Serodiagnosis of Crimean-Congo haemorrhagic fever.

Several methods for demonstrating antibody to Crimean-Congo haemorrhagic fever virus were compared on serum samples taken from 101 patients during the acute stage of illness and at intervals for up to 59 months thereafter, with emphasis on early detection of the immune response. The deaths of 23 patients on days 5-14 of illness were ascribed to the effects of the disease; two patients died later from other causes. Very few of the patients who died from the acute illness mounted an antibody response detectable by the methods tested. Four patients who died and 18 who recovered were treated with immune plasma collected from recovered patients. Treated patients acquired IgG antibody from the plasma, but it was possible to discern the onset of an endogenous IgM response in those individuals who survived the disease by all of the methods tested. Indirect immunofluorescence (IF) tests detected IgM and/or IgG antibodies at the earliest on day 4 of illness in about 10% of patients who survived the disease, and by day 9 all survivors had antibodies demonstrable by IF. A biotin-streptavidin IF technique offered no advantage over the standard IF test for the early detection of IgG antibody, but demonstrated higher antibody titres and detected IgM antibody earlier in about a quarter of the patients tested. An IgM-capture enzyme-linked immunoassay (ELISA) and an IgG sandwich ELISA demonstrated higher antibody titres than did IF tests, and detected antibody responses at an earlier stage of infection than did IF tests in about one-fifth of patients, but the reverse was true in a similar proportion of instances. A competition ELISA, which detected total antibody activity, produced lower titres than did the IgM and IgG ELISAs, but yielded results which were in close agreement with the findings in IF tests. It was concluded that the IF tests were most convenient for use in making a rapid serodiagnosis of the disease.     

Cell proliferation in human tumours growing in nude mice: renal cell carcinomas,larynx and hypopharynx carcinomas

Summary Cell proliferation of 51 human renal cell carcinomas and 9 larynx and hypopharynx carcinomas has been studied in vitro and using xenotransplants. The proliferative activity ([³H]thymidine labelling index) increases during the first passages in nude mice and then remains almost constant throughout subsequent passages. A comparison of cell kinetic parameters of 8 human renal cell carcinomas, 1 hypopharynx and 2 larynx carcinomas, with data of xenografts and of human tumours in situ published up to now, shows that the cell kinetic parameters of human tumour xenografts presently studied range between those of human tumours in situ and those of autochthonous or transplantable mouse tumours. S-phase durations and potential doubling times are considerably shorter in xenotransplants than in human tumours in situ, whereas the cycle time is about the same. This means that the growth fraction increases considerably after xenotransplantation. This change of human tumour cell proliferation after transplantation into nude mice should be kept in mind if one wishes to draw conclusions from the nude mouse model on conditions in human beings, particularly with respect to therapeutic regimens, which are frequently tested in the nude mouse model.Abbreviations used RCC renal cell carcinoma - HPC larynx or hypopharynx carcinoma - LI labelling index - PLM percentage of labelled mitoses - t _s S-phase duration - t _c cycle time - t _pot potential doubling time This work was supported by the Deutsche Forschungsgemeinschaft (Ma 876/2-1)     

Alterations of the levels of glycoproteins Ib-IX and IIb-IIIa in platelets stored at 22°C

Platelets stored in CLX™ blood bags, under normal blood banking conditions, were studied for up to 7 days to determine if changes ocurred in the levels of membrane glycoproteins (GP) Ib-IX and IIb-IIIa. Radiolabeled monoclonal antibodies (MAB) were used to estimate the number of glycoprotein molecules on the surface membrane of intact platelets. GP IX and GP IIb-IIIa levels remained essentially unaltered during storage. In contrast, the content of GP Ib at day 7 decreased by 45% of the total when fresh. The aggregation response to ristocetin, which requires GP Ib, was also diminished after 7 days. Addition of protease inhibitors, leupeptin and/or aprotinin did not appear to influence the degradation of this glycoprotein. We conclude that storage at 22°C has deleterious effects on the GP Ib content of platelets.     

Decreased sensitivity to experimental pain in adjustment disorder.

An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described. Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical pain on both sides of the body. We found an overall increase of pain thresholds and tolerances in AD patients as compared to controls, predominately on the right side of the body. Analogue findings have been reported for pain perception in major depressive disorder (MDD). Of the data obtained, only thermal pain threshold on the right arm correlated with the severity of depressive symptoms. Although the underlying pathology is elusive it is likely that the mechanisms for reduced pain sensitivity are comparable in MDD and AD.     

Surge Capacity Associated with Restrictions on Nonurgent Hospital Utilization and Expected Admissions during an Influenza Pandemic: Lessons from the Toronto Severe Acute Respiratory Syndrome Outbreak

Background Current influenza pandemic models predict a surge in influenza‐related hospitalizations in affected jurisdictions. One proposed strategy to increase hospital surge capacity is to restrict elective hospitalizations, yet the degree to which this measure would meet the anticipated is unknown. Objectives To compare the reduction in hospitalizations resulting from widespread nonurgent hospital admission restrictions during the Toronto severe acute respiratory syndrome (SARS) outbreak with the expected increase in admissions resulting from an influenza pandemic in Toronto. Methods The authors compared the expected influenza‐related hospitalizations in the first eight weeks of a mild, moderate, or severe pandemic with the actual reduction in the number of hospital admissions in Toronto, Ontario, during the first eight weeks of the SARS‐related restrictions. Results Influenza modeling for Toronto predicts that there will be 4,819, 8,032, or 11,245 influenza‐related admissions in the first eight weeks of a mild, moderate, or severe pandemic, respectively. In the first eight weeks of SARS‐related hospital admission restrictions, there were 3,654 fewer hospitalizations than expected in Toronto, representing a modest 12% decrease in the overall admission rate (a reduction of 1.40 admissions per 1,000 population). Therefore, influenza‐related admissions could exceed the reduction in admissions resulting from restricted hospital utilization by 1,165 to 7,591 patient admissions, depending on pandemic severity, which corresponds to an excess of 0.44 to 2.91 influenza‐related admissions per 1,000 population per eight weeks, and an increase of 4% to 25% in the overall number of admissions, when compared with nonpandemic conditions. Conclusions Pandemic modeling for Toronto suggests that influenza‐related admissions would exceed the reduction in hospitalizations seen during SARS‐related nonurgent hospital admission restrictions, even in a mild pandemic. Sufficient surge capacity in a pandemic will likely require the implementation of other measures, including possibly stricter implementation of hospital utilization restrictions.     

Safety assessment of high fructose corn syrup (HFCS) as an ingredient added to cigarette tobacco

A tiered testing strategy has been developed to evaluate the potential for new ingredients, tobacco processes, and technological developments to alter the biological activity that results from burning tobacco. A series of studies was initially conducted with cigarettes containing 3% high fructose corn syrup (HFCS) as an alternate tobacco casing material to corn syrup/invert sugar, including determination of selected mainstream cigarette smoke (MS) constituent yields, Ames assay, sister chromatid exchange (SCE) assay in Chinese hamster ovary (CHO) cells, a 30-week dermal tumor-promotion evaluation of cigarette smoke condensate (CSC) in SENCAR mice, and a 13-week subchronic inhalation study of MS in Sprague-Dawley rats. A second series of studies was conducted with cigarettes containing 3%, 4% and 5% HFCS including MS chemistry, Ames assay, SCE assay in CHO cells, and a neutral red cytotoxicity assays. Collectively, mainstream smoke chemistry, genotoxicity, dermal tumor-promotion, and inhalation toxicity studies demonstrated no differences between cigarettes with 3% HFCS and cigarettes with 3% corn syrup/invert sugar. Also, mainstream smoke chemistry and genotoxicity of cigarettes with 4% and 5% HFCS were not different from cigarettes with 3% HFCS. In conclusion, the addition of up to 5% HFCS to cigarette does not alter the mainstream smoke chemistry or biological activity of mainstream smoke or mainstream smoke condensate as compared to cigarettes with 3% corn syrup/invert sugar with regard to the parameters investigated and presented.