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Biomedical subjects

H Link

Publications and source records attributed to H Link.

At least 379 records · Page 21Linked to original sources
PubMed1991

Cells secreting antibodies to myelin basic protein in cerebrospinal fluid of patients with Lyme neuroborreliosis.

An autoimmune response to myelin basic protein (MBP) has been proposed to participate in the development of the chronic neurologic manifestations that may accompany Borrelia burgdorferi-induced Lyme disease. Using an immunospot assay, we counted cells secreting antibodies to MBP. Anti-MBP IgG antibody-secreting cells were detected in CSF from eight of 13 consecutive patients with Lyme neuroborreliosis irrespective of stage of disease. The numbers were between 1/370 and 1/5,000 CSF cells (mean, 1/1,250 in the 13 patients). The highest numbers were encountered in two patients with severe signs of CNS involvement. The numbers decreased in parallel with clinical improvement after treatment. Anti-MBP IgG antibody-secreting cells were also observed in the CSF from patients with a variety of other inflammatory diseases of the nervous system, and their role in the development of tissue damage remains unsettled. Anti-MBP IgG antibody-secreting cells were not detected in the patients' blood, reflecting accumulation of this autoantibody response to CSF.

Adult↗
PubMed1990

Allogeneic bone marrow transplantation for Langerhans' cell histiocytosis.

A group of proliferative diseases of the epidermal Langerhans' cells are commonly referred to as Langerhans' cell histiocytosis (LCH). A small number of the patients with this disease face an unfavorable disease course despite chemotherapy and radiation therapy. In LCH patients with a poor prognosis, allogeneic bone marrow transplantation (BMT) could be the appropriate treatment with proven antiproliferative effects and may be able to repopulate the recipient with stem cell-derived Langerhans' cells from the donor or correct the presumed underlying immunodeficiency. An LCH was diagnosed in a 15-year-old boy with multiple osteolytic lesions, anemia, and diabetes insipidus centralis. Repeated flare-ups of the disease had necessitated several courses of conventional chemotherapy including cyclophosphamide (CY), prednisolone (P), 6-mercaptopurine (6-MP), vincristine (VCR), and additional local irradiation without stable remission. Three years after first being diagnosed with LCH the patient underwent high-dose chemotherapy-radiation therapy followed by allogeneic BMT from his human lymphocyte antigen (HLA)-identical brother. Currently, he is alive and well and has been disease-free for more than 41 months after BMT.

Adolescent↗
PubMed1990

Early diagnosis of tuberculous meningitis by detection of anti-BCG secreting cells in cerebrospinal fluid.

A nitrocellulose immunospot assay to enumerate cells secreting anti-BCG antibodies was evaluated in the diagnosis of tuberculous meningitis. Among 25 Chinese patients with this disease diagnosed on clinical and cerebrospinal fluid (CSF) criteria, 24 had anti-BCG IgG antibody secreting cells in CSF, at a median value of 56 per 10(4) CSF cells. Among 6 patients examined within one week, 5 had antibody secreting cells in CSF, and all 19 patients examined 2-8 weeks after onset had such cells in CSF. Blood examined from 5 patients contained anti-BCG IgG or IgM antibody secreting cells, but usually at much lower numbers than in corresponding CSF, indicating that the specific antibody response is largely confined to CSF. Anti-BCG antibodies measured in parallel by ELISA were slightly raised in CSF in only 1 of the 6 patients examined within a week, whereas a good correspondence was seen between numbers of antibody secreting cells and antibody concentrations from the second week onwards. Detection of anti-BCG IgG antibody secreting cells has higher sensitivity and specificity than ELISA measurement of anti-BCG IgG antibodies, and represents a new, useful method for the early diagnosis of tuberculous meningitis.

Adolescent↗
PubMed1990

Antimyelin basic protein and antimyelin antibody-producing cells in multiple sclerosis.

The B-cell response to myelin and myelin basic protein was studied in patients with multiple sclerosis and in patients with acute aseptic meningoencephalitis by using a nitrocellulose immunospot assay. This method allows detection of single cells producing antibodies. Twenty-seven (79%) of 34 patients with multiple sclerosis had cells producing IgG antibodies against myelin, and 11 (57%) of 19 had cells producing IgG antibodies against myelin basic protein in cerebrospinal fluid (CSF), with mean values of 30 and 14 per 10(4) mononuclear cells, respectively. Total numbers of IgG-producing cells occurred at a mean number of 75 per 10(4) CSF cells. Cells producing antimyelin or anti-myelin basic protein antibodies of IgA or IgM isotypes were rarely found in CSF. Patients with acute aseptic meningoencephalitis less frequently showed CSF cells producing IgG antibodies against myelin and myelin basic protein. No cells producing antibodies against myelin or myelin basic protein were detected in peripheral blood of patients with multiple sclerosis or meningoencephalitis. Thus, a majority of patients with multiple sclerosis had CSF cells that produced IgG antibodies against myelin and myelin basic protein. These cells comprised a large proportion of the total IgG-producing cells. A pronounced B-cell response against autoantigens produced at the target for immune attack might be important in the pathogenesis of multiple sclerosis.

Adult↗
PubMed1990

Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia.

Mitoxantrone in combination with VP-16 proved to be effective in refractory and relapsed acute myeloid leukemia (AML), with 42% of patients achieving complete remission (CR). The aim of this study was to assess whether the addition of cytosine arabinoside increased the response rate at a tolerable toxicity. The regimen consisted of mitoxantrone (M) 10 mg/m2 i.v. days 4-8, cytosine arabinoside (A) 100 mg/m2 continuous infusion days 1-8, and etoposide (VP-16) (V) 100-120 mg/m2 i.v. days 4-8 (MAV protocol) for relapsed and refractory AML. Thirty-six patients were treated, with a median age of 51 (20-73) years. For induction therapy one to two MAV cycles and for consolidation therapy two courses were scheduled. Twenty-one (58.3%) patients attained a complete remission (CR), with a median duration of 4.5 (1-12+) months. The median survival of all patients was 5.5 (0.5-15.5+) months. Four patients died in CR from chronic infections or after consolidation therapy with MAV. In evaluable patients, times to greater than 500 granulocytes/microliters and greater than 25,000 platelets/microliters were 23 (7-46) and 23 (6-44) days, respectively. In 54 evaluable MAV courses the following toxicity was observed (WHO grades 3/4): 26%, nausea and vomiting: 9%, hemorrhage; 6%, bilirubinemia; 11%, diarrhea; 22%, mucositis; 6%, local infection; 20%, septicemia; 13%, fever of unknown origin; 2%, cardiac arrhythmia; 7%, congestive heart failure. We conclude that MAV therapy is a highly active antileukemic combination with acceptable toxicity, which is recommended for further clinical trials in untreated AML.

Adult↗
PubMed1990

High dose folinic acid/etoposide/5-fluorouracil in advanced gastric cancer--a phase II study in elderly patients or patients with cardiac risk.

Thirty-four consecutive patients with measurable advanced gastric cancer were treated in a disease oriented Phase II study with high-dose folinic acid (HDFA) 300 mg/m2 10 min. inf., followed immediately by etoposide 120 mg/m2 50 min. inf., followed immediately by 5-fluorouracil (5-FU) 500 mg/m2 10 min. inf., given on day 1,2,3 (ELF). Courses were repeated every 22-28 days. All patients who entered this study were older than 65 years or had underlying cardiac disease. Thirty-three patients were evaluable for response and toxicity (greater than or equal to 1 course). One patient was lost to follow up. The overall response rate was 48% (16/23) including 12% (4/33) complete remissions. Eight patients had minor responses or no change and 9 had progressive disease. Five of six patients with locally advanced and non-resectable disease had an objective response (1 CR, 4 PR's). The response rate in patients with metastatic disease was 41% (11/27). After a median observation time of 6.5 months, the median survival time was 10.5 months, with a median remission (CR + PR) duration of 8 months. Toxicity was manageable and included mild to moderate myelosuppression and gastrointestinal toxicities. One episode of life-threatening (Grade IV) leukopenia, and two episodes of severe diarrhea requiring hydration were noted. No treatment related death occurred. ELF is an effective combination in advanced gastric cancer and can be safely administered to elderly patients and patients with cardiac risk.

Aged↗
PubMed1990

Persistent anti-myelin basic protein IgG antibody response in multiple sclerosis cerebrospinal fluid.

Antibodies to myelin components, such as myelin basic protein (MBP), may play a role in pathogenesis of multiple sclerosis (MS) but results from determinations of anti-MBP antibodies are inconsistent. Enumeration of cells secreting antibodies represents a new approach to evaluate a specific antibody response regarding extent and localization, and reduces effects of e.g. antibody binding to target. Anti-MBP IgG antibody secreting cells were present in MS patients' cerebrospinal fluid (CSF) at a mean value of 1 per 833 cells, and they amounted to a mean value of about 2454 in the whole CSF compartment. Similar numbers were encountered in patients with other inflammatory neurological diseases (OIND). During follow-up, anti-MBP IgG antibody secreting cells persisted regarding frequency and numbers in MS, but decreased in OIND. Such cells were rarely detected in patients with tension headache. No correlations to clinical exacerbation of MS, disability or duration were discernable. In blood from MS and OIND patients, anti-MBP IgG antibody secreting cells were detected infrequently and at low numbers. The anti-MBP antibody response is strongly restricted to the IgG isotype. The anti-MBP IgG antibody response which is persistent and compartmentalized to the diseased organ, may be important for the development of MS.

Adult↗
PubMed1990

Oligoclonal Borrelia burgdorferi-specific IgG antibodies in cerebrospinal fluid in Lyme neuroborreliosis.

Cerebrospinal fluid (CSF) and serum from 45 patients with lymphocytic meningoradiculitis were examined by isoelectric focusing combined with immunoblotting to detect Borrelia burgdorferi-specific oligoclonal immunoglobulin G (IgG) bands. In pretreatment samples, 35 patients (78%) showed B. burgdorferi-specific oligoclonal IgG in CSF indicative of intrathecal antibody production. At 2, 3-6, and 6 weeks after onset, respectively, such bands were present in 5 (42%) of 12, 21 (88%) of 24, and in all of 9 patients (100%). Up to 1 year after therapy, specific oligoclonal bands in CSF tended to remain unchanged despite clinical recovery. B. burgdorferi-specific oligoclonal bands in serum were found in 7 patients. These bands had identical migration patterns as in CSF, but were fewer in number and in some patients showed a temporal evolution different from their CSF counterpart. Not all oligoclonal IgG in CSF reacted with B. burgdorferi. The 41-kDa flagellar antigen was shown to be a major antigen in the intrathecal immune response. The demonstration of B. burgdorferi-specific oligoclonal IgG in CSF is a sensitive and reliable indicator of Lyme neuroborreliosis.

Adolescent↗
PubMed1990

Age-specific prevalence of antibody to enterotoxigenic Escherichia coli in Ecuadorian and German children.

Serum samples from 1397 Ecuadorian children 0-5 years of age were tested by ELISA for antibodies to enterotoxigenic Escherichia coli (ETEC). A gradual prevalence and titer increase was seen for IgG antibodies to heat-labile enterotoxin in children 6-18 months old; 90% prevalences were reached in the second year of life. At this age less than 10% of West German children showed IgG antibodies to heat-labile enterotoxin. In Ecuador age-related ETEC-specific antibody titer increases correlated with age-related prevalence of diarrheal disease. On the other hand, pooled lipopolysaccharide from different ETEC-associated O serogroups could not be used as a seroepidemiologic marker of ETEC infections.

Age Factors↗
PubMed1990

B cells expressing CD5 are increased in cerebrospinal fluid of patients with multiple sclerosis.

By two-colour flow cytometric analysis, we found increased numbers of B cells co-expressing the pan-T cell marker CD5 and the B cell marker CD19 in cerebrospinal fluid (CSF) of 21 patients with multiple sclerosis (MS), compared with 17 control subjects with muscular tension headache. Only one patient with MS, but nine controls lacked CD5+ B cells in CSF. This difference was not observed in peripheral blood. Numbers of CD5+19+ B cells were increased in CSF compared with blood in MS, but not in the controls. In both groups, CD5+19+ B cells were not restricted to small resting lymphocytes, but were also found among larger-sized lymphocytes. The relative density of CD5 molecules and of CD19 molecules was lower in CD5+19+ than in CD5-19+ B cells and CD5+19- T cells. CD5+ B cells are assumed to be responsible for autoantibody production, and our results suggest a pathogenetic role of such cells, predominantly within the central nervous system, in MS.

Adult↗
PubMed1990

CD4+, CD8+, and CD4- CD8- T cells in CSF and blood of patients with multiple sclerosis and tension headache.

Two-colour flow cytometric analysis was performed on paired samples of peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with untreated multiple sclerosis (MS) and, for reference, subjects with muscular tension headache (TH) using anti-CD3, anti-CD4, anti-CD8, and anti-HLA-DR monoclonal antibodies in different combinations. CD4+/CD8+ T-cell ratio was increased in CSF compared to PB in both MS patients and TH subjects to a similar extent. This was mainly due to higher CD4+ T-cell levels in the CSF compartment. The proportion of HLA-DR+ T cells was higher in CSF than PB in both MS and TH; this increase of DR+ T cells in CSF was more prominent in MS. The level of CD4+ CD8+ T cells, which represent a subset of activated T cells, was not different between CSF and PB, either in MS or in TH. The proportion of CD4- CD8- T cells, which were found generally not to be blast cells, was lower in CSF compared to PB in both patient groups. However, their CSF level was higher and their PB level lower in MS compared to TH. Results point to an accumulation of activated T-helper cells in the CSF of both MS patients and healthy subjects. Fetal-type CD4- CD8- T cells bearing the unusual T-cell receptor gamma/delta seem to be selectively recruited to the CSF of MS patients.

Adult↗
PubMed1990

CSF immune variables in patients with narcolepsy.

Cerebrospinal fluid (CSF) and serum from 15 patients with narcolepsy were examined regarding presence of oligoclonal bands on isoelectric focusing, IgG index elevation as indicator of intrathecal IgG production and CSF/serum albumin ratios. Two of 15 patients (13%) showed oligoclonal IgG bands in CSF, one of whom had increased IgG index. Slight disturbance of blood-brain-barrier function as reflected by elevated CSF/serum albumin ratios was present in 4 other patients. The frequency of oligoclonal IgG bands in CSF from patients with narcolepsy is within the range of what is found in other neurological, non-inflammatory diseases. These findings do not support the hypothesis of an immune-mediated pathogenesis of narcolepsy.

Adolescent↗
PubMed1990

High-dose intravenous-penicillin in neurosyphilis: effect on intrathecal synthesis of IgG, IgM, IgA and IgD.

We evaluated occurrence and levels of intrathecal synthesis of IgG, IgM, IgA and IgD by calculating corresponding index values in 8 patients with definite and 4 with suspected or possible neurosyphilis, prior to, during and after high-dose intravenous penicillin therapy. Four patients with active neurosyphilis displayed intrathecal synthesis of IgG, IgM and IgA. Only 2 of them showed elevated IgD index, and both had taboparesis, pleocytosis and positive VDRL in CSF, and simultaneous elevation of the IgG, IgA and especially of the IgM indices. This suggests that intrathecal synthesis of IgD may occur in patients with severe CNS inflammation in response to diffuse CNS treponemal damage. Penicillin therapy incited transitory elevation of one or more of the immunoglobulin index values in most patients, possibly in response to massive treponemal lysis inside the CNS. Thereafter, the values became mostly normalized but exceptions occurred, including one patient who had elevated IgG and IgM index which persisted 31 months after therapy. Our data indicate that determinations of immunoglobulin indices performed on consecutive specimens from individual patients with neurosyphilis may be helpful in the evaluation of treatment.

Adult↗
PubMed1990

Interventional antimicrobial strategy in febrile neutropenic patients. Results of a multicenter study in 1,260 patients with hematological malignancies. The Interventional Antimicrobial Strategy Study Group, Paul Ehrlich Society for Chemotherapy.

In a prospective, randomized multicenter trial of the Paul Ehrlich society different concepts for sequential empirical antimicrobial strategy for the treatment of patients with neutropenia less than 1.0/nl and fever greater than 38.5 degrees C and/or documented infection were studied. In phase I, patients with unexplained fever (FUO) were randomized for the combination of acylaminopenicillin plus aminoglycoside or third-generation cephalosporin plus aminoglycoside or double beta lactam therapy. Non-responders received additional vancomycin or all three substances of phase I in phase II. In phase III, all patients with persistent fever were then treated with amphotericin B plus 5-flucytosine and rifampin and randomized for the continuation of the double beta lactam regimen or additional imipenem/cilastatin. 667 (52.9%) of 1260 evaluable patients had FUO during the whole study period, of which 62.5% could be cured in phase I, 43.2% of non-responders in phase II and 55% of persistently febrile patients in phase III. The overall rate of complete response was 79.5%. 2.8% were non-responders, 11.7% were not evaluable for response and 40 patients (6%) died during the study, 24 (60%) of whom due to the underlying disease or the toxicity of antileukemic therapy. A significant difference between the treatment groups could not be detected in either of the three study phases.

Agranulocytosis↗