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PubMed1984

Host-parasite interaction in serious infections due to gram-negative bacteria.

Gram-negative rods such as Enterobacteriaceae and Pseudomonadaceae are normal habitants of the digestive tract. However, if defense mechanisms of the host are compromised by underlying diseases such as malignant neoplasms, renal insufficiency, extensive traumata, or immunosuppressive therapy, invasion of the blood-stream can occur. Gram-negative septicaemia is associated with high morbidity and mortality, despite intensive care and administration of potent antibiotics. A central role in the pathophysiology of life-threatening bacteriaemia is attributed to endotoxin, a constituent of the gram-negative cell wall. This paper reviews current concepts of septic shock, the acquisition of gram-negative bacteraemia and the role of endotoxin. It also deals with a new approach to prevention and control of severe gram-negative infections using serotherapy based on the structure of endotoxin.

Animals↗
PubMed1996

Rabies encephalitis in a patient with AIDS: a clinicopathological study.

A 46-year-old man was bitten by a dog in Mali; anti-rabies vaccination was incomplete. Three months later he was admitted to hospital with fever and diarrhea. Human immunodeficiency virus (HIV) serology was positive and CD4 count was 70/mm3. His status worsened rapidly with confusion hydrophobia and hypersialorrhea. Despite anti-rabies serotherapy and vaccination, he died suddenly 12 days after admission. Immunofluorescence on cerebral tissue samples established rabies encephalitis. Neuropathology showed mild encephalitis with occasional Babès nodules and rare perivascular mononuclear cuffs. Intraneuronal Negri inclusion bodies were remarkably diffuse and abundant. They were clearly demonstrated by immunocytochemistry and electron microscopy. Apoptotic neurons were identified in the brain stem and hippocampus in the vicinity of inflammatory foci. In contrast, apoptosis could not be demonstrated in non-inflammatory areas, even where Negri bodies were numerous. There was no associated HIV encephalitis or opportunistic infection. The occurrence of rabies encephalitis in AIDS represents a random association, but is probably not exceptional as rabies is endemic in many countries and the AIDS epidemic is spreading worldwide. In this case, although the incubation duration and clinical presentation were comparable to those in classical rabies the T-cell-mediated immunosuppression may account for the weak inflammatory reaction and unusually abundant viral multiplication. This observation confirms that all those at risk for rabies, particularly immunocompromised patients, should receive complete anti-rabies treatment including vaccines and specific immunoglobulins, as soon as possible after infection.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Epidemiological and clinical characteristics of the scorpion envenomation in Tunisia.

This work deals with a clinical and epidemiological study of the scorpion envenomation in Tunisia, from 717 scorpion stings recorded during a year at the Sfax Hospital with a mortality rate of 0.35%, all the patients died being less 15 years old. The serotherapy with a specific antivenin made in the Institut Pasteur of Tunis is the main element of the therapeutics.

Adolescent↗
PubMed1985

Polymorphism and quantitative variations of toxins in the venom of the scorpion Androctonus australis Hector.

Using highly specific radioimmunoassays for toxins I, II and III of the scorpion Androctonus australis Hector, the concentrations of these neurotoxins have been determined in pooled as well as in individual samples. Variations were found that support polymorphism of scorpion toxins at an individual level. Radioimmunoassays were also used to detect toxin I of Buthus occitanus tunetanus and toxin II of Androctonus australis Hector and also antigenically homologous toxins in the venoms of several North African scorpions. These results are interpreted in terms of scorpion serotherapy.

Animals↗
PubMed1989

Epidemiological characteristics of scorpion sting in León, Guanajuato, México.

Poisoning with scorpion venom in the city of León, Guanajuato state, México, is a significant public health problem. The hospital of the Mexican Red Cross gave medical attention to 38,068 cases of envenomation by scorpion sting during 1981-1986; 77% of all accidents occurred among persons under 30 years of age. The 100% survival rate can be attributed to prompt serotherapy. Most stings were due to scorpions from the species Centruroides infamatus infamatus. Scorpion stings increase dramatically in the spring and are lowest during winter. The distribution of scorpions throughout the city is uniform and accidents occur at any time of day or night with no preference in regard to the sex of the affected persons. The epidemiological aspects of scorpion poisoning are emphasized.

Animals↗
PubMed1994

Androctonus crassicauda (Olivier), a dangerous and unduly neglected scorpion--I. Pharmacological and clinical studies.

Androctonus crassicauda venom has an i.v. LD50 in mice of 0.32 +/- 0.02 mg/kg, which makes the scorpion among the most toxic species in the world. Fifty-one non-fatal and one fatal cases of scorpion sting were presented. Pain and tenderness were very common following the sting. Generalized erythema occurred in 20-25% of all infants and children below the age of 5 years. Severe CNS manifestations including seizures, unconsciousness and marked irritability occurred mainly in infants and young children, while hypertension occurred in the majority of victims below the age of 11 years. Two pregnant victims were treated with antivenom with no bad consequences on mothers or foetuses. The fatal case described was inadequately treated with antivenom and presented a rare situation of intracranial coagulation in the basal cisterns or low in the cranial subarachnoid space. The victim developed moderate hydrocephalus of the communicating type with clear ventricular CSF and strongly xanthocromic fluid from lumbar puncture. The effects of A. crassicauda venom on isolated hearts, atria and anaesthetized rat blood pressure appeared to be mediated largely through stimulation of the autonomic nervous system with predominance of sympathetic stimulation and release of tissue catecholamines. Electrocardiograms recorded simultaneously with blood pressure changes showed evidence of ectopic foci during the hypertensive phase and ischaemia, inferior wall infarction and different degrees of heart block during the late hypotensive phase. Androctonus crassicauda venom was unique in following a three-compartment open model comprising a central compartment 'blood', a rapidly equilibrating 'shallow' tissue compartment and a slowly equilibrating 'deep' tissue compartment. The overall elimination half-life, t1/2 beta, was 24 hr, indicating that the venom has the slowest elimination among all known scorpion venoms. The long stay of the venom in the body might explain the increased risk of toxicity and the good potential for treatment with serotherapy even hours after the sting.

Adolescent↗
PubMed1995

The scorpion envenoming syndrome.

The pathophysiology of the scorpion envenoming syndrome is reviewed with emphasis on the body systems commonly affected. Concepts of the mechanisms underlying venom action, as can be explained by the recently discovered effects on ionic channels, are discussed. The results of clinical analysis of cases of scorpion sting victims and animal experiments with scorpion envenomation supporting these concepts are presented. The pharmacokinetic characteristics of scorpion venoms and their correlation to the magnitude of toxic effects are presented in relation to the potentials of therapeutic intervention. The pharmacological basis of the therapeutic usefulness and toxicities of the drugs commonly used in the treatment of scorpion envenoming is also projected. Finally, the results of a successful nation-wide clinical study with serotherapy of scorpion envenoming are presented and evaluated.

Animals↗
PubMed1986

The use of monoclonal antibodies for the identification and classification of acute myeloid leukemias.

We reviewed a library of monoclonal antibodies (MoAbs) detecting antigens on myelomonocytic cells and analysed their reactivity patterns as reported in the literature. On the basis of the frequency of positivity with the myelocytic variants (FAB M1-3) or monocytic variants (FAB M4/5) of acute myeloid leukemias, the MoAbs were assigned to one of four groups. MoAbs of Group I identified most cases of both the myelocytic and the monocytic cell lineages ('pan-myelomonocytic' reactivity) and can be used to identify acute myeloid leukemias regardless of the subtype. Group II comprised MoAbs which reacted with the majority of FAB M1-3 cases, but showed a preference in reactivity with AMMoL/AMoL cases (reactivity: myelocytic partly, monocytic predominantly). MoAbs of Group III stained most cases with monocytic phenotypes, but labelled only a small percentage of non-monocytic cases. These MoAbs are valuable tools for the detection of cases with monocytic features. Group IV MoAbs reacted with a small to intermediate percentage of myelocytic and/or monocytic cases. Besides their diagnostic application MoAbs might be used in new therapeutic approaches such as in-vivo serotherapy with MoAbs and purging of autologous bone marrow for transplantation. None of the described MoAbs appear to be leukemia-specific. Many MoAbs have been produced against non-myelomonocytic cells and were reactive with cells outside the myelomonocytic cell lineages and the hematopoietic system. Other MoAbs with apparent cell lineage-restricted reactivity regarding normal cells stained leukemic cells of other cell lineages. This phenomenon of translineage reactivity of leukemic cells with mutually exclusive markers indicating a biphenotypic marker profile might be the result of abnormal, disregulated gene expression. New classification systems of acute myeloid leukemias based on immunological marker profiles have been proposed. The analysis of reactivity of normal and malignant myelomonocytic cells with MoAbs has led to refined differentiation schemes of the normal hematopoiesis.

Antibodies, Monoclonal↗
PubMed1983

Monocyte chemotaxis mediated by formyl-methionyl-leucyl-phenylalanine conjugated with monoclonal antibodies against human ovarian carcinoma.

Availability of a chemically defined chemoattractant (fMLP) and of appropriate monoclonal antibodies may permit local manipulation of the inflammatory response to human tumors. fMLP has been conjugated with two monoclonal antibodies (OC125 and OC133) which react with human ovarian carcinomas. Conjugates retained the ability to bind to a human ovarian carcinoma line (OVCA433) judged by indirect immunofluorescence and by radioimmunoassay. The fMLP conjugate was maximally chemotactic for human blood monocytes and human peritoneal macrophages at protein concentrations of 300-900 micrograms/ml. Conjugates stimulated chemotaxis rather than chemokinesis. After incubation with an fMLP-antibody conjugate, antigen positive OVCA433 cells released chemotactic activity and attracted monocytes in vitro, whereas an antigen-negative ovarian cell line failed to do so. As monocytes can be important effectors of antibody dependent cell mediated cytoxicity, fMLP conjugates might increase monocyte concentrations at tumor sites and potentiate serotherapy for certain human neoplasms.

Antibodies, Monoclonal↗
PubMed1985

The use of monoclonal antibodies and flow cytometry to detect peripheral blood and bone marrow involvement of a diffuse, poorly differentiated lymphoma.

Using monoclonal antibodies and flow cytometry, we were able to characterize the phenotype of a diffuse, poorly differentiated lymphoma and to isolate subpopulations of cells from the blood and bone marrow that expressed the malignant phenotype even though the patient exhibited no absolute lymphocytosis. Because the circulating clone reacted with the anti-T cell monoclonal antibody T101, we initiated serotherapy with T101 as part of a phase I study. A 10 mg infusion of T101 resulted in the rapid clearance of normal T cells from circulation, but the clone showed evidence of modulation and was not cleared. Twenty-four hours following infusion, all cell populations had returned to pre-treatment levels. Our study suggests that, by using monoclonal antibodies and flow cytometry, blood and bone marrow involvement of a lymphoma can be demonstrated in patients without absolute lymphocytosis, a finding which may influence the staging and treatment of the disease.

Antibodies, Monoclonal↗
PubMed1991

Current status of immunotherapy of patients with HIV-infection.

Immunotherapy is receiving increasing attention as an approach to managing HIV-infection and its complications. As the immune response to HIV becomes better understood, new approaches to HIV immunotherapy are possible. Approaches under development include, first and foremost, the use of vaccines, not only for prophylaxis but also for therapy of established disease. Other approaches being studied include passive serotherapy, use of synthetic HIV-binding molecules such as CD4, immunorestoration and immunomodulation with immunomodulatory drugs, thymic hormones, cytokines and anti-infective immunotherapy directed against the opportunistic infecting organisms of HIV. The current role of these modalities as single agents and in combination and their potential role in the future is discussed.

Adjuvants, Immunologic↗
PubMed1995

Infections in liver transplantation: risk factors and strategies for prevention.

Infection affects up to 70% of liver transplant recipients and is the second most common complication after rejection and graft dysfunction. Identified risk factors for infection include: previous transplantation; type of biliary anastomosis; transfusion requirements at surgery; surgical complications; duration of operation; duration of postoperative ventilation; serological status of donor and recipient; steroid use and serotherapy for rejection; and pre- and post-transplant antibiotic usage. The majority of symptomatic infections are bacterial and relate to surgery (intra-abdominal, biliary and wound infections), ventilation and intravenous cannulae. Cytomegalovirus infections occur in 45-100% of recipients but are asymptomatic in the majority. Fungal infections are mostly due to Candida albicans but infections due to Aspergillus spp. occur in approximately 6% and carry a high mortality. There are very few prospective comparative trials of antimicrobial prophylaxis in this patient population. The management of these patients needs to be based on such studies.

Anti-Bacterial Agents↗
PubMed1982

Reactivation of Epstein-Barr virus in pregnant women: social factors, and immune competence as determinants of lymphoproliferative diseases-a hypothesis.

In normal pregnant women, reactivation of Epstein-Barr virus (EBV) frequently occurs. Cellular immune responses are apparently suppressed, but high titer EBV-specific antibodies of IgG class may compensate. The antibodies cross the placenta and protect the infant against primary infection for many months. Reactivation of EBV in pregnancy and oral excretion of virus by normal pregnant women could be one explanation why young children in large sibships (among families of low social classes) become infected early in life. Infants are likely infected by EBV from their pregnant mothers who shed virus in saliva. Moreover, the natural protection for several months in the perinatal period against Burkitt lymphoma and fatal EBV-induced lymphoproliferative diseases in congenitally immune deficient children is explained. The maturity and immunocompetence of the immune system at the time of primary infection by EBV and the size of the sibship seem to determine whether infectious mononucleosis occurs. Gammaglobulin derived from human cord blood may be a valuable source of viral-specific antibodies for serotherapy in immune deficient patients.

Adolescent↗
PubMed1992

Anti-idiotypic and anti-anti-idiotypic responses to a monoclonal antibody directed to the acetylcholine receptor binding site of curaremimetic toxins.

Serotherapy, an approach currently used to protect humans against animal bites or stings, is often too specific. To broaden antiserum paraspecificity, use of antibodies directed against areas shared by all members of a toxin family was previously proposed. MST2 is a mAb that recognizes all long-chain curaremimetic toxins (Charpentier et al. (1990) J. Mol. Recog. 3, 74-81). It binds to toxin residues that make contact with the toxin's target, e.g., the nicotinic acetylcholine receptor (AcChoR). We now show that MST2 also recognizes (-) nicotine, an agonist of AcChoR. Binding properties of MST2 therefore mimick, at least partially, binding properties of AcChoR. Injection in rabbits of MST2 mixed with adjuvant, elicited anti-idiotypic (anti-Id) antibodies that inhibited binding of the toxin to AcChoR. A proportion of these anti-Id antibodies specifically bound AcChoR and thereby mimicked the toxin. Furthermore, rabbits immunized with MST2 elicited auto-anti-anti-Id antibodies capable of binding the toxin. Our data provide a molecular explanation for the previously reported signs of myasthenia gravis as triggered by antibodies raised against cholinergic antagonists. Implications in the design of antisera to toxic proteins are discussed.

Animals↗
PubMed2006

Multiple myeloma: monoclonal antibodies-based immunotherapeutic strategies and targeted radiotherapy.

Multiple myeloma (MM) is an incurable B-cell malignancy of terminally differentiated plasma cells. Besides conventional treatments, several targeted therapies are emerging for MM. We review recent developments in monoclonal antibodies (MoAbs) and (radio)immunoconjugates-based targeted immunotherapeutic (serotherapies) strategies, as well as skeletal targeted radiotherapy (STR) in MM. MoAbs-based strategies include the targeting of cytokines and their receptors as well as toxins, drugs or radionuclide delivery to MM cells. Both targeted radioimmunotherapy (RIT) and STR have proved efficient in the treatment of radiosensitive tumours. We conclude that there is a need for more mechanistic investigations of drug action to identify novel therapeutic targets in myeloma cells, as well as in the bone marrow microenvironment.

Antibodies, Monoclonal↗
PubMed2006

Peptide arrays for the determination of humoral responses induced by active immunization with a monoclonal antibody against EpCAM.

Epithelial cell adhesion molecule (EpCAM) is an attractive target for monoclonal antibody serotherapy because it is over-expressed in approximately 70% of epithelial cancers and their metastatic lesions. IGN101, the immunogenic formulation of the murine monoclonal anti-EpCAM antibody Mab17-1A, has been shown to evoke a strong humoral immune response in both monkey studies and early clinical trials. Notably, there was a reduction in the number of circulating EpCAM-positive tumor cells in the peripheral blood of treated cancer patients. In contrast to earlier publications by other groups, we could not detect an anti-EpCAM immune response upon treatment with Mab17-1A using a conventional but optimized anti-EpCAM ELISA. Therefore, in a novel experimental setup, sera of healthy immunized monkeys, normal human donors and cancer patients immunized with IGN101 were tested for reactivity against a series of overlapping synthetic peptides encompassing the entire sequence of EpCAM prepared by SPOT synthesis on cellular supports. Using this method, sera from normal donors reacted with different peptides compared to sera from healthy monkeys. However, the peptides were clustered in the same regions of EpCAM. Cancer patients generally had a lower reactivity to EpCAM peptides and immunization with IGN101 induced reactivity against a different set of peptides. Antibodies cross-reacting with both the IgG2a framework and with the Mab17-1A idiotype were identified. In summary, our data indicate that some EpCAM peptides may be recognized in a species-specific manner. At least seven EpCAM-derived peptides could be of diagnostic interest (QCQCTSVGAQ, ERVRTYWIII, ALQKEITTRY, TYWIIIELKH, IADVAYYFEK, AYYFEKDVKG, GQTLIYYVDE), while four out of these seven peptides may also possess therapeutic relevance (TYWIIIELKH, ALQKEITTRY, IADVAYYFEK, AYYFEKDVKG).

Amino Acid Sequence↗
PubMed2005

Pediatric electrocardiograph abnormalities following Centruroides limpidus tecomanus scorpion envenomation.

Scorpionism is an endemic public health problem in Mexico [Hoffmann, C.C., 1936. La distribucion geografica de los alacranes peligrosos en la Republica Mexicana. Bol. Inst. Hygiene Mex. 2, 321; Hoffmann, C.C., Nieto, D.R., 1939. Segunda contribucion al conocimiento de los alacranes mexicanos. Anal. Inst. Biol. 10, 83-92; Mazzoti, L., Bravo-Becherelle, M.A., 1963. Scorpionism in the Mexican Republic. In: Keegan, H.L., McFarlane, W.V. (Eds.), Venomous and Poissonous Animals and Noxious Plants of the Pacific Area. Pergamon Press, London, pp. 119-131; Monroy-Velasco, J., 1961. Alacranes venenosos de Mexico. Rev. Mex. Cien. Med. Biol., Mex. 1, 1-23; Diaz-Najera, A., 1975. Listas y datos de distribucion geografica de los alacranes de Mexico. Rev. Inv. Salud. Publica. (Mex.) 35, 1; Velasco-Castrejon, O., Lara-Aguilera, R., Alatorre, H., 1976. Aspectos epidemiologicos y clinicos de la picadura de alacran en una area hiperendemica. Rev. Inv. Salud Publica. (Mex.) 36, 93-103; Dehesa-Davila, M., Possani, L.D., 1994. Scorpionism and serotherapy in Mexico. Toxicon 32 (9), 1015-1018]. In this prospective study, we assess cardiovascular disorders in children via electrocardiographic (ECG) recordings following envenomation by scorpion species Centruroides limpidus tecomanus found in the state of Colima, Mexico. We analyzed 113 cases between the ages of 5 and 14 years. Among the most frequent symptoms presented included local pain (99.1%) and paresthesia (75.2%), pruritus (36.3%), sialorrhoea (35.4%), and nystagmus (24.8%). Cardiovascular disorders were observed in 39.8% of cases, 71% of which were rhythm abnormalities. We find a significant association between the frequency of ECG alterations and age, whereby 8-9-year-old children are more likely to experience ECG alterations when compared with other tested age groups.

Adolescent↗
PubMed2004

Evaluation of diphtheria convalescent patients to serve as donors for the production of anti-diphtheria immunoglobulin preparations.

AIMS: The study was conducted to evaluate the possibility of selecting convalescent diphtheria patients to serve in emergency situations as donors for the production of anti-diphtheria immunoglobulin. To select suitable donors, the criterion of an antitoxin titer >/=3.0 IU/ml was used. In addition, the effects of treatment and the effect of immunization with diphtheria toxoid on the level of anti-diphtheria toxin antibodies were evaluated. SCOPE: Three groups of diphtheria patients were included in the study. The first group (n = 23) consisted of patients who had a basic antibiotic treatment, with or without serotherapy using horse antitoxin and/or human immunoglobulin. The second group (n = 12) comprised patients examined immediately after the onset of disease. The immunological history of this group was not known. The third group (n = 20) included patients with a known immunization history, treated only with antibiotics but having received a booster immunization with diphtheria toxoid. Antitoxin titers were measured using the toxin binding inhibition (ToBI) assay. CONCLUSIONS: In the first group, 47.8% (11/23) of the patients had a diphtheria antibody titer >/=3.0 IU/ml. For most of them, however, the antibody titers could have resulted from treatment with exogenous antibodies from horse antitoxin or human immunoglobulin (18/23). Only two of the 11 high-titer subjects had received antibiotics only. Among the second group, only two (16.76%) of the patients had an antibody titer of >/=3.0 IU/ml. In the third group 50% (10/20) of the patients showed an antibody titer of >/=3.0 IU/ml prior to vaccination, and therefore could be directly considered as donors. Three weeks after booster vaccination, 70% (14/20) had an antibody titer of >/=3.0 IU/ml and 1 year after booster vaccination, 28.6% (2/7) of the subjects still had titers of >/=3.0 IU/ml. In 40% of these patients, a decrease was observed 3-4 weeks after the booster dose. It was concluded that convalescent diphtheria patients could be considered as donors in an emergency situation, since approximately half of them showed antitoxin titers of >/=3.0 IU/ml.

Adolescent↗