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Biomedical subjects

M Reunanen

Publications and source records attributed to M Reunanen.

At least 37 records · Page 2Linked to original sources

Multiple-dose pharmacokinetic study with a slow-release carbamazepine preparation.

The pharmacokinetics, clinical efficacy and side effects of carbamazepine (CBZ) in the steady-state condition were studied using a slow-release preparation (SR), Neurotol Slow, and a conventional preparation (C), Tegretol. Eighteen adult epileptic patients under CBZ therapy were evaluated in this single-blind, randomized cross-over study. The previous daily CBZ dose was kept unchanged and divided into 2 daily doses during two 2 week study periods. At the end of each period blood samples were drawn at frequent intervals for 12 h after the administration of the morning CBZ dose. Serum concentrations of unchanged CBZ and its main metabolite, carbamazepine-10,11-epoxide (CBZE), were determined by HPLC. Peak concentrations of CBZ and CBZE were significantly lower, and the time-lapse before CBZ reached its peak was significantly longer during SR treatment. The fluctuations in serum CBZ and CBZE were significantly lower during SR treatment. There was no significant difference in bioavailability between the 2 preparations. The number of epileptic seizures was 31 during SR and 57 during C treatment. Side effects were more common during C treatment. The occurrence of dizziness was significantly lower with SR treatment than with C treatment. We conclude that greater stability in serum CBZ and CBZE concentrations can be obtained by using an SR of CBZ, without reducing the bioavailability of the drug.

Adult↗

T-lymphocyte subsets defined by double immunofluorescence in multiple sclerosis.

T-lymphocyte subpopulations were studied in the blood of 25 multiple sclerosis patients and 25 healthy age and sex-matched controls. Monoclonal antibodies labelled with different fluorochromes were used to define the percentages of CD4 (helper/inducer) and CD8 (suppressor/cytotoxic) positive cells and to dissect them into phenotypic subgroups. The results confirm the decrease in CD8 positive cells in the blood associated with multiple sclerosis. The subset showing the most marked decrease was the CD11 marker negative population, which has been reported to be associated with cytotoxicity rather than suppression. There was no significant decrease in the percentage of cells positive for both CD4 and CD45R markers reported to contain suppressor-inducer or naive T-helper cells in the MS patients. The results suggest that further dissection of T-cell subpopulations may clarify our understanding of this disease process.

Adult↗

Lymphocyte subsets in the cerebrospinal fluid in active multiple sclerosis.

We studied the relative number of lymphocyte subsets in the cerebrospinal fluid (CSF) of patients with active multiple sclerosis. The cells were double-labeled with monoclonal antibodies and were studied using a fluorescence-activated cell analyzer. The number of Leu2+Leu15+ cells and Leu3+Leu18+ cells was markedly reduced in the CSF but not in the peripheral blood of the patients. The number of Leu3+Leu18+ cells was reduced also in the CSF of control patients (patients with other inflammatory or infectious neurological diseases).

Flow Cytometry↗

Production of viral antibodies in vitro by CSF cells from mumps meningitis and multiple sclerosis patients.

Cerebrospinal fluid (CSF) cells from 4 mumps meningitis and 11 multiple sclerosis (MS) patients were cultured in vitro for 7 days with and without pokeweed mitogen (PWM) stimulation. The cells produced varying amounts of IgG without stimulation and no significant increase of IgG synthesis was observed after PWM stimulation. Antibodies against mumps, measles, rubella, herpes simplex, and adeno viruses were measured in the supernatants of the cultures by a sensitive enzyme immunoassay. In the mumps meningitis patients, the largest amount of antibody was against mumps virus but low amounts of antibodies with other specificities were also synthesized by CSF cells of one patient. The most commonly detected specificities in MS patients were against measles and rubella viruses, whereas antibodies against adeno and mumps viruses were detected in only one CSF cell supernatant. No antibodies produced against herpes simplex virus in vitro were detected in any of the supernatants. The amounts of viral antibodies produced in vitro and intrathecally were only partially correlated.

Antibodies, Viral↗

NK activity and NK-like non-specific cytolysis after PPD, rubella and measles antigen stimulation in multiple sclerosis.

Blood samples were collected from 14 pairs of multiple sclerosis (MS) patients and from age- and sex-matched healthy controls. The cytotoxic activity of peripheral blood mononuclear cells was tested against the K562 cell line on the day of collection and again after 3 days in vitro culture with medium or with purified protein derivative of tuberculin (PPD), inactivated rubella virus or inactivated measles virus antigen. Lymphocytes from MS patients had a lower spontaneous cytotoxic activity compared to the controls both on the day of collection (P less than 0.025) and after 3 days in culture with medium alone (P less than 0.025). The activity decreased during in vitro culture in both groups, but the decrease was greater among MS patients (P less than 0.05). In cultures with antigens, a strong increase of NK-like cell-mediated cytolysis (NK-like CMC) was noted especially in cultures stimulated with PPD. There were no significant differences in the increase of the activity among MS patients and control subjects. A significant correlation between the increase of NK-like CMC and the lymphocyte blast transformation response induced by each antigen was found.

Adult↗

Immunological findings during an acute relapse of subacute sclerosing panencephalitis in a patient with an unusually prolonged disease course.

A 171/2-year-old male subacute sclerosing panencephalitis patient underwent a disease relapse after an 8 year remission. A total of 14 paired peripheral blood/cerebrospinal fluid specimens were obtained during this relapse. These specimens were tested for 13 parameters of non-specific or measles virus-specific cell-mediated and humoral immunity. There was a rapid and significant fluctuation in all of these tests. Total loss of measles-specific T cells response was found during the relapse. The response re-appeared and measles-specific antibodies increased significantly later on. The results suggest that measles virus infection was reactivated in this patient and that the observed immunological changes could at least partially be explained by this.

Adolescent↗

Increased sister-chromatid exchange rate and its regression during prolonged incubation in lymphocyte cultures from patients with multiple sclerosis.

Peripheral venous blood lymphocytes from multiple sclerosis patients, cultured for 72 h in the presence of phytohemagglutinin, appeared to have a higher sister-chromatid exchange (SCE) rate than cells from matched controls. Prolongation of the incubation time to 9 days by adding interleukin-2 to the cultures, caused the cells from the MS patients to lose their increased SCE frequency, so that the mean rate no longer differed from that of the controls. The SCE rate of the controls did not change significantly on prolonged incubation.

Adult↗

Circulating immune complexes in patients with subacute sclerosing panencephalitis.

Levels of immune complexes (ICs) in serum and cerebrospinal fluid (CSF) specimens from subacute sclerosing panencephalitis (SSPE) patients were measured using a solid-phase C1q radioimmunoassay. Single or serial serum specimens were available from 19 patients, while serial CSF specimens were available from two patients. ICs isolated from one CSF specimen by C1q immobilized to Affi-Gel were analyzed for measles virus antigens by binding of measles virus-specific antisera and by polyacrylamide gel electrophoresis followed by Western blotting. Of 78 serum specimens analyzed, 36 (46%) were positive for ICs. When the 8 patients with 3 or more serum specimens were analyzed, 6 had fluctuating levels of ICs. Two of 5 CSF specimens obtained from a patient during acute disease onset were IC-positive, while a second patient exhibited a rapid increase and decrease of IC levels in 14 CSF specimens obtained during an acute disease exacerbation. Composition analysis of ICs isolated from one of the CSF specimens revealed the presence of antigens corresponding in size to measles virus polymerase, nucleoprotein, and possibly, hemagglutinin polypeptides. These results show that SSPE patients frequently have ICs, that IC levels fluctuate in both serum and CSF, and that the ICs are at least partially composed of measles virus antigens.

Antigen-Antibody Complex↗

Kidney growth after pyeloplasty in childhood.

The postoperative increase of the renal parenchyma, measured with planimetry on repeated urography films, was studied in 24 infants and children. All patients had been operated on because of unilateral stenosis of the pelvioureteral junction. When the results were analyzed in a pair-control manner the paired members were almost identical for age at operation, affected side, sex, presenting clinical sign and length of followup. The 12 patients who underwent a dismembered pyeloplasty displayed a significantly stronger mean catch-up growth of the relative parenchymal area than the 12 patients who underwent a nondismembered technique. Speculatively, this difference may reflect in part the protection of the growing renal parenchyma by the preoperatively compliant and wide renal pelvis, which had led to resection and dismembered correction.

Child↗

Antibodies in cerebrospinal fluid to white matter glycoproteins in multiple sclerosis patients.

Cerebrospinal fluid (CSF) specimens from 45 patients with multiple sclerosis (MS) and 45 age- and sex-matched controls with other neurological diseases (OND) were tested for antibodies to white matter (WM) membrane glycoprotein (GP) fractions prepared from MS and control WM membranes by lentil lectin chromatography. The binding of the CSF IgG to the 125I-labeled GP fractions was determined by immunoprecipitation using Protein A-Sepharose. CSF from patients with MS bound highly significantly more strongly to the GP fraction prepared from MS WM than did the OND CSF specimens (P less than 0.001). There was no such difference when control GP fraction was used as an antigen. No highly significant differences were observed when 20 paired serum specimens were tested. Electrophoresis of the immunoprecipitates showed that components with molecular weights (MWs) of 157,300, 135,600, 111,100, 93,000, 75,700, 63,300, 50,100, 24,300, 20,300 and 17,000 daltons were precipitated from the MS GP fraction by CSF specimens of both MS and OND groups, whereas components with MWs of 50,100, 24,300, 20,300 and 17,000 daltons were precipitated from the control GP fraction.

Adult↗

Volatile halocarbons in tap water as a problem in haemodialysis therapy.

The concentrations of volatile halocarbons in the tap water of Turku and of Turku University Central Hospital are quite high and are reduced but not eliminated during water treatment at the hospital. Before haemodialysis is started, only trichloromethane is found in the blood of the patients. Two hours later dichlorobromomethane and dibromochloromethane could also be found. These substances are absorbed, and possibly accumulate, in the body or are metabolised and excreted because all their concentrations are lower at the end of dialysis therapy. Therefore, maximum levels for volatile halocarbons in drinking water should be sufficiently low to prevent these substances being detected in body fluids and special care should be taken with hospital water.

Humans↗

Mitogen and antigen stimulation of multiple sclerosis cerebrospinal fluid lymphocytes in vitro.

Responses of cerebrospinal fluid (CSF) and peripheral blood (PB) lymphocytes from 20 MS patients to phytohemagglutinin (PHA), measles, rubella, mumps and herpes simplex virus antigens were followed during periods of from 6 to 13 months. Up to 6 examinations, each with 1-5 stimulants, were performed with a lymphocyte blast transformation test. Most of the patients responded with their CSF cells to PHA (14/19) and at least to some of the viral antigens tested (15/20) during the follow-up. Although the maximal responses of CSF and PB cells to PHA and measles virus antigen were of the same magnitude, non-reactive or weakly responding lymphocytes were more common in CSF than in PB. In 7 of 15 patients having viral antigen responsive CSF cells simultaneous reactivity to several antigens could be shown. The stimulation results of CSF lymphocytes did not correlate with the numbers of CSF leukocytes or the intrathecal IgG synthesis. A negative correlation was observed between the strength of the CSF cellular response to PHA or measles virus antigen and the rate of intrathecal antibody synthesis to measles virus antigen, suggesting that the stimulated cells may at least partially represent suppressor cells.

Adult↗

Characterization of immune complexes in multiple sclerosis by an antigen-specific immune complex radioimmunoassay.

Serum and cerebrospinal fluid samples from multiple sclerosis (MS) patients containing various levels of Clq-reactive immune complexes (IC) and samples from age- and sex-matched controls were tested by an antigen-specific IC radioimmunoassay which detects IC containing myelin membrane-related antigens. Positive reactivity in the assay was significantly associated with IC-containing MS sera (P less than 0.005) but such an association was not observed with MS cerebrospinal fluid. Analysis of longitudinal specimens revealed that the levels of the antigen-specific serum IC fluctuated with time. Significant correlation between serum levels of Clq-reactive IC and serum levels of IC containing myelin membrane-related antigens was observed (r = 0.62; P less than 0.001). Sucrose gradient centrifugation of sera from 1 patient showed that the IC had a peak density of 1.075 g/ml, indicating the presence of lipid material. The results suggest that serum IC of MS patients frequently contain myelin membrane-related antigens and that these antigens may be lipids or lipid-associated.

Antigen-Antibody Complex↗