A phenobarbital overdose: a case report

Background: Phenobarbital is a long-acting barbiturate, responsible for many cases of poisoning, from unintentional overdose or attempted suicide. We report a case of phenobarbital overdose in a patient with history of depression. Patients and Methods: A 60 year old woman was admitted to our Internal Medicine Unit for drowsiness, irritability, difficulties in the maintenance of an upright position, dysphasia and weakness. She was suffering from depression and epilepsy and treated with phenobarbital 150 mg/die. Results: At the admittance, she had high fever and neck stiffness; phenobarbital serum levels were 71.2 mcg/ml (3 times u.n.l.); aminotransferases were 12-17u.n.l. Arterial blood pressure was 80/50 mmHg. An inflammatory meningeal process was excluded by lumbar puncture; a brain and spinal cord CT scan excluded spine bone lesions and ischemic stroke. In the suspect of an overdose, a protocol of urine alkalinization was applied resulting in a reduction of phenobarbital levels below the therapeutic range in about 6 days, with state of consciousness, cognitive and behavioral functions improvement. A rapid normalization in aminotransferases levels was noted and serology for hepatitis viruses (HAV, HBV, CMV, EBV, HSV) resulted negative. Conclusions: In our patient phenobarbital was responsible for stupor, hypotension, hypertonicity and aminotransferases elevation, whereas fever was due to a concomitant pulmonary inflammatory process resolved after antibiotic therapy. Despite the use of these drugs has been progressively reduced, the number overdose reports remains still hig

A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol.

Abstract OBJECTIVES: The PCSK9 gene, encoding a pro-protein convertase involved in posttranslational degradation of low-density lipoprotein receptor, has emerged as a key regulator of plasma low-density lipoprotein cholesterol. In African-Americans two nonsense mutations resulting in loss of function of PCSK9 are associated with a 30% to 40% reduction of plasma low-density lipoprotein cholesterol. The aim of this study was to assess whether loss of function mutations of PCSK9 were a cause of familial hypobetalipoproteinemia and a determinant of low-plasma low-density lipoprotein cholesterol in whites. METHODS AND RESULTS: We sequenced PCSK9 gene in 18 familial hypobetalipoproteinemia subjects and in 102 hypocholesterolemic blood donors who were negative for APOB gene mutations known to cause familial hypobetalipoproteinemia. The PCSK9 gene variants found in these 2 groups were screened in 42 subjects in the lowest (95th) percentile, and 100 with the average plasma cholesterol derived from general population. In one familial hypobetalipoproteinemia kindred and in 2 hypocholesterolemic blood donors we found a novel PCSK9 mutation in exon 1 (c.202delG) resulting in a truncated peptide (Ala68fsLeu82X). Two familial hypobetalipoproteinemia subjects and 4 hypocholesterolemic blood donors were carriers of the R46L substitution previously reported to be associated with reduced low-density lipoprotein cholesterol as well as other rare amino acid changes (T77I, V114A, A522T and P616L) not found in the other groups examined. CONCLUSIONS: We discovered a novel inactivating mutation as well as some rare nonconservative amino acid substitutions of PCSK9 in white hypocholesterolemic individuals