Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities

To elucidate the mechanisms by which thiamine deficiency affects hepatic microsomal monooxygenase activities, the effect of thiamine deficiency on two constitutive cytochrome P450 isozymes, P450IIE1 and P450IIC11, was investigated, using weanling male Sprague-Dawley rats. The clinical signs of thiamine deficiency were apparent after feeding a thiamine-deficient diet for 3 weeks. Thiamine deficiency caused an increase in P450IIE1, which was determined by N-nitrosodimethylamine demethylase assay and immunoquantitation of P450IIE1. This increase in the P450IIE1 level was mainly attributed to thiamine deficiency per se but not to dietary restriction. Ketone bodies were not elevated in thiamine-deficient rats, whereas ketone bodies were elevated and may have served as inducing factors in calorically restricted pair-fed animals. Injections of pyruvate or pyrithiamine in addition to thiamine deficiency did not potentiate the induction effect. On the other hand, thiamine deficiency did not affect the level of P450IIC11 during the 3 weeks of feeding the thiamine-deficient diet. In addition, thiamine deficiency increased cytosolic glutathione S-transferase activity but not steroid isomerase activity. The present study demonstrates the specificity of thiamine deficiency per se in the induction of P450IIE1 which does not involve an increase in the ketone body level.     

Ischemic necrosis of the entire femoral head and rapidly destructive hip disease: potential causative relationship

 Objective. Rapidly destructive hip disease (RDHD) is an uncommon disorder of the hip that has been considered a disease of unknown cause and distinct from ischemic necrosis of the femoral head. The objective of this study was to investigate ischemic necrosis of the femoral head as one potential cause of RDHD. Design and patients. In 600 patients who underwent MR imaging of the hip, 20 cases of ischemic necrosis involving the entire femoral head in 18 patients (3%) were retrospectively studied with routine radiography and MR imaging. All patients had surgically confirmed ischemic necrosis of the femoral head. Results and conclusions. All patients showed rapid destruction of the femoral head on routine radiography and MR imaging as compared with the gradual onset of clinical symptoms. Plain radiographs showed several bone fragments at the inferomedial aspect of the femoral head (75%), acetabular erosions (55%), eccentric depression at the lateral articular surface of the femoral head conforming to the adjacent acetabulum (35%), and mild osteoarthritis (15%). Bone sclerosis was often present at sites of impaction between the femoral head and the acetabulum. MR imaging showed marked distention of the joint capsule in all cases. In 14 of 20 cases, the contents of the joint space showed predominantly low or intermediate signal intensity on T1- and T2-weighted images. Ischemic necrosis involving the entire femoral head may represent one of the causes of RDHD.     

Pituitary abscess in a pregnant woman.

Pituitary abscess is a rare and potentially lethal condition. Pituitary abscess in a pregnant woman has not been previously described. A 38-year-old pregnant woman (34 weeks gestation) with a pituitary mass complained of a progressive headache and sudden visual impairment. She was afebrile and had no inflammatory symptoms on admission. On MRI, the preoperative diagnosis was pituitary adenoma with sphenoid sinusitis. She underwent an uncomplicated transsphenoidal procedure for removal of the pituitary mass. The next day, labor commenced and a healthy preterm baby was delivered. Pathologic examination of the intrasellar mass showed polymorphonuclear cells, debris and no tumor cells. The sellar contents were cultured and Streptococcus viridans was grown. To our knowledge this is the first case of pituitary abscess reported during pregnancy. Although the patient was pregnant, the transsphenoidal approach was safe for the mother and the fetus. Surgical drainage and antibiotic therapy are required for the definitive treatment of this condition.     

Methacholine and adenosine 5'-monophosphate challenges in children with post-infectious bronchiolitis obliterans.

Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, but is also frequently demonstrated by children and adults with chronic obstructive lung diseases. AHR is usually measured by bronchial challenges using direct or indirect stimuli. The aim of this study was to compare these two types of bronchial challenge in children with post-infectious bronchiolitis obliterans (BO). Methacholine and adenosine 5'-monophosphate (AMP) challenges were used as tools for the evaluation of AHR to direct and indirect stimuli, respectively, in children with post-infectious BO (n = 28). These results were compared with those of asthmatic (n = 30) and control children (n = 25). Altogether, twenty-two patients (78.6%) with post-infectious BO were hyperreactive to methacholine with a provocative concentration causing a 20% fall in forced expiratory volume in one second (PC20) of <16 mg x mL(-1), but only six (21.4%) were hyperreactive to AMP with a PC20 of <200 mg x mL(-1). All patients with asthma responded positively to methacholine, and most (28, 93.3%) also responded positively to AMP. The majority of controls were insensitive to both challenges. Airway hyperresponsiveness to methacholine is a frequent, but by no means universal, finding in children with post-infectious bronchiolitis obliterans, but is usually not accompanied by airway hyperresponsiveness to adenosine 5'-monophosphate. This finding suggests that airway hyperresponsiveness in patients with post-infectious bronchiolitis obliterans has characteristics that differ from those of asthmatic subjects.     

Acute coronary syndromes

The first 150 words of the full text of this article appear below. Key points Coronary artery disease accounts for >30% ofdeaths in Western society. The diagnosis of myocardial infarctionshould be qualified by size, causation and time from occurrence. Mortalityis reduced by immediate or ‘primary’ percutaneouscoronary intervention or thrombolysis within the first 24 hof onset of ST-segment elevation myocardial infarction. Strategiesto reduce platelet activation (glycoprotein IIb/IIIa receptorantagonists, or clopidogrel) are now recommended in the treatmentof high-risk non-ST-segment myocardial infarction/unstable angina. Elevatedserum troponins may be the result of non-ischaemic myocardialdamage, especially in critical illness.