Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

ENDOSCOPIC PANCREATIC STENTING IN CHRONIC PANCREATITIS WITH DUCTAL DILATION PROXIMAL TO A STRICTURE: A SAFE and EFFECTIVE PROTOCOL

After removal of intraductal stones, a 10‐Fr or 7‐Fr pancreatic stent was placed in 16 patients with upstream ductal dilation proximal to a stricture of the main pancreatic duct. Stents were removed after a mean duration of 52.5 days. Nine patients underwent repeated stenting. About one year after removal of the initial stent, when the remaining upstream ductal dilation was found on follow‐up pancreatograms, the next stent was replaced. Repeated stenting improved outflow of pancreatic juice more effectively than one‐time stenting. Correlation between long‐term pain relief without recurrence of intraductal stones and reduction of duct diameter was also shown. Stent occlusion was observed in 14 of 30 stents. Stent occlusion was frequently associated with recurrence of pancreatitis and intraductal stones, and was also associated with morphologic changes in the pancreatic ductal system. Although there were no significant differences between stent patency of the initial stents and that of the next stents, stent patency of 10‐Fr stents was superior to that of 7‐Fr stents. 10‐Fr stents should be removed within 8 weeks and 7‐Fr stents should be removed within 4 weeks for the prevention of stent occlusion. Repeated stenting with short‐term stenting is therefore considered a safe and effective protocol of endoscopic pancreatic stenting.     

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.     

Effect of external high-frequency oscillation on severe cardiogenic pulmonary edema

Effective gas exchange can be maintained in animals without endotracheal intubation using external high-frequency oscillation (EHFO). The aim of this study was to evaluate the effect of EHFO in patients with respiratory failure due to severe cardiogenic pulmonary edema. Seven patients were ventilated with EHFO for 2h at 60 oscillations·min⁻¹, with a cuiras pressure of 36 cmH₂O (−26 to +10) and an inspiratory to expiratory ratio of 1:1, with EHFO. Blood gas values and hemodynamic parameters were measured. Significant increases were noted in cardiac index (2.3±0.5 to 2.5±0.5 l·m⁻²;P<0.05), stroke volume index (24±7 to 28±8 ml·m⁻²;P<0.05), and arterial O₂ pressure (Pao₂) (70±4 to 95±23 mmHg;P<0.01) without a change in pulmonary artery wedge pressure at 1 h after EHFO. The respiratory rate decreased from 28±3 to 22 ±3 breaths·min⁻¹ at 5 min after the termination of EHFO (P <0.01). Arterial CO₂ pressure (Paco₂) did not, however, decrease. Increased stroke volume without a change in pulmonary artery wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with EHFO. The use of EHFO may be effective not only for gas exchange but also for left ventricular function in patients with severe cardiogenic pulmonary edema.     

Carinal resection and reconstruction for recurrent lung cancer

A patient with a recurrent tumor in the trachea adjacent to the right main bronchus was treated by surgical resection 19 months after undergoing surgery for the primary cancer. The patient had previously undergone right upper lobectomy for T1N0M0 stage I squamous cell carcinoma. A carinal resection was performed which included 4 rings of the trachea, 2 rings of the righ main bronchus, and 1 ring of the left main bronchus. Reconstruction consisted of an end-to-end anastomosis of the trachea and left main bronchus, and an end-to-side anastomosis of the right and left main bronchi. The postoperative course was uneventful, and at present the patient is healthy 12 months following reoperation.     

Antihypertensive effect of synthetic atrial natriuretic factor in vasopressin-infused rats

To assess the pathophysiological role of atrial natriuretic factors in the regulation of blood pressure, we studied the effect of chronic infusion of a synthetic atrial natriuretic factor of 25 amino-acid residues on blood pressure and sodium-water excretion. Experimental subjects were rats with hypertension made by chronic infusion of vasopressin on regular intakes of sodium or on sodium loading with 1% NaCl as drinking water. When a subdepressor dose (150 micrograms/kg/day) of synthetic atrial natriuretic factor was delivered via an osmotic minipump into the jugular vein simultaneously with 7.2 U/kg/day of vasopressin infused intraperitoneally by another osmotic minipump, the expected elevation of systolic blood pressure was completely inhibited. This was not accompanied by any changes in urine volume and urinary sodium excretion. The antihypertensive effect was sustained throughout the experimental period lasting 3 days in rats on regular sodium intake (p less than 0.01) or on sodium loading with 1% NaCl as drinking water (p less than 0.01). These results indicate that a subdepressor dose of synthetic atrial natriuretic factor can modulate the vasopressor effect of vasopressin. Therefore it is suggested that an atrial natriuretic factor may be involved in the regulation of blood pressure via its antagonizing effect to vasopressin.     

Tissue renin content in superficial, midcortical, and juxtamedullary afferent arterioles in rabbits]

Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity.