Anne Beck

Early Volume Expansion During Diarrhea and Relative Nephroprotection During Subsequent Hemolytic Uremic Syndrome

OBJECTIVES To determine if interventions during the pre-hemolytic uremic syndrome (HUS) diarrhea phase are associated with maintenance of urine output during HUS. DESIGN Prospective observational cohort study. SETTINGS Eleven pediatric hospitals in the United States and Scotland. PARTICIPANTS Children younger than 18 years with diarrhea-associated HUS (hematocrit level <30% with smear evidence of intravascular erythrocyte destruction), thrombocytopenia (platelet count <150 × 10³/mm³), and impaired renal function (serum creatinine concentration > upper limit of reference range for age). INTERVENTIONS Intravenous fluid was given within the first 4 days of the onset of diarrhea. OUTCOME MEASURE Presence or absence of oligoanuria (urine output ≤ 0.5 mL/kg/h for >1 day). RESULTS The overall oligoanuric rate of the 50 participants was 68%, but was 84% among those who received no intravenous fluids in the first 4 days of illness. The relative risk of oligoanuria when fluids were not given in this interval was 1.6 (95% confidence interval, 1.1-2.4; P = .02). Children with oligoanuric HUS were given less total intravenous fluid (r = -0.32; P = .02) and sodium (r = -0.27; P = .05) in the first 4 days of illness than those without oligoanuria. In multivariable analysis, the most significant covariate was volume infused, but volume and sodium strongly covaried. CONCLUSIONS Intravenous volume expansion is an underused intervention that could decrease the frequency of oligoanuric renal failure in patients at risk of HUS.

Diastolic function and tachycardia in hypertensive children.

We investigated the prevalence and potential predictors of Doppler echocardiographic evidence of diastolic function in untreated hypertensive children. Doppler and M-mode echocardiographic values from 42 children (mean age 13, range 5-17 years) from a pediatric hypertension clinic were retrospectively reviewed and compared to data from 39 age and gender matched normotensive children in a control group. Compared to the participants in the control group, hypertensive patients had increased mean body mass index (29 v 19 kg/M2, P < .0001), peak mitral A velocity (57 v 42 cm/sec, P < .0001), isovolumic relaxation time (65 v 42 msec, P < .0001, resting heart rate (90 v 74 bpm, P < .0001), mitral E deceleration time (150 v 137 msec, P = .006), indexed left ventricular mass index (32 v 26 g/M2.7, P < .0001), relative left ventricular wall thickness (0.32 v 0.29, P = .02), and decreased ratio of peak mitral E velocity/peak mitral A velocity (1.7 v 2.1, P = .0001). Mean age, height, mitral E velocity, mitral A deceleration time, fractional shortening, and indexed left ventricular diastolic dimension were similar in patients and control group children. In the hypertensive patients, multivariate analysis demonstrated that heart rate (P = .0008) and systolic blood pressure (P = .03) were significant predictors of peak A velocity. In addition, heart rate (P = .0003), body mass index (P = .04), and indexed left ventricular diastolic dimension (P = .04) predicted the ratio of peak E/peak A velocity. None of the measures of diastolic function correlated with left ventricular mass index or relative wall thickness. Furthermore, none of the analyzed variables predicted isovolumic relaxation time or mitral E deceleration time. We conclude that untreated hypertensive children have Doppler indices suggestive of impaired left ventricular relaxation. Resting heart rate was the strongest predictor of abnormal diastolic indices.

Deer Sausage: A Newly Identified Vehicle of Transmission of Escherichia coli O157:H7

Five Missouri patients infected with Escherichia coli O157:H7 were studied for an epidemiologically plausible association. Case isolates, case interviews, and pathogen and meat XbaI pulsed field electrophoresis patterns were consistent with the common source being contaminated, fermented deer sausage, a previously unrecognized mode of transmission for Escherichia coli O157:H7.

Contaminated heparin-affected patient plasmas are associated with activated contact systems.

A published article ‘‘Contaminated heparin associated with adverse clinical events and activation of the contact system,’’ Kishimoto et al, New England Journal of Medicine, 2008; 358:2457-2467, demonstrated that contaminated heparin induced contact system activation. To better understand why only subpopulations of patients experienced contaminated heparin-induced anaphylactic reactions, we systematically examined the contact system proteins from 6 hemodialysis patient plasmas obtained from St Louis Children’s Hospital where contaminated heparin-induced anaphylactic reactions were initially established. We discovered that plasma from patients affected by contaminated heparin already showed an activated contact system. Therefore, the contaminated heparin-induced bradykinin production and the subsequent bradykinin-induced hypotension-associated adverse events revealed by an animal model and normal human plasma studies might not be the same molecular mechanism manifested by the affected patients. Heparin is the most highly sulfated naturally occurring glycosaminoglycan (GAG). Heparin is enriched in porcine, ovine, bovine intestines, or bovine lung entrails along with less sulfated GAGs, including heparan sulfate, dermatan sulfate, and chondroitin sulfate. These GAGs are made by all animal cells and are present in all tissues. Pharmaceutical grade heparin is prepared from crude heparin by the removal of the less sulfated GAGs, the so-called heparin by-product, from heparin. The highly charged heparin has much higher anticoagulation activities compared to the less sulfated heparin byproduct. In 2007 and 2008, hundreds of anaphylactic reactions and at least 149 deaths were associated with contaminated heparin. Published reports have suggested that the contaminants in heparin include an impurity, specifically dermatan sulfate, and a contaminant, oversulfated chondroitin sulfate (OSCS) presumed to derive from animal cartilage. We identified heparin contaminants as chemically oversulfated or chemically sulfated/desulfated heparin by-products. We further observed that treatment of normal human plasmas with several species of oversulfated GAGs, including OSCS, oversulfated heparan sulfate, oversulfated dermatan sulfate, and oversulfated heparin by-product (OS-HB), induced not only contact system activation (as indicated by the generation of kallikrein-like activity) but also thrombin-like activity. These observations suggest that the molecular mechanism underlying the contaminated heparin-associated adverse events might be more complex than the established model. To understand the contaminated heparininduced anaphylactic reactions, we systematically examined the contact system proteins from 6 hemodialysis patient plasmas. Patients H1 and H4 had typical anaphylactic reactions and patient H2 had delayed anaphylactic reactions induced by contaminated heparin during hemodialysis. The plasmas were obtained 4 and 5 months after the anaphylactic From the Departments of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA (YQ, JP, XZ, PW, HL, AMB, LZ); and Pfizer Inc. Chesterfield MO, USA (FFS).

Buyer beware! Doctor be aware!—Answers

Acute hyperphosphatemia with hypocalcemic tetany from exogenous phosphate load was diagnosed. The serum phosphorous level was 45.2 mg/dl, total calcium 5.1 mg/dl and ionized calcium 1.83mg/dl (normal range 4.40–5.40 mg/dl). An adult Fleet® enema (C.B. Fleet Co., Lynchburg, VA) has a volume of 118 ml and contains 19 g of monobasic sodium phosphate monohydrate, 7 g of dibasic sodium phosphate heptahydrate and 4.4 g of sodium [1]. Hypocalcemia is induced by calcium complexing with phosphate, and the magnitude of hypocalcemia is proportional to the degree by which the solubility product of calcium phosphate is exceeded. Although the exact threshold is impossible to determine, a product as low as 60 mg/dl has been associated with increased visceral calcification [2, 3]. Phosphorous is the sixth most abundant element in the human body, and under normal conditions most total body phosphorous exists in the bone in the divalent form (HPO4 ). Of the remaining phosphorous 10 % exists intracellularly, and only 1 % is found in the extracellular fluid of which 15 % is protein bound and another 5 % is complexed as salts with cations such as sodium, calcium and magnesium [4, 5]. Active absorption of dietary phosphorous occurs in the small intestine (duodenum and jejunum) via sodium phosphate cotransporter 2b (NaPi2b). Passive absorption takes place throughout the intestine, including the colon. As a reference, the typical adult diet contains 1 g of phosphorous daily. The recommended elemental phosphorous intake for a 6-year-old child is 500 mg per day. Our patient received 15.8 g (488.5 mmol) of elemental phosphate within 12 h. Control of plasma phosphate is normally maintained by altering renal excretion or redistribution within the body compartments. Phosphate is freely filtered at the glomerulus, and 85 % is reabsorbed into the blood at the level of the proximal tubule. Phosphate enters the proximal tubule cell against an electrical gradient via the NaPi2a and NaPi2c transporters, both of which are located along the brush border membrane [5]. Inhibition of proximal tubule reabsorption produces phosphaturia, which not uncommonly can cause hypophosphatemia. In our case, the large exogenous phosphorous load overwhelmed the limited ability of the gut and kidney to regulate phosphorous absorption and excretion. Hyperphosphatemia occurs from exogenous sources, as in our case, or from endogenous sources, such as tumor lysis syndrome or rhabdomyolysis. In clinical medicine, chronic kidney disease is the most common cause. Severe This article refers to the article that can be found at http://dx/doi.org/ 10.1007/s00467-012-2338-y E. Anyaegbu : T. Keefe Davis (*) :K. Hruska :A. Beck (*) Division of Nephrology, Department of Pediatrics, Washington University School of Medicine, Box 8208, 660 S. Euclid Ave, St. Louis, MO 63110, USA e-mail: davis_tk@kids.wustl.edu e-mail: beck_a@kids.wustl.edu

Buyer beware! doctor be aware!: Questions.

A 6-year-old girl presents to the emergency room with altered mental status. She is acutely non-verbal and unable to vocalize sounds. She has bilateral nystagmus and facial twitching. She has marked hypertonia with her wrists persistently flexed and her feet and toes hyperextended. Reflexes are not elicited. She does not withdraw from painful stimuli. She is accompanied by her parents who brought her by car. You learn she has a history of an imperforated anus repair and suffers from chronic constipation with megacolon. The repair was performed at the age of 2 by pull through with reanastomosis after previous diverting colostomy. In the past, she has been managed with an aggressive bowel regime including daily polyethylene glycol 3350 (MiraLax) and two pediatric Fleets enemas administered every other day. In spite of this regime, she developed persistent fecal soiling and recent clinical evaluation identified overflow incontinence. She was instructed to increase the dose to two adult Fleets enemas every other day. On the day of presentation, she complained of abdominal pain presumed to be due to constipation. Therefore, she received two Fleets enemas. She did not evacuate her bowels so a third enema was administered for a total of three adult Fleets enemas within 12 hours.