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At least 19 recordsLinked to original sources

Serotherapy of cancer: cellular changes in primary rat mammary carcinomas after infusion of syngeneic sera absorbed with protein A-Sepharose.

Serotherapy and plasma therapy have proved to be effective in the treatment of diverse neoplasms. The mechanisms of the tumoricidal or growth-inhibitory effects are unknown. We previously reported that activation of the alternative pathway of complement in absorbed sera correlated with the presence of anti-tumor activity. Complement components generated during absorption may serve as the initial mediators of cytotoxicity; for example, C5a may function in its role as a chemo-attractant. To further investigate the anti-tumor mechanisms, we undertook a series of sequential histological studies of in vivo changes in tumors following i.v. serotherapy. We found diffuse inflammatory cellular infiltrates in the interstitial compartments of primary mammary carcinomas of rats within 3-4 hr of administration of protein A-Sepharose absorbed syngeneic serum. The number of inflammatory cells was significantly higher in tumors from treated rats: total infiltrating cells (p = 0.002), eosinophils (p = 0.001), neutrophils (p = 0.001), macrophages (p = 0.001), lymphocytes (p = 0.004) and plasma cells (p = 0.001). Also, the mitotic index of tumor cells was significantly lower 4 hr after serotherapy when compared with that of untreated rat tumor cells. C3 in tumor tissue was decreased at 4 hr following serotherapy. Fibrosis was present in tumor nodules with retarded growth 5 weeks after the start of serotherapy. Localization of the infiltrating cells to tumor interstitial compartments prevents direct contact between inflammatory cells and neoplastic cells, making it unlikely that direct cell-cell killing occurs. Indirect cell killing within the tumor bed apparently occurs through several mechanisms involving interactions between serotherapy-initiated humoral mediators and inflammatory cells. The resulting anti-tumor effects include microvascular injury leading to localized ischemia, tumor infarction, and fibroblastic reactions obstructing tumor invasion and growth.

Animals↗

The effect of the serotherapy regimen used and the marrow cell dose received on rejection, graft-versus-host disease and outcome following unrelated donor bone marrow transplantation for leukaemia.

Unrelated donor (UD) transplantation is the only potentially curative therapy for many leukaemia patients but is associated with a high mortality and morbidity. We sought to identify factors that could be optimised to improve outcome following UD transplantation in adults. Data was retrospectively analysed on 55 patients sequentially receiving UD transplants for CML or acute leukaemia (AL), all of whom received serotherapy for the prevention of GVHD and rejection. All patients received standard conditioning regimens. The first 28 patients transplanted also received combined pre- and post-transplant serotherapy with Campath 1G (days -5 to +5) and standard dose CsA plus MTX as GVHD prophylaxis (protocol 1). The subsequent 27 patients received a 5-day course of pre-transplant serotherapy alone either with ATG (CML patients) or Campath 1G (AL patients) on days -5 to -1 inclusive, with high-dose CSA plus MTX (protocol 2). The incidence of acute GVHD was low with no patient receiving either protocol developing > grade 2 disease. The use of protocol 2 and the administration of a bone marrow cell dose above the median (2.17 x 10(8)/kg) were the most important factors predicting engraftment (P = 0.03 and P = 0.001, respectively) but this only remained significant for cell dose in multivariate analysis (P = 0.03). Overall survival for the group was 45% at 3 years and was influenced by both age (P = 0.02) and disease status at transplantation (P = 0.001). Receiving a cell dose above the median was also associated with a trend towards better survival (P = 0.08), due primarily to a reduction in the TRM to 8.2% compared with 54.5% in those receiving a lower cell dose (P = 0.002). We conclude that pre-transplant serotherapy alone is highly effective at preventing acute GVHD following UD BMT and that additional post-transplant serotherapy does not confer any benefit. Furthermore, a high marrow cell dose infused has a major effect in reducing transplant related mortality following UD BMT.

Adolescent↗

Serotherapy of acute lymphoblastic leukemia with monoclonal antibody.

We tested the efficacy of passive serotherapy in the treatment of acute lymphoblastic leukemia in four patients who had relapsed while receiving standard chemotherapeutic agents. Each patient received multiple intravenous infusions of J-5 monoclonal antibody specific for common acute lymphoblastic leukemia antigen (CALLA). In the three patients with circulating leukemic cells, there was a rapid decrease in circulating blasts that began immediately after antibody infusion, but not all leukemic cells were cleared, and remaining cells appeared to be resistant to further serotherapy. Although J-5 antibody was also demonstrable on bone marrow lymphoblasts immediately after antibody infusion in one patient, there was no change in bone marrow cellularity or differential during serotherapy. Analysis of the cell surface phenotype of leukemic cells during serotherapy and in vitro studies with patient cells suggests that resistance to serotherapy was mediated in part by antigenic modulation of CALLA in response to J-5 antibody.

Adolescent↗

Serotherapy of ovarian cancer.

The development of monoclonal antibodies has permitted the identification of several ovarian-tumor-associated antigens which might serve as targets for serotherapy in vivo. With the exception of antibodies directed against growth factor receptors, unmodified monoclonal reagents must activate complement (C') components or bind effector cells to destroy tumor targets. Antibody-dependent cell-mediated cytotoxicity (ADCC) may be particularly important for eliminating tumor cells in vivo. A shortage of functionally active effector cells can limit the efficacy of serotherapy with heteroantisera or monoclonal reagents. The use of immunostimulants such as Corynebacterium parvum has increased the number and activity of effector cells for ADCC within the peritoneal compartment of mice and of patients with ovarian cancer. Intraperitoneal serotherapy can achieve direct contact between antibody and microscopic deposits of ovarian tumor cells which persist following cytoreductive operations and cytotoxic chemotherapy. Conjugation of monoclonal antibodies with radionuclides, drugs or toxins might increase the potency of serotherapy and circumvent the effector shortage. Clinical studies to date have evaluated radionuclide conjugates for imaging and for therapy. Patients with a small volume of disease have responded to treatment. Preclinical models suggest that drug and toxin conjugates might also prove active. Recent studies have demonstrated a synergistic interaction between different immunotoxins. Ovarian carcinoma is likely to be a valuable clinical model for evaluating immunoconjugates which react with epithelial tumor cells.

Animals↗

Serotherapy of L1210 murine leukaemia--reasons for ineffectiveness of in vivo treatment by L.1 monoclonal antibody.

A monoclonal antibody (L.1), reacting in vitro specifically with L1210 leukaemia cells in a complement-dependent cytotoxicity assay (CDC), has been exploited for serotherapy studies. Different regiments of L.1 treatment of CD2F1 mice bearing the semi-syngeneic L1210 leukaemia did not prolong the life span of tumor-bearing animals. Moreover, the administration of L.1 did not enhance the antitumour effects of cyclophosphamide. Studies of in vivo localization showed that L.1 was able to bind specifically to L1210 leukaemic cells, although 30-40% of the cells remained negative. The presence of L.1 in mouse blood was demonstrated up to 15 days after the inoculation. On the other hand, in vivo administration of L.1 was probably accompanied by loss of the cytotoxic activity, perhaps through a mechanism of complement inactivation, since the presence of undiluted normal mouse serum in a CDC assay inhibited the cytotoxic activity of L.1. Moreover, serum from L.1-treated mice did not display any cytotoxic activity, although the presence of the antibody could be demonstrated by indirect immunofluorescence. Shedding of the antigen defined by L.1 was probably not responsible for the failure of the serotherapy, since the L.1 neutralizing antigen could be found in body fluids only long after the start of therapy.

Animals↗

Expression of serotherapy target antigens in Waldenstrom's macroglobulinemia: therapeutic applications and considerations.

Monoclonal antibody (mAb) therapy (serotherapy) has been successfully used in the treatment of many B-cell malignancies, among them lymphoplasmacytic lymphoma, an uncommon disorder that includes patients with the clinicopathological diagnosis of Waldenstrom's macroglobulinemia (WM). Rituximab, a mAb directed at CD20, was recently demonstrated by us and others to induce remissions and facilitate hematological recovery in patients with WM. The expression of CD20, along with targets of other mAbs which are commercially available, currently in clinical trials, or in preclinical development, have not been extensively studied or well documented in lymphoplasmacytic lymphoma. As such, we examined by flow cytometric analysis tumor cells from a large series of patients with the histopathlogical diagnosis of lymphoplasmacytic lymphoma and the clinicopathological diagnosis of WM for expression of the serotherapy target antigens CD20, CD22, CD40, CD52, IgM, MUC1 core protein, and 1D10. These studies demonstrated antigen expression on >or=50% of bone marrow tumor cells (CD19(+), kappa/lambda light chain-restricted), respectively, from patients as follows: CD20 (98.3%), CD22 (88.3%), CD40 (83.3%), CD52 (77.4%), IgM (83.3%), MUC1 core protein (57.8%), and 1D10 (50%). Both interpatient and intrapatient tumor clone antigen expression was heterogeneous. Combined mAb therapy might be a useful approach to cope with this variation, and could be tailored to target all members of the tumor clone for an individual patient.

Antibodies, Monoclonal↗

Decreased glycolipid antigen expression in lymphoma cell variants escaping from anti-glycolipid serotherapy.

Mice challenged with L5178Y lymphoma cells expression high levels of the glycolipid asialo GM2 (gangliotriosylceramide) were protected from tumor growth by passive administration of a monoclonal antibody specific for the glycolipid; in a few antibody-treated mice, ascites cells eventually proliferated which contained a reduced chemical quantity of the glycolipid antigen (3). We now report that the cells emerging from antibody-treated mice had abnormal marker chromosomes identical to those in the cells used for challenge, indicating that the emergent cells were progeny of the challenge inoculum. Flow cytometric analysis revealed that asialo GM2 was undetectable on the surface of greater than 95% of the tumor cells from antibody-treated mice, whereas surface display of H-2 determinants was unchanged from that of the cells used for challenge. Tumor cells arising in challenged but untreated mice consisted of a mixture of asialo GM2-positive and -negative cells, indicating the presence of selective pressures in these mice as well. None of the cells taken from tumor bearing mice differed significantly from the challenge cells in their susceptibility to natural killer cell attack, suggesting that resistance to natural killer cell lysis was not responsible for the proliferation of these cells in vivo. When cells derived from an antibody-treated mouse were used to challenge mice, serotherapy with anti-asialo GM2 had no effect on mouse survival. These results suggest that serotherapy may complement a host anti-tumor response, from which only asialo GM2 deficient cells can escape.

Animals↗

[Posture taken by members of the nursing staff during blood collection, intravenous drug administration and serotherapy].

The members of the Nursing Team are submitted, many times, to posture attacks either due to the own requirement of the action or the utilization of improper corporeal posture during its execution. The present study aims at inquiring the type, length, frequency and posture changes adopted by the members of the Nursing Team during the execution of blood collection techniques, administering of intravenous medication and serotherapy. Through direct observation were recorded 10 activities corresponding to each one of the mentioned techniques, realized in attendance of patients from a University Hospital internment unit. The results evidenced that blood collection activity was 50, 35% effectuated in the inclined standing position, followed by the standing straight position, 49, 64%. Intravenous medication administering was executed with frequent adoption of the standing straight posture, 51, 09% (in special with the arm in frontal expansion), 45, 74% in the inclined standing position and 3, 15% seated. Serotherapy technique was executed with predominant adoption of standing position (86, 88%) in special with the arms in frontal expansion and 13, 11% in the inclined standing position. The unnecessary adoption, many times, of inclined standing posture indicates that Nursing personnel have been making possible the happening of spinal column attacks mainly due to the bad utilization of corporeal mechanic. The authors suggest more attention to these aspects, mainly at Nursing courses.

Back Pain↗

A phase 1a clinical trial of LYM-1 monoclonal antibody serotherapy in patients with refractory B cell malignancies.

Ten patients with refractory B cell lymphomas were treated with weekly intravenous infusions of escalating doses of murine monoclonal antibody (MoAb) LYM-1 over four weeks. LYM-1 is a recently developed IgG2a murine MoAb that recognizes a polymorphic HLA-Dr antigen on surfaces of normal and malignant B cells but does not bind to any other normal tissues. MoAb LYM-1 has several advantages for serotherapy, since the antigen it recognizes is not shed from the cell surface and does not modulate in response to MoAb therapy. Furthermore, in vitro studies have indicated significant anti-tumour activity against lymphoma cell lines. In the current trial, dose-dependent levels of free LYM-1 were detected in the serum of all patients, but penetration of extravascular tumour tissues was poor. No significant toxicity or human anti-mouse antibody responses were observed in any patient. Clinical responses were minor and appeared to correlate with the number of infiltrating T cells seen in the initial lymphoma specimens. LYM-1 appears to be well-tolerated and has demonstrated several potential advantages as a therapeutic agent in patients with lymphoma. The mechanism of anti-tumour effect and plans for further clinical studies are discussed.

Adult↗

Scorpionism and serotherapy in Mexico.

In Mexico, scorpionism is an endemic public health problem. The exact number of human accidents is unknown, but partial statistics suggests numbers close to 200,000 per year. The documented number of fatality cases is in the order of 310 people per year. We currently use horse antiserum in patients who show a clear picture of intoxication. Our personal experience in treating 38,068 people, from which over 20,000 received serotherapy, shows that the antiserum is very effective, in that none of the patients died.

Animals↗

New procedures and parameters for better evaluation of Androctonus australis garzonii (Aag) and Buthus occitanus tunetanus (Bot) scorpion envenomations and specific serotherapy treatment.

New procedures describing intoxication with variable amounts of scorpion venoms (from 1 to 5 LD50) allowed us to introduce new parameters to evaluate Aag and Bot envenomations. Significant differences between the fatal limit time (FLT) and the last mortality time (LMT) were observed when the amount of Aag and Bot venom injected was equal to 1 LD50 and equal to or higher than 2 LD50. For Aag and Bot, the percentage of the fast mortality (FM) and the delayed mortality (DM) varied conversely when the amount of injected venom increased from 1 to 5 LD50. The relationship between the venom LD50 (from 2 to 20), the median protective dose (PD50) and the neutralizing activity of specific antivenom have been established. PD50 increased in a parallel manner with LD50. The neutralizing titres (LD50/ml) of Aag antivenom decreased from 74 +/- 3 to 44 +/- 2 and that of Bot antivenom from 52 +/- 2 to 36 +/- 1 when the number of LD50 injected increased from 2 to 20. Antivenom potency was evaluated using different protocols based on the presence or the absence of preincubation of the venom with the antivenom. In experiments where venom and antivenom were simultaneously but immediately injected, PD50 were twice as high as those found when venom and antivenom were preincubated (30 min at 37 degrees C). On the contrary, the corresponding neutralizing titres were two times lower. In an attempt to simulate accidental envenomations and subsequent serotherapy, Aag and Bot venom (4 LD50) were subcutaneously injected and the appropriate PD50S of antivenom were intravenously administered at different time intervals after envenomation. When the time of antivenom administration was shorter than the FLT, all envenomed mice might be protected by increasing volume of antivenom. However, when the antivenom is injected closer to the FLT only 50 to 60% of mice envenomed, respectively, by Aag and Bot could be saved even when more than 5 PD50 were injected.

Animals↗

Antivenom serotherapy and volume resuscitation partially improve peripheral organ ischemia in dogs injected with scorpion venom.

We tested the hypothesis that fluid resuscitation combined with antivenom serotherapy given after injection of scorpion venom may increase cardiac output (CO) and blood pressure (BP) and prevent the decline in bicarbonate, pH and gastric perfusion. Seventeen anesthetized, mechanically ventilated dogs were given 0.1 mg/kg i.v. venom of the scorpion Leiurus quinquestriatus. The dogs were randomized into three groups: six dogs were given venom alone; three dogs were given 6 ml of antivenom 1 minute before venom injection; eight dogs were given 6 ml of antivenom and 20 ml/kg of synthetic colloid solution, 20 min after venom injection. Parameters reflecting respiratory and circulatory functions were determined at baseline and 120 min after venom injection. Scorpion venom caused a decrease in CO, BP, pH and HCO3-. Gastric mucosal perfusion was severely affected as assessed by mucosal pH (pHi) and the gradient between mucosal and arterial pCO2 (delta pCO2). Antivenom given before venom injection prevented all the effects induced by the venom. Antivenom and fluid given 20 min after venom injection caused a marked increase in CO and BP, but had no effect on pH and HCO3- decline (compared with venom alone). Gastric perfusion slightly improved as the increase in delta pCO2 was attenuated. The combination therapy of antivenom and fluid in this dog model is superior to the therapy of each of them alone. The marked and long-standing improvement of CO is promising and may suggest improvement in HCO3- and pH with time.

Animals↗

Tetanus neonatorum--experience with intrathecal serotherapy at Muhimbili Medical Centre, Dar es Salaam, Tanzania.

In an attempt to lower the mortality rate of neonatal tetanus a study was undertaken to determine whether intrathecal serotherapy influences mortality from this disease. Sixty-six babies with tetanus neonatorum were studied. The mortality rate among babies who received intrathecal anti-tetanus serum (ATS) was 45% compared with 82% in the control group given intramuscular ATS (P congruent to 0.002). Infants who received intrathecal ATS also had fewer complications than controls (P less than 0.001) and the duration of hospital stay for the survivors was 19.3 days compared with 28.7 days for the control group (P less than 0.05). It is concluded that intrathecal ATS is superior to intramuscular ATS in the treatment of neonatal tetanus.

Female↗

CD20-directed serotherapy in patients with multiple myeloma: biologic considerations and therapeutic applications.

Clonotypic B cells circulating in patients with multiple myeloma (MM) express CD20, and it has been suggested that these cells may be clonogenic. Furthermore, 20% of patients with MM express CD20 on their bone marrow plasma cells (BMPCs). Therefore, the authors began a phase II clinical study to determine the activity of the anti-CD20 monoclonal antibody rituximab in MM patients. Nineteen previously treated MM patients received 375 mg/m2 rituximab per week for 4 weeks. Three months after initiation of treatment, patients were assessed for response and received a second course of therapy if their disease was stable (SD) or they achieved a partial response (PR). Six of 19 (32%) patients had either a PR (n = 1) or SD (n = 5), with a median time to treatment failure of 5.5 months (mean, 10.3 months; range, 3-27+ months). All six patients who had a PR or SD had CD20+ BMPC. Overall, rituximab therapy was well tolerated. Because most patients with MM poorly express CD20 on their BMPCs, the authors evaluated agents for their ability to induce CD20 expression and thereby facilitate rituximab binding on MM cells. These studies show that interferon-gamma (IFN-y) induced CD20 expression on MM BMPCs, MM B cells, and healthy donor BMPCs. In contrast, CD20 expression on chronic lymphocytic leukemia, follicular non-Hodgkin's lymphoma, healthy donor B cells, and progenitor cells was unaffected by IFN-y. Rituximab binding to the BMPCs of MM patients was also increased after culture with pharmacologically attainable levels of IFN-gamma (1-100 U/mL). In conclusion, these studies suggest that MM patients with CD20+ BMPCs may benefit from rituximab therapy. Furthermore, IFN-gamma induces CD20 expression on MM BMPCs and B cells and facilitates rituximab binding to MM BMPCs, providing the rationale for clinical trials to examine its use with CD20-directed serotherapies in MM.

Adult↗

Serotherapy of avian reticuloendotheliosis virus-induced tumors.

Immune serum, obtained from animals that had survived sublethal challenge with RE virus, was very effective in achieving tumor cures in chickens infected with this virus. The therapeutic effect could also be obtained by the immunoglobulin fraction of immune serum. The serum did not influence the development of an unrelated malignancy. Serotherapy studies in Bx and Tx recipients indicate that the B-cell or T-cell system of the host does not significantly contribute to the curative activity of immune serum. Absorption studies show that the curative effect is mediated by antibodies to tumor-associated transplantation antigens on tumor cells, not by antiviral antibodies.

Animals↗

Scorpion envenomation and serotherapy in Morocco.

A clinical and biologic study was conducted in Morocco to assess the efficiency of antivenom therapy for treating victims of scorpion stings. Epidemiologic and clinical data were collected from 275 patients envenomed by Androctonus mauretanicus mauretanicus and Buthus occitanus scorpions. Patients received antivenom or other drugs. Blood samples were collected at the time of hospital admission and 1 hr and 3 hr after treatment. Serum venom levels were quantified by using an ELISA. An association was found between clinical signs of envenoming and the level of venom in serum. Patients classified as grade II (moderate envenoming) had higher serum levels of venom level than patients classified as grade I (mild envenoming). At admission to the hospital, the mean venom concentration was not significantly different between the group not treated with antivenom, the group who received 2-5 ml of antivenom, and the group who received 10 ml of antivenom. A significant decrease in serum venom levels and an improvement in the clinical conditions were observed in patients administered 10 ml of antivenom. The lower decrease in serum venom levels in patients who received 2-5 ml of antivenom was due to lower doses of antivenom. No difference in the venom concentration was observed in patients who were not treated with antivenom. The absence of administration of antivenom increased the risk of developing clinical signs at the end of the hospitalization period. However, this risk was much higher when more than 1 hr elapsed between the time of the scorpion sting and the time of hospital admission. The results demonstrate that antivenom is effective in decreasing circulating venom and morbidity. Serotherapy is more efficient when given as soon as possible after envenomation and with adequate quantities of antivenom.

Adolescent↗

[The antecedents and creation of the Alfonso XIII Institute of Serotherapy, Inoculation and Bacteriology].

This article studies the establishment of the Alfonso XIII Institute of Serotherapy, Inoculation and Bacteriology in 1899, using the general press and the professional-scientific, medical and pharmaceutical press as its prime source, It aims to highlight the principal factors which led to its gestation and later development, as well as the circumstances which led to its creation, by analyzing the antecedents and orgins of the aforementioned institution.

Academies and Institutes↗

[Hemosorption in serotherapy (serosorption) in experimental acute diphtheric toxemia with the use of affinity sorbents].

In modeling acute diphtheric toxemia in guinea pigs, the authors propose to perform hemosorption using selective sorbents under continuous introduction of antitoxic immune sera into extracorporeal contour in front of sorption column. Combination of hemosorption with serotherapy in the same time interval may be denoted as serosorption. As specific sorbents, affine preparations imasorb A-700 and Imasorb G-700 were used. They selectively eliminate from the blood flow CIC produced by diphtheric toxin (anatoxin) and antitoxic rabbit and horse antibodies. Changes in the titers of the diphtheric toxin (anatoxin) and CIC in blood evidence for efficiency of selective sorbents were confirmed by immunohistochemical analysis of the preparations' granules after hemoperfusion.

Animals↗