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Evaluation of hepatoma chemotherapy by alpha-fetoprotein determination.

Effects of chemotherapy on twenty-nine histologically proved and alpha-fetoprotein (AFP) -positive hepatomas were evaluated by changes in serum AFP levels according to the criteria of our previous report. By transfemoral local infusion of mitomycin C, six of eight patients showed more than 50 per cent decrease of AFP levels and regression of the tumor, and the others showed fair effects. By single shot infusion, 50 per cent decrease of serum AFP levels and tumor regression were noted only in three of thirteen patients, and chemotherapy by systemic infusion in eight patients was much less effective. As evaluated by AFP levels, histologically well or moderately differentiated hepatocellular carcinomas responded better to chemotherapy than poorly differentiated ones.

Adult↗

Mesenteric vasodilator effect of 5-hydroxytryptamine: possible enteric neuron mediation.

The superior mesenteric blood flow response to intra-arterial injections (0.5-25 mug) and infusions (5-30 mug/min) of 5-hydroxytryptamine (5-HT, serotonin) was investigated in anesthetized cats in which nerve activity to the intestine was altered by surgical and pharmacological procedures. With the superior mesenteric periarterial nerves intact, low doses of 5-HT (less than 5 mug) produce vasodilatation, whereas higher doses produce vasoconstriction. When the periarterial nerves are cut either at the start of or during the experiments, vasodilatation is elicited over the entire dose range, and doses of 5-HT which initially produce vasoconstriction elicit vasodilatation after nerve sectioning and also after alpha-adrenergic receptor blockade. These vascular responses are not secondary to changes in arterial pressure or intestinal motility. The vasodilator response to 5-HT is unaffected by alpha- or beta-adrenergic or cholinergic receptor blockade, by ganglionic blockade, or by histamine receptor blockade, but is blocked by tetrodotoxin and also the 5-HT antagonist, dihydroergotamine.

Adrenergic alpha-Antagonists↗

[Regional chemotherapy of stomach cancers].

Fifty patients with a stomach cancer received regional chemotherapy by infusion. Two kinds of cancers were treated with this technique: cancers inaccessible with usual surgical treatment and some limited cancers. In most cases, the catheter was introduced by transcutaneous puncture of axillary artery. According to the site of the cancer, the extremity of the catheter was introduced into the left gastric artery, hepatic artery or coeliac trunk. Efficiency of the infusion was checked by arteriography and by gastric fibroscopic examination with intra-arterial injection of evans blue. The duration of the treatment was two weeks or three weeks. The chemotherapy was made on a sequential method, taking account of the tumoral cellular cycle. The results show an objective response in 80 per cent of the cases, 39 per cent of the non operable cancers were later accessible to surgery. This study shows that chemotherapy should be used in the treatment of any stomach's cancers before surgical treatment.

Adult↗

Concept of cytostatic therapy in advanced tumours of the head and neck.

In cases with inoperable tumours of the head and neck some benefit may still be derived from cytostatics and radiotherapy. One treatment concept is based on intraarterial infusion therapy (bleomycin, methotrexate), while the systemic intravenous application of cytostatic substances (bleomycin, cyclophosphamide) is considered as an alternative of the intra-arterial approach is ruled out. Of the 31 intra-arterially and the 30 intravenously treated patients (all except 2 had squamous cell carcinomas), 64,5% and 20%, respectively, went into remission. This documents the validity of our treatment concept.

Adult↗

Systemic arterial blood pH servocontrol of mechanical ventilation.

Servocontrol of mechanical ventilation using systemic arterial blood pH, measured by a dual-function pH/PCO2 intra-arterial sensor, as the controlled variable uas carried out in 30 dogs anesthetized with pentobarbital, 30 mg/kg. The control loop consisted of the animal, an intra-arterial dual-function pH/PCO2 sensor and sensor amplifier, a controller, and a Siemans-Elema 900 servoventilator. The system responded appropriately to changes in set-point pH from 7.30 to 7.50, as well as to infusions of lactic acid, which, with the control loop open, decreased systemic arterial blood pH 0.1 TO 0.2 PH units. Long-term (16 hr) ventilation of one dog with the systemic arterial blood pH servocontrol ventilator was shown to be feasible.

Acid-Base Equilibrium↗

Cardiovascular studies with impromidine (SK&F 92676), a new very potent and specific histamine H2-receptor agonist.

Impromidine (SK & F 92676) has recently been identified as a potent and specific histamine H2-receptor agonist. The present paper describes some cardiovascular studies with the drug. Impromidine lowers blood pressure in cats and rats by interaction with H2-receptors. During continuous intravenous infusions of impromidine, the fall in blood pressure is due to a reduction in total peripheral resistance; cardiac output increases during hypotension. The responses to impromidine are similar to responses to histamine in mepyramine-treated cats. Impromidine administered intra-arterially also causes vasodilatation in the femoral and mesenteric vasculature by interaction with H2-receptors. Impromidine stimulates all measured parameters including coronary flow in the isolated working heart of the guinea-pig. Dose-response curves to impromidine were displaced to the right in the presence of cimetidine.

Animals↗

Improvement in arterial oxygenation by saralasin infusion in man.

Simultaneous hemodynamic and blood gas measurements were performed in 26 hypertensive adults, who were cigarette smokers, before and after a 30-minute infusion of saralasin (5 microgram/kg/min) which is a highly specific competitive antagonist of angiotensin II (AII). The arterial pressure fell in nine, rose in seven and was unchanged in ten patients. The mean cardiac index for the entire group remained unchanged. Pulmonary arterial or wedge pressure, pulmonary vascular resistance, arterial PCO2 and pH did not change. Unrelated to the hemodynamic changes, the mean arterial oxygen pressure (PaO2) increased from 68.6 +/- 2.2 mm Hg to 73.9 +/- 2.1 mm Hg (P less than 0.001). In the absence of a significant increase in alveolar ventilation as indicated by an unchanged mean PCO2 and lacking a hemodynamic explanation, the mechanism for the rise in PaO2 is speculative at this stage. The possibility of an improvement in the distribution of ventilataion by saralasin infusion is under investigation.

Adult↗

Pyloroduodenal bleeding and intraarterial vasopressin: clinical results.

Intraarterial vasopressin infusions were given to 46 patients with pyloroduodenal hemorrhage. Hemorrhage was angiographically and clinically controlled in 15 patients, with recurrent bleeding in five. Bleeding was not controlled in 31 patients; seven of these underwent Gelfoam embolization, with bleeding controlled in three. It is concluded that intraarterial vasopressin infusions are not as effective in controlling pyloroduodenal hemorrhage as in other areas of the gastrointestinal tract.

Adolescent↗

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↗

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↗

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↗