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PubMed1975

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↗
PubMed1985

Distribution of radiolabeled multilamellar liposomes injected intralymphatically and subcutaneously.

The distribution of negatively charged multilamellar vesicles (MLV) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol administered subcutaneously (s.c.) and intralymphatically (i.l.) was studied in rats and dogs. In rats, the drainage of 99mTc-MLV from the s.c. space was slow, with 35% of the activity still remaining at the site of injection after 48 h and minimal systemic distribution (less than 5% at any time point). In the dog, 99mTc-MLV and 111In-MLV injected s.c. on the dorsal surface of a hindpaw were drained both by the lymphatic system and the systemic circulation; at 24 and 72 h, significant activity still remained at the site of injection. Lymphatic uptake was almost limited to the popliteal nodes and was enhanced by dividing the dose in several s.c. injections. Liver and kidney uptake was also observed, most likely as a result of direct liposome absorption into the systemic circulation. The i.l. administration (via left hindpaw) of 99mTc-MLV to a dog resulted in an immediate uptake in the abdominal and mediastinal lymph nodes, and in the liver and spleen. Compared with small unilamellar vesicles, MLV injected s.c. can provide a slower and more prolonged delivery of drugs to the regional lymph nodes.

Animals↗
PubMed2000

Transport of viral-size particulate matter after intravenous versus intralymphatic entry.

OBJECTIVE: Investigation of the transport of viral-size particles after intravenous versus intralymphatic injection and the functional validity of lymphatico-venous communications. METHODS: In the canine model, [99mTc] sulfur colloid particles (100-200 nm) were injected into either the principal vein or into the main lymphatic channel exposed at the paw. Samples of blood and lymph were collected at the groin from the cannulated femoral vein and from a major lymphatic vessel. Parameters including particle arrival time, concentration, flux, and accumulation were determined for a 45-minute period using gamma counting. RESULTS: After intralymphatic injection, particles arrived in the venous blood in an average of 4 seconds. The mean arrival time of particles in the lymph after intravenous injection was 25.4 +/- 6.44 minutes. Intralymphatic injection increased lymph flow and enhanced particle transport. Concentration values in the venous blood after intralymphatic injection and in lymph after intravenous injection were comparable. Flux values depended primarily on flow conditions. Particle accumulation in the lymph after intravenous injection was delayed, but continued to increase throughout the experiment. CONCLUSIONS: There are functional lymphatico-venous communications at the very peripheral level under physiological conditions, which allow rapid transport of viral-size particulate matter between the two pathways and may contribute to the spread of viral infection.

Animals↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1992

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↗
PubMed1988

Patent blue V encapsulation in liposomes: potential applicability to endolympatic therapy and preoperative chromolymphography.

The water soluble dark blue stain Patent Blue V was incorporated into liposomes to increase its depot properties. Experiments with intraperitoneal and intramuscular application in rats and with intralymphatic injections in rabbits showed a substantial difference between the pharmacokinetics of aqueous and liposomal solutions. Independent of the route of administration, the dye-stain remained much longer in the tissues using liposomes. Most notably, retroperitoneal lymph nodes in rabbits remained dark blue up to 28 days after hindlimb endolymphatic instillation of liposomal patent blue. This vastly superior depot effect may be clinically adaptable for endolymphatic therapy with cytostatic drugs to enhance nodal drug retention and concentration or for preoperative chromolymphography to facilitate nodal visualization at laparotomy.

Animals↗
PubMed1975

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↗
PubMedDate not supplied

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↗