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Biomedical subjects

J Frenkel

Publications and source records attributed to J Frenkel.

At least 55 records · Page 3Linked to original sources

[Major adverse reactions to propylthiouracil in 586 cases of hyperthyroidism].

Aiming to know the incidence and evolution of major adverse reactions to propylthiouracil in patients with hyperthyroidism, we performed a retrospective analysis of 586 patients treated between 1982 and 1992. All known complications associated to the use of propylthiouracil were considered major adverse reactions, when other causes were discarded. Eight patients (1.4% of the sample) had major adverse reactions: three had agranulocytosis, 3 hepatitis, 1 cholestasis and 1 vasculitis. All had a good evolution after discontinuing the drug. The patients with agranulocytosis were treated with antibiotics and the patient with cholestasis received prednisone. We conclude that major adverse reactions to propylthiouracil are infrequent, that they occur preferentially during the first months of treatment, earlier after reexposure and that there was no associated mortality.

Adolescent↗

Is technetium-99 m-pyrophosphate scintigraphy valuable in the diagnosis of cardiac amyloidosis?

Amyloidosis is a systemic disease frequently involving the myocardium and leading to functional disturbances of the heart. Amyloidosis can mimic other cardiac diseases. A conclusive clinical diagnosis of cardiac involvement can only be made by a combination of different diagnostic methods. In 7 patients with myocardial amyloidosis we used a combined first-pass and static scintigraphy with technetium-99 m-pyrophosphate. There was only insignificant myocardial uptake of the tracer. The first-pass studies however revealed reduced systolic function in 4/7 patients and impaired diastolic function in 6/7 patients. Therefore, although cardiac amyloid could not be demonstrated in the static scintigraphy due to amyloid fibril amount and composition, myocardial functional abnormalities were seen in the first-pass study.

Amyloidosis↗

Oligoclonal T cell proliferative disorder in combined immunodeficiency.

Oligoclonal lymphoid proliferations may occur in immunocompromised patients and in the elderly. So far these proliferations have been shown to be of B cell origin. We describe a patient with a combined immunodeficiency, characterized by profound hypogammaglobulinemia and the initial absence of T lymphocytes in the peripheral blood (PB). From the age of 4 yr CD3+ T cells appeared in PB in rising numbers. These cells mainly expressed the CD4-/CD8+ phenotype (CD4/CD8 ratio: 0.1). Despite the emergence of T lymphocytes no proliferation of PB mononuclear cells could be induced with phytohemagglutinin, concanavalin A, or pokeweed mitogen. Between the ages of 4 and 6 yr the patient gradually developed hepatosplenomegaly and an interstitial pulmonary infiltrate of unknown origin, necessitating biopsies of both liver and lung. Infiltrates consisting of CD8+ T lymphocytes were found in the liver as well as the lung. CD8+ T cells were also abundant in the bronchoalveolar lavage fluid. Southern blot analysis of mononuclear cells from PB and of a lung biopsy specimen was performed to investigate if a clonal T cell population was involved. Analysis of the T cell receptor beta genes revealed that at least three expanded T cell clones were present in PB, one of which had invaded the lung. Thus far, i.e. 2 yr after the initial detection of clonal T cell receptor beta gene rearrangements, there have been no clinical or histologic signs of malignant behavior. We conclude that this combined immunodeficiency patient has a benign oligoclonal T cell lymphoproliferative disorder. Similar proliferations might well occur in other immunodeficiency states, whether primary or acquired.

Antigens, Differentiation, T-Lymphocyte↗

Presence of osteocalcin and related higher molecular weight 4-carboxyglutamic acid-containing proteins in developing bone.

Development of a sensitive radioimmunoassay for the vitamin K-dependent bone protein osteocalcin in avian species has provided new information on the biosynthesis of this protein in bone. Chicken osteocalcin shares many structural features, including the sequence positions of its 3 gamma-carboxyglutamic acid (Gla) residues, with osteocalcins of human, monkey, cow, and rat, but is cryptic in the radioimmunoassays for these species. In the chicken assay system, the intact 50-residue (Mr = 5670) protein is required for immunoreactivity. Reduction and alkylation of the disulfide bond (Cys 23-Cys 29) or tryptic removal of the COOH-terminal pentapeptide abolish antibody binding activity. Decarboxylation of the 3 Gla residues enhances the affinity for antibody by 1.5- to 2-fold. Osteocalcin appears coincident with the very earliest detectable perichondral mineralization in developing long bone (tibiotarsus) of the 7- to 8-day-old chick embryo (stages 31-33). However, amino acid analysis demonstrates an excess of Gla in embryonic bone compared to the level of osteocalcin by radioimmunoassay. Two independent experimental approaches have partially resolved this paradox. First, extraction and gel filtration in 4 M guanidine hydrochloride of total bone proteins has revealed high molecular weight species which share antigenic determinants with osteocalcin, namely, 10,000 (+/- 1,000), 15,000 (+/- 2,000), 35,000 (+/- 5,000), and 85,000 (+/- 15,000), in addition to 5,670 osteocalcin. Second, a selective 3H exchange labeling procedure for Gla residues has revealed Gla-containing proteins in bone in the same molecular weight classes. One or more of these may represent precursors in the biosynthetic pathway for osteocalcin.

1-Carboxyglutamic Acid↗