Reference values for 75 g oral glucose tolerance test in pregnancy

A 75 g oral glucose tolerance test was performed in 212 pregnant women with no predisposing factors suggesting glucose intolerance to establish the normal pattern of glucose metabolism in pregnancy. Reference values for the test were established for the middle of pregnancy (14-20 weeks, n = 43) and late pregnancy (28-37 weeks, n = 168). One woman was excluded because she had diabetes that required treatment with insulin. There were statistically significant differences between the two groups for samples taken both one and two hours after the glucose load. Reference ranges for the interpretation of the glucose tolerance test in pregnancy should therefore take account of the period of gestation. Arbitrary upper limits of normal (represented by the 97.5 centile) two hours after a 75 g oral glucose load are proposed at 7.5 and 9.6 mmol/l for the second and third trimesters, respectively.     

Astrocyte RNA in relation to neuronal RNA depletion in Alzheimer's disease

Summary A new double-staining procedure, in which the techniques of immunocytochemistry of glial fibrillary acidic protein (GFAP) and quantitative microdensitometry of azure B-RNA were combined, was used to study nucleic acid alterations in fibrous astrocytes in Alzheimer's disease (AD). RNA contents of GFAP-positive cells of the hippocampal endplate (Rose's H₃-H₅ fields) and the dentate gyrus molecular layer were determined in ten autopsy-proven AD patients (ages 51–88) and ten age-matched, non-demented control. In addition, RNA contents of pyramidal neurons of the endplate were examined. While there were no differences in RNA contents of astrocytes of either region between AD patients and controls, neuronal RNA was markedly depleted. These data suggest that astrocytes maintain protein synthetic capabilities in AD and that RNA loss is limited to the neuronal compartment.Supported by Grants 1P01-AG05119 and 1P50-AG05144 from the National Institutes of Health and by a Small Research Project Award from the University of Kentucky Medical Center     

The cigarette controversy.

This study examines the history of the cigarette controversy using the tobacco documents as a roadmap to explore the following four questions: (a) What did tobacco companies know about the health risks of smoking and when did they know it? (b) What evidence is there that tobacco companies conspired to deliberately mislead the public about the health risks of smoking? (c) How were scientists involved in the cigarette controversy? (d) Have tobacco companies changed the way they do business since signing the 1998 Master Settlement Agreement? The tobacco companies knew and for most part accepted the evidence that cigarette smoking was a cause of cancer by the late 1950s. The documents also reveal that the tobacco companies helped manufacture the smoking controversy by funding scientific research that was intended to obfuscate and prolong the debate about smoking and health. Today, the tobacco companies acknowledge that smoking is a cause of disease, but they have not materially altered the way they do business. In our opinion, it is not sufficient for the tobacco industry to merely concede the obvious point that smoking is a cause of disease when it is evident that decades of misinformation has resulted in a public that is massively ignorant about the risks of smoking low-tar cigarettes, nicotine addiction, and secondhand smoke exposure. Public education efforts are still needed to correct these misperceptions along with government oversight to ensure that the industry is not permitted to mislead the public further. If the past 50 years have taught us anything, it is that the tobacco industry cannot be trusted to put the public's interest above their profits no matter what they say.     

Quality of life and Kaposi sarcoma: using preference techniques to value the health gains from treatment

The goal of this work was to investigate preference techniques to value potential health gains from treatments of Kaposi sarcoma (KS). The study was designed to take the form of face-to-face interviews with a sample of men with a history of HIV/AIDS ( n=15) or HIV/AIDS and KS ( n=17). The main outcome measure was quality of life (QoL) associated with various KS disease states expressed on a scale from 0 (death) to 1 (perfect health), obtained though time trade-off (TTO) and rating scale techniques. For cutaneous lesions only, the mean TTO preference score value was 0.27. In other words, the men were willing to trade a life expectancy of 5 years for a shorter period (1.4 years) in perfect health. More severe KS health states were rated lower (0.07-0.09). The mean rating scale value for cutaneous lesions only was 0.11 and ranged from -0.10 to -0.04 for the more severe conditions; these values were systematically lower than the TTO ( P=0.014). A large overall potential gain in QoL from treatment (partial response minus stable disease) was found for each condition to be reflected in both the TTO (from 0.31 to 0.55) and the rating scale (from 0.38 to 0.44). Respondents associate KS health states with extremely poor QoL and indicate that large gains are possible through modest treatment effects. While TTO returns higher values than the rating scale, potential gains from treatments were similar. The techniques appear to be suitable for application to QoL and economic evaluation of treatments of KS.     

AT base pairs are the main target for mutations at the hprt locus of rat skin fibroblasts exposed in vitro to the monofunctional alkylating agent N-ethyl-N-nitrosourea

Spectra of N-ethyl-N-nitrosourea (ENU)-induced mutations differwidely among various in vitro and in vivo mutational systems.To investigate possible reasons for these differences, a mutationalsystem is needed in which the same target gene is used for comparisonin the same type of cells in vitro and in vivo. In the presentstudy, this was achieved by analysing at the molecular level35 hprt mutant rat fibroblast clones obtained from cell populationsexposed in vitro to ENU and comparing the mutational spectrumwith the previously determined spectrum of ENU-induced hprtmutants in the same target cells exposed in vivo. Twenty-eightmutants contained a single base pair alteration in the hprtcoding sequence. Most of these changes were found at AT basepairs (19/28), the AT to TA transversion being the most frequentkind of mutation (12/19), which is probably caused by O²-ethylthymine.Transversions at AT base pairs showed all mutated T's to belocated in the nontranscribed strand of the hprt gene, suggestinga strand specific fixation of mutations induced by O²-ethylthymine,which appears to be a general feature of ENU- and ENNG-inducedhprt mutations in mammalian cells. GC to AT transitions, probablycaused by O⁶-ethylguanine, were detected at a lower frequency(7/28). This in vitro mutational spectrum was very similar tothat of the same target cells exposed in vivo to ENU. A comparisonof the mutational spectra in AGT-proficient and AGT-deficientrodent cells exposed to ethylating agents showed that in contrastto the situation in AGT-proficient rat fibroblasts, GC to ATbase pair changes (and not AT to TA) are the predominant mutationsin AGT-deficient hamster cells. ⁴To whom correspondence should be addressed     

Prevalence of juvenile periodontitis in a circumpubertal population

A cross-sectional radiographic screening was performed on bite-wing pairs (BW) from 1872 10-12 year old schoolchildren in the Greater Worcester, Massachusetts area to assess the prevalence of juvenile periodontitis (JP). The 3-stage screening process entailed: (1) visual identification of possible cases based upon a visual assessment of BW for interproximal crestal bone levels greater than or equal to 2 mm from the cemento-enamel junction (CEJ) on greater than or equal to 1 permanent first molar; (2) identification of probable cases based upon BW from possible cases measured with a transparent ruler calibrated in millimeters; (3) finally, clinical confirmation of JP in consenting probable cases. A total of 1038 subjects were eligible to be included in the study (greater than or equal to 3 mesial sites readable). Of the 1038 eligible subjects, 117 possible and 103 probable cases were identified in stage 1 and stage 2, respectively. A total of 99 probable cases could be contacted and 43 were examined clinically. Two cases of JP were confirmed clinically in stage 3, yielding a prevalence rate of 4.6/1000. Specifically, this report defines a rate of JP in 10-12 year-old schoolchildren for the first time. In addition, these results indicate that BW can be used to identify children with JP from large data sets. However, further studies including complete clinical and radiographic examinations are necessary to determine whether this method is adequate for large epidemiologic studies.     

Antigenic studies on an enzymatically sialylated carbohydrate: NeuAc(alpha 2-3)Gal(beta 1-3)GalNAc

Sialic acid residues are often the end moiety of the carbohydrate chain of biologically important glycoconjugates. It is difficult to study sialylated glycoconjugates because the purification of these compounds is often laborious yielding only very small amounts of oligosaccharides for study. Chemical synthesis of sialylated compounds is complicated by the labile nature of the sialic acid bond. In both of these cases the sialylated compounds would need to be conjugated to a polypeptide to be an effective immunogen, and again, such conjugation is fraught with problems due to the instability of the sialic acid linkage. We have developed a combined enzymatic and synthetic route for obtaining quantities of sialylated carbohydrates conjugated to a protein carrier in amounts sufficient for antigenic studies. The notable novelty of this protocol is the addition of sialic acid after the carbohydrate-protein conjugation step. Antiserum to the compounds was developed and after absorption, antibodies that demonstrate a requirement for sialic acid for their binding were produced and studied. CA 125 has been shown to be a prognostically significant marker for ovarian adenocarcinoma. The nature of the epitope involved has been analyzed with conflicting results. To attempt to resolve this conflict, we initiated studies on sialylated antigens with NeuAc alpha 2-3Gal beta 1-3GalNAc. This trisaccharide occupies the terminal region in a series of complex carbohydrates which have been suggested to be involved as the epitope. Hanisch et al. reported that the neuraminic acid was important for the reaction.