Isaiah D. Wexler

Treatment from birth of nonketotic hyperglycinemia due to a novel GLDC mutation

To determine whether the devastating outcome of neonatal‐onset glycine encephalopathy (NKH) could be improved by instituting treatment immediately at birth rather than after symptoms are already well established.

Morbidity and hospitalizations of adults with Down syndrome

Over the last decade a significant increase in the life expectancy of people with Down syndrome (DS) has been observed, which has caused a higher incidence of morbidity as they age. However, there is a lack of literature regarding morbidity and hospitalization of adults with DS. Analysis of 297 hospitalizations of 120 adults with DS aged 18-73 years hospitalized at Hadassah Medical Centers during the years 1988-2007 compared with data of the general population, hospitalized at the same period. At the age range 18-66 years, mean number of hospitalizations was significantly higher than the general population (P = 0.000001) with hospitalization also significantly longer (P = 0.0009). Exceptionally long hospitalizations were seen at the departments of internal medicine, dermatology and intensive care units. There was no significant difference in mortality between DS and the general population (P = 0.221). More than a fourth of the hospitalizations were caused by infectious diseases, mostly respiratory infections. Hypothyroidism was more prevalent compared with the estimated number reported by the literature (30.8% vs. 15%). Convulsive disorder was prevalent as well (15.8%). However, the prevalence of congenital heart disease, dementia, osteoporosis and obesity was found less than expected. Adults with DS are hospitalized more than the general population and for longer duration. The results of this study emphasize the need for preventive community-based medicine, awareness of co-morbidities and possible deterioration and to prepare the medical staff for a complex course of illness, expecting longer hospitalizations, arising from the complexity of this population.

Unintentional organophosphate intoxication in children

Objectives: To describe the demographic characteristics, clinical course, and outcome of children with acute organophosphate (OP) poisoning admitted to a regional medical center. Methods: The clinical charts of all children admitted to the pediatric wards in Hadassah University Hospital with a diagnosis of acute OP intoxication were reviewed. Results: During the study period (1989-2003), 31 children, mean age 5.6 ± 3.9 years, presented with manifestations of acute OP poisoning. In 71% of the patients, it was possible to identify the toxin, most commonly parathion and diazinone. The most common route of exposure was ingestion of agricultural products treated with OPs (71%). The major clinical manifestation was neurological, with most of the patients presenting with coma and/or seizures (71%). The classic muscarinic and nicotinic signs of intoxication including increased secretions, bradycardia, fasciculations, and miosis were less common in our patient population. Treatment included decontamination, administration of antidote, and supportive care. Most patients responded well to treatment, but 2 patients (6.4%) died. Conclusions: The manifestations of OP poisoning in children are different from those of adults. Pediatricians should be aware of these differences because in some cases, a history of OP exposure is not obtained.

Role of Heparanase on Hepatic Uptake of Intestinal Derived Lipoprotein and Fatty Streak Formation in Mice

Background Heparanase modulates the level of heparan sulfate proteoglycans (HSPGs) which have an important role in multiple cellular processes. Recent studies indicate that HSPGs have an important function in hepatic lipoprotein handling and processes involving removal of lipoprotein particles. Principal Findings To determine the effects of decreased HSPGs chain length on lipoprotein metabolism and atherosclerosis, transgenic mice over-expressing the human heparanase gene were studied. Hepatic lipid uptake in hpa-Tg mice were evaluated by giving transgenic mice oral fat loads and labeled retinol. Sections of aorta from mice over-expressing heparanase (hpa-Tg) and controls (C57/BL6) fed an atherogenic diet were examined for evidence of atherosclerosis. Heparanase over-expression results in reduced hepatic clearance of postprandial lipoproteins and higher levels of fasting and postprandial serum triglycerides. Heparanase over-expression also induces formation of fatty streaks in the aorta. The mean lesion cross-sectional area in heparanase over-expressing mice was almost 6 times higher when compared to control mice (23,984 µm2±5,922 vs. 4,189 µm2±1,130, p<0.001). Conclusions Over-expression of heparanase demonstrates the importance of HSPGs for the uptake of intestinal derived lipoproteins and its role in the formation of fatty streaks.

Hospitalization of Children with Down Syndrome

Introduction: Children with Down syndrome present with multiple medical problems in a higher prevalence compared with the general population, which may lead to hospitalizations. Methods: Analysis of 560 hospitalizations of 162 children aged 0–16 years with Down syndrome at Hadassah Medical Center during the years 1988–2007 compared with data on children in the general population, hospitalized at the same period. Data was collected from patient files and statistical data from the Ministry of Health. Results: Respiratory infections were the leading cause for hospitalization of children with Down syndrome. The number of hospitalizations of children with Down syndrome compared to the number of all children, who were hospitalized was surprisingly similar to their proportion in the general population. Eleven children died during their hospitalization (five heart failure, three sepsis, one respiratory tract infection, and one due to complication after surgery). Nine of the 11 had a congenital heart anomaly. Conclusion: Children with Down syndrome can present with complex medical issues and we support the concept of a multidisciplinary team that has experience and knowledge to serve as a “one stop shop” for these individuals and their families, with timely visits in which a comprehensive evaluation is performed, problems attended to and prevention plans applied. In this way, we may prevent morbidity, hospitalizations, and mortality.

Sudden onset unexplained encephalopathy in infants: think of cannabis intoxication

AbstractThe use of cannabis as both a therapeutic agent and recreational drug is common, and its availability is increasing as a result of legalization in many countries. Among older children, the manifestations of cannabis intoxication are numerous and include both neurological and systemic manifestations that are frequently non-specific. There have been only a few reports detailing cannabis intoxication in infants and toddlers. We describe three infants who presented to the emergency department with encephalopathic signs without prominent systemic manifestations. During the initial interview of caregivers, no history of exposure to neurotoxic agents was obtained. All three patients were subsequently diagnosed with cannabis intoxication based on urine toxic screens for delta-9-tetrahydrocannabinol (THC). The infants recovered with supportive care that included fluids and monitoring. The non-specific symptomatology of cannabis intoxication in infants together with the wide differential for unexplained acute onset encephalopathy may delay diagnosis and lead to inappropriate procedures and interventions such as antimicrobial treatments and imaging studies. Conclusion: Healthcare personnel of emergency rooms, urgent care centers, and general clinics should be aware of the potential risk of cannabis ingestion in young infants. A thorough medical history and toxic screen are warranted in all infants with unexplained decreased sensorium.What is Known:• Cannabis intoxication has been described mostly in adults and includes neurologic, mood changes, and general signs of hemodynamic distress.What is New:• We highlight the importance of including cannabis intoxication in the differential diagnosis of infants with unexplained changes in their mental status.

Treatment of sick children during low-intensity conflict.

The nature of war has evolved in the past generation and in many regions full-scale military confrontations with definable combat zones and easily identifiable combatants have been replaced by amorphous low-intensity conflicts in which battle-lines are often not clearly delineated. Nonmilitary personnel on both sides are involved and noncombatants are frequent casualties. Furthermore the drastic alterations to everyday life that take place during a full-scale war do not occur and civilian routines although often disturbed are maintained. The current intifada involving Israelis and Palestinians is frequently characterised as a low-intensity conflict in which there are explosive periods of violence followed by quiet intervals. During these lulls continuing verbal violence and political activities affect the relations of the two nations. The most devastating effect of the intifada has been a further deterioration in the relations between Arabs and Jews. Hatred and hostility have replaced the tenuous and tentative feelings of amity founded on the Oslo peace agreements; yet the two populations live entwined in the same geographical area. The antagonism between Israelis and Palestinians creates major challenges for health-care workers whose mission is to provide impartial and empathetic care to all. (excerpt)

Iatrogenic Cushing Syndrome due to Intranasal Dexamethasone

With increasing use of intranasal steroids for a wide range of pediatric upper airway disorders, the potential for iatrogenic CS with these agents should be considered. We describe a case of a 7-month-old infant who developed CS secondary to intranasal use of dexa-methasone. Written informed consent was obtained from the parents for publication of this case report.

Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis colorectal cancer in the same kindred.

Endoglin (CD105) is a proliferation‐associated protein that is strongly expressed in endothelial tissue and has a role in tumor angiogenesis. Mutations in endoglin are also linked to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an autosomal dominant disease associated with aberrant angiogenesis. We report an unusual association of HHT1 and Hereditary Nonpolyposis Colorectal Cancer (HNPCC) in the same kindred. Genetic analysis indicates that these 2 syndromes are genetically unrelated and separately segregated within the family. The mutation in the endoglin gene leads to a truncated protein. The mutation in the mismatch repair gene MLH1 causes a splicing defect, giving synthesis to an unstable mRNA from this mutated allele. The potential protective role of an endoglin mutation in patients with HNPCC is discussed.

Fetal Alcohol Syndrome

Over time ancient scripture, paintings and also medical reports on the effect of alcohol on the newborn have strongly suggested a link between maternal drinking during pregnancy and birth defects or cognitive disabilities. In the 1970s the fetal alcohol syndrome was described by French and American research groups. Maternal alcohol abuse during pregnancy can result in a specific pattern of malformations and neurocognitive deficits characteristics of this syndrome. Diagnostic criteria and classifications have been developed, and in the 1990s reports showed the long-term consequences for these children.