A review of GP records relating to methadone-associated deaths in the Lothian region of Scotland 1997-9

Aims : To ascertain the characteristics of patients whose death was associated with methadone intoxication during the period 1997-9 in the Lothian region of Scotland. Design : Patients were identified from death certificates. General practitioner records relating to methadone-associated deaths were reviewed in association with autopsy, toxicology and police reports. Deprivation categories (DepCat) were derived from the postal code of residence and the Carstairs index. Findings : There were 77 methadone-associated deaths in the Lothian Health Board area. GP records were obtained for 60 patients registered with a general practitioner. The majority of methadone-associated deaths (73%) occurred in persons who were not prescribed methadone at the time of their death. Thirty-eight persons were prescribed medication other than methadone or dihydrocodeine at the time of death. Thirty (79%) of those being prescribed for were receiving benzodiazepines. Forty-seven per cent had a history of excessive alcohol consumption. Fifty per cent had a reported psychiatric history. Sixty per cent had previously attended Accident and Emergency through deliberate self-harm or accidental overdose. Low socioeconomic status was found to be associated with the highest rate of methadone-related deaths. Conclusions : Given the variety of characteristics outlined it is likely that reducing drug-related deaths is a longer term aim, not amenable to one particular solution.     

Haplotype association of calpain 10 gene variants with type 2 diabetes mellitus in an Irish sample

Background  

Calpain 10 (CAPN10) gene may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM).     

In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30, a retinoid X receptor-specific retinoid.

The present study was conducted to compare the in vitro phase I and phase II metabolic profiles of (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30) in human, rat, and dog microsomes and to characterize and identify the associated metabolic kinetics and specific isozymes from human liver microsomes (HLM) responsible for metabolism, respectively. Data from these experiments revealed that nine (M1-M9) phase I metabolites along with a single glucuronide conjugate were observed across the species investigated. With the exception of glucuronidation, no evidence of metabolism was detected for phase II enzymes (data not shown). Significant differences between species with regard to metabolic profile, stability, and gender were noted. For the eight phase I metabolites detected in HLM, the specific isozymes responsible for the biotransformations were CYP2C8, CYP2C9, and CYP2C19, with minor contributions from CYP1A2 and CYP2B6. For the glucuronide conjugate, UGT1A9 was the major catalyzing enzyme, with a minor contribution from UGT1A3. Kinetic analysis of eight of the detected metabolites indicated that four seemed to follow classical hyperbolic kinetics, whereas the remaining four showed evidence of either autoactivation or substrate inhibition.     

31P nuclear magnetic resonance study of the effect of hypoxemia on neonatal status epilepticus

Prolonged neonatal seizures are often accompanied or exacerbated by hypoxemia. To determine the effects of hypoxemia on neonatal status epilepticus, we determined cerebral blood flow and cerebral metabolic state in groups of neonatal dogs subjected to hypoxia, to seizures during normoxia, or to seizures during hypoxia. The compensatory increase in cerebral blood flow was greatest in animals subjected to seizures during normoxia and somewhat less pronounced in animals made hypoxic. However, blood flow failed to increase in forebrain structures when animals were subjected to the combination of seizures and hypoxia. Accordingly, levels of adenosine triphosphate in forebrain (measured both by in vitro enzymatic analysis and by in vivo phosphorus-31 nuclear magnetic resonance spectroscopy) were depleted to the greatest degree in animals who were seizing while hypoxic. In addition, brain glucose was significantly reduced only in the seizure-hypoxia group. Systemic factors such as hypoxemia may play a critical role in the disruption of cerebral energy balance during neonatal status epilepticus.     

Occult bacteremia in children with simple febrile seizures

The controversy surrounding the diagnostic workup for simple febrile seizures has centered around the lumbar puncture. This focus has obscured the potential importance of other tests. A retrospective study was performed to determine the frequency of occult bacteremia in simple febrile seizures. In a pediatric emergency department, we identified 115 cases of simple febrile seizures in children treated as outpatients. Blood cultures were performed in 93 (81%) of 115 patients; five (5.4%) were positive. Children were less likely to have blood cultures performed if they were older than 24 months or had a medical history of simple febrile seizures. However, neither age nor history of febrile seizures affected the risk of bacteremia. These data suggest that patients with simple febrile seizures are at approximately the same risk for bacteremia as children with fever alone. Patients with simple febrile seizures should be treated in the same manner as other patients of the same age with regard to the performance of blood cultures.