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Biomedical subjects

I Schedel

Publications and source records attributed to I Schedel.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Post infection antiidiotype vaccination against HIV: results of a phase Ia pilot study].

The mAb IOT4A against the HIV-gp 120 binding site on CD4 was shown to elicit the production of specific anti-idiotypes in rabbits neutralising HIV-1 in vitro. This study was designed in order to determine the safety and efficacy of the mAb IOT4A for the immunization of HIV+ volunteers. 10 patients in stages WR2-WR4B of HIV-disease were given six s.c. injections of the mAb IOT4A as an alum precipitate (each 3 patients receiving 0.6 or 1.2 mg, 4 patients receiving 2.4 mg). 6 patients subsequently received a booster immunization with the same dose of the mAb IOT4A. The immunization schedule was accompanied by monitoring clinical, immunologic and virologic parameters. No systemic toxic or allergic effects of the idiotype vaccine were observed. 8/10 vaccinees displayed a delayed-type hypersensitivity at the location of antibody administration beyond the third injection. The relative and absolute CD4 count showed a sustained increase in 8/10 patients at the end of the booster immunization and an additional raise after booster immunization in 6/6 patients. 624 antigen levels became negative in 2/2 patients during vaccination. In 4/10 patients in increase in HIV/gp 120 antigen binding titres was observed. HIV neutralisation titer remained stable throughout the observation period, and no progression in HIV disease was observed in all patients included in this study. The administration of the mAb IOT4A as a vaccine in HIV-infected volunteers was well tolerated. The mAb ITO4A induced the production of specific anti-idiotypes, that might have been of clinical benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Anti-Idiotypic↗
PubMed1993

Symptomatic sulfadiazine crystalluria in AIDS patients: a report of two cases.

As the incidence of toxoplasma encephalitis (TE) in AIDS patients increases, sulfadiazine/pyrimethamine combination therapy is broadly administered. Two cases of acute and chronic renal sulfadiazine crystallization with acute renal failure and nephrolithiasis are reported. Controlled alkalinization of the urine and high fluid intake are recommended for prophylaxis of crystalluria.

AIDS-Related Opportunistic Infections↗
PubMed1992

Neutralization of HIV-1 by anti-idiotypes to monoclonal anti-CD4. Potential for idiotype immunization against HIV.

Anti-idiotypic antibodies were raised in rabbits against a panel of 11 murine mAb directed to the human CD4 receptor. Selection of mAb for vaccination was based on inhibition studies demonstrating that these mAb recognized CD4/V1 epitopes implicated in HIV-1-gp120 binding. Purified antisera showed high titer anti-Id activity and reacted specifically with Ag-combining site-related Id of the mAb used for their generation. Anti-Id either detected a private Id of the immunizing mAb or displayed a partial cross-reactivity with Id of other mAb to CD4. Eight anti-Id to six different mAb were shown to recognize determinants of recombinant HIV-1-gp120 or of HIV-1-gp160 as shown by ELISA and radioimmunoprecipitation assay. These anti-Id were capable of inhibiting HIV infection up to 100% in a MT-4 cell assay in vitro. In addition to neutralizing infectivity of cell-free virus, anti-Id to two mAb--the mAb IOT4a and 7.3F11--were also shown to inhibit HIV-induced syncytia formation up to 100%. Anti-Id to the mAb IOT4a, 7.3F11, and to the mAb anti-Leu3a interfered with rgp120 binding to cellular CD4 as assessed by flow cytometry. These results demonstrated that mAb specific for both CDR2- and CDR3-like regions of CD4 were capable of inducing HIV-1-gp120 cross-reacting anti-Id neutralizing HIV-1 in vitro. These studies may have implications for the development of a gp120 internal image based vaccine against HIV.

Animals↗
PubMed1992

Lack of clinical evidence for a specific HIV-associated glomerulopathy in 203 patients with HIV infection.

Several authors described a high incidence of proteinuria with frequent progression to nephrotic syndrome and/or renal failure in patients with HIV infection. Though renal histological changes were rather non-specific, the existence of a specific, HIV-associated glomerulopathy was postulated. We repeatedly investigated proteinuria and serum creatinine in 203 HIV-infected patients. One hundred and twenty-two patients (group 1) had early stages of the disease without opportunistic infections, 81 suffered from acute opportunistic infections (group 2). In patients with a positive qualitative test (Combistix), quantitative measurement (Biuret) for proteinuria was carried out; when proteinuria was greater than 0.5 g/24 h, SDS gel electrophoresis was performed. None of the patients of group 1 had a proteinuria greater than 0.5 g/24 h or an elevated serum creatinine. Eleven of 81 patients from group 2 had a proteinuria between 0.5 and 3 g/24 h; one further patient of group 2 developed a transient proteinuria of 7.7 g/24 h. Only three of the proteinuric patients showed a glomerular pattern in SDS gel electrophoresis, all three during acute CMV or EBV infections. Fourteen of 81 group 2 patients showed a transient elevation of serum creatinine (x +/- SD of the maximum serum creatinines: 225.3 +/- 163 mumol/l), most during pentamidine therapy for Pneumocystis carinii infection; one patient treated with high-dose acyclovir had to be temporarily dialysed. In the investigated 203 HIV patients no nephrotic syndrome and no sustained elevation of serum creatinine greater than 200 mumol/l was observed. All cases of proteinuria and elevation of serum creatinine were associated with severe opportunistic infections and the administration of potentially nephrotoxic antibiotics.

Adolescent↗
PubMed1992

Endotoxin concentration in neutropenic patients with suspected gram-negative sepsis: correlation with clinical outcome and determination of anti-endotoxin core antibodies during therapy with polyclonal immunoglobulin M-enriched immunoglobulins.

We carried out a study in patients with severe neutropenia from hematologic malignancy and suspected gram-negative sepsis to evaluate the clinical significance of endotoxin concentrations in plasma before and during a therapeutic intervention with a human polyclonal immunoglobulin M (IgM)-enriched immunoglobulin preparation (Pentaglobin; Biotest, Dreieich, Germany). Twenty-one patients with acute leukemia or non-Hodgkin's lymphoma entered the study upon the development of clinical signs of gram-negative sepsis and received the IgM-enriched immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 liter with 7.8 g of IgM, 7.8 g of IgA, and 49.4 g of IgG), in addition to standardized antibiotic treatment. Concentrations of endotoxin and IgM and IgG antibodies against lipid A and Re lipopolysaccharide (LPS) in plasma were determined by a modified chromogenic Limulus amebocyte lysate test and semiquantitative enzyme linked immunosorbent assay, respectively, before each immunoglobulin infusion and during the following 25 days. Seventeen patients were endotoxin positive; in five of these patients, gram-negative infection was confirmed by microbiologic findings. Prior to therapy, endotoxemia correlated significantly with the occurrence of fever, and a quantitative correlation between the endotoxin concentration and body temperature was found during the individual course of infection in 8 of the 17 patients. Overall mortality from endotoxin-positive sepsis was 41% (7 of 17) and 64% (7 of 11) in patients with symptoms of septic shock. Nonsurvivors had significantly higher maximum concentration of endotoxin in plasma compared with those of survivors at the first study day (median of 126 versus 34 pg/ml; P < 0.05) and during the whole septic episode (median of 126 versus 61 pg/ml; P < 0.05). In survivors, immunoglobulin therapy resulted in a significant decrease in endotoxin levels in plasma within the initial 18-h treatment period, from a pretreatment median value of 28 pg/ml to a value of 8 pg/ml (P< 0.05). In the seven patients who died from uncontrollable infection, no effect of therapy on endotoxin levels in plasma was observed. IgM and IgG antibodies against lipid A and Re LPS increased significantly under immunoglobulin treatment, with significant correlations between antibodies against lipid A and Re LPS. These data strongly suggest a prognostic significance of the endotoxin levels in plasma and a potential effect of treatment with a polyclonal IgM-enriched immunoglobulin preparation. Further studies are needed to substantiate these findings and to assess the impact on the clinical course by way of a prospective placebo-controlled clinical trial.

Adult↗
PubMed1991

Malnutrition and immune dysfunction in patients infected with human immunodeficiency virus.

STUDY OBJECTIVE: To determine forms of malnutrition and basal metabolism at different stages of immunological impairment in clinically stable patients infected with Human Immunodeficiency Virus (HIV). DESIGN: Cross sectional study. SETTING: 53 outpatients with HIV-infection classified according to the Walter Reed staging system (WR1 to WR6). MEASUREMENTS AND MAIN RESULTS: 87% of the patients showed some evidence of malnutrition. Reduced body weight was found in 53%, 68% and 25% had decreases in fat and body cell mass, 17% had visceral protein deficiency, whereas extracellular mass and serum triglyceride concentrations were increased in 58% and 30%, respectively. Reduced serum albumin and transferrin closely paralleled immunological depression, whereas alterations in body composition were manifest early during HIV-infection (WR3) and remained unchanged during the transition to the Acquired Immune Deficiency Syndrome itself. Resting metabolic rate increased from WR1 to WR3; it remained within the expected range during later stages (WR4-WR6), but was not appropriately reduced in response to the loss in body cell mass. CONCLUSIONS: HIV-infected patients display both, calorie and protein malnutrition. Immunological depression was independent of loss of body mass, but was closely associated to decreases in serum albumin values. Nutritional assessment and intervention should therefore be performed at an early stage of HIV-infection.

Adult↗
PubMed1991

Cytokine secretion by peripheral blood monocytes from human immunodeficiency virus-infected patients is normal.

We have measured the production of interleukin 1 (IL 1), interleukin 6 (IL 6), and tumor necrosis factor alpha (TNF alpha) by unstimulated monocytes and monocytes stimulated with lipopolysaccharide (LPS) isolated from the peripheral blood of patients infected with human immunodeficiency virus 1 (HIV-1) and healthy controls. Spontaneous and LPS-induced cytokine production were not significantly different between patients and controls. Median lipopolysaccharide-stimulated cytokine secretion for patients and controls was 1.7 and 4.3 U/ml for IL 1, 475 and 625 U/ml for IL 6, and 468 and 580 pg/ml for TNF alpha. Cytokine levels were not related to stage of disease. We conclude that in vivo HIV infection itself does not alter peripheral blood monocyte cytokine secretion.

Adolescent↗
PubMed1991

Treatment of gram-negative septic shock with an immunoglobulin preparation: a prospective, randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness of a polyclonal immunoglobulin (Ig) preparation containing IgG, IgM, and IgA as an adjunctive therapy for septic shock. DESIGN: Prospective, randomized clinical trial. SETTING: A clinical immunology ward at the center for internal medicine in a university hospital. PATIENTS: Fifty-five patients with septic shock were randomly allocated to two groups according to criteria of septic shock. INTERVENTION: One group of patients (n = 27) received a commercially available immunoglobulin preparation (containing high titers of antibodies specific for determinants to bacterial endotoxin) during the first 3 days after inclusion in the study. The other randomized group (n = 28) did not receive any immunoglobulin preparation. MEASUREMENTS AND MAIN RESULTS: During the period of less than or equal to 6 wks after the beginning of clinically apparent septic shock, death related to the septic process occurred in one (4%) of 27 patients who received immunoglobulin. By comparison, nine (32%) of 28 control group patients died during this period (p less than .01). Within the first 48 hrs after onset of the clinically apparent septic process, significantly increased activity of circulating endotoxin and simultaneously decreased specific IgG serum titers to lipid A were detected in the group of nonsurvivors. CONCLUSION: Administration of a polyclonal immunoglobulin preparation in the early phase of septic shock was associated with significantly improved survival.

Antibodies, Bacterial↗
PubMed1990

Molecular cloning and characterization of a German HIV-1 isolate.

The genetic diversity of HIV-1 is well documented. Except for the HIV-1 isolate LAV-1BRU, no nucleic acid sequence of a European isolate of HIV-1 has been published to date. To further investigate the extent of the genetic variability and the evolution of HIV-1, we have isolated, cloned, and subsequently sequenced HIV-1 from a German patient with AIDS-related complex. Comparative studies of the nucleic acid sequence revealed that this isolate, designated HAN2, is highly divergent from the North American and African subtypes of HIV-1 and may represent a European subtype of HIV-1. Furthermore, a full-length molecular clone was derived from this isolate which was infectious in human T-cell lines. Therefore this new isolate will be particularly useful for studies on the genetic evolution and biology of HIV-1 as well as for testing antiviral substances and for developing vaccines.

Amino Acid Sequence↗
PubMed1990

The interferon-induced Mx-homologous protein in people with symptomatic HIV-1 infection.

Twenty-six people with symptomatic HIV-1 infection were screened for the presence of interferon (IFN) alpha and IFN alpha antibodies in their sera and the presence of the IFN-induced intracellular Mx-homologous protein in their peripheral blood leukocytes. Eleven people had measurable IFN alpha levels ranging from 1 to 40 IU/ml. None of the sera tested was positive for IFN alpha binding or IFN alpha neutralizing antibodies in the assays employed. Twenty-five of the 26 people had significant levels of the Mx-homologous protein in their peripheral mononuclear cells. The Mx concentrations varied from 0.3 to 6 U/ml in the people studied. IFN alpha-positive people had significantly higher levels of the Mx homolog than IFN alpha-negative people (P less than 0.03). Furthermore, the Mx homolog content in Walter-Reed class 2 people was significantly lower than in Walter-Reed class 5/6 people (P less than 0.01). Our results suggest that the IFN system is activated in more than 90% of the people with lymphadenopathy-associated syndrome, AIDS-related complex and AIDS. Since acid-labile IFN alpha can induce the Mx homolog in vitro endogenously produced IFN alpha seems likely to be responsible for the high Mx homolog levels detected.

AIDS-Related Complex↗
PubMed1989

Modulation of cancer patients' immune responses by administration of anti-idiotypic antibodies.

Thirty patients with Dukes stage D colon carcinoma who had undergone operative removal of the primary tumor and had growing hepatic metastases each received four intradermal injections of 0.5-4 mg of alum-precipitated goat anti-idiotypic antibodies (anti-Id). The anti-Id had been produced against murine monoclonal antibody (mAb) CO17-1A, which defines a human colon carcinoma associated antigen. All patients elaborated anti-anti-Id that shared idiotopes with mAb CO17-1A, bound to tumor cells and isolated tumor antigen, and competed with the mAb for binding to tumor cells. The clinical response was monitored by ultrasonography, CT, radionuclide scanning, and serum marker assays. Six patients had partial tumor responses; five of these had received additional booster anti-Id injections along with chemotherapy. Seven patients had stabilized tumor; six had received additional anti-Id, with chemotherapy also in four. Conclusions about the clinical role of such immunization await further study, but in demonstrating a specific response to anti-Id, our results support the use of this approach in human immunotherapy against tumors or pathogens.

Antibodies, Anti-Idiotypic↗
PubMed1988

Induction and maintenance therapy in multiple myeloma: a multicenter trial of MP versus VCMP.

In a prospective multicenter trial, 320 untreated myeloma patients of stage II and III were randomized for remission induction into two groups receiving six monthly courses of either MP or VCMP treatment. Response rates were equal in both groups: 72% remission, 21% no change, 7% progress for patients evaluable by TCM changes and 56% remission, 11% no change, 33% progress for BJ- and non-secretory myelomas. The overall survival rate was 60% after 4 years. An unexpected finding was the significantly longer survival of MP treated patients compared to the VCMP group. After successful remission induction, patients were randomized into one group receiving maintenance treatment using the induction scheme q 8 weeks, and another group without further chemotherapy. Although patients in the latter group relapsed significantly earlier, differences between both groups concerning acquired resistance to first line therapy or survival have not been noticed to date.

Adult↗
PubMed1988

VBAMDex chemotherapy in advanced multiple myeloma.

In a phase II study 28 patients with advanced multiple myeloma were treated with a five drug regimen consisting of vincristine, BCNU, adriamycin, melphalan and dexamethasone. 11 out of 13 patients without prior chemotherapy showed significant remissions (greater than 25% tumor cells mass reduction), 7 of them had more than 75% TCM reduction. Out of 15 additional patients resistant to previous chemotherapy, 13 had significant remissions, including 9 patients with greater than 75% TCM reduction. No tumor progression was observed in either group of patients. The median follow-up of all patients was 12.75 months. 4 patients relapsed. Toxicity mainly related to the bone marrow was observed in 14 patients. This regimen might offer a promising alternative for the treatment of advanced multiple myeloma, but still has to be tested in a prospective randomized trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Crossreacting idiotypes of kappa-monoclonal immunoglobulins M in sera of patients with Waldenström's macroglobulinemia.

Seventeen anti-idiotypic antisera (anti-Id) were prepared against kappa-monoclonal IgM from patients with Waldenström's macroglobulinemia. Their reactivity against homologous and heterologous IgM was tested using an ELISA. Crossreacting idiotypes were only found in two out of 289 investigated antigen-antibody reactions. One anti-Id IgG crossreacted with determinants on polyclonal IgM. These rare crossreactions were observed in Waldenström's macroglobulinemia patients with and without polyneuropathy. The scarcity of common idiotypes on different monoclonal IgM does, however, not constitute a decisive argument against common or related antibody specificities of such monoclonal IgM.

Antibodies, Anti-Idiotypic↗
PubMed1987

Anti-idiotype immunization of cancer patients: modulation of the immune response.

Thirty patients with advanced colorectal carcinoma (CRC) were treated with alum-precipitated polyclonal goat anti-idiotypic antibodies (Ab2) to monoclonal anti-CRC antibody CO17-1A (Ab1) in doses between 0.5 and 4 mg per injection. All patients developed anti-anti-idiotypic antibodies (Ab3) with binding specificities on the surfaces of cultured tumor cells similar to the specificity of Ab1. Furthermore, the Ab3 competed with Ab1 for binding to CRC cells. Fractions of Ab3-containing sera obtained after elution of the serum immunoglobulins from CRC cells bound to purified tumor antigen and inhibited binding of Ab2 to Ab1. The Ab3, therefore, may share idiotopes with Ab1. Six patients showed partial clinical remission and seven patients showed arrest of metastases following immunotherapy. Four of the thirteen patients with measurable clinical responses had received Ab2 alone, whereas 9 patients had also received chemotherapy.

Antibodies, Anti-Idiotypic↗
PubMed1986

Severe hemolysis caused by antibodies against the mushroom Paxillus involutus and its therapy by plasma exchange.

It has been shown that fatal "poisoning" with the mushroom species Paxillus involutus is caused by antibodies against the fungus in sensitized patients. Because circulating immune complexes play an important role, therapeutic procedures which can eliminate those complexes could stop immune hemolysis. A 37-year-old patient became severely ill after repeated ingestion of sufficiently cooked Paxillus involutus. As a result of hemolysis with reversible shock symptoms, acute renal failure developed. Plasma exchange with 3,000 ml albumin 5% was carried out daily during the first 3 days after admission. Each plasma exchange lowered free hemoglobin and immune complex levels by 60%-75%. Acute renal failure was successfully treated with hemodialysis. Specific IgG-antibodies against membrane particles of Paxillus involutus were detected by hemagglutination tests in the serum of the patient. The sequence of reactions resulting from the testing procedures strongly suggests the formation of immune complexes. These complexes are likely to bind to erythrocytes acting as innocent bystanders. Activation of the complement system finally results in hemolysis and shock. In addition to adequate shock treatment elimination of these immune complexes by plasma separation seems to be the therapy of choice.

Adult↗
PubMed1986

Cytostatic drug sensitivity test for human multiple myeloma, measuring monoclonal immunoglobulin produced by bone marrow cells in vitro.

An in vitro cytostatic drug sensitivity test for human multiple myeloma has been developed, predicting differences in sensitivity of the individual tumor to various anticancer drugs. Bone marrow preparations containing the tumor cells were incubated with cytostatic drugs and cultured for 10 days. Using an enzyme-linked immunosorbent assay we measured tumor products--monoclonal immunoglobulin and beta 2-microglobulin--in the culture supernatants. The reduction of these products in vitro due to the drugs administered was compared with the patients' further clinical course during treatment with different standard cytostatic drug regimens. We found a predictive value of more than 80% for this easily performed test.

Antibodies, Monoclonal↗