Clinical criteria for the use of a decision-making framework for the medically compromised patient: hypertension and diabetes mellitus

In this article, clinical criteria for the staging of disease severity in patients with hypertension and diabetes mellitus are presented. This paper is intended to supplement a previous article by the authors on the use of clinical criteria for the classification of patients with ischemic heart disease and chronic obstructive pulmonary disease and the use of a decision-making framework for the medically compromised patient. Hypertension and diabetes mellitus are discussed in terms of pathophysiology, risk factors, clinical manifestations of disease and disease progression. The article will allow practitioners to stage patients with hypertension and diabetes mellitus and to apply this staging to the previously established clinical decision-making framework for medically compromised patients.     

Attacks on Fast Double Block Length Hash Functions

The security of hash functions based on a block cipher with a block length of m bits and a key length of k bits, where , is considered. New attacks are presented on a large class of iterated hash functions with a 2m -bit hash result which processes in each iteration two message blocks using two encryptions. In particular, the attacks break three proposed schemes: Parallel-DM, the PBGV hash function, and the LOKI DBH mode. Received 1 March 1996 and revised 16 December 1996     

Sequential DNA damage-independent and -dependent activation of NF-kappaB by UV

NF-kappaB activation in response to UV irradiation of HeLa cells or of primary human skin fibroblasts occurs with two overlapping kinetics but totally different mechanisms. Although both mechanisms involve induced dissociation of NF-kappaB from IkappaBalpha and degradation of IkappaBalpha, targeting for degradation and signaling are different. Early IkappaBalpha degradation at 30 min to approximately 6 h is not initiated by UV-induced DNA damage. It does not require IkappaB kinase (IKK), as shown by introduction of a dominant-negative kinase subunit, and does not depend on the presence of the phosphorylatable substrate, IkappaBalpha, carrying serines at positions 32 and 36. Induced IkappaBalpha degradation requires, however, intact N- (positions 1-36) and C-terminal (positions 277-287) sequences. IkappaB degradation and NF-kappaB activation at late time points, 15-20 h after UV irradiation, is mediated through DNA damage-induced cleavage of IL-1alpha precursor, release of IL-1alpha and autocrine/paracrine action of IL-1alpha. Late-induced IkappaBalpha requires the presence of Ser32 and Ser36. The late mechanism indicates the existence of signal transfer from photoproducts in the nucleus to the cytoplasm. The release of the 'alarmone' IL-1alpha may account for some of the systemic effects of sunlight exposure.     

The prevalence of antibiotic-resistant faecal Escherichia coli in healthy volunteers in Venezuela

Faecal samples were collected from healthy volunteers in two regions in Venezuela, the village of Grulla (n = 195) and the city of Mérida (n = 181), and analysed for the prevalence of antibiotic resistant faecal Escherichia coli as well as the antibiotic susceptibility of the strains isolated. The highest prevalences of resistance were observed for amoxicillin, oxytetracycline, sulfamethoxazole and trimethoprim. The percentages found for Grulla were 46, 38, 44 and 30%, respectively; for Mérida 39, 65, 56 and 36%, respectively. In Mérida, a significantly higher prevalence of resistance for oxytetracycline was found (P < 0.05). Significant differences in the distribution of the MIC values between Grulla and Mérida were observed for amoxicillin, chloramphenicol and oxytetracycline (P < 0.05). In Grulla, the most frequent pattern was resistance to amoxicillin only and in Mérida to oxytetracycline only. Amoxicillin resistance was due to production of TEM1 beta-lactamase.     

Differential capacities of CD4+, CD8+, and CD4-CD8- T cell subsets to express IL-18 receptor and produce IFN-gamma in response to IL-18

IL-12 and IL-18 have the capacity to stimulate IFN-gamma production by T cells. Using a T cell clone, we reported that IL-18 responsiveness is generated only after exposure to IL-12. Here, we investigated the induction of IL-18 responsiveness in resting CD8+, CD4+, and CD4-CD8- T cells. Resting T cells respond to neither IL-12 nor IL-18. After stimulation with anti-CD3 plus anti-CD28 mAbs, CD8+, CD4+, and CD4-CD8- T cells expressed IL-12R, but not IL-18R, and produced IFN-gamma in response to IL-12. Cultures of T cells with anti-CD3/anti-CD28 in the presence of rIL-12 induced IL-18R expression and IL-18-stimulated IFN-gamma production, which reached higher levels than that induced by IL-12 stimulation. However, there was a substantial difference in the expression of IL-18R and IL-18-stimulated IFN-gamma production among T cell subsets. CD4+ cells expressed marginal levels of IL-18R and produced small amounts of IFN-gamma, whereas CD8+ cells expressed higher levels of IL-18R and produced more IFN-gamma than CD4+ cells. Moreover, CD4-CD8- cells expressed levels of IL-18R comparable to those for CD8+ cells but produced IFN-gamma one order higher than did CD8+ cells. These results indicate that the induction of IL-18R and IL-18 responsiveness by IL-12 represents a mechanism underlying enhanced IFN-gamma production by resting T cells, but the operation of this mechanism differs depending on the T cell subset stimulated.