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Selective arterial infusion of vasoconstrictors for control of traumatic splenic hemorrhage.

The spleen of each of 20 mongrel dogs was traumatized by creating a wedge laceration, and selective arterial infusion was then performed with vasopressin in four dogs, pituitrin in eight, and epinephrine in eight. Infusion therapy with vasoconstrictors controlled the splenic hemorrhage in 19 of 20 dogs. The 15 dogs surviving the experimental period of four to eight weeks showed well-healed scars at the sites of lacerations. Three dogs had small contracted spleens as a result of massive infarction. The results of this experiment indicate that splenic hemorrhage in the experimental dogs can be controlled by selective infusion of pituitrin or vasopressin, but is more effectively controlled with epinephrine.

Animals↗

Occlusion site and outcomes in intra-arterial tenecteplase after successful endovascular therapy: a secondary analysis of the ANGEL-TNK trial.

BACKGROUND: Endovascular thrombectomy achieves macroreperfusion in large vessel occlusion (LVO) stroke, but only one-quarter of patients had excellent functional outcome. Adjunct intra-arterial (IA) tenecteplase could further improve the treatment effect, yet its efficacy across internal carotid artery (ICA) versus middle cerebral artery (MCA) M1/M2 occlusion remains unclear. OBJECTIVE: To evaluate whether IA tenecteplase improves 90-day functional outcomes in LVO patients stratified by occlusion site (ICA, MCA M1, MCA M2). METHODS: Prespecified secondary analysis of the ANGEL-TNK trial (multicenter, randomized, open-label, blinded endpoint) in 19 Chinese stroke centers. Participants were enrolled who had anterior circulation LVO, 4.5-24&#x2009;hours from symptom onset, and CT angiography (CTA)/magnetic resonance angiography (MRA)-proven ICA, M1, or M2 occlusion. INTERVENTION: Randomization (1:1) to IA tenecteplase (0.125&#x2009;mg/kg) or standard medical management after expanded Thrombolysis in Cerebral Infarction (eTICI) 2b50-3 reperfusion. MAIN OUTCOME MEASURE: The primary outcome was the rate of 90-day modified Rankin Scale (mRS) 0-1. RESULTS: There were 256 patients in the trial, including 71 (27.7%) ICA, 122 (47.6%) MCA M1, and 62 (24.2%) MCA M2. ICA occlusion patients treated with IA tenecteplase had higher rates of 90-day mRS 0-1 (39.4% vs 13.2%; relative risk (RR) 2.99; 95%&#x2009;CI 1.51 to 5.96; p=0.002) and mRS 0-3 (54.5% vs 42.1%; RR 1.30; p=0.048) versus controls, with a significant shift toward better mRS scores (median 3 (IQR 1-4) vs 4 (2-6); odds ratio (OR) 2.26; p<0.001). Post hoc analysis showed higher eTICI progression in ICA patients (51.5%) versus MCA M1 (37.9%) and M2 (25.7%). IA tenecteplase had a lower any intracranial hemorrhage within 48 hours in ICA patients (15.2% vs 39.5%; RR 0.38; p<0.001) compared with standard medical management. No significant benefits were observed in the MCA M1/M2 subgroups, and interaction effects were significant between ICA and MCA segments for functional outcomes and safety. CONCLUSIONS AND RELEVANCE: IA tenecteplase had a better functional outcome and lower hemorrhage risk in ICA occlusion compared with standard medical management but not in MCA M1/M2. Occlusion site is a critical determinant of response to IA tenecteplase. A pooled analysis of IA tenecteplase stratified by occlusion site strata is warranted.

Humans↗

Rapid dextran infusion in essential hypertension.

Hemodynamic parameters were studied before and after rapid dextran infusion in 34 men including 17 patients with sustained essential hypertension and 17 normotensive controls. In both groups of patients, dextran infusion induced a significant increase (p less than 0.001) in central venous pressure (CVP), cardiac output (CO), and stroke volume. The percent change in stroke volume was significantly higher in hypertensives (p less than 0.001) than in controls. Three indices of volume expansion were calculated: 1) the ratio between the change in CO and the change in volume, which was significantly higher in hypertensives (p less than 0.025), 2) the ratio between the change in CO and the change in CVP, which was similar in both groups, and 3) the ratio between the change in volume and the change in CVP, which was significantly reduced in hypertensives (p less than 0.001). In the overall population, the latter ratio was negatively correlated with the change in CO (or in stroke volume) induced by expansion ( r = -0.75). The results provided evidence that: 1) the slope of the relationship between CO and blood volume was steeper in hypertensives than in normotensives, and 2) the steeper slope was due to a reduction in the effective compliance of the vascular bed, causing a greater elevation in CO per unit rise in volume.

Adult↗

Bronchial artery infusion of mitomycin-C in advanced bronchogenic carcinoma.

Bronchial angiography was performed in 17 patients with advanced non-oat cell bronchogenic carcinoma. The patients were treated 1 to 5 times with infusions of 10 mg of mitomycin-C (MMC) into the tumor-feeding bronchial artery. All but 2 patients received in addition small doses of vincristine (intravenously) and bleomycin (intramuscularly) or only bleomycin to potentiate the effect of MMC. No major side effects occurred and the systemic toxicity was insignificant. An objective tumor reponse was encountered in 11/17 patients. Intraarterial chemotherapy is strictly local and therefore effective especially in patients with limited or locally advanced disease. In patients with more extensive disease an adjunctive therapy of a more regional or systemic modality must be given.

Adenocarcinoma↗

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↗

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↗