Needle core biopsy in the diagnosis of pediatric thyroid neoplasms: a single institution retrospective review.

PURPOSE: Our institution routinely utilizes needle core biopsy (NCB), instead of fine needle aspiration, in the evaluation of pediatric thyroid nodules. This practice initially arose from limited cytopathology services in our hospital. Given the lack of information regarding the utility of NCB in diagnosing pediatric thyroid neoplasms, we set out to review our institution's experience with this technique. METHODS: We performed a single institution retrospective chart review of all children who underwent thyroidectomy for primary thyroid pathology. RESULTS: Seventy-four patients, with a mean age of 12.9 ± 4.5 (SD) years, underwent partial or total thyroidectomy between 2002 and 2010. Seven of these patients had medically refractive hyperthyroidism. The remaining 67 patients had one or more thyroid nodules as identified by ultrasound. 24 (36 %) of these cases were malignant on final pathology. 14 (58 %) of the malignant cases were papillary thyroid carcinoma. 46 of the thyroid nodule cases underwent pre-operative NCB. Biopsy results for these patients were non-diagnostic in 6 (13 %), benign in 11 (24 %), atypical in 17 (37 %), and malignant in 12 (26 %). There were no complications arising from NCB. Sensitivity of NCB for diagnosing papillary carcinoma (PC) and follicular neoplasm was calculated at 0.88 (0.47-1.0, 95 % CI) and 0.84 (0.60-0.97, 95 % CI), respectively. Of the 28 patients not undergoing preoperative NCB, 12 underwent hemithyroidectomy, with one patient (8 %) requiring completion thyroidectomy for PC. Overall, the sensitivity of NCB in diagnosing PC and follicular thyroid neoplasms was 0.85 (0.55-0.99, 95 % CI), while the specificity was 0.63 (0.42-0.82, 95 % CI). CONCLUSIONS: Needle core biopsy appears to have a low rate of associated complications, and its sensitivity for diagnosing PC and follicular neoplasm is comparable to what has been reported for fine needle aspiration biopsy in a similar patient population.

Dietary protein causes a decline in the glomerular filtration rate of the remnant kidney mediated by metabolic acidosis and endothelin receptors.

Dietary casein promotes a progressive decline in the glomerular filtration rate (GFR) of remnant kidneys associated with metabolic acidosis and an endothelin-mediated increase in renal acidification. We tested whether diets that affect the acid-base status contributes to the decline of GFR through endothelin receptors in rats with a remnant kidney. Rats on a casein diet had metabolic acidosis at baseline and developed a progressive decline in GFR after renal mass reduction. Dietary sodium bicarbonate but not sodium chloride ameliorated metabolic acidosis and prevented the decrease in GFR but only after the sodium bicarbonate-induced increase in blood pressure was treated. Dietary soy protein did not induce baseline metabolic acidosis and rats with remnant kidney on a soy diet had no decrease in their GFR. By contrast, rats with a remnant kidney on soy protein given dietary acid developed metabolic acidosis and a decreased GFR. This decline in GFR was prevented in either case by endothelin A but not endothelin A/B receptor antagonism. Our study suggests that the casein-induced decline in GFR of the remnant kidney is mediated by metabolic acidosis through endothelin A receptors.

Dietary protein induces endothelin-mediated kidney injury through enhanced intrinsic acid production.

Dietary protein as casein (CAS) augments intrinsic acid production, induces endothelin-mediated kidney acidification, and promotes kidney injury. We tested the hypothesis that dietary CAS induces endothelin-mediated kidney injury through augmented intrinsic acid production. Munich-Wistar rats ate minimum electrolyte diets from age 8 to 96 weeks with 50 or 20% protein as either acid-inducing CAS or non-acid-inducing SOY. Urine net acid excretion and distal nephron net HCO3 reabsorption by in vivo microperfusion (Net J(HCO3)) were higher in 50 than 20% CAS but not 50 and 20% SOY. At 96 weeks, 50% compared the 20% CAS had higher urine endothelin-1 excretion (U(ET-1)V) and a higher index of tubulo-interstitial injury (TII) at pathology (2.25+/-0.21 vs 1.25+/-0.13 U, P<0.03), but each parameter was similar in 50 and 20% SOY. CAS (50%) eating NaHCO3 to reduce intrinsic acid production had lower Net J(HCO3), lower U(ET-1)V, and less TII. By contrast, 50% SOY eating dietary acid as (NH4)2SO4 had higher Net J(HCO3), higher U(ET-1)V, and more TII. Endothelin A/B but not A receptor antagonism reduced Net J(HCO3) in 50% CAS and 50% SOY+(NH4)2SO4 animals. By contrast, endothelin A but not A/B receptor antagonism reduced TII in each group. The data support that increased intake of acid-inducing dietary protein induces endothelin B-receptor-mediated increased Net J(HCO3) and endothelin A-receptor-mediated TII through augmented intrinsic acid production.

Regulation of kidney acid excretion by endothelins.

Endothelin (ET) is a potent vasoconstrictor that is now known to modulate kidney tubule transport, including kidney tubule acidification. Animals undergoing an acid challenge to systemic acid-base status and with some models of chronic metabolic acidosis have increased kidney ET production. Increased ET production/activity contributes to enhanced kidney tubule acidification that facilitates kidney acid excretion in response to an acid challenge to systemic acid-base status. The data to date support a physiologic role for ET in mediating enhanced kidney acidification in response to acid challenges, but do not support an ET role in maintaining kidney tubule acidification in control, non-acid-challenged states. ET increases acidification in both the proximal and distal nephron and appears to exert its effects both directly and indirectly, the latter through modulating the levels and/or activity or other mediators of kidney tubule acidification. ET also contributes to enhanced kidney acidification in some pathophysiologic states and might contribute to some untoward outcomes associated with these conditions. Whether ET should be a therapeutic target in treating and/or preventing some of these untoward outcomes remains an open question. This review supports continued research into the physiologic and possibly pathophysiologic role of ET in settings of increased kidney tubule acidification.

Vacuolar-type H+-ATPases at the plasma membrane regulate pH and cell migration in microvascular endothelial cells.

Microvascular endothelial cells involved in angiogenesis are exposed to an acidic environment that is not conducive for growth and survival. These cells must exhibit a dynamic intracellular (cytosolic) pH (pHcyt) regulatory mechanism to cope with acidosis, in addition to the ubiquitous Na+/H+ exchanger and HCO3--based H+-transporting systems. We hypothesize that the presence of plasmalemmal vacuolar-type proton ATPases (pmV-ATPases) allows microvascular endothelial cells to better cope with this acidic environment and that pmV-ATPases are required for cell migration. This study indicates that microvascular endothelial cells, which are more migratory than macrovascular endothelial cells, express pmV-ATPases. Spectral imaging microscopy indicates a more alkaline pHcyt at the leading than at the lagging edge of microvascular endothelial cells. Treatment of microvascular endothelial cells with V-ATPase inhibitors decreases the proton fluxes via pmV-ATPases and cell migration. These data suggest that pmV-ATPases are essential for pHcyt regulation and cell migration in microvascular endothelial cells.

Monitoring performance: longterm impact of trauma verification and review.

BACKGROUND: This study documents how the verification process at a Level I pediatric trauma center affected patient care through changes in care indicators (CIs) from predesignation through four postverification time frames. An important component of any verification program is its effectiveness, not only at the time of verification but during the time between "examinations." To date, few data exist describing the interval periods and the progression and maturation of a trauma program after initial verification. STUDY DESIGN: Forty-seven distinct CIs were monitored monthly through data generated from the trauma registry. Six distinct time periods were identified. PRE (January, June, October 1997), trauma care without monitoring; VER (November 1999 to September 2000), preparation for verification; and four postverification periods: P1 (January to June 2001), P2 (July to December 2001), P3 (January to June 2002), and P4 (July to September 2002). RESULTS: Between 1997 and 2002, trauma admissions increased from 200 per year to 313 per year. Mortality rate and Injury Severity Score distributions remained unaltered. Statistically significant (p < 0.05) quantitative and qualitative changes were observed in numbers (percent) of patients reaching clinical criteria. These included prehospital, emergency department, and hospital-based trauma competencies. Trauma patient evaluation (including radiology) and disposition out of the emergency department (<120 minutes) improved in each study section and remained high during the postverification time period. There was a strong pair-wise correlation (p < 0.005, Cronbach alpha 0.8) between CNS charting and acquisition of head CAT scans. Pediatric ICU duration of stay increased in both the (summer) P2 and P4 time periods. Prehospital and emergency department fluid monitoring remained unsatisfactory. CONCLUSIONS: Statistically significant changes in patient care indicators were noted to improve during the trauma center designation process, and other key deficiencies were identified and addressed. Maintaining these improvements requires constant monitoring or performance may revert below accepted levels.

Hypertension and the kidney.

Hypertension and kidney function are intimately related, with each having significant influences on the other. Given the major role played by the kidney in maintenance of extracellular fluid volume and peripheral vascular resistance, the kidney is justifiably a target of investigation to determine its potential role in essential hypertension. Conversely, hypertension is associated with progressive renal failure, and hypertension-associated end-stage renal disease is the second leading cause of end-stage renal disease in the United States. It is therefore important that we continue to investigate the hypertension/renal relationship in an effort to better understand the determinants of essential hypertension and to prevent a major cause of end-stage renal disease.

Surgery for ovarian masses in infants, children, and adolescents: 102 consecutive patients treated in a 15-year period.

BACKGROUND/PURPOSE: Ovarian pathology, although rare in children, must be included in the differential diagnosis of all girls who present with abdominal pain, an abdominal mass, or precocious puberty. METHODS: To improve clinical appreciation of these lesions, the authors reviewed the presentation, evaluation, and outcome of all patients with ovarian pathology surgically treated at their institution since 1985. RESULTS: One hundred two girls (aged 9.8 +/- 5.5 years; range, 2 days to 20 years) underwent 106 separate ovarian operations (43 salpingo-oophorectomies, 21 oophorectomies, 33 ovarian cystectomies, and 9 ovarian biopsies). Of those presenting with acute abdominal pain (n = 59), 25 (42%) had ovarian torsion (14 associated with a mature teratoma), and only 1 (2%) had a malignant tumor. In contrast, of those presenting with an abdominal mass (n = 23), 6 (26%) had malignancies. There was no age difference between those with benign disease (9.9 +/- 5.6 years; n = 96) and those with malignant tumors (8.6 +/- 3.9 years, n = 10). Nine children had 10 operations for presumed malignant tumors (3 dysgerminomas, 2 immature teratomas with foci of yolk sac tumor, 2 juvenile granulosa cell tumors, 1 yolk sac tumor, and 1 Sertoli-Leydig cell tumor). These patients all had unilateral salpingo-oophorectomy, 4 had chemotherapy, and all are now disease free at 8.4 +/- 4.1 years follow-up. CONCLUSION: Ovarian pathology remains a rare indication for surgery in girls less than 20 years of age. Because most of these lesions are benign, ovarian-preserving operations should be performed whenever feasible.

Primary peritoneal drainage for increasing ventilatory requirements in critically ill neonates with necrotizing enterocolitis.

BACKGROUND/PURPOSE: Primary peritoneal drainage (PPD) is an established therapy for premature neonates with necrotizing enterocolitis (NEC) and free intraperitoneal air. This study seeks to evaluate the efficacy of PPD in ill premature neonates with severe abdominal distension and increasing ventilatory requirements without free intraperitoneal air. METHODS: Eleven neonates (gestational age, 27 +/- 0.59 weeks; age, 25 +/- 4.3 days; birth weight, 862 +/- 67 g) with NEC underwent bedside PPD under local anesthesia for rapid clinical deterioration characterized by severe abdominal distension and increasing ventilatory requirements. None showed radiographic evidence of free intraperitoneal air. Mean airway pressure (MAP) and oxygenation-index (OI) were analyzed 24 hours before, immediately before and 24 hours after surgery. The patients were followed up to discharge from hospital. Statistical analyses were performed using analysis of variance (ANOVA) for repeated measures. RESULTS: Mean airway pressure (MAP) showed a significant difference (P <.05) increasing from 7.1 +/- 0.75 cm H2O 24 hours before surgery to 11 +/- 1.3 cm H2O immediately before surgery and decreasing to 9.9 +/- 1.1 cm H2O 24 hours after drainage. Likewise, OI measured at the same time intervals showed significant differences (P <.05) deteriorating from 5 +/- 1.2 to 26 +/- 6.9 then improving to 13 +/- 3.5. A significant quadratic effect (P <.03) was evident for MAP and OI (ie, values significantly rose then fell). There were six 30-day survivors (55%), and 3 survived to discharge (27%). Of the long-term survivors, 2 required operative fistula closure, and 1 needed no further surgery. CONCLUSION: Bedside PPD for increasing ventilatory requirements and abdominal distension in critically ill neonates with nonperforated NEC is a simple technique that offers rapid stabilization, although ultimate mortality rate remains high.

Prokinetic agents increase plasma albumin in hypoalbuminemic chronic dialysis patients with delayed gastric emptying.

Hypoalbuminemia is a surrogate of malnutrition in patients with end-stage renal disease undergoing chronic dialysis and commonly improves with prescription of adequate nutrition and dialysis. Nevertheless, some patients remain hypoalbuminemic for poorly understood reasons. We tested the hypotheses that chronic dialysis patients who remain hypoalbuminemic despite prescription of adequate nutrition and dialysis (1) have delayed gastric emptying, and (2) that prokinetic agents will increase plasma albumin (P(alb)) levels in patients with delayed gastric emptying. We retrospectively identified 99 of 343 hemodialysis and peritoneal dialysis patients with hypoalbuminuria (P(alb) < 3.5 mg/dL) and studied those who did not (hypoalbuminemic, n =15) and did (normoalbuminemic, n = 15) increase their P(alb) levels over the subsequent 6 months and met inclusion and exclusion criteria. Gastrointestinal symptom scores determined by an administered questionnaire were not different in hypoalbuminemic and normoalbuminemic patients. Conversely, the half-time (T(1/2)) for radionuclide gastric emptying was longer in hypoalbuminemic than normoalbuminemic patients (74.5 +/- 7.4 versus 46.7 +/- 4.6 minutes; P < 0.004). Hypoalbuminemic patients were prescribed prokinetics and followed prospectively for 6 months, during which time gastric T(1/2) decreased to 53.9 +/- 3.3 minutes (P < 0.01 versus initial) and P(alb) increased from 3.1 +/- 0.2 to 3.5 +/- 0.2 mg/dL (P < 0.004). The net increase in P(alb) level correlated with the net decrease in gastric T(1/2) (r(2) = 0.4; P < 0.04) by linear regression. The data show that some persistently hypoalbuminemic chronic dialysis patients have poor gastric emptying and increase their P(alb) levels in response to prokinetic agents.

A novel hemoglobin-adenosine-glutathione based blood substitute: evaluation of its effects on human blood ex vivo.

Chemically modified hemoglobin (Hb) solutions are under current investigation as potential red cell substitutes. Researchers at Texas Tech University have developed a novel free Hb based blood substitute product. This blood substitute is composed of purified bovine Hb cross-linked intramolecularly with o-adenosine-5'-triphosphate and intermolecularly with o-adenosine, and conjugated with reduced glutathione (GSH). In this study, we compared the effects of our novel blood substitute and unmodified (U) Hb, by using allogenic plasma as the control, on human blood components: red blood cells (RBCs), platelets, monocytes (Mo), and low-density lipoproteins (LDLs). The pro-oxidant potential of both Hb solutions on RBCs was examined by the measurement of osmotic and mechanical fragility, conjugated dienes (CD), lipid hydroperoxides (LOOH), thiobarbituric acid reactants (TBAR-S), isoprostanes (8-iso PGF2alpha) and intracellular GSH. The oxidative modification of LDLs was assessed by CD, LOOH, and TBAR-S, and the degree of apolipoprotein (apo) B cross-linking. The effects of Hb on platelets have been studied by monitoring their responses to the aggregation agonists: collagen, ADP, epinephrine, and arachidonic acid. Monocytes were cultured with Hb solutions or plasma and tested for TNF-alpha and IL-1beta release, then examined by electron microscopy. Results indicate that native UHb initiates oxidative stress of many blood components and aggravates inflammatory responses of Mo. It also caused an increase in RBC osmotic and mechanical fragility (p < 0.001). While the level of GSH was slightly changed, the lipid peroxidation of RBC increased (p < 0.001). UHb was found to be a stimulator of 8-iso PGF2alpha synthesis, a potent modulator of LDLs, and an effective potentiator of agonist induced platelet aggregation. Contrarily, our novel blood substitute did not seem to induce oxidative stress nor to increase Mo inflammatory reactions. The osmotic and mechanical fragility of RBCs was similar to that of the control. Such modified Hb failed to alter LDLs, increase the production of 8-iso PGF2alpha, but markedly inhibited platelet aggregation. The effect of this novel blood substitute can be linked with the cytoprotective and anti-inflammatory properties of adenosine, which is used as a cross-linker and surface modifier, and a modification procedure that lowers the hemoglobin pro-oxidant potential.

Peritoneal drainage as definitive treatment for neonates with isolated intestinal perforation.

BACKGROUND/PURPOSE: To better define the indications for peritoneal drainage (PD) in premature babies with intestinal perforation, the authors reviewed their experience with this procedure in a tertiary neonatal intensive care setting. METHODS: The charts of all neonates who underwent PD as initial treatment for intestinal perforation between 1996 and 1999 were reviewed. Those patients with pneumatosis intestinalis on abdominal radiograph had perforated necrotizing enterocolitis (NEC) diagnosed; whereas, those infants with no pneumatosis had isolated intestinal perforation diagnosed. The clinical characteristics and outcomes of these 2 groups were compared. RESULTS: Twenty-one premature neonates had primary PD between 1996 and 1999, 10 for isolated intestinal perforation and 11 for perforated NEC. Patients with isolated intestinal perforation had lower birth weights (708 v 949 g; P < .05), were less likely to have started feedings (30% v 91%, P < .05), and the perforation developed at an earlier age (10.6 v 28.0 d, P < .05) compared with the patients who had perforated NEC. Only 2 of 10 infants with isolated perforation required subsequent laparotomy (at 10 weeks for stricture and 12 weeks for a persistent fistula). For these patients, the long-term survival rate was 90%. In contrast, 8 of 11 infants with perforated NEC required laparotomy, and although the 30-day survival rate was 64%, the long-term survival rate was only 27%. CONCLUSIONS: Peritoneal drainage provides successful and definitive treatment for most premature babies with isolated intestinal perforation. For neonates with perforation caused by NEC, peritoneal drainage may provide temporary stabilization, but most of these infants require subsequent laparotomy, and few survive.

Risk factors for severe injuries associated with falls from playground equipment.

A case control study design was used to determine the risk factors for severe injuries associated with falls from playground equipment. Children presenting to the Hospital for Sick Children in Toronto because of falls from playground equipment (1995-1996) were identified through daily review of admissions and emergency department visits. Cases were defined as children with a severe injury (AIS > or = 2), whereas, controls were children with a minor injury (AIS < 2). Data on age, sex, socioeconomic status, prior experience on the equipment, previous playground injury, type of equipment, height of fall, undersurface, nature of injury, body part involved, and disposition were collected via telephone interview, field trip measurement, and mailed questionnaire. A total of 126 children were studied--67 cases and 59 controls. There were no differences between the two groups on age, sex, socioeconomic status, prior exposure to the equipment, or previous playground injury. Extremity fractures predominated in the case group, while, facial lacerations predominated in the control group. The median height of fall for cases was 199 cm, compared with 160 cm for controls (P = 0.021). Cases were also more likely to have fallen from a height of > 150 cm (73%), compared with controls (54%), P = 0.027. The majority of cases (82%) and controls (86%) fell onto an impact absorbing undersurface (P = 0.540). The median depth of impact absorbing undersurface, however, for both case and control injuries was 3 cm--well below the recommended safety standards. Height of fall was an important risk factor for severe injury associated with falls from playground equipment. Above 150 cm, the risk of severe injury was increased 2-fold.

Cigarette smoking is associated with augmented progression of renal insufficiency in severe essential hypertension.

Hypertension-associated renal disease is a major cause of end-stage renal disease (ESRD) in the United States, but its risk factors remain incompletely defined. Identification and correction of amendable ESRD risk factors among patients with essential hypertension could reduce ESRD prevalence. Patients referred by their primary care physician for hypertension management to an academic nephrology clinic during calendar year 1995 were followed up prospectively. Studied patients had no evidence of secondary hypertension, diabetes, or primary renal disease. All were treated pharmacologically toward a target mean blood pressure (MBP) of 100 mm Hg or less. The course of renal function during follow-up was assessed as the slope of the reciprocal of plasma creatinine concentration (1/P(cr)) plotted against months of follow-up and as the change in calculated glomerular filtration rate (GFR) in milliliters per minute per month. The following patient characteristics were prospectively examined as possible predictive factors for altered renal function: age, sex, ethnicity, initial MBP, initial P(cr) level, initial level of urine protein excretion, and smoking status. Fifty-three patients were enrolled, and follow-up data were available for 51 patients after a mean follow-up of 35.5 months. Despite MBP reduction from 126.8 +/- 1.3 to 96.5 +/- 1.1 mm Hg (P < 0.0001), P(cr) level increased from 1.5 +/- 0.1 to 1.9 +/- 0. 2 mg/dL (P < 0.01). Multivariate regression analysis showed that smoking, greater initial P(cr) level, and black ethnicity were the only examined parameters that independently predicted both a decrease in the 1/P(cr) slope and calculated GFR with at least 95% confidence. Smoking was by far the most powerful of the examined factors, with initial P(cr) and ethnicity being much less predictive. These studies show for the first time that smoking is an independent risk factor for renal function decline in patients with severe essential hypertension.

Postoperative ad lib feeding for hypertrophic pyloric stenosis.

PURPOSE: The aim of this study was to compare three methods of postoperative feeding after pyloromyotomy for hypertrophic pyloric stenosis (HPS). METHODS: The authors reviewed retrospectively the charts of 308 patients who underwent pyloromyotomy for HPS from 1984 to 1997. Nineteen patients had prolonged hospitalization for other reasons and were excluded from the study, leaving 289 patients for analysis. All procedures were performed by a single group of pediatric surgeons. The individual preferences of these surgeons resulted in three different feeding schedules: R, strictly regimented (>12 hours nothing by mouth, then incremental feeding over > or =24 hours), I, intermediate (>8 hours nothing by mouth, then incremental feeding over <24 hours), or A, ad lib (< or =4 hours nothing by mouth, with or without a single small feeding, then ad lib feedings). RESULTS: Of the 289 patients, 248 (80.5%) were boys. The average age of the patients was 5.64 weeks (range, 1 to 21 weeks). A total of 265 of 289 (92%) were full term. Thirty-nine of 289 (13.5%) had a family history positive for pyloric stenosis. A total of 104 of 289 (36%) were first-born infants, 89 of 289 (31%) were second born. The diagnosis of pyloric stenosis was made by a combination of physical examination findings and diagnostic image for most patients. An "olive" was palpated in 60.6% of the patients. Sixty percent (60.4%) of patients had an upper gastrointestinal series performed, and 42.5% were examined by ultrasonography. Overall, 53% of the patients had postoperative emesis. Only 3.5% had emesis that persisted greater than 48 hours after surgery. Patients fed ad lib after pyloromyotomy had slightly more emesis (2.2 A v. 1.2 R, and 0.7 I episodes, P = .002), but tolerated full feedings sooner than patients fed with a regimented or intermediate schedule. No patient required additional therapy or readmission after tolerating two consecutive full feedings, suggesting that this might be a suitable discharge criterion for most patients with HPS.

Improved blood substitute: evaluation of its effects on human endothelial cells.

The authors have previously documented that appropriate chemical and pharmacologic modification of the hemoglobin molecule are required to attenuate certain pathophysiologic reactions of the reticuloendothelium. The current study further investigates the molecular responses of human coronary artery endothelial cells to a high concentration (0.4 mmol) of 1) unmodified bovine hemoglobin; and 2) an improved blood substitute that comprises hemoglobin cross-linked intramolecularly with o-adenosine triphosphate and intermolecularly with o-adenosine, and conjugated with reduced glutathione. In this study, the scavenging effect of hemoglobins toward nitric oxide (NO) was evaluated by the measurement of nitrite (NO2-) and nitrate (NO3-) formation. The pro-oxidant effect of hemoglobin on endothelial cells was examined by the measurement of intracellular reduced glutathione, and by monitoring the formation of lipid hydroperoxides and 8-iso prostaglandin F2alpha, a novel potent vasoconstrictor, which is produced by a noncyclooxygenase mechanism involving free radical catalyzed peroxidation of arachidonic acid. The inflammatory reactions of endothelial cells were evaluated by the expression of the adhesion molecule, intracellular adhesion molecule-1, and the activation of nuclear transcription factor, nuclear factor kappaB. In additional, endothelial cell responses were investigated by analysis of intracellular ionized calcium concentrations. Results indicate that unmodified hemoglobin in a concentration of 0.4 mmol/L can aggravate endothelial cell oxidative and inflammatory responses. This hemoglobin produced a significant (p < 0.01) depletion of reduced glutathione, acceleration of lipid peroxidation, and a greater influx of Ca2+. The formation of 8-iso prostaglandin F2alpha increased compared with the control cells (p < 0.01). Unmodified hemoglobin was found to be a potent scavenger of NO, great activator of nuclear factor kappaB, and a stimulator of intracellular adhesion molecule-1 expression. Contrarily, the improved blood substitute did not appear to induce oxidative stress nor to increase the intracellular Ca2+. The concentration of 8-iso prostaglandin F2alpha was similar to that in the control cells, whereas the formation of NO2-/NO3- was much lower (p < 0.05) than in the unmodified hemoglobin group. The effect of an improved blood substitute can be linked with the anti-inflammatory and cytoprotective properties of adenosine, which is used as a cross-linker and surface modifier, and the type of the chemical modification procedure that lowers hemoglobin pro-oxidant potential.

Interactions between benzylamiloride and fura-2: studies in vitro and in cardiac myocytes.

Amiloride derivatives are commonly used inhibitors of Na+/H+- and Na+/Ca2+-exchange. Because they are fluorescent molecules the use of benzylamiloride (BZA), an inhibitor of Na+/Ca2+ exchange, in conjunction with Fura-2, a commonly used fluorescent Ca2+ indicator, might complicate interpretation of fluorescence data obtained. In vitro data show that BZA decreases the Fura-2 fluorescence at all useful wavelengths in a concentration-dependent manner. The Fura-2 ratio 340/380 (used to estimate intracellular Ca2+ ([Ca2+]in)) also decreased with increasing BZA concentrations. The Stern-Volmer relation suggests that this phenomenon is due to either static or dynamic quenching. Varying temperatures from 4 to 37 degreesC did not alter Stern-Volmer constants, consistent instead with fluorescence resonance energy transfer (FRET). The in situ relevance of these interactions was evaluated in adult rat cardiac myocytes which exhibit Na+/Ca2+ exchange reflected by rapid [Ca2+]in increase following Na+ removal. Pretreatment with BZA >/= 25 microM decreased the magnitude of Fura-2 changes induced by Na+ removal. Analysis of the individual Fura-2 useful wavelengths indicated that >/= 25 microM BZA altered the Fura-2 signal in a manner consistent with the quenching effects noted in vitro. Together, these data show that BZA interacts with Fura-2 in vitro and in situ and suggest caution when interpreting Fura-2 fluorescence data derived in conjunction with BZA.

Ultrasonographic and clinical predictors of intussusception.

OBJECTIVE: The objective of this study was to determine the positive and negative clinical predictors of intussusception and the correlation of ultrasonography and air enema in establishing this diagnosis. STUDY DESIGN: This was a prospective descriptive cohort study. SETTING: This study was performed in a tertiary care pediatric emergency department. PARTICIPANTS: Eighty-eight of 245 candidates were assessed for clinical predictors of intussusception. All 245 cases were examined for correlation between ultrasonography and air enema. INTERVENTIONS: A questionnaire, ultrasonography, and air enema were used. RESULTS: Thirty-five of the 88 patients assessed for clinical predictors were positive for intussusception. Significant positive predictors were right upper quadrant abdominal mass (positive predictive value [PPV] 94%), gross blood in stool (PPV 80%), blood on rectal examination (PPV 78%), the triad of intermittent abdominal pain, vomiting, and right upper quadrant abdominal mass (PPV 93%, p = 0.0001), and the triad with occult or gross blood per rectum (PPV 100%, p = not significant). Significant negative predictors were a combination of > or = 3 of 10 clinically significant negative features (negative predictive value 77%, p = 0.035). Of the total 245 cases, intussusception (as confirmed by doughnut, target, or pseudokidney sign) was ruled out by ultrasonography in 97.4%. Alternate ultrasound findings comprised 27% of negative cases. CONCLUSIONS: Excellent positive predictors of intussusception were identified prospectively. Although no reliable negative predictors were found, patients at low risk may be screened by ultrasonography.