Hypoxic preconditioning reverses protection after neonatal hypoxia-ischemia in glutathione peroxidase transgenic murine brain

The effect of hypoxic preconditioning (PC) on hypoxic-ischemic (HI) injury was explored in glutathione peroxidase (GPx)-overexpressing mice (human GPx-transgenic [hGPx-tg]) mice. Six-day-old hGPx-tg mice and wild-type (Wt) littermates were pre-conditioned with hypoxia for 30 min and subjected to the Vannucci procedure of HI 24 h after the PC stimulus. Histopathological injury was determined 5 d later (P12). Additional animals were killed 2 h or 24 h after HI and ipsilateral cerebral cortices assayed for GPx activity, glutathione (GSH), and hydrogen peroxide (H2O2). In line with previous studies, hypoxic PC reduced injury in the Wt brain. Preconditioned Wt brain had increased GPx activity, but reduced GSH, relative to naive 24 h after HI. Hypoxic PC did not reduce injury to hGPx-tg brain and even reversed the protection previously reported in the hGPx-tg. GPx activity and GSH in hGPx-tg cortices did not change. Without PC, hGPx-tg cortex had less H2O2 accumulation than Wt at both 2 h and 24 h. With PC, H2O2 remained low in hGPx-tg compared with Wt at 2 h, but at 24 h, there was no longer a difference between hGPx-tg and Wt cortices. Accumulation of H2O2 may be a mediator of injury, but may also induce protective mechanisms.

Spectral waveform analysis of intranodal arterial blood flow in abnormally large superficial lymph nodes in dogs

Objective-To evaluate pulsed-wave Doppler spectral parameters as a method for distinguishing between neoplastic and inflammatory peripheral lymphadenopathy in dogs. Sample Population-40 superficial lymph nodes from 33 dogs with peripheral lymphadenopathy. Procedures-3 Doppler spectral tracings were recorded from each node. Spectral Doppler analysis including assessment of the resistive index, peak systolic velocity-to-end diastolic velocity (S:D) ratio, diastolic notch velocity-to-peak systolic velocity (N:S) ratio, and end diastolic velocity-to-diastolic notch velocity ratio was performed for each tracing. Several calculation methods were used to determine the Doppler indices for each lymph node. After the ultrasonographic examination, fine needle aspirates or excisional biopsy specimens of the examined lymph nodes were obtained, and lymphadenopathy was classified as either inflammatory or neoplastic (lymphomatous or metastatic) via cytologic or histologic examination. Results of Doppler analysis were compared with cytologic or histopathologic findings. Results-The Doppler index with the highest diagnostic accuracy was the S:D ratio calculated from the first recorded tracing; a cutoff value of 3.22 yielded sensitivity of 91%, specificity of 100%, and negative predictive value of 89% for detection of neoplasia. Overall diagnostic accuracy was 95%. At a sensitivity of 100%, the most accurate index was the N:S ratio calculated from the first recorded tracing; a cutoff value of 0.45 yielded specificity of 67%, positive predictive value of 81%, and overall diagnostic accuracy of 86.5%. Conclusions and Clinical Relevance-Results suggested that noninvasive Doppler spectral analysis may be useful in the diagnosis of neoplastic versus inflammatory peripheral lymphadenopathy in dogs.

Use of pressure waves to confirm the correct placement of epidural needles in dogs

An epidural puncture was performed using the lumbosacral approach in 18 dogs, and the lack of resistance to an injection of saline was used to determine that the needle was positioned correctly. The dogs' arterial blood pressure and epidural pressure were recorded. They were randomly assigned to two groups: in one group an injection of a mixture of local anaesthetic agents was made slowly over 90 seconds and in the other it was made over 30 seconds. After 10 minutes contrast radiography was used to confirm the correct placement of the needle. The mean (sd) initial pressure in the epidural space was 0.1 (0.7) kPa. After the injection the mean maximum epidural pressure in the group injected slowly was 5.5 (2.1) kPa and in the group injected more quickly it was 6.0 (1.9) kPa. At the end of the period of measurement, the epidural pressure in the slow group was 0.8 (0.5) kPa and in the rapid group it was 0.7 (0.5) kPa. Waves synchronous with the arterial pulse wave were observed in 15 of the dogs before the epidural injection, and in all the dogs after the epidural injection.

Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study

BACKGROUND AND OBJECTIVES: Data suggest that atorvastatin may be nephroprotective. This subanalysis of the Treating to New Targets study investigated how intensive lipid lowering with 80 mg of atorvastatin affects renal function when compared with 10 mg in patients with coronary heart disease. DESIGN, SETTING, PARTICIPANTS, ; MEASUREMENTS: A total of 10,001 patients with coronary heart disease and LDL cholesterol levels of <130 mg/dl were randomly assigned to double-blind therapy with 10 or 80 mg/d atorvastatin. Estimated GFR using the Modification of Diet in Renal Disease equation was compared at baseline and at the end of follow-up in 9656 participants with complete renal data. RESULTS: Mean estimated GFR at baseline was 65.6 +/- 11.4 ml/min per 1.73 m2 in the 10-mg group and 65.0 +/- 11.2 ml/min per 1.73 m2 in the 80-mg group. At the end of follow-up (median time to final creatinine measurement 59.5 months), mean change in estimated GFR showed an increase of 3.5 +/- 0.14 ml/min per 1.73 m2 with 10 mg and 5.2 +/- 0.14 ml/min per 1.73 m2 with 80 mg (P < 0.0001 for treatment difference). In the 80-mg arm, estimated GFR improved to > or = 60 ml/min per 1.73 m2 in significantly more patients and declined to < 60 ml/min per 1.73 m2 in significantly fewer patients than in the 10-mg arm. CONCLUSIONS: The expected 5-yr decline in renal function was not observed. Estimated GFR improved in both treatment groups but was significantly greater with 80 mg than with 10 mg, suggesting this benefit may be dosage related.

Upregulation of toll-like receptors in chronic enteropathies in dogs

Background: Inflammatory bowel disease (IBD) is thought to result from a dysregulated interaction between the host immune system and commensal microflora. Toll-like receptors (TLRs) recognize microbe-associated molecular patterns (MAMPs), but their role in enteropathies in dogs is unknown. Hypothesis: That there is a dysregulation of TLRs recognizing bacterial MAMPs in dogs with IBD. Animals: Sixteen healthy beagles and 12 dogs with steroid-treated (ST) and 23 dogs with food-responsive (FR) diarrhea. Methods: Prospective, observational study. mRNA expression of canine TLR2, 4, and 9 was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies obtained before and after standard therapy. Samples from control dogs were taken at necropsy, with additional biopsies of stomach, jejunum, ileum, and mesenteric lymph node in 6 dogs. Results: There were significant differences (Pin expression of TLR2, 4, and 9 between the 6 sampled locations in healthy control dogs (lymph node > small intestine >/= colon). Before therapy, ST expressed more mRNA than control dogs for all 3 receptors (P < .05). There were no significant differences between pretreatment and posttreatment values, even though 32/35 dogs improved clinically. No associations were found when comparing receptor mRNA expression with either histology or clinical activity scores. Conclusions and Clinical Importance: Bacteria-responsive TLR2, 4, and 9 are upregulated in duodenal and colonic mucosa in IBD. This might lead to increased inflammation through interaction with the commensal flora. The absence of significant changes after therapy despite clinical improvement might point toward the existence of a genetic predisposition to IBD as described in human IBD.

Plasma and urinary catecholamines as related to renal function in man

To assess the relationship between renal plasma flow (ERPF) or glomerular filtration rate (GFR) and the levels of norepinephrine (NE) or epinephrine (E) in plasma or urine in the presence of progressive degrees of non-oliguric renal functional impairment, these variables were assessed simultaneously in 18 normal subjects, 72 with parenchymal kidney disease and 14 with essential hypertension. ERPF and GFR were lower (P less than 0.01 to 0.001) in the groups with renal disease (mean +/- SD, 340 +/- 230 and 68 +/- 43 ml/min/1.73 m2, respectively) or essential hypertension (434 +/- 101 and 97 +/- 25 ml/min/1.73 m2) than normal subjects (597 +/- 133 and 118 +/- 14 ml/min/1.73 m2). Plasma and urinary NE and E did not differ significantly among groups and were unrelated with ERPF or GFR (range 4 to 160 ml/min/1.73 m2), except for reduced (P less than 0.001) urinary NE and E excretion in the presence of a GFR less than 20 ml/min. Subgroups with renal disease and a normal (N = 39) or high blood pressure (N = 33) also were comparable in their plasma and urinary NE and E, while ERPF and GFR tended to be lower in hypertensive patients. It is concluded that a chronic reduction in excretory kidney function may have no relevant impact on circulating levels of NE and E per se, although their urinary excretion falls distinctly at the stage of advanced renal failure. These aspects deserve consideration when pathogenetic or diagnostic studies of catecholamines are performed in normotensive or hypertensive patients with impaired kidney function.

The influence of non-matching implant and abutment diameters on radiographic crestal bone levels in dogs

BACKGROUND: It has been shown that different implant designs and different vertical implant positions have an influence on crestal bone levels. The aim of the present study was to evaluate radiographic crestal bone changes around experimental dental implants with non-matching implant-abutment diameters placed submucosally or transmucosally at three different levels relative to the alveolar crest. METHODS: Sixty two-piece dental implants with non-matching implant-abutment diameters were placed in edentulous spaces bilaterally in five foxhounds. The implants were placed submucosally or transmucosally in the left or the right side of the mandible. Within each side, six implants were randomly placed at three distinct levels relative to the alveolar crest. After 12 weeks, 60 crowns were cemented. Radiographs were obtained from all implant sites following implant placement, after crown insertion, and monthly for 6 months after loading. RESULTS: Radiographic analysis revealed very little bone loss and a slight increase in bone level for implants placed at the level of the crest or 1 mm above. The greatest bone loss occurred at implants placed 1 mm below the bone crest. No clinically significant differences regarding marginal bone loss and the level of the bone-to-implant contact were detected between implants with a submucosal or a transmucosal healing. CONCLUSIONS: Implants with non-matching implant-abutment diameters demonstrated some bone loss; however, it was a small amount. There was no clinically significant difference between submucosal and transmucosal approaches.

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (alphaSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5'-nucleotidase (5'NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model.

Relationship between renal resistance index and renal function in liver transplant recipients after cessation of calcineurin inhibitor

End stage renal disease is a major complication after orthotopic liver transplantation (OLT). Vasoconstriction of renal arterial vessels because of calcineurin inhibitor (CNI) treatment plays a pivotal role in the development of renal insufficiency following OLT. Renal resistance can be measured non-invasively by determining the resistance index (RI) of segmental arteries by color-coded duplex ultrasonography, a measure with predictive value for future renal failure. Sixteen OLT patients on long-term CNI therapy were recruited prospectively and randomly assigned either to receive the m-TOR inhibitor sirolimus (SRL) or to continue on CNI treatment, and were followed for one yr. Serum creatinine (crea) declined after conversion to SRL, whereas it tended to increase in patients remaining on CNI (meanDelta crea SRL: -27, -18, -18, -15 micromol/L; meanDelta crea CNI: 4, 5, 8, 11 micromol/L at 1, 3, 6, 12 months, p = 0.02). RI improved after switching to SRL and was lower on SRL than on CNI (meanDeltaRI SRL: -0.04, -0.04, -0.03, -0.03; meanDeltaRI CNI: -0.006, 0.004, -0.007, -0.01 after 1, 3, 6, 12 months, p = 0.016). Individual changes of RI correlated significantly with individual changes of crea (r = 0.54, p < 0.001). Conversion from CNI to SRL can ameliorate renal function accompanied by a reduction of intrarenal RI after OLT.

A feasibility study evaluating an in situ formed synthetic biodegradable membrane for guided bone regeneration in dogs

PURPOSE: The aim was (1) to evaluate the soft-tissue reaction of a synthetic polyethylene glycol (PEG) hydrogel used as a barrier membrane for guided bone regeneration (GBR) compared with a collagen membrane and (2) to test whether or not the application of this in situ formed membrane will result in a similar amount of bone regeneration as the use of a collagen membrane. MATERIAL AND METHODS: Tooth extraction and preparation of osseous defects were performed in the mandibles of 11 beagle dogs. After 3 months, 44 cylindrical implants were placed within healed dehiscence-type bone defects resulting in approximately 6 mm exposed implant surface. The following four treatment modalities were randomly allocated: PEG+autogenous bone chips, PEG+hydroxyapatite (HA)/tricalcium phosphate (TCP) granules, bioresorbable collagen membrane+autogenous bone chips and autogenous bone chips without a membrane. After 2 and 6 months, six and five dogs were sacrificed, respectively. A semi-quantitative evaluation of the local tolerance and a histomorphometric analysis were performed. For statistical analysis, repeated measures analysis of variance (ANOVA) and subsequent pairwise Student's t-test were applied (P<0.05). RESULTS: No local adverse effects in association with the PEG compared with the collagen membrane was observed clinically and histologically at any time-point. Healing was uneventful and all implants were histologically integrated. Four out of 22 PEG membrane sites revealed a soft-tissue dehiscence after 1-2 weeks that subsequently healed uneventful. Histomorphometric measurement of the vertical bone gain showed after 2 months values between 31% and 45% and after 6 months between 31% and 38%. Bone-to-implant contact (BIC) within the former defect area was similarly high in all groups ranging from 71% to 82% after 2 months and 49% to 91% after 6 months. However, with regard to all evaluated parameters, the PEG and the collagen membranes did not show any statistically significant difference compared with sites treated with autogenous bone without a membrane. CONCLUSION: The in situ forming synthetic membrane made of PEG was safely used in the present study, revealing no biologically significant abnormal soft-tissue reaction and demonstrated similar amounts of newly formed bone for defects treated with the PEG membrane compared with defects treated with a standard collagen membrane.

Pulmonary renal syndrome in childhood: a report of twenty-one cases and a review of the literature

In adults, the term specific pulmonary renal syndrome describes disorders with pulmonary and glomerular manifestations and includes Wegener's granulomatosis, Goodpasture disease, and systemic lupus erythematosus. Nonspecific pulmonary renal syndrome refers to either pulmonary disease complicating glomerular disease, or glomerular diseases following pulmonary disease. Since little is known regarding pulmonary renal syndrome in childhood, we reviewed the charts of 21 pediatric patients with pulmonary renal syndromes treated by the Department of Pediatrics, University of Bern between 1991 and 1998; we also reviewed the pediatric literature that deals with specific pulmonary renal syndromes. Specific pulmonary renal syndrome was noted in 3 children with systemic vasculitis (Wegener granulomatosis, N = 2; microscopic polyangiitis, N = 1) and 2 with systemic lupus erythematosus. Nonspecific pulmonary renal syndrome was observed in 12 patients with pulmonary edema (N = 9), pulmonary thromboembolism (N = 2), and pulmonary infection (N = 1) complicating the course of a glomerular disease, and in 4 children with a pulmonary disease followed by a glomerular disease. Review of the literature disclosed 52 cases of specific pulmonary renal syndrome other than systemic lupus erythematosus: Wegener granulomatosis (N = 28), Goodpasture disease (N = 13), and Henoch-Schönlein purpura (N = 11). In addition, hemolytic uremic syndrome complicated pneumococcal pneumonia in 32 cases. We conclude that pulmonary renal syndromes need to be looked for in childhood. Apart from Wegener granulomatosis, Goodpasture disease, and systemic lupus erythematosus, Henoch-Schönlein purpura and hemolytic-uremic syndrome occasionally have both pulmonary and renal features.

Treatment of acute renal failure in the intensive care unit: lower costs by intermittent dialysis than continuous venovenous hemodiafiltration

Intermittent and continuous renal replacement therapies (RRTs) are available for the treatment of acute renal failure (ARF) in the intensive care unit (ICU). Although at present there are no adequately powered survival studies, available data suggest that both methods are equal with respect to patient outcome. Therefore, cost comparison between techniques is important for selecting the modality. Expenditures were prospectively assessed as a secondary end point during a controlled, randomized trial comparing intermittent hemodialysis (IHD) with continuous venovenous hemodiafiltration (CVVHDF). The outcome of the primary end points of this trial, that is, ICU and in-hospital mortality, has been previously published. One hundred twenty-five patients from a Swiss university hospital ICU were randomized either to CVVHDF or IHD. Out of these, 42 (CVVHDF) and 34 (IHD) were available for cost analysis. Patients' characteristics, delivered dialysis dose, duration of stay in the ICU or hospital, mortality rates, and recovery of renal function were not different between the two groups. Detailed 24-h time and material consumption protocols were available for 369 (CVVHDF) and 195 (IHD) treatment days. The mean daily duration of CVVHDF was 19.5 +/- 3.2 h/day, resulting in total expenditures of Euro 436 +/- 21 (21% for human resources and 79% for technical devices). For IHD (mean 3.0 +/- 0.4 h/treatment), the costs were lower (Euro 268 +/- 26), with a larger proportion for human resources (45%). Nursing time spent for CVVHDF was 113 +/- 50 min, and 198 +/- 63 min per IHD treatment. Total costs for RRT in ICU patients with ARF were lower when treated with IHD than with CVVHDF, and have to be taken into account for the selection of the method of RRT in ARF on the ICU.

Comparative study of vertebral fractures and luxations in dogs and cats

The purpose of this retrospective study was to compare patterns of vertebral fractures and luxations in 42 cats and 47 dogs, and to evaluate the impact of species-related differences on clinical outcome. Data regarding aetiology, neurological status, radiographic appearance and follow-up were compared between the groups. The thoracolumbar (Th3-L3) area was the most commonly affected location in both cats (49%) and dogs (58%). No lesions were observed in the cervical vertebral segments in cats, and none of the cats showed any signs of a Schiff-Sherrington syndrome. Vertebral luxations were significantly more frequent in dogs (20%) than in cats (6%), whereas combined fracture-luxations occurred significantly more often in cats (65%) than in dogs (37%). Caudal vertebral segment displacement was mostly dorsal in cats and ventral in dogs, with a significant difference in direction between cats and large dogs. The clinical outcome did not differ significantly between the two populations, and was poor in most cases (cats: 61%; dogs: 56%). The degree of dislocation and axis deviation were both significantly associated with a worse outcome in dogs, but not in cats. Although several differences in vertebral fractures and luxation patterns exist between cats and dogs, these generally do not seem to affect outcome.

Effects of adjunct electroacupuncture on severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease

OBJECTIVE: To compare severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease treated with a combination of conventional analgesics and electroacupuncture (EAP) or with conventional analgesics alone. DESIGN: Controlled clinical trial. ANIMALS: 15 dogs undergoing surgery because of acute thoracolumbar disk disease. PROCEDURES: Dogs were alternately assigned to treatment (conventional analgesics and adjunct EAP) and control (conventional analgesics alone) groups. Analgesic treatment was adjusted as necessary by the attending clinician, who was not aware of group assignment. Pain scores were assigned 1, 3, and 12 hours after surgery and every 12 hours thereafter for 72 hours by the same individual who performed acupuncture treatments. RESULTS: Total dose of fentanyl administered during the first 12 hours after surgery was significantly lower in the treatment group than in the control group, but dosages of analgesics administered from 12 through 72 hours after surgery did not differ between groups. Pain score was significantly lower in the treatment group than in the control group 36 hours after surgery, but did not differ significantly between groups at any other time. CONCLUSIONS AND CLINICAL RELEVANCE: Results provided equivocal evidence that adjunct EAP might provide some mild benefit in regard to severity of postoperative pain in dogs undergoing hemilaminectomy because of acute thoracolumbar intervertebral disk disease.