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The possibility of objective estimation of the peritonitis severity by the nose skin autoflora, leucocytic intoxication index (LII) and central lymph toxicity was studied on 25 dogs. The forearm skin autoflora, LII and central lymph toxicity were estimated clinically in 86 patients. The advantage of the endolymphatic therapy with kanamycin over its intramuscular injection was shown.
A new procedure for antibiotic administration via endolymphatic route was developed. Experiments performed on 34 dogs revealed differences in the pharmacokinetics of gentamicin in the central lymph after its administration in a dose of 4 mg/kg via endolymphatic and intramuscular routes: the maximum levels of 590 and 23 mg/kg were determined in 15 and 45 minutes respectively. In 1 hour the concentrations decreased to 17 and 10 mg/kg. When gentamicin was administered endolymphatically it remained in the lymph and blood in concentrations of 0.2 and 0.8 mg/kg respectively for 24 hours. The kinetics of gentamicin in the blood serum within the first 6 hours after its administration by both routes did not differ significantly. After endolymphatic administration high concentrations of gentamicin (56-36 mg/g) were determined in the paraaortal and retroperitoneal lymph nodes in 10-24 hours. Within the period of the 4th to the 13th day its concentrations of at least 5 mg/g were detected. The changes in the structure of the lymph nodes observed 18-48 hours after the antibiotic endolymphatic administration were reversible and returned to normal by the 96th hour. The first experience with the clinical use of the endolymphatic route of gentamicin administration showed its high efficacy in 84.8% of the patients with severe purulent inflammatory diseases of the organs of the abdominal cavity. The antibiotic was used in a dose of 80 mg once a day. The treatment course consisted of 5-6 infusions. Perspectives of the further experimental and clinical investigation of the procedure are indicated. Endolymphatic administration of antibiotics makes it possible to increase the efficacy of antibiotic therapy of a number of severe inflammatory infections.
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The article deals with the treatment of infectious complications in persons with severe concurrent trauma. Microbiological study of the wound discharge and damaged tissues showed staphylococci and blue pus bacillus to be the principal causative agents of infectious complications. In view of the poor response of the immune system to the opportunistic flora, the performance of passive immunization with antistaphylococcal and antipseudomonal plasma is pathogenetically grounded. Taking into account the involvement of the lymphatic system in the infectious process, endolymphatic administration of the immune plasma is suggested.
The lymphotropic infusion of antibiotics through the Brun point in combination with Dibazol to patients operated upon for acute gangrenous and perforating appendicitis has not only antiinflammatory action, but also stimulates the immunobiological non-specific reactivity of organism and reduces lethality from 3.5% to 0.41% and makes time of the hospital and ambulatory treatment 10 days shorter. The amount of suppurative complications was reduced from 62% to 18.3%.
The report deals with an investigation of the relationship between thymal cortical lymphocytes metabolism and antitumor response in Wistar rats with ovarian tumors, injected with Thio-TEPA intramuscularly and endolymphatically. Antitumor response and enzymatic indexes coordination appeared to be higher with the latter route.
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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.
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PURPOSE: A phase I/II trial was conducted to evaluate clinical and immunologic responses after intralymphatic and intranodal injections of mature dendritic cells. EXPERIMENTAL DESIGN: Fourteen patients with a metastatic melanoma received matured dendritic cells, loaded with Melan-A/MART-1 and/or NA17-A peptides and keyhole limpet hemocyanin. The cells were matured overnight with Ribomunyl, a toll-like receptor ligand, and IFN-gamma, which ensured the production of high levels of interleukin-12p70. Dendritic cells were injected at monthly intervals, first into an afferent lymphatic and then twice intranodally. Immunologic responses were monitored by tetramer staining of circulating CD8(+) lymphocytes and delayed-type hypersensitivity tests. RESULTS: Dendritic cell vaccination induced delayed-type hypersensitivity reactivity toward NA17-A-pulsed, keyhole limpet hemocyanin-pulsed, and Melan-A-pulsed dendritic cells in 6 of 10, 4 of 11, and 3 of 9 patients, respectively. Four of the 12 patients analyzed by tetramer staining showed a significantly increased frequency of Melan-A-specific T cells, including one patient vaccinated only with NA17-A-pulsed dendritic cells. Furthermore, 2 of the 12 analyzed patients had a significant increase of NA17-A-specific T cells, including one immunized after an optional additional treatment course. No objective clinical response was observed. Two patients were stabilized at 4 and 10 months and three patients are still alive at 30, 39, and 48 months. CONCLUSIONS: Injections into the lymphatic system of mature peptide-loaded dendritic cells with potential TH1 polarization capacities did not result in marked clinical results, despite immunologic responses in some patients. This highlights the need to improve our understanding of dendritic cell physiology.
Dendritic cells (DC) represent potent APCs that are capable of generating tumor-specific immunity. We performed a pilot clinical trial using Ag-pulsed DC as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly injections of DC enriched and activated from their PBMC. DC were cocultured ex vivo with recombinant mouse prostatic acid phosphatase as the target neoantigen. Following enrichment, DC developed an activated phenotype with up-regulation of CD80, CD86, and CD83 expression. During culture, the DC maintained their levels of various adhesion molecules, including CD44, LFA-1, cutaneous lymphocyte-associated Ag, and CD49d, up-regulated CCR7, but lost CD62 ligand and CCR5. In the absence of CD62 ligand, such cells would not be expected to prime T cells efficiently if administered i.v. due to their inability to access lymphoid tissue via high endothelial venules. To assess this possibility, three patient cohorts were immunized with Ag-pulsed DC by i.v., intradermal (i.d.), or intralymphatic (i.l.) injection. All patients developed Ag-specific T cell immune responses following immunization, regardless of route. Induction of IFN-gamma production, however, was seen only with i.d. and i.l. routes of administration, and no IL-4 responses were seen regardless of route, consistent with the induction of Th1-type immunity. Five of nine patients who were immunized by the i.v. route developed Ag-specific Abs compared with one of six for i.d. and two of six for i.l. routes. These results suggest that while activated DC can prime T cell immunity regardless of route, the quality of this response and induction of Ag-specific Abs may be affected by the route of administration.
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