Biomedical subjects
Publications and source records attributed to M Richter.
In order to characterize physicochemical properties of binders rheological behaviour, wetting ability and film-formation tendency of the binder solutions were investigated. The results obtained were related to granule and tablet properties.
The pharmacological properties of a genetically engineered recombinant hirudin (r-hirudin) were studied in animal experiments. r-Hirudin proved to be a well tolerated substance. I.v. injection of up to 200 mg/kg did not lead to perceptible functional or morphological changes. There were no treatment-related effects on the cardiovascular system of dogs and rats after administration of up to 10 mg/kg. After long-term treatment (4 weeks, 1.0 mg/kg daily), no r-hirudin-related histopathological, haematological or biochemical changes could be found. Formation of antibodies was not detectable. Absorption, distribution, and elimination of r-hirudin were studied in dogs and rats. Pharmacokinetics could be best described by an open two-compartment model with first-order kinetics. After i.v. injection in dogs, r-hirudin is distributed into the extracellular space and eliminated through the kidneys in active form by glomerular filtration. After i.v. administration, a half-life of about 1 h was estimated; s.c. administration prolonged the apparent half-life. Pulmonary absorption was shown. Enteral absorption, placental transfer as well as transfer through the fetal integument were very low. r-Hirudin did not pass the blood-brain barrier. The efficacy of r-hirudin in preventing both venous and arterial thrombosis, vascular shunt occlusion or disseminated intravascular coagulation was demonstrated in rats. Depending on the dose, r-hirudin was able to prevent or reduce stasis-induced venous thrombosis, prolong the patency of an extracorporeal arteriovenous shunt, reduce the incidence of arterial thrombosis caused by vascular wall lesions as well as of microthrombosis induced by thrombin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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The abilities of unfractionated mononuclear cells (MNC), monocytes (98-99% pure), and lymphocytes (98-99% pure) to carry out the lysis of target cells in the ADCC, NK, NOCC, and MICC assays were compared. Lymphocytes by themselves were able to lyse the CRBC (ADCC), K-562 (NK), and RRBC (MICC) target cells. The monocytes were very effective in the lysis of the CRBC (MICC) target cells. However, the lysis of two other target cells--RRBC (NOCC) and HRBC (ADCC)--required the simultaneous presence of both lymphocytes and monocytes in order to effect optimal lysis. Soluble factor(s) secreted by the cytotoxic cells capable of lysing the target cells were detected only in the NK assay. The activity of the soluble cytotoxic factor (NKCF) was only 25-40% of that exhibited by the cytotoxic NK cells and it was secreted by the cytotoxic cells after 48 hr of culture and not 24 hr of culture which is the usual assay condition. The NKCF was cytotoxic only to the NK target cells and not to the target cells used in the ADCC, NOCC, and MICC cytotoxic assays. Different classes of lymphocytes were cytotoxic in the monocyte-independent assays [ADCC (CRBC), NK (K-562), and MICC (RRBC)]. The null lymphocytes and the T lymphocytes were the primary cytotoxic cells in the ADCC and MICC assays, respectively, whereas the T, B, and null cells were almost equally cytotoxic in the NK assay. With respect to the monocyte-dependent assays [ADCC (HRBC), NOCC (RRBC), and MICC (CRBC)], the cytotoxic activity of any one class of lymphocytes failed to approach that of the unfractionated MNC. The T cells were the most cytotoxic; the B cells exhibited limited cytotoxic activity in only the ADCC assay and the null cells showed no cytotoxic activity. However, the combination of T and non-T cells and, to a lesser extent, T and B cells, exhibited much greater cytotoxic activity than the individual cells and together were as cytotoxic as the unfractionated MNC. It is concluded that, depending upon the selection of the target cells, lysis in the ADCC, NK, NOCC, and MICC assays may be effected by lymphocytes only, by monocytes only, by both monocytes and lymphocytes, or as a result of lymphocyte-monocyte collaboration. In the latter instance more than one class of lymphocytes must be present in order for maximum cytotoxic activity to be expressed.
Temporomandibular dislocation and subluxation are two pathological situations both characterized by hypermobility of the condyle. We believe that when luxation is recurrent and when subluxation becomes painful or is accompanied by disc dysfunction, surgical intervention is indicated. We are impressed by Gosserez and Dautrey's (1967) method of augmentation of the tubercle, or extra-articular obstruction, which is a modification of Leclerc and Girard's (1943) original procedure. The advantages of this technique are described and results are based on a series of 38 patients.
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Outbred rabbits were immunized intravenously with 10(9) sheep erythrocytes (SRBC) and/or horse erythrocytes (HRBC) and sacrificed 1 to 60 days later. At the height of the immune response (Day 7 postimmunization), antibody-forming cells identified by their ability to form hemolytic plaques in the plaque-forming cell (PFC) assay were detected only in the spleen. The splenic PFCs were totally inhibited if they were first incubated with the autologous thymus cells (immune thymus suppressor cells or ITSCs) for 4 hr prior to assaying for PFCs. Incubation of the spleen mononuclear cells with cells of any of the other lymphoid organs of the immunized rabbit for up to 6 hr did not inhibit the PFCs to any significant degree. There is no MHC restriction in the suppressor activity of the ITSCs since they could totally suppress the PFCs of autologous and allogeneic 7-day immune spleen cells. Neither thymus cells nor cells of any of the other lymphoid organs of the unimmunized rabbit could inhibit allogeneic 7-day immune splenic PFCs. The ITSCs from rabbits immunized with SRBC could be isolated by rosetting with the immunizing antigen, SRBC, but not with the non-cross-reacting antigens HRBC, human erythrocytes (HuRBC), and rabbit erythrocytes (RRBC), and vice versa, thus demonstrating the antigenic specificity of the suppressor cells. The thymus cells, but not the cells of any of the other lymphoid organs of the SRBC-immunized rabbit, secreted a factor referred to as immune thymus suppressor factor (ITSF) during incubation for 4 hr at 37 degrees C which could, by itself, totally suppress the splenic PFC. ITSF could be absorbed out of solution by incubation with the immunizing antigen, SRBC, but not with the non-cross-reacting antigens HRBC, HuRBC, and RRBC. Similarly, the ITSF secreted by the thymus cells of the HRBC-immunized rabbit could be absorbed out of solution by incubation with the immunizing antigen, HRBC, but not with the SRBC, HuRBC, and RRBC. ITSF is therefore antigen specific as is its parent ITSC. The cells of the lymphoid organs of unimmunized rabbits did not secrete a suppressor factor during incubation in vitro. ITSCs capable of totally inhibiting the PFCs were detected in the immunized rabbits by Day 5 post-primary-immunization; the ITSCs were capable of secreting ITSF which could totally inhibit the PFCs by Day 7 post-primary-immunization. Although the ITSCs were detected in a suppressive state up to Day 40 post-primary-immunization, they lost their capacity to secrete ITSF by Day 21 post-primary-immunization.(ABSTRACT TRUNCATED AT 400 WORDS)
Rabbits immunized intravenously(iv) with sheep erythrocytes(SRBC) (primary response) pass through a period which begins at about Day 35 postprimary immunization and extends to about Day 120 during which time all detectable spontaneous AFC (immediate PFC) and memory AFC(cells which generate PFC in culture) are detected only in the spleen. Prior to Day 30 postprimary iv immunization, large numbers of immediate PFC are detected in the circulation and the bone marrow as well as in the spleen. By Day 120 postprimary iv immunization, memory cells can be detected in significant numbers in the thymus and the popliteal lymph nodes (PLN) as well as in the spleen. The number of memory cells in the PLN and thymus increases over the course of the following 6 months. Rabbits splenectomized on Day 40 postprimary iv immunization and subjected to reimmunization iv with 10(9) SRBC 1, 5, or 8 months later were unable to give significant secondary immune responses. Only the thymus and PLN cells, cultured in vitro with the antigen(SRBC), 1, 5, or 8 months postprimary immunization, generated secondary immune(PFC) responses and these responses were feeble at best. The failure of the immunized rabbit to give a significant secondary immune response to SRBC if splenectomy was first carried out at a time postprimary iv immunization when all memory cells to the original antigen are sequestered only in the spleen (i.e., days 40 to 100) constitutes an animal model which provides a credible immunological explanation for the postsplenectomy syndrome which affects a minority of splenectomized individuals. These individuals, like the rabbits splenectomized on Day 40 postprimary immunization, lack the capacity to evoke a strong secondary immune response to particular infectious microorganisms and succumb in a few days with fulminant septicemia unless aggressive chemotherapy is instituted upon initial sign of infection.
Normal adult outbred rabbits were immunized intravenously (iv) with sheep erythrocytes (SRBC). At varying times thereafter, the different lymphoid organs were investigated for spontaneous and culture-induced antibody secreting cells by the aqueous hemolytic plaque-forming cell (PFC) technique. During the phase of active antibody formation (Days 3 to 30), immediate PFC, indicative of spontaneous antibody synthesis and secretion, were detected principally in the spleen. In the early postimmune memory period (Days 30 to 90), memory cells capable of generating PFC following secondary immunization in in vitro culture with SRBC were detected only in the spleen. However, by 4 months postimmunization, memory cells were detected in the thymus and popliteal lymph node (PLN) as well as in the spleen. The number of memory cells in the thymus and PLN was significantly higher by 6 months postprimary iv immunization and was even further elevated by 9 months postprimary iv immunization. Following in vivo secondary immunization by the iv injection of SRBC 2 or 6 months postprimary immunization, immediate PFC were detected in large numbers in the spleen, the bone marrow, and the blood, marginally in the PLN and not at all in the thymus. Similar results were obtained at 9 months following primary immunization with SRBC with the exception that large numbers of immediate PFC were detected in the PLN following secondary iv immunization. Following culture of these lymphoid cells for 5 days in vitro with SRBC, the thymus and PLN cells, as well as the spleen cells, generated large numbers of PFC. Since immediate PFC were never detected among the freshly isolated thymus cells whereas thymic cell cultures 6 and 9 months postprimary iv immunization invariably generated large numbers of PFC following secondary immunization in vitro, the thymus memory cells would appear to be inaccessible to particulate antigen injected intravenously; they can only be detected following activation by the antigen in culture. The PFC generated by thymus memory cells (and spleen and PLN) were totally inhibited by the inclusion of sheep anti-rabbit IgG into the PFC assay. This finding demonstrates unequivocally that the plaques induced by thymus cells, just as the plaques induced by spleen and PLN cells, are antibody mediated and not false plaques. Therefore, the thymic PFC cells must be antibody-secreting B-memory cells since T cells do not synthesize or secrete immunoglobulins.
Rabbits were splenectomized (splx) and immunized intravenously (iv) with sheep erythrocytes (SRBC) 14 days later. At the height of the primary immune response on Day 8 postimmunization, significant numbers of plaque-forming cells (PFC), that is, antibody-forming cells (AFC) synthesizing and secreting antibodies, were detected in the popliteal lymph nodes (PLN) and lesser numbers were detected in the bone marrow and the circulation. No PFC were detected in any of the other lymphoid organs. Rabbits were sacrificed at 1, 2, 6, or 9 months post-primary iv immunization and cell cultures of the lymphoid organs were set up with the antigen, SRBC, to induce secondary immune responses in vitro. Only the PLN cells challenged with SRBC in vitro 1 month post-primary immunization generated PFC and only PLN and thymus cells generated PFC in vitro at the three other challenge periods, thus demonstrating the existence of memory cells in only these two lymphoid organs in the splx rabbits. Following in vivo secondary immunization iv with SRBC 2, 6, or 9 months post-primary iv immunization. PFC were consistently detected only in the PLN and the bone marrow and inconsistently in the circulation. No PFC were detected in the thymus or in any of the other lymphoid organs. Paradoxically, neither the bone marrow nor the circulating mononuclear cells of these rabbits generated PFC during in vitro culture with SRBC, whereas the thymus cells and the PLN cells generated many PFC in culture with SRBC. These results demonstrate that the thymus contains memory cells following primary immunization of the splx rabbit which are not accessible to particulate antigens injected intravenously, possibly due to a blood-thymus barrier to particulate antigen, and therefore cannot be activated in vivo into secondary antibody formation. The results also indicate that the AFC detected in the circulation and in the bone marrow following primary iv immunization, which do not generate PFC in antigen-stimulated cultures in vitro, are degenerating cells whereas the AFC in the PLN and thymus, which generate many PFC in antigen-stimulated cultures in vitro, constitute the noncirculating precursors of the long-lived memory cells in the splx rabbit. This role of the thymus and PLN as reservoirs for memory cells in the immunized splx rabbit is not influenced by nor is it a result of splx since the thymus and PLN have both been shown to be the major sources of memory cells, along with the spleen, in the immunized nonsplx rabbit.
For more than 10 years homologous bone stored at -20 degrees C has been used to fill large bone cavities after cystectomy. This article outlines the principles of collecting, storing, and preserving the homograft, presents special aspects of the surgical technique, and reports long-term results.
In order to demonstrate pharmacokinetic and pharmacodynamic interactions between fentanyl and buprenorphine, 3 groups of patients (n = 30) were compared, receiving either fentanyl (0.005 mg/kg b.w.) or buprenorphine (0.01 mg/kg b.w.) or both opioids as analgesic during surgery for disc protrusion. For a period of 4 h haemodynamic parameters were monitored and blood samples were taken for determination of the following concentrations: ADH, ACTH, cortisol, glucose, unbound glycerol, fentanyl and buprenorphine. Blood gas analyses were performed up to 2 h postoperatively. Although in all groups haemodynamic parameters were constant, there was an increase in factors related to operative stress (cortisol, glucose, unbound glycerol, postoperative acidosis) after the combination of both opioids, while postoperative ventilatory parameters in this group were not improved by the partial agonist buprenorphine. Plasma levels were not affected by combined application, except for a slight elevation of buprenorphine concentrations during additional use of fentanyl. Buprenorphine, at least in higher dosages, seems to antagonize analgesia induced by fentanyl, although respiratory depression is even more pronounced. It may be assumed, that with partial agonists the relation of agonistic and antagonistic activity may be different, depending on the dosage used and on the respective pharmacologic effect observed during investigation.