Consultation: more than one dimension.
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Biomedical subjects
Publications and source records attributed to C Alvarez.
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The efficacy and safety of ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy was investigated in an open pilot study. Five patients received 1 gm/day of ursodeoxycholic acid during 20 days and another three patients received two identical periods of treatment separated by a 14-day interval free of the drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with ursodeoxycholic acid. In the three patients who received two periods of treatment with ursodeoxycholic acid, pruritus and the laboratory alterations relapsed in the second week after the drug was discontinued, but they improved again when ursodeoxycholic acid was readministered. No adverse reactions were detected in the mothers or in their babies. All newborns were thriving normally during a follow-up period that lasted 5 mo after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials.
We investigated the effect of levamisole on pancreatic infection in a model of acute pancreatitis (AP) in cats. Animals with and without AP received Escherichia coli intravenously. Blood was then taken at intervals for culture. AP reduced phagocytic function by 28% as measured by the rate of bacterial disappearance from the blood (p less than 0.03). In other cats, AP was induced, and E. coli were placed into the pancreatic duct. Levamisole was given orally in some cats; the remainder were untreated. Control cats (neither AP nor levamisole) also received E. coli. Seven days later, pancreases from all control cats were sterile. In AP cats, the pancreatic infection rate was 73%. Levamisole reduced the rate of infection to 22% (p less than 0.03). We concluded that phagocytic function was impaired in cats with AP. Levamisole reduced the rate of pancreatic infection.
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1. The effects of histamine on isolated goat middle cerebral artery were examined using two experimental approaches: recording of isometric tension and measurement of [3H]-noradrenaline efflux. 2. Cumulative addition of histamine (10(-7)-3 x 10(-2)M) and 2-pyridylethylamine (2-PEA, 10(-6)-3 x 10(-2)M) produced concentration-dependent contractile responses. Preincubation with diphenhydramine (10(-7), 10(-6)M) or cimetidine (10(-7), 10(-6)M) competitively inhibited the histamine-induced contractile response. 3. Endothelium denudation enhanced the contractile effects of histamine. 4. Transmural electrical stimulation elicited contractions which were enhanced by histamine (10(-7)M), 2-PEA (10(-6)M) and dimaprit (10(-4)M). Diphenhydramine (10(-5)M) inhibited the action of histamine, but cimetidine did not. 5. Noradrenaline (10(-8)-10(-4)M) elicited concentration-dependent contractions which were unaffected by histamine (10(-7)M). 6. In arteries preloaded with [3H]-noradrenaline, transmural electrical stimulation induced an increase in the tritium efflux, which was enhanced in the presence of histamine (10(-7)M). 7. Therefore, histamine contracts cerebral arteries via specific non-endothelial H1-receptors, and enhances perivascular adrenergic neurotransmission through specific presynaptic H1-receptors by a mechanism involving increases in noradrenaline release.
Glucose tolerance and insulin effects on glucose production and utilization by various tissues were studied in 70-day-old anesthetized rats submitted to food restriction from the fetal stage. Basal and glucose-induced plasma insulin levels were reduced in food-restricted rats without alterations in glucose tolerance. Insulin action was quantified by using the euglycemic-hyperinsulinemic clamp technique. Glucose turnover rates were measured by using D-[6-3H]glucose. Exogenous insulin failed to decrease glucose production in food-restricted rats. Weight-related whole body glucose utilization was higher in restricted rats than in controls both in the basal (21.9 +/- 0.7 vs. 9.4 +/- 0.6 mg.min-1.kg-1) and hyperinsulinemic states (37.5 +/- 1.1 vs. 14.0 +/- 1.2 mg.min-1.kg-1). Local glucose utilization by peripheral tissues was estimated by a 2-deoxy-D-[1-3H]glucose technique. In both basal and hyperinsulinemic conditions glucose utilization was increased in various adipose and muscle tissues of the food-restricted rats as compared with the controls. Thus we conclude that food restriction leads to an increase in the insulin-mediated glucose uptake by various peripheral tissues and to insulin resistance in the liver.
The objective of this study was to investigate quantitative and qualitative intrathecal IgG synthesis in 51 patients with clinically definite multiple sclerosis, taking previous immunosuppressive treatment into account. Four formulae were used to assess quantitative synthesis. Oligoclonal bands (OB) were investigated using isoelectric focusing (IEF) and silver staining. Abnormal quantitative values were detected in 42 (82%) patients, whereas OB occurred in 38 (74.5%) patients. Steroid therapy lowered quantitative synthesis in 6 out of 9 patients when given within 3 months before lumbar puncture (LP). Untreated patients with OB systematically had abnormal formulae. Patients treated with corticosteroids 10 or more months prior to LP had abnormal formulae. This fact suggests a transient depressor effect of steroids on quantitative synthesis. OB were present in patients recently treated with corticosteroids. Quantitative synthesis was higher in patients with OB than in those without OB. Azathioprine treatment did not significantly lower quantitative synthesis. We conclude that for routine purposes evaluation of intrathecal immunoglobulin synthesis could begin by performing quantitative tests. IEF seems to be mandatory for patients with normal formulae who have recently been treated with steroids.
The low-pressure duct perfusion model reliably produces acute pancreatitis in cats. The main pancreatic duct is made permeable in one of several ways: the perfusion of glycodeoxycholic acid along the main pancreatic duct, the administration of intragastric ethanol, the stimulation of pancreatic secretion into an obstructed duct, or the creation of acute hypercalcemia. Active pancreatic enzymes are then perfused through the main pancreatic duct via a catheter inserted into the duct in the tail of the gland, and acute edematous pancreatitis results. Simultaneous infusion of 16,16-dimethylprostaglandin E2 converts acute edematous into acute hemorrhagic pancreatitis. Histologically, the characteristic changes of human acute pancreatitis are manifest 24 h later: necrosis, polymorphonuclear leukocyte infiltrate, hemorrhage and edema.
The regulation of liver glycogen turnover in the neonatal period differs from that of the adult state. Little is also known about the regulation exerted by GH in the first period of life. To shed light on the regulation of glycogen production and in particular to study the role of GH on liver glycogen accumulation, we investigated the effect of GH administration in control or GH-deficient neonatal rats. A slow-release GH preparation was injected subcutaneously on days 9 and 12 of life, in normal and neonatally treated rats with thyroxine or cortisol. Seventy-two hours after the last GH administration, liver glycogen was increased without concomitant elevation of plasma insulin and corticosterone levels and in addition without sequential inactivation of glycogen synthase. These data strongly suggest that the current concepts on the regulation of the hepatic synthesis of glycogen should be revised.
Pulmonary arterial hypertension and compulmonale were found in a woman with inactive systemic lupus erythematosus (SLE). The patient died of right heart failure 5 years later. Postmortem study showed SLE reparative lesions, plexogenic arteriopathy and vasculitis in the lung vessels. Since no active SLE was found, the pulmonary vasculitis was attributed to plexogenic arteriopathy.
A common cause of the Cushing's Syndrome (CS) is nodular suprarenal hyperplasia (NSH), which is characterized by the presence of nodes in both suprarenal glands. Its pathophysiology is not well known and its diagnosis is quite difficult due to the heterogenicity of the biochemical and radiological data. We analyzed the suprarenal gammagraphies (SRG) of 7 patients with anatomopathological diagnosis of NSH. Bilateral uptake was observed in all cases and in five patients, such bilateral uptake presented a clear asymmetry. We believe that these observations demonstrate a bilateral suprarenal affectation and are of great use in order to orientate the diagnosis of NSH and, especially, in order to differentiate it from other suprarenal diseases causing CS, like adenomas, in which uptake is unilateral.
The effect of intraduodenal ethanol on exocrine pancreas of the rat in basal conditions has been studied. The pancreatic flow rate significantly increased to a maximum of 148% of basal after intraduodenal ethanol whereas only slight increases of protein output were observed. Ethanol perfusion in previously atropinized animals also elicited a significant increase of the flow rate up to a maximum of 177% of basal values but this increase appeared later than that observed in non-atropinized animals. Our results show that the ethanol action is successively stimulant followed by a simultaneously dual and antagonic effect (stimulant and inhibitory). Furthermore, this ethanol effect is mediated by cholinergic mechanisms. Finally, no effect of ethanol on portal plasma secretin and VIP levels was observed in atropinized or non-atropinized animals.
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We describe the presence of EDS type II in a family whose diagnosis was lately established by medical consultation of one of its members suffering from hyperuricemia and gout. We stress the relevance of an early diagnosis of this syndrome as a means to prevent and reduce as much as possible cardiovascular, hemorrhagic and surgical systemic complications associated to this disease.
Pancreatic blood flow and its relationship to pancreatic interstitial pressure were investigated in a model of chronic pancreatitis in cats using a hydrogen gas-clearance technique with an intraductal electrode. The intraductal technique correlated well with blood flow measurements made using gamma-labeled microspheres (r = 0.88, P less than 0.001). In control cats, the basal blood flow of 69.1 +/- 9.5 mL.min-1.100 g-1 increased by 25% to 86.2 +/- 11 mL.min-1.100 g-1 with secretory stimulation (P less than 0.05). Interstitial pressure was -0.02 +/- 0.3 mm Hg and did not change significantly with stimulation. In cats with chronic pancreatitis, basal interstitial pressure was 1.8 +/- 0.5 mm Hg and basal blood flow 39.9 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Stimulation of the chronic pancreatitis gland increased the pressure to 3.0 +/- 0.4 mm Hg (P less than 0.01) and reduced flow 15% to 34.2 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Papaverine increased blood flow in control and chronic pancreatitis cats without altering tissue pressure, suggesting that despite the reduced basal blood flow, the ability to increase blood flow was preserved in chronic pancreatitis. The increased interstitial pressure associated with secretion appeared to limit the gland's normal hyperemic response in this model of chronic pancreatitis.
BACKGROUND: The mechanism by which ethanol predisposes to acute pancreatitis, especially in established chronic pancreatitis, is not known. Here we studied the effects of acute ethanol ingestion on pancreatic blood flow in chronic pancreatitis, a setting characterized by diminished basal blood flow to the pancreas. METHODS: Obstructive pancreatitis was created by partial duct ligation for 3 weeks in nine cats. Controls (n = 8) were not operated on. Blood flow was measured in anesthetized animals with a hydrogen gas clearance technique and an intraductal electrode. Pancreatic interstitial pressure, systemic and portal blood pressures, and serum ethanol levels were recorded, and pancreatic vascular resistance was calculated. Measurements were made before and for 2 hours after 20 cc of 40% (wt/vol) ethanol was instilled into the stomach. RESULTS: Basal flow was reduced in the obstructed pancreas to 51% of normal. Both groups showed an acute decrease in blood flow when ethanol was given. A more steep (50% of baseline) and a more prolonged (120 minutes) fall was observed in the pancreatitis group than in controls (31% and 60 minutes, respectively). The decline in blood flow correlated with increases in interstitial pressure and vascular resistance. CONCLUSIONS: Acute ethanol ingestion sharply reduces pancreatic blood flow, especially in glands with chronic pancreatitis.
We examined the effects of extracellular Ca2+ withdrawal and of Ca2+ entry blockers on goat cerebrovascular responses to prostaglandin F2 alpha (PGF2 alpha). We measured isometric tension in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. PGF2 alpha produced concentration-dependent contractions of isolated arteries. The contractions were partially inhibited by incubation in Ca(2+)-free medium (by 63.1 +/- 1.8% without ethyleneglycol-bis-(beta-amino-ethylether)-N,N,N',N'-tetra-a cetate (EGTA), and by 82.4 +/- 3.7% with EGTA). The Ca2+ entry blockers inhibited PGF2 alpha-elicited contraction and relaxed PGF2 alpha-precontracted arteries (nicardipine, 91.4 +/- 9.8%; nimodipine, 73.1 +/- 2.0%; and verapamil, 50.5 +/- 4.5% relaxation of the active tone). Injection of PGF2 alpha into the cerebral circulation produced dose-dependent reductions in CBF (34.4 +/- 2.1% after 30 micrograms) which were inhibited during infusion of Ca2+ entry blockers (nicardipine 10 micrograms/min, 14.7 +/- 1.5%; nimodipine 10 micrograms/min, 13.6 +/- 1.3%; and verapamil 100 micrograms/min, 13.7 +/- 2.3% of flow reduction). We conclude that PGF2 alpha-elicited contraction of goat cerebral arteries is mainly mediated by extracellular Ca2+ influx through Ca2+ channels sensitive to Ca2+ entry blockers. The anticonstrictor effects of Ca2+ entry blockers observed in vitro are consistent with their inhibitory effect on the PGF2 alpha-induced CBF reductions.