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Biomedical subjects

H Deicher

Publications and source records attributed to H Deicher.

At least 19 recordsLinked to original sources
PubMed1997

Positron emission tomography and magnetic resonance imaging for cerebral involvement in patients with systemic lupus erythematosus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains difficult to diagnose, particularly since structural abnormalities may not be revealed by magnetic resonance imaging (MRI). Glucose utilisation was measured by positron emission tomography (PET) in 35 SLE patients to detect signs of CNS involvement. The patients were examined by a standardised neurological examination, a battery of tests to evaluate neuropsychological performance and MRI. Antineuronal antibodies were determined to investigate their putative role in CNS involvement in SLE. Twenty patients had distinct neurological (17) and/or psychiatric (3) symptoms. Ten patients had pronounced cognitive impairment. Neurological and cognitive deficits were thus found to be unrelated disorders in SLE. Global glucose utilisation of SLE patients did not differ significantly from that of normal controls, nor were differences found between SLE patients with or without neurological or cognitive abnormalities. On MRI of the brain, the number and size of white matter lesions correlated with the presence of neurological deficits but were unrelated to the severity of cognitive impairment. Within the normal range, lower global glucose utilisation tended towards lower values with increasing number and size of white matter lesions. Patients with lesions larger than 8 mm also showed distinctly increased IgG anticardiolipin antibody titres, whereas measuring antineuronal antibodies did not reveal any relation to the variables investigated. We conclude that the demonstration of CNS lesions by MRI can contribute confirmatory evidence for CNS involvement in SLE, but PET or the presence of antineuronal antibodies adds little if any information beyond that obtained by clinical examination, neuropsychological testing, and MRI.

Adult↗
PubMed1997

Detection of Ureaplasma urealyticum in urine of patients with systemic lupus erythematosus and healthy individuals by culture and polymerase chain reaction.

A method was developed to detect Ureaplasma urealyticum in urine by the polymerase chain reaction (PCR). A 457-bp fragment of the urease gene of U. urealyticum was amplified by PCR. Before PCR, components disturbing the amplification had to be reduced. This was possible by diluting the urine 1 in 10 with distilled water and by the extraction of the U. urealyticum DNA. Urine specimens from 41 patients with systemic lupus erythematosus (SLE) and 21 healthy individuals were treated by the dilution method and investigated by PCR for U. urealyticum DNA. The results were compared with those obtained by culture and the detection rates of PCR and culture were found to be identical. Also there was no difference in the detection rates of U. urealyticum from urine of SLE patients and healthy individuals; 10 (24.4%) of the 41 urine specimens from SLE patients and five (23.8%) of the 21 urine specimens from healthy individuals gave positive results for U. urealyticum. The results of this study do not indicate a decisive role for U. urealyticum in SLE.

Adolescent↗
PubMed1996

CD4-imitating human antibodies in HIV infection and anti-idiotypic vaccination.

Anti-idiotypic vaccination against HIV infection aims at inducing an anti-gp120 immune response through anti-CD4 Abs mimicking epitopes of the gp120 molecule. The mAb IOT4a induces anti-gp120 Abs in rabbits. This study investigates the presence of human serum Abs cross-reacting with anti-CD4 mAbs and gp120 during HIV infection and after parenteral vaccination with IOT4a. Ten HIV-infected volunteers without immunodeficiency were inoculated s.c. with 0.6, 1.2, or 2.4 mg IOT4a. Six booster injections followed until day 35. Sera from study patients, 80 HIV-positive, and 43 seronegative controls were examined by a panel of assays, including an ELISA using competition against biotinylated recombinant CD4, flow cytometry assaying inhibition of anti-CD4 mAbs and biotinylated gp120 binding to CD4-positive lymphocytes, and an IOT4a immunoblot. After vaccination, an increase in competitive binding activity, which was quantitative in ELISA and flow cytometry, was observed. In the ELISA, competition against biotin-CD4 was quantitatively quenched by preincubating sera with r-gp120 or anti-CD4 mAbs such as IOT4a and Leu3a. Naive sera or sera from blood donors had no such effect in the assays employed, while 5/80 HIV sera showed binding qualities similar to vaccinees. These results suggest that 1) CD4 internal-image Abs emerge in a small proportion of HIV-positive individuals, and 2) parenteral vaccination with mAb IOT4a can induce a gp120 cross-reacting immune response that inhibits gp120 binding to CD4.

Adult↗
PubMed1996

Weight gain and increased concentrations of receptor proteins for tumor necrosis factor after patients with symptomatic HIV infection received fortified nutrition support.

OBJECTIVE: To determine whether certain nutrients and dietary factors act as modulators of the immune system and improve the nutritional status of immunocompromised patients. DESIGN: Controlled, double-blind, crossover phase trials of the effects of a fortified formula in patients infected with the human immunodeficiency virus (HIV). Patients consumed a control formula for 4 months and a study formula for 4 months. SUBJECTS: Ten men with symptomatic HIV infection who were following stable medication regimens and had no malignancies, mycobacteriosis, or additional virus infection requiring systemic treatment. INTERVENTION: Formula fortified with alpha-linolenic acid (1.8 g/day), arginine (7.8 g/day), and RNA (0.75 g/day) and a standard formula. MAIN OUTCOME MEASURES: Nutritional status determined by anthropometric, bioelectrical, biochemical, and dietary assessment; energy expenditure determined by indirect calorimetry; disease progression; CD4 lymphocyte counts; HIV p24 antigen plasma concentrations; tumor necrosis factor (TNF) receptor proteins; and compliance control parameters. STATISTICAL ANALYSES PERFORMED: Student's t tests for paired and unpaired data. RESULTS: Fortified nutrition resulted in a weight gain (+ 2.9 kg/4 months vs -0.5 kg/4 months with the control formula, P < .05), an incorporation of eicosaenoic acid into erythrocyte cell membranes (+ 47% of baseline values, P < .05), and increased plasma arginine concentrations (96.8 +/- 45.1 vs 51.8 +/- 20.9 mumol/L, P < .01). The serum concentrations of the soluble tumor necrosis factor receptor (sTNFR) proteins increased during the study period (sTNFR 55 = + 0.23 vs -0.40 ng/mL, P < .001; sTNFR 75 = + 0.90 vs -0.36 ng/mL, P < .01), whereas no changes in CD4+ lymphocyte counts were observed. CONCLUSION: Increasing dietary intakes of n-3 polyunsaturated fatty acids, L-arginine, and RNA increased body weight, possibly by modulating the negative effects of TNF.

Adolescent↗
PubMed1996

Pyridinium cross-links in multiple myeloma: correlation with clinical parameters and use for monitoring of intravenous clodronate therapy--a pilot study of the German Myeloma Treatment Group (GMTG).

The relevance of quantitative determinations of urinary deoxypyridinolines (DPY) and pyridinolines (PY), and of serum type I collagen carboxyterminal cross-linked telopeptides (ICTP), has been evaluated for patient monitoring in multiple myeloma (MM). In 178 untreated MM patients, a clear correlation was found between ICTP concentrations, bone destructions and serum calcium levels. Furthermore, serum ICTP, urinary DPY and PY concentrations were estimated before and during treatment in a further 33 MM patients randomly allocated to four groups receiving intravenous melphalan/prednisone (MivP) chemotherapy alone, or MivP in combination with three different doses of i.v. clodronate. 1800 mg of i.v. clodronate combined monthly with MivP induced a rapid and sustained reduction in bone resorption parameters to the normal range, a result not obtained with either MivP alone, or with a lower clodronate dose. While confirming the relevance of determining pyridinium cross-links for estimating bone resorption in MM, our data indicate that measurements of these parameters could be useful for dose finding and monitoring of bisphosphonate therapy.

Adult↗
PubMed1996

Autoantibody against a 58 kD molecule in a patient with neutropenia and NK cell deficiency.

A patient with Evans' syndrome is described who developed intermittently an immunocytopenia consisting of autoimmune neutropenia and natural killer (NK) cell deficiency. During this time an autoantibody binding to a 58 kD antigen expressed on granulocytes, activated NK cells and Epstein-Barr virus (EBV) transformed B cells was present. Incubation of activated NK cells and NK cell clones with the autoantibody leads to a significant inhibition of NK activity. Therefore the autoantibody may detect a functionally important activation molecule.

Adult↗
PubMed1996

Percutaneous endoscopic gastrostomy in AIDS and control patients: risks and outcome.

OBJECTIVES: Wasting is a major feature of advanced HIV infection. Enteral nutrition via percutaneous endoscopic gastrostomy (PEG) is a safe and efficient therapy in malnutrition, but limited experience exists in wasted HIV patients. Here we report on outcome and risk of PEG-feeding in HIV patients compared with HIV-seronegative patients and with HIV patients without PEG. METHODS: In 47 HIV-infected patients, PEG was placed because of wasting (n = 33), neurologic deficits (n = 11), or dysphagia (n = 3). Clinical, immunological, and nutritional data were compared with those of i) 15 HIV patients who refused PEG placement despite an appropriate indication, ii) 76 HIV patients without signs of malnutrition, and iii) 43 miscellaneous PEG patients. RESULTS: PEG was as safe in HIV-infected as in HIV-seronegative patients. PEG feeding resulted in significant increases of body weight (+3.3 +/- 3.6 kg, p < 0.001), serum albumin concentration (+4.5 +/- 7.2 g/L, p < 0.005), and total iron-binding capacity (+9.5 +/- 11.5 mumol/L, p < 0.001). Moreover, our data indicate that PEG feeding may improve survival in wasted AIDS patients. CONCLUSIONS: PEG feeding is safe and effective in the treatment of the AIDS wasting syndrome. Further prospective investigations are necessary to answer the question of whether treatment of wasting improves patient survival.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients.

Although malnutrition and wasting are known features of human immunodeficiency virus (HIV) infection, their incidence and possible association with immunologic impairment are largely unknown, as is the prognostic value of the nutritional state. Nutritional, clinical, and immunologic parameters were measured in 100 outpatients in different stages of HIV infection. In addition, 39 patients with AIDS were prospectively followed for a mean period of 343 (range, 53-650) days. Sixty-three percent of the patients showed evidence of malnutrition, 21% suffered from wasting. A reduced body cell mass and decreased serum albumin levels were observed in 32 and 14%, respectively, predominantly in more advanced disease stages. Fourteen of 39 AIDS patients died after a mean survival of 212 days. Survivors showed significantly larger initial body cell mass values and higher initial serum albumin levels compared with nonsurvivors, whereas CD4+ lymphocyte counts, disease complications, and medication were all similar in both groups. Kaplan-Meier analyses revealed a significantly prolonged survival in patients with a body cell mass > 30% of body weight or serum albumin levels exceeding 30 g/L. Factor analyses indicated that the parameters of nutritional state were independent from each other and from CD4+ lymphocyte counts. Malnutrition occurs frequently during HIV infection and increases with disease progress. It strongly predicts patient survival independent of CD4+ lymphocyte counts.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Functional and biochemical characteristics of a soluble B lymphocyte proliferation-inhibiting activity produced by bone marrow cells from multiple myeloma patients.

Several mechanisms are discussed as inducers for polyclonal hypogammaglobulinemia in multiple myeloma. A soluble noncytotoxic activity which inhibits in vitro the proliferation of normal polyclonal spleen B lymphocytes was measured in the supernatant of cultured bone marrow mononuclear cells from multiple myeloma patients. In addition, human B lymphoblastic cell lines (CESS, Daudi) and human T lymphocytes were sensitive to the antiproliferative effect of the suppressor activity, while other cell lines (RPMI 8226, IM9, CTL6, L1210, HL-60, and K562) were not. The activity was detected in a 5-kDa fraction and was stable to heating (30 min, 56 degrees C) and proteolytic enzymes. Extraction experiments using chloroform:methanol (2:1) suggest a lipid character of the suppressor activity.

B-Lymphocytes↗
PubMed1995

Significance of antibodies to cardiolipin in unselected patients with systemic lupus erythematosus: clinical and laboratory associations. The SLE Study Group.

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion (P < 0.001), thrombocytopenia (P < 0.01), livedo reticularis (P < 0.01) and a positive direct Coombs test (P < 0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test (P < 0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis.

Adolescent↗
PubMed1995

Characterization of B-cell lines from SLE patients and their relatives.

Epstein-Barr-virus (EBV)-transformed lymphoblastoid B-cell lines were generated from peripheral blood lymphocytes of 55 patients with systemic lupus erythematosus (SLE) and 44 healthy relatives. All donors have previously been extensively characterized with regard to clinical, serologic, and genetic parameters. Here, peripheral blood lymphocytes and lines were characterized for cell surface antigens. Furthermore, autoantibody production and proliferation rate of the cell lines were monitored. A significant difference between patients and relatives was the lower proliferation rate of EBV-transformed cell lines of the SLE patients. All SLE cell lines are available for interested researches and can be obtained from the European Cell Bank, Salisbury, UK.

Antigens, Surface↗
PubMed1995

Effect of increased protein intake and nutritional status on whole-body protein metabolism of AIDS patients with weight loss.

The aim of this study was to investigate nutritional status and protein metabolism during total parenteral nutrition (TPN) in AIDS patients with weight loss. Six patients on treatment for AIDS-associated complications were investigated and reviewed TPN that supplied energy equivalent to 1.5 times the resting energy expenditure (REE). Amino acid (AA) supply increased from 0.6 g/kg body weight (BW)/d on days 1 to 3 and 1.2 on days 4 to 6 to 1.8 on days 7 to 9. Nonprotein energy was given as equicaloric amounts of glucose and fat emulsion. There were repeated measurements of nitrogen balance and whole-body protein turnover (WBPT) using a bolus 15N-glycine method on the morning of days 3, 6, and 9. Principal findings were as follows: (1) increasing the supply of AAs significantly improves nitrogen balance in AIDS patients; (2) there is no simple linear effect of increasing amounts of AAs on WBPT in AIDS patients; (3) WBPT is high and variable in these patients; and (4) mean WBPT of each patient is significantly correlated with body cell mass (BCM) as a proportion of BW (P < .001, r = .92). We conclude that poor nutritional status in AIDS patients with weight loss is associated with high WBPT. However, these patients can attain at least transiently positive nitrogen balance with sufficient protein intake, predominantly through an increase in whole-body protein synthesis (WBPS).

Acquired Immunodeficiency Syndrome↗
PubMed1995

A comparison of polychemotherapy and melphalan/prednisone for primary remission induction, and interferon-alpha for maintenance treatment, in multiple myeloma. A prospective trial of the German Myeloma Treatment Group.

406 untreated multiple myeloma patients of stage I (n = 54), II (n = 148) and III (n = 204) were enrolled in the trial. 51/54 stage I and 60/148 stage II patients were asymptomatic and followed without treatment until disease progression (progression free survival: 60% after 4 years for stage I versus 50% after 1 year for stage II). Symptomatic patients of stage I (n = 3/54) and II (n = 88/148) presenting with tumour progression, received melphalan 15 mg/m2 intravenously (i.v.) and prednisone 60 mg/m2 oral days 1-4 (MP). Stage II disease remission rate was 59%, and 50% tumour related survival (TRS) was 59 months. Stage III patients were randomised to receive MP or VBAMDex (vincristine/BCNU/doxorubicin/melphalan/dexamethasone) treatment. 43% of MP treated patients responded compared with 64% of the VBAMDex group. 50% TRS was 36 months in both groups without a detectable difference. 117 responders of stage II and III with stable disease were randomised to receive either IFN-alpha (5 x 10(6) IU, subcutaneous (S.C.) 3 times per week) or no maintenance treatment. The relapse rate in both groups was 50% after 13 months. No survival benefit for IFN alpha treated patients was observed (50% TRS: 45 months).

Aged↗
PubMed1995

Autoantibodies against eukaryotic protein L7 in patients suffering from systemic lupus erythematosus and progressive systemic sclerosis: frequency and correlation with clinical, serological and genetic parameters. The SLE Study Group.

Recent studies have shown that sera of patients suffering from systemic autoimmune diseases contain autoantibodies directed against the eukaryotic ribosomal protein L7 [1]. In the present study we screened a large panel of sera from patients with systemic lupus erythematosus (SLE) for the presence of anti-L7 autoantibodies and their relationship to clinical, serological and genetic parameters of SLE. By means of an ELISA employing recombinant protein L7 as antigen we detected anti-L7 autoantobodies in 172 of 506 SLE sera (34%). Negative correlations were observed between the presence of anti-L7 autoantibodies, serum IgG levels and proteinuria; a potentially positive relationship existed with lung fibrosis. In order to analyse further this possibility we screened sera of 129 patients suffering from progressive systemic sclerosis (PSS) for anti-L7 reactivity; 45 of these patients had lung fibrosis. Of the PSS patients, 41% exhibited anti-L7 autoantibodies, but positive reactions were evenly distributed among patients with and without lung fibrosis. Protein L7 thus represents a major autoantigen of systemic autoimmune diseases, but does not so far define a distinct subpopulation of patients.

Autoantibodies↗
PubMed1995

Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: a histopathological evaluation of biopsies from 153 untreated patients.

A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.

Bone Marrow↗
PubMed1995

Tumor-directed cytotoxicity in multiple myeloma--the basis for an experimental treatment approach with interleukin 2.

There is growing evidence that in multiple myeloma (MM) tumor-directed immune responses exist, might influence tumor progress and could be putative targets for immunotherapeutic approaches. Peripheral blood T lymphocytes are capable of suppressing monoclonal immunoglobulin production of autologous myeloma plasma cells in vitro. This activity can be enhanced by stimulation with mitogens, OKT3 monoclonal antibody or interleukin 2 (IL-2), and is obviously mediated by cytolytic T lymphocytes as demonstrated in a cytotoxicity assay using purified MM plasma cells as targets. The lytic activity is significantly higher when the effectors are prestimulated with irradiated autologous MM plasma cells. Based on these results 18 MM patients of advanced stages with tumor progress received 9 x 10(6) IU/m2 recombinant IL-2 (Proleukin) twice daily on days 1 and 2 and 0.9 x 10(6) IU/m2 twice daily for five subsequent days per week s.c. from days 3-56 (q 12 weeks). During therapy the number of eosinophils increased 15-fold, CD4+ T lymphocytes were activated as demonstrated by CD25 antigen expression and CD56+ natural killer (NK) cells expanded in the peripheral blood. NK cell activity and lymphokine-activated killer cell activity were significantly enhanced. IL-2 therapy induced endogenous IL-2 production and elevated soluble IL-2 receptor serum concentrations. Tumor response was observed in 6/17 evaluable patients. These data indicate that low-dose IL-2 treatment can stimulate immune enhancement in MM patients despite their characteristic tumor-induced immunodeficiency, and has proven to have limited efficacy in advanced MM patients.

Antibodies, Monoclonal↗