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At least 19 recordsLinked to original sources

Direct intralymphatic injection of radiolabeled 111In-T101 in patients with cutaneous T-cell lymphoma.

Direct intralymphatic administration of radiolabeled monoclonal antibody in targeting antigen-bearing lymphoma cells in regional lymph nodes of patients with cutaneous T-cell lymphoma was evaluated. Seven consecutive patients undergoing staging lymphangiography received intralymphatic infusions of 111In-T101 to evaluate lymph node involvement. This procedure was accomplished without significant complication. The 111In-T101 rapidly distributed throughout the regional lymphatic compartment and passed into the systemic circulation. Tumor-bearing sites in the inguinal-femoral lymph nodes retained from 0.42 to 4.8% of the injected dose of radiolabeled antibody. Three patients were upstaged to Stage IVA based on tumor involvement found after radiolymphoscintigraphy-directed biopsy of groin lymph nodes, selected because of intense radioactivity by gamma camera imaging. Compared with previously reported s.c. antibody administration, there was a marked reduction in the radioactive exposure of normal tissues at the injection sites in the lower extremities. Direct intralymphatic delivery of 111In-T101 appears to be a feasible, efficient method for delivering therapeutic doses of radiolabeled antibody.

Adult

Intralymphatic injection of BCG into rhesus monkeys.

Since the route of administration of BCG may have an important function in immunotherapy, we investigated intralymphatic administration to direct BCG to the lymph nodes. Multiple injections of high doses of BCG were administered to 6 rhesus monkeys via the dorsal lymphatics of the lower limb. A suppurative lymphadenitis was observed along the lower limb and in the inguinal area in 5 of the 6 monkeys. However, many of the complications reported with other routes of administration were not observed. Granulomatous reactions and histiocytic responses developed in lymph nodes on the injected sides of the pelvis and distant nodes as well as in the liver. The intralymphatic route is the method by which high doses of nonspecific immunostimulants were delivered to regional lymph nodes. The efficacy of this approach remains to be established in tumor-bearing animals and humans.

Animals

Distribution and consequences of cell suspensions following intralymphatic infusion.

The fate and consequences of intralymphatic injections of cells was investigated in dogs. The distribution of intact radiolabeled cells was determined in vivo by whole body gamma scanning. Comparison of distributions resulting from intralymphatic, subcutaneous, intradermal and intravenous routes of administration showed that the distribution and duration of radiolabel in various organs varied with the route of administration. Following intralymphatic injection, radiolabel was concentrated in first echelon lymph nodes draining the site of injection and was retained in these nodes for over 4 weeks. Histologic studies showed intense cortical and paracortical lymphopoiesis to be associated with the retention of intralymphatically injected tumor cells by first echelon lymph nodes. Serial histologic examination of lymph nodes from intralymphatically injected inbred beagles revealed that the consequent lymphopoiesis persisted for 5 weeks. In vitro evaluation of peripheral blood and lymph node lymphocyte cytotoxicity to the injected cells indicated that retention and nodal lymphopoiesis was associated with the development of direct lymphocyte cytotoxicity. The effects of concommitant tumor burden, cytotoxic drugs and ionizing radiation were also investigated and suggest that the therapeutic potential for use of the intralymphatic route has not yet been realized.

Animals

A phase I study of active specific intralymphatic immunotherapy (ASILI).

Twenty-one patients with advanced malignancies who had exhausted or refused conventional modalities of treatment were entered in a Phase I toxicology trial of active specific intralymphatic immunotherapy (ASILI). The patients were immunized with 1 X 10(7) to 1.2 X 10(8) viable autochthonous or allogeneic irradiated tumor cells intralymphatically each month and received no other antineoplastic treatment. To date, 274 intralymphatic injections have been performed and except for one case of bacterial lymphangitis, no adverse side effects have been observed. ASILI did not significantly alter peripheral blood lymphocyte counts, absolute E-rosette forming cell levels, or EA-rosette forming cell levels. PHA reactivity of peripheral blood lymphocytes increased slightly in all but one patient tested. Seven out of nine patients who had not had delayed hypersensitivity to recall antigens developed positive reactions following ASILI. Sixteen out of twenty patients tested also developed reactivity to their immunizing cells after treatment. Objective regression (greater than 50% reduction of tumor mass) was observed in five out of nineteen evaluable patients. Six patient showed stabilization of tumor growth and eight patients continued to progress under treatment.

Adult

Endolymphatic isotope and BCG in the management of malignant melanoma.

Endolymphatic isotope therapy had such promising early clinical results that the M.R.C. (Medical Research Council) U.K. set up a clinical trial in 1966. This was to compare the effect of endolymphatic isotope therapy with the results of standard methods in the treatment of lower limb malignant melanoma. The interim report had three groups for analysis: Standard Methods (S); Endolymphatic Satisfactory (ES); and Endolymphatic Unsatisfactory (EU). This third group was a subdivision, as a significant number of patients did not have the correct endolymphatic treatment. The five-year survival figures expressed as actuarial percentages were ES=78.8%; S=82.3%; and EU=57.3%. Lymph node recurrence showed a significant difference: ES=2.3%; EU=12%; and S=19%. The conclusions were that endolymphatic isotope therapy was justified in specialized centres where good results could be obtained. Further animal experiments using the VX2 tumour in rabbits indicated that BCG given intracutaneously or intravenously had no therapeutic effect, whereas when applied by intralymphatic injection BCG was successful in treating lymph node metastases. Nineteen patients with poor-prognosis malignant melanoma have received endolymphatic BCG. The clinical results are recorded in this paper and are sufficiently encouraging to warrant its continued use.

Animals

Vitiligo-like depigmentation and morpheas after specific intralymphatic immunotherapy for malignant melanoma.

We report the case of a patient with stage 2 malignant melanoma (MM), who received a specific immunotherapy consisting of intralymphatic injections of irradiated MM cells. She developed subsequently vitiligo-like leukoderma and several plaques of localized scleroderma. Simultaneously an increase in the patient's cytotoxic activity against MM cells was detected in vitro. The responsibility of immune phenomena and specific immunotherapy for the appearance of depigmentation and morpheas is discussed.

Aged

Accelerated cytodifferentiation of antibody-secreting cells in guinea-pig lymph nodes stimulated by sheep erythrocytes and lymphokines.

Lymphokines, produced in response to structurally unrelated antigens, altered the course of a primary anti-sheep erythrocyte plaque-forming cell response within the regional lymph nodes of normal guinea-pigs. Intralymphatic injection of a small dose of lymphokines (0-5-8 mug) 1 day after antigen priming accelerated the rate of indirect plaque-forming cell cytodifferentiation between the 5th and the 9th days of the response. This effect was not related to changes in the level of antigen trapping by lymph node macrophages, but the lymphocyte mitogenic activity may have been important for the response since there was a significant increase in [3H]thymidine incorporation within the lymphokine-treated nodes on the 3rd day following immunization.

Animals

Vestibular effects of antibiotics introduced in the inner ear. Behavioral and electrophysiological studies in the frog.

The aim of this study was to find a rapid and suitable method for testing the toxicity of drugs upon the vestibular end organs. The experiments were performed in the frog and the action of two antibiotics, streptomycin sulphate and penicillin G, was studied by carefully observing the equilibrium behaviour of the animals and recording the spontaneous activity of the nerve of the horizontal semicircular canal. The results obtained show that: 1) injection of streptomycin sulphate (20 microgram) directly into the labyrinthic cavity elicited disorders of the equilibrium and reduced the spontaneous activity of the horizontal canal nerve; 2) these disorders were reversible or not depending on the animal; 3) there is a good correlation between behavioral observations and electrophysiological data (i.e. the activity of the ampullary nerve was low in frogs whose behaviour was impaired at the time of sacrifice; the activity did not differ from controls when the normal behaviour was completely restored); 4) injection of penicillin G or 0.7% NaCl into the labyrinthic cavity had no effect on the equilibrium of the frogs or on the activity of the ampullary nerve; 5) intramuscular or intralymphatic injections of streptomycin sulphate produced a neuromuscular block but did not alter the activity of the ampullary nerve. In conclusion, the question of ototoxicity is discussed.

Action Potentials

A pilot study of intralymphatic interleukin-2. I. Cytotoxic and surface marker changes of peripheral blood lymphocytes.

Patients with metastatic solid tumors were treated with six escalating doses of weekly intralymphatically injected recombinant interleukin 2 (i.l. IL-2). Nine patients completed the treatment and were evaluated for immunologic features of their peripheral blood lymphocytes (PBLs). The patients' PBL counts increased 4 days after the first i.l. IL-2 injection. The cell counts remained higher than baseline in week 6 prior to the last i.l. IL-2 injection. However, the PBL number decreased below baseline 1 day after the sixth injection, and recovered to normal levels after 3 days more. Natural killer (NK) activity showed similar changes when calculated as total activity per ml of blood. In vitro 1 h treatment of PBLs with IL-2 greatly enhanced NK cytotoxicity. The enhancement was only slight in the first week of i.l. IL-2 treatment, but was significantly greater on day 35 (7 days after dose 5) and day 39 (4 days after dose 6). In contrast, the increase was similar to the baseline on day 36, the day after the sixth injection. No lymphokine-activated killer activity was detected in the patients' PBLs with or without short-term in vitro IL-2 treatment. Besides the NK cytotoxic function, lymphoid subpopulations were evaluated numerically for total T cells (CD3/OKT3), T-cell subsets (CD4/OKT4 and CD8/OKT8), B cells (OKB7), NK cells (CD56/NKH1/Leu19, CD16/Leu11), and monocytes/NK cells (CD11b/OKM1). The activation markers (HLA-DR, CD25/Tac, and CD38/OKT10/Leu17) were also included. Intralymphatic IL-2 treatment had no effect on the PBL surface marker expression in the first week of treatment. However, by week 6, the percentages of cell populations expressing the NK-associated antigens CD56, CD16, and CD11b were significantly increased. In contrast, the percentage of CD3-positive T cells showed no change or a marginal decrease. Prior to and after i.l. IL-2 treatment, the CD56-positive cells in the PBLs were predominantly CD16 positive and CD3 negative. The i.l. IL-2 treatment did not induce PBL proliferation, or changes in the expression of CD25 (Tac), HLA-DR, CD38, CD4, CD8, CD57, or OKB7 in the patients' PBL. These results indicate that i.l. IL-2 treatment does affect the total number of PBLs, the cells expressing NK activity, and NK-associated surface markers.

Antigens, Differentiation

Lymph drainage from the vulva and the foot as demonstrated by 198Au.

From the central part of the labium majus the lymphatic transport of 198Au is invariably bilateral to inguinal and pelvic lymph nodes. Thus, bilateral inguinal and low pelvic lymph-adenectomy is logical in the treatment of carcinoma of the vulva. 198Au injected subcutaneously and Lipiodol injected intralymphatically in the dorsum of the foot were transported exclusively to ipsilateral inguinal and pelvic lymph nodes. Thus, there is no need for contralateral lymphadenectomy in malignancies on the dorsum of the foot.

Female

Lymph transport before and after regional lymphadenectomy as demonstrated with 99Tcm. Preliminary experiences.

The lymphatic transport of a radioactive tracer injected intralymphatically on the dorsum of the foot was determined before and after surgery in 3 patients with vulvar carcinoma. The centrally recorded activity curves showed different time courses before and after inguinal lymphadenectomy, suggesting that the lymphatic transport is short-circuited via lymphovenous anastomoses after lymphadenectomy. Thus, non-radical surgery for primary carcinoma combined with lymphadenectomy will increase the risk of haematogenous spread.

Female

Comparative metabolism of histamine in two Amphibia anura.

The metabolism of histamine has been compared in Rana ridibunda and Discoglossus pictus, both Amphibia anura. An intralymphatic injection of 14C-histamine (5 microCi) was administered to the animals and the total radioactivity excreted in the urine was measured 24, 48, and 72 hours later. The metabolites excreted in the urine at 24 hours were analyzed by thin-layer chromatography and subsequent autoradiography. In both species approximately 60--70% of the injected dose was found in the urine by 72 hours. In Rana ridibunda two histamine metabolites were found: imidazoleacetic and methylimidazoleacetic acid. The present results suggest that the catabolism of histamine differs in the two species.

Amphibians

[Clinical pharmacokinetics of kanamycin in endolymphatic therapy of peritonitis].

The pharmacokinetics of kanamycin in patients with peritonitis was studied after its intramuscular, endolymphatic and lymphotropic administration. Endolymphatic administration of kanamycin provided an increase in its activity in the inflamed tissues of the peritoneum and omentum and markedly prolonged its halflife as compared to those after the routine intramuscular administration of the drug. Lymphotropic administration of kanamycin failed to provide the same effect. Endolymphatic therapy of the patients during the postoperative period provided a decrease in the lethality, development of complications and the terms of the treatment in the hospital. The therapeutic effect of the endolymphatic administration of kanamycin to the patients with peritonitis proved to be high. The more efficient antibiotic therapy of the cases was likely due to favourable shifts in the pharmacokinetics of kanamycin after its endolymphatic administration.

Adolescent

[Lymphotropic antibiotic therapy of obstetrical suppurative-septic diseases].

The pharmacokinetics and efficacy of gentamicin after its direct and indirect endolymphatic administration were comparatively studied. It was shown that the time course of the blood pharmacokinetics of the antibiotic was almost the same as under the both conditions. Therefore, in many cases the less complicated and more available indirect endolymphatic therapy may replace the direct labor-consuming and traumatic endolymphatic administration of drugs.

Cesarean Section

[The 5-fluorouracil content of the pancreas and parapancreatic tissues when it is administered regionally into the tissue of the round ligament of the liver].

In the experiment on 31 dogs there was shown a significant increase of 5-fluorouracil concentrations in the pancreas and parapancreatic tissues with regional methods of its administration in the fat of the round ligament of the liver. A more prolonged preservation of the drug concentrations at the therapeutic level in the blood was observed. The most effective method of the cytostatic therapy is the regional lymphotropic method.

Animals

[An experimental validation of the endolymphatic administration of pharmacological preparations for stimulating intestinal peristalsis in emergency surgery on the abdominal cavity].

Experiments were conducted on 75 rabbits to study the efficacy of endolymphatic administration of aceclidine, obsidan, and cerucal for stimulation of the intestine in its experimental paresis. The stimulating effect of the pharmacological agents was found to be of a longer duration in endolymphatic that in intravenous administration. This allowed endolymphatic pharmacological stimulation of the intestine to be suggested for the use in abdominal surgery.

Abdomen

[A lymphotropic method of therapy for patients with fresh forms of syphilis (clinical and experimental research)].

Experimental study of benzylpenicillin procain salt kinetics in lymphotropic and intramuscular administration of 600,000 U has revealed a more intensive saturation of the lymph system and a longer persistence of high concentrations of the drug in the blood serum, organs and tissues of the body after lymphotropic administration, as against intramuscular one. Comparison of the efficacies of 16-day courses of therapy of patients with fresh syphilis with benzylpenicillin procain salt administered lymphotropically (once daily, 600,000 U) or intramuscularly (twice daily, the same dose) has shown the advantages of the former method as regards the therapeutic, pharmacokinetic, and economic aspects.

Adolescent