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Intra-arterial chemotherapy of head and neck tumours.

The benefits and complications of regional chemotherapy in the treatment of head and neck tumours are discussed. Intra-arterial chemotherapy has been employed in 72 cases of preoperative, postoperative and palliative management. Cytostatic treatment consisted of combined Vincristine, bleomycin, methotrexate, and mitolactol administration by a Watkins-USCI or Sharp chronofusor. In cases of preoperative treatment the tumour regression was in the range of 50-80%. Tumours of the gingiva, parotid gland, maxilla and tonsil responded very well, tumours of the tongue less well to the treatment. The most dangerous complication is thrombosis of the common carotid artery; to avoid this complication the prothrombin index was reduced and kept at the 30-40% level.

Antineoplastic Agents↗

Vasodilation, fibrinolysis, and thrombolysis with intraarterial infusion of urokinase in the canine superior mesenteric artery.

Urokinase, the plasminogen activator from human urine, produces a dose-dependent increase in blood flow in the canine superior mesenteric artery when injected intraarterially at doses from 10(-1) to 10(3) units kg-1. This vasodilation persists despite blockade of beta-adrenergic and histamine H1 and H2 receptors as well as inhibition of plasminogen activation, suggesting that these mechanisms are not involved. Infusion of urokinase at 10(2) CTA (Committee on Thrombolytic Agents) units kg-1 min-1 does not produce a sustained vasodilation, but is effective in achieving complete lysis of thrombi within 100 min in the superior mesenteric arterial circulation. Increasing the dose slightly to 125 CTA units kg-1 min-1 results in unwanted clotting abnormalities without attaining a vasodilator level. Decreasing the dose to 75 CTA units kg-1 min-1 still results in complete thrombolysis. In contrast to the results in the femoral circulation, the dose required for fibrinolysis-thrombolysis does not overlap with that for vasodilation in the superior mesenteric artery. Nevertheless, these experiments provide some basis for the use of intraarterial urokinase infusion in the treatment of nonocclusive mesenteric ischemia and, perhaps, thrombotic occlusion of the superior mesenteric artery.

Animals↗

The role of chemotherapy in the management of cancer of the head and neck: a review.

Although experience with drug therapy of advanced or recurrent squamous cell carcinoma of the head and neck is limited, several agents have produced convincing and reproducible tumor regression in these patients. Methotrexate has had the widest usage, and produces 30-50% response rates; bleomycin, hydroxyurea, and adriamycin appear to be somewhat less effective. Location of the malignancy and previous x-ray treatment appear to be important determinants of responsiveness to methotrexate, while degree of differentiation has not yet been shown to be an important factor for response to this drug. Attempts to improve the response rate and duration of chemotherapeutic response by utilizing combinations of drugs, or use of drugs to sensitize the tumor to x-ray treatment, or to reduce the bulk of tumor before x-ray treatment, are reviewed; they have been only moderately encouraging. Intra-arterial chemotherapy appears to have a therapeutic advantage over intravenous treatment; however, the morbidity associated with the former approach limits its usefulness for routine usage. The use of drugs as adjuncts following surgery and/or radiation therapy or immunotherapy are newer approaches that have not been investigated sufficiently, but are promising areas for investigation.

Bleomycin↗

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↗

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↗