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Significant Inverse Correlation (significant + inverse_correlation)
Selected AbstractsEffect of food restriction on ghrelin in adult male rats and its relation to male reproductive hormonesANDROLOGIA, Issue 2 2010H. M. Abou Heif Summary Ghrelin is an endogenous ligand for growth hormone secretagogue (GHS) receptor (GHS-R). It has recently emerged as an orexigenic food intake controlling signal acting upon hypothalamic centres. To study the effect of food restriction on ghrelin level and its relation to male reproductive hormones, 32 adult male albino rats divided into two groups: Group I (8 rats as a control group) fed ad libitum for 21 days and 24 rats as Group II (food-restricted group) fed 30% of ad libitum intake of food consumed by the control group. Rats were weighed every 3 days. Group II rats were further subdivided into three subgroups: IIa, IIb and IIc that were killed at days 8, 16 and 21 from the start of food restriction respectively. Ghrelin level was assayed by ELISA technique in serum samples and tissue homogenates prepared from the stomach and hypothalamus. In addition, male reproductive hormones: testosterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were assayed in serum by chemiluminescence. Mean body weight of food restricted rats was observed to decrease during the period of the experiment. Food restriction produced a significant increase of serum ghrelin and a significant decrease of both gastric and hypothalamic ghrelin in group II when compared with group I. The changes in ghrelin level varied with the duration of food restriction. Significant inverse correlation was found between serum ghrelin and each of gastric and hypothalamic ghrelin in group II. A significant decrease of testosterone, FSH and LH were found in food restricted rats compared with controls. The decrease was significantly related to the duration of food restriction. Significant inverse correlation was detected between serum ghrelin and each of the male reproductive hormones in food restricted group II rats. Thus ghrelin could be one of the hormones responsible for the suppression of male reproductive axis in case of negative energy balance. [source] Selective Control Assessment of the Lower Extremity (SCALE): development, validation, and interrater reliability of a clinical tool for patients with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2009EILEEN G FOWLER PhD PT Normal selective voluntary motor control (SVMC) can be defined as the ability to perform isolated joint movement without using mass flexor/extensor patterns or undesired movement at other joints, such as mirroring. SVMC is an important determinant of function, yet a valid, reliable assessment tool is lacking. The Selective Control Assessment of the Lower Extremity (SCALE) is a clinical tool developed to quantify SVMC in patients with cerebral palsy (CP). This paper describes the development, utility, validation, and interrater reliability of SCALE. Content validity was based on review by 14 experienced clinicians. Mean agreement was 91.9% (range 71.4,100%) for statements about content, administration, and grading. SCALE scores were compared with Gross Motor Function Classification System Expanded and Revised (GMFCS-ER) levels for 51 participants with spastic diplegic, hemiplegic, and quadriplegic CP (GMFCS levels I , IV, 21 males, 30 females; mean age 11y 11mo [SD 4y 9mo]; range 5,23y). Construct validity was supported by significant inverse correlation (Spearman's r=-0.83, p<0.001) between SCALE scores and GMFCS levels. Six clinicians rated 20 participants with spastic CP (seven males, 13 females, mean age 12y 3mo [SD 5y 5mo], range 7,23y) using SCALE. A high level of interrater reliability was demonstrated by intraclass correlation coefficients ranging from 0.88 to 0.91 (p<0.001). [source] An increased proportion of inflammatory cells express tumor necrosis factor alpha in idiopathic achalasia of the esophagusDISEASES OF THE ESOPHAGUS, Issue 5 2009A. Kilic SUMMARY Achalasia is a motility disorder characterized by the absence of coordinated peristalsis and incomplete relaxation of the lower esophageal sphincter. The etiology remains unclear although dense inflammatory infiltrates within the myenteric plexus have been described. The nature of these infiltrating cells is unknown. The aim of this study was to evaluate the expression of proinflammatory cytokines , namely, tumor necrosis factor alpha and interleukin-2 , in the distal esophageal muscle in patients with achalasia. Lower esophageal sphincter muscle from eight patients undergoing myotomy or esophagectomy for achalasia of the esophagus were obtained at the time of surgery. Control specimens consisted of similar muscle taken from eight patients undergoing operation for cancer or Barrett's esophagus. The expression of tumor necrosis factor alpha and interleukin-2 were assessed by immunohistochemistry. The total number of inflammatory cells within the myenteric plexus were counted in five high power fields. The percentage of infiltrating cells expressing tumor necrosis factor alpha or interleukin-2 was calculated. Clinical data including demographics, preoperative lower esophageal sphincter pressure, duration of symptoms, and dysphagia score (1 = no dysphagia to 5 = dysphagia to saliva) were obtained through electronic medical records. Statistical comparisons between the groups were made using the unpaired t -test, Fisher's exact test, or Mann,Whitney U test, with a two-tailed P -value less than 0.05 being considered significant. The total number of inflammatory cells was found to be similar between the groups. A significantly higher proportion of inflammatory cells expressed tumor necrosis factor alpha in achalasia as compared with controls (22 vs. 11%; P= 0.02). A similar percentage of infiltrating cells expressed interleukin-2 (40 vs. 41%; P= 0.87). Age, gender, preoperative lower esophageal sphincter pressure, or dysphagia score were not correlated to expression of these cytokines. There was, however, a significant inverse correlation between duration of symptoms and the proportion of inflammatory cells expressing tumor necrosis factor alpha in achalasia (P= 0.007). In conclusion, a higher proportion of infiltrating inflammatory cells expressed tumor necrosis factor alpha in achalasia. Furthermore, this proportion appears to be highest early in the disease process. Further studies are required to more clearly delineate the role of tumor necrosis factor alpha in the pathogenesis of this idiopathic disease. [source] Right Ventricular Dimensions and Function in Isolated Left Bundle Branch Block: Is There Evidence of Biventricular Involvement?ECHOCARDIOGRAPHY, Issue 5 2008Jeroen Van Dijk M.D. Background: Isolated left bundle branch block (LBBB) may be an expression of idiopathic cardiomyopathy affecting both ventricles. The present study was conducted to evaluate right ventricular (RV) dimensions and function in asymptomatic LBBB patients with mildly depressed left ventricular (LV) function. Methods: Fifteen patients with asymptomatic LBBB in whom coronary artery disease, hypertension, and valvular pathology was excluded were studied. Fifteen healthy volunteers and 15 idiopathic dilated cardiomyopathy LBBB patients served as controls. RV long axis and tricuspid annulus diameter were obtained, as were tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity (Sm) of the RV free wall annulus. Tricuspid regurgitation (TR) jets (peak TR jets) were used for RV pressure assessment. Results: RV dimensions were comparable between the asymptomatic LBBB patients and controls. RV functions of healthy volunteers and asymptomatic LBBB patients were similar (TAPSE: 24 ± 3 and 24 ± 4 mm, Sm: 13 ± 2 and 13 ± 3 cm/s, respectively), whereas functional parameters in idiopathic dilated cardiomyopathy patients were significantly reduced (TAPSE: 19 ± 5 mm, Sm: 9 ± 2 cm/s, both P < 0.01 by analysis of variance [ANOVA]). For the three groups combined, a significant inverse correlation between RV pressure (peak TR jets) and RV function (Sm) was observed (r =,0.52, P = 0.017). Conclusions: In patients with an asymptomatic LBBB, RV dimensions and function are within normal range. The present study suggests that screening of RV functional parameters in asymptomatic LBBB patients is not useful for identification of an early-stage cardiomyopathy, and RV dysfunction is merely a consequence of increased RV loading conditions caused by left-sided heart failure and does not indicate a generalized cardiomyopathy affecting both ventricles. [source] Effects of age on the cardiac and vascular limbs of the arterial baroreflexEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2003C. M. Brown Abstract Background Healthy ageing has several effects on the autonomic control of the circulation. Several studies have shown that baroreflex-mediated vagal control of the heart deteriorates with age, but so far there is little information regarding the effect of ageing on sympathetically mediated baroreflex responses. The aim of this study was to assess the effects of ageing on baroreflex control of the heart and blood vessels. Materials and Methods In 40 healthy volunteers, aged 20,87 years, we applied oscillatory neck suction at 0·1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0·2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was maintained at 0·25 Hz. Blood pressure, electrocardiographic RR intervals and respiration were recorded continuously. Spectral analysis was used to evaluate the magnitude of the low-frequency (0·03,0·14 Hz) and high-frequency (0·15,0·50 Hz) oscillations in the RR interval and blood pressure. Responses to neck suction were assessed as the change in power of the RR interval and blood pressure fluctuations at the stimulation frequency from baseline values. Results Resting low- and high-frequency powers of the RR interval decreased significantly with age (P < 0·01). However, the low-frequency power of systolic blood pressure did not correlate with age. Spontaneous baroreflex sensitivity (alpha-index) showed a significant inverse correlation with age (r = ,0·46, P < 0·05). Responses of the RR interval and systolic blood pressure to 0·1 Hz neck suction stimulation were not related to age, however, the RR interval response to 0·2 Hz neck suction declined significantly with age (r = ,0·61, P < 0·01). Conclusions These results confirm an age-related decrease in cardiovagal baroreflex responses. However, sympathetically mediated baroreflex control of the blood vessels is preserved with age. [source] Protein deficiency balance as a predictor of clinical outcome in hereditary spherocytosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2005S. Rocha Abstract:, Vertical and horizontal interactions between membrane constituents account for integrity, strength and deformability of the erythrocyte. Disruption of vertical interactions caused by membrane protein deficiencies in hereditary spherocytosis (HS), favor membrane vesiculation with development of spherocytic cells. Our aim was to evaluate the hematological and clinical presentation of HS according to the type and amount of protein deficiency. We studied 81 Portuguese individuals, 71 belonging to 21 families plus 10 unrelated subjects, and found that 51 of them were HS patients. Patients were classified as presenting mild, typical or severe HS, according to laboratory results and clinical follow-up. We performed screening tests and the standardized electrophoretic membrane protein analysis to identify and quantify protein deficiencies. We found band 3 and ankyrin deficiencies as the major causes for HS. The ratios between the value of the primary and/or secondary protein deficiencies showed significantly different values according to the severity of HS, and a significant inverse correlation with the severity of HS was observed. In mild HS, the ratios between protein deficiencies reflected equivalent protein deficiencies, while an unbalance was observed in typical HS, which was enhanced in severe HS. Our data suggest that the relative quantification of each major membrane protein and of the ratios between the values of protein deficiencies may be helpful in providing additional data about the clinical outcome of HS. [source] Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 7 2005M. Zorzon To determine the effects of high dose methylprednisolone (HDMP) pulses on bone mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS patients who received regular pulses of HDMP as well as pulses of HDMP for relapses, 18 MS patients who received HDMP at the same dose schedule only for relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral neck and we assessed biochemical markers of bone metabolism and turnover. The average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and 28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured at lumbar spine and femoral neck and biochemical indices of bone metabolism did not differ in MS patients and controls. BMD measures were not associated with lifetime methylprednisolone dosage. In partial correlation analysis, controlling for age, gender and menopausal status there was a significant inverse correlation between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r = ,0.31, P =0.05). In conclusion, treatment with repeated HDMP pulses was not associated with osteoporosis in patients with MS who participated in a trial of methylprednisolone. However, osteopenia was observed more frequently in MS patients than healthy controls. Our data are reassuring, as them suggest that repeated pulses of methylprednisolone do not result in substantially increased risk of osteoporosis in MS patients. Moreover, osteopenia was found only in patients treated for relapses, who had a significantly higher EDSS score than patients in the HDMP group, suggesting that decreased mobility may contribute to bone loss more than corticosteroid use. BMD should be monitored in patients with MS, regardless of the use of methylprednisolone. [source] Migraine Headache Recurrence: Relationship to Clinical, Pharmacological, and Pharmacokinetic Properties of TriptansHEADACHE, Issue 4 2003Gilles Géraud MD Background and Objectives.,Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo. Methods.,Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters. Results.,Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = ,1.0, P = .0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = ,0.68, P = .034), but 5-HT1D receptor potency was not correlated with recurrence (r = ,0.20, P = .54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P = .53) and for therapeutic gain, ,0.11 (P = .71). Conclusion.,The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence. [source] Scintigraphic evaluation of intrapulmonary shunt in normoxemic cirrhotic patients and effects of terlipressinHEPATOLOGY RESEARCH, Issue 10 2010George Kalambokis Aim:, The magnitude of intrapulmonary shunt (IPS) in cirrhotic patients without hypoxemia remains undefined. We evaluated the severity and clinical correlations of IPS in normoxemic cirrhotics, and possible IPS alterations after terlipressin treatment. Methods:, Fifteen patients with alcoholic cirrhosis without hypoxemia were studied at baseline and after the administration of 2 mg of terlipressin. The IPS fraction was evaluated by lung perfusion scan after the i.v. injection of technetium-99m -labeled macroaggregated albumin (99mTc-MAA) and calculation of brain uptake (positive value ,6%). Cardiac output (CO), pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were evaluated by Doppler echocardiography. Mean arterial pressure (MAP) was measured and the ratio MAP/CO was calculated as an index of systemic vascular resistance (SVR). Portal vein velocity (PVV) and portal venous flow (PVF) were also assessed by Doppler ultrasonography. Results:, Three patients (20%) had an IPS fraction of more than 6%. A significant inverse correlation with platelet count (P = 0.001) and a direct correlation with Child,Pugh score (P = 0.06), PVV (P = 0.07) and PVF (P = 0.07) were noted. IPS fractions decreased significantly after terlipressin administration (P = 0.00001); the IPS fraction fell below 6% in all three patients with positive baseline values. Terlipressin treatment induced a significant decrease in CO (P = 0.003) and significant increases in MAP (P = 0.0003), SVR (P = 0.0003), SPAP (P = 0.001) and PVR (P = 0.01). Conclusion:, IPS fractions detected by 99mTc-MAA lung scan were inversely correlated with platelet count and directly with liver disease severity, and found abnormal in 20% of normoxemic cirrhotic patients. Terlipressin reduced significantly the magnitude of the shunt. [source] New method of dynamic color doppler signal quantification in metastatic lymph nodes compared to direct polarographic measurements of tissue oxygenationINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Thomas Scholbach Abstract Tumor growth depends on sufficient blood and oxygen supply. Hypoxia stimulates neovascularization and is a known cause for radio- and chemoresistance. The objective of this study was to investigate the use of a novel ultrasound technique for the dynamic assessment of vascularization and oxygenation in metastatic lymph nodes. Twenty-four patients (age 44,78 years) with cervical lymph node metastases of squamous cell head and neck cancer were investigated by color duplex sonography and 17 (age 46,78 years) were investigated additionally with polarography. Sonography was performed after contrast enhancer infusion under defined conditions. Intranodal perfusion data (color hue, colored area) were measured automatically by a novel software technique. This allows an evaluation of blood flow dynamics by calculating perfusion intensity,velocity, perfused area, as well as the novel parameters tissue resistance index (TRI) and tissue pulsatility index (TPI),for each point of a complete heart cycle. Tumor tissue pO2 was measured by means of polarographic needle electrodes placed intranodally. The sonographic and polarographic data were correlated using Pearson's test. Sonography demonstrated a statistically significant inverse correlation between hypoxia and perfusion and significant TPI and TRI changes with different N-stages. The percentage of nodal fraction with less than 10 mmHg oxygen saturation was significantly inversely correlated with lymph node perfusion (r = ,0.551; p = 0.021). Nodes with a perfusion of less than 0.05 cm/sec flow velocity showed significantly larger hypoxic areas (p = 0.006). Significant differences of TPI and TRI existed between nodes in stage N1 and N2/N3 (p = 0.028 and 0.048, respectively). This new method of dynamic signal quantification allows a noninvasive and quantitative assessment of tumor and metastatic lymph node perfusion by means of commonly available ultrasound equipment. © 2004 Wiley-Liss, Inc. [source] Telomerase activity and telomere length in acute leukemia: correlations with disease progression, subtypes and overall survivalINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010Y. WANG Summary The progressive shortening of telomeres and the activation of telomerase are considered to be one of the important mechanisms in cellular immortalization and disease progression. Bone marrow samples were collected from 148 patients with acute leukemia (AL). Based on the stage of the disease, patients were divided into the newly diagnosed group, the relapsed group and the complete remission (CR) group. telomerase activity (TA) was examined by PCR-ELISA, and telomere length (TL) was examined by Southern blot analyses. TA and TL were analyzed in relation to AL stage and subtype. Five-year survival was analyzed using Kaplan,Meier survival curve. TA in AL patients was higher than healthy individuals. TA level was the highest in the relapsed group, followed by the newly diagnosed group, and then the CR group. TA had no difference between acute nonlymphocytic leukemia (ANLL) group and acute lymphocytic leukemia (ALL) group. But TA in group of subtype M3 was lower than other subtypes of ANLL. TL in AL group was shorter than the control group. TL was the shortest in the relapsed group, followed by the newly diagnosed group, and finally the CR group. TL exhibited an inverse correlation with TA. The group of patients with high TA had a significantly poorer five-year-survival than that of low TA group. TA is elevated and TL is shortened in AL patients. There is a significant inverse correlation between TL and TA. Patients in late-stage disease had shorter TL and higher TA than those in early stages. The shortened TL and elevated TA correlated with disease progression and relapse, and they may serve as prognostic factors for AL patients with poor outcome. M3 subtype is special with relative lower TA and long-lasting survival than other subtypes. [source] TNF-, Mediates p38 MAP Kinase Activation and Negatively Regulates Bone Formation at the Injured Growth Plate in Rats,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2006Fiona H Zhou Abstract TNF-, is known to inhibit osteoblast differentiation in vitro and yet it is essential for bone fracture repair. Roles of TNF-, in the bony repair of injured growth plate were examined in young rats treated with a TNF-, antagonist. The results show that TNF-, mediates p38 activation, which influences the recruitment, proliferation, and osteoblast differentiation of mesenchymal cells and negatively regulates bone formation at the injured growth plate. Introduction: TNF-, inhibits expression of osteoblast differentiation factor cbfa1 and osteoblast differentiation in vitro and yet TNF-, signaling is essential for bone fracture healing. Roles of TNF-, in the bony repair of injured growth plate cartilage are unknown. Materials and Methods: Roles of TNF-, in the activation of p38 mitogen activated protein (MAP) kinase and the subsequent bony repair of the injured growth plate were examined in young rats receiving the TNF-, inhibitor ENBREL or saline control. Activation of p38 was determined by Western blot analysis and immunohistochemistry. Inflammatory cell counts on day 1, measurements of repair tissue proportions, and counting of proliferative mesenchymal cells on day 8 at growth plate injury site were carried out (n = 6). Expression of inflammatory cytokines TNF-, and IL-1,, fibrogenic growth factor (FGF)-2, cbfa1, and bone protein osteocalcin at the injured growth plate was assessed by quantitative RT-PCR. Effects of TNF-, signaling on proliferation, migration, and apoptosis of rat bone marrow mesenchymal cells (rBMMCs) and the regulatory roles of p38 in these processes were examined using recombinant rat TNF-,, ENBREL, and the p38 inhibitor SB239063 in cultured primary rBMMCs. Results: p38 activation was induced in the injured growth plate during the initial inflammatory response, and activated p38 was immunolocalized in inflammatory cells at the injury site and in the adjacent growth plate. In addition, activation of p38 was blocked in rats treated with TNF-, antagonist, suggesting a role of TNF-, in p38 activation. Whereas TNF-, inhibition did not alter inflammatory infiltrate and expression of TNF-, and IL-1, at the injured growth plate on day 1, it reduced mesenchymal infiltrate and cell proliferation and FGF-2 expression on day 8. Consistently, TNF-, increased proliferation and migration of rBMMCs in vitro, whereas p38 inhibition reduced rBMMC proliferation and migration. At the injured growth plate on day 8, TNF-, inhibition increased expression of cbfa1 and osteocalcin and increased trabecular bone formation at the injury site. There was a significant inverse correlation between TNF-, and cbfa1 expression levels, suggesting a negative relationship between TNF-, and cbfa1 in this in vivo model. Conclusions: These observations suggest that TNF-, activates p38 MAP kinase during the inflammatory response at the injured growth plate, and TNF-,-p38 signaling seems to be required for marrow mesenchymal cell proliferation and migration at the growth plate injury site and in cell culture. Furthermore, TNF signaling has an inhibitory effect on bone formation at the injured growth plate by suppressing bone cell differentiation and bone matrix synthesis at the injury site. [source] Monitoring 6-thioguanine nucleotide concentrations in Japanese children and adolescents with inflammatory bowel diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2010Yoshikazu Ohtsuka Abstract Background and Aim:, 6-Mercaptopurine (6-MP) and azathioprine (AZA) are widely used as maintenance therapy in children with inflammatory bowel disease (IBD). However, proper 6-thioguanine nucleotide (6-TGN) concentrations in Japanese children with IBD have not been reported. Methods:, This retrospective review examines 32 ulcerative colitis (UC) patients and 19 Crohn's disease (CD) patients (12.87 ± 3.56 years) who required 6-MP or AZA to maintain disease remission. All patients were treated with 6-MP or AZA for at least 3 weeks prior to this study in addition to previous treatment. 6-MP dose, 6-TGN levels, assayed by high-performance liquid chromatography, as well as laboratory data were evaluated. Results:, Thirty-five children were successfully kept in remission with 6-MP and AZA therapy after weaning off corticosteroids. Overall, 123 measurements (59 active disease, 64 in remission) were analyzed. The mean 6-TGN concentration of the entire study population was 499.61 ± 249.35 pmol/8 × 108 red blood cell. The mean 6-MP dose in patients with active disease (0.910 ± 0.326 mg/kg per day) was significantly higher than for patients in remission (0.749 ± 0.225) (P = 0.0016). A significant inverse correlation was found between white blood cell counts and 6-TGN concentrations (r = 0.275, P < 0.002). Two patients experienced leukopenia with alopecia, and four transiently experienced increased serum levels of pancreatic enzymes, although no thiopurine S-methyl transferase mutations were confirmed. Conclusion:, The doses of 6-MP or AZA needed to maintain remission in Japanese children with IBD are lower than those reported in Western countries. However, 6-TGN concentrations in this population are higher than previously reported. [source] Prevalence of undiagnosed coeliac syndrome in osteoporotic womenJOURNAL OF INTERNAL MEDICINE, Issue 4 2001R. Nuti Abstract.,Nuti R, Martini G, Valenti R, Giovani S, Salvadori S, Avanzati A (Institute of Internal Medicine, Metabolic Disease Unit, University of Siena, Siena, Italy). Prevalence of undiagnosed coeliac syndrome in osteoporotic women. J Intern Med 2001; 250: 361,366. Objectives.,The aims of the study were to quantify the prevalence of asymptomatic coeliac disease (CD) in a cohort of osteoporotic females, and to investigate the features of bone loss. Design and subjects.,We studied 255 women (mean age 66.6 ± 8.5 SD) with primary osteoporosis (WHO diagnostic criteria). After the first CD screening with the measure of serum IgG antigliadin antibodies (IgG-AGA), 53 women showed a positive test: antibodies to tissue transglutaminase (TG-ab) were subsequently determined to confirm the diagnosis of CD. Bone metabolism was evaluated by: serum and urinary calcium, serum and urinary phosphate, serum alkaline phosphatase, urinary crosslaps, serum 25(OH)D and serum parathyroid hormone. Results.,High levels of IgG-AGA and TG-ab were observed in 24 patients with a prevalence of serological disease of 9.4%. These women were characterized, in comparison with the other patients, by a statistically significant reduction in serum 25(OH)D (17.8 ± 7.2 vs. 55.1 ± 20.3 nmol L,1, P < 0.01) together with a significant increase of iPTH (65.1 ± 29.7 vs. 35.1 ± 20.0 pg mL,1; P < 0.01). Patients with high TG-ab levels showed also slightly raised values of urinary crosslaps (288 ± 88 vs. 270 ± 90 ,m mol,1 Cr). In IgG-AG positive patients a statistically significant inverse correlation was found between 25(OH)D serum levels and log-transformed TG-ab values (r: ,0.95, P < 0.001). Intestinal biopsies were obtained in 10 TG-ab positive women and verified CD in six patients. Conclusions.,These data support the hypothesis that patients with undiagnosed celiac disease develop high remodelling processes related to calcium malabsorption, secondary hyperparathyroidism and unavailability of vitamin D with a consequent more marked bone loss. [source] Expression levels of MDR1, MRP1, MRP4, and MRP5 in peripheral blood mononuclear cells from HIV infected patients failing antiretroviral therapyJOURNAL OF MEDICAL VIROLOGY, Issue 5 2008Ombretta Turriziani Abstract The aim of the study was to evaluate the mRNA expression of four relevant ABC-transporter genes [MDR1 (P-glycoprotein; Pgp), MRP1, MRP4, and MRP5] in HIV-positive individuals failing treatment and analyze the association between the levels of their expression and viral load, CD4 cell count, and therapeutic history. Ninety-eight HIV-positive samples and 20 samples from healthy donors were analyzed, retrospectively. Peripheral blood mononuclear cells (PBMCs) from HIV1-positive individuals were collected at the time of virological failure. Expression of mRNA of Pgp, MRP1, MRP4, and MRP5 in PBMCs was evaluated by real-time PCR. A high inter-individual variability was observed in both HIV-positive individuals and healthy donors but the expression levels of all mRNA analyzed were significantly higher in the HIV-infected group (P,<,0.05). A weak but significant inverse correlation was observed between CD4 cell counts and expression levels of MRP4 and MRP5. Comparison of mRNA expression between individuals with different therapeutic histories showed that expression of MRP4 and MRP5 genes in patients who were both protease inhibitor (PI) and non-nucleoside reverse transcriptase inhibitor (NNRTI)-experienced was significantly higher than in patients who were PI experienced but NNRTI-naďve. In conclusion, the mRNA expression of Pgp, MRP1, MRP4, and MRP5 varies among HIV-infected patients and healthy donors but is significantly higher in HIV-positive patients than in donors. The expression of MRP4 and MRP5 seems to correlate with CD4 cell counts. The same protein seems to be overexpressed in patients receiving NNRTIs. J. Med. Virol. 80:766,771, 2008. © 2008 Wiley-Liss, Inc. [source] The effect of highly active antiretroviral therapy for HIV on the anti-HCV specific humoral immune responseJOURNAL OF MEDICAL VIROLOGY, Issue 2 2004Esteban Herrero-Martínez Abstract The effect of highly active antiretroviral therapy (HAART) on HCV replication is controversial, with some studies reporting no effect and others increases, reductions and even clearances of HCV RNA after treatment. In this study, the effect of HAART was investigated on the titre of anti-HCV specific antibodies and on the relationship between these antibodies and HCV RNA level in a cohort of 24 patients with inherited bleeding disorders. A significant inverse correlation between antibodies to both total HCV proteins and HCV RNA (R,=,,0.42, P,=,0.05) and between antibodies to HCV envelope glycoproteins and HCV RNA (R,=,,0.54, P,=,0.01) was observed pre-HAART. The relationship disappeared or was obscured after therapy (R,=,0.24, P,=,0.30 and R,=,0.16, P,=,0.50, respectively). Thus, we show that HAART affects the HCV specific humoral immune responses without affecting the HCV RNA level. J. Med. Virol. 72:187,193, 2004. © 2004 Wiley-Liss, Inc. [source] Gastritis OLGA-staging and gastric cancer risk: a twelve-year clinico-pathological follow-up studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2010M. RUGGE Aliment Pharmacol Ther,31, 1104,1111 Summary Background, Intestinal-type gastric cancer (GC) still ranks among the high-incidence, highly lethal malignancies. Atrophic gastritis is the cancerization field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy-based) ranking of GC risk. Aim, To test the gastritis OLGA-staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression. Methods, Ninety-three Italian patients were followed up for more than 12 years (range: 144,204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow-up (T2). Results, All invasive or intra-epithelial gastric neoplasia were consistently associated with high-risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P < 0.001). OLGA-staging at T1 predicted both the OLGA stage (Kaplan,Maier log-rank test, P = 0.001) and the neoplasia at T2 (Kaplan,Maier log-rank test, P = 0.001). Conclusions, This long-term follow-up study provides the first evidence that gastritis OLGA-staging conveys relevant information on the clinico-pathological outcome of gastritis and therefore for patient management. According to OLGA-staging and H. pylori- status, gastritis patients could be confidently stratified and managed according to their different cancer risks. [source] Shock Coordinated with High Power of Morphology Electrogram Improves Defibrillation Success in Patients with Implantable Cardioverter DefibrillatorsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 9 2002ALEXANDER BERKOWITSCH BERKOWITSCH, A., et al.: Shock Coordinated with High Power of Morphology Electrogram Improves Defibrillation Success in Patients with Implantable Cardioverter Defibrillators. Animal studies have suggested that the success of defibrillation may depend on the properties of VF waveform obtained from the morphology electrogram (ME) at the time of the shock. The reliable identification of depolarization events in the fibrillatory signal can be achieved using adaptive estimation of the instantaneous signal power (P). The aim of this study was to investigate if a high P of the ME (PME) was related to ventricular DFT and if the upslope in ME can be associated with the depolarization event. A total of 575 VF (mean duration 10 s) episodes recorded and stored during ICD implantation in 77 patients with ventricular arrhythmias were used for analysis. The DFT was defined using a double step-down test. The values of PME immediately before pulse delivery (Pshock) and shock outcomes were registered. The differences between Pshock of successful and failed defibrillation were tested with the Mann-Whitney U test. The relationship between individual medians of Pshock (Pmed) and DFT was analyzed using the Kruskall-Wallis H-test. The coincidence between identified depolarization and upslope in ME was tested using the chi-square test. A P value of 0.05 was set for an error probability. The Pshock in case of failed defibrillation was significantly lower than Pshock in successful cases by the pulses of any strength (P < 0.001). The test revealed a significant inverse correlation between Pmed and DFT with P < 0.001. The depolarization corresponded to the upslope of ME in 85% of cases. This study demonstrated that a high value of instantaneous power of ME indicates the optimal time for shock delivery. The implementation of this algorithm in ICDs may improve the defibrillation efficacy. [source] Peroxisome proliferator-activated receptor gamma in human prostate carcinomaPATHOLOGY INTERNATIONAL, Issue 5 2009Yasuhiro Nakamura Peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear hormone receptor superfamily of transcription factors. Peroxisome proliferator-activated receptor gamma (PPAR,) plays an important role in the regulation of lipid homeostasis, adipogenesis, insulin resistance, and development of various organs. Agonists of PPAR, have been also reported to inhibit proliferation of prostate carcinoma cells as in other human malignancies, and these synthetic ligands have been used in differentiation-mediated therapy of various human carcinomas associated with high levels of PPAR,. The significance of PPAR, expression, however, was unknown in human prostate carcinoma tissues. The purpose of the present study was therefore to examine the immunolocalization of PPAR, in human prostate cancer tissues (40 cases) and correlate the findings with clinicopathological features of the patients in order to evaluate its possible biological significance. Twenty-nine patients were positive for PPAR, immunoreactivity (73%) and a significant inverse correlation was detected between PPAR, immunoreactivity, pT stage (P = 0.036), and serum concentration of prostate-specific antigen (P = 0.0004). In conclusion, PPAR, immunoreactivity is considered to be a new clinicopathological parameter of human prostate cancer. [source] Expression of KiSS-1 Gene and its Role in Invasion and Metastasis of Human Hepatocellular CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2009Zang Shengbing Abstract KiSS-1 has been identified as a putative metastasis-suppressor gene in human melanomas and breast cancer cell lines. Although loss of KiSS-1 expression has been associated with progression and poor prognosis of various cancers, the exact role of KiSS-1 expression in HCC is not well-defined. Our study investigated KiSS-1 expression levels in HCC and its role in invasion and metastasis of human HCC. The expression levels of KiSS-1 and MMP-9 protein were determined by tissue microarray (TMA) serial sections, immunohistochemistry and semi-quantitative image analysis. All clinical and histological data obtained were subjected to statistical analysis. The expression of KiSS-1 protein in HCC and intrahepatic metastasis lesions was significantly lower (P < 0.01) when compared with non-tumor liver tissue and normal liver tissue. Multivariate analysis revealed a significant inverse correlation between KiSS-1 expression and ,1 TNM stage, (F = 7.113, P < 0.01) and ,2intrahepatic metastasis (t = 2.898, P < 0.01). Loss of KiSS-1 in intrahepatic metastasis versus primary carcinomas was statistically significant (P<0.01). We also found a negative correlation between KiSS-1 and MMP-9 expression in HCC (r = -0.506, P < 0.01). We conclude that loss of KiSS-1 during HCC metastasis, along with a concomitant upregulation of MMP-9 suggests a possible mechanism for cell motility and invasion during HCC metastasis, with KiSS-1 emerging as a possible therapeutic target during HCC metastasis. Anat Rec, 292:1128,1134, 2009. © 2009 Wiley-Liss, Inc. [source] Serum leptin correlates in infertile oligozoospermic malesANDROLOGIA, Issue 5 2007S. Hanafy Summary Leptin is an adipocyte-secreted protein that participates in the regulation of energy homeostasis. Eighty men were investigated; fertile normozoospermia as a control (n = 30) and infertile oligozoospermia (n = 50). The patients underwent estimation of body weight (kg), height (cm), calculation of body mass index (BMI), semen analysis, serum leptin and testosterone hormones. Mean body weight was significantly higher in infertile oligozoospermia compared with controls. Mean height, BMI and serum testosterone levels showed nonsignificant differences between the two groups. Infertile oligozoospermia had significantly higher mean serum leptin level than controls (mean ± SD; 6.88 ± 8.65, 16.3 ± 13.98 ng ml,1, P < 0.01). Serum leptin demonstrated significant positive correlation with age, body weight, BMI and significant inverse correlation with serum testosterone. It had nonsignificant correlation with the height and sperm concentration. These results are suggestive of a link between the adipocyte derived hormone, leptin and male reproduction. [source] Patterns of growth of juvenile pink abalone Haliotis corrugata fed re-hydrated natural feeds at a laboratory and a hatcheryAQUACULTURE NUTRITION, Issue 3 2009E. SERVIERE-ZARAGOZA Abstract The feasibility of obtaining a similar growth response from juvenile pink abalone Haliotis corrugata at a research laboratory and a hatchery, when using natural feeds was evaluated. Four macroalgae, Egregia menziesii, Eisenia arborea, Macrocystis pyrifera, Gracilaria sp., and the surfgrass Phyllospadix torreyi were used as feeds. Response patterns of abalone were very similar at both facilities in terms of final length, weight, and survival, varying from 13.0 to 15.50 mm, 0.31 to 0.52 g, and 60.0% to 78.6%, respectively. Better growth was obtained when E. menziesii, M. pyrifera, and Gracilaria sp. were offered. Poor results were obtained with surfgrass. The feed conversion ratio was determined at the laboratory and did not vary significantly, ranging from 42.3 to 199.0; although a significant inverse correlation was observed with growth rate. Growth in length and weight and survival rates varied within 1.6,20.2 ,m day,1, 0.123,1.664 mgday,1, 0.4,0.64%day,1, respectively. Mean growth rate in length (14.7,m day,1) and weight (1.18 mg day,1) at the hatchery were significantly higher than that obtained at the laboratory (9.4 ,m day,1 and 0.77 mg day,1), which is most likely a consequence of more suitable water temperature at the hatchery. Mean survival rate was significantly higher at the laboratory (53.1%day,1) than at the hatchery (46.1%day,1). [source] Reduced CD4+,CD25, T cell sensitivity to the suppressive function of CD4+,CD25high,CD127,/low regulatory T cells in patients with active systemic lupus erythematosusARTHRITIS & RHEUMATISM, Issue 7 2008Ram Kumar Chowdary Venigalla Objective CD4+,CD25high regulatory T (Treg) cells play a crucial role in the maintenance of self tolerance and prevention of organ-specific autoimmunity. The presence of many in vivo,preactivated CD4+,CD25++ T cells in patients with systemic lupus erythematosus (SLE) poses a difficulty in discriminating CD25++ activated T cells from CD25high Treg cells. To overcome this problem, we analyzed the phenotype and function of CD4+,CD25high,CD127,/low natural Treg (nTreg) cells isolated from the peripheral blood of patients with SLE. Methods CD4+,CD25high,CD127,/low nTreg cells and CD4+,CD25, responder T (Tresp) cells from patients with SLE and normal donors were separated by fluorescence-activated cell sorting. Cell proliferation was quantified by 3H-thymidine incorporation, and immunophenotyping of the cells was done using FACScan. Results Comparable percentages of CD4+,CD25high,FoxP3+ T cells were observed in patients with SLE and normal donors. Proliferation of SLE nTreg cells sorted into the subset CD4+,CD25high,CD127,/low was significantly decreased compared with that of SLE nTreg cells sorted into the subset CD4+,CD25high (mean ± SEM 2,223 ± 351 counts per minute versus 9,104 ± 1,720 cpm, respectively), while in normal donors, these values were 802 ± 177 cpm and 2,028 ± 548 cpm, respectively, confirming that effector cell contamination was reduced. Notably, the suppressive activity of nTreg cells was intact in all groups. However, CD4+,CD25, Tresp cells isolated from patients with active SLE were significantly less sensitive than those from patients with inactive SLE to the suppressive function of autologous or normal donor CD4+,CD25high,CD127,/low nTreg cells. Furthermore, a significant inverse correlation was observed between the extent of T cell regulation in suppressor assays and the level of lupus disease activity. Conclusion This study is the first to show that, in human SLE, impaired sensitivity of Tresp cells to the suppressive effects of a comparably functional, highly purified nTreg cell population leads to a defective suppression of T cell proliferation in active SLE. Studies aiming to define the mechanisms leading to Tresp cell resistance might help in the development of highly specific, alternative immunotherapeutic tools for the control of systemic autoimmune diseases such as SLE. [source] Verapamil buffering effect on the abrupt elevation in blood pressure, linkage with microcirculatory blood flowAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 2-3 2008J. Gmitrov Summary 1 We studied the effects of verapamil on sudden elevation in blood pressure, microcirculation and arterial baroreflex sensitivity (BRS). 2 Thirty experiments (10 controls and 20 with verapamil) were performed in rabbits sedated using pentobarbital infusion (5 mg kg,1 h,1). 3 BRS, mean femoral artery blood pressure (MAP), heart rate (HR) and ear lobe skin microcirculatory blood flow, estimated using microphotoelectric plethysmography (MPPG), were simultaneously measured during 30 min of verapamil infusion (20 ,g kg,1 min,1). BRS was assessed from HR and MAP responses to intravenous phenylephrine (Ph) and by power spectral analysis using transfer function (TF) from MAP to the HR (BRSPh,TF). 4 Verapamil significantly increased microcirculatory blood flow, and decreased BRSPh,TF and phenylephrine-induced abrupt elevation in MAP (MAPAE). 5 A significant inverse correlation was found between verapamil-induced changes in MAPAE, BRS and in microcirculatory blood flow, measured before phenylephrine blood pressure ramps (,MAPAE with ,BRSTF, r = ,0.47, P < 0.036; ,MAPAE with ,MPPG, r = ,0.49, P < 0.025). 6 These results suggest involvement of the arterial baroreflex and vascular blood pressure-buffering mechanisms, their enhancement by verapamil, and thus a potential benefit of verapamil in cardiovascular conditions where patients present with abrupt high elevations in blood pressure. [source] Changes of plasma vascular endothelial growth factor level after uterine artery embolisation for leiomyomataBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2005Takashi Takeda Uterine artery embolisation (UAE) has become an alternative treatment for symptomatic uterine leiomyomata. Most reports suggest that it is well tolerated and effective, although there have been no reports of studies of biological parameters after UAE. In this study, we analysed the plasma level of vascular endothelial growth factor (VEGF) and the pulsatility index (PI) of uterine arteries before and after UAE. The level of plasma VEGF increased significantly after UAE (on day 1 and day 3) and decreased on day 7, and then increased again on day 30. The level of VEGF reached a peak value within three days after UAE. A significant inverse correlation was found between uterine artery PI and the level of VEGF on day 30, suggesting that VEGF may have negative effect on the efficacy of treatment of uterine leiomyomata by UAE. [source] Circulating free nitrotyrosine and cognitive declineACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010L. Coppola Coppola L, Pastore A, Adamo G, Coppola A, Manzella D, Gombos I, Luongo M, Mastrolorenzo L. Circulating free nitrotyrosine and cognitive decline. Acta Neurol Scand: 122: 175,181. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To determine if the circulating nitrotyrosine level significantly correlates with parameters measuring cognitive abilities. Materials and methods,,, One-hundred and twelve community-living subjects (ranging in age from 27 to 98 years) were evaluated for cognitive abilities [Mini Mental State Examination (MMSE) score] and circulating free nitrotyrosine plasma level, as well as for several variables that might influence cognitive abilities (age, education) and nitrotyrosine level (body mass index, haematological parameters, cardiovascular and inflammatory indices). Results,,, In the sub-group of cognitively impaired subjects (score at MMSE <23.9), but not in that of cognitively not impaired subjects, a significant inverse correlation exists between nitrotyrosine level and MMSE score (r = ,0.378; P < 0.02). Conclusions,,, The finding, if confirmed by longitudinal studies, could play a role in the management of the subjects with Mild Cognitive Impairment, the clinical condition considered as a transitional state between the changes of cognitive ability in normal aging and dementia. [source] Clinicopathologic significance of dysadherin expression in cutaneous malignant melanomaCANCER, Issue 8 2005Immunohistochemical analysis of 115 patients Abstract BACKGROUND The E-cadherin,mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, the authors reported a novel cell membrane glycoprotein, dysadherin, which has an anti,cell-cell adhesion function and down-regulates E-cadherin. METHODS Expression of both dysadherin and E-cadherin was investigated immunohistochemically in 115 patients with cutaneous malignant melanoma to determine the correlation between the 2 molecules and their associations with both patient survival and the clinicopathologic features of the tumors. RESULTS Dysadherin and E-cadherin were expressed at the cell membranes of melanoma cells. Fifty-two percent of the tumors showed dysadherin immunopositivity, and 91% of the tumors showed reduced E-cadherin immunopositivity. There was no significant inverse correlation between dysadherin expression and E-cadherin expression. Increased dysadherin expression was significantly correlated with nodular subtype (P = 0.042), Clark level (P < 0.001), tumor thickness (P < 0.001), ulceration (P = 0.008), lymph node metastasis (P < 0.001), high TNM classification (P < 0.001), and poor patient survival (P < 0.001). Multivariate analysis of patient survival revealed that increased dysadherin expression was a significant predictor of poor survival (P < 0.001). CONCLUSIONS Thus, increased expression of dysadherin was a significant indicator of poor prognosis in patients with cutaneous malignant melanoma. Cancer 2005. © 2005 American Cancer Society. [source] In vivo IL-10 and TGF-, production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stabilityCLINICAL TRANSPLANTATION, Issue 2 2004Josefina Alberú Abstract:, Background:, Interleukin-10 (IL-10) and transforming growth factor-, (TGF-,) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-, by blood mononuclear cells correlates with excellent long-term graft function. Methods:, A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-, were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors. Results:, There was no correlation between IL-10 or TGF-, with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 ± 465, range 12.5,1929.3 pg/ml, and 189 ± 170, range 4.17,485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-, among the same groups (134.7 ± 79.2, range 68,421 pg/ml, and 121.4 ± 25.8, range 75,151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-, in kidney transplant recipients (p = 0.03). Conclusions:, The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-, and IL-10 may be of paramount importance in graft acceptance. [source] The association between leukocyte telomere length and cigarette smoking, dietary and physical variables, and risk of prostate cancerAGING CELL, Issue 4 2009Lisa Mirabello Summary Telomeres consist of nucleotide repeats and a protein complex at chromosome ends that are essential to maintaining chromosomal integrity. Several studies have suggested that subjects with shorter telomeres are at increased risk of bladder and lung cancer. In comparison to normal tissues, telomeres are shorter in high-grade intraepithelial neoplasia and prostate cancer. We examined prostate cancer risk associated with relative telomere length as determined by quantitative PCR on prediagnostic buffy coat DNA isolated from 612 advanced prostate cancer cases and 1049 age-matched, cancer-free controls from the PLCO Cancer Screening Trial. Telomere length was analyzed as both a continuous and a categorical variable with adjustment for potential confounders. Statistically significant inverse correlations between telomere length, age and smoking status were observed in cases and controls. Telomere length was not associated with prostate cancer risk (at the median, OR = 0.85, 95% CI: 0.67, 1.08); associations were similar when telomere length was evaluated as a continuous variable or by quartiles. The relationships between telomere length and inflammation-related factors, diet, exercise, body mass index, and other lifestyle variables were explored since many of these have previously been associated with shorter telomeres. Healthy lifestyle factors (i.e., lower BMI, more exercise, tobacco abstinence, diets high in fruit and vegetables) tended to be associated with greater telomere length. This study found no statistically significant association between leukocyte telomere length and advanced prostate cancer risk. However, correlations of telomere length with healthy lifestyles were noted, suggesting the role of these factors in telomere biology maintenance and potentially impacting overall health status. [source] Cross-sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire in patients with IPFRESPIROLOGY, Issue 6 2008Shouchun PENG Background and objective: This study was performed to confirm the cross-sectional and longitudinal construct validity of the Saint George's Respiratory Questionnaire (SGRQ) for the measurement of health-related quality of life (HRQoL) in patients with IPF. Methods: Sixty-eight patients with IPF responded to the SGRQ and pulmonary function tests (PFT), dyspnoea testing, arterial blood gas analysis, 6-min walk tests (6MWT) and high-resolution computed tomography were performed in a baseline study. A follow-up study was performed on 45 of these patients. Results: In the baseline study HRQoL as measured by the SGRQ was substantially impaired in IPF patients, especially in symptoms and activity domains. A significant decline in HRQoL was observed in the activity domain during follow up. TLC and changes in TLC showed the most significant inverse correlations with each SGRQ domain (r < ,0.3, P < 0.05). In a stepwise multiple regression analysis, TLC contributed most significantly to each SGRQ component baseline score. Similar results were also observed during follow up. There was a significant correlation between total CT scores and each component of the SGRQ (r > 0.3, P , 0.001). Changes in ground-glass opacity on CT (CT-alv) were also correlated with changes in each SGRQ domain (r > 0.3, P , 0.001). Stepwise multiple regression analysis showed that interstitial opacity on CT (CT-fib) contributed to variation in the baseline activity score, and that changes in CT-alv independently contributed to overall changes in the SGRQ domains during follow up. The dyspnoea score, and changes in the dyspnoea score, correlated significantly with the SGRQ sores, with the exception of the symptoms score, in both the baseline and follow-up studies. Conclusions: HRQoL as assessed by the SGRQ showed good cross-sectional and longitudinal construct validity in patients with IPF. However, additional studies are required to analyse the reliability and responsiveness so that the SGRQ can be used in patients with IPF. [source] | ||||||||||||||||||||||||||||