Autoantibodies to tissue transglutaminase as predictors of celiac disease

Our aim was to study the prognostic value of growth hormone (GH) -stimulated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP) score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7) with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were followed prospectively for three years. Six patients (40%) died during the follow-up period, of whom half had a CP score <9. Mean serum IGF-I levels 24 hr after rhGH injection (group 1 vs group 2, 17.4 +/- 6.8 vs 7.4 +/- 0.7 nmol/liter) predicted survival with 93% accuracy. Levels <10 nmol/liter portended a poor prognosis, with 15% survival at one year, whereas levels >10 nmol/liter had a 100% survival rate at one and two years, respectively. Baseline IGF-I (9.98 +/- 2.0 vs 6.38 +/- 0.8 nmol/liter), GHBP (9.2 +/- 3 vs 5.7 +/- 0.8%/50 microl), and IGFBP-3 serum levels at baseline (1.7 +/- 0.3 vs 0.86 +/- 0.2 mg/liter) and at 24 hr (2.04 +/- 0.38 vs 0.99 +/- 0.3 mg/liter) did not add to the predictive value of stimulated IGF-I levels at 24 hr and were less accurate in predicting the outcome in comparison to CP score (80%). We conclude that stimulated IGF-1 <10 nmol/liter may be a true predictor of a negative prognosis in patients with liver cirrhosis.     

Long-term graft outcome is not necessarily affected by delayed onset of graft function and early acute rejection

Cytogenetic and molecular genetic investigations in cancer are important tools to address problems of oncogenesis and tumor progression, of classification, and of diagnosis of tumors. A combination of advanced molecular genetic, cytogenetic, and (immuno) histopathologic analysis will contribute significantly to the elucidation of the oncogenic steps that lead to immortalization and subsequent malignant behavior. In this review written on the occasion of Dr. Avery Sandberg's 75th anniversary, we will present a model for the pathogenesis of renal cell tumors based on a new cytomorphologic classification and our (cyto)genetic analysis of about 175 renal cell tumors, together with the accumulated data in the literature.     

Unknown primary carcinoma: randomised studies are needed to identify optimal treatments and their benefits

This is a retrospective review of 101 patients with unknown primary carcinoma (UPC) treated between 1989 and 1994, on whom data were collected prospectively. 92 patients received platinum-based chemotherapy and 9 had single agent 5-fluorouracil (5-FU). In the platinum group, an objective response rate of 37.2% was seen, with a median duration of 4.5 months (range 1.9-17.5). There were no responses with 5-FU alone, while median survival was 6.4 months and was not different from the platinum group (P = 0.09). Considerable symptomatic resolution was noted, although the contribution of chemotherapy alone to this is difficult to define. The impact of tumour response on quality of life and survival in UPC requires further elucidation in prospective studies with a "best supportive care' arm. The superiority of platinum-based treatments reported in selected subgroups cannot be applied to the whole spectrum of UPC.     

Theory, explanation, and a third generation of theoretical development in social gerontology

Efforts at cumulative knowledge building in social gerontology have been lax, judging from research articles published in journals between 1990 and 1994. Too little attention has been paid to the cumulative development of theory; readers are left with many empirical generalizations but underdeveloped explanations by which to interpret findings and build upon them in subsequent research. To assist future theory development in social gerontology, we review seven theoretical perspectives referenced most frequently in recent journals: (1) social constructionist, (2) social exchange, (3) life course, (4) feminist, (5) age stratification (age and society), (6) political economy of aging, and (7) critical theory. We suggest that, taken together, these represent a "third generation" of explanation in social gerontology, noting their debt to older and more established traditions in social science theory. We argue that authors and journal reviewers should place more emphasis on theory development - which means, most simply, the construction of explicit explanations in accounting for empirical findings - if knowledge development about social aspects of aging is to be cumulative, systematic, and incremental.     

The JC and BK human polyoma viruses appear to be recent introductions to some South American Indian tribes: there is no serological evidence of cross-reactivity with the simian polyoma virus SV40

In an effort to understand the unusual cytogenetic damage earlier encountered in the Yanomama Indians, plasma samples from 425 Amerindians representing 14 tribes have been tested for hemagglutination inhibition antibodies to the human JC polyoma virus and from 369 Amerinds from 13 tribes for hemagglutination inhibition antibodies to the human BK polyoma virus. There is for both viruses highly significant heterogeneity between tribes for the prevalence of serum antibody titers >/=1/40, the pattern of infection suggesting that these two viruses only relatively recently have been introduced into some of these tribes. Some of these samples, from populations with no known exposure to the simian polyoma virus SV40, also were tested for antibodies to this virus by using an immunospot assay. In contrast to the findings of Brown et al. (Brown, P., Tsai, T. & Gajdusek, D. C. (1975) Am. J. Epidemiol. 102, 331-340), none of the samples was found to possess antibodies to SV40. In addition, no significant titers to SV40 were found in a sample of 97 Japanese adults, many of whom had been found to exhibit elevated titers to the JC and BK viruses. This study thus suggests that these human sera contain significant antibody titers to the human polyoma viruses JC and BK but do not appear to contain either cross-reactive antibodies to SV40 or primary antibodies resulting from SV40 infection.     

Metabolism of naturally occurring propenylbenzene derivatives. III. Allylbenzene, propenyl benzene, and related metabolic products

The acidic and neutral urinary metabolites of allylbenzene, propenylbenzene, 1'-hydroxyallylbenzene, and cynnamyl alcohol were identified and related through a common metabolic scheme. The rat metabolizes allylbenzene to 1'-hydroxyallylbenzene which can rearrange to yield cinnamyl alcohol whick is further metabolized. This mechanism is proposed to account for the appearance of "propenyl type" metabolites from allylbenzene compounds. Propenylbenzene is oxidized to cynnamyl alcohol. Both 1'-hydroxyallylbenzene and cunnamyl alcohol are excreted unchanged in the neutral extract when given to rats. Allylbenzene and 1'-hydroxyallylbenzene yield basic ninhydrin-positive metabolites. Allylbenzene is first oxidized on the benzylic carbon to form 1'-hydroxyallylbenzene, which is further oxidized to form phenyl vinyl ketone, which condenses with the secondary amines piperidine and dimethylamine to form tertiary aminopropiophenones (Mannich bases). Analogous compounds, cinnamyl alcohol and propenylbenzene, do not yield Mannich base metabolites. This proposed metabolic scheme is consistent with the chemical mechanism operative in the synthesis of Mannich base from allylbenzene via chromic acid oxidation followed by amine addition.     

Evaluation issues in the Drake Chemical Workers Notification and Health Registry Study

The Drake Chemical Workers' Health Registry combined notification of workers about bladder cancer risk with access to a free program for screening and diagnosis. Evaluation of the project has given rise to several findings and new research questions. Findings in this article illustrate the following evaluation issues: 1) studying the combination of strategies that are most effective and cost effective to notify workers of their disease risks, 2) determining the realistic yield from strategies to gain participation in health screening and other protective services for notified workers, 3) identifying the notification strategies that were most effective for different kinds of participants, 4) using process evaluation to identify key activities for ensuring continued participation of cohort members in screening, and 5) examining the extent to which participants are willing to quit smoking to protect their health.