Biomedical subjects

J A Rump

Publications and source records attributed to J A Rump.

30 records · Page 2Linked to original sources

PubMed1992

Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum.

Diarrhoea and weight loss are found in more than 50% of patients with the acquired immunodeficiency syndrome (AIDS). In some patients the symptoms can be very severe, leading to death even in the absence of opportunistic infections. In 30% of these patients, enteric pathogens cannot be identified, and approximately only half of the identifiable aetiologic agents of diarrhoea in patients infected with the human immunodeficiency virus (HIV) were treatable with antibiotics. Immunoglobulins from bovine colostrum (Lactobin, Biotest, Dreieich, FRG) contain high titers of antibodies against a wide range of bacterial, viral and protozoal pathogens as well as against various bacterial toxins. Lactobin (LIG) is quite resistant to 24-h incubation with gastric juice. In a multi-center pilot study 37 immunodeficiency patients with chronic diarrhoea [29 HIV-infected patients, 2 patients with common variable immunodeficiency (CVID), one unidentified immunodeficiency, five patients with graft versus host disease (GvHD) following bone marrow transplantation] were treated with oral LIG (10 g/day for 10 days). Good therapeutic effects were observed. Out of 31 treatment periods in 29 HIV-infected patients 21 gave good results leading to transient (10 days) or long-lasting (more than 4 weeks) normalisation of the stool frequency. The mean daily stool frequency decreased from 7.4 to 2.2 at the end of the treatment. Eight HIV-infected patients showed no response. The diarrhoea recurred in 12 patients within 4 weeks (32.4%), while 19 patients were free of diarrhoea for at least 4 weeks (51.3%). In 5 patients intestinal cryptosporidiosis disappeared following oral LIG treatment. LIG treatment was also beneficial in 4 out of 5 GvHD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

Possible role of IL-2 deficiency for hypogammaglobulinaemia in patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) patients are unable to produce specific immunoglobulins after antigen contact in vivo. The aim of this study was to investigate whether in some cases of CVID a decreased de novo synthesis of IL-2 might be the cause of immunodeficiency and whether this deficiency can be corrected by IL-2 supplementation in vitro. Mononuclear cells from 17 CVID patients and from 10 healthy controls were cultured with monoclonal anti-CD3 antibody OKT3, pokeweed mitogen (PWM) or tetanus toxoid (TT) to stimulate IL-2 synthesis. In parallel, in vitro IgG and IgM synthesis was stimulated with Staphylococcus aureus Cowan I (SAC), PWM or TT in the presence or absence of IL-2. While lymphocytes of 11 out of 17 patients produced low to normal amounts of IL-2 upon stimulation with anti-CD3, only three patients showed low IL-2 production in response to PWM and five in response to TT. Regarding immunoglobulin synthesis in vitro, five patients completely failed to produce IgM or IgG upon stimulation with PWM, SAC or TT irrespective of the addition of IL-2. By contrast, four patients did not show any defect in vitro and synthesized normal amounts of IgM and IgG with any of the three stimuli. Finally, eight patients could be reconstituted for PWM-, SAC- and TT-induced IgM and/or IgG synthesis in vitro, by adding IL-2 to the culture system. This enhancing effect of IL-2 could be blocked by adding anti-IL-2 receptor antibodies to the cultures. Our findings indicate that a defective IL-2 synthesis after antigen stimulation may be one reason for the impaired immunoglobulin production in some cases of CVID.

Adult↗

PubMed1992

[A new type of ANCA in sera of patients with ulcerative colitis: effects of therapy and disease severity on serum titer].

Sera of 108 patients with chronic inflammatory bowel disease (IBD) and 13 control sera were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) by an indirect immunofluorescence test. 37 out of 64 sera (58%) from patients with ulcerative colitis (UC) produced a fine granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typically diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA) seen in active Wegener's granulomatosis (WG). Only 1 of the 44 sera from patients with Crohn's disease and none of the control sera showed positive p-ANCA reactions. Only 1 of the 64 CU sera was positive for antinuclear antibodies, and another one showed a positive reaction in the anti-proteinase-3 ELISA which is specific for WG. Antibodies against myeloperoxidase were negative in the CU sera. 31 out of the 37 p-ANCA-positive sera (84%) were obtained from patients with high disease activity. p-ANCA titers became negative after long-term steroid therapy and after complete colectomy. These preliminary data suggest that ANCA screening may be of value in differentiating IBD and in monitoring disease activity and drug effects in UC patients.

Adult↗

PubMed1991

Primary antiphospholipid syndrome (PAPS). Two case reports and therapeutic implications.

Antiphospholipid antibodies (aPL) interfere with the coagulation system and can cause thrombosis and other clotting disorders. The combination of recurrent venous thrombosis, arterial embolism and recurrent fetal loss is nowadays considered to be primary antiphospholipid syndrome (PAPS), provided an underlying systemic lupus erythematosus (SLE) has been excluded and aPL have been detected. We report on two patients with PAPs, and show the course of their IgG- and IgM-anticardiolipin antibody (aCL) titers during immunosuppressive therapy with prednisone and azathioprine or cyclophosphamide. Over a period of 18 months this therapy was effective in preventing relapses of thrombo-embolism and other complications. Therapy with cyclophosphamide resulted in normalization of the aCL titers in one of the two reported cases. Azathioprine treatment reduced the aCL titer in the other patient, without fully normalizing it. Based on our observation, we propose to treat PAPS-associated severe and recurrent thrombo-embolic complications by aggressive immunosuppression, including azathioprine and cyclophosphamide.

Adolescent↗

PubMed1991

[Immunologic defects in the lymphatic system of the intestinal mucosa in common variable immunodeficiency (CVID) syndrome].

The humoral immune system of the intestinal mucosa of patients with common variable immuno deficiency (CVID) syndrome was studied immunohistologically using antibodies against immunoglobulin (Ig) A1-2, M and G1-4, against the J chain and the secretory component. In 9/13 CVID-patients IgA-positive cells were totally absent whereas a total IgM-defect was found only in 3/14 patients. Considerable numbers of J chain-positive cells were present in all CVID-patients irrespective of the extent of the Ig-defect indicating the presence of early B-cells unable to differentiate and to produce Ig. There was a strong expression of the secretory component in the cytoplasm and at the surface of enterocytes even in those CVID-patients who were totally defective in IgA- and IgM-positive cells.

Humans↗

PubMed1990

A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease.

Sera of 64 patients with chronic inflammatory bowel disease (IBD) were screened for antibodies against neutrophil cytoplasmic antigens (ANCA) using an indirect immunofluorescence technique on ethanol-fixed human neutrophil granulocytes. 20 of 34 sera (59%) from patients with ulcerative colitis (UC) produced a fine-granular and perinuclear ANCA staining pattern (p-ANCA) clearly different from the typical diffuse and granular cytoplasmic ANCA fluorescence (c-ANCA, synonym ACPA) seen in active Wegener's granulomatosis (WG). The majority of the 20 p-ANCA positive UC patients had a high inflammatory disease activity. Among the 14 p-ANCA negative UC patients nine were without steroids; five of them had active disease, two were inactive and two had previously undergone colectomy. The remaining five patients still had active disease but received steroids for more than 4 weeks. Only 3 of the 30 sera from patients with Crohn's disease (CD) showed positive p-ANCA reactions. To narrow the specificity of the p-ANCA reaction all 64 sera were tested by ELISA for antibodies against anti-proteinase-3 (WG specific) and on HEp-2 cells for antinuclear (ANA) and anticytoplasmic antibodies. Ten p-ANCA positive UC sera were also tested in a myeloperoxidase ELISA. Only one UC serum reacted positively in the proteinase-3-ELISA and another one produced a weakly positive anti-nucleolar ANA fluorescence on HEp-2 cells. None of the tested sera reacted with myeloperoxidase suggesting that the p-ANCA staining pattern of granulocytes is not restricted to anti-myeloperoxidase antibodies as reported in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

[Effects of IL-2 and IL-6 on the immunoglobulin synthesis of lymphocytes from CVID patients].

Peripheral blood lymphocytes from five hypogammaglobulinemic patients suffering from common variable immunodeficiency (CVID) were stimulated with Staphylococcus aureus Cowan I (SAC) and pokeweed mitogen (PWM). The assays were substituted with interleukin-2 (IL-2) and interleukin-6 (IL-6) in different combinations. In three patients who were deficient for IgM in vivo a combination of SAC and IL-2 induced a normal IgM synthesis in vitro. In these patients a deficient IL-2 synthesis is probably the cause of CVID. In only one patient a "class switch" from IgM to IgG was detectable. Stimulation with PWM which is T-cell-dependent induced in one out of the five patients a normal IgM synthesis. Another CVID patient showed no defect in IgM or IgG synthesis in vitro. With these in vitro assays it seems possible to identify CVID patients who might profit from a therapy with human IL-2 in vivo.

Adult↗

PubMed1989

[ACPA reaction in atypical Wegener's disease. Diagnostic test].

Clinical and biopsy findings in six patients (aged 29-64 years), suspected of having Wegener's granulomatosis, were not diagnostic. Cardinal signs were skin necroses, isolated deficits of cranial nerves, sudden amaurosis, renal failure with shunt sepsis and lung opacities suspicious of tumour. Only positive tests for anti-cytoplasmatic antibodies (ACPA) in serum made the diagnosis and led to appropriate treatment. This simple yet highly specific immunofluorescence test should be performed in every case of vasculitis of uncertain cause, even if typical clinical signs of Wegener's granulomatosis are at first absent.

Adult↗

PubMed1989

[Unusual immunoglobulin gene rearrangements in patients with immunodeficiency].

In a 64-year-old patient with typical common variable immunodeficiency (CVID) DNA prepared from peripheral blood lymphocytes (PBL) showed a prominent immunoglobulin heavy chain (IgH) gene rearrangement; the immunoglobulin light chain (IgL) genes were found to be in the germline configuration. In contrast, a 13-year-old girl with a hitherto unidentified immunodeficiency showed polyclonal IgH gene rearrangements and a dominant IgL gene rearrangement. In both cases neither monoclonal B-lymphocytes nor monoclonal immunoglobulins were detectable. Our explanation for this unusual observation is that V-gene use in a given B-cell is not entirely random. This may be the consequence of a maturation arrest of B-cells.

Adolescent↗

PubMed1986

Biosynthesis of gangliosides in primary cultures of rat hepatocytes. Determination of the net synthesis of individual gangliosides by incorporation of labeled N-acetylmannosamine.

The ganglioside content of rat hepatocytes increases several-fold during the first 6 days in monolayer culture. To correlate increased levels with rates of de novo synthesis, the incorporation of N-acetyl-[6-3H]D-mannosamine into individual gangliosides was determined. The calculation of synthetic rates was made possible by the simultaneous measurement of the specific radioactivity of the immediate sialic-acid donor, CMP-Neu5Ac. The CMP-Neu5Ac content of hepatocytes was found by HPLC analysis to be 30.5 nmol/g of plated cells. The specific radioactivity of this precursor pool reached a constant plateau 5 h after addition of the labeled N-acetyl-mannosamine and remained constant for at least 70 h. The incorporation into individual gangliosides was measured in primary cultures of rat hepatocytes between 72 and 144 h after seeding. During this period, the increase in ganglioside levels was greatest. The highest rates of incorporation were seen in GD1a followed by GM3, GM1, GD3 and the polysialylated compounds. The following rates of synthesis (nmol per 60 h and mg of protein) were calculated: GD1a 0.68, GM3 0.59, GM1 0.36, GD3 0.13 and GT1 0.02. These values are compared with the net increase of the gangliosides as measured by the resorcinol reaction.

Animals↗

PubMed1985

Age- and hormone-dependent ganglioside patterns of rat hepatocytes in primary culture.

Using an improved procedure for the quantitative extraction of all glycolipids from small tissue samples the hepatic ganglioside pattern of rats was analysed during development. While this parameter remained fairly constant in adult animals, hepatocytes in primary culture showed drastic changes both in content and relative distribution among the various ganglioside species. The content of lipid-bound sialic acid increased several-fold during 6 days in monolayer and the pattern changed in favour of the higher sialylated forms. Dexamethasone delayed this transition and enhanced the content of GD1a and GM1 relative to GM3. The ganglioside content was also dependent on the density of hepatocytes in the primary culture. If the cell density was insufficient for formation of a confluent monolayer, higher ganglioside-sialic acid contents were found and the relative amount of GD3 increased after 3-4 days. These results support the notion that gangliosides are involved in cellular differentiation and cell-cell contact.

Aging↗

PubMedDate not supplied

[Indications for eye examination of HIV patients--screening parameters for cytomegalovirus retinitis].

BACKGROUND: To reduce the burden of frequent visits at the physician we have checked (I) for which ocular manifestations in HIV-infection screening of asymptomatic patients is worthwhile and (II) which parameters may indicate patients at risk for CMV-retinitis. PATIENTS AND METHODS: The clinical data of 215 HIV-infected patients were analyzed retrospectively. Only those ocular manifestations were considered suitable for screening that (a) endanger vision, (b) are treatable, (c) can be diagnosed sufficiently early and (d) are common. Furthermore (1) CDC-stage, (2) CD4+ count, (3) HIV-retinopathy, (4) CMV-uria and (5) CMV-antibodies were checked for their usefulness in indicating patients at risk for CMV-retinitis. RESULTS: Ophthalmological screening of asymptomatic HIV-patients should focus on cytomegalovirus (CMV)-retinitis because early diagnosis of this common blinding disease improves the visual outcome. 85 of 215 HIV-infected patients had a CD4+ count less than 50 cells/microliters 25% of these patients developed CMV-retinitis (21/85). The risk for CMV-retinitis rose to 38% (13/34) when the low CD4+ count was accompanied by CMV-uria. The proportion of patients with CMV-retinitis did not increase when HIV-retinopathy had been diagnosed earlier (12/48 = 25%). CMV-serology and CDC-classification were not helpful in screening for CMV-retinitis. CONCLUSIONS: We recommend the following ophthalmological screening scheme for HIV-patients without ocular symptoms: (1) patients with a CD4+ count < 100 cells/microliters should be checked every third month and (2) those with a CD4+ count < 50 cells/microliters and CMV-uria every sixth week.

AIDS-Related Opportunistic Infections↗