Presentation of the Julius Friedenwald Medal to Basil I. Hirschowitz, M.D.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D J Levinson.
Explore the source record for details and available documents.
A 45-year-old man presented with bilateral lower extremity claudication due to aortitis and periaortic fibrosis. This variety of aortitis has been described in the pathologic literature as chronic periaortitis, a subset of idiopathic retroperitoneal fibrosis. The association of this aortitis with abdominal aortic aneurysm has been described in the surgical literature as inflammatory abdominal aortic aneurysms. These entities are thought to be secondary to the same disease process. We review the possible etiology, diagnostic considerations, and management of these aortidites.
Erdheim-Chester disease is a rare pathologic entity characterized by symmetrical radiodensities in the metaphyseal and the diaphyseal portions of the long bones. Fibrosis, osteoblastic cortical bone deposition, and fibroxanthomatous granulomas with lipid-laden macrophages and multinucleated giant cells, which have a particular tropism for connective and adipose tissues, are the pathologic hallmarks. To our knowledge, 27 cases have been reported in the literature since the entity was first described in 1930. Protean clinical features range from a focal and asymptomatic process to a multisystemic infiltrative disease. We describe the clinical course of a new case and review the extensive pathologic findings at autopsy, including those demonstrated by light and electron microscopy and cytochemical and immunocytochemical studies.
The presence of crystal proven podagra coincident with a 52% decrease in plasma urate after a 3-day course of total parenteral nutrition (TPN) prompted a study of urate excretion in 9 patients with Crohn's disease. By Day 9 in those receiving TPN, plasma urate decreased 58% (p less than 0.001), while fractional urate excretion increased 94% (p less than 0.005). Twenty-four hour urate excretion and serum creatinine were not significantly altered. These findings persisted for the duration of TPN. In 2 patients with ileocolitis, the addition or deletion of either lipid emulsion or multivitamin infusions during TPN had no effect on urate values. Rather, the amino acid load or a specific constituent appears to be the causal factor. These data suggest that hypouricemia due to extensive net urate excretion is common during TPN therapy. Finally, patients with established gout may be at risk for acute gouty attacks during TPN therapy.
We report a young woman with systemic lupus erythematosus complicated by pseudotumor cerebri which resolved with high dosage corticosteroid therapy. The cause of the raised intracranial pressure proved to be thrombosis of the torcular herophili and lateral sinuses. Despite laboratory evidence of a hypercoagulable state, the presence of a lupus anticoagulant could not be shown.
Superactive phosphoribosylpyrophosphate (PRPP) synthetases were characterized in fibroblasts and erythrocytes from 5 unrelated men with gout and/or hyperuricemia and uric acid overproduction. The kinetic basis of enzyme superactivity in all patients was increased maximal reaction velocity. Affinities of the enzymes for substrates and activators and responsiveness to inhibitors were normal, and levels of immunoreactive enzyme in patient and control fibroblast and erythrocyte extracts were comparable. Enzymes purified to homogeneity from 2 patients confirmed the presence of isolated catalytic defects. Altered physical properties of certain of the superactive enzymes suggested the presence of several distinctive structural defects among the aberrant forms. Fibroblasts from each affected patient showed increased PRPP concentration and generation, as well as accelerated rates of all PRPP-requiring purine nucleotide synthetic pathways. These findings support the concept that enzyme superactivity results in uric acid overproduction as a consequence of increased rates of PRPP and purine nucleotide synthesis. Cultured cells from female relatives of 2 patients showed evidence for the heterozygous carrier state, as measured both by enzyme activities and by rates of PRPP and purine synthesis. The clinical phenotype in 4 patients was limited to early adult-onset gout and its consequences, whereas the fifth patient expressed a familial constellation of hyperuricemia, sensorineural deafness, ataxia, and renal insufficiency. The severity of the derangements in PRPP synthetase and in PRPP and purine synthesis in cells from the 5 patients, however, was comparable. The neurologic accompaniments of enzyme superactivity found in 1 family described here, and in 2 others described previously, thus may not necessarily be consequences of primary defects in PRPP synthetase.
Studies were performed to elucidate the ontogeny of a single class of androgen binding protein in male rat liver cytosol which exhibits characteristics of a ligand specific, high affinity (Kd = 2.3 nM), 8S-receptor capable of nuclear translocation. Detectable levels of receptor first appear at 45 days of age in the male and reach maximum concentration at 65 days. Barely detectable levels are seen in females throughout the duration of study (80 days). Gonadectomy in both sexes (65 days) and androgen treatment of oophorectomized females do not alter the normal development of sexual differentiation of the high affinity androgen receptor. After neonatal castration (2 days) and DES replacement however, receptor sites do not undergo differentiation and adult males exhibit female levels. Conversely, neonatal androgen replacement in 2-day castrates partially restores the level of binding sites to control males values (TP, 71%; DHT, 51%). Neonatal castration without replacement retards but does not fully eliminate sexual differentiation of levels of receptor sites in adult males. Likewise, neonatal androgen treatment in females results in a partial masculinization of binding sites. Following hypophysectomy, levels of receptor sites in females are similar to intact or hypophysectomized males; sexual differences in the adult are abolished. These studies suggest that sexual differentiation of specific liver cytosol androgen binding sites in the adult may be partially programmed at birth by testicular androgen and furthermore, adult sexual dimorphism is maintained through an inhibitory influence of the pituitary in the female.
The binding of radiolabelled methyltrienolone 17 beta-hydroxy-17 alpha-methyl-estra-4,9,11-trien-3-one (R1881) to adult male rat liver cytosol has been characterized in the presence of Na-molybdate to stabilize steroid-hormone receptors, and triamcinolone acetonide to block progestin receptors. Using sucrose density gradient analysis, male liver cytosol contains a [3H] R1881 macromolecular complex which sediments in the 8-9S region. 8S binding of R1881 to male rat serum, female liver cytosol or cytosol from a tfm rat cannot be demonstrated. Further metabolism of [3H] R1881 following 20h incubation with male rat liver cytosol was excluded: In the 8S region 97% of [3H] R1881 was recovered by thin layer chromatography. Characteristics of this [3H] R1881-8S binding protein include high affinity (Kd = 2.3 +/- 41 nM) and low binding capacity (18.8 +/- 3.3 fmol/mg cytosol protein), precipitability in 0-33% ammonium sulfate, and translocation to isolated nuclei following in vivo R1881 treatment. Whereas, the cytosol R1881-receptor is competed for by dihydrotestosterone, testosterone, and estradiol, [3H] estradiol binding in the 8S region is not competitive with androgens but does compete with diethylstilbestrol. The nuclear androgen binding site has a Kd = 2.8 nM for [3H] R1881, and is androgen specific (testosterone greater than 5 alpha-dihydrotestosterone greater than estradiol greater than progesterone greater than cyproterone acetate greater than diethylstilbestrol greater than dexamethasone greater than triamcinolone). Since a number of liver proteins including the drug and steroid metabolizing enzymes are, in part, influenced by the sex-hormone milieu, the presence of a specific androgen receptor in male rat liver may provide valuable insight into the regulation of these proteins.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
To further delineate the mechanism responsible for the differences in xanthine oxidase activity in male and female Sprague-Dawley rats, a sensitive and specific radioimmunoassay (RIA) was developed for the measurement of hepatic xanthine oxidase. The RIA could detect as little as 5 mg of liver enzyme. Specificity of the RIA was confirmed by 1) Ouchterlony double immuno-diffusion in which a single precipitin band exhibited xanthine oxidase activity, when crude liver homogenate and an enzyme-specific stain were used; 2) parallelism between purified 125I-labeled xanthine oxidase and serial dilutions of crude liver homogenate; 3) a linear correlation between xanthine oxidase activity and the level of enzyme protein; and 4) a single protein band coincident with purified xanthine oxidase, when an immunoprecipitate prepared from antisera and crude liver homogenate was analyzed on sodium dodecyl sulfate (SDS) polyacrylamide gels. Whether xanthine oxidase activity was assayed in the absence of nicotinamide adenine dinucleotide (NAD+) (oxidase form) or in the presence of NAD+ (dehydrogenase), male values were consistently higher, and both forms of the enzyme correlated significantly with each other. When purified to homogeneity, neither form of the enzyme was appreciably affected by 17 beta-estradiol or testosterone propionate. When the RIA was employed, levels of hepatic xanthine oxidase were significantly greater in male than in female rats. We concluded from these data that increased xanthine oxidase activity in the male corresponds to a greater quantitative complement of xanthine oxidase protein. Furthermore, lower xanthine oxidase activity in the female cannot be explained by immunologically cross-reactive material without enzyme activity nor by a direct sex-steroid enzyme interaction.
IN previous work we have begun to articulate a conception of psychiatry as a profession and to show how this conception may be useful in examining specific controversial issues such as national health insurance and the concept of prevention in psychiatry (Astrachan, Levinson, and Adler 1976; Adler, Levinson, and Astrachan 1978). We define a profession not in terms of its varied theories or forms of practice, but in terms of the major tasks it must perform and the perspectives it takes regarding these tasks. Historically, psychiatry has been committed to four major tasks. These interconnected tasks have been sanctioned by society, and all must be addressed if psychiatry is to retain its credibility and legitimacy. In practice, the tasks frequently are intertwined, yet they are conceptually distinct. In the present paper, we use this conception of psychiatry as a framework for the analysis of the many approaches that have been taken to the understanding and treatment of schizophrenia. Each task is defined in terms of a problematic condition to be controlled or eliminated: illness, defect, deviance, impeded growth. The rationale for work on each task is given by a corresponding theoretical perspective. There is marked disagreement, and often bitter controversy, about the validity of different theories, the value of different treatments, and even the legitimacy of various approaches. Let it be clear, then, that our goal is not to evaluate specific concepts and techniques, nor to argue that one task or perspective is more legitimate than any other. Our goal, rather, is to clarify the nature of the disagreement and to present a comprehensive framework within which different approaches to schizophrenia can be understood and compared and then reconnected in practice.
The effect of maturation, castration, and sex hormonal treatment on hepatic xanthine oxidase activity (XOA) was evaluated in Sprague-Dawley rats. In mature rats XOA was 59% greater in males than in females, whereas in the immature animal the differences between sexes were insignificant. Pubescence resulted in a twofold increase in activity in the male which was prevented by prepubertal orchiectomy. Conversely, prepubertal oophorectomy caused a twofold increase in XOA in females. Urinary uric acid excretion paralleled XOA in rats fed 1% oxonic acid. XOA was significantly elevated in females after postpubertal castration or testosterone treatment while orchiectomy or estradiol-17 beta treatment in the mature male showed no effect. In summary, these data suggest that androgens are required during puberty for full expression of hepatic XOA, and furthermore, an ovarian suppressive effect is evident. In the adult rat only the female responds appreciably to hormonal manipulation.
To investigate the possibility that genetic factors are involved in the outcome of gold salt therapy for arthritis, histocompatibility antigens (HLA) were determined for 32 patients treated with gold salts. A comparison of patients who achieved remission following gold therapy with those who did not failed to demonstrate any difference in HLA antigens. Patients who had experienced adverse reactions during gold therapy were found to have an increased frequency of the HLA-B12 antigen. Gold toxicity occurred in 69.2 per cent (9/13) of patients with the B12 antigen, compared with 26.3 per cent (5/19) of patients without the antigen (P = 0.035).
Explore the source record for details and available documents.
Bidirectional renal urate tranport was studied in both control and gouty subjects. 99.3% of filtered urate undergoes reabsorption as assessed by pyrazinamide suppression of urate secretion. The maximum uricosuric response to benzbromarone, equated with the minimum secretory rate, amounted to 50% of the filtered load in normal persons and was lower in gouty normoproducers. Since benzbromarone selectively inhibits reabsorption of secreted urate, the difference between secreted and excreted uric acid becomes a valid measure of urate reabsorption distal to the secretory site and amounts to 80% of the secreted load in both groups. These data conform to a 4-component model of renal urate handling in man.
A 26-year-old woman was found to have an abnormally sensitive excretory response to a rise in plasma urate with a markedly increased ratio of uric acid to creatinine clearance (exceeding 35%). Uric acid was studied before and after administration of pyrazinamide and benzbromarone. In the presence of pyrazinamide urinary uric acid decreased markedly just as in normal subjects. The uricosuric response to benzbromarone was reduced. No other renal tubular or metabolic abnormalities were found. It appears that the abnormality is related to an isolated defect in postsecretory reabsorption of urate.
Explore the source record for details and available documents.