Growth failure,risk of hospitalization and death for children with end-stage renal disease

Growth failure remains a significant problem for children with chronic renal insufficiency and end-stage renal disease (ESRD). We examined whether growth failure is associated with more-frequent hospitalizations or higher mortality in children with kidney disease. We studied data on prevalent United States pediatric patients with ESRD in 1990 who were followed through 1995. Patients were categorized according to the standard deviation score (SDS) of their incremental growth during 1990: severe (<–3 SDS), moderate growth failure (>–3 and <–2 SDS), and normal growth (>–2 SDS). Among 1,112 prevalent pediatric dialysis and transplant patients (<17 years, Tanner I–IV), those with severe and moderate growth failure had higher hospitalization rates {relative risk (RR) 1.14 [95% confidence interval (CI) 1.1, 1.2] and 1.24 [95% CI 1.2, 1.3]} respectively than those with normal growth after adjustment for age, gender, race, cause and duration of ESRD, and treatment modality (dialysis or transplant) in 1990. Kaplan-Meier survival analysis showed 5-year survival of 85% and 90% for patients with severe and moderate growth failure, respectively, compared with 96% for patients with normal growth (P<0.001, log-rank). Cox proportional hazards analysis revealed that those with severe (RR 2.9, 95% CI 1.6, 5.3) and moderate growth failure (RR 2.01, 95% CI 1.1, 3.6) had an increased risk of death compared with youths with normal growth, after adjustment. A higher proportion of deaths in the severe and moderate growth failure groups were attributed to infectious causes (22% and 18.7%, respectively) than in the normal growth group (15.6%). We conclude that growth failure is associated with a more-complicated clinical course and increased risk of death for children with kidney failure. Received: 15 August 2001 / Revised: 14 January 2002 / Accepted: 15 January 2002     

Comparing dual-stream and standard cardiopulmonary bypass in pigs

BACKGROUND: Dual-stream (DS) and standard cardiopulmonary bypass (CPB) were compared. METHODS: A DS catheter inserted into the distal ascending aorta across the arch pumps blood through an upper lumen (maximum 2.25 L/min) directed by a bloodstreaming baffle toward the arch vessels. A separate lower lumen pumps blood (maximum 3.75 L/min) into the aorta caudad to the inflated baffle. The baffle is flat and horizontal along the catheter. When the baffle is collapsed the heart or both lumens may perfuse all organs. For 30 minutes 8 randomized CPB pigs had corporeal cooling to 32 degrees C and for 30 minutes had rewarming to 36 degrees C. Eight randomized DS pigs had 25 degrees C upper lumen cooling for 60 minutes. Lower lumen blood flow was streamed at 32 degrees C for 30 minutes, then rewarmed to 36 degrees C for 30 minutes. RESULTS: The change in relative lower lumen to brain blood flow as determined by brain-counted microspheres (15 micron) injected into the ascending aorta was less for DS brains than controls during full flow (DS 63.4+/-129.5 versus CPB 2,585.4+/-250.8, p < 0.001), and when injected into the ejecting-heart left atrium just after weaning off only lower lumen blood flow (DS 250.8+/-297.3 versus CPB 1,159.1+/-782.3, p < 0.001). DS brain temperatures were lower at an equal pump-off core temperature of 36 degrees C+/-0.5 degrees C (DS 31.6 degrees C+/-3.2 degrees C versus CPB 36.5 degrees C+/-1.7 degrees C, p < 0.025). Jugular O2 saturations were not different. CONCLUSIONS: DS-CPB prioritizes pump-filtered separate cold blood flow to the brain over a blood-streaming baffle to wash away potentially surgery related air and particulate matter arising from the heart or ascending aorta.     

Effect of necrosis modulator necrox-7 on hepatic ischemia-reperfusion injury in beagle dogs

Objective

The liver is susceptible to ischemia-reperfusion (IR) injury during inflow occlusion for hepatectomy. There is no effective pharmacologic agent available to prevent the release of high-mobility-group box 1 (HMGB1) or to ameliorate IR injury. This pilot study sought to develop a model in beagle dogs for the purpose of testing the efficacy of a necrosis modulator, necrox-7, to prevent hepatic IR injury in beagle dogs.

Methods

Six male beagle dogs were randomly assigned to the control group (group A; n = 3) or the treatment group (group B; n = 3). Under general anesthesia, group B received intravenous infusion of necrox-7 (13 mg/kg over 20 minutes) followed by 60 minutes of left hepatic inflow occlusion and 60 minutes of reperfusion. Both groups were tested for serum biochemicals, hematology values, liver biopsies, and plasma HMGB1 levels over a 48-hour period.

Results

The maximum alanine transferase (ALT), aspartate transferase (AST), and lactate dehydrogenase (LDH) levels among group A versus group B were: ALT 868.3 ± 337.4 IU/L vs 274.3 ± 72.6 IU/L (P = .041); AST 1,024.7 ± 246.5 IU/L vs 505.3 ± 66.7 IU/L (P = .024); and LDH 962.7 ± 226.2 IU/L vs 552.7 ± 62.4 IU/L (P = .039). Liver biopsy demonstrated marked necrosis and inflammatory infiltrates in group A, whereas group B showed little evidence of IR injury. The plasma HMGB1 concentration was significantly lower among group B versus A.

Conclusion

This pilot study developed a hepatic IR injury model, demonstrating that necrox-7 reduced hepatic necrosis secondary to IR injury in a large animal setting.     

Use of 2.0 mini plate system as reduction plate

Fracture stabilization and reduction using temporary plates during intramedullary tibial nailing was introduced as a novel concept in fracture surgery by Benirschke et al. (Orthop Trans 18:1055–1056, 1995). The concept of temporary reduction using one-third tubular plates proved useful in aiding metaphyseal and periarticular fracture fixation also. However, planning the strategic location of final plate was the main limitation with this technique using one-third tubular plates. We used 2.0 mini plates as provisional reduction plates that solved the issue of planning and placement of plates. The main advantage of our technique is that the final definitive plate can be applied directly over the mini plates. Here, we will describe our technique using relevant fracture case in metaphyseal–periarticular location.     

Prostate calculi in cancer and BPH in a cohort of Korean men：presence of calculi did not correlate with cancer risk

Prostatic calculi are common and are associated with inflammation of the prostate. Recently,it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer （PCa） in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography （TRUS） and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings,patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume.The correlations between PCa risk and age,serum total PSA levels,prostate volume,and prostatic calculi were analyzed. Patient age and PSA,as well as the frequency of prostatic calculi in the biopsy specimens,differed significantly between both the groups （P〈0.05）. In the PCa group,the Gleason scores （GSs） were higher in patients with prostatic calculi than in patients without prostatic calculi （P = 0.023）. Using multivariate logistic regression analysis,we found that patient age,serum total PSA and prostate volume were risk factors for PCa （P = 0.001）,but that the presence of prostatic calculi was not associated with an increased risk of PCa （P = 0.13）. In conclusion,although the presence of prostatic calculi was not shown to be a risk factor for PCa,prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men.     

The long-term outcomes of transplantation of kidneys with multiple renal arteries

Kidneys with multiple renal arteries are increasingly procured for transplantation. To compare the outcomes of kidney transplantation using allografts with multiple arteries, we studied long-term graft function and survival according to their number of arterial anastomoses during an 18-year period from July 1, 1990, through December 31, 2008, in which only the recipient's external iliac artery or internal iliac artery was used for anastomosis (n = 1186). The recipients were divided into four groups: group I, single renal artery with single anastomosis (n = 890, 75.0%); group Il, multiple renal arteries, single anastomosis (n = 26, 2.2%); group Ill, multiple renal arteries, multiple anastomoses (n = 236, 19.9%); and group IV, polar artery ligation (n = 34, 2.9%). We compared the following variables patient and graft survivals; mean creatinine levels at 1 and 6 months, as well as 1-, 3-, and 5-years posttransplant; the number of acute rejection episodes, and the rates of vascular and urologic complications. The creatinine values and incidences of acute rejection episodes did not differ significantly (P = 0.399 and P = 0.990, respectively). There were no significant differences among the four groups in graft survival (P = 0.951), patient survival (P = 0.751), incidence of vascular (P = 0.999) or urologic complications (P = 0.371). The four groups were subdivided according to the recipient arterial anastomosis to the main graft renal artery. The subdivided groups showed no significant differences in graft or patient survival, or complications rates. The results indicated that multiplicity of renal arteries in kidney transplantation did not adversely affect allograft or patient survival compared with single renal artery transplantation. Moreover, the type of the arterial anastomosis (main renal artery end-to-end anastomosed to internal iliac artery or end-to-side anastomosed to external iliac artery appeared to not affect graft or patient survival or the incidence of vascular or urologic complications.     

Altered expression of K+ -Cl- cotransporters affects fast paired-pulse inhibition during GABA receptor activation in the gerbil hippocampus

K+ -Cl- cotransporter (KCC) plays an important role in maintaining neuronal activity. However, the effect of seizure activity or pharmacological manipulation of GABAergic transmission on KCC expression remains to be clarified. Therefore, the present study was performed to investigate whether seizure activity or GABA receptor agonist treatment changes KCC expression in the gerbil hippocampus. Furthermore, the effect of blockade of KCC on inhibitory transmission in the dentate gyrus was identified following applications of GABA receptor agonists. The distribution of KCC immunoreactivity in the hippocampus was similarly detected between seizure-resistant (SR) and seizure-sensitive (SS) gerbils. Baclofen (a GABAB receptor agonist) treatment markedly increased KCC expression in the gerbil hippocampus. Baclofen treatment significantly reduced paired-pulse inhibition in the dentate gyrus. Furosemide (a KCC inhibitor) treatment amplified the effect of baclofen on paired-pulse responses. In contrast, muscimol (a GABAA receptor agonist) treatment reduced KCC expression. Enhanced paired-pulse inhibition by muscimol treatment was not affected by furosemide treatment. These findings suggest that seizure activity in the gerbil may not affect KCC expression in the hippocampus. In addition, altered KCC immunoreactivity induced by baclofen or muscimol may play an important role in maintaining or regulating inhibitory transmission during GABA receptor activation.     

Ischemia-related changes of glial-derived neurotrophic factor and phosphatidylinositol 3-kinase in the hippocampus: their possible correlation in astrocytes

In the present study, we observed the changes of endogenous expression of glial-cell-line-derived neurotrophic factor (GDNF) and phosphatidylinositol 3-kinase (PI-3 kinase) in the gerbil hippocampus after transient forebrain ischemia and investigated the correlation between GDNF and PI-3 kinase in the ischemic hippocampus. In the sham-operated group, GDNF and PI-3 kinase immunoreactivity was not found in any cells in the hippocampal CA1 region. GDNF, not PI-3 kinase, immunoreactivity was expressed in non-pyramidal cells in the CA1 region at 6 h after ischemic insult. At 12-24 h after ischemia, GDNF and PI-3 kinase immunoreactivity in the CA1 region was similar to that of the sham-operated group. From 2 days after ischemic insult, GDNF- and PI-3-kinase-immunoreactive astrocytes were detected in the CA1 region, and GDNF and PI-3 kinase immunoreactivity in astrocytes was highest in the CA1 region 4 days after ischemic insult. Moreover, at this time point, GDNF and PI-3 kinase were co-localized in some astrocytes. Western blotting showed that ischemia-related changes of GDNF and PI-3 kinase protein levels were similar to the immunohistochemical changes after ischemia. These results suggest that GDNF and PI-3 kinase may be related to delayed neuronal death and that GDNF and PI-3 kinase may be involved in activation of astrocytes.     

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE epsilon4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE epsilon4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.