Nephrotoxicity of iodine contrast media

The antipsychotics are a chemically diverse group of heterocyclic compounds, which ameliorate many symptoms of schizophrenia. Most of the antipsychotics are very lipophilic and cross lipoidal membranes freely. When administered orally, they are well absorbed and undergo substantial pre-systemic elimination (bioavailability: 10-70%), are highly bound to plasma proteins (75-99%) and tissues, and are extensively distributed (VD: 100-1000 L). Primary route of elimination for most of antipsychotics is hepatic metabolism and biotransformation produces active metabolites. There is no linear relationship between the concentration of parent compound and different metabolites, and clinical relevance of pharmacologically active metabolites is not well understood. There are wide interindividual variabilities in pharmacokinetics, which result in large differences in steady-state plasma concentrations on the same dose regimen. The existence of optimal therapeutic ranges for most antipsychotics remains controversial. One of the major problems is the lack of well-designed studies that involve sufficient numbers of patients to clearly establish a therapeutic range for these drugs and is further complicated by the presence of a large number of pharmacologically active metabolites. However, the pronounced interindividual kinetic variabilities, combined with problems of noncompliance and drug interactions, and the delayed onset of clinical response in relation to initiation of treatment with antipsychotics are reasons why drug monitoring in conjunction with clinical status of the patient can be useful. Indications for antipsychotic drug monitoring include lack of response, non-compliance, toxicity, and drug interactions when other drugs are coadministered.     

Evaluation of contrast media for bronchography

BACKGROUND: Bronchography is occasionally needed for the evaluation and management of some congenital pulmonary anomalies as well as some acquired diseases, usually of the tracheo- bronchial tree. There is currently no effective, approved contrast agent for this imaging techniq ue. OBJECTIVE: We evaluated five agents (barium sulfate, iohexol, propyliodone oily, propyliodone aqueous, and perflubron) in terms of image quality, histologic changes, and effects on hemodynamics, blood gases, and standard laboratory tests in New Zealand White rabbits. MATERIALS AND METHODS: Animals were anesthetized and intubated. Each contrast agent (0.25 ml/kg) was administered intratracheally. Three animals in each group had intravenous lines placed for blood sampling and blood pressure monitoring and were sacrificed at 1 h. An additional three animals for each agent were sacrificed at 24 h and 1 week after imaging. Blood samples were taken immediately before contrast instillation and at 1 h postbronchography. Fluoroscopic images were recorded on standard VHS video tape and evaluated in blind fashion. Segments of lung tissue and bronchi were obtained for histologic examination. RESULTS: Necrosis and/or inflammatory infiltrates were noted in 78 % of the bronchograms performed with propyliodone aqueous, 67 % with propyliodone oily, 55 % with perflubron, and 33 % with iohexol 120, 240 and 350. No histologic damage was observed with barium. The propyliodones gave the best-quality imaging results and the most histologic changes. Iohexol, in any concentration, gave the least acceptable images and a moderate number of histologic changes. Barium sulfate demonstrated acceptable images with virtually no histologic changes. CONCLUSION: From the histologic and imaging results, barium is the best available contrast material for bronchography.     

Risk of hyperthyroidism in examinations with contrast media

Nanoliter volumes of human tear fluid were collected by means of a capillary tube without inducing tearing and were analyzed for glucose content. The tear fluid was subjected to two enzymatic reactions to generate a fluorescent compound that is proportional to the concentration of glucose in the sample. CE with laser-induced fluorescence (LIF) detection was used to monitor the fluorescent species generated, hence glucose in the tear samples. The reproducibility of the method for six different preparations was < 9% relative standard deviation (RSD). The procedure was compared with the glucose dehydrogenase method for the determination of glucose in blood before using it to determine glucose in tear fluid. Blood and tear samples were collected from six healthy human subjects. The results showed that the higher glucose content in tear samples is consistent with the higher glucose content in blood samples. The glucose concentration of the tear samples analyzed ranged from 128 to 166 microM, and that of blood ranged from 3.3 to 4.3 mM.     

Local and systemic effects of water-soluble contrast media and barium in rats with chronic small bowel obstruction

RATIONALE AND OBJECTIVES: The local effects on the small intestine and systemic changes produced by different contrast media in small bowel obstruction, with time courses of 4 days, were evaluated. MATERIALS AND METHODS: Four groups, each with 10 normal rats and another four groups (also each with 10 rats) that had ligation of the terminal ileum (obstructed rats) for 4 days were given 3 mL of barium, meglumine sodium diatrizoate, iohexol, or saline (control animals). Radiographs were taken immediately, 1 and 4 hours after administration of contrast media. Immediately before sacrifice, blood samples were taken to determine the hematocrit (Hct), hemoglobin (Hb), white blood cell count (WBC), red blood cell count (RBC), and serum sodium, and potassium and chloride concentrations. Specimens of small bowel were taken for histologic and morphometric analysis. RESULTS: In obstructed rats, the image quality with iohexol improved on final radiographs despite being diluted in the great intestinal contents. There was an improvement in the serum electrolyte concentrations in the obstructed animals that were given any one of the contrast media, the best improvement being in the iohexol groups. A shortening of the length of epithelial cells when any one of the contrast media was administered was observed, as was an increase in the lymphatic space area in the diatrizoate group in normal rats. In the bowel proximal to the obstruction, the lymphatic space area was increased in the diatrizoate group and the size of the epithelial cells was higher in the diatrizoate and iohexol groups compared to the barium and saline groups. CONCLUSION: Our results suggest that iohexol offers good radiologic efficacy and excellent systemic and local tolerance in small bowel obstruction.     

Alpha-adrenergic reactivity of the microcirculation in conscious spontaneously hypertensive rats

The goal of this study was to determine the functional distribution of alpha 1- and alpha 2-adrenoceptors in the striated muscle microcirculation. Experiments were performed in intact conscious spontaneously hypertensive rats (SHR) that were provided with a dorsal microcirculatory chamber to allow microvascular diameter measurements. Administration of selective alpha 1- and alpha 2-agonists, phenylephrine and azepexole, respectively, induced different patterns of microvascular constriction. alpha 1-Adrenoceptor stimulation showed a preferential constriction of large arteries and venules. The entire arteriolar microvasculature was sensitive to alpha 2-adrenoceptor stimulation, whereas the venular vessels did not respond to azepexole. The selective alpha 1- and alpha 2-antagonists prazosin and yohimbine showed patterns of vasodilator activity comparable to those of the corresponding agonists. The specificity of the drug-induced effects was verified by comparing their effects with those of graded hemorrhage, a non-pharmacological method for blood pressure lowering. In the range of blood pressure decreases comparable to that obtained by alpha-adrenoceptor antagonists, graded hemorrhage did not influence microvascular diameters. These results show a differential functional distribution of alpha 1- and alpha 2-adrenoceptors along the microvascular tree in striated muscle of conscious SHR.     

Changes in mesenteric microcirculation in rats following repeated skin burns

Acute experiments were conducted on rats; repeated extensive burn of a convalescent who formerly sustained the burn disease was better tolerated, led tono fatal outcome and was accompanied by moderate microcirculatory disturbances. The smae burn was accompanied in intact rats by a severe shock followed by death, intravascular aggregation of erythrocytes and significant microcirculatory disturbances leading to disturbance of tissue nutrition. It is supposed that the results obtained could serve as an indirect proof that toxemia played an important role in the genesis of intravascular aggregation of erythrocytes in burn shock.     

Effect of radiation and contrast media on chromosomes. Preliminary report

Measurements of chromosome aberrations or micronuclei in lymphocytes obtained from 7 patients indicate that angiocardiography produced chromosome damage corresponding to an average absorbed dose of about 50 rads. This is an order of magnitude larger than was estimated from the exposure rate. Experiments on lymphocytes suspended in solutions of methylglucamine and sodium diatrizoate (Renografin) or sodium diatrizoate alone (Hypaque) indicate that the chromosome damage observed in the patients is due in larger part to two effects: (a) an increased absorption of x rays as compared to blood and (b) a breakage of chromosomes even in the absence of x rays.     

Harmonic imaging of porcine intraovarian arteries using sonographic contrast medium: initial findings

BACKGROUND AND STUDY AIMS: The role of the needle knife at endoscopic retrograde cholangiopancreatography (ERCP) remains controversial, with conflicting views being held on the value and safety of this device. The aim of the present study was to assess prospectively the value and safety of suprapapillary fistulosphincterotomy (FS) in the endoscopic management of biliary disease. PATIENTS AND METHODS: Suprapapillary fistulosphincterotomy was performed when biliary cannulation had failed after attempting to opacify the bile duct for 30 minutes, initially with a standard diagnostic cannula and then by further attempts with a tapered cannula. The second indication for suprapapillary fistulosphincterotomy was inability to obtain satisfactory cannulation with the sphincterotome in patients in whom cholangiopancreatography showed pathology requiring endoscopic sphincterotomy. Using this technique, an opening was created into the intraduodenal segment of the common bile duct at a point on the vertical axis 3-5 mm proximal to the papillary orifice. The opening was then cannulated, and extended as required to facilitate clearance of stones or stent insertion. RESULTS: Of 531 consecutive patients, 83 (16%) underwent suprapapillary fistulosphincterotomy, and biliary cannulation was achieved in 74 of the 83 (89%). If suprapapillary fistulosphincterotomy had not been used, the diagnostic success rate would have fallen from 513 out of 531 (97%) to 451 out of 531 (85%) (P = 0.0001); the clearance rate for duct stones would have fallen from 150 out of 156 (96%) to 130 out of 156 (83%) (P = 0.0003); and successful stent insertion would have fallen from 52 out of 59 (88%) to 38 out of 59 (64%) (P = 0.0044). There were no fatalities following suprapapillary fistulosphincterotomy. Complications occurred in five of the 83 patients (6%) who underwent fistulosphincterotomy, compared with five of the 448 patients (1%) who did not undergo the procedure (P = 0.01). CONCLUSIONS: Our results suggest that suprapapillary fistulosphincterotomy is a valuable adjunct in the management of biliary disease at ERCP, but, in view of the increased risk of complications, it should be reserved for patients in whom the index of suspicion for biliary disease is high and further endoscopic treatment is likely.