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PubMedDate not supplied

[Intralymphatic drug therapy--a pathogenetically substantiated method of treatment in peritonitis].

The method of endolymphatic drug therapy (EDT) suggested by the authors has some advantages over the method of endoarterial therapy (which has proved to be effective in clinical practice) because it is aimed not only at control of the microbial flora, but also at correction of rheologic and microcirculatory disorders, improvement of the processes of tissue respiration and metabolism, stimulation of the intestine, prevention of the damaging effect of enzymes, toxins, and poisons on the organs and tissues of the body, and at correction of disorders of the immune status with promotion of the barrier function of the lymph nodes and the lymphatic system as a whole. EDT may be recommended for wide use in the clinic in the treatment of patients with peritonitis and other serious surgical infections unresponsive to the generally applied methods of management.

Adjuvants, Immunologic↗
PubMed1998

[The arteriolymphatic administration of antibiotics in treating patients with suppurative-inflammatory diseases of the abdominal cavity organs].

Experimental study of pharmacokinetics of Gentamicin was carried out in 23 dogs. Three different modes of its intralymphatic administration were used: intranodular inguinal, lymphotropic retroperineal and arterio-lymphatic. It has been established, that arterio-lymphatic mode of introduction of antibiotics (as well as regional endolymphatic and lymphotropic) warrants high concentration of antibiotics in venous blood and lymph. The peculiarity of arteriolymphatic administration is regional effect of accumulation of the antibiotic in organs and tissues of abdominal cavity of corresponding arterial region. Arteriolymphatic infusions of antibiotics have been introduced into complex of drug treatment of patients with pyogenic and inflammatory disorders of abdominal organs. The clinical testing has revealed high curative effect of this made of antibiotics administration.

Animals↗
PubMed1990

A pilot study of intralymphatic interleukin-2. II. Clinical and biological effects.

Interleukin-2 (recombinant methionyl human interleukin-2 alanine 125; IL-2) was administered intralymphatically to 12 patients with advanced cancer in a phase I trial. Doses were administered once a week for 6 weeks in a dosage escalation schedule; patients were entered in four groups at successively higher starting dosages. Toxicity occurred in a profile similar to that seen with intravenous IL-2. The maximum tolerated dose with this route/schedule was 275,000 units/kg, a figure not higher than expected with intravenous administration. T1/2 alpha was prolonged to 54 min from the 13 min figure we obtained with IL-2 given intravenously. Granulocytosis and eosinophilia were seen, along with lymphocytosis following initial lymphopenia. Anti-IL-2 antibodies were seen in 42% of patients (compared to 16% with this agent given intravenously), suggesting increased immunogenicity of this route/schedule. No clinical response was achieved. Immunologic effects will be reported separately but are summarized.

Adolescent↗
PubMed1995

[The intralymphatic administration of adoptive immunotherapy (LAK) in the treatment of patients with metastatic cancer and resistant to conventional therapies. Apropos 50 patients].

Between January 1990 to December 1993, we administered LAK immunotherapy using intralymphatic route to 50 patients with metastatic cancer resistant to conventional therapies. In the preparations of the immunotherapy, followed the technique described by Pizza G. et al. The age of our patients ranged between 50 to 75 years and their Karnosfsky's indexes were above 70%. The histological type of the metastasis was determined by cytology and the size by Rx, ECO and/or TAC before and after the administration of the immunotherapy. In the intralymphatic administration, we followed the technique described by Pizza G. et al. The immunological therapy was administrated on days 1, 21, 90 and 111 and the clinical responses were assessed by RC, RP, SD and F. The immunological behaviour of the host was assessed through the determination of lymphoid populations (CD2, CD3, CD4, CD5 and CD8) and natural killer cells were studied with monoclonal antibodies CD3 and CD16. Such immunological study was carried out before the administration of each immunotherapy series. In 12 out of 50 patients (24%), we were able to administer the four LAK series. Such patients were subsequently studied, observing that although tumoral lesions did not increase in size, they did not disappear and, thus, they were classified as clinical stables. Clinical and analytical toxicity were null. The immunological study showed changes in immunological parameters, however these changes were not statistically significant.

Aged↗
PubMed1982

[Intralymphatic administration of BCG-CWS in advanced malignant melanoma].

BCG-CWS was administrated into lymphatic vessels in the treatment of advanced malignant melanoma metastasized to the lymph node of the posterior peritoneum. Side effects consisted of fever, lymphangitis, a decrease in urinary output and a slight rise in serum GOT, there being no serious side effects. Clinically, tumor mass in the abdomen cleared but metastases to the other organs increased, and the patient died of general dispersion of the disease. At autopsy, the abdominal mass became flat, with the cut surface of yellowish brown color. Histologically, this mass formed necrosis made up of destroyed tumor cells and histiocytes. BCG-CWS mediated histiocyte response appeared to destroy tumor cells. Thus, it is possible that local administration BCG-CWS could elicit a potent response even in advanced carcinoma. Since the contact of BCG-CWS with tumor cells produced this response, administration of BCG-CWS into the lymphatic vessels may be indicated where the lymph current to the metastasized lymph node is not obstructed. This treatment would be effective particularly in the case of micrometastasis, and there is a possibility that it could elicit a specific response.

Aged↗
PubMed1992

[Intralymphatic administration of adoptive (LAK) immunotherapy in the treatment of patients with metastatic cancer resistant to conventional therapies].

Between January, 1990 and May, 1991, we administered LAK immunotherapy using the intralymphatic route to 25 patients with metastatic cancer resistant to conventional therapies. In the preparation of the immunotherapy, we followed the technique described by Pizza G. et al. The age of our patients ranged between 50 and 75 years and their Karnofsky's indexes were above 70%. The histological type of the metastasis were determined by Rx, ECO and/or CAT before and after the administration of the immunotherapy. In the intralymphatic administration, we followed the technique described by Pizza G. et al. The immunological therapy was administered on days 1, 21, 90 and 111 and the clinical response was assessed by RC, RP, EE and F. The immunological behaviour of the host was assessed through the determination of lymphoid populations (CD2, CD4, CD5 and CD8) and cytolytic cells were studied with monoclonal antibodies CD and CD16. Such immunological study was carried out before the administration of each immunotherapy series. In 7 out of 25 patients (28%), we were able to administer the four LAK series. Such patients were subsequently studied, observing that, although tumoral lesions did not increase in size, they did not disappear and, thus, they were classified as clinically stable. Clinical and analytical toxicity was null. The immunological study did not show any statistically significant changes and the activity of cytotoxic cells (NK) was not modified.

Aged↗
PubMed1984

[Intralymphatic administration of antibiotics in the complex treatment of suppurative complications in patients with neurosurgical pathology].

The efficacy of endolymphatic route of gentamicin and ceporin administration was studied in 89 patients with neurosurgical pathological processes complicated by acute pneumonia (80 patients) and meningoencephalitis (9 patients) usually after ineffective antibiotic therapy according to the routine methods. The antibiotics were used in accordance with the antibiograms of the causative agents isolated from the bronchial tree or CSF. The endolymphatic use of gentamicin or ceporin once a day in doses of 80 mg or 1 g respectively provided rapid sanation and arresting of the inflammatory foci, lowering of the intoxication level, more rapid promotion of the positive time course of the clinico-roentgenological and laboratory indices and decreasing of the recovery periods by 1.5-2 times in 86 per cent of the patients with pneumonia. The endolymphatic administration of gentamicin in a dose of 80 mg twice a day or ceporin in a dose of 1 g twice a day allowed one to maintain the antibiotic therapeutic levels in the cerebrospinal fluid and to obtain satisfactory clinical results in the combined treatment of meningoencephalitis. The endolymphatic administration of the drugs was well tolerated by the patients and no adverse reactions were observed. This route of administration of antibiotics and in particular broad spectrum antibiotics may be recommended for urgent antibacterial therapy of especially severe neurosurgical patients with pyo-inflammatory complications and patients who did not respond to the routine antibiotic therapy.

Adolescent↗
PubMed1988

Treatment of recurrent squamous cell carcinoma of the head and neck with low doses of interleukin-2 injected perilymphatically.

Ten patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line purified by high pressure liquid chromatography for 10 days. Two hundred units of IL-2 in 0.5 ml were injected 1.5 cm from the insertion of the sternocleidomastoid muscle on the mastoid. When possible, courses were repeated at 45-day intervals. IL-2 was ineffective in two patients who had already undergone functional or radical neck dissection. By contrast, in six patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. The injections were occasionally followed by moderate local swelling and lymph node pain, but no systemic disturbances.

Adult↗
PubMed1990

Endolymphatic chemotherapy in gynecologic cancer.

Bleomycin oil suspension was infused preoperatively into the bilateral pedal lymphatic vessels of 18 patients with cancer of the vulva, uterine cervix, and endometrium. The object of this technique was to reduce the number of local recurrences in pelvic and abdominal lymph nodes. Except in the case of two patients, it was possible to infuse both extremities. Side effects of the treatment were generally mild. In a postoperative study of the surgical specimens, metastases were found in 18 lymph nodes. All of these showed selective necrosis of existing metastases and conservation of the morphology of healthy nodes. Necrosis of the primary tumor was occasionally produced.

Bleomycin↗
PubMed1979

A clinical trial of endolymphatic therapy in malignant melanoma: interim report of the progress of the Medical Research Council trial.

This report presents the interim results of the MRC trial on the treatment of Stage I melanoma of the lower limb by endolymphatic therapy. Over a 10-year period a group of 146 patients has been entered into the trial. Although total recurrence rates were not significantly affected by endolymphatic therapy, recurrence in the lymph nodes was largely prevented. More patients in the standard treatment group needed the more major procedure of block dissection. The survival rates for the endolymphatic and standard treatment groups did not differ significantly.

Adolescent↗
PubMed1997

Deletion of alloantigen-reactive thymocytes as a mechanism of adult tolerance induction following intrathymic antigen administration.

Direct injection of foreign antigen into the adult thymus is a potent route of antigen delivery for the induction of tolerance in vivo. In this report, we demonstrate that tolerance to C57BL/10 (H2b/BL10) alloantigens can be induced in CBA/Ca (H2k/CBA) mice by intrathymic (IT) administration of BL10 spleen leukocytes coincident with transient peripheral immunomodulation of CD4+ T cells using a depleting anti-CD4 monoclonal antibody. T cell receptor (TCR) transgenic mice (BM3.6; H2k) expressing a CD8-independent TCR specific for H2Kb were used as recipients to facilitate investigation of the mechanisms responsible for tolerance induction by allowing visualization of events in the thymus following IT injection. IT administration of 5 x 10(7) BL10 spleen leukocytes and concomitant transient peripheral T cell depletion in BM3.6 mice resulted in a substantial H2Kb-specific deletion of transgenic-TCR+ (tg-TCR) thymocytes which was dependent on the level of tg-TCR expression. IT deletion and the failure to export CD8+ T cells to the peripheral lymphoid organs correlated with the induction of tolerance to H2Kb; TCR transgenic mice that had received IT injection of BL10 splenocytes and peripheral T cell depletion accepted a H2Kb+ cardiac allograft indefinitely. Analysis of tolerant BM3.6 mice revealed that there were low numbers of CD8+ T cells in the periphery giving rise to a substantially reduced reactivity in vitro despite the fact that no donor cells or IT deletion were observed in the thymi of the majority of tolerant mice. These results demonstrate for the first time that IT injection of foreign alloantigen into an adult thymus results in the deletion of thymocytes expressing a TCR specific for the injected alloantigen and suggest that this is an important mechanism of tolerance induction following IT injection of alloantigen in vivo. Furthermore, analysis of tolerant TCR-transgenic mice suggests that IT deletion is not required for the maintenance of tolerance, and that peripheral mechanisms enforce continued hyporesponsiveness to H2Kb following transplantation.

Animals↗
PubMed1997

Thymic T cell export is not influenced by the peripheral T cell pool.

The peripheral T cell pool is maintained both by export of naive T cells from the thymus and by post-thymic expansion of activated/memory T cells. However, it is not known whether the thymus can alter its output following peripheral T cell depletion. Using intrathymic injection of fluorescein isothiocyanate to detect recent thymic emigrants (RTE), we directly tested whether the thymus is able to alter the number of RTE or the CD4:CD8 ratio of RTE emigrating to the periphery in response to in vivo depletion of total peripheral T cells or CD4 T cells, respectively. Depletion of peripheral T cells was achieved with anti-Thy-1 or anti-CD4, at doses that did not affect thymocyte numbers. Depletion of greater than 70% of peripheral T cells by treatment with anti-Thy-1 in vivo did not alter the number or cell cycle status of RTE trafficking to lymph nodes or spleen during the peripheral reconstitution phase (6, 9, 12 days). Similarly, depletion of the majority of CD4 T cells, which significantly reduced the peripheral CD4:CD8 T cell ratio, did not alter the total number or the proportion of CD4+ CD8- RTE in peripheral lymphoid organs. These data clearly indicate that thymic output is not influenced by downstream alterations in peripheral T cell pool size or CD4:CD8 ratio. Rather we contend that thymic T cell export is internally regulated by as yet undefined mechanisms.

Animals↗
PubMedDate not supplied

Interleukin-2 injected around tumor-draining lymph nodes in head and neck cancer.

Twenty patients with recurrent, inoperable head and neck squamous cell carcinoma received perilymphatic injections of natural interleukin-2 (nIL-2) for 10 days. Ten patients received 200 units (U) of nIL-2; five 1,000 U; and five 5,000 U. Irrespective of the location of the recurrence, the injections were always performed 1.5 cm below the insertion of the sternocleidomastoid muscle on the mastoid. When the ipsilateral lymphatic chain was still present, they were performed on the same side as the tumor site, whereas when it had been stripped as a result of previous surgery, they were contralateral. Patients who had undergone bilateral neck dissection were injected on the tumor side. Whenever possible, the treatment was repeated after 45-day intervals. In 13 patients (65%) with bilateral or contralateral lymph nodes, complete or partial disappearance of the lesion was observed. Despite these marked responses, the tumor always relapsed, and subsequent IL-2 courses were poorly effective. There were no systemic disturbances during or after treatment, but only moderate local swelling and pain.

Adult↗