Electronic interface for emergency department management of asthma: A randomized control trial of clinician performance

Objectives: To evaluate the effectiveness of an integrated and dynamic electronic decision support system for management of acute asthma in the ED. Methods: A randomized trial was conducted comparing clinician performance using this electronic interface compared with paper documentation in a simulation scenario. The outcomes were documentation of asthma‐related information and consultation times. Results: Use of this electronic interface was associated with significantly higher rates of documentation in 7 out of 10 variables, including provision of written short‐term asthma management plans. After adjustment for participant seniority, there was no significant difference in consultation times. Conclusion: In a simulation trial, use of this electronic interface was associated with improvements in clinical and discharge documentation. Further studies are required to test this prototype in clinical practice.     

Schizencephaly: diagnosis and progression in utero

Schizencephaly is an unusual condition of obscure etiology. Most theories of pathogenesis postulate an in utero insult leading to maldevelopment rather than destruction of brain. The cause has most often been described as vascular or idiopathic dysgenesis. The authors report a case in which two in utero ultrasound (US) examinations performed at 31 and 36 menstrual weeks demonstrated progressive deterioration of the relatively narrow, symmetrical clefts connecting the lateral ventricles with the subarachnoid space into broad defects that corresponded to the entire distribution of the middle cerebral arteries. The findings in this case document progressive destruction of brain tissue in utero and are consistent with a vascular cause rather than a failure of formation of portions of the cerebral mantle.     

A highly sensitive and specific chemiluminescent enzyme-linked immunosorbent assay for diagnosis of active Trypanosoma cruzi infection

BACKGROUND: Chagas' disease is transmitted to man either by the bite of insects harboring Trypanosoma cruzi or by the transfusion of blood from infected donors. The conventional serologic testing as presently used in blood banks in South America is unsatisfactory, because of a high number of inconclusive and false-positive results. Other methods such as polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) with recombinant antigens have been proposed, but inherent difficulties have so far precluded their adoption in the large-scale screening required by blood banks. STUDY DESIGN AND METHODS: A highly sensitive and specific chemiluminescent ELISA using a purified trypomastigote glycoconjugate antigen and a complex epimastigote antigen was devised for the diagnosis of active T. cruzi infection. RESULTS: Chemiluminescent ELISA was 100-percent sensitive in the diagnosis of 100 cases of confirmed Chagas' disease. Inconclusive results and false-positive reactions were eliminated in a panel of 115 sera.The specificity of the chemiluminescent ELISA was 100 percent with a purified trypomastigote glycoconjugate antigen and 99.7 percent with a complex epimastigote antigen when applied to 1000 normal human sera and 288 heterologous sera from patients with other infections, including leishmaniasis, and vaccinated individuals. CONCLUSION: The chemiluminescent ELISAs provide a test that is highly sensitive (purified trypomastigote glycoconjugate and complex epimastigote antigens) and specific (purified trypomastigote glycoconjugate antigen) for Chagas' disease diagnosis. It can be used in blood bank screening and to monitor the treatment of patients undergoing chemotherapy.     

Trastuzumab for early breast cancer: current status and future directions

The human epidermal growth factor receptor 2 (HER2) is overexpressed/amplified in up to 25% of breast cancer patients, and this feature is associated with an aggressive phenotype, a high recurrence rate, and reduced survival. Until recently, combination chemotherapy was the most effective and only adjuvant treatment for HER2-positive patients. Trastuzumab, a monoclonal antibody directed against the HER2 extracellular domain, has recently demonstrated highly reproducible and astonishing benefit in halving the recurrence rate and reducing mortality in five adjuvant breast cancer trials. But such unfettered success has come at a cost, both in terms of cardiotoxic risk and substantial financial burden. Though trastuzumab has been able to significantly improve clinical outcomes of many patients with early breast cancer, the reality is that an unacceptable proportion will still relapse. Beyond trastuzumab, what is the next step for these HER2-positive breast cancers? This review first discusses the individual results of the five adjuvant trastuzumab studies in terms of efficacy and safety, highlighting their similarities and differences. It also evaluates the current status of trastuzumab as a result of these studies and explores the possible future direction for HER2-positive breast cancers in light of recent advances in translational oncology.     

Angiotensin receptors: distribution, signalling and function

Angiotensin II (Ang II) is a multi-functional hormone that plays a major role in regulating blood pressure and cardiovascular homoeostasis. The actions of Ang II are mediated by at least two receptor subtypes, designated AT(1) and AT(2). In addition, other angiotensin receptors have been identified which may recognize other angiotensin peptide fragments; however, until now only the AT(1) and AT(2) receptor have been cloned in animals or humans. Most of the well-described actions of Ang II, such as vasoconstriction, facilitation of sympathetic transmission, stimulation of aldosterone release and promotion of cellular growth are all mediated by the AT(1) receptor. Much less is known about the function of the AT(2) receptor, but recent studies suggest that it may play a role in mediating anti-proliferation, cellular differentiation, apoptosis and vasodilatation. In this review, we discuss recent advances in our understanding of Ang II receptors, in particular, their distribution, signalling and function.     

Amineptine, a tricyclic antidepressant, inhibits the mitochondrial oxidation of fatty acids and produces microvesicular steatosis of the liver in mice

Microvesicular steatosis of the liver has been reported in two subjects receiving amineptine (a tricyclic antidepressant metabolized by beta-oxidation of its acyl chain). A similar disease is observed after ingestion of drugs which inhibit hepatic mitochondrial fatty acid beta-oxidation, or in subjects with various inborn defects in this metabolic pathway. We therefore determined the effects of amineptine on the mitochondrial oxidation of fatty acids in mice. In vitro, the formation of beta-oxidation products during incubation of palmitic acid with mouse liver mitochondria and the various cofactors necessary for beta-oxidation was inhibited by 27, 33, 46 and 57% respectively, in the presence of 0.25, 0.5, 1 and 2 mM of amineptine. Inhibition was reversible. Tricarboxylic acid cycle activity, assessed by the in vitro formation of [14C]CO2 from [1-14C]acetyl coenzyme A by mouse liver mitochondria, was inhibited by 22, 23, 47, 54, 60 and 62%, respectively, in the presence of 0.0625, 0.125, 0.25, 0.5, 1 and 2 mM of amineptine. In vivo, administration of amineptine, 0.5 and 0.75 mmol.kg-1, inhibited by 70 and 84%, respectively, the exhalation of [14C] CO2 during the first 3 hr after the administration of a tracer dose of [U-14C]palmitic acid. Administration of amineptine, 0.0625, 0.25, 0.5 or 1 mmol.kg-1, 6 hr before the measurement, increased hepatic triglycerides by 73, 139, 295 and 320%, respectively. After 1 mmol.kg-1, accumulation of hepatic triglycerides was maximum at 24 hr, reaching 5-fold the control value; liver histology at that time showed microvesicular steatosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic cor pulmonale

Chronic cor pulmonale is defined as right heart hypertrophy and/or chronic right heart failure. There are many etiologies, but the common cause is increased right heart work from pulmonary hypertension. Etiology can be conveniently discussed by assuming two prototypes, the asphyxial or hypoxic type and the vascular obliterative type. A common cause of the asphyxial type is chronic obstructive pulmonary disease, and the obliterative type is represented by chronic pulmonary thromboembolic disease or primary pulmonary hypertension. Pathology is discussed, emphasizing the cardiac manifestations of chronic cor pulmonale including data of specific cardiac chamber size. An overview of hemodynamics is given, and the use and limitation of electrocardiography and chest x-rays are discussed. The exciting potential use of echocardiography for the serial non-invasive measurement of anatomical and pathophysiological features is outlined, along with the value of a careful physical examination and the proper utilization of laboratory tests in the diagnosis of chronic cor pulmonale. In the patient with the asphyxial type, the treatment of pulmonary infectious exacerbations, the role of corticosteroids, digoxin, diuretics, phlebotomy, bronchodilators (theophylline, beta adrenergic agonists, and anticholinergics), and long-term oxygen therapy is noted. The controversy surrounding the use of vasodilators and calcium blockers in these patients is discussed. Treatment aspects of the vascular obliterative type, including the role of vasodilators, calcium blockers, prostacyclin, anticoagulants, and overall strategy are discussed. A brief note is mentioned of the promising role of surgical therapy in chronic thromboembolic disease causing chronic cor pulmonale.     

Naratriptan: biological profile in animal models relevant to migraine

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT_1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT_1B and 5HT_1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC₅₀ values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC₅₀ value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD₅₀ dose = 193 g kg⁻¹) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID₅₀ = 4.1 g kg⁻¹). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT_1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2-3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.