Erling Sagen

The calcium and magnesium content of the human lens and aqueous humour. A study in patients with hypocalcemic and senile cataract.

Abstract. Previous observations of raised calcium content in mature senile cataract are confirmed in the present study. Also human hypocalcemic cataract showed increased amounts of calcium in accordance with previous observations in animals. On the other hand, the magnesium content of the lens was not influenced by cataract development. The calcium aqueous/serum ratio was similar in all examined groups (normal, hypocalcernic‐, incipient‐, and mature senile cataract). whereas the corresponding magnesium ratio was elevated in the cataract patients. This observation may indirate a possible connection between magnesium metabolism and the development of rataract.

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.

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

SummaryConcentrations of methotrexate (MTX) and 7-hydroxymethotrexate (7-OH-MTX) were determinded 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 porportional 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.

Determination of porphyrins by high performance liquid chromatography: fluorescence detection compared to absorbance detection

A comparison is made between determination of porphyrin methyl esters by high performance liquid chromatography (HPLC) with absorbance detection and with fluorimetric detection. Detection limits with absorbance detection vary from 0.8 pmol for 2-COOH-porphyrins to 5 pmol for 8-COOH-porphyrins. With fluorometric detection the corresponding figures are 0.04 pmol and 0.4 pmol. Fluorimetric detection also has a better reproducibility, and it is more specific than absorbance detection. The use of HPLC with fluorimetric detection thus permits rapid, highly efficient and specific quantitative detection and identification of porphyrins in complex biological samples.

Vitamin B6 in plasma – sample stability and the reference limits

Abstract Quantitatively, the most important B6 vitamer in plasma is pyridoxal-5′-phosphate (p-PLP). The prerequisite for the use of p-PLP measurements in patients with poor nutritional status is an appropriate reference interval, together with knowledge of the stability of vitamin B6 in plasma samples. We used blood samples from healthy blood donors to derive the reference limits for p-PLP, and to examine its stability for 24 hours at room temperature and at 4–8°C. P-PLP was measured using high performance liquid chromatography (HPLC). The reference interval in adults was 23–223 nmol/L. P-PLP was stable for 24 h at room temperature and at 4–8°C, allowing time for normal specimen transport.

Pharmacokinetics of folinic acid in children with acute lymphoblastic leukemia

We analyzed folinic acid (FA) levels in the serum samples of 20 children with acute lymphoblastic leukemia (ALL). Mean age of the patients was 7.7 years (SD, 3.96 years), median age 6.8 years, and range 2.6–17.4 years. The patients received 96 infusions of methotrexate (MTX) at a dose of 8 g/m2. A total of 320 serum samples — taken during different periods of rescue therapy — were analyzed. Determination of MTX, 7-OH-MTX, and FA levels was performed by high-performance liquid chromatography (HPLC) with electrochemical detection.

Increased magnesium in aqueous humour from patients with senile cataract

Abstract A previous observation of increased aqueous magnesium in eyes with senile cataract has been re‐examined in a totally different material. The serum and aqueous level of calcium and magnesium from 34 patients with senile cataract were tested against comparable values from 4 patients with choroidal melanoma. In contrast to calcium, the magnesium aqueous/serum ratio was significantly higher in the cataract group. Possible explanations are suggested.