The Nuremberg Racial Laws: The End of Jewish Medical Teaching in Germany. Who Were the Last Jewish Medical Professors in Berlin?

BACKGROUND: On 7 April 1933, the Nazi Law for the Restoration of the Professional Civil Service was enacted. The law triggered the dismissal of most Jewish medical staff from German universities. A few Jewish professors in Berlin were permitted to continue their academic activity with restrictions. Those professors were gradually dismissed as laws and restrictions were enforced. OBJECTIVES: To identify the last Jewish medical professors who, despite severe restrictions, continued their academic duties and prepared students for their examinations in Berlin after the summer of 1933. METHODS: We reviewed dissertations written by the medical faculty of Berlin from 1933 to 1937 and identified Jewish professors who mentored students during those years. RESULTS: Thirteen Jewish tutors instructed dissertations for the medical examinations after the Nazi regime seized power. They were employees of different university hospitals, including the Jewish hospitals. We did not identify Aryan students instructed by Jewish professors. The professors were active in different medical disciplines. Half of the reviewed dissertations were in the disciplines of surgery and gynecology. The last Jewish tutors were dismissed in October 1935. However, some of their studies were submitted for examination after that date. CONCLUSIONS: After the Nazi regime seized power, academic activities and medical research by Jewish professors declined but did not stop. However, these professors worked with only Jewish students on their theses. Most dissertations were approved and examined after the Jewish academics were dismissed by the university, in some cases even after they left Germany.

sTREM-1 as a diagnostic biomarker for acute appendicitis in children.

BACKGROUND: The typical history of acute appendicitis is observed in less than 60% of cases. Therefore, searching for a surrogate marker is mandatory. Our goal was to determine whether the soluble triggering receptor expressed on myeloid cells (sTREM-1) is an efficient biomarker for acute appendicitis. METHODS: sTREM-1 serum levels were measured in addition to carrying out routine diagnostic tests (urine dipstick, complete blood count and CRP) in children admitted to the Emergency Department with suspected appendicitis. Statistical analysis was performed in order to examine whether sTREM-1 was a significant predictor of appendicitis. RESULTS: Fifty three of 134 children enrolled in the study were diagnosed with appendicitis. There was no significant difference in serum sTREM-1 levels (p = 0.111) between children with or without appendicitis (n = 81). Leukocytes, neutrophils and CRP were significantly elevated in the appendicitis group (p < 0.001). The appendix diameter was significantly larger and the Alvarado score significantly higher in the appendicitis group (p < 0.001). CONCLUSION: serum sTREM-1 is not a good marker for acute appendicitis. Customary tests in addition to a proper patient history and physical examination are still the most effective methods to diagnose acute appendicitis.

Environmental Tobacco Smoke Exposure Among Children by Urinary Biomarkers and Parent Report.

OBJECTIVE: The goal of this study was to describe environmental tobacco smoke (ETS) exposure using urinary biomarkers and its correlation with parent report, among children presenting to emergency room. METHODS: This is a case control study among children aged 3 to 12 years at a tertiary pediatric emergency department in Israel. Children with respiratory (case) or gastrointestinal (control) symptoms were recruited and their accompanying parent completed a short survey. Urine samples were obtained and analyzed for nicotine, cotinine trans-3'-hydroxycotine. Clinical data were extracted from medical records. We compared tobacco exposure using urinary biomarkers, parent report, and Pearson's product-moment correlation, including 95% confidence intervals, between cases and controls. RESULTS: Forty-nine cases with respiratory symptoms and 96 controls with gastrointestinal symptoms were enrolled in the study. Parent-reported ETS exposure in the previous month was higher in the cases compared to control (71.4% vs 57.3%), although the difference was not statistically significant. The mean values of detectable biomarkers did not differ by between cases and controls. However, there was a correlation between urinary biomarkers and reported ETS exposure (0.278-0.460 for various biomarkers) only among cases. CONCLUSIONS: The majority of children in this study had detectable nicotine urinary biomarkers, regardless of their symptoms. However, correlation between parental report and urinary biomarkers was only found among children with symptoms potentially related to ETS. These findings imply that parents of children without respiratory symptoms may underestimate exposure. Efforts to educate parents and caregivers on the risks associated with exposure to ETS should be intensified, regardless of illness.

The proportion of errors in medical prescriptions and their executions among hospitalized children before and during accreditation.

OBJECTIVE: To evaluate the rate of medication related errors in the pediatric ward and pediatric emergency department (PED), before and after implementing intervention strategies according to the Joint Commission International (JCI) accreditation program. DESIGN: A retrospective cross-sectional study that included chart review. SETTING: A university affiliated pediatric ward and PED. PARTICIPANTS: Children 0-18 years old admitted on February 2013 (before the JCI program) and February 2014 (during implementation of the JCI program). INTERVENTION(S): A training program designed to meet the JCI official standards on medication prescribing. MAIN OUTCOME MEASURE(S): The number of prescribing and medication administration errors in the 2 years. RESULTS: We collected 937 valid prescription orders and 924 administration orders (1861 medical orders) from February 2013, and 961 valid prescription orders and 958 administration orders (1919 medical orders) from February 2014. There was a significant reduction in prescribing errors from 6.5 to 4.2% between years 2013 and 2014 (P = 0.03). There was no significant difference in administration error rates between the two periods (104 (11.3%) in the first period and 114 (11.9%) in the second; P = 0.61). CONCLUSIONS: The errors rate we found was within the range described in the literature. Quality assurance interventions can significantly reduce medication prescribing errors.

The role of dexamethasone in decreasing early recurrence of acute intussusception in children: A retrospective study.

BACKGROUND: Early recurrent intussusception (RI) is a concern after a successful pneumatic reduction. Steroids have been suggested as a treatment that decreases early RI. The purpose of this study was to examine the role of dexamethasone in decreasing early RI. METHODS: A retrospective review of 174 pediatric patients that underwent successful pneumatic reduction was conducted. Two groups were identified: group 1 that received intravenous dexamethasone (0.5mg/kg/dose) on diagnosis or immediately after the reduction maneuver, and group 2 that were not given dexamethasone. RESULTS: There were 113 boys and 61 girls ranging in age from 2 to 36months. There were no statistical differences between the groups except for younger age in the dexamethasone group (P=0.03). There was no significant difference (p=0.08) in the rate of early RI between the non-steroid group (5.4%, 4/74) and the steroid group 14% (14/100). Mean admission length was 30h. The majority of RIs occurred in the first 8h of admission. CONCLUSIONS: We found that premedication of children with idiopathic intussusception with dexamethasone did not decrease early RI. LEVEL OF EVIDENCE: Level III retrospective comparative study.

Association of Acetaminophen and Ibuprofen Use With Wheezing in Children With Acute Febrile Illness.

BACKGROUND: Many infants and children receive acetaminophen and/or ibuprofen during febrile illness. Previously, some studies have linked acetaminophen and ibuprofen use to wheezing and exacerbation of asthma symptoms in infants and children. OBJECTIVE: To assess whether acetaminophen or ibuprofen use are associated with wheezing in children presenting to the emergency department (ED) with febrile illness. METHODS: This was a cross-sectional study of children who presented with fever to the pediatric ED between 2009 and 2013. The data were collected from questionnaires and from the children's medical files. Patients with wheezing in the ED were compared with nonwheezing patients. Associations between medication use and wheezing were assessed using univariate and multivariate analyses. The multivariate analysis adjusted for potential confounding variables (ie, age, atopic dermatitis, allergies, smoking, antibiotics use, etc) via propensity scores. RESULTS: During the study period, 534 children admitted to the ED met our inclusion criteria, of whom 347 (65%) were included in the study. The use of acetaminophen was similar in children diagnosed with wheezing compared with those without wheezing (n = 39, 81.3%, vs n = 229, 82.7%, respectively). Ibuprofen use was significantly lower in children diagnosed with wheezing (n = 22, 52.4%, vs n = 168, 69.4%, respectively). In multivariate analysis, acetaminophen was not associated with a higher rate of wheezing during acute febrile illness (adjusted odds ratio [OR] = 0.76, 95% CI = 0.24- 2.39), whereas ibuprofen was associated with a lower risk of wheezing (adjusted OR = 0.36, 95% CI = 0.13-0.96). CONCLUSIONS: Our study suggests that acetaminophen and ibuprofen are not associated with increased risk for wheezing during acute febrile illness.

Abdominal injuries following bicycle-related blunt abdominal trauma in children.

BACKGROUND: The aim of this study was to confirm our clinical impression that intra-abdominal handlebar injuries are progressively increasing in number and severity in the latest years. METHODS: A retrospective analysis of data concerning 132 patients admitted to our department of pediatric surgery during a 10-year period (between 2003 and 2012), following bicycle-related blunt abdominal trauma, was performed. Patients were divided into two groups: those who fall from their bicycle (N.=43) and those who sustained direct impact from the handlebars (N.=89) and compared. RESULTS: Number of admitted patients due to bike related injury was increased during a 10-year period. The bikes used by 91.6% of the participants were the high quality BMX, with rigid and strong handlebars. The average age for both groups was 10.3 years (4-16 years). Boys were injured more than girls. Thirty patients from both groups sustained severe abdominal visceral injuries, 25 from the handlebar group and 6 from the fall group (P=0.018). The overall average length of hospital stay was 3.04 days, with 36 cases (27.36%) requiring pediatric intensive care unit (PICU) admission (N.=26 of the handlebar group and N.=10 of the fall group, P=0.024). Eight children sustaining handlebar injuries required abdominal surgery compared to only one case for the fall group (P=0.018), when excluding extra-abdominal procedures. CONCLUSIONS: Number of pediatric patients admitted due to bike related injury has been gradually increasing. Children who suffer from direct impact of the handlebars are more likely to require abdominal operative intervention and PICU admission than those who fall. Preventive measures are urgently needed in order to defeat this trend.

The Risk of Serious Bacterial Infection in Neutropenic Immunocompetent Febrile Children.

Only few reports have looked into the risk of invasive bacterial infection in children with neutropenia that is not malignancy related. The objective of the current study was to determine the clinical significance of neutropenia as a predictor of serious bacterial infection (SBI) in immunocompetent children. We conducted a retrospective case-control study including children 3 months to 18 years of age with fever ≥ 38°C hospitalized or presenting to the emergency department. Patients who had neutropenia ≤ 1000 ANC/µL and had a blood culture taken were matched for age with the consecutive febrile patients for whom a blood culture was taken. The main outcome was the rate of SBI. SBIs were more prevalent among the control group than in the group of children with neutropenia, 19/71 and 6/71, respectively (P = 0.0005). More children were treated with antibiotics among the control group than in the group of children with neutropenia, 39/71 and 20/71, respectively (P < 0.0001). Acute-phase reactants including CRP and platelets were higher in the control group. We concluded that immunocompetent patients with fever and moderate neutropenia do not carry a higher risk for SBIs compared with patients with fever who do not have neutropenia.

The effect of hyperbaric oxygen therapy on kidneys in a rat model.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) is used for treating various medical conditions. As far as known yet, HBOT is safe with few major side effects that are easy to avoid using a proper protocol. Renal tubular damage was observed in rats exposed to HBOT in a preliminary study conducted in our institution. Aim. We aim to assess whether HBOT causes renal damage and, if so, whether this is dose dependent. METHODS: Thirty-one rats were randomly assigned to three groups. The first group received 10-days HBOT, 100% oxygen at a pressure of 2 atmospheres absolute (2 ATA) for 60 minutes/day, the second received the same treatment for 5 days and the third served as the control. Rat weight, survival, renal function tests, and renal histopathology were analyzed. RESULTS: There were no significant changes in renal function tests in the plasma (cystatin C, urea, creatinine, and electrolytes) between the groups. No significant differences were observed in weight gain or renal histopathological evaluation between all groups. CONCLUSION: HBOT in this protocol does not cause renal impairment in a rat model, which reinforces the assumption that HBOT is safe in healthy rats, regarding renal function. Further research should be focused on the effect/safety of HBOT on nonhealthy kidneys.

Computed tomography is not justified in every pediatric blunt trauma patient with a suspicious mechanism of injury.

OBJECTIVE: Computed tomography (CT) has become an important tool for the diagnosis of intra-abdominal and chest injuries in patients with blunt trauma. The role of CT in conscious asymptomatic patients with a suspicious mechanism of injury remains controversial. This controversy intensifies in the management of pediatric blunt trauma patients, who are much more susceptible to radiation exposure. The objective of this study was to evaluate the role of abdominal and chest CT imaging in asymptomatic pediatric patients with a suspicious mechanism of injury. METHODS: Forty-two pediatric patients up to 15 years old were prospectively enrolled. All patients presented with a suspicious mechanism of blunt trauma and multisystem injury. They were neurologically intact and had no signs of injury to the abdomen or chest. Patients underwent CT imaging of the chest and abdomen as part of the initial evaluation. RESULTS: Thirty-one patients (74%) had a normal CT scan. Two patients of 11 with an abnormal CT scan required a change in management and were referred for observation in the Intensive Care Unit. None of the patients required surgical intervention. CONCLUSION: The routine use of CT in asymptomatic pediatric patients with a suspicious mechanism of blunt trauma injury is not justified.

Pediatric scoliosis surgery--is postoperative intensive care unit admission really necessary?

BACKGROUND: It is common practice for patients to be admitted to the intensive care unit following scoliosis surgery, because of the prolonged anesthesia, the need for efficient pain control and the known immediate postoperative complications. However, this may be unnecessary in many patients. PURPOSE: We aimed to establish possible associations between pre- and perioperative parameters and early postoperative complication rates, in particular the need for prolonged mechanical ventilation (>1 day), and the presence of major complications in children undergoing primary spinal fusion by thoracolumbar spine instrumentation. METHODS: We conducted a retrospective review of children undergoing primary scoliosis surgery at a university-affiliated general hospital from 1998 to 2008. RESULTS: Surgical approaches were as follows: anterior spinal fusion, posterior spinal fusion, and combined anterior and posterior fusion. Prior to mid-2005, anesthesia included morphine; thereafter, remifentanil was used. Major complications correlated significantly with neuromuscular scoliosis (NMS) (OR, 4.94; 95% CI, 1.02-24.05), comorbidity conditions (OR, 3.47; 95% CI, 1.16-10.42), and anterior or combined fusion (OR, 7.81; 95% CI, 2.12-28.57). Late extubation correlated significantly with NMS (OR, 31.25; 95% CI, 1.06-100.00) and morphine use during anesthesia (OR, 17.91; 95% CI, 1.44-222.9). CONCLUSIONS: Relatively young, healthy idiopathic scoliosis children receiving intraoperative remifentanil sedation and undergoing posterior fusion can be successfully managed in regular wards in the immediate postoperative period. However, intensive care unit admission should be considered in NMS patients, patients with comorbidity conditions, those undergoing anterior or combined spinal fusion, and patients whose anesthesia involves long-acting opioids.

Thrombophilia, left ventricular dysfunction and intracardiac thrombi in children.

BACKGROUND AND OBJECTIVES: Reports on the incidence of intracardiac thrombi (ICT) have increased over the last few decades, but ICT are still relatively rare among children. Left ventricular systolic dysfunction and dilatation may contribute to the formation of ICT, especially when a hypercoagulable state exists. The aim of this study was to describe the incidence of ICT in children suffering from cardiac failure with left ventricular dysfunction and to identify risk factors on admission for developing ICT. SUBJECTS AND METHODS: We conducted a retrospective chart review of children up to 18 years of age admitted to the Pediatric Intensive Care Unit due to cardiac failure with left ventricular dysfunction between January 1, 2003 and December 31, 2008. RESULTS: Twenty-one patients were admitted with clinical signs of cardiac failure and echocardiographic findings compatible with dilated cardiomyopathy or acute myocarditis. Dilated cardiomyopathy was diagnosed in 11 patients (52%). Adenoviruses and enteroviruses were suspected to be the cause of acute myocarditis in 5 cases. The personal or family history of hypercoagulable states were obtained from 19 out of 21 patients (90%). Among patients with a hypercoagulable state, 3 out of 7 developed ICT compared with none out of 12 among patients without hypercoagulability (p=0.043). Two of these 3 patients experienced an embolic event. CONCLUSION: Cardiac failure with left ventricular dysfunction may predispose the patient to ICT and increase the risk of thromboembolism, especially when an underlying hypercoagulable state exists. The hypercoagulable state must be carefully evaluated on admission in these patients.

Intraperitoneal N-acetylcysteine for acute iron intoxication in rats.

Free radical formation and release of oxidant agents have been suggested as possible mechanisms for tissue damage in acute iron intoxication. N-acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used as an antidote for various intoxications. Our aim was to determine whether intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic oral doses of iron. Male Wistar rats were studied in three phases. In the first phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p. NAC) and observed for survival. In the second phase, rats were assigned to groups 3 (400 mg/kg elemental iron orally) and 4 (400 mg/kg elemental iron, followed by 150 mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died within 90 minutes after iron administration, a third phase was conducted in order to allow for comparison of iron and transaminase serum levels after the administration of iron and NAC (group 5: n = 10). Mortality was significantly lower in rats treated with iron and NAC, compared to those treated with iron (P = 0.016). Median serum iron level was significantly lower among rats treated with iron and NAC, compared with rats treated with iron alone (P = 0.002). In a rat model of acute iron intoxication, i.p. administration of NAC may decrease serum iron levels and mortality.

Blunt pancreatic trauma in children.

PURPOSE: To report our experience with blunt pancreatic trauma in pediatric patients and evaluate several various management strategies. METHODS: Ten children admitted over the last 10 years with pancreatic blunt trauma were included in the present series. RESULTS: The average time from injury to hospital admission was 2.4 days. All injuries resulted from accidents: bicycle handlebar injuries (5), being kicked by a horse (2), falls from a height (2), and injury sustained during closure of an electric gate (1). Additional systemic and abdominal injuries were recorded in 7 patients. The amylase levels at the time of patient admission were normal in 3 patients, mildly raised in 4 patients, and elevated in 3 patients. Abdominal computed tomography was performed in 10 patients, ultrasonography in 5, and endoscopic retrograde cholangiopancreatography (ERCP) in 4. Pancreatic injuries comprised 4 grade I, 3 grade II, and 3 grade III injuries. Grade I and II injuries were successfully managed by conservative treatment. The 3 children with grade III trauma and pancreatic ductal injury in the neck (1), body (1), and tail (1) of the gland were surgically treated, having an uneventful postoperative stay of 8-14 days and no complications during the 1-year follow-up period. CONCLUSION: The present study supports early ERCP as an essential part of the initial patient evaluation when pancreatic transection is highly suspected.

Hyperbaric oxygen treatment reduces mortality in acute iron intoxication in rats.

Acute iron intoxication is one of the leading causes of overdose morbidity and mortality in children. The toxicity of iron has been postulated to be related to free radical formation and subsequent lipid peroxidation. Hyperbaric oxygen treatment can result in a number of beneficial biochemical, cellular and physiological effects, and has recently been shown to induce cellular protection against ischaemia, and in some cases against free radical formation. In the current study, we aimed to investigate the effects of hyperbaric oxygen treatment on mortality in acute iron intoxication in rats. After iron administration, 57 animals were divided into two groups: a treatment group receiving hyperbaric oxygen treatment (n = 30) and a control group (n = 27), and followed for 48 hr for signs of severe intoxication. In the second part of the study, 21 animals were divided into a treatment group receiving hyperbaric oxygen treatment (n = 10) and a control group (n = 11), and markers of oxidative stress were evaluated. We showed a significant reduction in mortality in hyperbaric oxygen-treated animals from 17 of 27 (62.9%) among untreated rats to 6 of 30 (20%). Surprisingly, in the treatment group, levels of oxidative stress markers were higher. We postulate that hyperbaric oxygen has a potentially beneficial effect in acute iron intoxication.

Oral N-acetylcysteine has a deleterious effect in acute iron intoxication in rats.

Acute iron intoxication is associated with depletion of reduced glutathione in hepatocytes and changes in the glutathione system enzymes. We hypothesized that treatment with N-acetylcysteine (NAC), a glutathione reducing agent and an antioxidant, would reduce mortality in acute iron intoxication. We used a rat model to test this hypothesis. Male rats were assigned to 4 groups. Group 1 received 400 mg/kg elemental iron by oral gavage, group 2 received the same dose of iron followed by NAC, group 3 received NAC only, whereas group 4 received distilled water. Iron and liver transaminases in the blood, and glutathione system enzymes in the liver and erythrocytes were measured. Mortality in group 2 was significantly higher after 2, 6, and 24 hours compared with group 1 (P < .001). No deaths were observed in groups 3 and 4. Serum iron levels were significantly higher in group 2 rats compared to group 1 rats (P < .001). Hepatic and erythrocyte glutathione system enzymes were significantly lower among rats in group 2 compared to rats in group 1. The administration of NAC probably increased the absorption of iron through the gastrointestinal tract, causing higher serum iron levels with significant hepatic damage. These results indicate that in a rat model of acute iron intoxication, orally administered NAC may increase mortality.

Hepcidin in acute iron toxicity.

BACKGROUND: Hepcidin regulates extracellular iron concentration by inhibiting iron release from macrophages and preventing iron absorption in the intestine. Our objective was to evaluate the expression of hepcidin in the liver in acute iron poisoning in a rat model. METHODS: Male Wistar rats were assigned to group 1, who received 750 mg/kg elemental iron (LD(50)) by gavage, and group 2 (control), who received distilled water. Iron concentrations and liver transaminases were measured in the serum. Hepcidin messenger RNA levels were measured in the liver. RESULTS: Mean serum iron levels, aspartate aminotransferase, alanine aminotransferase, and uric acid were significantly higher in group 1 compared to group 2 (P < .0001, P = .01, P < .0001, and P = 0.0001, respectively). Hepcidin messenger RNA levels in the liver were significantly higher in the study group (P = .005). CONCLUSIONS: In acute iron intoxication, hepcidin expression in the liver significantly increased. Further studies are needed to determine whether hepcidin levels correlate with the severity of the intoxication.

Changes in serum hepcidin levels in acute iron intoxication in a rat model.

Hepcidin is an important and recently discovered regulator of iron homeostasis. Acute iron intoxication is one of the leading causes of overdose mortality in children. It is difficult to estimate the degree of iron intoxication since iron serum levels do not correlate with the actual clinical severity. In the current study we aimed to investigate whether serum hepcidin levels are elevated in acute iron intoxication. Rats were divided into two iron dose groups and one control group. Each group was further subdivided into four time groups following the administration of iron. Levels of hepcidin, iron and liver enzymes were measured, and animals were followed for signs of toxicity. Serum hepcidin levels were significantly higher in the group treated with toxic doses of iron (p=0.005). No significant difference in serum iron levels was found between the groups. In acute iron intoxication serum hepcidin levels increase significantly and remain elevated for at least 6h. We postulate that beyond the first hour after iron administration, serum hepcidin levels provide a better estimate of the amount of iron intake than do serum iron levels.

Depletion of glutathione system enzymes of the liver and erythrocytes in a rat model of acute iron poisoning.

ABSTRACT The proposed mechanism of iron-induced hepatotoxicity is free radical formation. It was hypothesized that the glutathione system of the liver and erythrocytes will be affected by acute iron poisoning. Male Wistar rats, 6-8 weeks of age, were assigned to one of three groups. Group I received distilled water, group II received 400 mg/kg elemental iron, and group III received 750 mg/kg elemental iron. All groups were gavage fed. Iron concentration, glutathione, and glutathione system enzymes were then measured in the liver and erythrocytes. The hepatic level of reduced glutathione (GSH) was significantly lower in groups II (3.1 +/- 4.6 mumol/mg protein) and III (4.7 +/- 4.6 mumol/mg protein) in comparison with group I (11.5 +/- 6.2 mumol/mg protein) (p < 0.001). Hepatic levels of glutathione S-transferase (GST) were higher and glutathione peroxidase (GPX) levels were lower in group III compared to groups II and I (p < 0.001 and p < 0.001). Compared to group I, glutathione reductase (GR) was lower in groups II and III (p < 0.001). There was no correlation between GSH, oxidized glutathione (GSSG), GST, GR, and GPX levels in the erythrocytes and in the liver (p = 0.41, p = 0.48, p = 0.49, p = 0.53, p = 01.4, and p = 0.84, respectively). In conclusion, acute iron intoxication in rats is associated with depletion of reduced glutathione in the liver.

Repeated supratherapeutic doses of paracetamol in children--a literature review and suggested clinical approach.

UNLABELLED: The safety of paracetamol when given in the recommended dosage is well documented. However, in recent years there have been many reports of liver failure associated with repeated exposure to supratherapeutic doses of paracetamol. This paper reviews the literature on chronic supratherapeutic paracetamol exposure in children and the different dosing guidelines. Based on which, we suggest the following approach: liver injury secondary to repeated dosing of paracetamol should be considered when a child has received more than 75 mg/kg/d for at least 2 d, or if risk factors for paracetamol toxicity have been identified. Liver transaminases, coagulation factors, and paracetamol serum concentrations should be measured in these children and in symptomatic children with vomiting, right upper quadrant abdominal pain, and jaundice who have taken paracetamol. Treatment with N-acetyl cysteine should be started regardless of paracetamol concentrations if transaminases or INR are elevated. CONCLUSION: Liver injury secondary to repeated dosing of paracetamol is rare but may result in severe morbidity and mortality. The cumulative dose of paracetamol should not exceed 75 mg/kg/d. Children treated with higher doses for more than 2 d should be evaluated for possible liver injury and treated with N-acetyl cysteine if evidence of liver injury is found.