Clinical and epidemiologic evaluation of pressure ulcers in patients at a university hospital in Turkey.

OBJECTIVE: We sought to measure the incidence of pressure ulcer development at a university health center in Turkey, and to determine whether the Waterlow Pressure Sore Risk (PSR) Scale score predicted pressure ulcer development, stage, or number of ulcers. DESIGN: We prospectively evaluated patients who were hospitalized at our university-based medical center. SETTING AND SUBJECTS: We analyzed data from 22,834 patients hospitalized at the Baskent University Adana Teaching and Medical Research Center in Ankara, Turkey from January 1, 2004 to December 31, 2004, including 360 patients who developed pressure ulcers. INSTRUMENTS: The Waterlow PSR Scale was used to assess pressure ulcer risk. In addition, age, sex, the ward or unit in which the patient was hospitalized, reason for hospitalization, and location and stage of ulcers were collected on a data form designed specifically for this study. METHODS: A single nurse physiotherapist assessed all patients daily during their hospitalization. When a pressure ulcer was diagnosed by the nurse physiotherapist, a physician staged the pressure ulcers based on the US National Pressure Ulcer Advisory Panel (NPUAP) staging system. RESULTS: Three hundred sixty out of 22,834 patients developed 1 or more pressure ulcers, resulting in an incidence rate of 1.6%. Most ulcers (59.2%) occurred in patients hospitalized in the intensive care unit (n = 213). A positive correlation between the Waterlow PSR Scale score and number of ulcers per patient (r: 0.178, P < .01) was identified. No significant correlation was found linking Waterlow PSR Scale score and ulcer stage or the development of a single ulcer. CONCLUSION: We found significantly lower pressure ulcer incidence rates than those commonly reported in the literature, which we believe is principally attributable to short hospital stays and a strong emphasis on preventive nursing care. While high Waterlow PSR scale Scores correlated positively with development of multiple ulcers, this did not predict ulcer stage or the presence of a single pressure ulcer.     

Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139

Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO*) metabolites (nitrite and nitrate [NO(2)(-) and NO(3)(-)]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F(2 alpha) remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE(2), LTB(4), and NO*, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.     

Increased Levels of Inflammatory Mediators in Children and Adults Infected with Vibrio cholerae O1 and O139

Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E₂ (PGE₂), leukotriene B₄ (LTB₄), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO^·) metabolites (nitrite and nitrate [NO₂⁻ and NO₃⁻]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F_2α remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE₂, LTB₄, and NO^·, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.     

Extra-chromosomal telomeric DNA in cells from Atm(-/-) mice and patients with ataxia-telangiectasia

Ataxia-telangiectasia (AT) is an autosomally recessive human genetic disease with pleiotropic defects such as neurological degeneration, immunodeficiency, chromosomal instability, cancer susceptibility and premature aging. Cells derived from AT patients and ataxia-telangiectasia mutated (ATM)-deficient mice show slow growth in culture and premature senescence. ATM, which belongs to the PI3 kinase family along with DNA-PK, plays a major role in signaling the p53 response to DNA strand breaks. Telomere maintenance is perturbed in yeast strains lacking genes homologous to ATM and cells from patients with AT have short telomeres. We examined the length of individual telomeres in cells from ATM(-/-) mice by fluorescence in situ hybridization. Telomeres were extensively shortened in multiple tissues of ATM(-/-) mice. More than the expected number of telomere signals was observed in interphase nuclei of ATM(-/-) mouse fibroblasts. Signals corresponding to 5-25 kb of telomeric DNA that were not associated with chromosomes were also noticed in ATM(-/-) metaphase spreads. Extrachromosomal telomeric DNA was also detected in fibroblasts from AT patients and may represent fragmented telomeres or by-products of defective replication of telomeric DNA. These results suggest a role of ATM in telomere maintenance and replication, which may contribute to the poor growth of ATM(-/-) cells and increased tumor incidence in both AT patients and ATM(-/-) mice.     

Factor V gene (1691A and 4070G) and prothrombin gene 20210A mutations in patients with Behçet's disease

OBJECTIVES: Beh?et's disease (BD) is a chronic inflammatory disorder of still unknown etiology, characterized by endothelial cell injury/dysfunction and thrombosis and/or aneurysm of large blood vessels. Thrombophilia may play a role in the pathogenesis of thrombosis in BD. The common inherited gene defects, factor V (FV) 1691A (Leiden) and prothrombin (PT) 20210A, are known risk factors for thrombosis. The FV 4070G polymorphism was shown to influence circulating FV levels and to contribute to the activated protein C resistance phenotype. The aim of the study was to evaluate the role of FV 1691A, FV 4070G and PT 20210A gene mutations in Turkish BD patients with and without venous thrombosis. METHODS: Seventy-one patients with BD (27 with venous thrombosis) and 91 healthy subjects were included in the study. FV 1691A, FV 4070G, and PT 20210A mutations were determined by a method based on PCR-RFLP. RESULTS: The frequency of FV 1691A heterozygous mutation in BD patients with venous thrombosis (25.9%) was significantly higher than that in healthy subjects (8.8%; OR = 3.63; 95% CI 1.18-11.2). Although the frequency of this mutation in patients with venous thrombosis was higher than that in the patients without venous thrombosis (11.4%), the difference did not reach a statistically significant level (OR = 2.73; 95% CI 0.77-9.70). In BD patients with thrombosis, the frequencies of FV 4070G and PT 20210A were not significantly different compared to the BD patients without venous thrombosis and healthy subjects. CONCLUSIONS: Our results suggest that the FV 1691A, FV 4070G, and PT 20210A mutations are unlikely to play an important role in the pathogenesis of thrombosis in patients with BD.     

Improved high-performance liquid chromatography assay of doxorubicin: Detection of circulating aglycones in human plasma and comparison with thin-layer chromatography

Summary We compared doxorubicin and metabolite pharmacokinetic data obtained from thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) assay of plasma samples from six patients who had been treated with doxorubicin. Duplicate 1-ml samples were extracted with chloroform: isopropanol (1:1) and assayed using a sensitive HPLC system incorporating a dual pump gradient with tetrahydrofuran as the mobile phase and fluorescence detection. Duplicate 1-ml samples from the same specimens were assayed using a modification of a previously described TLC assay. Areas under the curve for doxorubicin by HPLC (3.36±2.30 M · h) and TLC (4.16±2.50 M · h) were not significantly different (P=0.5). Terminal half-life of doxorubicin by HPLC (28.0±6.98 h) and TLC (23.2±7.8) (P=0.29) and the calculated total-body clearances by HPLC (0.55±0.29 l/min) and TLC (0.45±0.23) (P=0.55) were not significantly different. Areas under the curve for doxorubicinol by HPLC (2.75±1.4 M · h) and TLC (2.53±7.1 M · h) (P=0.73) showed no significant differences. HPLC detected a mixed 7-deoxydoxorubicinol aglycone-doxorubicin aglycone peak, 7-deoxydoxorubicin aglycone, and two nonpolar, unidentified metabolites. TLC detected the following aglycone metabolites: doxorubicin aglycone, doxorubicinol aglycone, 7-deoxydoxorubicinol aglycone, an unidentified polar metabolite, and several unidentified nonpolar metabolites. From these data we conclude that HPLC and TLC detect concentrations of doxorubicin and doxorubicinol from human plasma equally well to concentrations of 7.0 nM (4 pmol injected doxorubicin). Aglycones do circulate in human plasma at concentrations above the detection limits of both assays. Doxorubicinol aglycone, which is detected by TLC but not by HPLC, may be formed from artifactual breakdown of doxorubicinol during TLC development. Unidentified nonpolar compounds seen on HPLC and TLC may represent further doxorubicin metabolism than previously described.