[JEWISH MEDICAL STUDENTS FROM THE BRITISH MANDATE OF PALESTINE/ERETZ ISRAEL - THEIR FINAL MD EXAMINATION IN BERLIN DURING THE THIRD REICH].

INTRODUCTION: Two Jewish medical students who were forced to discontinue their study upon the raise of the Nazi regime, returned/ immigrated to Palestine and did their internship in Palestine. A third student, although faced with many procedural limitations, was able to continue most of his studies in Berlin including passing the MD examination. The first two students returned, after some years, to Berlin to sit for the Doctor examination which enabled them to gain a permanent medical license in Palestine. We describe the different backgrounds of the 3 students which enabled them to do the examination at Berlin's medical faculty during the Nazi regime. The follow up of the three, revealed glorious medical career during the British mandate and during the first years of the new state of Israel. The Dissertations were signed and supported by three leading Professors of the Berlin's Faculty. Two of them were found to have a National-Socialistic background.

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.

The Kristallnacht Pogrom. The End of Jewish Medical Study in Germany: Who were the Last Jewish Medical Students in Berlin?

BACKGROUND: In April 1937 it was forbidden for German Jewish students to sit for examinations. However, a few Jewish medical students were able to continue studying at Berlin University. The order to expel all Jewish students from German Universities was published on the morning after Kristallnacht (November 1938) and was strictly imposed. OBJECTIVES: To identity the last Jewish medical students who managed, in spite of the severe restrictions, to continue their study and apply for the examinations in Berlin from summer 1937 through 1938. METHODS: Reviews of the dissertations written in the medical faculty of Berlin during 1937-1938 identified the Jewish students. We presented their demographic and academic characteristics. RESULTS: Sixteen Jewish students were identified: six Germans, six Americans, and four Eastern Europeans. Their average age was 18.7 ± 1.0 years, 22.5 ± 2.0 years, and 20.8 ± 2.5 years, respectively. The last Jewish student took the exams in July 1938 and submitted a thesis one month later. One German student was half Jewish. Five gained the rights to take the examinations as foreign students by renouncing their German citizenship. They were the main group affected by the government's restrictions. The American and the Eastern European students were more protected by law. CONCLUSIONS: Each of those groups had different academic careers. The Americans were the last Jewish students allowed to study in Germany. It seems that they were less aware of the national socialist atmosphere in the medical faculty in Berlin during 1937-1938.

Hospitalization due to horse-related injuries: has anything changed? A 25 year survey.

BACKGROUND: Horse riding and horse handling are dangerous. There is a lack of knowledge concerning the incidence of hospitalization due to horse-related injuries and types of injuries in Israel. During the last two decades we have observed an increasing incidence of hospitalizations due to horse-related injuries at our medical center as well as the frequent involvement of pediatric patients. OBJECTIVES: To investigate these injuries with respect to type, incidence and modes of prevention. METHODS: We conducted a retrospective study of medical records for all patients admitted to Assaf Harofeh Medical Center due to horse-related injury between January 1984 and December 2008. A telephone questionnaire was used to complete the data. RESULTS: Eighty-nine subjects (267 injuries) were included in the study. Most of them were not professional horse riders or horse handlers. Helmet use was reported in only 28% of the participants. The number of subjects with horse-related injuries and the percentage of pediatric involvement increased during the study period. Falling from a horse was the most frequent cause of injury (60.67%), followed by being kicked (13.4%). Head and extremities were the most affected areas. On admission, 33.7% had a potential severe injury score. Forty-two participants (47%) had underlying fractures, mostly in the upper extremities. In the pediatric population, 16.2% (vs. 0% adults) rode horses for therapeutic reasons. Seventeen subjects reported having long-term consequences. CONCLUSIONS: The findings are similar to those described in other parts of the world. Horseback riding-related injuries are increasing, which emphasizes the need for safety education programs in Israel.

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.

Hemoptysis in children: a single institutional experience.

OBJECTIVES: The purpose of this study was to describe a single institutional experience with pediatric diffuse pulmonary hemorrhage, with an emphasis on etiology, clinical course, and outcome. METHODS: The medical records of pediatric patients admitted to Assaf Harofeh Medical Center between the years 2002 and 2011 because of hemoptysis and pulmonary infiltrates on chest radiographs were retrospectively reviewed. RESULTS: Sixteen patients were identified. All the participants had respiratory complaints, and bloody cough was the presenting symptom in 11 patients. Twelve patients were admitted to the pediatric intensive care unit: 10 required mechanical ventilation, 9 had diffuse pulmonary infiltrates, and 8 required transfusions of blood products. Eight patients had an infectious disease (1 had tuberculosis). Two patients had severe coagulopathy. Three patients had diffuse bronchiectasis (1 had immunodeficiency). Cardiac failure was identified in 1 patient. Cocaine-induced pulmonary hemorrhage was identified in an adolescent. In 4 infants, the cause of pulmonary hemorrhage was not identified. Bronchoscopy and computed tomography were each performed in 9 patients. Five patients died during the acute phase of the illness because of severe hypoxia and multiorgan failure. CONCLUSIONS: At our institution, hemoptysis is a rare but potentially life-threatening symptom. The etiology is heterogeneous. Clinical signs and chest radiographs are important for classifying the severity of the disease. Minor hemoptysis with focal findings on chest radiograph has a favorable short-term prognosis, with infectious diseases being involved in most cases.

Remifentanil use in pediatric scoliosis surgery-an effective alternative to morphine (a retrospective study).

PURPOSE: The unique properties of remifentanil make it ideal for pediatric use despite a lack of wide randomized clinical trials and fear of adverse events due to its high potency. We aimed to consolidate preliminary conclusions regarding the efficacy of remifentanil use in pediatric scoliosis surgery. MATERIALS AND METHODS: The medical charts of children with idiopathic scoliosis who underwent primary spinal fusion between 1998 and 2007 at a large tertiary university-affiliated hospital were retrospectively reviewed and divided into two groups according to anesthetic regime (remifentanil vs. morphine). Demographic, surgery-related details and immediate postoperative course were recorded and compared. RESULTS: All 36 remifentanil children were extubated shortly after termination of surgery, compared to 2 of the 84 patients in the morphine group. The remaining patients in the morphine group were extubated hours after surgery [5.4 hours; standard deviation (SD) 1.7 hours]. Six remifentanil children were spared routine intensive care hospitalization (vs. 2 morphine children-significant difference). Shorter surgeries [5.6 hours (SD 1.82 hours) vs. 7.14 hours (SD 2.15 hours); p=0.0004] were logged for the remifentanil group. To achieve controlled hypotension during surgery, vasodilator agents were used in the morphine group only. A comparison of early postoperative major or minor complication rates (including neurological and pulmonary complications) between the two groups yielded no significant differences. CONCLUSION: Remifentanil use can shorten operating time and facilitate earlier spontaneous ventilation and extubation, with less of a need for intensive care hospitalization and no increase in significant complications.

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.

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.

Use of adult criteria for slice imaging may limit unnecessary radiation exposure in children presenting with hematuria and blunt abdominal trauma.

OBJECTIVE: To examine whether it would be safe to use adult criteria for imaging in pediatric blunt renal trauma and hematuria. MATERIAL AND METHODS: From 1999 to 2007, 46 consecutive children were admitted for renal trauma and hematuria. All had abdominal computed tomography (CT) scan. Patients were divided into 2 groups: microhematuria and macrohematuria. Outcomes analyzed were presence of renal injury per CT, grade of renal injury, and indication for and details of surgical intervention. RESULTS: Twenty-seven patients (59%) had microhematuria. Nineteen (41%) had macrohematuria. On abdominal CT scan, no injury was found in 18 patients with microhematuria (67%) and 3 (16%) with macrohematuria. Two microhematuria patients required surgical intervention. In both cases, no actual renal intervention was performed during surgery. Three macrohematuria patients required surgical intervention; all had renal relevant procedures. The performance of the macro-microhematuria distinction in the prediction of renal injury on CT scan is relatively poor: sensitivity 59%, specificity 14%, positive predictive value (PPV) 84%, and negative predictive value (NPV) 62%, whereas the performance of macrohematuria criteria in the prediction of renal-relevant injury is sensitivity 100%, specificity 61%, PPV 18%, and NPV 93%. CONCLUSIONS: The yield of abdominal CT in pediatric renal trauma is low in patients presenting with microhematuria. Our data suggest that it may be possible that adult criteria for renal imaging are sufficient for children with abdominal blunt trauma and microhematuria. Adopting such strategy will result in substantial reduction in exposure to radiation, supposedly without increasing the patient's risk.

Riding a bicycle: do we need more than a helmet?

BACKGROUND: To assess pediatric bicycle-related traumatization in view of types of injuries, incidence and modes of prevention. METHODS: Retrospective study of pediatric cases admitted to the pediatric intensive care unit of a university-affiliated level II trauma hospital in Israel over 12 consecutive years. RESULTS: Forty-six patients (three girls, 43 boys) with bicycle-related injuries formed 1% of the total pediatric intensive care unit admissions during the study period. The number of patients with bicycle-related injuries increased significantly during recent years (1996-2001 vs 2002-07: P = 0.003). Most of the cases presented abdominal injuries (54.4%) followed by head (32.6%) and chest (13%) injuries. The median age of patients with abdominal trauma was significantly lower in comparison to patients with other types of injuries (P = 0.002). Abdominal cases required longer hospitalization compared with other patients (P = 0.003). Falling from a bicycle was the main mechanism of injury in abdominal cases (88%) (P = 0.003). Motor vehicle impacts were the main mechanism of injury in patients with head (60%) and chest (66.6%) trauma. CONCLUSION: The incidence of severe bicycle-related injuries requiring intensive care hospitalization is increasing and abdominal trauma forms the main portion of those injuries. We suggest introducing a trunk-protective measure for young bicyclists. Exact information on the mechanism of the injury is important for evaluating the injured patient more accurately.

Infantile encephalopathy due to vitamin deficiency in industrial countries.

INTRODUCTION: Severe avitaminosis causing life-threatening conditions in the infantile age group is extremely uncommon and has been reported in babies with malabsorption receiving prolonged inadequate vitamin supplements. CASE REPORTS: We report two infants who presented with neurological deterioration. Immediate work-up and treatment for infectious and inborn metabolic disorders were initiated and the diagnosis, made with a few days delay, was prolonged avitaminosis of thiamine (B1) and cobalamin (B12). B1 deficiency was suspected when further neurological deterioration was observed during administration of intravenous fluids containing glucose in an infant with high lactate levels in the cerebrospinal fluid. High transketolase activity that normalized after thiamine treatment and the findings in the MRI and MRS of the brain confirmed the suspected diagnosis. B12 deficiency was suspected in an infant of a strict vegetarian mother who presented with neurological deterioration and severe megaloblastic anemia. The diagnosis was confirmed when low serum levels of B12 and methylmalonic aciduria were detected and treatment with B12 resulted in normalization of urinary methymalonic acid. CONCLUSION: Avitaminosis, even in industrialized countries, should be considered in an atypical age group with no known risk factors. Early diagnosis and prompt treatment may accomplish a quick recovery with fewer sequelae.

Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy.

Hemorrhagic shock and encephalopathy syndrome: clinical course and neurological outcome.

The syndrome of hemorrhagic shock and encephalopathy is associated with an acute onset of diarrhea, followed by shock, disseminated intravascular coagulopathy, multiorgan failure, and encephalopathy. The etiology of this syndrome is unknown, and despite intensive treatment, the outcome is often fatal or associated with severe neurological sequelae. Two infants aged 6 and 9 months were admitted with this syndrome within a 24-hour time interval. The authors hereby present the clinical course and a prospective evaluation of the neurological outcome. A review of the literature regarding this infrequent syndrome is presented.

Left ventricular thrombus: an unusual cause of stroke.

An 8-year-old boy was admitted to the hospital with multiple abdominal and pelvic injuries following a motor vehicle accident. During hospitalization, signs of stroke developed. Evaluation discovered the cause to be emboli originating from a large left ventricular thrombus, most probably as a result of cardiac injury. Anticoagulation therapy was initiated, the cardiac mass resolved completely within 3 days, and neurologic status subsequently improved. When possible, echocardiography should be used as part of the workup of pediatric patients after multiple trauma, even without obvious signs of chest involvement.

Risk factors affecting the immediate postoperative course in pediatric scoliosis surgery.

STUDY DESIGN: A retrospective analysis of pediatric records of idiopathic scoliosis (IS) and neuromuscular scoliosis (NMS) etiology, in a search for complications and their risk factors immediately following surgical repair. OBJECTIVE: To evaluate the influence of pre- and intraoperative parameters on the postoperative course and lay the cornerstone for a course-prediction model. SUMMARY OF BACKGROUND DATA: Only a few studies have addressed the immediate postoperative complications of pediatric scoliosis surgery. METHODS: Our study included all children who underwent spinal fusion for scoliosis in our hospital between 1998 and 2006. The following data were collected: curve etiology, Cobb angle, number of fused vertebrae, fusion approach, and the addition of thoracoplasty. We evaluated the influence of this data on the rate of delayed extubations, length of intensive care unit (ICU) hospitalization, and the presence of major and minor immediate postoperative complications. RESULTS: The study included 126 children (95 IS and 31 NMS). Delayed extubations were recorded in 17 children (3% of IS vs. 45% of NMS). The most common major and minor complications were pulmonary and hematological-biochemical, respectively. Overall pulmonary complications (major and minor) were recorded in 38 children. Major complications (of any category) were recorded in 19 children. Average length of ICU hospitalization was 3.8 days. The rate of complications in the NMS group was significantly higher than in the idiopathic group. Posterior fusions were associated with a significantly lower rate of pulmonary complications and shorter ICU hospitalizations, in comparison to anterior and combined fusions. Cobb angle, number of fused vertebrae, and the addition of thoracoplasty did not correlate with any postoperative parameters. CONCLUSION: While NMS etiology, anterior and combined fusions correlated with a worse course, the Cobb angle, number of fused vertebrae, and the addition of thoracoplasty did not. Optimization of postoperative care should be carried out accordingly. Scoliosis surgery is safe even in extreme curves and long fusions. Thoracoplasty can be added whenever indicated, in order to improve the overall outcome.

Superior mesenteric artery syndrome after scoliosis repair surgery: a case study and reassessment of the syndrome's pathogenesis.

We carried out a retrospective analysis to investigate the prevalence of superior mesentery artery syndrome (SMAS) in children who underwent scoliosis surgical repair at our hospital between 1998 and 2006 and to reassess the syndrome's pathogenesis. Among 133 consecutive pediatric patients, two cases were identified, both 13-year-old girls with idiopathic scoliosis, undergoing surgery using third-generation instrumentation systems. Conservative management achieved resolution of the symptoms without recurrence. SMAS prevalence in our series was 1.6%. SMAS might occur after derotation and translation forces application, and even with nonextreme corrections. Low BMI and significant weight loss at presentation are not mandatory.

Thiamine deficiency in infants: MR findings in the brain.

BACKGROUND AND PURPOSE: Thiamine deficiency is extremely rare in infants in developed countries. To our knowledge, its MR findings in the brain have not been reported. The purpose of this study was to investigate the brain MR findings in infants with encephalopathy due to thiamine deficiency. METHODS: The study group included six infants aged 2-10 months with encephalopathy who had been fed with solely soy-based formula devoid of thiamine from birth. All underwent MR evaluation at admission and follow-up (total of 14 examinations). In one patient, MR spectroscopy (MRS) was performed. RESULTS: In five patients T2-weighted, fluid-attenuated inversion recovery, or proton-attenuated sequences showed bilateral and symmetric hyperintensity in the periaqueductal area, basal ganglia and thalami. Five had lesions in the mammillary bodies, and three, in the brain stem. In all six patients, the frontal region (cortex and white matter) was clearly involved. At presentation, MRS of the periaqueductal area showed a lactate doublet. On long-term follow-up, three of four patients had severe frontal damage; in two, this occurred as part of diffuse parenchymal loss, and in one, it was accompanied by atrophy of the basal ganglia and thalami. CONCLUSION: Thiamine deficiency in infants is characterized by involvement of the frontal lobes and basal ganglia, in addition to the lesions in the periaqueductal region, thalami, and the mammillary bodies described in adults. MRS demonstrates a characteristic lactate peak.

Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula.

OBJECTIVE: Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1), specifically manufactured for the Israeli market. The source was identified on November 6, 2003, when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus, ophthalmoplegia, and vomiting. Wernicke's encephalopathy was suspected, and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula, raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities, and the thiamine level was found to be undetectable (<0.5 microg/g). The product was pulled from the shelves, and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis, clinical course, and outcome of 9 affected infants in our care. METHODS: After the index case, an additional 8 infants were identified in our centers by medical history, physical examination, and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay, wherein the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15%; a value of 15% to 25% indicates thiamine deficiency, and >25% indicates severe deficiency. Blood lactate levels (normal: 0.5-2 mmol/L) were measured in 6 infants, cerebrospinal fluid lactate in 2 (normal: 0.5-2 mmol/L), and blood pyruvate in 4 (normal: 0.03-0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula. RESULTS: Early symptoms were nonspecific and included mainly vomiting (n = 8), lethargy (n = 7), irritability (n = 5), abdominal distension (n = 4), diarrhea (n = 4), respiratory symptoms (n = 4), developmental delay (n = 3), and failure to thrive (n = 2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection: acute gastroenteritis (n = 2); upper respiratory infection (n = 2); and bronchopneumonia, acute bronchitis, and viral infection (n = 1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis, and 2 had high cerebrospinal fluid lactate levels. Patient 1, our index case, was hospitalized for upbeat nystagmus and ophthalmoplegia, in addition to daily vomiting episodes since 4 months of age and weight loss of 0.5 kg. Findings on brain computed tomography were normal. Blood lactate levels were high, and TPPE was 37.8%. Brain magnetic resonance imaging (MRI) revealed no abnormalities. Patient 2, who presented at 5 months with lethargy, vomiting, grunting, and abdominal tenderness, was found to have intussusception on abdominal ultrasound and underwent 2 attempts at reduction with air enema several hours apart. However, the lethargy failed to resolve and ophthalmoplegia appeared the next day, leading to suspicions of Wernicke's encephalopathy. Laboratory tests showed severe thiamine deficiency (TPPE 31.2%). In patients 1 and 2, treatment led to complete resolution of symptoms. The third infant, a 5-month-old girl, was admitted on October 10, 2003, well before the outbreak was recognized, with vomiting, fever, and ophthalmoplegia. Her condition deteriorated to seizures, apnea, and coma. Brain MRI showed a bilateral symmetrical hyperintense signal in the basal ganglia, mamillary bodies, and periaqueductal gray matter. Suspecting a metabolic disease, vitamins were added to the intravenous solution, including thiamine 250 mg twice a day. Clinical improvement was noted 1 day later. TPPE assay performed after treatment with thiamine was started was still abnormal (17.6%). Her formula was substituted after 4 weeks, after the announcement about the thiamine deficiency. Although the MRI findings improved 5 weeks later, the infant had sequelae of ophthalmoplegia and motor abnormalities and is currently receiving physiotherapy. All 3 patients with neurologic manifestations were fed exclusively with the soy-based formula for 2 to 3.5 months, whereas the others had received solid food supplements. Longer administration of the formula (ie, chronic thiamine deficiency) was associated with failure to thrive. For example, one 12-month-old girl who received the defective formula for 8 months presented with refusal to eat, vomiting, failure to thrive (75th to <5th percentile), hypotonia, weakness, and motor delay. Extensive workup was negative for malabsorption and immunodeficiency. On admission, the patient had Salmonella gastroenteritis and sepsis and was treated with antibiotics. After thiamine deficiency was diagnosed, she received large doses of thiamine (50 mg/day) for 2 weeks. Like the other 5 infants without neurologic involvement, her clinical signs and symptoms disappeared completely within 2 to 3 weeks of treatment, and TPPE levels normalized within 1 to 7 days. There were no side effects. As part of its investigation, the Israel Ministry of Health screened 156 infants who were fed the soy-based formula for thiamine deficiency. However, by that time, most were already being fed alternative formulas and had begun oral thiamine treatment. Abnormal TPPE results (>15%) were noted in 8 infants, 3 male and 5 female, all >1 year old, who were receiving solid food supplements. Although their parents failed to notice any symptoms, irritability, lethargy, vomiting, anorexia, failure to thrive, and developmental delay were documented by the examining physicians. None had signs of neurologic involvement. Treatment consisted of oral thiamine supplements for 2 weeks. CONCLUSIONS: Clinician awareness of the possibility of thiamine deficiency even in well-nourished infants is important for early recognition and prevention of irreversible brain damage. Therapy with large doses of thiamine should be initiated at the earliest suspicion of vitamin depletion, even before laboratory evidence is available and before neurologic or cardiologic symptoms appear.

The role of the central nervous system in heatstroke: reversible profound depression of cerebral activity in a primate model.

BACKGROUND: The neurological manifestations of heatstroke victims vary. The exact sequence of the central nervous system (CNS) changes during lethal hyperthermia has only been partially explored, and the data covering the post-resuscitation CNS changes, which in most cases lead to secondary cardiac arrest, are insufficient. HYPOTHESIS: Following heating of the organism to cardiopulmonary arrest, successful resuscitation may be achieved by standard cardiopulmonary resuscitation (CPR), plus glucose and surface cooling. There is a characteristic sequence of neurological responses to hyperthermia preceding cardiopulmonary arrest, and questionable reversibility following successful resuscitation. METHODS: We exposed 12 pigtail monkeys under light anesthesia to total body hyperthermia (cerebral T = 42 degrees C) until cardiac arrest. We monitored EEG, mean arterial pressure (MAP), intracranial pressure (ICP), epidural temperatures, PaO2, PaCO2, serum sodium, osmolality, blood glucose, pupillary diameter, light response, corneal reflex, extremity movement, and seizures. RESULTS: During hyperthermia EEG frequency decreased and amplitude increased, followed by burst suppression pattern of the EEG. Then during severe hypoglycemia, EEG seizure activity and isoelectric EEG occurred when MAP and cerebral perfusion pressure (CPP) decreased while ICP was almost unchanged. Pupils were first responsive to light and became gradually unresponsive with maximal dilation, correlating with low CPP. After temporarily successful cardiopulmonary resuscitation (restoration of spontaneous circulation), normal EEG tracing and reversibility of the unresponsive pupils were observed. As shock led to secondary rearrest, deterioration with depression of all cerebral functions was documented. Some 147 min after restoration of spontaneous circulation, brains were macroscopically (and microscopically) normal in six of the eight monkeys. CONCLUSIONS: The acute cerebral derangements during and after lethal hyperthermia are reversible. The cause of death is probably not CNS damage, but systemic hemodynamic deterioration.