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[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

[Effect of obsidan on lymph flow and lymphatic microvessels].

Life-time microscopy showed possible direct effects of obsidan on lymph vessels and flow in the experiment. With local application of the drug there was a short-term constriction, higher frequencies and lower amplitudes of lymphangionic pulsation; during its intramuscular injection, sustained dilator effects, two-phase shifts in the frequency and limitation of pulse amplitude were seen. With the two routes of obsidan administration heterogenous, unpersistent changes in the linear velocity of lymph flow were observed.

Animals

[Accumulation of gentamicin in biological fluids, organs and tissues during regional lymphotropic therapy with antibiotics].

Gentamicin distribution in biological fluids, organs and tissues, lymph nodes was studied on 70 dogs. Three administration routes were compared: lymphotropic, intramuscular and regional subcutaneous. The lymphotropic route for the drug administration was recommended not long ago. It was shown that the lymphotropic route provided the antibiotic accumulation mainly in some of the abdominal organs as compared to intramuscular administration. Regional lymphotropic administration of the antibiotic to the experimental animals resulted in higher gentamicin levels in the regional lymph nodes and regional organs as compared to the levels observed after the antibiotic regional subcutaneous administration in the same doses.

Animals

[Pharmacolymphography].

With the goal of accelerating the contrast-medium injection at the lymphography and improving the contrasting of the vessels and node conduction system the authors applied a variety of pharmacological preparations: Ridol (G. Richter), Nospanum (Quinoine, HPR), Arfonadum (Hoffman-La Rochet, Switzerland), Xavinum (Quinoine) etc. in 110 cases of various malignant neoplasms. All the selected drugs are, to a greater or lesser extent, of a vasodilative effect. It has been found that Ridol together with the combination of Novocaine and Nospanum produce a pronounced lymphotropic effect. Pharmacolymphography with these preparations contributes to the shortening of the time necessary for the injection of contrast-medium and also improves the image of the intermediate node sinuses and of the thoracic duct.

Adolescent

Lymphocyte emigration from high endothelial venules in rat lymph nodes.

Sequential events during lymphocyte emigration from high endothelial venuses (HEV) were studied by scanning and transmission electron microscopy combined with regional perfusion techniques. The results indicate that blood lymphocytes selectively adhere to HEV surfaces through microvilli which attach to shallow pits on the luminal surfaces of high endothelial cells. These intercellular contact points resist hydrodynamic and osmotic shearing forces, but can be disrupted by treatments which remove endothelial glycocalyx, hydrolyse lymphocyte surface glycoproteins, or chelate divalent cations. After this initial attachment phase, lymphocytes enter apical clefts between endothelial cells where they assume a motile configuration characterized by loss of microvilli and formation of irregular surface folds. Intramural lymphocytes adhere to adjacent endothelial cells through macular and villous contacts. Fibrillar electron-dense material traverses the 15-20 nm gap at these points of adhesion. Microtubules and microfilaments are also seen around areas of cytoplasmic constriction in these motile lymphocytes. The migrating lymphocytes show cytoplasmic polarity which is oriented in the direction of movement as they pass through extracellular spaces in the venular wall and cross successive laminations in the perivascular sheath to enter the node. Since these lymphocytes enter channels between endothelial cells which are stained by intralymphatic injections with horseradish peroxidase, it is suggested that their entry into the node depends upon migration along a chemotactic gradient.

Animals

[Intralymphatic antibacterial therapy of acute cholecystitis].

Clinical examination of 34 patients showed that lymphotropic administration of antibiotics creates concentrations in organs and tissues involved in the inflammatory process in acute cholecystitis which are 1.63-14.95 times higher than those produced by intramuscular injection. Study of the course of the clinical picture of the disease in 122 patients with acute destructive cholecystitis revealed the high efficacy of this method of antibiotic therapy: the laboratory indices of the inflammation became normal within a shorter period of time, the inflammatory process in the gallbladder was arrested more rapidly, the number of postoperative complications fell 2.6 times, and the terms of hospital-stay of the patients reduced by 1.3 times. Lymphotropic antibiotic therapy is more pathogenetic in the management of acute destructive cholecystitis.

Acute Disease

[Pharmacokinetics of gentamicin after its regional endolymphatic and lymphotropic administration to dogs].

It was shown that intralymphatic+ inguinal administration of gentamicin provided its high concentrations in central lymph, blood and ++para-aortic lymph nodes and increased the antibiotic levels in the abdominal organs 2.33 to 6.66 times as compared with its intramuscular administration while lymphotropic retroperitoneal administration of gentamicin provided more prolonged maintenance of the antibiotic therapeutic concentrations in lymph of the thoracic lymphatic duct, central blood, ++para-aortic lymph nodes and the abdominal organs in comparison to its intramuscular administration. Intralymphatic+ inguinal administration of drugs providing the highest concentrations in all the organs of the abdominal cavity and the ways of the infection penetration is useful in therapy of severe inflammatory diseases of the abdominal organs inclined to generalization and lymphotropic retroperitoneal administration of drugs is useful in therapy of less severe purulent inflammatory processes in the abdominal cavity.

Animals

Experimental induction of caseous lymphadenitis in sheep by intralymphatic inoculation of Corynebacterium ovis.

Lesions histologically similar to those of natural caseous lymphadenitis developed in sheep popliteal lymph nodes following injection of viable Corynebacterium ovis cells into afferent lymphatic ducts. Histopathological examination of affected lymph nodes suggested that exotoxin might be involved in the establishment, progressive development and persistence of caseous lymphadenitis lesions through localised cytotoxicity.

Animals

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

[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

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