Johan Waldenström

Fasting Serum Insulin Concentration and Early Insulin Response as Risk Determinants for Developing Diabetes

Among a cohort of 348 women aged 50 on entering a 12‐year prospective study, the incidence of diabetes was increased (17.1%) during follow‐up in those who initially had fasting glucose concentration above the upper quintile, a fasting serum insulin concentration above the upper quintile (14.9%), a disappearance rate of glucose below the lowest quintile in an IV glucose tolerance test (12.7%), or early insulin response below the lowest quintile (17.1%). The incidence in all women was 4.9%. By multivariate analysis, the highest risk was for high fasting serum insulin concentration. Obesity and treatment with antihypertensive drugs further increased the risk. An initial low early insulin response was not however a prerequisite for the development of manifest diabetes. Determination of fasting insulin concentration, especially in overweight hypertensive subjects, is of value in order to find out which subjects are at high risk of developing diabetes.

Karyotypic evolution in Ph-positive chronic myeloid leukemia in relation to management and disease progression

In a prospective study of 32 patients with chronic myeloid leukemia the frequency of chromosome abnormalities in addition to the Philadelphia chromosome (Ph) increased when the disease progressed. Before metamorphosis, 10 patients (31%) had developed additional abnormalities. Such abnormalities were present in three of them at the time of diagnosis; in the other seven, they were detected late in the chronic phase. New clonal abnormalities heralded or accompanied a more malignant phase of the disorder, usually a blastic leukemia. During metamorphosis, 78% of the patients had additional abnormalities, which in 68% of these cases comprised at least one of +8, +22q- or i(17q). Clones with additional abnormalities disappeared in eight cases, either spontaneously or in association with cytostatic therapy during the chronic or blastic phase. Involvement of chromosome #8, usually in the form of a trisomy, was found in 7 of 12 patients treated with busulfan, but was not found in any of the 10 hydroxyurea-treated patients, of whom 8 were splenectomized early during the chronic phase. Cells from the spleen, obtained by fine needle aspiration or splenectomy were cytogenetically examined in 18 cases during the chronic phase, but abnormalities in addition to the Ph were noted in only one patient, who was examined in the late chronic phase. The same abnormalities were present in bone marrow cells of this patient.

STRUCTURE AND FUNCTION OF TRANSFER RNA. I. SPECIES SPECIFICITY OF TRANSFER RNA FROM E. COLI AND YEAST.

The valyl, phenylalanyl and leucyl RNA synthetases have been partially purified from yeast. The species specificity of these enzymes and the corresponding enzymes from Escherichia coli has been studied with regard to yield and reaction rate. All of the yeast enzymes could esterify transfer RNA from E. coli while, of the E. coli enzymes, only valyl RNA synthetase could esterify yeast RNA. The leucyl RNA synthetase from yeast only recognized about 60% of the sites available on E. coli RNA. The reaction rates were in every case considerably lower with heterologous RNA than with homologous RNA. The chromatographic behaviour of amino acyl RNAs synthesized with homologous and non-homologous enzymes has been studied on methylated albumin columns.

Cytogenetic studies of bone marrow and extramedullary tissues and clinical course during metamorphosis of chronic myelocytic leukemia

Of 33 consecutive patients with chronic myelocytic leukemia, examined during metamorphosis, 82% showed chromosome abnormalities in addition to the Ph1. Aberrations most frequently encountered were +8 (39%), +22q - (30%), and i(17q) (18%). Translocations other than the Ph1 were observed in four cases and - Y clones in four cases. Discrepancies in the cytogenetic pattern between bone marrow and extramedullary tissues or blood were noted in a total of 15 patients. In six cases, transformation occurred in extramedullary organs at a time when it was not present in the marrow. In three cases the bone marrow transformation was preceded by a lymph node blastic infiltrate; in one case, by a skin infiltrate; and in one case, by a subdural blastoma. Clonal abnormalities additional to the Ph1 were identified in the tumor tissue from all these cases. Patients with primary extramedullary transformation tended to have a lower median age at onset of metamorphosis, shorter survival, and higher incidence of chromosome abnormalities than the cases without extramedullary involvement. Patients with only Ph1-positive cells and no other anomalies had a slightly longer duration of metamorphosis and longer total survival. Basophilia and thrombocytopenia were more marked in cases with i(17q) than in the rest of the series.

Hepatic Dysfunction After Open-Heart Surgery

In a prospective study, 93 patients were observed up to nine months after open-heart surgery using hypothermia, hemodilution and cold cardioplegia. In the first two weeks frequent determinations were made of serum aminotransferase, alkaline phosphatases (ALP), lactic dehydrogenase isoenzymes, gamma glutamyltransferase (GT), total and free bilirubin and bile acids. Plasma hemoglobin was measured at the end of the operation. After the first period, aminotransferases, alkaline phosphatases and bilirubin were determined monthly. On the first postoperative day almost all of the patients showed abnormal aspartate aminotransferase (ASAT) activity and ASAT/ALAT (alanine aminotransferase) greater than 1, and about 25% had hyperbilirubinemia. The findings suggested early postoperative leakage of enzymes not only from the myocardium, but also from the liver. After two weeks the patients presented another pattern of liver dysfunction, with abnormal ALAT in 50%, ASAT/ALAT less than 1, and abnormal ALP and GT in 28 and 45%, respectively. Eight patients were judged to have post-transfusion hepatitis of non-A, non-B type. Six of them had abnormal aminotransferases for more than six months.

Quantitative determination of plasma hemoglobin using dicarboxidine.

Since the demonstration of the potentially carcinogenic risk in workers using benzidine and o-tolidine, the use of these substances in laboratories has been limited. As a consequence of this there is a need for replacing these substances in, for example, the determination of plasma hemoglobin concentration. We have tested dicarboxidine, y,y’-(4,4’-diamino-3,3’-biphenylenedioxy)dibutyric acid dihydrochloride, which AB Kabi, Sweden has manufactured as a chromogenic reagent for quantitative determination of the hemoglobin concentration in plasma, instead of benzidine in the peroxidase reaction modified by Bing and Baker [ 11. This substance is considered much less carcinogenic than benzidine [2].

An isotachophoretic method for the determination of hypoxanthine in serum

Abstract Analytical isotachophoresis was used for the determination of hypoxanthine in serum. 5-Fluorouracil was used as the internal standard. The inclusion of spacers in the system greatly improved the separation and quantification. The method can readily be adapted to microscale and thus can be used in pediatric practice. The method is applicable to hypoxanthine concentrations above 10 nmol/liter.

A modified method for the determination of Na-K-ATPase

A modified method for determination of adenosine triphosphatase (ATPase) activities, with special reference to Na-K-ATPase, in human erythrocytes using 2 mmol/l ethylenediamine tetraacetic acid in the hemolyzing solution is presented. This modification gives stable day to day activities with a good power of discrimination. Small blood volumes and only standard laboratory equipment are needed.