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Intralymphatic antibiotic delivery for reducing acute prosthetic graft infection.

The lymphatic system has been implicated as a source of synthetic graft contamination when grafts are implanted in the presence of a distal septic focus. In previous studies, radical lymphatic excision and ligation were shown to reduce acute graft sepsis. However significant lymphedema precluded its clinical application. The present study was undertaken to evaluate methods for reducing acute graft sepsis while avoiding lymphatic obstructive complications. Twenty dogs were divided into one control and two experimental cohorts. Femoral interposition grafts were placed in each dog. A hind paw septic focus was introduced and therapy included a control (Group I--no therapy), intravenous antibiotics in Group II and intralymphatic antibiotics in Group III. Graft, blood and tissue cultures from each dog were taken at 48 hours. Lymphatic antibiotic therapy resulted in significantly improved graft culture results when compared to the control (p = 0.0003) and intravenously treated animals (p = 0.007). Blood cultures in the intralymphatically treated group were also significantly better (p = 0.003) than the control group.

Animals

[Targeting delivery of liposomal adriamycin by intra-lymphatic infusion].

OBJECTIVE: To assess the feasibility of delivering liposomal adriamycin (lipo-ADM) to the regional lymph nodes via intralymphatic infusion in a rabbits model. METHODS: The plasma and tissue ADM levels were measured by high performance liquid chromatography (HPLC) at 0.5 hour, 1 hour, 6 hours, 12 hours, 1 day, 7 days, 14 days, 28 days. RESULTS: The maximum ADM level (Cmax) in the lymph nodes of lipo-ADM was 91.23 micrograms/g, which was 2 times higher than that of the free-ADM group. The area under the ADM concentrations-time curve (AUC) of the regional lymph nodes of lipo-ADM and free-ADM was 138.34 micrograms/day x g-1, 31.86 micrograms/day x g-1 respectively (P < 0.01). The pathological features showed that the lipo-ADM group had more microabscess, necrosis and fibrosis in the lymph nodes than those of the free-ADM group. The histological changes of heart were absent or slight in the lipo-ADM group. CONCLUSIONS: lipo-ADM has a high affinity for lymphatic tissue. Intralymphatic infusion of lipo-ADM may be useful for the treatment of lymphnode metastasis in ovarian cancer.

Animals

[Intralymphatic B.C.G. infusions. Preliminary results (40 cases)].

A new route of administration for BCG aimed at stimulating immunity in cancer patients is presented. 40 patients received an intra-lymphatic infusion of BCG and in 20 lymphnode dissection was carried out for bacteriological and histological study. Details of technique and the results are given with regard to the effects of BCG on pelvic and pre-vertebral nodes after injection via a foot vessel.

BCG Vaccine

Regional intralymphatic infusion (ILI) of irradiated tumor cells with evidence of distant effects.

A case of canine lymphoma with radiographically-documented involvement of the para-aortic nodes is reported. Intralymphatic infusions (ILI) of cultured irradiated autochthonous tumor cells to remote lymph node bearing areas were associated with a dramatic initial shrinkage of the para-aortic lymphadenopathies. Three ILI timing schedules were used consecutively during a course of 10 treatments, allowing a comparison of responses in the same animal. The reported case suggests that a normal lymph node can be effectively "stimulated" by the same agent approximately every 3 weeks. A possible schedule for intralymphatic infusion is proposed for further investigation.

Animals

Immunosuppressive effect of intra-lymphatic irradiation.

The effect of intra-lymphatic administration of Lipiodol-l131 on the number of T and B lymphocytes, and on the in vivo response to common antigens and to DNCB, was investigated in uremic patients in the pre-transplant period. T lymphocytes have been detected by rosette formation with sheep erythrocytes (E) and B lymphocytes by rosette formation with erythrocytes sensitized with antibody and complement (EAC). After irradiation it was observed a lymphopenia due to a statistically significant decrease in the number of both T and B peripheral blood lymphocytes and a depletion of these cells in the irradiated lymph nodes. Their ability to give delayed hypersensitivity response to common antigens in vivo was lost after intralymphatic irradiation. Two patients were able to develop sensitization to DNCB and this reaction was supressed in one of them by irradiation. These effects of intralymphatic irradiation on the immune system favours further study of this method in clinical renal transplantation.

B-Lymphocytes

[Intralymphatic therapy of peritonitis].

The lymphatic system catheterization methods, the appropriate catheterization side choice were developed by the authors. It was established that the peritonitis progress is accompanied by endolymphatic therapy effect lowering, what demands the application of active organism detoxication methods, hepatoprotective and immunocompensatory therapy.

Anti-Bacterial Agents

Intralymphatic interleukin-2 treatment of a hemophiliac AIDS patient with defective interleukin-2 production.

To improve immune functions in an interleukin-2 (IL-2) deficient hemophiliac AIDS patient suffering from severe Pneumocystis carinii pneumonia, treatment with IL-2 was started in addition to standard antimicrobial therapy. Highly purified IL-2 was administered subcutaneously and then repeatedly intralymphatically in a manner similar to pedal lymphography. No toxicity was observed. The patient temporarily improved clinically as well as with regard to immunological functions. Particularly the in vitro response to phytohemagglutinin (PHA) could partly be restored, and skin tests revealed improved response to recall antigens. These findings indicate that IL-2 can be administered safely and effectively by the intralymphatic route and may--in addition to antibiotics--be of value in AIDS patients with severe opportunistic infections.

Acquired Immunodeficiency Syndrome

Iotasul, a water-soluble (non-oily) contrast medium for direct and indirect lymphography: radiological and morphological investigations in dogs.

Radiological, light microscopic and electron microscopic findings after direct and indirect lymphography with Iotasul, a new non-ionic water-soluble (not oily) contrast medium, are reported. The results of the studies in 18 dogs clearly show that the roentgenological demonstration of the lymph system following intralymphatic administration of Iotasul in the dog is not inferior to that following the use of conventional oily con contrast medium passes quickly to the lymphatic system and the lymph nodes and is eliminated within 24 hours. The complications and tissue reactions known from oily contrast media are not observed following use of the new water-soluble contrast medium. Furthermore, studies of the fine structures show unequivocally that no morphologically detectable changes attributable to the contrast medium occur either in the region of the injection or in the lymph vessels, lymph nodes and organs such as kidney, liver, lung, spleen and myocardium. Preliminary studies indicate that the new contrast medium offers the possibility of indirect demonstration of lymph vessel regions and groups of lymph nodes (indirect lymphography) which have largely escaped detection by the previous routine lymphographic examination.

Animals

IL-2/LAK cell treatment for advanced cancers with emphasis on a novel administration.

Interleukin-2 (IL-2) is a substance produced by activated blood cells called helper T-lymphocytes and has been shown to stimulate the body's immune system. IL-2 may cause certain tumors to regress when administered intravenously to laboratory animals and humans. Lymphokine activated killer (LAK) cells are white blood cells that have been stimulated with IL-2 in vitro. LAK cells are capable of killing tumor cells both in vitro and in vivo, especially when given along with IL-2. Although this form of treatment has been found to be effective in patients with certain cancers who no longer benefit from standard forms of therapy, the anti-cancer effects of IL-2/LAK cell treatment are limited by the serious, life-threatening side effects of high-dose intravenous administration, and by the high cost. A treatment program with low-dose, intralymphatically-administered LAK/IL-2 in patients with advanced cancer is a promising alternative which circumvents these major problems and concerns, while maintaining high response rates.

Blood Component Transfusion

[Intensive intralymphatic and lymphotropic therapy in children].

Study of the effect of endolymphatic therapy with antibiotics and antioxidants on lipid peroxidation and endotoxicosis level in children in critical state showed that endolymphatic infusion of nonenzymatic antioxidants (vitamin E, unithiol) and wide-spectrum antibiotics noticeably reduced the activity of free-radical lipid peroxidation and accelerated detoxication in comparison with the control group.

Adjuvants, Immunologic

[Lymphographically detectable long-term changes caused by endolymphatic radionuclide therapy (ELRT) in the infradiaphragmatic lymph system].

In sixteen patients who had been treated 42 months before on an average for malignant melanomas of the lower extremity (stage I) by a unilateral endolymphatic therapy with 32P/131J-Lipiodol UF, bipedal lymphography with oily contrast medium was performed. In consequence of the high-dosed intralymphatic radiotherapy the lymph nodes of the treated side are markedly reduced in size and number; fourteen out of the sixteen patients, however, showed lymph nodes of normal size and structure which had not been coloured during ELRT. On the basis of this phenomenon, a possible mechanism of formation of metastases in previously treated lymph nodes is discussed. The presentation and extent of radiogenic reactions in the lymph vessels correspond to the changes known for percutaneous irradiation.

Diaphragm

Intralymphatic steroid therapy for lymphoedema: preliminary studies.

Lymph node fibrosis is a significant feature in patients with primary lymphoedema. Its importance in causing obstruction to the flow of lymph has lead to this study which is an attempt to reduce the effect of fibrosis by treatment with a corticosteroid preparation administered by direct intralymphatic infusion. In a pilot study, twenty patients received an intralymphatic infusion of Clobetasol propionate in Ultra-fluid Lipiodol (18 lower limb, 2 face). Clinical improvement occurred in eight of the patients with leg oedema over a period of up to nine months. Both face-affected patients were helped by this form of therapy. In patients with lymphoedema of the lower limb with lymph node abnormalities, it was advantageous if the lymph vessels leading up to the nodes were patent.

Adolescent

[Intralymphatic antibiotic therapy of inflammatory complications in colonic cancer].

In 18 patients with the inflammatory complications of colonic cancer before and after the operation, kanamycin, or one of the antibiotics of a cephalosporin group was administered into the lymphatic vessels of the upper third of a thigh at a daily dose of 20-25 mg/kg of body weight. After 3-4 days, the state of the patients considerably improved. All the patients underwent radical operations with primary restoration of intestinal continuity. There were no progression of purulent complications, postoperative lethality.

Adult

[Intralymphatic administration of open radionuclides in complex treatment of rheumatoid arthritis].

A new method was developed for the treatment of patients with rheumatic arthritis using therapeutic effect of radioactive colloid aurum in the lower limb lymphatic vessels. Altogether 50 patients with various degrees of activity and stages of disease were treated. A positive therapeutic effect was observed in 84%. The method of endolymphatic radiotherapy with radioactive colloid aurum made it possible to give up cytostatic and glucocorticoid therapy and to reduce a dosage of nonsteroid antiinflammatory drugs.

Adult