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Biomedical subjects

H Link

Publications and source records attributed to H Link.

At least 433 records · Page 24Linked to original sources
PubMed1987

HLA-DR antigen expression on T cells from cerebrospinal fluid in multiple sclerosis and aseptic meningo-encephalitis.

HLA-DR expression on T lymphocytes in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and acute aseptic meningo-encephalitis (AM), and from blood only from healthy controls was examined by a new double-immunofluorescence labelling assay using species-specific second layers on prefixed cell samples. Thirteen of 16 patients with AM (81%) had an elevated percentage of DR positive T cells in CSF against only two of 20 patients with MS (10%). Our data indicate that AM, an acute infection of the central nervous system (CNS), is accompanied by accumulation in CSF of activated, DR positive T cells as a reflection of actively involved cellular immunity within the CNS, while this accumulation of DR positive T cells is not seen in MS, a chronic inflammatory CNS disease, despite some of the patients being examined during clinical exacerbations.

Acute Disease↗
PubMed1987

Intrathecal production of neopterin in aseptic meningo-encephalitis and multiple sclerosis.

Neopterin levels in cerebrospinal fluid (CSF) and serum were measured with a sensitive radioimmunoassay in patients with multiple sclerosis (MS), aseptic meningo-encephalitis (AM), other mostly non-inflammatory neurological diseases, and controls with tension headache or psychoneurosis. Elevated levels of neopterin were found in CSF in most patients during acute phase of AM, and normalization after clinical recovery. The elevation in CSF was not reflected in serum. Only four of 24 MS patients--three of them examined during exacerbation--had slight elevation of neopterin in CSF and all had normal serum levels. Neopterin levels in CSF correlated with mononuclear cell count. The elevation of neopterin observed in CSF in inflammatory CNS diseases despite low cell numbers in CSF compared to blood might reflect a high activation level of cells locally in the CNS. Neopterin in CSF is a valuable marker of acute cellular immune response.

Adult↗
PubMed1986

Lung diseases after bone marrow transplantation. Results of a clinical, radiological, histological, immunological and lung function study.

The case histories of 72 subsequently treated patients - 44 with acute leukemia, 10 with chronic myeloid leukemia, 16 with severe aplastic anemia and 2 with neuroblastoma - were analyzed after bone marrow transplantation (BMT) with respect to pulmonary diseases. Thirty-eight patients suffered from a total of 51 pulmonary complications, which led to death in 20. Of 13 patients, 3 died of bacterial pneumonia, all of them during granulocytopenia; 2 of 6 patients died of fungal pneumonia and 2 out of 3 of a mixed bacterial-mycotic infection. Adult respiratory distress syndrome (ARDS) led to death in 2 patients. A granulocyte count under 500/microliter correlated significantly (P less than 0.002) with the fatal outcome of bacterial, fungal and ARDS pneumonia as well as with bronchitis. Viral pneumonia led to death in 8 of 9 patients; in each there was a significant correlation (P less than 0.05) with graft-versus-host disease (GvHD). Patients with repeated episodes of pulmonary illness had significantly more chronic GvHD (P less than 0.05); several of these patients displayed a reduction in helper T cells and an increase in suppressor T cells in the peripheral blood. The natural killer (NK) cells were reduced and the percentage of activated NK cell level lay between 6% and 69%. B-cells were absent or deficient. These findings explain in part the absence of specific antibody reactivity. Five of these patients also contracted GvHD-associated obstructive bronchiolitis, which did not respond to therapy. Pulmonary infiltrates of unknown origin (including idiopathic interstitial pneumonia) occurred in 8 of the patients (11.1%), with a fatal outcome in 3 patients. Significant changes (P less than 0.05) in lung function after BMT appeared in the form of reduced vital capacity (VC) increased residual volume (RV) and an increase in RV expressed as the percentage of total lung capacity. Pulmonary diseases were the most common complication and cause of death in our patients after BMT.

Adolescent↗
PubMed1986

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

Acyclovir↗
PubMed1986

Acute folic acid deficiency after bone marrow transplantation.

After bone marrow transplantation (BMT), megaloblastic bone marrow changes are often observed that can only be partially explained by drug effects. Our goal was to find out whether folic acid deficiency represented an additional factor. The serum folic acid concentrations of 41 patients were determined regularly before and after BMT. A 2nd degree polynomial regression analysis revealed a clear and acute drop in folic acid concentrations within 7-9 days after BMT. In 19 patients the level fell below 3.0 ng/ml, the range of folic acid deficiency. The mean folic acid values without oral administration of folic acid after BMT lay significantly below the mean values with substitution (P less than 0.001). If a case of acute graft versus host disease (GvHD) was more severe than grade I, the mean folic acid levels were significantly lower (P less than 0.01). Patients with megaloblastic bone marrow changes after BMT had significantly lower folic acid values than those without such changes (P less than 0.01). The 18 patients with folic acid deficiency had a significantly higher rate of megaloblasts, binucleate erythropoietic precursors, Howell-Jolly bodies, giant myelocytes, and giant metamyelocytes in bone marrow smears than the remaining 23 patients (P less than 0.05). Folic acid deficiency did not slow down the increase in leukocytes, granulocytes, thrombocytes, or reticulocytes after BMT. There were 8.2%-9.7% hypersegmented neutrophils in the blood (normal 5%) after BMT both with and without folic acid deficiency. Folic acid deficiency after BMT was caused by insufficient intake combined with simultaneous decreased intestinal resorption and increased requirements for the regeneration of bone marrow and intestinal mucosa.

Adolescent↗
PubMed1986

[Bone marrow transplantation in severe aplastic anemia].

Bone marrow transplantations were performed on 15 patients (aged 5-39 years) with severe aplastic anaemia. Twelve patients are alive 76-1930 days (median 668 d) after transplantation, with complete haematopoetic recovery. Total-body radiation with 3.6 Gy in four patients, cyclosporin A administration to ten patients and buffy-coat transfusion to nine patients entirely prevented early rejection. Two patients died of pneumonia (aspergillus; varicella-zoster virus), one patient died of bleeding from a splenic-artery aneurysm. In patients under the age of 40 years with severe aplastic anaemia bone marrow transplantation as early as possible after diagnosis is the treatment of choice if HLA-identical siblings are available as donors. In patients over 40 years treatment should at first be tried with antithymocyte globulin.

Acute Disease↗
PubMed1986

[Bone marrow transplantation in chronic myeloid leukemia. Influence of gnotobiotic measures, especially antiviral prophylaxis].

Bone marrow from HLA-identical siblings was transplanted in 14 patients with chronic myeloid leukaemia (CML), including one patient in acceleration phase and one in chronic phase following 2 blast crises. Restoration of the bone-marrow occurred in all cases and Philadelphia chromosome could not be detected in any of the patients after the transplantation. Two patients died due to lung complications. Twelve patients who received antiviral prophylaxis (aciclovir per os, anti-CMV-hyperimmunoglobulin) after the transplantation are in very good condition with 140 to 790 days complete clinical and cytogenetic remission. Bone-marrow transplantation, as a curative measure for patients with CML up to the age of 45 (50), should be included in therapy schemes when an HLA-identical sibling is available.

Acyclovir↗
PubMed1986

Monosymptomatic sensory symptoms and cerebrospinal fluid immunoglobulin levels in relation to multiple sclerosis.

Of 53 patients with monosymptomatic paresthesiae, 55% had oligoclonal bands and 28% an elevated cerebrospinal fluid (CSF) IgG index. Over a mean observation period of 64 months, nine patients developed clinically definite multiple sclerosis (MS); all of these patients had IgG bands, illustrating the prognostic importance of this CSF aberration. Two lumbar punctures more than one year apart were performed in 31 of the patients, of whom 20 had oligoclonal bands. This abnormality was constant between the time of punctures in all subjects except one, thus behaving as in MS. Similarly, the CSF findings in the 11 patients without oligoclonal bands remained normal over the observation period. The majority of patients with oligoclonal bands had cells in their CSF producing immunoglobulin of one or more of the three main classes, while none of those without oligoclonal bands displayed immunoglobulin-producing cells in CSF. Occurrence of oligoclonal bands in CSF is common in patients with paresthesiae and increases the risk for future development of MS.

Adolescent↗
PubMed1986

Immunoglobulin abnormalities in cerebrospinal fluid and blood over the course of lymphocytic meningoradiculitis (Bannwarth's syndrome).

The conditions of 5 patients with untreated lymphocytic meningoradiculitis (Bannwarth's syndrome, probably equivalent to Lyme disease) with serologically confirmed infection resulting from Borrelia spirochetes were followed with repetitive lumbar punctures up to 221 days after the onset of symptoms. Using a protein A plaque assay, high numbers of IgG-, IgM-, and IgA-producing cells were found in the cerebrospinal fluid (CSF), whereas there were mostly normal numbers of immunoglobulin-producing cells in peripheral blood. A markedly increased CSF IgM index and an elevated IgG index were observed in all patients during the early phase, reflecting production of these immunoglobulins within the central nervous system. All patients had oligoclonal IgG bands in the CSF that persisted during follow-up; in the 2 patients tested, the bands contained Borrelia antibodies. Most serum immunoglobulin concentrations were normal and in only 1 patient was it possible to detect in serum some of the oligoclonal IgG bands present in CSF. Declining numbers of CSF cells producing immunoglobulin and decreasing immunoglobulin index values were observed during follow-up, but 3 patients had an elevated CSF IgM index in the presence of normal IgG and IgA indices when examined during the later phases of disease. An intense and prolonged IgM response within the central nervous system seems to be a characteristic of the disease.

Adult↗
PubMed1986

Measles IgM antibodies in cerebrospinal fluid and serum in subacute sclerosing panencephalitis.

Using a direct enzyme-linked immunosorbent assay (ELISA), we examined serum and cerebrospinal fluid (CSF) from six patients with subacute sclerosing panencephalitis (SSPE) and control subjects for presence of measles-virus-specific IgM antibodies. All samples from the SSPE patients contained demonstrable titers of measles antibodies. The levels of measles IgM antibodies were higher in CSF diluted 1:5 than in serum diluted 1:50, reflecting a local production of IgM antibodies in the central nervous system. Antibody titers remained constant over the course of SSPE in three of the patients followed for three to six months. The IgM ELISA had high sensitivity as well as specificity and was not complicated by false-positive reactions owing to the presence of rheumatoid factor.

Antibodies, Viral↗
PubMed1986

Immunoglobulin abnormalities in the cerebrospinal fluid during bacterial meningitis.

11 patients with bacterial meningitis, examined during the course of the disease for immunoglobulin (Ig) abnormalities in the cerebrospinal fluid (CSF), all had an increased CSF IgM index equal to (CSF/serum IgM):(CSF/serum albumin), indicating intrathecal IgM production. Seven patients had a slightly increased CSF IgG index, and 7 a slightly increased IgA index. Six of the 11 patients had an increased IgM index in the presence of normal indices for IgG and IgA. Follow-up revealed the return of these values to normal. Four patients had identical oligoclonal IgG bands in the CSF and serum, probably representing a systemic immune response, but in only one case were oligoclonal bands suggestive of intrathecal IgG production found. No oligoclonal IgA response was demonstrable in the 4 patients examined. Antigen-immunofixation or antigen-absorption studies revealed evidence of a specific, intrathecal IgG antibody response in only 2 patients, while a search for IgG antibodies against aetiologically unrelated bacterial and viral antigens was negative. With the exception of IgM production, therefore, a humoral intrathecal immune response is less common in bacterial than in aseptic meningitis.

Adolescent↗
PubMed1986

Viral IgM and IgG antibody synthesis within the central nervous system in mumps meningitis.

With the use of enzyme-linked immunosorbent assay (ELISA) for demonstration of specific viral antibodies in 21 patients with mumps meningitis (MM), 19 (91%) displayed evidence for synthesis within the central nervous system (CNS) of IgG antibodies and 11 (52%) of IgM antibodies. Only one MM patient did not show local antibody production, but he had high mumps IgM titers in serum. Elevated IgG and IgM indices reflecting local IgG and IgM production, were found in 4 (19%) and 17 (81%) of the patients, respectively, and frequently did not coincide with local synthesis of specific antibodies. None of 21 control patients with acute aseptic meningitis of other etiology showed evidence for a local antibody response against mumps. In one of the MM patients, local production of measles IgM antibodies was demonstrated, reflecting an IgM response within the CNS against an antigen unrelated to the disease. This study concludes that in less serious CNS infections, such as MM, highly sensitive methods as ELISA are needed to demonstrate intrathecal specific viral immune response.

Adolescent↗
PubMed1986

Lung function changes after allogenic bone marrow transplantation.

The lung function of 21 patients with leukaemia (11 with acute myeloid leukaemia, six with acute lymphatic leukaemia, four with chronic myeloid leukaemia) and of five with severe aplastic anaemia was tested before and after allogenic bone marrow transplantation. Vital capacity (VC) was lowered in patients with leukaemia before transplantation. VC and FEV1 fell significantly after transplantation. Residual volume (RV) and RV as a percentage of total lung capacity (RV % TLC) were already increased and rose significantly after transplantation. Patients with severe aplastic anaemia had noticeably increased RV and RV % TLC, values that did not change after transplantation. In contrast to the patients with aplastic anaemia, the patients with leukaemia had significantly reduced VC, RV, RV % TLC, and FEV1 before and after transplantation. The specific airway resistance (sRaw) was raised significantly before and after transplantation in the leukaemic patients. In addition, transfer coefficient (Kco) fell significantly more after transplantation in the patients with leukaemia than in those with severe aplastic anaemia. In three patients with histologically established obstructive bronchiolitis in conjunction with chronic graft versus host disease after transplantation, VC, FEV1 and FEV1 % VC fell, while RV, RV % TLC, and sRaw rose; Kco was far below normal. On the basis of these findings it is concluded that in patients with leukaemia obstructive disorders of ventilation develop or, if they are already present, worsen. In patients with severe aplastic anaemia lung function was not impaired in the early phase after transplantation. These differences are probably due to the more intensive immunosuppressive and cytotoxic preparatory regimen before transplantation in the leukaemic patients. Obstructive bronchiolitis, a complication of graft versus host disease, first manifests itself in a typical rise in specific airway resistance and must be treated early.

Adolescent↗
PubMed1986

TAD-induction therapy for 175 adults with acute myeloid leukemia, followed by consolidation and maintenance therapy. The joint study of Ulm and Tübingen.

175 patients with acute myeloid leukemia were treated between February 1980 and March 1985 with a TAD-induction therapy, three intensified consolidation cycles (COAP, COAP, AD), and a two-year mild maintenance therapy. The median age of the patients was 44 years, range 15-68 years. 62.3% of all patients attained complete remission and 13.7% partial remission. The median duration of remission was 10 months and the median survival time of patients in complete remission was 20 months. Patients older than 50 years had a higher early death rate (17.6) than younger patients (8.9%), but no difference was found in remission rates or in the median duration of remission and of survival. These results are in line with those of comparable studies.

Adolescent↗
PubMed1986

Age adapted induction and intensified consolidation therapy in acute myelogenous leukemia.

52 patients entered a study for remission induction and intensified consolidation in AML. Group I (age less than or equal to 50 years) received a combination of DNR, ara-C and VP16-213 for induction and early consolidation and HDara-C/DNR for late consolidation. Of 34 evaluable patients (25 first diagnosis, 9 first relapse), 27 achieved CR. 13 patients received 1-2 courses of HDara-C/DNR. Toxic symptoms of HDara-C/DNR were severe myelosuppression, infections, skin reactions, diarrhea and hepatotoxicity. CNS toxicity was not observed. 2 patients died from infection. The duration of granulocytopenia (less than 500/microliter) was 7-43 days (range) and of thrombocytopenia (less than 25,000/microliter) 5-34 days (range). Patients of group II (age greater than 50 years) received a modified regimen with reduced toxicity. Their number is too small for evaluation as yet.

Aclarubicin↗
PubMed1985

IgG production within the central nervous system: a critical review of proposed formulae.

Demonstration of intrathecal IgG production is employed in the diagnosis of various neurological disorders. This pathological IgG fraction in cerebrospinal fluid (CSF) can be visualized directly as oligoclonal bands by electrophoresis or isoelectric focusing or can be calculated as "excess" or "synthesized" IgG according to different formulae. A comparison of the results obtained with isoelectric focusing and with five formulae showed that even though three of the formulae discriminated well between a reference population and patients with multiple sclerosis, all five gave wrong and misleading results in the presence of blood-brain barrier damage, as defined by an abnormally raised CSF/serum albumin ratio. A mathematical and statistical evaluation of the different formulae showed only those based on covariance between CSF/serum IgG and CSF/serum albumin to be valid, and these only when values of CSF/serum albumin were normal. Among the five formulae the IgG index (equal to CSF/serum IgG:CSF/serum albumin) is unique in having a comparatively small and constant maximal relative error resulting from the variation coefficients of the IgG and albumin assays. In the case of blood-brain barrier damage, there exists currently no valid procedure to calculate intrathecally produced IgG; in such instances sensitive electrophoretic or isoelectric focusing methods demonstrating oligoclonal IgG bands are most appropriate to demonstrate intrathecal IgG production.

Adult↗