Thomas R. Koch

Detection of central nervous system metastasis with cerebrospinal fluid beta‐2‐microglobulin

Beta‐2‐microglobulin determinations in cerebrospinal fluid (CSF) of patients with leukemia, lymphoma, and oat cell carcinoma were performed to evaluate the utility of this test in early detection of metastasis to the central nervous system (CNS). In the presence of CNS disease, significantly higher levels (P < 0.001) were found than in normals or patients without CNS disease. Serial measurements were performed on two patients, and in all cases beta‐2‐microglobulin became elevated coincident with CNS relapse, and returned to normal as remission was achieved. Serial testing of CSF beta‐2‐microglobulin, in patients with cancers known to invade the CNS, should facilitate prompt treatment of CNS metastasis. Cancer 52:101‐104, 1983.

A column chromatographic method for the determination of 5-hydroxytryptamine (serotonin) and 5-hydroxyindole acetic acid in cerebrospinal fluid.

A method is described for measurement of 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in cerebrospinal fluid. 5-HT and 5-HIAA are isolated from columns of Biorex BR-70 and Sephadex G-10 with recoveries of 85 and 89% respectively. The indoles are quantitated by fluorometric measurement of the ortho-phthaldialdehyde derivatives in acidic solution. Correction for interfering 5-methoxytryptamine and 5-methoxyindole acetic acid is accomplished by a second measurement at alkaline pH. Thin-layer chromatographic analysis of column eluates has revealed no other interfering indoles in the 5-HT and 5-HIAA fractions. Preliminary results in normal cerebrospinal fluid samples have been in the ranges 10--60 ng/ml 5-HIAA and 0--13 ng/ml 5-HT.

Lead accumulations in brain, blood, and liver after low dosing of neonatal rats.

Newborn rat pups were treated in seven groups: Group 1, the control, was untreated and killed at birth (day 1); Groups 2, 3, and 4 were treated on postnatal days 1 through 10 with respectively saline or lead acetate, 5.0 mg/kg and 7.5 mg/kg body weight; Groups 5, 6, and 7 were treated with the same respective dosages on days 11 through 20. Cerebellum, cerebral cortex, brainstem plus hippocampus, liver, and blood were analyzed for lead. Neonatal rats killed at birth all contained some lead, the cerebellum having the highest concentration. Tissue from most treated groups accumulated lead in a dose-dependent manner. A comparison of lead concentrations between the organs of rats dosed days 1–10 and rats dosed days 11–20 indicated that the latter accumulated less lead per gram of tissue (p < 0.05) than their younger litter mates.

Inaccuracies in digoxin measurement

Six commercial digoxin immunoassay kits were evaluated for their accuracy of calibration and their extent of interference by digoxin-like immunoreactive substance (DLIS). Calibration accuracy was investigated with digoxin reference standards in pooled human serum. The Abbott and Becton Dickinson kits underestimate while the other kits overestimate digoxin concentration. The magnitude of this bias generally increases with increasing concentration of digoxin. Sera from digoxin-free patient populations with potential DLIS interference--pregnant women, newborns, hypertensives, and uremics--were analyzed with each kit. Healthy subjects not on digoxin therapy served as controls. Groups with DLIS interference, as exemplified by a significant difference of p less than 0.05 from controls, are: Abbott--newborns and pregnant women; Becton Dickinson--newborns and pregnant women; Dade--no difference; Dupont--newborns, uremics, pregnant women, and hypertensives; Kallestad--newborns; and Syva--newborns. The limitations of each individual digoxin method should be realized for DLIS interference and bias, and patient results from that method should be interpreted accordingly.

Evaluation of the new beckman electrophoretic method for CK-MB: Comparison with ion exchange chromatography and investigation of a reference outpatient population

We evaluated the performance of a CK isoenzyme kit utilizing agarose electrophoresis with fluorescence scanning of an overlay paper rather than the gel. We compared this method to ion exchange chromatography with mini-columns of DEAE Sephadex using samples from hospitalized patients and from a reference population of ambulatory outpatients with common, chronic medical conditions. The detection limit, precision and linearity of the electrophoretic method were acceptable, but the method overestimated CK-MB, requiring a different reference range for clinical application. There were inter-racial differences within the reference population for total CK and for the percent of CK-MB using either method. We discuss the significance of our findings with respect to clinical decision limits for CK-MB.