Development and application of a radioimmunoassay to detect interleukin-1 in rat peripheral circulation. We describe the development and application of a radioimmunoassay to detect circulating interleukin (IL)-1 beta concentrations in the rat. No IL-1 immunoreactivity above the detection limit of the assay (100 pg/ml) could be detected in plasma of control rats. In contrast, immunoreactive IL-1 was detected after intravenous administration of rat recombinant IL-1 beta (rrIL-1 beta) or bacterial lipopolysaccharide (LPS) to rats. The effect of LPS on plasma immunoreactive IL-1 concentrations was time and dose dependent. The immunoreactive IL-1 response to LPS was prevented by in vivo macrophage depletion induced by liposome-directed macrophage suicide technique. Gel filtration of plasma from LPS-treated rats revealed the presence of a high and a smaller molecular form of immunoreactive IL-1. The small molecular immunoreactive IL-1 peak coeluted with rrIL-1 beta and probably represents the 17-kDa form of IL-1 beta. In conclusion, our data support the hypothesis that IL-1 secreted by macrophages can act as a humoral signal molecule to induce the immunological, metabolic, and neuroendocrine changes in response to bacterial LPS.


Chronic infusion of TNF-alpha reduces plasma T4 binding without affecting pituitary-thyroid activity in rats. In the present study the effects of continuous administration of tumor necrosis factor-alpha (TNF-alpha), in a dose not affecting body temperature and food intake, on pituitary-thyroid function of rats were investigated. Male rats, bearing a venous catheter to allow repeated blood sampling, were intraperitoneally equipped with osmotic minipumps that continuously delivered recombinant human TNF-alpha (8.0 micrograms/day ip) or saline for 7 days. Infusion of TNF-alpha resulted in a significant decrease of plasma total thyroxine (T4) levels during days 2-5 of infusion as compared with the levels in saline-infused rats. This suppression of plasma T4 concentrations was caused by a decreased binding of T4 in plasma, as indicated by an increased percentage of free T4. TNF-alpha infusion did not significantly affect free T4 levels in plasma nor basal and thyrotropin-releasing hormone-stimulated TSH levels. The decreased binding of T4 was, at least partially, caused by a reduction of T4-binding prealbumin (TBPA) levels in plasma, which were significantly reduced during the first 3 days of TNF-alpha infusion. Plasma levels of free fatty acids were not affected by TNF-alpha. TNF-alpha treatment did not influence the plasma 3,5,3'-triiodothyronine (T3)-to-T4 ratio nor hepatic 5'-deiodinase activity. Plasma reverse T3 levels remained undetectable both in control and TNF-alpha-treated rats. Taken together, our findings indicate that chronic infusion of rats with TNF-alpha in a subpyrogenic and subanorectic dose induces a transient decrease of plasma T4 binding without affecting pituitary-thyroid activity and peripheral thyroid hormone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)


Dose-dependent effects of aluminum on osteocalcin synthesis in osteoblast-like ROS 17/2 cells in culture. This in vitro study evaluates the effect of aluminum (Al3+) on osteocalcin, a small protein that is produced by the osteoblast. After stimulation with various doses of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3; 10(-11) to 10(-9) M], osteocalcin was consistently lower in the culture medium of ROS 17/2 osteoblastic cells conditioned with 5 microM Al(3+)-saturated transferrin (AlTR) than in apotransferrin (ApoTR)-treated controls. In a second experiment, cultures were conditioned with various doses of AlTR or ApoTR (1.6-8.0 microM) and stimulated with 10(-9) M 1,25(OH)2D3. High doses of AlTR (4.8-8.0 microM) resulted in lower medium and unchanged intracellular content of osteocalcin than treatment with equal amounts of ApoTR. However, in the same experiment, lower doses of AlTR or ApoTR (1.6 and 3.2 microM) yielded different results, i.e., increased medium and intracellular contents of osteocalcin in the Al(3+)-treated cells. Expression of osteocalcin mRNA was not altered in cultures conditioned with low (1.6 microM) or high (8.0 microM) concentrations of AlTR or ApoTR. Similarly, no effect of Al3+ was observed on total protein content, the rate of total protein synthesis, and the degradation of secreted osteocalcin in cultures conditioned with various doses of AlTR or ApoTR. These findings suggest that AlTR affects osteocalcin synthesis in a specific manner, without concomitant effects on the rate of total protein synthesis or on the rate of degradation of osteocalcin. This effect is dose dependent, i.e., low doses of AlTR stimulate and high doses suppress osteocalcin synthesis and/or secretion, and it appears to be posttranscriptional, since the expression of osteocalcin mRNA is not affected.


Effect of gender, body composition, and equilibration time on the 2H-to-18O dilution space ratio. Physiological sources of variation in the 2H-to-18O dilution space ratio (DSR) were examined in 34 males and 20 females (4-78 yr; 14.7-143.2 kg; 1.8-61.0% body fat). Dilution spaces were obtained by time 0 extrapolation of isotope washout over 10-14 days, and body composition was obtained by underwater weight (adults) or bioelectrical impedance (children). The mean DSR was 1.050 +/- 0.015 (range 1.029-1.111), significantly higher (P < 0.001) than the traditionally assumed value of 1.029 based on exchange over 4 h. Use of the value 1.029 causes a systematic 8% overestimate of energy expenditure from doubly labeled water, relative to use of the value 1.05. The DSR was not related to body composition or age but was significantly higher (P < 0.05) in males (1.052 +/- 0.016) than in females (1.044 +/- 0.012). This gender effect was not explained by differences in the number of exchangeable hydrogens in the body. We conclude 1) variation in the 2H-to-18O DSR is not explained by body composition but is influenced by the chemical availability of exchangeable hydrogens to undergo exchange; 2) because the DSR is not easily predicted, use of the observed dilution spaces are recommended; 3) if a fixed DSR is used, values of 1.044 and 1.052 are recommended in females and males, respectively.


Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. The apparent mineralocorticoid excess syndrome of patients ingesting large amounts of licorice or its derivatives is thought to be caused by the antagonism by these compounds of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). 11 beta-HSD inactivates cortisol and corticosterone, allowing the more abundantly produced glucocorticoids access to the mineralocorticoid receptor (MR) in the kidney, where they act as mineralocorticoids. We have found that the infusion of both glycyrrhizic acid, an active principle of licorice, and carbenoxolone, a synthetic analogue, into a lateral ventricle of the brain [intracerebroventricular (icv)] of a rat, at a dose less than that which has an effect when infused subcutaneously, produces hypertension. Furthermore, the hypertension produced by the oral administration of carbenoxolone or glycyrrhizic acid is blocked by the icv administration of RU 28318, an MR antagonist, at a dose below that which has an effect on blood pressure when infused subcutaneously. While the oral administration caused saline polydipsia and polyuria typical of chronic systemic mineralocorticoid excess, the icv licorice derivatives produced hypertension without affecting saline appetite. Sensitizing the rats to mineralocorticoid hypertension by renal mass reduction and increasing salt consumption was not necessary for the production of hypertension. These findings provide additional evidence for a central role in blood pressure control by mineralocorticoids that is distinct from their renal effects. They also suggest that more is involved in licorice-induced hypertension than only inhibition of 11 beta-HSD.


Effect of training on insulin-mediated glucose uptake in human muscle. During insulin stimulation whole body glucose uptake is increased in trained compared with untrained humans. However, it is not known which tissue is responsible. Seven young male subjects bicycle trained one leg for 10 wk at 70% of maximal O2 consumption (VO2max). Sixteen hours after last exercise bout, a three-step euglycemic hyperinsulinemic clamp (clamp 1) was performed (insulin levels, means +/- SE: 9 +/- 1, 53 +/- 3, 174 +/- 5, and 2,323 +/- 80 was microU/ml), with measurement of arteriovenous differences and blood flow in both legs. After 6 days of detraining subjects were restudied, having exercised the untrained leg 16 h before. VO2max for trained (T) and untrained (UT) legs was 52 +/- 2 vs. 44 +/- 2 ml.min-1.kg-1 (P < 0.05). In clamp 1 glucose uptake in T and UT legs was 1.0 +/- 0.2 vs. 0.5 +/- 0.1 mg.min-1.kg-1 (basal), 9.7 +/- 2.3 vs. 6.7 +/- 1.7 (P < 0.05) (step I), 19.2 +/- 2.8 vs. 14.3 +/- 2.0 (P < 0.05) (step II), and 22.8 +/- 2.3 vs. 18.6 +/- 2.2 (P < 0.05) (step III). During insulin infusion lactate release (P < 0.05) [8.9 +/- 1.8 vs. 2.9 +/- 0.9 mumol.min-1.kg-1 (step I), 24.6 +/- 3.1 vs. 12.5 +/- 2.6 (step III)] and glycogen storage (P < 0.1) calculated by indirect calorimetry [6.7 +/- 2.3 vs. 5.0 +/- 1.7 mg.min-1.kg-1 (step I), 16.8 +/- 2.1 vs. 14.1 +/- 1.8 (step III)] were always higher in T than in UT legs. Release of glycerol, free fatty acids, and tyrosine and clearance of insulin were not influenced by training. Insulin-mediated glucose uptake was not increased after detraining or a single bout of exercise. In conclusion, training increases sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle by local mechanisms. Glycolysis and glycogen storage are equally enhanced. The training effect represents a genuine adaptation to repeated exercise but is short lived. Insulin clearance in muscle is not influenced by training.


A reexamination of the effect of exercise on rate of muscle protein degradation. The purpose of this study was to examine the effect of exercise on the rate of protein degradation in rat skeletal muscle. The rates of total and myofibrillar protein degradation were determined by the measurement of the rates of release of tyrosine and 3-methylhistidine, respectively, from the perfused single rat leg. This method measures the rate of protein degradation in the entire lower leg and does not suffer from the limitations inherent in methods that rely on urinary excretion. The rate of total protein degradation was increased by exercise and involved increased flux through the lysosomal pathway, while the breakdown of myofibrillar protein was unchanged. The changes in the rates of protein degradation during the recovery period were greatly influenced by energy intake. Again the rate of myofibrillar protein degradation was unchanged or slightly increased during the recovery period, after either level or downgrade running. Exercise did prevent the increase in the rate of total protein degradation caused by food restriction, which may have important implications in weight reduction diets.


Metabolic acidosis reverses the increase in serum 1,25(OH)2D in phosphorus-restricted normal men. We tested the hypothesis that in humans, metabolic acidosis can disorder the metabolism of 1,25-dihydroxyvitamin D [1,25(OH)2D] by impairing the capacity for a sustained physiological stimulus to increase renal production of this hormone. Specifically, in seven healthy men in whom restriction of dietary phosphorus had doubled their serum concentration of 1,25(OH)2D, we induced metabolic acidosis of moderate severity with oral NH4Cl, administered for 7 days. With induction of acidosis, the serum concentration of 1,25(OH)2D decreased sharply and remained decreased and near constant throughout the period of acidosis, the decrease amounting to one-half of the increment induced by phosphorus restriction alone. The serum concentration of free 1,25(OH)2D also decreased, since the measured free fraction of 1,25(OH)2D was unaffected by NH4Cl. The decrease in serum 1,25(OH)2D was accounted for by a 16% increase in its metabolic clearance rate and by a 19% decrease in its production rate. Metabolic acidosis induced a modest increase in the concentrations of blood ionized calcium and serum phosphorus. Multiple linear regression analysis revealed that serum levels of 1,25(OH)2D varied inversely and significantly with those of plasma hydrogen ion (R = -0.77, P < 0.001), but not with those of blood ionized calcium or serum phosphorus. These data demonstrate in humans that metabolic acidosis can substantially reverse the increase in serum concentration of 1,25(OH)2D induced by phosphorus restriction. The data provide evidence that acidosis can restrict the increase in renal production and serum concentration of 1,25(OH)2D effected by a sustained physiological stimulus.


Regulation of electrolyte and fluid secretion in salivary acinar cells. The primary secretion from exocrine gland cells is a fluid rich in Na+ and Cl- with a plasmalike ionic composition. Activation of specific receptors on the plasma membrane by hormones and neurotransmitters, which leads to activation of the phosphoinositol metabolism, results in release of Ca2+ from internal Ca2+ stores. Intracellular free Ca2+ concentration ([Ca2+]i) then rises simultaneously at both the basolateral and luminal parts of the acinar cell, reaching maximum values within 1 s after stimulation. In parotid acinar cells, increased [Ca2+]i activates the opening of maxi K+ channels located on the basolateral membrane and Cl- channels presumably located on the luminal membrane, resulting in rapid loss of K+ and Cl- and water and cell shrinkage. Extracellular electroneutrality is maintained by a paracellular Na+ flux into the lumen. Because of the simultaneous activation of K+ and Cl- channels, secretion occurs at a virtually constant membrane potential of about -60 mV. After maximal muscarinic cholinergic stimulation, loss of K+, Cl-, and water results in an approximate 25% reduction in cell volume within 10-15 s after receptor activation. Concomitant with loss of Cl-, there is a loss of HCO3- from the cell, causing a decrease in intracellular pH of 0.1 pH units because of the carbonic anhydrase-mediated conversion of CO2 into H+ and HCO3-. H+ generated from the metabolism and HCO3- production is compensated for by extrusion of H+ by a Na(+)-H+ exchange mechanism, which is responsible for approximately 75% of net Na+ gain that occurs after stimulation. Increased [Na+]i activates the Na(+)-K+ pump, which in turn extrudes Na+ from the cells. In both the unstimulated and stimulated states, cellular production of HCO3- can drive a net uptake of Cl- via the Cl(-)-HCO3- exchange mechanism operating in parallel with the Na(+)-H+ exchanger. The operation of the Cl(-)-HCO3- exchanger is, together with a Na(+)-K(+)-2Cl- cotransport system, essential for maintainance of a high [Cl-]i both in the unstimulated state and during Cl- reuptake.


Actions of 5-hydroxytryptamine on myenteric neurons in guinea pig gastric antrum. Intracellular recording methods were used to study the actions of 5-hydroxytryptamine (5-HT) on 257 myenteric neurons in the guinea pig gastric antrum. Application of 5-HT caused three types of postsynaptic responses. A fast-activating depolarizing response was accompanied by a decreased input resistance and desensitized quickly to repeated applications. It was mediated by a 5-HT3 receptor. A slowly activating depolarization, accompanied by an increase in the input resistance and enhancement of the excitability, was mainly observed in after hyperpolarizing/type 2 neurons. It was suppressed by the prokinetic benzamide compound renzapride, while classical 5-HT1-4 receptor antagonists had no effect, suggesting the involvement of a 5-HT1p receptor as described in small intestinal neurons. A long-lasting hyperpolarizing response, accompanied by a decreased input resistance, was observed in a small subset of neurons. This response seemed to be mediated by a 5-HT1a receptor. Superfusion of 5-HT caused a dose-dependent inhibition of the stimulus-evoked nicotinic cholinergic fast excitatory postsynaptic potential (EPSP), which was mediated by a presynaptic 5-HT1a receptor. 5-HT also presynaptically inhibited the slow EPSP.


Neuroimmune interactions: role for cholinergic neurons in intestinal anaphylaxis. The role of cholinergic neurons in mediating chloride secretion in anaphylaxis was assessed in muscle-stripped segments of distal colon from guinea pigs immunized to bovine milk. beta-Lactoglobulin evoked a concentration-dependent increase in short-circuit current (Isc) in immune, but not nonimmune, tissues. The Isc response to beta-lactoglobulin was reduced by piroxicam, pyrilamine, and cimetidine. Tetrodotoxin and atropine reduced the Isc response to beta-lactoglobulin in immune animals, whereas mecamylamine and ICS 205-930 were ineffective. beta-Lactoglobulin evoked a concentration-dependent increase in acetylcholine (ACh) release in immune, but not nonimmune, animals. In immune tissues after challenge with beta-lactoglobulin, ACh release paralleled the change in Isc. Piroxicam, cimetidine plus pyrilamine, or a combination of piroxicam, cimetidine, and pyrilamine significantly reduced the release of ACh after beta-lactoglobulin challenge. Histamine, dimaprit, and prostaglandins E2 evoked an increase in ACh release. These results suggest that beta-lactoglobulin releases prostaglandins and histamine probably from mast cells. Secretory responses that occur when immune animals are challenged with beta-lactoglobulin result, in part, from activation of cholinergic neurons that utilize muscarinic synapses for transfer of signals to the epithelium.


Spatial analysis of transcriptional activation in fetal rat jejunal and ileal gut epithelium. In the week before birth (days 15-21 of the 22-day gestation period), the fetal rat small intestinal epithelium undergoes rapid proliferation and differentiation. The developing gut changes from a mesenchymal tube lined by endoderm to a complex absorptive surface composed of differentiated epithelium overlying nascent villi. To begin to characterize the molecular events that take place in nascent intestinal epithelial cells as cytodifferentiation proceeds from jejunum to ileum, we examined spatial, temporal, and cellular patterns of transcriptional activation of the rat liver fatty acid-binding protein (L-FABP) and apolipoprotein (apo) AIV genes. In situ hybridization analyses revealed that transcription of both genes is activated in the jejunum between fetal days 17 and 18, yet their expression is not initiated in the ileum until 1-2 days later. Transcriptional activation proceeds in a "wavelike" fashion along the horizontal length of the gut and coincides with villus morphogenesis. As nascent villi emerge, heterogeneous cellular accumulation of L-FABP mRNA occurs in both fetal jejunal and ileal epithelium, but persists only in the ileum. In contrast, cellular expression of apo AIV mRNA in nascent epithelium is predominantly homogeneous in both regions of the gut. These results indicate that transcriptional activation in the fetal gut epithelium is a complex, dynamic process that is spatially regulated along the horizontal axis of the intestine. Initiation of transcription in enterocytes is closely linked to villus morphogenesis and histological cytodifferentiation.


Hepatic Na(+)-dicarboxylate cotransport: identification, characterization, and acinar localization. Rat liver perfusion studies suggest that the transport of alpha-ketoglutarate (KG) and related dicarboxylates exhibits acinar heterogeneity, in that the uptake and subsequent metabolism of these organic anions appears to occur predominantly in the perivenous region. However, the isolated perfused liver as an experimental model cannot distinguish intra-acinar differences in either the rate of solute uptake and/or efflux or intracellular binding and/or metabolism. Therefore, the driving forces and acinar localization of KG transport were examined using rat basolateral liver plasma membrane vesicles (blLPMV) isolated from control animals and animals treated 24 h before with selective perivenous and periportal toxins [carbon tetrachloride (CCl4) and allyl alcohol (AA), respectively]. In control blLPMV, [14C]KG uptake into an osmotically sensitive space was markedly stimulated by an inwardly directed Na+ gradient but not by inwardly directed gradients of other monovalent cations. The Na+ ionophore, gramicidin, had a small but significant inhibitory effect on Na(+)-dependent KG uptake, demonstrating that KG uptake was not the result of an intravesicular positive Na+ diffusion potential. The protonophore, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, had no effect on Na+ gradient-driven KG uptake, indicating that KG uptake was not the indirect result of coordinated activities of Na-H and KG-OH exchange. Na+ gradient-driven KG uptake was electrogenic (occurring with the net transfer of positive charge), and cis-inhibited by other tricarboxylic acid cycle intermediates, including succinate, fumarate, and malate and by citrate, but not by the dicarboxylates oxalate and malonate nor by glutamate and taurocholate (TC).(ABSTRACT TRUNCATED AT 250 WORDS)


Modulation of cat antral slow waves by ion substitution, Ca2+ and K+ channel blockade, and ACh stimulation. Two distinct slow waves can be recorded from smooth muscle cells on the submucosal border (submucosal cells) and the myenteric border (myenteric cells) in the circular layer of the cat antrum. The present studies examined the effects of decreasing extracellular Na+ ([Na+]o) or Ca2+ concentration ([Ca2+]o), Ca2+ and K+ channel blockade, and acetylcholine (ACh) stimulation on "submucosal" and "myenteric" slow waves using intracellular recording techniques. Decreasing [Na+]o (30 mM) reduced the upstroke depolarization of slow waves from submucosal cells but had no effect on the upstroke depolarization of myenteric cells. Decreasing [Ca2+]o (0.5 mM) decreased the upstroke depolarization in cells from each area. Neither cadmium (200 microM) nor nifedipine (100 microM) had any effect on the upstroke depolarizations from both submucosal and myenteric slow waves. In contrast, nickel (5 mM), a nonselective Ca2+ channel blocker, decreased the upstroke depolarizations of slow waves from submucosal and myenteric cells. Slow waves from myenteric cells normally exhibit a plateau phase of several seconds duration. The amplitude of the plateau potential could be decreased by lowering [Na+]o or [Ca2+]o or by nickel, cadmium or nifedipine. In the presence of 30 mM Na+ slow waves from submucosal cells appeared to develop plateau potentials. K+ channel blockade with tetrabutylammonium (TBA, 5 mM) or cesium (10 mM) increased the upstroke depolarization and delayed membrane repolarization in slow waves from submucosal cells. TBA and cesium also increased the upstroke depolarization from myenteric cells but did not delay membrane repolarization. ACh (1 and 3 microM) caused the generation of plateau potentials in slow waves from submucosal cells and increased slow-wave duration.(ABSTRACT TRUNCATED AT 250 WORDS)


Patterns of electrical activity and neural responses in canine proximal duodenum. The patterns of electrical activity and neural inputs to the proximal duodenum between the pyloric sphincter and the sphincter of Oddi were studied in muscles of the dog. Smooth muscle cells in the most proximal region were electrically quiescent, but slow waves were recorded in all regions distal to the first few millimeters. Electrical activity was recorded from circular muscle cells near the myenteric and submucosal surfaces of the circular layer, and slow wave activity was similar in both regions. The nature of neural inputs was also characterized. With electrical field stimulation, responses in cells near the submucosal surface were predominantly excitatory junction potentials (EJPs); near the myenteric border responses were either inhibitory junction potentials (IJPs) or biphasic responses (i.e., small EJPs followed by IJPs). EJPs were blocked by atropine. IJPs were nonadrenergic and noncholinergic (NANC), and several experiments suggested that nitric oxide (NO), or a NO-releasing compound, serves as the inhibitory neurotransmitter in this region. Exogenous NO caused hyperpolarization of membrane potential. IJPs and the hyperpolarization response to NO were sensitive to apamin. These data describe the myogenic mechanisms and neurogenic apparatus that appear to regulate motility in the most proximal region of the duodenum.


Differential effects of ATP-MgCl2 on portal and hepatic arterial blood flow after hemorrhage and resuscitation. Although ATP-MgCl2 administration after hemorrhage and resuscitation restores the decreased hepatic blood flow, it is not known whether this is due to the increase in portal blood flow or hepatic arterial blood flow. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal shed blood volume was returned in the form of Ringer lactate (RL). The animals were resuscitated with four times the volume of the shed blood with RL, during and after which ATP-MgCl2 (50 mumol/kg body wt) or an equal volume of normal saline was infused intravenously over 95 min. Cardiac output and organ blood flow were determined by 85Sr-labeled microspheres at 90 min after the completion of resuscitation. The results indicate that portal blood flow and total hepatic blood flow decreased significantly after hemorrhage and resuscitation. ATP-MgCl2 treatment, however, restored these parameters to sham values. In contrast, hepatic arterial blood flow did not change significantly after either hemorrhage and resuscitation or ATP-MgCl2 infusion. Moreover, the depressed cardiac output was normalized and coronary blood flow was higher than shams after ATP-MgCl2 treatment. Unlike small intestinal blood flow, blood flows to the stomach, spleen, pancreas, mesentery, and cecum were not markedly affected with ATP-MgCl2 infusion. Thus the restoration of hepatic blood flow with ATP-MgCl2 treatment under such conditions is due to the increased portal blood flow, i.e., solely due to the increased small intestinal blood flow.


Osmolarity reduction transiently increases K+ conductance of confluent rat hepatocytes in primary culture. Rat hepatocytes in confluent primary cultures were impaled with conventional microelectrodes. Reducing extracellular osmolarity by 80 mosmol/l leads to a transient hyperpolarization of cell membranes (maximum after 5 min) from -40 +/- 4 to -51 +/- 2 mV (n = 7). This hyperpolarization is blocked by 1 mmol/l Ba2+ and 0.5 mmol/l quinine. In ion substitution experiments, increasing K+ 10-fold (from 2.7 to 27 mmol/l) depolarizes membrane voltage by 9 +/- 2 mV in normosmotic solutions. In hyposmotic solutions this depolarization is increased to 20 +/- 1 mV at the time of maximum hyperpolarization and decreases thereafter to 8 +/- 2 mV (n = 4). Cable analysis reveals a transient decrease of specific membrane resistance that exactly parallels the increase in membrane voltage response to high K+. In addition, electrical coupling between cells continuously decreases under hyposmotic conditions, indicating that intercellular communication is affected. Reducing Cl- 100-fold (from 116.5 to 1.2 mmol/l; HCO(3-)-free solutions) depolarizes hepatocytes by 24 +/- 3 mV under normosmotic conditions. In hyposmotic solutions, this effect is increased to 39 +/- 4 mV at maximum hyperpolarization and decreases again to 26 +/- 3 mV (n = 8). This transient increase in the voltage response to Cl- removal is abolished by 0.5 mmol/l quinine (n = 5) and 1 mmol/l Ba2+ (n = 5), suggesting that it is indirect via changes in K+ conductance. This concept is corroborated by ion substitution experiments (HCO(3-)-free conditions), which show that under hyposmotic conditions voltage response to high K+ is considerably decreased in low Cl- solutions.(ABSTRACT TRUNCATED AT 250 WORDS)


Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats. Aspirin, one of the most widely used drugs in the world, consistently produces gastric mucosal injury, but the pathogenic mechanisms are incompletely understood. The present study was designed to determine the role of neutrophils in aspirin-induced acute gastric mucosal injury. Gastric mucosal lesions induced by acidified aspirin (300 mg/kg) were completely prevented in rats that had been rendered profoundly neutropenic by anti-neutrophil serum. Aspirin-induced acute gastric mucosal lesions were also significantly, albeit incompletely, reduced in rats that had been rendered moderately neutropenic by methotrexate. Moreover, in the methotrexate-induced neutropenia model, the neutropenia-associated mucosal protection against aspirin-induced injury could be reversed by leucovorin rescue. Aspirin caused a marked and statistically significant reduction in gastric mucosal 6-ketoprostaglandin F1 alpha synthesis, but no significant changes in gastric mucosal leukotriene synthesis. Thus no gastric mucosal lesions were observed in profoundly neutropenic rats that were treated with aspirin, despite the marked inhibition of prostaglandin synthesis. These findings demonstrate that aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process.


Uptake and metabolism of circulating fatty acids by rat intestine. The present study was designed to investigate the uptake and metabolism of circulating fatty acids by the intestinal mucosa in rats actively absorbing glyceryl trioleate given intraduodenally to determine the plasma fatty acid contribution to mucosal triacylglycerol. Rats with duodenal, femoral vein, carotid artery, and mesenteric lymph duct cannulas were used. [3H]oleate was constantly infused into the femoral vein while glyceryl trioleate was infused into the duodenum (135 mumol/h). After 5 h of infusion, a mass and radioactive steady state existed in the plasma and mucosa. At 6 h of infusion, the plasma oleate specific activity was sixfold greater than mucosal oleate and 50 times greater than mucosal triacylglycerol oleate; 86% of the mucosal oleate disintegrations/minute were in triacylglycerol. Chylomicron triacylglycerol oleate specific activity was less than that of the mucosa. Furthermore, the percentage of mucosal triacylglycerol acyl groups composed of oleate was greater than the percentage of oleate in mucosal free fatty acids. The data indicate that fatty acids are taken up by the mucosa during active fat absorption and metabolized primarily to triacylglycerols by the mucosa. The triacylglycerols in the mucosa synthesized from circulating fatty acids are selected against as a precursor of chylomicron triacylglycerol. The results support our previous hypothesis suggesting that the mucosa has at least two pools of neutral lipid (J. Lipid Res. 23: 1009-1019, 1982) and that steady-state conditions as performed here yield different results from previous work using bolus tracer injection techniques.


Serum complement mediates endotoxin-induced cysteinyl leukotriene formation in rats in vivo. To investigate potential mediators responsible for cysteinyl leukotriene formation during endotoxemia, male Fischer rats received an intravenous bolus injection of 5 mg/kg Salmonella enteritidis endotoxin and cysteinyl leukotrienes were measured by gas chromatography-mass spectrometry. The biliary excretion of leukotriene (LT) C4 (0.20 +/- 0.02 pmol.min-1.g liver-1) and N-acetyl-LTE4 (0.37 +/- 0.07 pmol.min-1.g-1) was increased by 190 and 1,000%, respectively, during the first 30 min after endotoxin injection. Endotoxin also caused a temporary reduction of hepatic ATP levels by 84%. Depletion of serum complement almost completely abolished the endotoxin-induced increase of cysteinyl leukotrienes in bile without affecting the biliary excretion mechanism. Intravenous injection of activated complement factors caused cysteinyl leukotriene formation and reduced the hepatic ATP content similar to endotoxin. Depletion of glutathione in the liver prevented cysteinyl leukotriene formation and the complement-induced ATP depletion. It is concluded that endotoxin-induced cysteinyl leukotriene generation in vivo is mediated predominantly through activation of complement. The vasoconstrictive cysteinyl leukotrienes are then responsible for ATP depletion in the liver.


L-glutamine with D-glucose stimulates oxidative metabolism and NaCl absorption in piglet jejunum. To explore the relationship between intestinal fluid absorption and oxidative metabolism, we measured the effects of amino acids and glucose on piglet jejunal ion transport and oxygen consumption (QO2) in vitro. Jejunal QO2 was stimulated by L-glutamine and D-glucose but not by the nonmetabolizable organic solutes methyl beta-D-glucoside or L-phenylalanine. QO2 was maximally enhanced by the combination of D-glucose and L-glutamine (5 mM). Even though 5 mM L-glutamine was previously found to be insufficient to stimulate NaCl absorption, 5 mM L-glutamine enhanced jejunal NaCl flux when combined with equimolar mucosal D-glucose. Either D-glucose or methyl beta-D-glucoside caused an increase in short-circuit current (Isc), an increase in Na+ absorption in excess of Isc, and a decrease in Cl- secretion, when L-glutamine was substituted for D-glucose (10 mM) on the serosal side. This relationship suggests that mucosal sugars, if combined with L-glutamine, enhance neutral NaCl absorption as well as electrogenic Na+ flow. (Aminooxy)acetate, an inhibitor of alanine aminotransferase, abolished the stimulation of QO2 and the NaCl-absorptive response to L-glutamine. We conclude that the oxidative metabolism fueled by L-glutamine is linked to a NaCl-absorptive mechanism in the intestine. We propose that the CO2 produced by glutamine metabolism yields carbonic acid, which dissociates to H+ and HCO3-, which may stimulate parallel antiports in the apical membrane.


Quantitative assessment of epithelial lining fluid in the lung. Current techniques for the measurement lung epithelial fluid (ELF) volume depend on the dilution by a known volume of wash fluid (bronchoalveolar lavage) of a resident solute, such as urea, in the ELF or of a foreign solute introduced at known concentration in the lavage fluid. Knowledge of the ELF volume allows calculation of solute ELF concentrations. Urea concentration in ELF is assumed to be the same as in plasma. Although epithelial permeability to urea is low, entry of urea from tissues to lavage fluid occurs during the procedure and may lead to erroneous estimates of ELF volume as may loss of foreign solutes. Ideally, the extent of urea entry or of foreign solute loss should be estimated in each lavage. Other cautions are 1) equal osmolality of wash fluid and plasma, 2) minimizing residence time of wash fluid, 3) minimizing wash fluid-to-ELF volume ratio, and 4) adequate analytic procedures.


Influence of extracellular matrix in tumor necrosis factor-induced increase in endothelial permeability. We examined the possibility that alterations of the extracellular matrix (ECM) contribute to the tumor necrosis factor-alpha (TNF-alpha)-induced increase in endothelial monolayer permeability. Endothelial permeability to 125I-labeled albumin was determined using bovine pulmonary microvessel endothelial cell (BPMVE) monolayers grown to confluence on microporous (0.8 microns diam) gelatin- and fibronectin-coated polycarbonate filters. Treatment of BPMVE with TNF-alpha (10(2) to 10(4) U/ml for 4-24 h) produced concentration- and time-dependent increases in endothelial permeability that paralleled the changes in morphology from cobblestone to elongated cells and the formation of prominent intercellular gaps and actin stress fibers. We examined the role of ECM in these changes using filters coated with ECM made by the BPMVE. Fresh BPMVE seeded onto filters coated with ECM produced by TNF-alpha-treated BPMVE had two- to threefold higher 125I-albumin permeability values than BPMVE monolayers seeded onto filters coated with ECM from control cells (P < 0.05). BPMVE seeded onto ECM from TNF-alpha-treated BPMVE also developed intercellular gaps and centralized actin filaments characteristic of the TNF-alpha-treated BPMVE. This effect was not attributable to TNF-alpha adsorbed to ECM. Polyacrylamide gel electrophoresis of ECM extracted from BPMVE treated with TNF-alpha showed decreased fibronectin. These findings suggest that the TNF-alpha-induced increase in endothelial permeability involves the loss of fibronectin and remodeling of the ECM. The increase in endothelial permeability may be secondary to decreased endothelial cell-ECM contacts resulting in elongation of cells and formation of intercellular gaps.


Platelets and a platelet-released factor enhance endothelial barrier. The role of platelets in the maintenance of endothelial barrier is examined in an in vitro model of the microvasculature. Human platelets (6,000/microliters) perfused through a cell column of endothelial-covered microcarriers decrease paracellular permeability of sodium fluorescein (mol wt 342) to 63% of baseline values. This effect is reversible and a second application and removal of platelets produces a similar response. This effect occurs within 5 min and reverses within 10 min after platelet removal. The reduction in permeability is not due to mechanical obstruction of endothelial junctions, since the number of recirculating platelets is not reduced and releasate from unstimulated 2-h platelet incubations also decreases permeability. Releasate from platelets stimulated with 0.1 U/ml of thrombin for 15 min have the same permeability reducing effect. In this system, the platelet factors serotonin (10(-3) M) and ADP (10(-4) M) have no effect on permeability. However, the platelet factors adenosine (10(-4) M), ATP (10(-5) M), and beta-agonists decrease permeability. None of these appear to account for platelet permeability activity, since activity is not blocked by agents directed against these mediators (adenosine deaminase, apyrase, 8-phenyltheophylline, or propranolol). The active factor(s) is stable at -20 degrees C, heat stable, sensitive to trypsin, and has an apparent molecular weight > 100. We conclude that unstimulated platelets release a factor(s) that enhances endothelial barrier in vitro and may be important in maintenance of the normal in vivo barrier.


Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea. The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.


Effect of an anti-Mo1 MAb on ozone-induced airway inflammation and airway hyperresponsiveness in dogs. Ozone inhalation causes neutrophil migration into the airway and airway hyperresponsiveness in dogs. The leukocyte adhesion molecule Mo1 (CD11b/CD18) is a heterodimeric glycoprotein the expression of which is necessary for neutrophil adhesion to endothelium. To evaluate the contribution of Mo1 to ozone-induced neutrophil influx and airway hyperresponsiveness, six dogs were treated intravenously with an Anti-Mo1 monoclonal antibody (3.75 mg/kg in normal saline) that binds to both human and canine Mo1, or the diluent alone, 1.5 h before inhaling ozone (3 ppm for 30 min), or dry air. Airway responses to doubling doses of inhaled acetylcholine (ACh) were measured before and after inhalation of ozone. Neutrophil influx was assessed by bronchoalveolar lavage (BAL) performed after the second ACh inhalation. Treatment with anti-Mo1 prevented the ozone-induced influx of neutrophils into BAL. After diluent and inhaled dry air, the neutrophil count in BAL was 1.49 +/- 1.26 (SE) x 10(4) (5.0% of total cells). After diluent and inhaled ozone, the neutrophil count increased to 7.27 +/- 3.22 (SE) x 10(4) (22.6% of total cells) (P < 0.05). After anti-Mo1 and inhaled ozone, the neutrophil count was 1.48 +/- 0.62 (SE) x 10(4) (8.5% of total cells). Treatment with anti-Mo1 also significantly reduced the number of eosinophils in BAL after ozone. Ozone-induced ACh airway hyperresponsiveness was not prevented by treatment with anti-Mo1. These results indicate that expression of Mo1 is necessary for ozone-induced neutrophil migration into the airway lumen.


Teaching medical physiology in Brazil.

Teaching medical physiology in Brazil. An analysis of physiology teaching in Brazil is carried out based on data collected from a questionnaire sent to 78 medical schools. It investigates faculty graduate degrees, time spent on teaching, audiovisual equipment available, evaluation of student performance, books in current use, and areas of research. Local results as compared with those from an international sample have shown a preference for lectures and that large departments are more concerned with research, but changes are underway to introduce computer simulations and modular instruction as a means to improve teaching.


Electroencephalography and evoked potentials: a PC-based analysis program for laboratory courses in physiology. A computer program (EEG Analysis) was developed for the preclinical laboratory course in physiology held for medical and dental students. It offers an off-line analysis of a set of typical and frequently occurring physiological and pathological electroencephalogram (EEG) and evoked potential (EP) recordings, which are stored in an IBM-compatible personal computer (PC) system. The users are requested to measure and analyze the data sets and to work through a base of questions relevant in the frame of the particular topic. The program is structured in several exercises: calibration, pickup of non-EEG signals (eye movements, chewing), waveforms in EEG recordings from awake subjects (alpha-waves, beta-waves), desynchronization of cerebral activity (visual activation, acoustic activation, mental activation), habituation of cerebral activity upon acoustic stimuli, EEG recordings from asleep subjects (different sleep stages, sleep-specific EEG signals), epileptic seizures, and EPs (principle of averaging, visually evoked potentials in different cortical areas). The program runs under MS-DOS and is network capable. The software structure ensures maximal flexibility for rapid changes and adaptations of the program to specific needs of a particular EEG course. The program has been used for three years, and the response from > 800 students has been consistently positive.


The use of Apple Macintosh computers and Hypercard in teaching physiology laboratories. A network of Apple Macintosh computers has been integrated into existing undergraduate physiology laboratories. Hypercard software programs replace the traditional laboratory handout; the text contains a number of buttons linked to cards that provide additional information on a particular subject. This additional information includes theory, the use of various instruments, expected results, and details on how to perform data analysis. This system of information layering allows students to work independently, at their own pace, and allows them to learn as much or as little as they consider necessary. Each computer is interfaced with a MacLab/4 data-acquisition unit, which permits the computer screen to display a four-channel chart recorder or a two-channel oscilloscope.


Project labs in physiology.

Project labs in physiology. Projects in which students design and carry out their own experiments can be a basis for physiology laboratories. A sequence of such projects is described and evaluated informally. It is argued that these inquiry-oriented project labs serve to motivate and teach students important concepts and attitudes about the nature of science and their ability to participate actively in it. Although physiology laboratories are a standard part of physiology courses, teachers are not always clear about the purposes of these activities. At least three categories of purpose seem important: the conceptual, the motivational, and the technical. As laboratories are being replaced in some cases by videodisc or computer simulations, it is important to see which purposes can be served by simulations and which cannot. Project-based laboratories, even more than standard laboratories, can serve the technical, motivational, and conceptual purposes for our laboratory teaching.


A faculty research and training program for undergraduates in the sciences. Faculty enthusiasm, with actual hands-on involvement, is a critical factor in establishing student research interest and excitement in a university or college science environment. Such faculty involvement is infectious to students and therefore key to restoring United States leadership in science and technology in the next decades. Most scientists acknowledge that they were initially attracted into scientific careers through one or two notable teachers who served as role models. However, with the introduction of so-called "big science" and its distraction of university faculty away from meaningful, direct student contacts, and with associated withdrawal of funding from "little science" in the college teacher's laboratory, research languishes in nearly all undergraduate teaching institutions. The inspiring college science teacher seems essentially gone, tired or burnt out, unable to keep pace with the rigorous demands of an active research lab while simultaneously meeting the exhausting load of 15-18 (or more) contact teaching hours per week. With all of the associated lecture preparations, student counseling, and Dean's committee assignments, the teacher has little or no scholarly "think time" or opportunity to inspire even the bright students. Without the teacher's honest and evident involvement and deep commitment, the student fails to experience the essential impact of a convincing role model. It is therefore necessary to restore the college science teacher's opportunity and aspirations to be personally involved in research. This can only be accomplished by providing time, facilities, incentives, and encouragement to do what originally attracted the teacher into a career in science and teaching in the first place.(ABSTRACT TRUNCATED AT 250 WORDS)


The Predictions Table: a tool for assessing students' knowledge. The Predictions Table (PT), a tool for determining students' knowledge, is described. The PT is a matrix consisting of a group of variables and a set of time periods. Students enter in the PT their qualitative predictions of the effects of a perturbation on a physiological system. The instructor or a teaching program can then evaluate the students' knowledge from these entries. An example is given from the teaching program CIRCSIM, which deals with blood pressure regulation. It shows the way that the program uses errors in the students' PT entries. CIRCSIM was evaluated and was found to have a statistically significant effect. It reduced the number of errors that students made in predicting the responses of the cardiovascular system to a perturbation. Also, students who worked in groups had significantly greater improvement than did control students. Using CIRCSIM also significantly reduces the number of relationship errors that the students make. They made even fewer errors when an instructor was present in the computer classroom while the students used CIRCSIM.


Use of computer-assisted courseware in teaching neuroscience: the Graphic Brain. We describe the development of a computer-assisted instructional tool for the neurosciences. Designed to run on readily available MS-DOS computers, the Graphic Brain utilizes computer-generated static and animated images and accompanying text to assist in instruction of neuroanatomy and neurophysiology. We have used the Graphic Brain in our medical neuroscience course and report that, as measured anecdotally and by test scores, it facilitates student comprehension of the space- and time-varying aspects of anatomy and physiology. When the Graphic Brain is used as an adjunct to lecture, we find that we can cover the same material in 75% of the time required using traditional methods.


Complex medical case histories as portals to medical practice and integrative, scientific thought. Complex clinicopathological conferences from the New England Journal of Medicine are used to introduce first-year medical and graduate students to scientific reasoning at the level of the whole organism and to help them mobilize and integrate the knowledge obtained in their previous studies. The approach involves outlining the etiology of the case history. This becomes a framework for thought allowing students to easily cope with the profusion of data. The method is cost effective: a single professor can interact with a large class, yet engage students on a one-to-one basis. It is a powerful adjunct to, but does not replace, lecture or small group activities such as problem-based learning. An annotated case history involving diabetes mellitus is provided.


Sensory adaptation: extracellular recording from locust wing hinge stretch receptor. Good student laboratory exercises that do not require much manipulative or technical expertise of the student and that have minor equipment demands are hard to find. One experiment that has these desirable characteristics is the description of adaptation of the firing frequency of the locust forewing stretch receptor after elevation of the wing. Unambiguous recordings of the activity of the stretch receptor can be made using a simple monopolar hook electrode inserted into the thoracic cavity of a decapitated locust. Elevation movements of the forewing are simple to perform and measure. The response of the stretch receptor as a function of time and the stimulus history is monitored. Within a relatively short time it is possible to collect enough data to characterize thoroughly the adequate stimulus of a single sensory neuron. There is considerable scope for student innovation, and several important concepts of sensory physiology can be discussed.


[Status of the oxygen transport system of hemoglobin in physiological pregnancy and pregnancy complicated by iron deficiency anemia]. The oxygen-binding properties of Hb molecule are unchanged in the third trimester of normal pregnancy and in pregnancy complicated by slight iron-deficiency anemia. Hb affinity to oxygen in whole blood is formed under the effect of the three main ligands H+, CO2, and 2,3-DPH. The development of hypocapnia in pregnant women results in elevation of pH values, reduction of pCO2, increase of intraerythrocytic 2,3-DPH concentration by 15-18%. Variously directed effects of H+, CO2, and 2,3-DPH on Hb affinity to O2 result in normal P50 values and therefore the Hb-O2 dissociation curve is not shifted to the right. Thus, in pregnant women with alkalosis 2,3-DPH effect on Hb affinity to oxygen completely eliminates H+ and CO2 effects but not compensates for Hb deficiency in the blood.


[Oxygen transport function of blood in late pregnancy toxemia in women with anemia]. The parameters of central hemodynamics and blood oxygen transport function were studied in 59 patients with anemia and late gestosis. The findings evidence that the status of central hemodynamics is mostly responsible for the oxygen supply. Marked reduction of the volumes of the stroke and cardiac ejection is observed with the gestosis augmentation. This may also be parallelled by an essential lowering of the effective and actual oxygen transport. Combined therapy of patients with late gestosis, suffering from anemia, aimed first of all, at liquidation of the peripheral arterial spasm and enhancement of cardiac productivity, is conducive to considerable improvement of oxygen transport.


[Acid-base equilibrium and blood gases in pregnant women with habitual abortion after metabolic therapy]. Blood oxygen transport, pH, acid-base status, urinary ketone level and urobilinogen were studied in 52 pregnant women in whom pregnancy ran a normal course and in 56 ones with a history of habitual abortions, treated for metabolic disorders. Signs of metabolic acidosis in the presence of respiratory alkalosis at the expense of pulmonary hyperventilation were detected in women with normal pregnancy. Follow-up of acid-base status and gases of blood, aciduria and ketonuria in pregnant women with a history of habitual abortions has revealed in them respiratory alkalosis signs presenting in hypoxemia and reduced oxygen saturation and ketonuria. Metabolic therapy included in combined therapeutic schemes for such patients actively influenced the processes of metabolic acidosis and ketonuria compensation, probably at the expense of its normalizing effect on intracellular metabolism. Metabolic therapy of pregnant women liable to spontaneous abortions, due to ovarian hypofunction had a marked antihypoxic effect, normalized the bicarbonate system status and was therefore conducive to improvement of oxygen transport to maternal tissues and the fetus.


[Endometrial Chlamydia infection in women with habitual abortion]. Endometrial, endocervical, and urethral specimens were obtained from 16 nonpregnant women with a history of habitual abortions. Chlamydia were isolated from the endometria of 4 women, but only in one case chlamydial intracytoplasmic incorporations in endometrial cells were detectable by the Romanovsky Giemza staining. Endometrial Chlamydia infection was diagnosed in 5 of the 16 patients. No Chlamydia were isolated from the cervix uteri or urethra of 2 patients with endometrial involvement. The study has demonstrated that eradication of intrauterine chlamydial infection before pregnancy improves the efficacy of treatment of habitual abortions. It is possible that asymptomatic chlamydial endometrial infection is injurious for the placenta.


[Study of fetal movements in normal spontaneous uterine activity and in its disorders by the end of pregnancy]. Parallel recording of spontaneous uterine activity and fetal movements, carried out in 102 pregnant women at the end of the third pregnancy trimester have shown a linear relationship between fetal movements and disorders of spontaneous uterine activity. The detected disorders permit a more objective assessment of fetal status and a timely start of corrective therapy.


[Immunologic aspects of the fetal growth retardation syndrome]. Serial measurements of allo- and autoimmune lymphocytotoxic antibodies (LCT-AB), circulating immune complexes (CIC) and heterophilic hemolysins were carried out over pregnancy weeks 24-40 in 63 pregnant women with small-for-date fetuses, 63 ones with other pregnancy complications, and in 15 ones with normal pregnancy. The mean allo- and auto-LCT-AB levels remained unchanged over the course of pregnancy and were virtually the same in all the examinees. CIC and heterophilic hemolysin levels were found growing in women with small-for-date fetuses starting from pregnancy week 28, as against the two reference groups. A direct relationship between abnormally high heterophilic hemolysin levels and blood rheology disorders could be traced. The incidence of unfavorable perinatal outcomes was increasing if heterophilic hemolysin levels surpassed 1.1 U optic density and the placenta was thin. These results permit considering the small-for-date fetus syndrome as a manifestation of immunity conflict in pregnancy.


[Morphological evaluation of fetal development after administration of Poterium sanguisorba for correction of fetoplacental circulation]. Polyphenol preparation of Poterium sanguisorba was tried for the treatment of experimental pregnancy abnormalities. The teratogenic and embryotoxic effects of the preparation administered in a dose of 0.75 LD50 were studied. The therapeutic doses of the drug are characterized by an immunostimulating effect on the mother and help correct the fetoplacental circulation and improve the fetal morphofunctional status.


[Ambulatory abortion, its advantages and economic effectiveness]. Presents data on abortions carried out by vacuum aspiration method in the earliest periods of unplanned pregnancy with the menses delay of up to 20 days in 622 women. The operation was performed in an outpatient setting. The incidence of immediate complications has made up 2.2%, late ones 4.13%; these values are much lower than after abortions during pregnancy weeks 6-12 (6.6 and 14.6%, respectively). The cost of such abortions, including the cost of treatment of late and immediate complications, makes up 9 rubles, whereas routine D&C costs 49 rubles. Vacuum aspiration abortion, carried out if menstrual bleeding is delayed by 16 to 20 days, is an effective, simple, and economic method of pregnancy discontinuation.


[A method of vacuum aspiration in early pregnancy in women with a history of severe gynecologic diseases]. Early (with the regular menstrual period absent for 6 to 20 days) artificial abortions were carried out in 61 women with a history of uterine myomas, cicatrix on the uterus, and developmental defects of the genitals. Analysis of early complications has shown that their incidence is virtually the same as in healthy women: 3.3%. Vacuum aspiration is an effective and safe method for early artificial abortions. A course of rehabilitation measures in the postoperative period reduces the incidence of early complications and is conducive to timely recovery of the normal cycle.


[Analysis of lochial acid-base equilibrium in an uncomplicated course of the postpartum period and in endometritis]. Lochial acid-base status was analyzed in 45 puerperants in whom the postpartum period ran an uncomplicated course or was complicated by endometritis. The normal course of the puerperium is associated with the development of metabolic acidosis in the uterine cavity, and this acidosis is completely compensated for at the expense of gas alkalosis. In slight endometritis metabolic acidosis augments, and grave endometritis is associated with the development of marked acidosis at the expense of the development of tissue hypoxia in the presence of metabolic acidosis.


[Structural changes in the endometrium of puerperae with high risk of development of endometritis in the postpartum period]. The endometrium of 72 puerperae referred to a high-risk group in respect of developing infectious complications was examined on days 3-18 of the puerperium. The periods of epithelialization and regeneration onset in abnormal course of the puerperium were detected, and the morphologic criteria of these processes specified. In cases with cesarean sections these processes started 2-3 days later than after spontaneous delivery. Bacteriologic examination of the uterine cavity contents is an indirect test for the detection of an infection; the final diagnosis may be made only after a comprehensive assessment of the endometrial status.


[Thymogen in the complex treatment of inflammatory diseases of the female genital system]. Thymogen, a new immunomodulating drug made in this country, was used in combined therapy of 46 patients with acute endomyometritis, exacerbations of chronic salpingo-oophoritis, purulent tubo-ovarian formations. Thymogen therapy was conducive to normalization of lymphocyte counts, absolute counts of T and B lymphocytes, increase of T lymphocyte functional activity. The drug is characterized by a desensitizing effect and induces no complications. Marked clinical effect recommends the immunomodulator thymogen for combined therapy of patients with inflammatory diseases of the uterus and its appendages.


[Prevention of hemorrhage in women with retroperitoneal pelvic tumors by embolization of the internal iliac arteries]. Presents data on the clinical course and surgical treatment of 26 patients with retroperitoneal tumors and hemangiomas of the pelvis. The diagnosis was confirmed by x-ray, echographic, computer tomographic, and angiographic data on pelvic vessels. To prevent bleedings, embolization of the internal iliac arteries and their branches as far as the 3-4th order was carried out in 9 patients with angiodysplasias and 4 with retroperitoneal pelvic tumors. Endovascular occlusion of the main vessels not only permitted surgery with the minimal blood loss, but was conducive to better visualization of the tissues and made the operation less traumatic.


[Diagnostic and surgical laparoscopy in polycystic ovary syndrome]. A total of 202 patients with polycystic ovaries were involved in examination. The study has distinguished the laparoscopic signs of polycystic ovaries: smooth glossy tightly stretched surface of the ovaries with a characteristic vascular pattern or loops; the presence of subcapsular cysts. Ovarian section shows small cysts with transparent or yellowish contents. The histologic signs are thickening of the protein coating, increased count of primary, secondary and cystic atretic follicles (by 2-5 times) and a lowered level of tertiary follicles. Clinical and hormonal signs include disordered rhythm of the menstrual cycle, stable anovulation, a high (over 2) LH/FSH index, an elevated T level. Laparoscopic resection of the ovaries to make their size normal is a method of choice among this technique, standard or wide ovarian biopsy.


[Prognostic possibilities in genital endometriosis]. A total of 64 patients with genital endometriosis were examined. The reference group included 120 phenotypically healthy women. The dermatoglyphic pattern of patients with genital endometriosis was defined, pointing to a genetic predisposition to genital endometriosis and reflecting the risk of its development. Together with other clinical and laboratory criteria, the dermatoglyphic studies permit an early diagnosis of endometriosis.


[Vestibular symptomatology and response to treatment with heterocyclic drugs]. Around 40 percent of the patients that we consult due to vertigo of a probable vestibular origin present an associated depressive syndrome. A study with patients with depressive symptoms and vestibular pathology of diverse aetiology in inactive phase is presented. Treatment using amitriptyline improves de evolutive prognosis of vestibular manifestations while observing a lower reappearance of symptomatology.


[Update of surgical criteria in thyroid pathology]. Review of an aleatory sample composed by 100 patients suffering some thyroid disorder, operated at ENT Department of the Hospital, during the last 5 years. Statistical evaluation of the significance and reliability of several parameters, clinical items, diagnostic tests and surgical judgements contrasted with the corresponding nowadays bibliography.


[Thyroglossal duct cysts].

[Thyroglossal duct cysts]. Perusal of records concerning 14 patients diagnosed and operated for Cysts of the thyrolingual duct, in the last 5 years (1984-1989). In this term the AA. have had at their disposal the newly diagnostic methods introduced at their Hospital. Among the clinic features considered in the paper, for instance, the age, they point out the differences verified between the own series and that of other authors. In the first decade only 28.57%; 35.71% in the second decade; and beyond 30 years again 35.71% of cases. Sixty-seven was de elder one. As well is emphasized the sexes distribution: 72% account for men and 28% for women, in the AA's statistics. None of the operated showed malignancies and postoperative recurrences were null.


[Surgical pathology of the parathyroid glands]. This paper deals on the experience, in the work's milieu of the AA., about the surgery of the parathyroid glands. After some considerations regarding the embryology, morphology, pathophysiology and symptomatology of the parathyroids and the causes of its surgical pathology, they describe the cases treated at their Department. Contribution with the results gained through the diagnostic methods used by them. Lastly compare the own experience with that of other surgeons, in the light of the bibliographical review of the subject done.


[Neck adenopathies in epidermoid carcinomas of the piriform sinus: a retrospective study and 5-year survival]. Retrospective survey done with 27 patients of epidermoid carcinoma of the piriform sinus in order to ascertain the degree of regional spread--both clinic and histologic--of the neoplasm and also set up the relation between the actual adenopathies, the rate of recurrences and the actuarial survival at 5 years post-treatment term. The checked results show the bad prognosis of such tumors irrespective of the most aggressive surgery (partial hemipharyngectomy plus total laryngectomy plus neck dissection and postoperative X-ray therapy). The actuarial survival accounts for 29.6 percent after 5 years. The AA. confirm a great lymphophile tendency with an invasion percentage amounting to 55.6 percent but with a certain clinic-histologic disagreement. Relation between the frequency of adenopathies (clinical and histological), the survival and the recurrences at 5 years is indicative to a great extent that adenopathies are a pejorative circumstance of these neoplasms.


[Metastatic parotid tumors. Review of 28 cases]. A series of 28 patients with tumors metastatic to the parotid gland are reported. The most frequent histologic types were squamous cell carcinoma and melanoma. Most primary tumors occurred in the head and neck. A review of similar cases published in the literature reveals the lack of uniform criteria for the appropriate therapeutic approach for metastatic parotid gland tumors.


[Pharyngostoma following total laryngectomy]. Prospective study following 32 total laryngectomees with the aim of compare the efficacy of the pharyngo-esophageal closure alternatively stiching with vicryl and catgut. The use of vicryl resulted in 31 percent pharyngocutaneous fistulae versus 61 percent with catgut.


[Cervical lymphangioma].

[Cervical lymphangioma]. Reporting a cervical Lymphangioma with satisfactory postoperative recovery. Bibliographic survey relating to the several approaches to diagnosis as well as schedules of treatment.


Vaginal reconstruction by skin grafts: a scanning electron microscopic evaluation. In order to evaluate the morphofunctional pattern of transplanted skin structural and ultrastructural studies on biopsies taken from surgically created neovaginae in three cases of vaginal agenesis were performed one and two years postoperatively. Two of the cases were associated with a rudimentary uterus, while the remaining one involved testicular feminization. Neovaginae were constructed by directly prolonging a pre-existing perineal introitus, to form a vesicorectal pouch, which was lined inside with gluteal skin autografts. All three patients reported satisfactory psychosexual behavior one year after operation. Light microscopy of the bioptic fragments demonstrated, even two years after surgery, features generally similar to those of the normal dermis and epidermis, and a keratinization rate as a rule, that did not range significantly from the norm. Scanning electron microscopy also confirmed the maturation of the cornified cells, since these were often seen to be desquamating and exhibited structures usually found in normal skin, such as double edges on the luminal surface--usually considered to be the morphological expression of squamous cell overlapping--and microwrinkles on disrupted apical and basal cytoplasmic flaps, which are considered reciprocal cell-gearing devices. Our results seem to indicate, therefore, that the transplanted skin, maintaining, on the whole, its integrity and viability despite an environment differing somewhat from the external one with regard to moisture, pH and temperature, shows a good adaptability, at least until the above mentioned time lapses.


Fine structure of the dorsal lingual epithelium of the crab-eating monkey, Macaca irus. Light and electron microscopic observations of the dorsal lingual epithelium of the crab-eating monkey, Macaca irus, revealed three different regions: the epithelium on the anterior side of the filiform papillae, the epithelium on the posterior side of the filiform papillae, and the interpapillar epithelium. Whereas the basal and suprabasal cells are similar throughout, differences characterize the intermediate and surface layers. Keratohyalin granules appear predominantly in the intermediate layer of the epithelium on the anterior side of filiform papillae. In the epithelium on the posterior side of the filiform papillae, no keratohyalin granules are seen and, instead, tonofibrils are prominent. The cells begin to be significantly flattened. In the interpapillar epithelium, no keratohyalin granules and tonofibrils are seen, and the tonofilaments occupy almost the entire cytoplasm of the cells of the intermediate and surface layers, with the cells having larger volumes in these layers.


Development of the chick tongue. A scanning electron microscopical investigation. With the aim of clarifying certain morphological aspects of lingual development, chick tongues between the 8th day of incubation and hatching and also during the early postincubation period were investigated by means of the Scanning Electron Microscope. During this time, the tongue anlage underwent some remarkable morphogenetic changes, mostly involving the superficial epithelium but also including the appearance of the lingual glands at the level of the lingual root. With regards to the epithelium, it was possible to observe that in the first days of the incubation period examined, the superficial cells appeared dome-shaped, with microvilli on the apical surface; later they tended to become more flattened, and the microvilli were replaced by a thick net of microplicae. During the final days of incubation, and after hatching desquamative phenomena became evident. At no site of the tongue rudiment were taste buds ever observed, possibly because of the different functional role played by the avian tongue in comparison with that of the mammals.


Ultrastructure and histochemical aspects of the oropharyngeal epithelium of Siren intermedia Le Conte. The present electron microscopical and histochemical study of the oropharyngeal epithelium (OEPI) in Siren intermedia describes its various differentiated and developing cell types and cell contents. The OEPI is multilayered; it consists of a basal layer, a middle cell layer and a pavement layer. Three cell types are found in the pavement layer: pavement cells (PC), goblet cells (GC), and mitochondria-rich cells (MRC). These originate from basal cells and mature in the middle cell layer. The MRC is equipped with a tubule system that seems to be responsible for gaseous exchange. MRC and GC probably appear only in the caudal portions of the oropharynx. Electron microscopically, the goblet cell type appears uniform, except for the production of secretory granules; rostrad, these are largely PAS-positive and occipitad alcianophilic. The production of mucin granules is lower in the PC, where they accumulate as loose aggregations in the cell apex. Their contents react strongly to alcian blue. Only electron-lucent (loose) mucosubstances are exocytosed; they form the apically-situated acidic mucous coat of the PC. The possible osmoregulatory function of these mucins is discussed in relation to the model suggested by Kirschner (1982, in Gomme 1984).


A preliminary study of craniofacial classification. Cephalographic evaluations often hinge on univariate statistical analyses of their component dimensions. These analyses generally depict a progressive increase in cephalometric form with age. Such analyses are, however, complicated by the varied inter-dimensional correlations. But when the cephalometric dimensions were combined together in cluster analysis, complex associations between various age groups were noted in the 1-18 year range. Such multivariate analyses revealed far more complex craniofacial age changes than traditionally envisaged. These data therefore indicated the need for further investigation of such "normocephalic gold standards" before their value in craniofacial evaluation can be established.


Collagen fibril ultrastructure alters after glycanolytic digestion. Fixed fragments of bovine nasal septum cartilage were digested for six hours either with testicular hyaluronidase or streptomyces hyaluronidase or flavobacter chondroitinase ABC, and observed with a transmission electron microscope. Collagen fibril diameters (D) were measured to evaluate the effect of enzymatic digestion on the fibril size. This resulted in an increased frequency (17% to 47%) of "thin" fibrils (80 to 32 nm), followed by a decrease (65% to 31%) of the frequency of "mid" fibrils (32 to 64 nm). The frequency of "thick" fibrils (over 64 nm) showed a moderate increase (18% to 22%). Considering the relationship between fibril diameter, fibril volume and collagen content, the apparently relevant increase in number of the "thin" fibrils corresponds to an alteration of only 4% of the total collagen. On the other hand the increase of the "thick" fibrils implies a conspicuous alteration of 20% of the total collagen. The observed fibril rearrangement after digestion may be explained in terms of the wrap of matrix proteoglycans around each fibril. The enzymatic removal of the proteoglycans could make "mid" collagen fibrils free to regress into "thin" as well as to merge together into "thick" fibrils.


[Non-invasive evaluation of venous obstruction. Reflux and function of the muscular mass of the calf with air plethysmography]. An study about the use of Air Plethysmography on venous occlusions is presented. Also, a comparison between Plethysmography and others non-invasive methods was made.


[Giant cervical angioma caused by "malignant" arteriovenous fistulae]. A case of angioma by malignant AV fistula (described by F. Martorell in 1970) is reported. Such kind of fistulas have usually a lethal course. The case reported underwent a surgical correction, and after a following of 10 years, no major complications have been reported.


[Importance of morphologic evaluation of carotid lesions in their correlation with cerebral ischemic pathology]. Authors present a review of 182 atheromatous plaques into the extracranial carotid trunks. Diagnosis of such pathologies were made by Eco-Doppler on 615 patients. Objective was to determinate the emboligen potential of the plaques following structural and functional criteria. Almost all the symptomatic plaques with functional disturbances showed some structural injury with emboligen potential. Two third parts of all the symptomatic diseases hemodynamically no-significant were associated with plaques with emboligen power. On stenosis higher than 70%, functional criterium was more important for study than structural criterium.


[Treatment of complications of in situ saphenous by-pass]. The early and late (2-12 months) complications of in situ bypass for 24 patients (limb salvage procedures) were presented. The early complications were: 1. Overlook branches of saphenous vein developed into A-V fistulas which religated (2 patients). 2. Graft occlusions (2 patients). A successful thrombectomy was carried out on one patient, while an above knee amputation was performed on the other patient. 3. A deep venous thrombosis (one being crural, the other femoral) was treated with medication therapy. We recorded late complications: two graft occlusions (after 3 and 6 months) where redo surgery was impossible for distal progression of occlusion disease. The following procedures must be done: per-operative angiography, adequate technique of anastomoses and defects of the femoral vein, postoperative application of medication therapy, observation of patients in the later post-operative period and routine control with Doppler US (1, 3, 6, 12 months).


Fibrinolytic enhancement in diabetic microangiopathy with defibrotide. Skin microcirculation was evaluated in 117 patients with diabetic microangiopathy over a period of six months. They were divided into two groups. Group 1 (64 patients) was treated with oral defibrotide, a new profibrinolytic drug, in association with diet and oral antidiabetic drugs. Group 2 (53 patients) was treated only with diet and antidiabetic agents. The microcirculation was studied by means of laser-Doppler flowmetry transcutaneous partial pressure of oxygen and carbon dioxide pressure measurements, and evaluation of capillary filtration. After six months, patients in group 1 improved their microcirculatory parameters in association with an improvement in signs and symptoms. Moreover, 30 patients in group 1 and 36 in group 2 were followed up for eighteen months, and the authors observed that the deterioration of the microcirculatory parameters was significantly slowed in diabetics treated with defibrotide. A decrease in plasma fibrinogen during defibrotide treatment was observed in all treated patients in association with an increased fibrinolytic activity. In conclusion, it appears that defibrotide, enhancing fibrinolysis, improved the microcirculation in diabetics, preventing further, progressive deterioration.


Effect of single oral administration of nilvadipine on cerebral blood flow in chronic cerebral infarction. The effect of nilvadipine, a newly developed calcium antagonist, on regional cerebral blood flow (rCBF) was investigated in 7 patients with chronic cerebral infarction. rCBF was measured by the 133Xenon inhalation method. Patients were given a single dose of 4 mg of nilvadipine after the first measurement of rCBF, and the second measurement was done one hour after the administration. All patients had hemiparesis and 2 of them had mild to moderate mental deterioration, but all patients could walk to the outpatient clinic by themselves. (1) rCBF of the affected side significantly increased by 22.7% after single oral administration of nilvadipine (p < 0.05). The increase of rCBF was significantly marked in frontal regions of the affected hemispheres. (2) No significant changes in blood pressure or end tidal partial pressure of carbon dioxide were observed during the examination. These results indicate that nilvadipine has a potent selective vasodilatory action on the cerebral arteries in patients with cerebral infarction.


[Inguinal pulsatile hematoma secondary to malignant melanoma invasion]. A case of an inguinal pulsatile hematoma, secondary to a malignant melanoma, is reported. Considerations about such type of diseases are made. Importance of anatomical Pathology is also noted.


Physical manipulation of subcutaneously implanted cardiac muscle in rat increased plasma atrial natriuretic peptide concentration. To examine the effects of physical stretch on cardiac muscle endocrine activity, the authors transplanted whole neonatal hearts subcutaneously into the back and the ears of the correspondent mother (n = 9). Seven days later, physical manipulation was applied on the implanted heart by stretching the skin and the subcutaneous tissue encasing the implanted cardiac muscle, for a period of five to ten minutes. Such manipulation was repeated approximately every seven days postoperatively for a total of two to four times for each rat. The plasma atrial natriuretic peptide (ANP) levels were measured by radioimmunoassay prior to and immediately following manipulation. Postmanipulation plasma ANP levels were found to increase from the premanipulation levels. At two weeks postimplant, the average increase was 290% with the highest single-specimen increase being nearly twelvefold. The increases observed at two and three weeks following implantation had Signed Rank Test p values of 0.015 and 0.042 respectively. The viability of the implanted hearts was confirmed by cell culture. Light microscopic immunocytochemistry detected ANP immunoreactivity in the implanted cardiocytes. The elevated plasma ANP concentration induced by the manipulation appeared to be correlated with the functional status of the implanted cardiocytes. (1) Subcutaneously transplanted neonatal myocardiocytes survived for at least three to four weeks while retaining the ability to produce ANP. (2) Physical manipulation of implanted heart induced ANP release. Therefore, cardiac ANP production and release is indeed stimulated by physical stretching.


[Hemodynamic evaluation of the patient with microvarices]. The present study included 21 lower limbs with micro varicosities, 56 lower limbs with retrograde flow-varicosities (positive Rivlin) and 35 health lower limbs. Technics used for diagnosis were: Doppler ultrasonography and strain gauge plethysmography. We found a higher incidence of valvular failure on the varicose patients with retrograde flow (showing changes on their viscoelastic features of their venous walls). On the contrary, patient with microvaricosities showed an hemodynamics similar to the healty patient: we did not found any difference on the variables analyzed between the two groups. We conclude that the presence of microvaricosities has no influence on the analyzed hemodynamic parametres.


Diagnosis of coronary artery disease with Tc 99m-methoxy isobutyl isonitrile and transesophageal pacing. Recently the use of a new radioactive agent with physical and biological properties more favorable than those of thallium 201, methoxy-isobutyl-isonitrile (MIBI) labeled with technetium 99m (Tc 99m), has permitted simultaneous performance of perfusion and function studies in ischemic cardiopathy. Transesophageal atrial pacing (TAP) technique has evolved as an alternative provocative test of ischemia. The authors compared the capability of Tc 99m-MIBI myocardial scintigraphy, combined with TAP, with that of Tc 99m-MIBI, combined with maximal stress test, in the diagnosis of ischemic cardiopathy. They studied 11 patients with a clinical history of angina pectoris. Myocardial scintigraphy was performed at rest, after stress test, and after TAP. Finally, all the patients underwent coronary angiography. The analysis of myocardial perfusion images on both Tc 99m-MIBI associated with TAP and with stress demonstrated, in 165 myocardial segments examined: 143 normal, 20 reversible defects, 2 irreversible defects. The concordance of localization between coronarographic data and scintigraphic reversible and irreversible defects was 85%. In conclusion TAP proves to be a valid and sensitive provocative test of ischemia when combined with myocardial scintigraphy and with Tc 99m-MIBI.


Hyperfibrinogenemia and hyperviscous plasma in hypertensive Africans. Changes in plasma fibrinogen concentrations (PFC) and relative plasma viscosity (RPV) were investigated in 61 Nigerian Africans while they were being treated for essential hypertension. The association of these hemorheologic variables with blood pressure was examined. An analogous study was done on 30 normotensive controls for comparison. The hypertensive patients had, overall, a significant increase in both PFC and RPV (p < 0.001) as compared with control values. However, 44.3% of the hypertensive patients had PFC and RPV values within the defined normal limits. This indicates that in a proportion of the hypertensives, treatment notwithstanding, PFC and RPV are altered only within the physiologic limits. Comparison of PFC and RPV with the degree of hypertension (mild: diastolic blood pressure (DBP) = 90mmHg; moderate: DBP = 91-99mmHg; severe: DBP > or = 100mmHg) showed significant stepwise increases at the moderate and severe levels as compared with the mild level of hypertension. The hyperfibrinogenemia and concomitant hyperviscous plasma observed in the present study could either play a role in the pathogenesis of the hypertension or be the consequence of the hypertension itself, at least in some patients.


[Various hemodynamic characteristics of the venous circulation of the lower limbs in the patient with recurrent varices]. The present study included a control group of 30 lower limbs without venous disease, a group of 30 lower limbs with primary varicosities and a group of 30 lower limbs with recidivant varicosities. Technics used for diagnosis were: Doppler ultrasonography and "strain-gauge" plethysmography. We found a relentisement of the venous flow on patients with recidivant varicosities. No differences on basal and maximal flow between primary and recidivant varicosities have been reported. It seems that no disturbances on the arterial flow are present. It seems also that patients with recidivant varicosities have no special incidence of valvular failure.


Critical degree of renal arterial stenosis that causes hypertension in dogs. The minimum degree of renal arterial stenosis needed to cause hypertension was identified by renal arterial angiography of anesthetized dogs. The effects of renal nerves and prostanoids on the critical stenosis were also examined. The left renal artery was constricted concentrically by a radiolucent constrictor device, and the stenosis of the artery was evaluated by cineangiography with the kidney either innervated or denervated. At this time, renal blood flow, renal perfusion pressure, and systemic blood pressure were serially monitored. In another group of dogs, renal venous and aortic blood samples were taken as the stenosis increased; these were assayed for prostaglandin E2 and plasma renin activity. The same experiments were done again after treatment with a cyclooxygenase inhibitor, aspirin DL-lysine (54 mg/kg). With the kidney either innervated or denervated, systemic blood pressure began to increase when the stenosis was more than 70% of the diameter of the renal artery; the renal blood flow decreased when the stenosis was more than 75% of the diameter. Aspirin treatment attenuated the increase in blood pressure but did not affect the autoregulation of the renal blood flow when stenosis was 70% or less. Prostaglandin E2 production increased in the stenotic kidney when the stenosis was more than 70%; aspirin inhibited prostaglandin synthesis and suppressed the stimulation of renin release. These results suggest that whether there is innervation or not, the critical degree of renal arterial stenosis that causes hypertension is more than about 70% of the diameter in the presence of renal prostaglandins; in their absence, the critical point above which hypertension occurs is 75% or more.


Skin blood flow and current perception in pentoxifylline-treated diabetic neuropathy. There are several anecdotal reports of improvement in diabetic sensory neuropathy following a course of pentoxifylline therapy. Pentoxifylline theoretically could improve skin blood flow, thus reducing ischemia at axonal endings. The authors used laser Doppler techniques to measure skin blood flow and measured sine wave current perception thresholds (CPTs) in pentoxifylline-treated diabetic patients with sensory neuropathy. Twenty-four patients completed a six-month course of treatment. These patients had a predominantly "stocking" neuropathy; all the major abnormalities on clinical, laser Doppler, and current perception testing were found on the lower extremity. Seventeen of the 24 patients reported symptomatic improvement. A careful, graded neurologic examination confirmed that improvement, with a decrease in symptom score on the lower extremity (SSDW) from a baseline of 5.0 +/- 0.7 to 3.5 +/- 0.7 (p < 0.01) and of physical score (PSDW) from baseline 22.0 +/- 2.0 to 16.0 +/- 1.9 (p < 0.01) after six months. On the lower extremity, there was an increase in laser Doppler measured flow score (FS) both at 35 degrees and at 44 degrees C. FSDW (35 degrees) increased from 10 +/- 2 to 14 +/- 3 at six months (p < 0.05). FSDW (44 degrees) increased from 58 +/- 5 to 77 +/- 7 at six months (p < 0.01). There was an improvement in sine wave current perception measured by current perception threshold score (TS). TSDW dropped from 150 +/- 32 to 84 +/- 28 at six months (p < 0.03). In patients with diabetic sensory neuropathy, pentoxifylline appears to improve skin blood flow. Current perception thresholds improve in tandem, corroborating improvement in clinical neurologic findings.(ABSTRACT TRUNCATED AT 250 WORDS)


Contemporary treatment of venous lower limb ulcers. The postphlebitic syndrome is a significant management problem that affects a large number of patients. Primary prophylaxis of deep-vein thrombophlebitis would reduce the risk of developing the postphlebitic syndrome and should be considered in high-risk patients. Patients who have had a phlebitis should be monitored with noninvasive tests of the deep venous circulation for the development of venous valve incompetence. Patients with venous hypertension should be placed in compression stockings to prevent the postphlebitic syndrome. In patients who progress to venous ulceration, several aggressive measures must be undertaken. Systemic treatment includes management of obesity, edema, immobility, poor nutrition, and comorbid illnesses. Some patients may require a short hospitalization of bed rest, lower limb elevation, and daily dressings and wound care. Outpatient therapy requires sustained compression of 35 to 40 mmHg at the ankle for many months to allow the ulcer to heal. The standard bandage material is Unna's boots, which is applied every one to two weeks by a trained nurse. Cadexomer iodide is an effective local treatment that helps debride the ulcer and accelerate healing. Finally, pentoxifylline therapy has also been shown to significantly improve the healing of venous ulcers.


[Airway involvement in the postoperative period of carotid endarterectomy. Report of a case]. We report a case of a fifty-seven year old man that was diagnosed a bilateral carotid disease and a carotid endarterectomy was practiced on him in the left carotid, and afterwards in a 12 day lapsus of time, the same was done in the right carotid. In the course of the immediate post-operative period, the patient presented a neck haematoma which required its removal and afterwards he developed a glottis oedema which called for the realisation of a tracheotomy in order to control the airway.


Venous occlusion secondary to subluxation of the shoulder--a case report. This is the case report of an eighty-seven-year-old woman who was seen because of swelling of her left upper extremity and breast of one week's duration. She had a history of severe arthritis of the knees and had been wheelchair-bound for seven years. Venography showed compression of the cephalic vein and thrombosis of the distal basilic vein with extension into the axillary and subclavian veins. To the author's knowledge, this is the first case report of venous thrombosis in association with subluxation of the shoulder.


Aortitis syndrome with fatal acute aortic regurgitation due to aortic dilatation and aortic valve perforation--a case report. This is a case report of a fifteen-year-old female with aortitis syndrome complicated by acute fatal aortic regurgitation due to the aortic valve perforation, as well as to aortic dilatation, which was confirmed by the autopsy. Aortic valve perforation was first recognized as the important cause of acute aortic regurgitation in the aortitis syndrome in this report.


Pacemaker malfunction due to subcutaneous emphysema--a case report. The authors describe a cas of pacemaker malfunction due to a critical increase of impedance resulting from air entrapment in the pacemaker pocket.


[Patient-controlled analgesia: effect of adding continuous infusion of morphine]. This double blind study aimed to assess the effects of a continuous intravenous (i.v.) infusion of morphine added to an intermittent bolus patient controlled analgesia on morphine demand and related side-effects. Patients scheduled for abdominal and thoracic surgery (ASA 2 or 3) were randomly allocated postoperatively to three groups (n = 10 each): group 1 were given i.v. boluses of 2 mg of morphine (lockout interval = 15 min); the other two groups were given the same boluses as well as a continuous i.v. infusion of either 1 mg.kg-1 of morphine (group 2) or 2 mg.kg-1 (group 3). Pain was assessed with a visual analog scale before starting analgesia, and after 1, 2, 3, 4, 8, 16, 24 and 36 h. Total and bolus morphine doses were recorded at the same time. Breathing rate and the level of sedation were measured every hour and blood gases every time 40 mg of morphine had been consumed. Morphine administration was stopped if breathing rate decreased to less than 10 c.min-1, the patient became too sedated, or PaCO2 rose to more than 45 mmHg. Pain scores were similar in the three groups. Total amounts of morphine were higher in groups 2 (56.8 +/- 23.8 mg) and 3 (116.2 +/- 41.8 mg) compared with group 1 (38.2 +/- 17.8 mg) (p < 0.05). Morphine administration was stopped in 5 patients in group 3 and in 1 in group 2 because PaCO2 had risen to more than 45 mmHg. Therefore, a continuous i.v. infusion is not required in patients receiving PCA, all the more so as this has deleterious respiratory effects.


[Effects of nifedipine premedication on peroperative hypothermia]. The intraoperative time-course of core temperature in patients premedicated with nifedipine (n = 30) was compared to that of control patients (n = 30). Distal oesophageal temperature (TCORE) was recorded every five minutes during total hip replacement in 60 adults ranked ASA 1 to 2. Patients in the control group were only premedicated with 100 mg of oral hydroxyzine. The treatment group consisted of 30 patients taking nifedipine for blood pressure control or coronary insufficiency. They were given 10 mg sublingual nifedipine as well as the hydroxyzine premedication. Anaesthesia was induced with thiopentone, fentanyl and vecuronium, and maintained with nitrous oxide in oxygen and halothane in a semi-closed circuit. The slopes of the time-course for TCORE were established for each patient, using two linear regressions, between 0 and 0.5 h and from 1 to 2 h. The two groups did not differ in age, weight, ambient temperature, blood pressure, heart rate, and volume of unwarmed blood transfused. TCORE differed significantly from the 25th minute on until the end of the study period. Contrary to all expectation the TCORE at 2 h was higher in the nifedipine group (34.85 +/- 0.09 degrees C) than in the control group (34.01 +/- 0.14 degrees C, p < 0.001). TCORE decreased more rapidly in the control group during the first study interval (0 to 0.5 h), -1.50 +/- 0.60 degrees C.h-1 vs -2.34 +/- 1.02 degrees C.h-1 (p < 0.001). The second slopes did not differ particularly (-0.96 +/- 1.32 degrees C.h-1 vs -0.90 +/- 0.42 degrees C.h-1 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


[Postoperative shivering: analysis of main associated factors]. This study was carried out in 75 female patients, ranked ASA 1 or 2, during recovery from balanced general anaesthesia. It aimed to find out the main determinants of postoperative shivering and its thermal effects. Skin and oesophageal temperature were recorded every ten minutes. Mean skin and body temperatures, and the intraoperative energy balance were calculated. There was no additional source of heating. Shivering was ranked from 0 to 2. Statistical analysis showed that the starting mean core and body temperatures were the only factors correlated with shivering and its intensity, whereas mean skin temperatures, age and opioid doses were not. Between 33.5 and 36.5 degrees C, there was a linear relationship between the oesophageal temperature at the end of anaesthesia and the incidence of shivering. A decrease of 1 degrees C in core temperature increased the probability of shivering by 33%. At 35.4 degrees C, 50% of patients shivered. There was a homogenous group of patients whose oesophageal temperature at the end of anaesthesia was between 35 and 36 degrees C. In this group, there was no significant difference between starting skin temperatures, whether the patient shivered or not. However, the core temperature of those within that group that did shiver returned to normal levels more quickly than in those that did not shiver. These data underlined the essential role played by core temperature at the end of anaesthesia in postoperative shivering and its intensity, as well as the heat producing value of shivering. It would therefore seem logical to prevent postoperative shivering by avoiding intraoperative hypothermia.


[Prevention of postoperative nausea and vomiting by ondansetron]. This study was carried out to assess the efficacy of oral ondansetron, a new 5HT3 receptor antagonist, in patients undergoing thyroid surgery. It included 60 patients, randomly assigned to two groups, and receiving orally, 1 h before induction of anaesthesia, either 8 mg of ondansetron (n = 29) or a placebo (n = 30). One patient was excluded. The same anaesthetic protocol, consisting of 3 to 5 micrograms.kg-1 of fentanyl, 4 to 6 mg.kg-1 of thiopentone, and 0.5 mg.kg-1 of atracurium, was used in all. Anaesthesia was maintained with 50% nitrous oxide in oxygen with 0.8 to 1% endtidal concentration of isoflurane and additional boluses of 0.1 mg of fentanyl as required. The incidence and intensity of nausea, graded mild, moderate or severe, and the incidence of vomiting were recorded postoperatively. During the first twelve hours after surgery, 40% of patients in the placebo group had nausea (16.7% mild, 20% moderate and 6.7% severe), and 50% vomited. In the ondansetron group, nausea and vomiting occurred in 13.8% and 20.4% of patients respectively. The 4 patients in the latter group complained of major nausea. The differences between the groups were statistically significant: p = 0.025 for nausea and p = 0.042 for vomiting. It is concluded that oral ondansetron, 8 mg taken orally 1 h before surgery, significantly reduces the incidence of nausea and vomiting during the first twelve postoperative hours. As it is easy to use and has no side-effects, it might be of interest in day-case surgery patients, despite its high cost.