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Biomedical subjects

M Tenenbein

Publications and source records attributed to M Tenenbein.

At least 19 recordsLinked to original sources

Leaded gasoline abuse: the role of tetraethyl lead.

Volatile substance abuse is practised worldwide however reports of the abuse of leaded gasoline have been limited to northern Canada, southwestern USA and the Australian Outback. Chronic, heavy abuse of leaded gasoline results in an encephalopathy, cerebellar and corticospinal symptoms and signs, dementia, mental status alterations, and persistent organic psychosis. Much of this is due to the hydrocarbons of gasoline while the tetraethyl lead contributes to the altered mental status and is responsible for the persistent psychosis. Lead chelation therapy is not rational and has not been shown to benefit these patients.

Administration, Inhalation

Leukocytosis, hyperglycemia, vomiting, and positive X-rays are not indicators of severity of iron overdose in adults.

To determine whether leukocytosis, hyperglycemia, vomiting, and opacities in abdominal radiographs are indicators of a serum iron concentration of > 300 micrograms/dL in adult iron overdose patients, a retrospective medical record review was undertaken at a university medical center of all patients older than 12 years of age for whom clinical data were collected before deferoxamine therapy and within 6 hours of iron ingestion. Forty-three patients met the inclusion criteria; 37 were female. The mean and range serum iron concentrations were 382 micrograms/dL and 58 to 710 micrograms/dL, with 34 patients having values of > 300 micrograms/dL. There were no statistically significant relationships between iron concentration of > 300 microgram/dL and leukocytosis, hyperglycemia, vomiting, and opacities in abdominal radiographs (P > .05). Sensitivities, specificities, and positive and negative predictive values indicate poor performance of these parameters as clinical predictors of serum iron concentration of > 300 micrograms/dL. Leukocytosis, hyperglycemia, vomiting, or the presence of opacities in abdominal X-rays are not indicators of a serum iron concentration of > 300 micrograms/dL in adults. These parameters should not be used to assess the severity of iron overdose or to guide its management.

Adolescent

Infant walker injuries persist in Canada after sales have ceased.

OBJECTIVE: To identify the source of acquisition of infant walkers and attitudes regarding the continuing use of walkers following an injury to an infant in order to design preventive strategies. DESIGN: Descriptive and retrospective. SETTING: Emergency department of a children's hospital involved in primary, secondary and tertiary care. PATIENTS: All patients presenting with injuries associated with infant walkers over a 42-month period. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Source of acquisition of infant walker and actions taken after the injury. RESULTS: The demographic and outcome data of the 36 patients were similar to previous reports. The caretakers of 26 patients were reached by telephone. Eight walkers were purchased in the United States and 18 were second-hand acquisitions (new walkers are not available for sale in Canada). Only two families continued using their walkers in the same fashion as prior to the injury. CONCLUSIONS: Although new infant walkers are not sold in Canada, injuries associated with their use continue. An aggressive public education campaign discouraging infant walker use and an incentive driven recall campaign to retrieve circulating walkers are seen as complimentary preventive strategies. A similar approach should be considered in other countries that choose to regulate infant walkers.

Accidental Falls

Neonatal withdrawal from maternal volatile substance abuse.

AIM: To determine whether neonates born to mothers who are volatile substance abusers are at risk for an abstinence syndrome. METHODS: A consecutive sample of infants born to volatile substance abusing mothers was studied over four years, in a university affiliated medical centre with a variable mix of primary, secondary, and tertiary care patients. Infants were clinically scored with the Finnegan Neonatal Abstinence Scoring System. Those who fulfilled a priori scoring criteria were treated with phenobarbital and scoring was continued. RESULTS: There were 48 babies of whom 32 fulfilled the criteria for pharmacotherapy. All eight babies with the characteristic odour, and 15 of the 21 born to mothers with that odour, fulfilled these criteria. The typical symptoms were excessive and high pitched cry, sleeplessness, hyperactive Moro reflex, tremor, hypotonia, and poor feeding. Mean age of onset of treatment was 27.1 hours and mean duration was 5.8 days. Treatment was judged effective in 17 of 27, while benefit was borderline in three and absent in seven. CONCLUSIONS: It is suggested that there is an identifiable neonatal volatile substance abuse abstinence syndrome. The characteristic chemical odour in the neonate or mother is a marker for its occurrence, and phenobarbital treatment seems to be effective. The Finnegan Scoring System seems to be useful for grading its severity.

Acidosis

Benefits of parenteral deferoxamine for acute iron poisoning.

OBJECTIVE: To review the benefits of deferoxamine for the treatment of iron poisoning. METHODS: Both the basic science and clinical literature on deferoxamine were reviewed by comprehensive computer literature search. This was supplemented by references identified from bibliographies of pertinent articles and books. RESULTS: The basic science literature supports deferoxamine as an attractive antidote for iron poisoning. There were no dose response studies in the human or animal literature. There were no randomized controlled trials or case controlled studies of patients with toxicity (serum iron concentration > 500 micrograms/dL). All data were descriptive and anecdotal. Therefore fundamental parameters such as indications for administration, dose, route and duration of therapy are unclear and efficacy is unproven. CONCLUSION: Deferoxamine is attractive for the treatment of iron poisoning despite the lack of knowledge for its optimal use and remains the drug of choice for the treatment of significant iron poisoning.

Administration, Oral

Methanol half-life during ethanol administration: implications for management of methanol poisoning.

STUDY OBJECTIVE: To determine the half-life of methanol in methanol-poisoned patients who are treated with ethanol but not with hemodialysis. DESIGN: Case series. SETTING: University Hospital, University of Manitoba. PARTICIPANTS: Three methanol-poisoned patients treated with ethanol but not with hemodialysis and three similar patients identified by a literature review. RESULTS: Plots of terminal concentration versus time data were inconsistent with zero-order kinetics and were adequately explained by an apparent first-order process. The median half-life of methanol in these patients was 43.1 hours, with a range of 30.3 to 52.0 hours. CONCLUSION: Because of the significantly increased risk of toxicity and complications during ethanol monotherapy, we suggest that hemodialysis be considered for methanol-poisoned patients who are treated with ethanol infusion.

Adult

The abstract and the academic clinician.

The abstract is an essential element of all phases of the research process--submission of proposals for funding, presentation at scientific meetings, and ultimately, publication. Thus, the writing of effective abstracts is an important skill for the academic clinician. Like all skills, it requires significant time and effort for its acquisitions and practice for its maintenance. The structured abstract provides guidance for both format and content, and is an important innovation.

Abstracting and Indexing

Does iron deficiency raise the seizure threshold?

To determine the effect of iron status on the seizure threshold, measures of iron sufficiency were prospectively evaluated in 51 children presenting to a pediatric emergency department with a febrile illness with (26) or without (25) an associated febrile seizure. A higher proportion of children from the febrile seizure group had a family history of mental retardation (5/26 versus 0/25, P = .02) or of previous febrile seizures (10/26 versus 2/23, P = .01). The two groups were otherwise comparable for age, sex, race, family history of afebrile seizures, temperature at presentation, white blood cell count, differential, and vitamin and antibiotic use. Patients with febrile seizures were less frequently iron deficient as defined by a free erythrocyte protoporphyrin level above 0.80 ng/L (2/23 versus 10/25, P < .01), hemoglobin concentration less than 110 g/L (1/26 versus 6/25, P < .03), hematocrit less than 0.30 L/L (0/22 versus 4/25, P < .02), mean corpuscular hemoglobin less than 20 pg (0/25 versus 3/24, P < .04), mean corpuscular volume less than 65 fL (0/26 versus 4/24, P < .02), and platelet count higher than 550 x 10(9)/L (0/26 versus 3/25, P < .04). This association was even stronger when adjusted for differences in family history. None of the patients in the febrile seizure group was being treated for iron deficiency at presentation, whereas three of 25 controls used an iron supplement (P < .04). Iron deficiency may protect against the development of febrile seizures.

Anemia, Iron-Deficiency

Survival after a severe iron poisoning treated with intermittent infusions of deferoxamine.

Iron poisoning is the most common cause of overdose mortality in children under six years of age and there are no reports of survival with iron levels > 2687 mumol/L (> 15,000 micrograms/dL). A 22-month-old male was brought to the emergency department by his parents after ingesting an estimated 50 ferrous sulfate tablets (60 mg elemental iron/tablet) several hours earlier. Despite spontaneous emesis and gastric lavage his condition deteriorated and he was found to have a serum iron of 2992 mumol/L (16,706 micrograms/dL). During the first four days in the intensive care unit, he developed coma, metabolic acidosis, hypovolemic and cardiogenic shock, liver failure, coagulopathy and adult respiratory distress syndrome. He was treated with a unique deferoxamine dosage schedule (25 mg/kg/h for 12 h/d x 3 d), mechanical ventilation, Swan-Ganz catheter monitoring, dopamine/nitroprusside therapy, blood product, bicarbonate, electrolyte and volume replacement. After a prolonged hospital course complicated primarily by gastric outlet obstruction he was dismissed on full oral feedings, gaining weight, and neurologically intact. Swan-Ganz catheter monitoring guided the management of this patient's shock, iron-induced cardiac failure, and deferoxamine mesylate induced adult respiratory distress syndrome. Further experience and research is required to determine the most appropriate deferoxamine mesylate dosing schedule and our experience expands the range for possible survival after massive iron overdose.

Deferoxamine

Intravenous pentazocine and methylphenidate abuse during pregnancy. Maternal lifestyle and infant outcome.

OBJECTIVE: To report the effects of intravenous abuse of pentazocine hydrochloride and methylphenidate hydrochloride during pregnancy. DESIGN: Retrospective chart review. PATIENTS: All pregnant women and their offspring, whose hospital records indicated prenatal abuse of pentazocine and methylphenidate during the 2-year study period. RESULTS: The median for maternal age was 22 years and the median number of prenatal visits was two. Twenty mothers had sexually transmitted diseases, 27 abused alcohol, 10 abused other drugs, and all smoked cigarettes. Eight infants were premature, and 12 were growth retarded. Four infants had congenital anomalies: fetal alcohol syndrome (two [twins]), structural heart defect (one), and polydactyly (one). Eleven infants were treated for neonatal abstinence syndrome. Seventeen infants had normal developmental quotients, and four had low-normal developmental quotients. CONCLUSIONS: Intrauterine exposure to pentazocine and methylphenidate appears to be associated with prematurity, growth retardation, and signs of neonatal withdrawal, but not with any particular teratogenic anomaly or severe developmental delay.

Adolescent

Pulmonary toxicity of deferoxamine in iron-poisoned mice.

Previously we have shown that a group of patients treated for iron overdose with prolonged deferoxamine (DFO) infusion died of adult respiratory distress syndrome (ARDS). We now describe a model to investigate the mechanism of this pulmonary toxicity. Mice treated with 1 oral dose of iron (Fe) and then multiple injections of DFO, or with the chelated product ferrioxamine alone, did not develop lung lesions, even at doses which induced mortality. To potentiate any possible free radical reaction, other groups of mice were treated similarly while exposed to 75-80% O2 over a 4-day period. Ten of 12 mice receiving 0.75 mg Fe and then DFO (10 mg, 4 times/day for 4 days) with hyperoxia died suddenly. At autopsy the lungs were dark red and solid; sections showed hyaline membranes and alveolar exudates of edema, fibrin, and PMN. Electron microscopy showed massive destruction of the alveolar epithelium; using cerium chloride, a free radical reaction product was demonstrated at the alveolar surface. Lung lavage fluid contained 10-12 x normal levels of protein when the Fe-DFO-O2 group was compared to air or O2 controls. Mice receiving DFO or Fe, plus O2, showed only slight injury and a small increase in alveolar protein. The results indicate that Fe plus DFO generates free radicals in the lung, a reaction potentiated by hyperoxia to produce an ARDS-like picture. This suggests that the pulmonary toxicity of DFO in iron-poisoned patients is due to its prooxidant activity resulting in free radical destruction of the airblood barrier.

Animals