Combined suprascapular nerve block and axillary nerve block approach vs. peri-articular infiltration analgesia for postoperative pain management following arthroscopic shoulder surgery: a randomized clinical trial.

OBJECTIVE: Postoperative pain following shoulder surgery is a devastating situation. Several approaches, including regional nerve blocks such as combined suprascapular nerve block and axillary nerve block (SSNB+ANB) and peri-articular infiltration (PAI) analgesia, have been investigated to manage postoperative pain. This study aimed to compare the effects of PAI and SSNB+ANB on postoperative pain scores and analgesic consumption after arthroscopic shoulder surgery. PATIENTS AND METHODS: A single-center prospective, randomized interventional study with a two-arm parallel design was performed. Sixty patients with arthroscopic shoulder surgery were randomized to SSNB+ANB (n=30) and PAI (n=30) group. Postoperative pain scores, analgesic requirements, and complications were evaluated in the postoperative anesthesia recovery unit and during the postoperative 24 hours. RESULTS: The age of patients in Group PAI was significantly higher than in Group SSNB+ANB (p<0.001). Groups were similar, considering demographic and clinical characteristics (p>0.05). The length of anesthesia and surgery was significantly longer in Group PAI (p=0.009 and p=0.025). Although there was no significant difference in the amount of change in pain scores for postoperative 24 hours (p=0.537), postoperative pain scores were significantly higher in Group SSNB+ANB group than Group PAI during postoperative 24 hours except for the 12th-hour evaluation (p<0.05). Postoperative opioid requirement and rescue analgesic medications were significantly higher in Group SSNB+ANB (p<0.001 and p=0.001). The number of postoperative nausea and vomiting attacks was similar (p=0.317). CONCLUSIONS: PAI seems to be a more feasible and practical analgesic approach for managing postoperative pain after arthroscopic shoulder surgery regarding pain score and cumulative analgesic requirement.

Feasibility of fast-track elements in pediatric surgery.

BACKGROUND: We recently showed that fast-track pathways could be applied to only one third of patients undergoing routine pediatric surgery. The aim of this study was to investigate various fast-track elements in various procedure types irrespective of the applicability of a whole fast-track pathway. METHODS: Patients undergoing routine surgical procedures from April 2009 to April 2010 were included in the study. 11 groups of procedures were differentiated and quality criteria were established for 8 fast-track elements: analgesia, postoperative nutrition, postoperative mobilization, applicability of minimally invasive surgery when appropriate, hospital stay, postoperative symptoms, complications, and parental evaluation. A fast-track element was considered as successfully applied if used in at least 75% of patients. The hospital stay was compared with data from the German reimbursement system (G-DRG). RESULTS: A total of 203 patients were included. Optimal analgesia was achieved in all procedure types except in oncologic surgery (58%) and ureteral reimplantation (71%). Significant nausea and vomiting occurred only after Kasai operation and "other laparoscopic procedures". Early nutrition was achieved in all procedures except after fundoplication (67%) and Kasai operation (62%). Early postoperative mobilization was not successful after hypospadias repair (40%) and ureteral reimplantation (43%). Minimally invasive techniques could not be applied in 48% of thoracic procedures and in 58% of oncological patients. There were no fast-track associated complications. In 4 of 11 procedure types, the mean hospital stay was significantly reduced compared to G-DRG data. There were 4 readmissions (2%). 2 weeks after discharge 94% of interviewed parents evaluated fast-track treatment as excellent. CONCLUSION: Fast-track elements in pediatric surgery increase patient comfort, reduce hospital stay, and achieve a high patient satisfaction. We wish to emphasize the benefits of using fast-track elements irrespective of whether a whole fast-track protocol is applicable.

Incidence of PTLD in pediatric renal transplant recipients receiving basiliximab, calcineurin inhibitor, sirolimus and steroids.

Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9%) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged < or =5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient- (D+/R-) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age < or =5 years (RH 3.2, 95% CI: 1.1-9.6, p = 0.034) and EBV D+/R- status (RH 7.7, 95% CI: 1.6-35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.

The effects of dimethylsulfoxide in experimental obstructive jaundice.

MATERIAL AND METHODS: Thirty rats were divided into three groups, as sham, control and DMSO groups. Laparatomy was performed on each animal in the control and DMSO groups and common bile ducts were ligated. Common bile duct was observed but was not ligated for the rats in the sham group. Saline solution injection (1.5 mg/kg/intraperitoneally (i.p.)) was begun on the first day of surgical procedure and repeated once a day for the next 5 days. The same procedure was performed with DMSO (1.5 mg/kg/i.p.) instead of saline in the DMSO group. The rats were sacrificed on the postoperative seventh day, at which time venous blood and liver tissue specimens were taken. MAIN OUTCOME MEASUREMENTS: On the 7th postoperative day, the bilirubin, AST, ALT, ALP and GGT levels of the control and DMSO groups were significantly higher in comparison with the sham group (p < 0.01). On the 7th postoperative day, the erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the control and DMSO groups were significantly lower than those of the sham group (p < 0.01), but there was no statistical difference between the two groups (p > 0.05). Erythrocyte and liver malondialdehyde (MDA) levels in the control and DMSO groups were significantly higher compared with the sham group (p < 0.01). However, the MDA levels were significantly lower in the DMSO group compared to the control group (p < 0.01). CONCLUSION: It is stated that free oxygen radicals seem to play a role in the liver tissue injury, secondary to obstructive jaundice. In our experimental study, exogenic DMSO seems to have decreased lipid peroxidation and to have improved some of the parameters of liver tissue injury due to the obstructive jaundice in rats.

Platelet-derived growth factor receptor beta regulates migration and DNA synthesis in metanephric mesenchymal cells.

Platelet-derived growth factor (PDGF) B-chain and PDGF receptor beta (PDGFR beta) are essential for glomerulogenesis. Mice deficient in PDGF B-chain or PDGFR beta exhibit an abnormal glomerular phenotype characterized by total lack of mesangial cells. In this study, we localized PDGFR beta in the developing rat kidney and explored the biological effects of PDGF in metanephric mesenchymal cells in an attempt to determine the mechanism by which PDGF regulates mesangial cell development. Immunohistochemical and in situ hybridization studies of rat embryonic kidneys reveal that PDGFR beta localizes to undifferentiated metanephric mesenchyme and is later expressed in the cleft of the comma-shaped and S-shaped bodies and in more mature glomeruli in a mesangial distribution. We also isolated and characterized cells from rat metanephric mesenchyme. Metanephric mesenchymal cells express vimentin and alpha-smooth muscle actin but not cytokeratin. These cells also express functional PDGFR beta, as demonstrated by autophosphorylation of the receptor as well as activation of phosphatidylinositol 3 kinase in response to PDGF B-chain homodimer. PDGF B-chain also induces migration and proliferation of metanephric mesenchymal cells. Taken together with the fact that PDGF B-chain is expressed in the glomerular epithelium and mesangial area, as demonstrated in the human embryonic kidney, we suggest that PDGF B-chain acts in a paracrine fashion to stimulate the migration and proliferation of mesangial cell precursors from undifferentiated metanephric mesenchyme to the mesangial area. PDGF B-chain also likely stimulates proliferation of mesangial cell precursors in an autocrine fashion once these cells migrate to the glomerular tuft.

Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney.

BMP-7, a member of the bone morphogenic protein subfamily (BMPs) of the transforming growth factor-beta superfamily of secreted growth factors, is abundantly expressed in the fetal kidney. The precise role of this protein in renal physiology or pathology is unknown. A cDNA that encodes rat BMP-7 was cloned and used as a probe to localize BMP-7 mRNA expression by in situ hybridization in the adult rat kidney. The highest expression of BMP-7 mRNA could be seen in tubules of the outer medulla. In glomeruli, a few cells, mainly located at the periphery of the glomerular tuft, showed specific and strong signals. Also, high BMP-7 mRNA expression could be localized to the adventitia of renal arteries, as well as to the epithelial cell layer of the renal pelvis and the ureter. Preliminary evidence suggests that BMP-7 enhances recovery when infused into rats with ischemia-induced acute renal failure. We examined BMP-7 mRNA expression in kidneys with acute renal failure induced by unilateral renal artery clamping. BMP-7 mRNA abundance as analyzed by solution hybridization was reduced in ischemic kidneys after 6 and 16 h of reperfusion compared with the contralateral kidney. In situ hybridization in ischemic kidneys showed a marked decrease of BMP-7 mRNA in the outer medulla and in glomeruli. Utilizing rat metanephric mesenchymal cells in culture, we also demonstrate that BMP-7 induces epithelial cell differentiation. Taken together, these data suggest that BMP-7 is important in both stimulating and maintaining a healthy differentiated epithelial cell phenotype.

Epidermal growth factor inhibits Na-Pi cotransport in weaned and suckling rats.

In the present study, we determined the effect of epidermal growth factor (EGF; 10 microgram/100 g body wt) on sodium gradient-dependent phosphate transport (Na-Pi cotransport) regulation in suckling (12-day-old) and weaned (24-day-old) rats. Weaned rats had higher proximal tubular brush border membrane vesicle (BBMV) Na-Pi cotransport activity (232 +/- 16 in weaned vs. 130 +/- 9 pmol. 10 s-1. mg protein-1 in suckling rats, P < 0.05). Chronic treatment with EGF induced inhibition of BBMV Na-Pi cotransport in both suckling (130 +/- 9 vs. 104 +/- 7 pmol. 10 s-1. mg protein-1, P < 0. 05) and weaned rats (232 +/- 16 vs. 145 +/- 9 pmol. 10 s-1. mg protein-1, P < 0.005). The inhibitory effect was selective for Na-Pi cotransport as there was no inhibition of Na-glucose cotransport. Weaned rats had a higher abundance of BBMV NaPi-2 protein than suckling rats (increase of 54%, P < 0.001) and a twofold increase in NaPi-2 mRNA. The EGF-induced inhibition of Na-Pi transport was paralleled by decreases in NaPi-2 protein abundance in both weaned (decrease of 26%, P < 0.01) and suckling (decrease of 27%, P < 0.01) animals. In contrast, there were no changes in NaPi-2 mRNA abundance. We conclude that proximal tubule BBMV Na-Pi cotransport activity, NaPi-2 protein abundance, and NaPi-2 mRNA abundance are higher in weaned than in suckling rats. EGF inhibits Na-Pi cotransport activity in BBMV isolated from suckling and weaned rats, and this inhibition is mediated via a decrease in NaPi-2 protein abundance, in the absence of a change in NaPi-2 mRNA.

An overview of renal trauma.

The topic of renal trauma has offered many substantial and poignant issues of debate over the years, such as classification schemes, management techniques, imaging and diagnostic preferences, and post-traumatic sequelae. This overview presents the most recent and applicable arguments and data surrounding the treatment of renal trauma. Various classification structures have been proposed and utilized for over a century, yet they do not all focus on the different features of trauma presentation (pathogenesis, morphologic implications, symptoms, predisposing conditions) in an equal manner. The traditional controversy between observation and invasive surgery with trauma patients still exists, yet new methods of treatment protocol have been proposed for patients in traumatic shock. Concerning the state of the patient, it has been recognized that children with pretraumatic renal abnormalities are more prone to serious injury, but it is still undecided whether renal trauma will predispose a child to later pathologies such as arterial hypertension. Modern advances in imaging, and diagnostic procedures have dramatically shifted the reliance on intravenous pyelograms to computed tomography, yet the question remains of how much imaging actually is needed in the average patient presenting with renal trauma. Pertinent issues such as these are presented, with main emphasis on literature published within the past 18 months.

Effect of glucocorticoids on neonatal rabbit renal cortical sodium-inorganic phosphate messenger RNA and protein abundance.

Administration of glucocorticoids to neonates increases proximal tubule volume absorption by increasing glucose, bicarbonate, and amino acid transport. We have recently demonstrated that glucocorticoids may contribute to the maturational decrease in phosphate transport. This study examines the maturation of NaPi-6 [the regulated proximal tubule sodium-inorganic phosphate (Na-Pi) transporter] mRNA and protein abundance and the mechanism for the decrease in phosphate transport by glucocorticoids. Weaned young rabbits (5 wk) had a 2-fold greater brush border membrane NaPi-6 protein abundance than that measured in adults. Renal cortical NaPi-6 mRNA abundance was comparable in neonates (less than 10 d of age) and adults. Renal brush border membrane vesicles from dexamethasone-treated neonatal rabbits (10 micrograms/100 g of body weight for 4 d) had a lower rate of Na-Pi transport than vehicle-treated controls (46.8 +/- 6.5 versus 71.0 +/- 9.0 pmol 32P/10 s/mg of protein, p < 0.05). Abundance of NaPi-6 protein in brush border membrane vesicles was 3-fold lower in newborn rabbits treated with pharmacologic doses of dexamethasone than in vehicle-treated controls. NaPi-6 mRNA abundance was the same in both groups. NaPi-1, a brush border membrane phosphate transporter which is also an anion channel, mRNA, and protein abundance was not affected by glucocorticoids. These data demonstrate that there is a maturational decrease in NaPi-6 protein abundance and that glucocorticoids decrease neonatal phosphate transport, at least in part, by reducing the number of Na-Pi transporters.

Epidermal growth factor inhibits Na-Pi cotransport and mRNA in OK cells.

The present study examined the effect of epidermal growth factor (EGF) on Na-Pi cotransport in a tubular epithelial cell line derived from the opossum kidney (OKP cells). EGF caused a time- and dose-dependent decrease in Na-Pi cotransport. The inhibition of Na-Pi cotransport by 10(-8) M EGF was first demonstrable after 18 h with maximal effect seen at 24 h. EGF inhibited Na-Pi cotransport by decreasing the maximal velocity (10.8 +/- 0.9 in control vs. 4.9 +/- 0.8 nmol 32Pi.4 min-1.mg protein-1 in EGF, P < 0.001). Northern blot analysis indicated that EGF caused a significant decrease in NaPi-4 mRNA abundance. The abundance of NaPi-4 mRNA relative to beta-actin and/or glyceraldehyde-3-phosphate dehydrogenase mRNA was decreased by twofold in OK cells treated with EGF for 4 h and threefold in OKP cells treated with EGF for 24 h. Thus the decrease in NaPi-4 mRNA abundance preceded the decrease in Na-Pi cotransport activity. Inhibition of transcription with actinomycin D and protein synthesis with cycloheximide prevented the inhibition of Na-Pi cotransport. Furthermore, inhibition of phospholipase C activity with U-73,122 also significantly blocked the inhibitory effect of EGF on Na-Pi cotransport. The results indicate that EGF-induced decrease in OKP Na-Pi cotransport is mediated through a decrease in NaPi-4 mRNA and activation of the phospholipase C signaling pathway.

Cellular mechanisms of acute and chronic adaptation of rat renal P(i) transporter to alterations in dietary P(i).

Recently, the cDNA for a Na-P(i) cotransport system of rat kidney cortex (NaPi-2) has been identified by expression cloning. Using polyclonal antibodies raised against this renal Na-P(i) cotransport system, and using the polymerase chain reaction after reverse transcription of mRNA in microdissected nephron segments, we recently demonstrated that NaPi-2-related mRNA and protein is expressed in the brush-border membranes (BBM) of the proximal tubules of rat kidney. The purpose of the present study was to study the cellular mechanisms involved in adaptation of rat renal Na-P(i) cotransporter to acute and chronic alterations in dietary P(i). Compared with rats fed chronically (7 days) a high-P(i) diet (1.2%), in rats fed chronically a low-P(i) (0.1%) diet the 3.4-fold increase in BBM Na-P(i) cotransport rate (chronic upregulation) was associated with a 2.2-fold increase in renal cortical NaPi-2 mRNA and a 4.9-fold increase in BBM NaPi-2 protein abundances. In contrast, compared with rats fed chronically (7 day) a high-P(i) diet, in rats fed acutely (2 h) a low-P(i) diet the 1.5-fold increase in Na-P(i) cotransport rate (acute upregulation) was associated with a 1.8-fold increase in NaPi-2 protein but no change in NaPi-2 mRNA abundance. Similarly, compared with rats fed chronically a low-P(i) diet, in rats fed acutely (2 h) a high-P(i) diet the 1.9-fold decrease in Na-P(i) cotransport rate (acute downregulation) was associated with a 3.8-fold decrease in NaPi-2 protein but no change in NaPi-2 mRNA abundance.(ABSTRACT TRUNCATED AT 250 WORDS)

Maturational effects of glucocorticoids on neonatal brush-border membrane phosphate transport.

Previous studies have implicated glucocorticoids as an important factor in the postnatal maturational increase in proximal tubule volume absorption, Na+/H+ antiporter, Na(HCO3)3 symporter, and Na(+)-K(+)-ATPase activity. The present study examined whether glucocorticoids are also a potentially important factor in the maturational decrease in proximal tubule phosphate transport. Renal BBMs were prepared from neonatal rabbits who received dexamethasone (10 micrograms/100 g body weight) or vehicle. Brush-border membrane vesicles from dexamethasone-treated neonates had a lower rate of Na-phosphate cotransport than controls (50.8 +/- 3.6 versus 29.2 +/- 2.6 pmol 32P(i)/10 s/mg protein, p < 0.001). This decrease was due to a decrease in the Vmax with no change in the affinity of the transporter for phosphate. The dexamethasone-induced decrease in BBM Na-phosphate transport was not due to a reduction in transporters as assayed by phosphate-protectable Na-dependent equilibrium binding of phosphonoformic acid. Dexamethasone treatment caused an increase in the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene and trimethylammonium-1,6-diphenyl-1,3,5-hexatriene (i.e. a decrease in membrane fluidity). Brush-border membranes from dexamethasone-treated neonates had a decrease in sphingomyelin and an increase in phosphatidylcholine and phosphatidylinositol content but no change in cholesterol or total phospholipid content. These data are consistent with glucocorticoids playing a role in the postnatal maturational decrease in proximal tubule phosphate transport by altering membrane characteristics.

Etiology of sustained hypertension in children in the southwestern United States.

We reviewed the records of 132 children with persistent hypertension who were evaluated by our pediatric nephrology services between 1987 and 1991. Eighty-nine (67%) of these children were found to have renal or renovascular disease, 30 (23%) had primary hypertension and 13 (10%) had a non-renal cause for their hypertension. Glomerulonephritis (n = 37) and reflux nephropathy (n = 26) were the most frequent renal disorders identified. Renal artery thrombosis was the most common cause of hypertension in the neonatal period (in 6 of 12 neonates, 50%) whereas cystic kidney disease was the most common cause of hypertension in the 1st year of life (in 9 of 30 infants, 30%). The prevalence of primary hypertension increased with age; this diagnosis was made in 16 of 46 (35%) hypertensive patients between 12 and 18 years of age and, more surprisingly, in 8 of 27 (30%) children between 7 and 11 years of age. These data confirm that secondary hypertension is the most common cause of hypertension in children but suggest that primary hypertension is more prevalent than previously recognized in patients between 7 and 18 years of age.

Low-Pi diet increases the abundance of an apical protein in rat proximal-tubular S3 segments.

Dietary phosphate (Pi) restriction is associated with an adaptive increase in proximal-tubular apical brush-border membrane (BBM) sodium-dependent Pi transport (Na-Pi cotransport). Adaptation to Pi restriction is dependent on de novo protein synthesis; however, it is not known whether the proteins involved represent newly synthesized Na-Pi cotransporters or some other (regulatory) proteins. Recently the cDNA for a Na-Pi cotransport system of rabbit kidney cortex (system NaPi-1) has been identified by expression cloning. The purpose of this study was to determine if the adaptive increase in Na-Pi cotransport in response to dietary Pi restriction in the rat is associated with an increase in the abundance of a NaPi-1-related protein. To answer this question we took advantage of the cross-reactivity of polyclonal antibodies raised against a C-terminal peptide of the NaPi-1 protein with a protein of BBM isolated from rat kidney cortex. On Western blots, a positive reaction with a protein with an apparent molecular mass of 100 kDa was observed in BBM isolated from juxtamedullary cortex and, to a lesser extent, in BBM isolated from superficial cortex. In immunohistochemical studies anti-(NaPi-1)-antiserum-mediated immunofluorescence was observed predominantly in S3 segments where the immunoreaction was restricted to the brush borders. Compared to control BBM, in BBM isolated from the juxtamedullary cortex of rats fed a low-Pi diet, there was a twofold increase in the abundance of the 100-kDa protein. In the same membrane vesicles Na-Pi cotransport was increased threefold. The results of this study demonstrate specific expression of a 100-kDa apical protein in S3 cells of rat proximal tubules. Increased abundance of the 100-kDa protein due to chronic Pi restriction suggests an involvement of this protein in the (chronic) adaptive response of S3 cells to a low-Pi diet.