Central venous catheters were placed in 37/41 patients and intravenous fluid administered to 40/41 patients (median duration of 5 days). Faecal management systems were inserted in 21/41 patients, urinary catheters placed in 27/41 and blood component therapy administered to 20/41 patients. CONCLUSIONS: EVD is commonly associated life-threatening electrolyte imbalance and organ dysfunction. We believe that the enhanced levels of protocolized care, scale and range of medical interventions we report, offer a blueprint for the future management of EVD in resource-limited settings.

Cross-circulation study of natriuretic factors in postobstructive diuresis.

To study the role of circulating natriuretic factors in the postobstructive diuresis that occurs after relief of bilateral, but not unilateral ureteral ligation, cross-circulation was carried out between normal recipient rats and donor rats have either 24-h bilateral (BUL) or unilateral (UUL) ureteral ligation. With BUL donors, there was a rapid marked increase in sodium and water excretion in the recipient rats, sustained for 80-140 min, with a peak approximately 10 times control values. With UUL donors, no significant natriuretic response occurred. Changes in glomerular filtration rate, renal plasma flow, blood pressure, hematocrit, or circulating levels of aldosterone or Pitressin did not explain the diuresis-natriuresis produced by cross-circulation with BUL donors. Differences in the intrinsic renal damage produced by bilateral as compared to unilateral ureteral obstruction did not appear to account for this response, since UUL donors given an acute urea load and urine reinfusion caused a similar diuresis-natriuresis. Moreover, normal donor rats given a urea load also caused a diuresis-natriuresis nearly equal to that produced by BUL rats, and the relationship between increased urea excretion and sodium excretion or urine flow in the recipients was not different in the two groups. Total urine reinfusion for 3 h in donor rats produced a significant, although less marked, diuresis-natriuresis in recipient animals, with only a slight elevation of the blood urea nitrogen level, much less increase in urea excretion rate, and no significant relationship between urea excretion and sodium excretion or urine flow. The results indicate that potent natriuretic factors, which act by decreasing the tubular reabsorption of sodium and water, are present in the blood of rats with bilateral, but not unilateral, ureteral ligation. High blood and urine urea levels appear to be the factors responsible for the marked natriuresis-diuresis occurring in normal rats during cross-circulation with BUL donors, although suggestive evidence of other natriuretic factors in urine reinfused intravenously was also obtained. The data suggest that urea osmotic diuresis is an important mechanism for determining the striking difference between the postobstructive diuresis observed after relief of bilateral as compared to unilateral ureteral ligation.

The role of the medullary collecting ducts in postobstructive diuresis.

Medullary collecting duct function was studied by direct microcatheterization techniques in rats undergoing postobstructive diuresis. Significant net addition of water and sodium to the duct was demonstrated during postobstructive diuresis after relief of 24-h bilateral ureteral ligation. This striking abnormality in function was associated with reduced delivery of sodium and water to the collecting duct compared to sham-operated controls. To examine the role of circulating factors in this phenomenon, another group of rats was studied that underwent 24 h of total urine reinfusion into the femoral vein. Natriuresis and diuresis were similar to the postobstructive group, but absolute collecting duct reabsorption of sodium and water was normal. The natriuresis and diuresis in rats with urine reinfusion resulted from increased delivery of fluid and sodium to the medullary collecting duct. A third group of rats was studied with 24-h unilateral ureteral ligation as well as urine reinfusion from the contralateral normal kidney. Without urine reinfusion there was no diuresis-natriuresis but with urine reinfusion the diuresis and natriuresis after relief of unilateral obstruction was similar to that after relief of bilateral obstruction. Moreover, net addition of sodium and no significant water reabsorption were demonstrated in the medullary collecting duct of such animals. The results indicate that (a) the medullary collecting duct is the critical nephron segment affected by ureteral obstruction, since postobstructive diuresis occurred despite reduced delivery of fluid from the more proximal nephron; (b) the net addition of sodium to the medullary collecting duct observed during postobstructive diuresis is probably a direct effect of obstruction, since it was found during postobstructive diuresis after relief of bilateral or unilateral ureteral ligation, but not with urine reinfusion alone; and (c) blood-borne factors are important in the development of postobstructive natriuresis and diuresis, and probably act by increasing the fraction of filtered sodium and water delivered from the proximal and distal tubule to the collecting duct.