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Biomedical subjects

I Romslo

Publications and source records attributed to I Romslo.

At least 37 records · Page 2Linked to original sources

Comparative study on the pharmacokinetics of 7-hydroxy-methotrexate after administration of methotrexate in the dose range of 0.5-33.6 g/m2 to children with acute lymphoblastic leukemia.

Concentrations of 7-hydroxy-methotrexate (7-OH-MTX) were determined in serum samples obtained after 266 infusions of methotrexate administered to 58 children with acute lymphoblastic leukemia. The dose of methotrexate (MTX) was in the range of 0.5-33.6 g/m2. Pharmacokinetic parameters (metabolic index, drug/metabolite ratio, half-life) of 7-OH-MTX and their relationship to the kinetics of methotrexate were analyzed. A great variability was observed in the extent and time-course of the metabolite formation. The concentration of the metabolite was higher than that of the parent compound at any examined time after the end of the 24 hours' infusion. The increase of 7-OH-MTX levels at the end of the methotrexate infusion was found to be proportionate to the increase of the dose of MTX. Males had significantly higher metabolite levels than did females (P less than 0.01) in the dose range of 0.5-8.0 g/m2. The age of the patients also significantly influenced the rate of the metabolite formation. The serial number of the treatment courses did not have effect on the metabolism of MTX. Dose dependency of the elimination half-life of the metabolite was found. Although a tendency was observed that patients in continuous complete remission had higher metabolite levels than those who relapsed, the difference was not significant. Further studies are needed to determine the clinical importance of 7-OH-MT.

Adolescent↗

Brain-stem auditory evoked potentials in multiple sclerosis: the relation to VEP, SEP and CSF immunoglobulins.

One hundred patients with multiple sclerosis (MS) were analysed retrospectively with respect to investigations of brain-stem auditory evoked potentials (BAEP), pattern reversal visual evoked potentials (VEP), somatosensory evoked potentials (SEP), and cerebrospinal fluid immunoglobulins (CSF-IG). BAEP were abnormal in 42% of those with normal VEP and SEP examinations, and in 38% of patients with normal CSF-IG. The chance of obtaining at least one abnormal EP was lower in patients with normal CSF-IG than in patients with abnormal CSF. When a "dispersion ratio" was included in the criteria for BAEP abnormality, the sensitivity increased compared with conventional BAEP criteria. We recommend that BAEP should still be included in the EP test battery for patients with suspected MS.

Adult↗

7-Hydroxymethotrexate concentrations in serum and cerebrospinal fluid of children with acute lymphoblastic leukemia.

Concentrations of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) were determined by HPLC in the serum and cerebrospinal fluid (CSF) of 29 children with acute lymphoblastic leukemia. CSF and serum samples were obtained at the end of 104 infusions of MTX given in a dose range of 0.5-8.0 g/m2. Concentrations, distribution ratios in serum and CSF for MTX and 7-OH-MTX, and the metabolic index were analyzed with regard to the MTX dose, age and clinical state of the patients. A wide inter-patient (2- to 12-fold) but narrower (1.1- to 3.5-fold) intra-patient variability of the concentrations was observed. A dose-proportional increase in the metabolite concentration was found in serum. On the other hand, the elevation of the level of metabolite in CSF was less than proportional to the dose. The CSF/serum distribution data suggest the existence of a saturable carrier system for MTX and 7-OH-MTX between serum and CSF that has lower affinity for 7-OH-MTX. No correlation was found between concentrations of MTX and 7-OH-MTX in the serum of patients receiving the same dose of MTX. No significant difference was observed in the values for metabolic index between relapsed patients and those who were in continuous complete remission. A significant correlation was found between age and metabolic index: the younger the patient, the higher the metabolite concentration measured in serum.

Aging↗

Pyrophosphate-loaded hepatocytes show increased iron uptake from transferrin.

Exogenously added pyrophosphate was found associated with hepatocytes in suspension, particularly in the presence of calcium ions. The cell-associated pyrophosphate was recovered with the stroma fraction. Pyrophosphate thus bound did not affect cellular ATP, leakage of lactate dehydrogenase or trypan blue exclusion. Compared to control cells, pyrophosphate-loaded hepatocytes showed an approximately 70% increase in iron accumulation from transferrin. The excess iron was handled by the pyrophosphate-loaded cells as control cells. The relevance of pyrophosphate to hepatocyte iron uptake is discussed.

Adenosine Triphosphate↗

Long-term effectiveness of the Burch colposuspension in female urinary stress incontinence.

Of 91 women who underwent Burch colposuspension, 86 were available for clinical, urodynamic and isotope renographic follow-up examinations 5 years after surgery for evaluation of late complications and long-term effectiveness in urinary stress incontinence. A repeat urodynamic examination was accepted by 76 patients. Stress incontinence was cured in 71% of the patients with a stable bladder preoperatively, and in 57% with stress incontinence and detrusor instability (non-significant difference). Cure rate was not significantly related to age, hormonal status or previous anterior vaginal repair. The urodynamic measurements at follow-up showed a significant increase in the functional urethral length in the cured group, as compared with the improved group. The mean maximum urethral closure pressure was reduced in both groups. Symptomatic detrusor instability was found in 18% of the preoperative stable bladders, while 67% of the unstable bladders had become stable. Only 29% of the patients with a preoperative unstable bladder had a normal lower urinary tract function at follow-up. Late voiding difficulties were observed in 3% of the study group; enterocele, requiring surgical repair, developed in 7%. One patient suffered a damaged kidney due to undetected ureteral obstruction after surgery. Irritative bladder symptoms such as urgency, frequency, stranguria and nocturia represent a long-term problem after colposuspension. At the 5-year follow-up, only 52% of the study group were completely dry and free of complications, and about 30% needed further incontinence therapy. This may be due to some neurogenic factor which is not corrected by surgery.

Adult↗

Anemia in general practice.

Among 4928 consecutive consultations in urban general practice in Mid-Norway anemia was found in 106 patients. Eighty-nine patients had their anemia worked out and treated by their general practitioner, 11 patients were referred to hospital or specialist, and in 6 patients no clear-cut reason for the anemia could be found. The patients could be broadly divided into four groups: iron deficiency in pregnancy (48%), iron deficiency secondary to bleeding (21%) anemia of chronic diseases (17%) and miscellaneous (7%).

Adolescent↗

Anemia in general practice. Which laboratory tests are requested--how are the results interpreted and what are the consequences to patient care.

Laboratory tests requested in patients with anemia by general practitioners were recorded together with the diagnostic problem, the practitioners' interpretation of the test results and the consequences to the further work-up and treatment of the patients. There is broad agreement as to selection of tests to diagnose fairly well-established clinical entities. With more composite or complex disease patterns, the request patterns differ, not only with the diagnostic problem, but more so with the physicians. Some tests are requested with results very seldom outside the reference range (e.g. cobalamins and folate) and some on indications notoriously prone to give false positive results (e.g. serum iron in patients with anemia of chronic diseases). As part of future quality control programs proper use of laboratory tests should be important topics as joint projects between clinical chemists, general practitioners and clinicians.

Adolescent↗

Rescue after intermediate and high-dose methotrexate: background, rationale, and current practice.

Pharmacologic rescue methods used in combination with intermediate and high-dose methotrexate therapy are reviewed, with special emphasis on rescue with nucleosides and folinic acid. The mechanism of action, pharmacokinetics, and clinical applications of the rescue agents are described in detail in view of the literature and also of the own findings of the authors. In spite of the promising results of the in vitro studies and in vivo experiments in animal models, the clinical value of thymidine as a rescue agent remains to be determined. Currently, the only indication to use thymidine instead of folinic acid following high-dose methotrexate is to prevent toxicity related to extremely high methotrexate levels in patients with delayed elimination of methotrexate. In spite of the widespread application of folinic acid rescue, the exact mechanism of its action is not fully understood. The rescue dose and schedule in the majority of clinical protocols is empirical, and the start of the rescue administration is too early, allowing less than 36 to 42 hours of exposure to methotrexate. Clinical and laboratory findings indicate that while the early start of FA administration is unnecessary for protecting normal cells, it is potentially dangerous in terms of reduction of the antitumor effect of methotrexate. Our findings suggest that less than the most widely used 12-15 mg/m2 per dose rescue may be sufficient in preventing methotrexate related toxicity in patients with normal elimination of the drug. In addition, reducing the dose of the rescue may be beneficial to achieve better therapeutic results with high-dose methotrexate. Due to methodological problems, the pharmacokinetics of folinic acid rescue has not been excessively studied in humans. Recent data indicate that the pharmacokinetics of folinic acid in children is characterized by great intra- and interpatient variability. The effect of food on the bioavailability of folinic acid has not yet been studied, though it is most frequently administered orally. The introduction of the pure l-stereoisomer of the rescue agent in the clinical practice may eliminate potential interactions with the d-isomer, and may also simplify the introduction of therapeutic drug monitoring for folinic acid as well. This could lead to more rational clinical use of folinic acid as a rescue agent following intermediate and high-dose methotrexate therapy.

Cell Survival↗

Griseofulvin-induced protoporphyria revisited.

In nude mice grieofulvin given by intraperitoneal injections produces a severe porphyric state within 1 week. Compared with peroral administration of griseofulvin to produce experimental porphyria, this model is much more efficient and can be more easily controlled.

Animals↗

Uptake of iron from transferrin by isolated rat hepatocytes. A redox-mediated plasma membrane process?

The uptake of iron from transferrin by isolated rat hepatocytes varies in parallel with plasma membrane NADH:ferricyanide oxidoreductase activity, is inhibited by ferricyanide, ferric, and ferrous iron chelators, divalent transition metal cations, and depends on calcium ions. Iron uptake does not depend on endosomal acidification or endocytosis of transferrin. The results are compatible with a model in which iron, at transferrin concentrations above that needed to saturate the transferrin receptor, is taken up from transferrin predominantly by mechanisms located to or contiguous with the plasma membrane. The process involves labilization and reduction of transferrin-bound iron by cooperative proton and electron fluxes. A model which combines the plasma membrane mechanism and the receptor-mediated endocytosis mechanism is presented.

Animals↗

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin concentrations in anaemic subjects.

Day-to-day variations in serum iron, serum iron binding capacity, serum ferritin and erythrocyte protoporphyrin were determined on 2 successive days in 48 patients with anaemia. The correlation coefficients between the paired determinations were 0.86, 0.89, 0.95 and 0.95, and the day-to-day coefficients of variation (in per cent) were 33, 11, 12 and 13 for serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin, respectively. Thus, in patients with anaemia, day-to-day variations in serum iron, serum iron binding capacity, erythrocyte protoporphyrin and serum ferritin are at least as high as in healthy controls. The results indicate important limitations in the use, particularly, of serum iron in the clinical investigation of anaemia.

Adolescent↗

Cholescintigraphy in the diagnosis and follow up of hepatobiliary injury.

Cholescintigraphy is a simple and reliable way of detecting a liver injury accompanied by biliary leakage and is also well suited to assess the effectiveness of treatment and to follow recovery. To emphasize these points, a case report of a patient suffering from a severe injury to the liver is presented.

Adult↗