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Objective: To describe outcomes of horses with temporohyoid osteoarthropathy (THO) treated with partial ceratohyoidectomy., Animals: 10 client-owned horses., Procedures: Medical records from 2 institutions were examined for records of horses with THO treated with partial ceratohyoidectomy between 2010 and 2021. History, signalment, clinical signs, diagnostics, medications, and surgery-related details were recorded. Horses with a minimum of 6 months follow-up were recruited for neurologic and imaging examinations in the hospital or field where radiography of the basihyoid-ceratohyoid articulation were performed along with CT, when available., Results: 10 horses with THO were included (9 unilateral; 1 bilateral). Nine planned partial ceratohyoidectomies were performed in 8 horses, whereas 2 horses had preoperatively planned complete ceratohyoidectomies transitioned to partial ceratohyoidectomies during surgery due to intraoperative complications. Postoperative complications occurred mostly in transitioned surgeries (obstructed airway, tongue mobility issues, and incisional hemorrhage), whereas only 1 horse with a planned ceratohyoidectomy had postoperative complication of rhabdomyolysis. All complications resolved before hospital discharge. Neurologic signs improved in all 10 horses, with 2 showing complete resolution. Nine horses were available for radiographic follow-up, 6 of which also had head CT scans. A space between the ceratohyoid and basihyoid bones was measurable on radiography in all 9 horses, and was confirmed on CT. Three horses demonstrated proliferation of either ceratohyoid or basihyoid bones. The 9 horses with unilateral disease returned to previous work, and the horse with bilateral disease was retired., Clinical Relevance: Partial ceratohyoidectomy is a surgical option for treatment of THO that provides similar clinical outcomes to published reports on ceratohyoidectomy.

Purpose: Accumulation of visceral, but not subcutaneous, adipose tissue is highly associated with metabolic disease. Inflammation inciting from adipose tissue is commonly associated with metabolic disease risk and comorbidities. However, constituents of the immune system, lymph nodes, embedded within these adipose depots remain under-investigated. We hypothesize that, lymph nodes are inherently distinct and differentially respond to diet-induced obesity much like the adipose depots they reside in., Methods: Adipose tissue and lymph nodes were collected from the visceral and inguinal depots of male mice fed 13 weeks of standard CHOW or high fat diet (HFD). Immune cells were isolated from tissues, counted and characterized by flow cytometry or plated for proliferative capacity following Concanavalin A stimulation. Lymph node size and fibrosis area were also characterized., Results: In HFD fed mice visceral adipose tissue accumulation was associated with significant enlargement of the lymph node encased within. The subcutaneous lymph node did not change. Compared with mice fed CHOW for 13 weeks, mice fed HFD had a decline in immune cell populations and immune cell proliferative ability, as well as, exacerbated fibrosis accumulation, within the visceral, but not subcutaneous, lymph node., Conclusions: Obesity-induced chronic low-grade inflammation is associated with impaired immunity and increased susceptibility to disease. Excessive visceral adiposity and associated inflammation driven by diet likely leads to obesity-induced immune suppression by way of lymph node/lymphatic system pathophysiology.

Suture zones are abundant on Antarctic ice shelves and widely observed to impede fracture propagation, greatly enhancing ice-shelf stability. Using seismic and radar observations on the Larsen C Ice Shelf of the Antarctic Peninsula, we confirm that such zones are highly heterogeneous, consisting of multiple meteoric and marine ice bodies of diverse provenance fused together. Here we demonstrate that fracture detainment is predominantly controlled by enhanced seawater content in suture zones, rather than by enhanced temperature as previously thought. We show that interstitial seawater can reduce fracture-driving stress by orders of magnitude, promoting both viscous relaxation and the development of micro cracks, the incidence of which scales inversely with stress intensity. We show how simple analysis of viscous buckles in ice-penetrating radar data can quantify the seawater content of suture zones and their modification of the ice-shelf's stress regime. By limiting fracture, enhancing stability and restraining continental ice discharge into the ocean, suture zones act as vital regulators of Antarctic mass balance.

Obesity-related adverse health consequences occur predominately in individuals with upper body fat distribution commonly associated with increased central adiposity. Visceral adipose tissue accumulation is described to be the greatest driver of obesity-induced inflammation, however evidence also supports that the intestines fundamentally contribute to the development of obesity-induced metabolic disease. The visceral adipose depot shares the same vasculature and lymph drainage as the small intestine. We hypothesize that the visceral lymph node, which drains adipose tissue and the gastrointestinal tract, is central to the exacerbation of systemic pro-inflammation. Male C57BL/6 mice were fed CHOW or high fat diet (HFD) for 7 weeks. At termination the mesenteric depot, visceral lymph node and ileum, jejunum and Peyer's patches were collected. Cytokine concentration was determined in adipose tissue whereas immune cell populations where investigated in the visceral lymph node and intestinal segments by flow cytometry. Visceral adipose tissue and the gastrointestinal tract mutually influence immune cells enclosed within the visceral lymph node. HFD increased visceral lymph node immune cell number. This likely resulted from 1.) an increase in immune cells migration from the small intestines likely from activated dendritic cells that travel to the lymph node and 2.) cytokine effluent from visceral adipose tissue that promoted expansion, survival and retention of pro-inflammatory immune cells. Overall, the visceral lymph node, the immune nexus of visceral adipose tissue and the small intestines, likely plays a fundamental role in exacerbation of systemic pro-inflammation by HFD-induced obesity. The research of Tim Bartness greatly enhanced the understanding of adipose tissue regulation. Studies from his laboratory significantly contributed to our awareness of extrinsic factors that influence body fatness levels. Specifically, the work he produced eloquently demonstrated that adipose tissue was more complex than an insulating storage center; it was connected to our brains via the sympathetic and sensory nervous system. Mapping studies demonstrated that adipose tissue both receives and sends information to the brain. Further, his lab demonstrated that nervous system connections contributed to lipolysis, thermogenesis and adipocyte proliferation and growth. The work of Tim Bartness will continue to influence adipose tissue research. As such, Tim Bartness directly inspired the following research. Adipose tissue extrinsic factors are not limited to the peripheral nervous system. The lymphatic system is an additional extrinsic factor that cross talks with adipose tissue, however its role in this context is under emphasized. Here we begin to elucidate how the lymphatic system may contribute to the comorbidities associated with visceral adipose tissue accumulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The protective effects of lower body subcutaneous adiposity are linked to the depot functioning as a "metabolic sink" receiving and sequestering excess lipid. This postulate, however, is based on indirect evidence. Mechanisms that mediate this protection are unknown. Here we directly examined this with progressive subcutaneous adipose tissue removal. Ad libitum chow fed mice underwent sham surgery, unilateral or bilateral removal of inguinal adipose tissue or bilateral removal of both inguinal and dorsal adipose tissue. Subsequently mice were separated into 5 week chow or 5 or 13 week HFD groups (N = 10 per group). Primary outcome measures included adipocyte distribution, muscle and liver triglycerides, glucose tolerance, circulating adipocytokines and muscle insulin sensitivity. Subcutaneous adipose tissue removal caused lipid accumulation in femoral muscle proximal to excision, however, lipid accumulation was not proportionally inverse to adipose tissue quantity excised. Accumulative adipose removal was associated with an incremental reduction in systemic glucose tolerance in 13 week HFD mice. Although insulin-stimulated pAkt/Akt did not progressively decrease among surgery groups following 13 weeks of HFD, there was a suppressed pAkt/Akt response in the non-insulin stimulated (saline-injected) 13 week HFD mice. Hence, increases in lower body subcutaneous adipose removal resulted in incremental decreases in the effectiveness of basal insulin sensitivity of femoral muscle. The current data supports that the subcutaneous depot protects systemic glucose homeostasis while also protecting proximal muscle from metabolic dysregulation and lipid accumulation. Removal of the "metabolic sink" likely leads to glucose intolerance because of decreased storage space for glucose and/or lipids.

Objectives: The spatial proximity of adipose depots to secondary lymph nodes allows a unique relation between the two systems. Obesity, predominately visceral adiposity, links to numerous diseases; hence, we postulate that secondary lymphatics within this region contributes to disease risk., Material and Methods: Male C57BL/6 mice were fed standard CHOW (18% kcal fat) or Western diet (45% kcal fat) for 7 weeks. Visceral and subcutaneous lymph nodes and associated adipose depots they occupy were excised. Lymph node morphology and resident immune cell populations were characterized via histopathology, immunofluorescence and flow cytometry. Adipose tissue immune cell populations were also characterized., Results: Obesity caused lymph node expansion, increased viable cell number and deviations in immune cell populations. These alterations were exclusive to visceral lymph nodes. Notably, pro-inflammatory antigen presenting cells and regulatory T cells increased in number in the visceral lymph node. Obesity, however, reduced T regulatory cells in visceral lymph nodes. The visceral adipose depot also had greater reactivity towards HFD than subcutaneous, with a greater percent of macrophages, dendritic and CD8 + T cells. Immune cell number, in both the visceral and subcutaneous, however decreased as adipose depots enlarged., Conclusion: Overall, HFD has a greater influence on visceral cavity than the subcutaneous. In the visceral lymph node, but not subcutaneous, HFD-induced obesity decreased cell populations that suppressed immune function while increasing those that regulate/activate immune response., (© 2017 John Wiley & Sons Ltd.)

The land-terminating margin of the Greenland Ice Sheet has slowed down in recent decades, although the causes and implications for future ice flow are unclear. Explained originally by a self-regulating mechanism where basal slip reduces as drainage evolves from low to high efficiency, recent numerical modeling invokes a sedimentary control of ice sheet flow as an alternative hypothesis. Although both hypotheses can explain the recent slowdown, their respective forecasts of a long-term deceleration versus an acceleration of ice flow are contradictory. We present amplitude-versus-angle seismic data as the first observational test of the alternative hypothesis. We document transient modifications of basal sediment strengths by rapid subglacial drainages of supraglacial lakes, the primary current control on summer ice sheet flow according to our numerical model. Our observations agree with simulations of initial postdrainage sediment weakening and ice flow accelerations, and subsequent sediment restrengthening and ice flow decelerations, and thus confirm the alternative hypothesis. Although simulated melt season acceleration of ice flow due to weakening of subglacial sediments does not currently outweigh winter slowdown forced by self-regulation, they could dominate over the longer term. Subglacial sediments beneath the Greenland Ice Sheet must therefore be mapped and characterized, and a sedimentary control of ice flow must be evaluated against competing self-regulation mechanisms.

Objectives: Adipose tissue plays a fundamental role in glucose homeostasis. For example, fat removal (lipectomy, LipX) in lean mice, resulting in a compensatory 50% increase in total fat mass, is associated with significant improvement in glucose tolerance. This study was designed to further examine the link between fat removal, adipose tissue compensation and glucose homeostasis using a peroxisome proliferator-activated receptor γ (PPAR γ; activator of adipogenesis) knockout mouse., Material and Methods: The study involved PPARγ knockout (FKOγ) or control mice (CON), subdivided into groups that received LipX or Sham surgery. We reasoned that as the ability of adipose tissue to expand in response to LipX would be compromised in FKOγ mice, so would improvements in glucose homeostasis., Results: In CON mice, LipX increased total adipose depot mass (~60%), adipocyte number (~45%) and changed adipocyte distribution to smaller cells. Glucose tolerance was improved (~30%) in LipX CON mice compared to Shams. In FKOγ mice, LipX did not result in any significant changes in adipose depot mass, adipocyte number or distribution. LipX FKOγ mice were also characterized by reduction of glucose tolerance (~30%) compared to shams., Conclusions: Inhibition of adipose tissue PPARγ prevented LipX-induced increases in adipocyte expansion and produced a glucose-intolerant phenotype. These data support the notion that adipose tissue expansion is critical to maintain and/or improvement in glucose homeostasis., (© 2016 John Wiley & Sons Ltd.)

An important element in the process of helping students learn to work interprofessionally is figuring out how to design high-impact learning experiences that engage students in meaningful learning that is collaborative and experiential and can transform students understanding of their own and others' roles in the health care process. In this article, a model for interprofessional education, the Integrated Model for Interprofessional Education (IMIPE), is shared for introducing students in the health professions to the roles and responsibilities of some of the other healthcare professionals with whom they will work in practice. The IMIPE is a process model developed by an interprofessional faculty team used as the focal point of a pilot educational event for students from nursing, occupational therapy, physician assistant studies, and social work. The IMIPE is a derived model that combines concepts of holism, participation, and practical education, grounded in the adult educational philosophy of progressivism. Progressive adult education is focused on practical knowledge and problem-solving skills. The model uses collaborative, experiential, and transformative learning approaches to foster outcomes of communication, critical reflection, teamwork, ethics, and recognition of patient-client needs. These outcomes represent those identified by the World Health Organization and the Interprofessional Education Collaborative Expert Panel.

We hypothesized that there was differential vasomotor dysfunction in the microcirculation between nondialyzed and dialyzed chronic kidney disease (CKD) patients. During live donor kidney transplantation procedures, skin arterioles (SkA; internal diameter = 120 +/- 5 microm) from donors (n = 27) and recipients (nondialysis = 15; dialysis = 20) were dissected from the abdominal wall at the incision site. In vivo aortic pulse wave velocity (PWV) was also measured. In the in vitro isometric force measurement, nondialyzed SkA exhibited comparable contraction to donor SkA, whereas dialyzed SkA had 60 and 40-50% increase in contraction in response to depolarization and agonist (that is, phenylephrine, serotonin and endothelin-1) stimulation, respectively. The acetylcholine-induced relaxation in the nondialyzed SkA was decreased by 50% compared with dialyzed SkA. However, pre-incubation with superoxide dismutase greatly enhanced the relaxation response in the nondialyzed, but not in the dialyzed SkA and donor SkA. Pre-incubation with N(G)-nitro-L-arginine methyl ester (L-NAME) elevated the resting tension and left-shifted the concentration response curve of phenylephrine-stimulated contraction in the donor-SkA. L-NAME only increased the resting tension in the nondialyzed vessel. In vitro stiffness positively correlated with PWV (R(2) = 0.302, p = 0.001), and dialyzed SkA was 60% stiffer than nondialyzed and donor SkA. The acetylcholine relaxation was negatively correlated with PWV in donors and recipients (R(2) = 0.282, p = 0.01). In conclusion, we have uniquely demonstrated differential microvasculature dysfunction between nondialyzed and dialyzed CKD patients., (Copyright 2009 S. Karger AG, Basel.)

Background: Recent in vitro studies suggest that inducible nitric oxide synthase (iNOS) activity mediates endothelial dysfunction. Rheumatoid arthritis (RA) is a chronic inflammatory condition and is associated with endothelial dysfunction and increased risk of cardiovascular disease. The aim of the study was to establish the contribution of iNOS to endothelial function., Methods: Forearm blood flow (FBF) was measured during intra-arterial infusions of acetylcholine (ACh), sodium nitroprusside (SNP), N(G)-monomethyl-l-arginine (l-NMMA) and aminoguanidine (AG) in 12 RA patients and 13 healthy control subjects. Levels of C-reactive protein (CRP) and myeloperoxidase (MPO) were assessed. FBF data are presented as mean percentage changes in the ratio (infused/control arm) of FBF + or - SEM., Results: FBF response to ACh was reduced in patients with RA compared to controls (179 + or - 29 v. 384 + or - 72%, respectively; P=0.01), but SNP response was not (P=0.5). FBF response to AG differed between patients and controls (-15 + or - 2% v. 13 + or - 4%, respectively; P<0.001), whereas the response to l-NMMA did not (P=0.4). In a multiple regression model log CRP, AG response and LDL were found to be independent predictors of endothelial function (R(2)=0.617, P<0.001)., Conclusion: RA patients have endothelial dysfunction and increased iNOS activity in comparison to controls. Furthermore, CRP and iNOS activity were independently associated with endothelial function. Our data demonstrates that inflammation is a key mediator in a process of endothelial dysfunction possibly via activation of iNOS and increased production of MPO.

Dysregulation of matrix metalloproteinase (MMP)-2 in the vasculature has been suggested to be associated with increased prevalence of cardiovascular disease and renal injury. In this descriptive study, we hypothesized that arterial MMP-2 activity is elevated in the presence of cardiovascular risk factors such as diabetes, hypertension, smoking and ageing, and that it correlates with the degree of kidney function. MMP-2 activity in internal mammary arteries (n = 37) was measured using gelatinolytic zymography, and cutoffs were determined using sample-derived medians. Patient demographics and clinical data were analyzed, and the estimated glomerular filtration rate (eGFR) was calculated. High MMP-2 activity (>60,000 units) was associated with age, hypertension and diabetes (p = 0.0034, 0.06 and 0.0034, respectively). Multivariate analysis showed that age and diabetes were independent predictors of high MMP-2 activity. There is a trend towards increased MMP-2 activity and reduced eGFR (p = 0.010). The current exploratory work describes that the activity of MMP-2 in the internal mammary artery is correlated with age, hypertension, diabetes and eGFR. It is the first report suggesting that MMP-2 in the arterial vasculature could be the possible mediator crucial in linking the progression of kidney function to cardiovascular disease., ((c) 2008 S. Karger AG, Basel.)

Objectives: The aim of this study was to investigate the effect of simvastatin and ezetimibe on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in a cohort of rheumatoid arthritis (RA) patients., Background: Rheumatoid arthritis is a chronic inflammatory condition associated with increased cardiovascular risk. Statins reduce inflammation and disease activity in RA patients, but whether this is due to pleiotropism or cholesterol lowering per se is unclear., Methods: Twenty patients received 20 mg simvastatin or 10 mg ezetimibe each for 6 weeks in a randomized double-blind crossover study. Disease activity, blood pressure, aortic pulse wave velocity (PWV), brachial artery flow-mediated dilation (FMD), and serum inflammatory markers were measured before and after each treatment., Results: Both ezetimibe and simvastatin significantly reduced total cholesterol (-0.62 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l, respectively; p < 0.001), low-density lipoprotein cholesterol (-0.55 +/- 0.55 mmol/l and -1.28 +/- 0.49 mmol/l; p < 0.0001), and C-reactive protein (-5.35 +/- 9.25 mg/l and -5.05 +/- 6.30 mg/l; p < 0.001). Concomitantly, Disease Activity Score (-0.55 +/- 1.01 and -0.67 +/- 0.91; p = 0.002), aortic PWV (-0.69 +/- 1.15 m/s and -0.71 +/- 0.71 m/s; p = 0.001), and FMD (1.37 +/- 1.17% and 2.51 +/- 2.13%; p = 0.001) were significantly improved by both drugs., Conclusions: This study demonstrates that both ezetimibe and simvastatin reduce disease activity and inflammatory markers to a similar extent in patients with RA. Therapy is also associated with a concomitant reduction in aortic PWV and improvement in endothelial function. This suggests that cholesterol lowering per se has anti-inflammatory effects and improves vascular function in RA.

Isolated systolic hypertension is associated with increased cardiovascular risk. It is thought to result from large artery stiffening, which is determined by structural components within the vasculature but also by functional factors including NO and endothelin-1. We hypothesized that endothelial dysfunction would account for increased arterial stiffness in patients with isolated systolic hypertension. The aim of this study was to investigate the relationship between endothelial function and arterial stiffness in these patients along with control subjects. We studied 113 subjects: 35 patients with isolated systolic hypertension (mean age+/-SD: 68+/-6 years), 30 age-matched control subjects (65+/-5 years), and 48 young control subjects (37+/-9 years). Aortic pulse wave velocity (PWV) was derived by sequential carotid/femoral waveform recordings. Conduit artery endothelial function was determined by flow-mediated dilatation. Aortic PWV was higher (9.65+/-2.56 m/s versus 8.26+/-0.85 m/s; P=0.009), and flow-mediated dilatation was lower (2.67+/-1.64% versus 4.79+/-3.1%; P=0.03) in patients with isolated systolic hypertension compared with age-matched control subjects. Similarly, aortic PWV was also higher, and flow-mediated dilatation lower, in older versus young control subjects (8.26+/-0.85 m/s versus 7.09+/-1.01 m/s and 4.79+/-3.1% versus 6.94+/-2.7%; P=0.004 for both). Overall, aortic PWV correlated inversely with flow-mediated dilatation (r=-0.3; P=0.001), which remained significant after adjustment for confounding factors (P=0.01). Patients with isolated systolic hypertension have higher aortic PWV and decreased endothelial function compared with age-matched control subjects. Our results suggest that endothelial function contributes significantly to increased arterial stiffness in patients with isolated systolic hypertension and with age.

Objective: The workup of hypoglycemia requires frequent glucose sampling. We designed these studies to determine if the Continuous Glucose Monitoring System (CGMS) and the GlucoWatch G2 Biographer (GW2B) are sufficiently accurate to use in nondiabetic children. Study design Fifteen healthy children (aged 9-17 years, 11 boys) wore a GW2B and a CGMS during a 24-hour period, and reference serum glucose was measured hourly during the day and half-hourly overnight., Results: Compared with the reference glucose, the median absolute difference in concentrations measured by the GW2B (487 pairs) was 13 mg/dL, and the difference measured by the CGMS was 17 mg/dL (668 pairs), with 30% and 42% of values using the GW2B and CGMS, respectively, deviating >20 mg/dL from the reference value. The GW2B reported values <60 mg/dL in 73% of subjects, the CGMS in 60% of subjects. In none of these episodes was serum glucose truly low. Spurious high glucose concentrations also were observed with the sensors. The mean reference glucose was lowest at 5 am (89 mg/dL) and highest at 11:30 pm (106 mg/dL) during the 24-hour period., Conclusions: Neither the CGMS nor the GW2B is accurate enough to establish population standards of the glycemic profile of healthy children and cannot be recommended in the workup of hypoglycemia in nondiabetic youth.

Objective: Arterial stiffness, an independent determinant of cardiovascular risk, is regulated by both structural and functional factors, including endothelium-derived nitric oxide. Endothelial dysfunction is associated with acute and chronic systemic inflammation. However, the role of systemic inflammation in arterial stiffening has not been determined. The aim of this study was to investigate the relationship between inflammation and arterial stiffness in patients with antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) as a model of systemic inflammation., Methods: Thirty-one patients with AASV (15 with active disease) and 32 age-matched controls were studied. Pulse wave velocity (PWV) and the augmentation index (AIx) were assessed noninvasively and related to serum levels of C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha., Results: In subjects with active disease, the AIx, PWV, and level of CRP were elevated compared with that in controls (mean +/- SEM 31 +/- 3% versus 22 +/- 2% [P = 0.003], 9.2 +/- 0.7 versus 7.5 +/- 0.3 meters/second [P = 0.03], and 16.0 +/- 4.0 versus 1.1 +/- 0.1 mg/liter [P < 0.001], respectively). However, PWV and the AIx were not significantly different between patients with disease in remission and controls (8.0 +/- 0.5 versus 7.5 +/- 0.3 meters/second and 19 +/- 3% versus 22 +/- 2%, respectively). The CRP level was positively correlated with both PWV and the AIx. Multiple regression analysis indicated that age, mean arterial pressure (MAP), and CRP were independently related to PWV, and that age, MAP, CRP, sex, and heart rate were associated with the AIx., Conclusion: These data indicate that AASV is associated with increased arterial stiffness, and that stiffness correlates with the degree of active inflammation.

Immune-mediated renal disease (IMRD) accounts for 20 - 30% of the cases of end stage renal failure. It frequently occurs in the context of multi-system autoimmune disorders, including systemic lupus erythematosus (SLE) and primary systemic vasculitis. Current therapies are partially effective and comprise the combination of steroids with an immunosuppressive, such as cyclophosphamide. Their toxicity contributes to the morbidity and mortality of these disorders, and long-term treatment is necessary to prevent relapse. There is a clear need for better-targeted, more effective and less toxic therapy. Advances in our understanding of the immunopathogenesis of inflammatory autoimmune renal disease have identified potential targets for newer agents and have improved the monitoring of therapeutic responses. Recent experience with newer therapies in IMRD is reviewed. This has typically involved small, non-randomised, open-label trials and has addressed reversible features of disease activity. Larger, randomised comparisons to standard therapy are needed along with assessment of long-term efficacy and safety.

Background: Renal involvement is frequently present in antineutrophil cytoplasmic autoantibody (ANCA)-associated systemic vasculitis and is an important cause of end-stage renal failure (ESRF)., Methods: This retrospective, multicenter, sequential cohort study reports presenting features and outcome of 246 new patients diagnosed in London, UK, between 1995 and 2000., Results: Diagnostic subgroups were microscopic polyangiitis, 120 patients (49%); Wegener's granulomatosis (WG), 82 patients (33%); renal-limited vasculitis, 33 patients (13.5%); and Churg-Strauss angiitis, 11 patients (4.5%). Median age was 66 years, 57% were men, and median creatinine level at presentation was 3.87 mg/dL (342 micromol/L). ANCA was present in 92%. Cumulative patient survival at 1 and 5 years was 82% and 76%, respectively. Mortality was associated with age older than 60 years (P < 0.001), development of ESRF (P < 0.001), initial creatinine level greater than 2.26 mg/dL (200 micromol/L; P = 0.01), and sepsis (P < 0.048). ESRF occurred in 68 patients (28%), of whom 47% died. Fifty-six patients who presented with a creatinine level greater than 5.65 mg/dL (500 micromol/L) survived, and 31 patients (55%) achieved dialysis independence. Relapse occurred in 34% after a median of 13 months and was more common in patients with WG (P = 0.048) and proteinase 3-ANCA (P = 0.034). Leukopenia occurred in 41% and was associated with sepsis (P < 0.001)., Conclusion: Mortality and morbidity of ANCA-associated systemic vasculitis are improving compared with previous series, but remain high. Renal vasculitis often affects older patients, who have a particularly poor outcome. Early diagnosis improves outcome. Leukopenia, caused by immunosuppressive therapy, should be avoided because of the close association with sepsis and death.

In-vitro morphological changes and proliferation of cells of the cumulus oophorus, in particular cells of the corona radiata, were seen to differ between individuals and between oocytes of the same cohort in an unselected series of 159 IVF cycles. Cell proliferation did not relate to indications for treatment, type and length of ovarian stimulation, age of patient, ovarian response and quality of oocyte, fertilization rate or embryo morphology. A direct relationship, however, was demonstrated between the proliferative capacity of these cells and the incidence of clinical pregnancy. No pregnancies resulted when there was an absence of morphological change or proliferation of these cells. In cycles where the proliferative capacity of these cells varied between oocytes of a single cohort the pregnancy rate was 40% per cycle, and in cycles where cells associated with all oocytes underwent extensive proliferation the pregnancy rate was 49% (P < 0.001). Thus, regardless of the apparent quality of gametes or embryo, no pregnancies arose if the cumulus-corona complex was incapable of replication. We have, therefore, identified two populations of oocytes based on the proliferative capacity of cumulus-corona cells in vitro, one being associated with a failure of implantation.

Lipid and lysosomal enzyme levels in the tissues of a strain of mice afflicted with an autosomal rescessive neuroviscereal storage disorder were examined. Sphingomyelinase and glucocerebrosidase activities were consistently diminished in a wide variety of tissues obtained from the affected mice. The activities of these enzymes were clearly attenuated in new-born mice, which at this age, were otherwise indistinguishable from littermates and age-matched controls. The deficiency of sphingomyelinase was more pronounced than glucocerebrosidase. There was progressive accumulation of sphingomyelin, glucocerebroside, lactosylceramide and unesterified cholesterol in the tissues of these mice in the postnatal period. Gangliosides GM2 and GM3 accumulated in the brain of the animals, and GM3 and asialo-GM2 were stored in the liver. Furthermore, there was a large increase in the quantity of hepatic bis(monoacylglycero)phosphate. The accumulation of lipids was parallelled by a progressive elevation in the activity of several lysosomal hydrolases in various tissues. Heterozygous mice were biochemically indistinguishable from normal controls. The phenotypic manifestations in these metabolically mutated animals are compared with those in Niemann-Pick disease and Gaucher's disease in humans.

A morphological survey of the central nervous system of a NCTR-Balb/C mouse afflicted by neurovisceral storage disease was performed. It has been demonstrated that this mutant is characterized by primary dysmyelination, which is evident as early as 12 days of age. The failure of myelin formation in the CNS was shown by histochemical and ultrastructural methods. Inasmuch as neither lipid-containing macrophages nor infiltrating mononuclear cells were apparent, secondary demyelination could be excluded. The multiform ultrastructural appearance of the storage material in the various CNS cell types suggested heterogeneity of the accumulated substances. The storage materials which reacted positively with periodate-Schiff reagent, but not with other histochemical stains, are most likely the accumulated gangliosides and neutral glycosphingolipids identified previously in this mutant's brain. Considering the probable role of cholesterol ester in the early phases of myelinogenesis, in conjunction with the fact that the NCTR-Balb/C mouse carries a defect in the esterification of exogenously derived cholesterol, it is possible that the later metabolite is relevant to the impaired myelin formation.

The routes by which viable organisms shed by the surgical team reach the wound are not yet fully understood. Bacteriologic studies show that shedding is greater in surgeons than their assistants or scrub nurses, and is increased by activity and temperature, but is primarily related to the individual's shedding characteristics. Comparison of the ability of 3 types of cotton gowns to contain the surgical team's bacterial effluent shows that the body exhaust system gowns developed by Charnley are superior to more conventional gowns. It is clear that viable organisms can penetrate very closely woven Ventile (pore size 10 microns) as well as balloon cloth (pore size 50 microns). Ventile used without a body exhaust system does not appear to increase gown efficiency. Penetration of gown material by organisms from the surgical team is responsible for 20% of wound contamination. The gown glove cuff junction is an important leakage point for organisms shed by the surgical team. A newly designed "mitt" cuff more effectively seals this area than the conventional stockinette cuff.

Energy levels exist in mammalian cells which result in the absorption of microwaves between 66 and 76 gigahertz. Many of these energy levels occur when water molecules associate with the various chemical groups of macromolecules. The absorption spectra of cells between 66 and 76 gigahertz, therefore, is determined by the structure of in vivo water lattices, and these seem to reflect indirectly the structural makeup of macromolecules or macromolecular complexes. Tumor cells absorb 66-, 68-, and 70-gigahertz microwaves less strongly and 69-, 72-, and 75-gigahertz microwaves more strongly than normal cells. These differences in the strength of attenuation at each frequency suggest that either the ratio of RNA to DNA or the relative number of certain types of chemical groups in tumor cells is different from that in normal cells.