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To evaluate the organ specificity of pancreatic phospholipase A2 (PLA2) and the diagnostic value of the elevation of serum PLA2 levels in patients with serious diseases not involving the pancreas, we studied the organ distribution of PLA2 in autopsy specimens and serum level of PLA2 in patients who required admission to an intensive care unit (ICU). PLA2 was measured by a specific radioimmunoassay (RIA), using monoclonal antibody against human pancreatic PLA2. Organ distribution of PLA2 revealed that the pancreas showed a much higher content of pancreatic PLA2 immunoreactivity than any other organ. An abnormally high value of serum PLA2 was observed in 18 of 30 patients (60%) at ICU. Both serum PLA2 and pancreatic isoamylase were elevated in 11 patients (37%). Of 11 patients with hyperphospholipasemia and hyperamylasemia, serum creatinine was elevated in five patients and blood urea nitrogen in nine patients. Serum PLA2 levels did not always rise comparably to serum creatinine and blood urea nitrogen levels. Serum PLA2 values showed the best correlation with serum lactate dehydrogenase levels among routine blood-chemistry tests. The elevation of serum PLA2 was ascribable to renal dysfunction or ischemic pancreatic damage secondary to circulatory collapse with multiple organ failure.
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PMID:Elevation of serum phospholipase A2 in patients at an intensive care unit. 178 39

During Ramadan, Moslems are required strictly to avoid fluids and nourishment from dawn to sunset. Heat stress during such abstinence represents a substantial health hazard. In the Federal Republic of Germany (FRG) where numerous Moslems, particularly of Turkish origin, perform heat work and other heavy labour, we observed moderate to severe health disturbances in such labourers during Ramadan, e.g.: tachycardia, severe headaches, dizziness, nausea, vomiting and circulatory collapse. The severe dehydration of these workers was demonstrated by substantial increases in their hematocrit, serum protein, urea, creatinine, uric acid and electrolyte imbalance. Because of the evidence of the substantial health hazard to Islamic workers in such situations, we have strongly urged employers to refrain from assigning Islamic workers to heat work or heavy daytime work during Ramadan; we have therefore limited systematic studies of health problems during Ramadan to persons performing only moderate work. Even under these conditions signs of dehydration were found in the 32 labourers monitored. Some of these labourers also had to interrupt their observance of Ramadan due to health problems, e.g.: acute gout due to serum uric acid increase, or circulatory insufficiency. In light of the observed potentially harmful pathophysiological effects, the danger of dehydration of Islamic workers due to heat work during Ramadan should be taken very seriously.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The health risks of occupational stress in islamic industrial workers during the Ramadan fasting period. 181 40

Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats (SHRSP) were investigated. Betaxolol was provided in a dose of 33 +/- 1.8 mg/kg/day, orally in drinking water, throughout the experimental period. The chronic treatment with betaxolol inhibited the development of hypertension in SHRSP and reduced values of blood urea nitrogen, creatinine, total cholesterol, free cholesterol, triglyceride, phospholipid and HDL-cholesterol in serum. Treatment with betaxolol apparently inhibited the incidence of hypertensive lesions such as cardiac fibrosis, mesenteric vasculitis, proliferative and/or necrotic vasculitis and glomeruli showing collapse or vasculitis in the kidneys. To shorten the time before the onset of hypertension and the subsequent stroke, SHRSP were kept on a SP diet containing 0.39% Na instead of the F-2 diet. When the SHRSP were kept on the SP diet, all of the control SHRSP had cerebral apoplexy and severe hypertensive lesions in the heart and kidney. When betaxolol was chronically administered to SHRSP, cerebral apoplexy and hypertensive lesions in the heart and kidney were inhibited, but the effect on blood pressure was slight. Treatment with betaxolol reduced serum creatinine levels. Our observations show that betaxolol reduces blood pressure and potently inhibits hypertensive complications in SHRSP.
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PMID:[Antihypertensive effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, in stroke-prone spontaneously hypertensive rats (SHRSP)]. 197 70

The effects of angiotensin II (AII) upon medullary hypoxic injury and kidney function were investigated in vitro and in vivo. Synthetic AII added to perfusate of isolated rat kidneys reduced perfusion flow from 48 +/- 2 ml min-1 (+/- SE) to 19 +/- 1 (P less than 0.001) without altering glomerular filtration rate (GFR), raising filtration fraction from 1% to 3% (P less than 0.001). AII-extended hypoxic injury to medullary thick ascending limbs (mTAL) from 66 +/- 4% of tubules to 79 +/- 3 (P less than 0.05) in correlation with filtration fraction (r = 0.8, P less than 0.001). Addition of indomethacin (10(-4) mol l-1) further extended medullary hypoxic damage to 89 +/- 2% of mTAL (P less than 0.001). Uninephrectomized rats kept in metabolic cages were given AII by continuous infusion (0.1-0.8 microgram min-1) and indomethacin (10 mg kg-1 day-1) for 24 h. Creatinine clearance declined from 1.3 +/- 0.1 ml min-1 to 0.6 +/- 0.06 (P less than 0.001). Morphological examination revealed either selective necrosis of mTAL (in 12 +/- 4% of tubules) or luminal collapse (in 63 +/- 8%). Both necrosis and collapse correlated inversely with creatinine clearance and with each other (r = -0.5, P less than 0.001), the latter correlation suggesting protection from hypoxic injury by cessation of solute delivery. By increasing filtration fraction and decreasing blood flow, AII decreases renal oxygen supply while maintaining oxygen consumption for solute reabsorption. AII may predispose to acute renal failure by augmenting medullary hypoxia.
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PMID:Angiotensin II augments medullary hypoxia and predisposes to acute renal failure. 211 85

Perioperative hemodynamic changes of hemodialysed patients were investigated and the changes of emergency cases (group E, n = 8) were compared with those of scheduled ones (group S, n = 13). By preoperative hemodialysis (HD), the values of blood urea nitrogen, serum creatinine, serum potassium, serum bicarbonate, and hematocrit were adjusted within normal range in group E, with no significant difference from those of group S. On the other hand, concerning the effect of preoperative removal of body water by HD, cardio-thoracic ratio (CTR, 53.6 +/- 3.1%) and pulmonary artery diastolic pressure (PADP, 11.6 +/- 5.0 mmHg) of group E were significantly higher than those of group S (CTR = 46.9 +/- 4.5%, PADP = 7.8 +/- 3.0 mmHg), indicating that the removal of body water by preoperative HD might be less in group E. However, group E patients required more administration of fluid and pressor agents in order to maintain their blood pressure and/or cardiac output during operation. Although with less water removal preoperatively and more fluid intraoperatively, postoperative PADP was significantly reduced (8.3 +/- 3.0 mmHg) in group E, suggesting that the requirement of perioperative water is more in group E. We conclude that the safe perioperative hemodynamic management for emergency surgery of hemodialysed patients requires following points; (1) The excessive removal of body water by preoperative HD should be avoided. (2) Intraoperative fluid infusion should be adequate so that they do not fall into hemodynamic collapse.
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PMID:[Perioperative hemodynamic changes and management of hemodialysed patients]. 224 11

1. The toxicokinetics of paraquat were studied in 18 cases of acute human poisoning using a specific radioimmunoassay. Plasma paraquat concentration exhibited a mean distribution half-life (t1/2 alpha) of 5 h and a mean elimination half-life (t1/2 beta) of 84 h. Cardiovascular collapse supervened early during the course of the intoxication and was associated with the distribution phase. Death related to pulmonary fibrosis occurred late and was associated with the elimination phase. 2. Pharmacokinetic analysis of urine paraquat excretion confirmed the biphasic decline of paraquat. Moreover, renal paraquat and creatinine clearances were not correlated but renal paraquat clearance was never higher than the renal creatinine clearance. 3. Tissue paraquat distribution was ubiquitous with an apparent volume of distribution ranging from 1.2 to 1.6 l/kg. Muscle could represent an important reservoir explaining the long persistence of paraquat in plasma and urine for several weeks or months after poisoning.
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PMID:Toxicokinetics of paraquat in humans. 232 51

A pig grower ration containing olaquindox at a concentration of 778 mg/kg was accidentally fed to 10 respectively 16 weeks old weaner pigs. The subsequent intoxication was characterized by poor growth and long-term disturbances of renal function and electrolyte metabolism. A deficiency of aldosterone, produced by a selective degeneration of the arcuate zone of the adrenal cortex, is probably the cause of the hyponatremia, hyperkalemia and hemoconcentration observed. Simultaneously plasma levels of urea and creatinine were elevated five- to eightfold. Due to hyperkalemia episodes with collapse, paralysis and severe electrocardiographic changes occurred several times. Two pigs died in the course of such attacks. Individuals, which transiently showed distinct clinical symptoms of intoxication, did not show any signs of disease 15 or 18 weeks later. Therefore it may be assumed, that the lesions of the adrenals, heart and skeletal muscle caused by olaquindox intoxication are reversible in some cases.
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PMID:[Clinical and hematological changes after olaquindox poisoning in fattening pigs]. 251 27

Since human acute renal failure (ARF) is frequently the result of multiple rather than single insults, we used a combination of treatments to induce ARF in rats. Uninephrectomized, salt-depleted rats injected with indomethacin developed ARF after administration of radiocontrast. After 24 h, the plasma creatine rose from 103 +/- 3 to 211 +/- 22 mumol/liter (mean +/- SE) and the creatinine clearance dropped from 0.7 +/- 0.1 to 0.2 +/- 0.04 ml/min (P less than 0.001). Severe injury was confined to the outer medulla and comprised necrosis of medullary thick ascending limbs (mTALs), tubular collapse, and casts. Other nephron segments were free of damage except for the proximal convoluted tubules which showed vacuole formation originating from lateral limiting membranes that resembled changes reported in human contrast nephropathy. Cell damage to mTALs included mitochondrial swelling, nuclear pyknosis, and cytoplasmic disruption with superimposed calcification; these changes were most severe in the deepest areas of the outer medulla, away from vasa recta in zones remote from oxygen supply. The fraction of mTALs with severe damage was 30 +/- 7% (range 2-68) and the extent of injury was correlated with a rise in plasma creatinine (r = 0.8, P less than 0.001). Thus, the nature of mTAL injury was similar to the selective lesions observed in isolated kidneys perfused with cell-free medium and was shown to derive from an imbalance between high oxygen demand by actively transporting mTALs and the meager oxygen supply to the renal medulla. Combined multiple renal insults in the rat produce ARF that resembles the clinical syndrome of contrast nephropathy and is characterized by selective mTAL injury conditioned by medullary hypoxia.
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PMID:Acute renal failure with selective medullary injury in the rat. 340 11

Adult female Wistar rats were injected with 1 mg/kg body weight of uranyl nitrate (UN). Evaluation of renal function, histopathology studies, and determination of plasma erythropoietin (Ep) titers after exposure to 456 mb for 16 h were performed at 1, 2, 7, 10, 15, and 21 days after drug injection. Plasma urea and creatinine concentrations markedly increased during the first seven days after injection, reaching maximal values on day 7 and decreasing thereafter. Significant increases in urine volume and significant depressions in urine osmolality also were observed; both alterations were most marked on day 7 after injection. A coagulative necrosis of the epithelium of proximal convoluted tubules, desquamation of the necrotic cells, and dilation or collapse of the tubular lumen were observed; the lesions were more marked on day 7. Plasma Ep levels in UN-treated rats exposed to hypobaria were markedly lower than in noninjected controls similarly exposed. Measurements were performed one, two, and seven days after UN injection, with maximal depression observed on day 7. These observations indicate that there is a correlation between the extent of both tubule damage and degree of renal dysfunction and plasma Ep production during exposure to hypoxia in UN-treated rats. This suggests that the renal Ep component is derived primarily from tubular cells.
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PMID:Relationship between severity of renal damage and erythropoietin production in uranyl nitrate-induced acute renal failure. 369 9

The association of reflex sympathetic dystrophy in one or more extremities with vertebral crush fracture syndrome is reported in six cases. In two of them the reflex sympathetic dystrophy preceded the vertebral crush fractures. The 99mTc-methylene diphosphonate scintigraphy results of the skeletons of 42 consecutive patients suffering from vertebral collapse and of 30 matched controls without osteoporosis have been evaluated by three independent observers for abnormal uptakes in the extremities. An abnormal radioactive bone tracer uptake in the extremities has been observed in 15 osteoporotics (36%) and 8 controls (29%). In most cases, osteoporotics and controls, the abnormal uptake was of the zonal type in a localized area, probably reflecting bone remodeling due to localized degenerative changes. An abnormal uptake of the segmental type involving multiple joints and even multiple extremities, as seen in reflex sympathetic dystrophy, was observed in 7 patients of the osteoporotic group (17%) and in none of the control group (P less than 0.05). The patients with an abnormal segmental uptake were younger and had a significantly higher mean 24 h calcium:creatinine ratio as well as a higher urinary hydroxyproline excretion. These observations and results suggest that in some cases of idiopathic osteoporosis there might be a relation between reflex sympathetic dystrophy and vertebral crush fracture syndrome, the vertebral crush fracture syndrome being the axial type of reflex sympathetic dystrophy.
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PMID:Vertebral crush fracture syndrome and reflex sympathetic dystrophy. 371 88


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