The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit

As selective inhibitors of the extraneuronal monoamine uptake system (uptake2) suitable for in-vivo studies were not available, the question of whether uptake2 plays a definite role in vivo is largely unresolved. We attempted to resolve the question by using 1,1'-diisopropyl-2,4'-cyanine iodide (disprocynium24), a novel agent that blocks uptake2 in vitro with high potency. Anaesthetized rabbits were infused with 3H-labelled noradrenaline, adrenaline and dopamine, and catecholamine plasma clearances as well as rates of spillover of endogenous catecholamines into plasma were measured before and during treatment with either disprocynium24 or vehicle. Four groups of animals were studied: group I, no further treatment: group II, monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) inhibited; group III, neuronal uptake (uptake1) inhibited; group IV, uptake1 as well as MAO and COMT inhibited. Disprocynium24 (270 nmol kg-1 i.v. followed by an i.v. infusion of 80 nmol kg-1 min-1) did not alter heart rate and mean arterial blood pressure, but increased cardiac output by 22% and decreased the total peripheral vascular resistance by 16% with no difference between groups. When compared with vehicle controls, catecholamine clearances (normalized for the cardiac output of plasma) were decreased and spillover rates increased in response to disprocynium24. Although there were statistically significant between-group differences in baseline clearances (which decreased in the order: group I > group II > group III > group IV), the drug-induced clearance reductions relative to vehicle controls were similar in groups I to IV and amounted to 29-38% for noradrenaline, 22-31% for adrenaline and 16-22% for dopamine. Hence, there was still a significant % reduction in catecholamine clearances even after the combined inhibition of MAO and COMT, and there was no increase in the % reduction of clearances after inhibition of uptake1. Noradrenaline spillover increased in response to disprocynium24 in all four groups by 1.6- to 1.9-fold, whereas a 1.5- to 2.0-fold increase in adrenaline and dopamine spillover was observed in groups II and IV only. The results indicate that disprocynium24 interferes with the removal of circulating catecholamines not only by inhibiting uptake2, but also by inhibiting related organic cation transporters. As disprocynium24 increased the spillover of endogenous catecholamines into plasma even after inhibition of MAO and COMT, organic cation transporters may also be involved in the removal of endogenous catecholamines before they enter the circulation.     

Yield of positive blood cultures in pediatric oncology patients by a new method of blood culture collection

The purposes of this study were to estimate the proportional contribution of uranium dust exposure to urinary excretion of the metal, and to examine the influence of hand contamination on the elimination of uranium from the urine of workers who performed different jobs. The study was based on records taken from a gaseous diffusion plant in 1956. Regression techniques were used to investigate the relationship between uranium concentration in urine and exposure variables, including the concentration of uranium dust and the incidence of hand contamination. The proportional contribution of airborne to urinary uranium was estimated by the slope of this relationship. It is concluded that the workers eliminated uranium at relatively constant rates per unit air concentration (0.67 to 1.27 micrograms/L per micrograms/m3). In addition to airborne uranium, hand contamination significantly contributed to the elimination among maintenance crew, but not among production workers. Furthermore, the production index was shown to be a useful surrogate for airborne and urinary uranium.     

The effect of low-and high-dose adjunctive mitomycin C in trabeculectomy

Selenium is a powerful antioxidant regulating the activity of the glutathione peroxidase enzymes, which catalyse the detoxification of hydrogen peroxide and organic hydroperoxides. Selenium deficiency has been implicated in the aetiopathogeny of Keshan disease, an endemic cardiomyopathy observed in China, and in other cases of congestive cardiomyopathy in subjects on artificial nutrition. However, the evidence from case-control and prospective studies for an association between low selenium status and cardiovascular diseases remains controversial. Mechanisms whereby selenium protects against such diseases include increased resistance of low-density lipoproteins against oxidative modification, modulation of prostaglandin synthesis and platelet aggregation, and protection against toxic heavy metals. The therapeutic benefit of selenium administration in the prevention and treatment of cardiovascular diseases still remains insufficiently documented.     

Single injection thermodilution. A flow-corrected method

BACKGROUND: Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output. METHODS: To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle. RESULTS: A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction. CONCLUSION: It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.     

Effect of zinc on the epithelial lining of mice epididymis--a light microscopic study

Intraperitoneal zinc chloride was administered at 7.5 micrograms/g body weight and 15 micrograms/g body weight to 10-12 weeks old Swiss albino mice for 5 consecutive days. Control animals were given normal saline. The testis and epididymis were dissected and examined under the light microscope. Micrographs of the testes appeared normal in both treated and nontreated animals. However the group of animals treated with the higher dosage of zinc chloride showed evidence of rupture and collapse of the epididymal epithelial lining. The testes were not affected probably because of (a) known higher testicular concentration of metallothioneins which can bind the zinc and consequently detoxify the metal and (b) "stratified" epithelium comprising of spermatogenic and Sertoli cells.     

Do exclusively breast-fed infants require extra protein?

It has been argued that the growth rate of exclusively breast-fed infants may be limited by their protein intake. This issue was examined using data from an intervention study in Honduras in which infants were randomly assigned to be exclusively breast-fed for the first 6 mo (EBF; n = 50), or to receive preprepared solid foods (including egg yolk) in addition to breast milk beginning at 4 mo (n = 91). Neither weight gain nor length gain from 4 to 6 mo differed between groups despite a 20% higher protein intake (as well as significantly higher intakes of iron, zinc, calcium, vitamin A, and riboflavine) in the latter group. The 20 infants with the highest protein intakes in that group were matched to 20 EBF infants on the basis of energy intake; protein intake was 1.46 +/- 0.09 versus 1.10 +/- 0.17 g/kg/d, respectively (p < 0.001), but growth rate did not differ between groups. Similarly, the 20 infants with the lowest protein intakes in the EBF group were matched (by energy intake) to 20 infants given solid foods; protein intake was very low in the former compared with the latter (0.81 +/- 0.13 versus 1.04 +/- 0.20 g/kg/d; p < 0.001), yet there was still no difference in growth. Infant morbidity was relatively low and did not influence the results. These analyses indicate that protein intake is not likely to be a limiting factor with regard to growth of breast-fed infants from 4 to 6 mo of age.     

Accurate three-dimensional reconstruction of intravascular ultrasound data. Spatially correct three-dimensional reconstructions

BACKGROUND: The geometrical accuracy of conventional three-dimensional (3D) reconstruction methods for intravascular ultrasound (IVUS) data (coronary and peripheral) is hampered by the inability to register spatial image orientation and by respiratory and cardiac motion. The objective of this work was the development of improved IVUS reconstruction techniques. METHODS AND RESULTS: We developed a 3D position registration method that identifies the spatial coordinates of an in situ IVUS catheter by use of simultaneous ECG-gated biplane digital cinefluoroscopy. To minimize distortion, coordinates underwent pincushion correction and were referenced to a standardized calibration cube. Gated IVUS data were acquired digitally, and the spatial locations of the imaging planes were then transformed relative to their respective 3D coordinates, rendered in binary voxel format, resliced, and displayed on an image-processing workstation for off-line analysis. The method was tested by use of phantoms (straight tube, 360 degrees circle, 240 degrees spiral) and an in vitro coronary artery model. In vivo feasibility was assessed in patients who underwent routine interventional coronary procedures accompanied by IVUS evaluation. Actual versus calculated point locations were within 1.0 +/- 0.3 mm of each other (n = 39). Calculated phantom volumes were within 4% of actual volumes. Phantom 3D reconstruction appropriately demonstrated complex morphology. Initial patient evaluation demonstrated method feasibility as well as errors if respiratory and ECG gating were not used. CONCLUSIONS: These preliminary data support the use of this new method of 3D reconstruction of vascular structures with use of combined vascular ultrasound data and simultaneous ECG-gated biplane cinefluoroscopy.