Approach to the patient with metabolic acidosis: Newer concepts

Summary: A new classification for patients with metabolic acidosis is provided: a pathophysiological classification. to recognize an overproduction of acids which results in a hydrogen ion (H⁺) gain the number of new anions retained in the body is added to those excreted in the urine when the cation accompanying them was not H⁺ or ammonium (NH₄⁺). the first tools are to recognize new anions that were added during the overproduction of acids. the nature of these anions can be recognized by assessing their fractional excretion. the second set of tools focuses on an assessment of NH₄⁺ in the urine using urine anion and osmolar gaps. the clinical approach suggested focuses on detecting an emergency (severity of H⁺ accumulation, toxic alcohols and/or dyskalaemias). the second step analyzes the expected responses to acidaemia; here the focus is on the P_CO2 in vital organs and the rate of excretion of ammonium. the principles used for diagnosis and treatment of metabolic acidosis are illustrated by a case example.     

Pseudoaneurysms complicating organ transplantation: roles of CT, duplex sonography, and angiography

In a retrospective study of proved pseudoaneurysms (PAs) in 15 patients with transplanted organs (11 liver, three kidney, one pancreas), the results of computed tomography (CT), duplex sonography, and angiography were reviewed. Of the 15 cases of PA, eight occurred at the arterial anastomosis and seven were nonanastomotic. Three of the eight anastomotic PAs were caused by infection. Of the seven nonanastomotic PAs, four were caused by percutaneous biopsy, two were caused by infection, and one was of undetermined cause. In nine (60%) of the 15 patients the PAs were incidentally detected at imaging studies performed for other reasons. Diagnosis requires a high degree of suspicion. CT was performed in nine cases and duplex sonography in ten. The diagnosis of PA was made with CT in six (67%) patients and with duplex sonography in five (50%). CT and duplex sonography could not enable diagnosis when the PA was small, when the arterial anastomosis was not included in the field of study, or when enhancement with intravenously administered contract material was suboptimal. Angiography depicted the PAs in all 15 patients. In three liver transplant recipients with gastrointestinal tract bleeding, the causative PAs were detected only with angiography.     

Cost comparison of intraoperative autologous versus homologous transfusion

The cost of autologous transfusions using semiautomated instruments in 52 orthopedic cases, 75 coronary artery bypass graft (CABG) cases, and 218 aortic aneurysm cases was compared to the cost of equal amounts of homologous blood. While none of the orthopedic cases reached cost equivalence (median cost deficit per case, +97), 31 percent of the CABG cases (median cost deficit per case, +61) and 56 percent of the thoracic aortic aneurysm cases (mean cost surplus per case, +30) did so. In most cases, the major orthopedic and CABG procedures do not reach cost equivalence and might be served better by other means of autologous blood recovery. The more expensive semicontinuous flow devices are more cost-effective for higher-yield cases, such as major aortic aneurysm procedures.     

Use of comprehensive screening methods to detect selective human CAR activators

The so-called human xenosensors, constitutive androstane receptor (hCAR), pregnane X receptor (hPXR) and aryl hydrocarbon receptor (hAhR), participate in drug metabolism and transport as well as in several endogenous processes by regulating the expression of their target genes. While the ligand specificities for hPXR and hAhR are relatively well described, this property of hCAR still remains fairly unclear. Identifying hCAR agonists for drug development and for studying hCAR biology are hindered mainly by the unique properties of the receptor, such as the high constitutive activity and complex signaling network but also by the lack of robust and reliable assays and cellular models. Here, validated reporter assays for these three xenosensors are presented and thereafter used to screen a large set of chemicals in order to find novel selective hCAR ligands. We introduce a novel selective hCAR agonist, FL81, which can be used as a stable positive control in hCAR activity assays. Our established receptor-selective ligand identification methods consisting of supporting biological assays and molecular modeling techniques are then used to study FL81 as well as other discovered ligands, such as diethylstilbestrol, o,p′-DDT, methoxychlor and permethrin, for their ability to specifically activate hCAR and to regulate the CYP enzyme expression and function.