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Sodium acetylsalicylate and the role of prostaglandins in the mechanism of intradental pain.

In order to study the effect of sodium acetylsalicylate and the role of prostaglandins on intradental nerve impulse activity experiments were performed on the teeth of anaesthetized cats. Nerve impulse activity was induced by mechanical and chemical stimuli and recorded by means of electrodes inserted into dentinal cavities. It was shown that such activity could not be blocked by sodium acetylsalicylate or indomethacin given locally or i.v. PGE2 failed to excite the sensory units when given locally (3.5 microng/ml) or intraarterially (35-140 ng/min) alone or in combination with mechanical and thermal stimuli or combined with local application of histamine (10 mg/ml) or bradykinin (10 mg/ml). Intraarterial infusion or arachidonic acid, a precursor to PGE2, PGF2 alpha PGG2 and PGH2 failed to change the excitability even on applying local stimuli to the pulp or with local application of histamine or bradykinin. These findings seem to indicate that the increased sensitivity of the tooth to thermal stimuli seen during acute pulpitis is not due to formation of prostaglandins.

Administration, Topical↗

Effect of local or parenteral application of ACTH or hydrocortisone on bovine corpus luteum function.

Studies were conducted to determine the effect on corpus luteum (CL) function of ACTH or hydrocortisone administered by ovarian perfusion on day 11 of the oestrous cycle or by carotid infusion on days 2-9 of the oestrous cycle. No significant local effects on CL function were observed during the ovarian perfusion study. Continuous carotid infusion of ACTH or hydrocortisone on days 2-9 resulted in a decreased slope of the progesterone increase during the infusion period. However, no difference in plasma progesterone level on days 9-11 between control and treated cycles was detected and there was no difference between treated and control CL at day 11 with regard to CL weight or progesterone content. The data suggest a possible direct effect of hydrocortisone on either the hypothalamus or pituitary which results in decreased progesterone secretion but not CL development. No residual effect was observed.

Adrenal Cortex Hormones↗

The effect of PGI2 on canine renal function and hemodynamics.

The effect of prostaglandin I2 (prostacyclin) on renal and intrarenal hemodynamics and function was studied in mongrel dogs to elucidate the role of this novel prostaglandin in renal physiology. Starting at a dose of 10(-8) g/kg/min, PGI2 decreased renal vascular resistance and redistributed the blood flow away from the outer cortex (zone 1) and towards the juxtamedullary cortex (zone 4). At 3 X 10(-8) g/kg/min, the renal vascular resistance decreased even further, but at this dose the mean arterial blood pressure also declined 13% indicating recirculation of this prostaglandin. PGI2 infusion at a vasodilatory dose resulted in natriuresis and kaliuresis. With a decline in filtration fraction, these changes were most likely secondary to the hemodynamic effects of this prostaglandin. Unlike PGE2, PGI2 had no direct effect on free water clearance indicating lack of activity at the collecting duct. PGI2 may be the important renal prostaglandin involved in modulating renal vascular resistance and intrarenal hemodynamics as well as influencing systemic blood pressure.

Animals↗

Control of variceal bleeding by superior mesenteric artery vasopressin infusion.

Liver function and clotting tests were evaluated in 39 patients with variceal bleeding prior to superior mesenteric artery vasopressin infusion. In six patients with mild hepatic dysfunction (Child's class A), permanent control of hemorrhage was achieved in all six and all survived the hospitalization. In 21 patients with moderate dysfunction (Child's class B), permanent control of hemorrhage was achieved in 13 (62%) and temporary control for 24 hr or longer in the remaining eight (38%). Survival in class B was 67% (14 of 21). In only four of 12 patients with severe hepatic dysfunction (Child's class C) was control of hemorrhage achieved (33 percent). None of these patients survived. Therapeutic failure also was associated with clotting derangements and the initial bleeding rate. It is concluded that the effectiveness of vasopressin in variceal hemorrhage is a function of the underlying liver disease and derangements in clotting function.

Adult↗

A controlled comparison of continuous intraarterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices.

Infusions of intraarterial vasopressin (IAV) into the superior mesenteric artery have been shown to be effective in controlling hemorrhage from esophagogastric varices. Intravenous infusions of vasopressin (IVV), which can be initiated rapidly and require less sophisticated equipment and personnel, have also been reported to control variceal hemorrhage. We undertook a controlled clinical trial to compare these two routes of administration. Twenty-two cirrhotic patients with massive hemorrhage from varices were randomized to receive either IVV or IAV. Intraarterial vasopressin was begun at 0.1 U/min and increased progressively as needed to 0.2, 0.3, 0.4, and 0.5 U/min. Intravenous vasopressin was begun at 0.3 U/min and increased progressively as needed to 0.6, 0.9, 1.2, and 1.5 U/min. Hemorrhage was controlled in 5 of 10 episodes (50%) with IVV and in 6 of 12 episodes (50%) with IAV. Seven of the ten episodes treated with IVV (70%) ended fatally compared with 9 of 12 treated with IAV (75%). Side-effects and complications occurred with similar frequency in the two groups. The two routes of administration are equal in effects, side-effects, and complications. We recommend that IVV, which can be administered more easily, be given a brief therapeutic trial early in the management of hemorrhage from varices.

Adult↗

Acute myocardial infarction: intracoronary application of nitroglycerin and streptokinase.

In five patients with acute myocardial infarction, the effects of both intracoronary nitroglycerin (NTG) and subsequent intracoronary streptokinase application were evaluated. In addition, transluminal recanalization was performed in one of these patients. Injection of NTG into the infarct-related coronary artery resulted in improved distal filling of the subtotally occluded left circumflex artery in one patient, and in transient patency of the completely occluded right coronary artery in a second patient. In a third patient patency of the totally occluded left anterior descending artery (LAD) was achieved by transluminal recanalization with a guide wire. In a forth patient with occulsion of the LAD, there was no response to intracoronary NTG and mechanical recanalization was not attempted. Subsequent intracoronary infusion of streptokinase (1,000--2,000 U/min for 15--60 min) resulted in a further and long-term reduction of narrowing at the site of acute occlusion in patients I-III and in opening of the completely occluded LAD in patient IV. Improvement of lumen was paralleled by alleviation of symptoms. In a fifth patient, in whom the LAD was subtotally occluded, the degree of coronary obstruction could not be changed by intracoronary application of NTG or by lysis. In this patient, symptoms and ECG changes improved with reduction of pathologically elevated blood pressure values. The findings suggest that myocardial infarction had been caused by thrombotic occulsion in four patients, and that spasm of the infarct vessel could have been an additional factor in two of these patients. In the fifth patient, an increase of afterload in the presence of a subtotal lesion might have caused the critical imbalance between oxgen supply and demand, resulting in cell death.

Cardiac Catheterization↗

Combined intra-arterial actinomycin D and radiation therapy for surgically unresectable hypernephroma.

One primary goal of preoperative radiotherapy for hypernephroma is to reduce the volume of tumor and, therefore, improve the possibility of resection. It is important that this goal be accomplished promptly so that 4 to 6 weeks after radiation therapy nephrectomy can be attempted. A longer waiting period may allow fibrosis of the normal surrounding tissues and make surgery more difficult. In addition, longer waiting periods could theoretically increase the probability of metastasis. Therefore, we plan to continue clinical investigation on the use of combined intra-arterial actinomycin D and radiotherapy as a possible useful means of improving the possibility of prompt surgical resection, since theoretically this regimen may be a method of increasing the effective radiation dose to the hypernephroma without increasing the effective radiation dose to surrounding normal tissue, such as bowel. The method may also have merit as an improved means of palliating selected patients with metastases who are symptomatic from a bulky primary hypernephroma.

Adenocarcinoma↗

Parotid salivary flow and composition during infusion of acetylcholine and atropine into the carotid artery of conscious sodium-replete sheep.

The rate of salivary flow and the concentrations of the major electrolytes in parotid saliva and arterial plasma of conscious sodium-replete sheep were measured during resting salivary secretion and when salivary flow was either increased by intracarotid infusion of acetylcholine at 10-30 nmol. min-1 for 20 min or reduced by intracarotid infusion of atropine at 14 nmol. min-1 for 50 min. During both treatments salivary phosphate concentration was always negatively correlated with salivary flow and salivary bicarbonate concentration was always positively correlated with flow. The chloride concentration of the saliva during the acetylcholine infusion experiments was positively correlated with salivary flow whereas when atropine was infused the chloride concentration was negatively correlated with flow. Acetylcholine infusion caused the potassium concentration of the saliva to increase significantly resulting in a marked increase in the total rate of loss of potassium in the saliva. The salivary potassium concentration fell significantly at the onset of the atropine infusion and then rose progressively so that the potassium concentration was elevated by the end of the infusion. In both treatments the concentrations of sodium and hydrion were negatively correlated with salivary flow rate. The maximum sodium concentration which occurred in the low-flow saliva of the atropine infusion was substantially higher than the concentration that would be achieved by equilibrium with the aqueous phase of arterial plasma. It was concluded that the negative correlation between salivary flow and sodium concentration occurred because the reabsorption of sodium from the saliva by the excurrent duct system was minimal in sodium-replete sheep which would have low levels of mineralocorticoids in the circulation. The inconsistency between this study and previous reports presumably reflects differences in the criteria used to define the sodium status of the animals.

Acetylcholine↗

Renal function in sheep during infusion of alkali metal ions into the renal artery.

1. The effect on renal function of 1 M solutions of LiCl, NaCl, KCl, RbCl and CsCl and 3 M-NaCl infused close-arterially to the kidney for 10 min at 0-7ml./min has been studied in nine experiments on four unilaterally nephrectomized sheep. The levels of flow, electrolyte concentration and electrolyte excretion in the urine were measured before, during and for 50 min after the infusions. 2. The infusion of 1-M-NaCl produced little change in urine flow and composition whereas 3 M-NaCl resulted in relatively small increases in urine flow and sodium excretion. 3. The infusion of lithium, potassium, rubidium and caesium resulted in marked increases in urine flow, urinary sodium concentration and excretion, urinary potassium excretion and osmolal clearance while the urinary potassium concentration decreased. 4. Changes in urine flow and urinary pH during the infusions of all the alkali ions except sodium were consistent with increased urinary bicarbonate excretion. 5. The osmolal clearance was increased by the infusion of lithium, potassium, rubidium and caesium, but equivalent increases in the rate of solutefree water reabsorption did not occur. 6. The infusion of caesium resulted in a depression of the glomerular filtration rate (G.F.R.) which was not observed when the other alkali ions were infused. 7. The effects of lithium, potassium and rubidium on urine flow and composition were rapid in onset and the residual effects on these ions, on cessation of infusion, were relatively short. The effects on caesium were slow in onset and prolonged in duration. 8. It was concluded that lithium, potassium, rubidium, and caesium altered urine flow and electrolyte excretion by acting upon common mechanisms which were predominantly intra-renal and located in the proximal segment of the nephron.

Aminohippuric Acids↗

Transcatheter occlusion of the gastroduodenal artery.

The gastroduodenal arteries of 7 patients were occluded for treatment of duodenal bleeding in 4, hepatic devascularization in 2, and redistribution of blood flow for intra-arterial chemotherapy in one patient. In 6 patients, occlusion was performed with Gianturco coils, and with Gelfoam in one. No major complication was encountered. This approach was successful in the control of bleeding from peptic ulcers, arteriovenous malformation and invasion of duodenum by retroperitoneal metastatic lymph nodes from carcinoma of the testicle. Occlusion of the gastroduodenal artery was utilized for further dearterialization of hepatic neoplasms. Redistribution of hepatic blood flow was accomplished by the occlusion of the gastroduodenal and replaced right hepatic arteries allowing infusion of chemotherapeutic agents into the entire liver through the left hepatic artery.

Adenoma, Bile Duct↗

Controlled blocking of hepatic artery flow with enzymatically degradable microspheres combined with oncolytic drugs.

A new method for intermittent hepatic arterial flow arrest has been used in combination with intraarterial 5-fluorouracil (5-Fu) for the treatment of secondary liver neoplasms in 12 patients. Polysaccharide microspheres with a half-life of 1 h were infused together with 5-Fu via a percutaneously introduced catheter into the hepatic artery. There were no significant side effects to the treatment. Clinical effects and overall survival were comparable to those of hepatic artery ligation.

Clinical Trials as Topic↗

Cerebrovascular response to infused 5-hydroxytryptamine in the baboon. Part 2. 5 Hydroxytryptamine infusion in estrogen and progesterone treated animals.

The effect of intracarotid infusion of 5-hydroxytryptamine (5-HT) on cerebral blood flow was studied in five female baboons 7 days after intramuscular injection of slow release estrogen and progesterone. The control values for total cerebral blood flow, grey matter flow, and white matter flow were 38.9, 57.5, and 11.0 ml/min/100 gm of tissue respectively. There was a statistically significant decrease in total, grey and white matter blood flow during infusion of 5-HT at dosages ranging from 0.5 to 10.0 microng/kg/min. The study indicates that in female baboons pretreated with estrogen and progesterone, intracarotid infusion of 5-HT produces a dose dependent decrease in cerebral blood flow, which did not occur in control animals.

Animals↗

Blood-brain barrier opening by isotonic saline infusion in normotensive and hypertensive animals.

The blood-brain barrier to intravascular Evans blue-albumin was opened in monkeys and rabbits by infusing isotonic saline for 15 s into the common carotid artery, when the external carotid was clamped temporarily and the lingual was catheterized for measuring pressure. Barrier opening correlated better with infusion pressure than with infusion rate, and occurred at carotid artery pressures above 170 mmHg. Systemic hypertension induced by Aramine increased barrier vulnerability by causing a higher net carotid artery pressure to be attained at a given infusion rate.

Animals↗

Studies of phenolic steroids in human subjects. XIX. Renal conjugation of 15alpha-hydroxyestradiol-3-sulfate.

In order to elucidate further the role of the kidney in the conjugation and excretion of 15alpha-hydroxy-estrogens, we synthesized doubly and singly labeled 15alpha-hydroxyestradiol-3-sulfate (15alpha-OHE-S) and determined its urinary excretory pattern after administering differently labeled 15alpha-OHE2-S into the renal artery and concomitantly into a peripheral vein and by the infusion of doubly labeled 3H-15alpha-OHE2-S-35S into the renal artery. The excretion of radioactivity in the early urinary samples and the conjugate pattern in these urines were determined. About twice as much radioactivity was excreted in the early urine samples originating from the renal artery injection than from samples obtained following peripheral administration, indicating renal conjugation and excretion of the 15alpha-OHE2-S. The latter was preponderantly excreted as the S-NAG with only a small part (about 10%) of the administered sulfate being hydrolyzed to the aglycone. The latter was then either conjugated with N-acetylglucosamine (NAG) or glucuronide, probably also in the kidney. Most of the 15-alpha-OHE2-S could not be accounted for, possibly because of biliary excretion and enterohepatic circulation. The results obtained and those already published indicate that the human kidney is capable of conjugating 15alpha-OHE2, its NAG, and its sulfate conjugates.

Adult↗

Hepatic artery infusion of 5-FUDR after prior systemic 5-fluorouracil.

Twenty-one patients with disseminated colon carcinoma and clinically significant liver metastases were treated with 5-FUDR via hepatic artery infusion (HAI). All patients had previously received systemic chemotherapy consisting of either 5-fluorouracil aone or in combination with other agents. At the time of the initiation of the HAI, clinical disease in all patients was progressing. A PR of hepatic metastases was noted in eight patients (35%) with a median and mean duration of response of 4.5 and 5.0 months respectively. The median and mean survival from the start of HAI for responders was 8.0 and 9.0 months and for nonresponders was 1.0 and 1.6 months respectively. It appears that a significant response rate can be achieved with HAI of 5-FUDR in spite of previous exposure to fluorinated pyrimidines.

Adult↗

Surgical treatment of chronic osteomyelitis of the mandible resistant to intraarterial infusion of antibiotics: report of case.

A 47-year-old man with chronic osteomyelitis of the mandible is described. The patient had frequent episodes of acute and subacute exacerbation at varying intervals for a period of six years in spite of extended antibiotic therapy. Intraarterial infusion of antibiotics through the superficial temporal artery also failed to cause any improvement. He was finally treated successfully by surgical intervention.

Cephalexin↗

Cerebrovascular response to intracarotid infusion of 5-hydroxytryptophan and L-DOPA in cats.

Intracarotid administration of 5-hydroxytryptophan (10 mg/kg) results in a slight vasoconstriction of cerebral vessels. L-DOPA (20 mg/kg) administered by the same route enhances cerebral blood flow. The effect on cerebral blood flow of L-DOPA (20 mg/kg) following intracarotid 5-hydroxytryptophan (10 mg/kg) administration shows a potentiation of cerebral blood flow response in non-pretreated as well as in nialamide- and reserpine-pretreated cats.

5-Hydroxytryptophan↗