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PubMed2005

p53 mutations and human papillomavirus infection in oral squamous cell carcinomas: correlation with overall survival.

PURPOSE: The study investigated the pattern of p53 gene mutations and human papillomavirus (HPV) infection concerning their relation to overall survival in patients with oral squamous cell carcinomas of the tongue and floor of the mouth. PATIENTS AND METHODS: The presence of HPV infection in 50 patients, and p53 gene mutations (42 patients from the same group) in the tumour specimens were analysed by polymerase chain reaction and single-stranded conformational polymorphism method. The follow-up period ranged from 12 to 48 (median 29) months. RESULTS: p53 mutations were identified in 11/42 tumours. HPV infection was detected in 32/50 cases, mostly HPV16 (10/32), HPV18 and HPV31 (6/32). A significantly higher incidence of HPV infection was found among smokers (p<0.05) and among patients with poor oral hygiene (p<0.01). The highest incidence of p53 mutations was detected in tumours of histological grade I and nuclear grade III. Patients with p53 mutation or with HPV infection had significantly shorter overall survival when compared with those that were without p53 mutations (p<0.01) or HPV infection (p<0.05). HPV-infected patients with p53 mutation had the worst prognosis when compared with patients with HPV infection only (p<0.01) or with patients negative for both HPV and p53 (p<0.01). CONCLUSION: The results stress once more the importance of HPV for the prognosis of survival of patients with squamous cell carcinoma of lower parts of the oral cavity. The presence of p53 mutations in HPV-infected tumours was associated with an even poorer prognosis for the patients.

Adult↗
PubMed2006

Macrophage entry mediated by HIV Envs from brain and lymphoid tissues is determined by the capacity to use low CD4 levels and overall efficiency of fusion.

HIV infects macrophages and microglia in the central nervous system (CNS), which express lower levels of CD4 than CD4+ T cells in peripheral blood. To investigate mechanisms of HIV neurotropism, full-length env genes were cloned from autopsy brain and lymphoid tissues from 4 AIDS patients with HIV-associated dementia (HAD). Characterization of 55 functional Env clones demonstrated that Envs with reduced dependence on CD4 for fusion and viral entry are more frequent in brain compared to lymphoid tissue. Envs that mediated efficient entry into macrophages were frequent in brain but were also present in lymphoid tissue. For most Envs, entry into macrophages correlated with overall fusion activity at all levels of CD4 and CCR5. gp160 nucleotide sequences were compartmentalized in brain versus lymphoid tissue within each patient. Proline at position 308 in the V3 loop of gp120 was associated with brain compartmentalization in 3 patients, but mutagenesis studies suggested that P308 alone does not contribute to reduced CD4 dependence or macrophage-tropism. These results suggest that HIV adaptation to replicate in the CNS selects for Envs with reduced CD4 dependence and increased fusion activity. Macrophage-tropic Envs are frequent in brain but are also present in lymphoid tissues of AIDS patients with HAD, and entry into macrophages in the CNS and other tissues is dependent on the ability to use low receptor levels and overall efficiency of fusion.

AIDS Dementia Complex↗
PubMed2024

Extreme overall mushroom genome expansion in Mycena s.s. irrespective of plant hosts or substrate specializations.

Mycena s.s. is a ubiquitous mushroom genus whose members degrade multiple dead plant substrates and opportunistically invade living plant roots. Having sequenced the nuclear genomes of 24 Mycena species, we find them to defy the expected patterns for fungi based on both their traditionally perceived saprotrophic ecology and substrate specializations. Mycena displayed massive genome expansions overall affecting all gene families, driven by novel gene family emergence, gene duplications, enlarged secretomes encoding polysaccharide degradation enzymes, transposable element (TE) proliferation, and horizontal gene transfers. Mainly due to TE proliferation, Arctic Mycena species display genomes of up to 502 Mbp (2-8&#xd7; the temperate Mycena), the largest among mushroom-forming Agaricomycetes, indicating a possible evolutionary convergence to genomic expansions sometimes seen in Arctic plants. Overall, Mycena show highly unusual, varied mosaic-like genomic structures adaptable to multiple lifestyles, providing genomic illustration for the growing realization that fungal niche adaptations can be far more fluid than traditionally believed.

Genome, Fungal↗
PubMed1996

Impact of the implantable defibrillator on mortality: the axiom of overall implantable cardioverter-defibrillator survival.

As soon as it was established that the implantable cardioverter-defibrillator (ICD) effectively prevents sudden death, it became axiomatic that whether the ICD will prolong overall survival depends entirely on the population of patients to which it is applied. This axiom of overall ICD survival immediately reveals the only vital question that remains regarding usage of the ICD; namely, How does one select those patients in whom prevention of sudden death by the ICD will also prolong life? This axiom also reveals the essential futility of randomized trials now being conducted for the purpose of discerning the true efficacy of the ICD. Claims to the scientific high ground notwithstanding, if a study asks the wrong question from the beginning, then the design of that study (including whether the study is randomized or nonrandomized), is completely irrelevant. Ideally, funds now being spent on these randomized trials should be diverted to the design and initiation of more appropriate trials, trials that will teach us to select patients for the ICD more effectively. At the very least, however, we should recognize the problems inherent in the ongoing trials, so that when their results are finally published (and are loudly touted by whichever faction feels vindicated by them), we will not be carried away into inappropriate clinical behavior.

Arrhythmias, Cardiac↗
PubMed1986

Overall and regional lung function in dogs exposed acutely to ozone.

Regional distribution of ventilation and overall function of the lungs were compared in anesthetized, paralyzed, mechanically ventilated dogs exposed to ozone. Three animals were exposed at each concentration (0,0.13,0.22, and 0.45 ppm ozone) for 3 hr. There were no significant changes in pulmonary flow resistance, dynamic compliance, or flow rates derived from maximum forced expiratory maneuvers. The distribution of inspired gas was determined using air containing 13N and a positron camera to follow wash-in in each of 80 or more regions of the lung. The mean wash-in time (T) and its standard deviation did not change in sham-treated dogs, but T increased by 40 to 100% in exposed animals. Dogs showing increases in T also had increased frequency dependence of compliance (correlation significant at P less than 0.05). The changes in 13N wash-in reflected less uniform distribution of ventilation, with the greatest disparity occurring between central and marginal regions. Altered regional mechanical function, in the absence of overall changes, suggested that the initial effect of ozone was on the small airways. The measurement may be a sensitive indicator of acute irritation in the lung periphery.

Animals↗
PubMed1989

Delayed fertilization during in vitro fertilization and embryo transfer cycles: analysis of causes and impact on overall results.

This study evaluated possible causes of delayed fertilization during in vitro fertilization (IVF) cycles, its repetitiveness, and its influence on IVF results in 23 patients (27 cycles) with delayed fertilization of greater than or equal to 1 preovulatory oocyte(s). In 15 cycles, reinsemination with husband's semen was performed at 18 hours. Possible causes of delayed fertilization were oocyte defects (10 cycles, 37.0%), sperm defects (4 cycles, 14.8%), oocyte and sperm defects (4 cycles, 14.8%), and no detectable gamete defects (9 cycles, 33.3%). Overall fertilization rate was 47.9%. No pregnancies were observed in 10 patients with one embryo transferred. Recurrence rate of delayed fertilization per patient was 17.3%; overall ongoing pregnancy rate/cycle was 10.3%. Although repetitiveness of delayed fertilization is low, it seems to impact negatively on IVF results.

Embryo Transfer↗
PubMed1987

Measuring overall health: an evaluation of three important approaches.

There is growing recognition that meaningful measures of health-related quality of life must be used to evaluate health care interventions. We examined the practicality and validity of three promising measures of overall health: the General Health Rating Index (GHRI), the Quality of Well-being Scale (QWB), and the Sickness Impact Profile (SIP). Practicality was assessed in terms of interviewer training required, administration time, and respondent burden. Content validity, convergent construct validity, and tests of discriminant validity were also evaluated. Although differing in theory and application, we found that each instrument performed according to the claims of the developers and could provide useful, valid data on overall health. The GHRI may be preferred where brief, self-administered forms are required; the QWB has advantages when health assessments are used to calculate cost-effectiveness; and the SIP is a versatile, easy to understand measure dealing with a wide range of specific dysfunctions. It is worth the required effort to include well-studied measures such as these in any trial intended to provide definitive information on the effectiveness of health care interventions.

Activities of Daily Living↗
PubMed1996

Techniques for improving overall consistency of serial ECG analysis.

The techniques that improve the overall repeatability of computer interpretation of electrocardiograms (ECGs) that have been recorded several minutes apart from patients in a clinically stable condition are described. Estimates of the normal amounts of variability present in many ECG parameters that are used in the identification of a variety of cardiac abnormalities have been adopted in conjunction with smoothing techniques to form the basis of the new methodology. When applied to the Glasgow ECG analysis program, these new methods improve overall repeatability by about 31% when tested on a set of 263 pairs of ECGs. Randomly generated noise was added to the test set and an additional technique aimed at removing noise from the ECG tracings was used in conjunction with the smoothing methods. The observed improvement over the original repeatability was 63%.

Adult↗
PubMed2002

Skeletal fractures negatively correlate with overall survival in men with prostate cancer.

PURPOSE: We assessed the correlation of skeletal fracture with survival in men with prostate cancer on chronic androgen suppressive therapy. MATERIALS AND METHODS: A total of 195 consecutive patients on chronic androgen suppression for prostate cancer were evaluated for the history and type of skeletal fracture. Correlation with overall survival was performed via multivariate analysis. RESULTS: Of these 195 men 24 reported skeletal fracture since the diagnosis of prostate cancer. Median overall survival was 121 and 160 months in men without and with a history of skeletal fracture since the diagnosis of prostate cancer, respectively (p = 0.04). A history of skeletal fracture was retained as a negative predictor of survival on forward stepwise regression analysis (RR = 7.4, p = 0.007). CONCLUSIONS: Our results suggest that skeletal fracture in patients with prostate cancer is an independent and adverse predictor of survival. Consideration for screening men at greatest risk via bone mineral density measurements and initiating empirical skeletal therapies (bisphosphonates, estrogens and so forth) may be warranted. This recommendation awaits validation through prospective randomized trials.

Adenocarcinoma↗
PubMed2003

Fenton oxidation of cork cooking wastewater--overall kinetic analysis.

In the present work, the possibility of using chemical oxidation through Fenton's reagent for the pre-treatment of cork cooking wastewaters was exploited. Aiming both the selection of the best operating conditions (pH, Fe2+:H2O2 ratio and initial H2O2 concentration) and the evaluation of the overall reaction kinetics, trials were performed in a batch reactor. Operating at pH = 3.2, H2O2 concentration = 10.6 g/L and Fe2+:H2O2 ratio = 1:5 (by weight), about 66.4% of total organic carbon (TOC), 87.3% of chemical oxygen demand (COD) and 70.2% of biochemical oxygen demand (BOD5) were removed and an increase of the BOD5/COD ratio from 0.27 to 0.63 was achieved. In the temperature range 20-50 degrees C, the best performance was obtained at 30 degrees C. The kinetic study was undertaken at different initial TOC concentrations and temperatures. Overall kinetics can be described by a second-order followed by a zero-order rate equation and the apparent kinetic constants at 30 degrees C are k = 2.3 x 10(-4) L/mg min and k0 = 26.0 mg/L min, respectively. The experiments performed at different temperatures confirmed the global kinetic model and allowed to calculate the global activation energy for the second-order reaction (70.7 kJ/mol).

Hot Temperature↗
PubMed2002

Overall haemostasis potential assays performed in thrombophilic plasma: the effect of preactivating protein C and antithrombin.

INTRODUCTION: The overall haemostatic potential (OHP) assay records fibrin polymerisation in plasma by areas under the opacity curve. The authors reported high area values in pregnancy, and still higher values in preeclampsia. We wanted to see if the assay detects thrombophilia, and particularly, if the area values were high in congenital combined protein S (PS) and the FV R506Q Leiden mutation, since low protein S and increased activated protein C (APC) resistance occur in pregnancy and preeclampsia. MATERIALS AND METHODS: The original overall haemostatic potential assay and our modified version with Protac and pentasaccharide to enhance inhibition by activation of protein C and by antithrombin (AT) were performed in plasma from 18 persons with thrombophilia. Seven had combined protein S deficiency and heterozygous FV Leiden mutation. RESULTS: In the original assay, median area values in controls and thrombophilic plasma samples were similar. In the modified assay, area values tended to be lower in controls than in the thrombophilia group (P=0.035). The enhanced inhibition reduced area values more in control plasmas (median reduction 34.7%) than in thrombophilic plasmas (median reduction 2.2%) (P=0.0017). The responses to activation were also low in warfarin-treated patients with thrombophilia. CONCLUSIONS: High area values in pregnancy with the original assay are probably not caused by insufficient inhibition. The response to activation of protein C and antithrombin, as calculated by the difference between the original and a modified assay, was subnormal in thrombophilic plasma, but there was an overlap with the results in controls.

Adult↗
PubMed2003

Is platelet aggregation a more important contributor than platelet adhesion to the overall platelet-related primary haemostasis measured by PFA-100?

BACKGROUND: Platelet-related primary haemostasis (PRPH), measured in PFA-100 as a closure time (CT), reflects platelets' combined ability to adhere and aggregate under higher shear stress. The inputs of platelet aggregation and platelet adhesion into the real values of CT remain unknown, and this poor discrimination results in the complexity of the PFA-100 measurement. OBJECTIVE: To estimate the particular contributions of two physiological phenomena, platelet aggregation and adhesion, and the importance of various membrane receptors underlying platelets' capability of the plug formation in PFA-100 cartridges. MATERIALS AND METHODS: Effects of various blockers antagonizing ligands binding to platelet surface membrane receptors (antagonists of GPIIb-IIIa complex, collagen receptors and purinoreceptors), and aurintricarboxylic acid (ATA), the antagonist of GPIb-von Willebrand factor (vWF) interaction, were monitored in 47 healthy donors with the use of PFA-100 and whole blood electrical aggregometry (WBEA). RESULTS: PFA-100 collagen/ADP CT was the most sensitive in probing the effect of platelet membrane receptor antagonists acting via the blockade of GPIIb-IIIa complex and those antagonizing GPIb-vWF interaction (GR144053F, Integrilin, ATA), whereas the other blockers, acting on collagen receptors or purinoreceptors, remained much less efficient. For the examined GPIIb-IIIa and GPIb antagonists, the overall variability in WBEA explained a very significant part (30-60%) of the overall variability in PFA-100 CT. CONCLUSIONS: GPIIb-IIIa-mediated platelet aggregation and von Willebrand factor interactions with GPIb and/or GPIIb-IIIa seem to be the major determinants of PFA-100 CT. On the contrary, other platelet receptors participating in platelet aggregation and/or platelet adhesion are of secondary importance and minor significance in blood flow at higher shear stress monitored in PFA-100.

Adult↗
PubMed2003

Family income a strong predictor of coronary heart disease events but not of overall deaths among Turkish adults: a 12-year prospective study.

OBJECTIVE: The objective of this study was to assess whether family income affected future deaths and coronary heart disease (CHD) events. DESIGN: A prospective population-based survey (the Turkish Adult Risk Factor study) was used. SETTING: The setting was numerous communities in all geographic regions of Turkey surveyed between 1990 and 2001/2002. SUBJECTS: The subjects were a random sample of 2704 men and women 20 years of age or over at baseline examination. METHOD: Monthly family incomes were categorized by the participants into four increasing brackets. Information on the mode of deaths was obtained from first-degree relatives and/or health personnel of the local heath office. The diagnosis of definite or suspected CHD among survivors was based on history, physical examination of the cardiovascular system, and Minnesota coding of resting ECGs. CHD event was defined as newly developed fatal or nonfatal myocardial infarction, new onset stable angina, and/or myocardial ischemia following the baseline survey. After exclusion of participants with CHD at onset, 250 deaths and 297 fatal and nonfatal CHD occurred among 2704 men and women (mean age 41.6+/-15) during a mean 10.0 years of follow-up. MAIN RESULTS: All-cause deaths failed to be significantly associated with income brackets in logistic regression analysis when adjusted for age, sex, and three major risk factors. Systolic blood pressure and cigarette smoking were significant independent predictors of overall mortality. In regard to fatal and nonfatal CHD, even after adjusting for age, sex and three major risk factors, a significant excess was noted in the two lowest brackets as opposed to the high income bracket (relative risk 1.56 and 1.75, respectively, P<0.03). CONCLUSIONS: Family income in the Turkish community was not predictive of overall mortality, but was strongly predictive of future CHD events independent of age, sex, and three major factors, posing a huge coronary risk on the individual and the society.

Adult↗
PubMed2003

Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme.

BACKGROUND: Patients with chronic heart failure (CHF) are at high risk of cardiovascular death and recurrent hospital admissions. We aimed to find out whether the use of an angiotensin-receptor blocker could reduce mortality and morbidity. METHODS: In parallel, randomised, double-blind, controlled, clinical trials we compared candesartan with placebo in three distinct populations. We studied patients with left-ventricular ejection fraction (LVEF) 40% or less who were not receiving angiotensin-converting-enzyme inhibitors because of previous intolerance or who were currently receiving angiotensin-converting-enzyme inhibitors, and patients with LVEF higher than 40%. Overall, 7601 patients (7599 with data) were randomly assigned candesartan (n=3803, titrated to 32 mg once daily) or matching placebo (n=3796), and followed up for at least 2 years. The primary outcome of the overall programme was all-cause mortality, and for all the component trials was cardiovascular death or hospital admission for CHF. Analysis was by intention to treat. FINDINGS: Median follow-up was 37.7 months. 886 (23%) patients in the candesartan and 945 (25%) in the placebo group died (unadjusted hazard ratio 0.91 [95% CI 0.83-1.00], p=0.055; covariate adjusted 0.90 [0.82-0.99], p=0.032), with fewer cardiovascular deaths (691 [18%] vs 769 [20%], unadjusted 0.88 [0.79-0.97], p=0.012; covariate adjusted 0.87 [0.78-0.96], p=0.006) and hospital admissions for CHF (757 [20%] vs 918 [24%], p<0.0001) in the candesartan group. There was no significant heterogeneity for candesartan results across the component trials. More patients discontinued candesartan than placebo because of concerns about renal function, hypotension, and hyperkalaemia. INTERPRETATION: Candesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure. Ejection fraction or treatment at baseline did not alter these effects.

Adolescent↗
PubMed2002

A multicentre randomized/controlled trial of a conventional versus modestly accelerated radiotherapy in the laryngeal cancer: influence of a 1 week shortening overall time.

BACKGROUND AND PURPOSE: To compare in a phase III study the loco-regional control, disease-free survival and overall survival induced by an accelerated regimen (AF) as compared with conventional regimen (CF) and to analyze the early and late post-radiation morbidity in both arms. MATERIALS AND METHODS: Patients with age < or = 75, WHO 0-1, suitable for a radical course of radiotherapy T1-T3, N0, M0, stage of glottic and supraglottic laryngeal cancer were randomized to either CF: 66Gy given in 33 fractions over 45 days or AF: 66Gy given in 33 fractions over 38 days (2 fractions every Thursday). A total of 395 patients were included from 05.1995 to 12.1998. RESULTS: Early toxicity: At the end of radiotherapy patients treated with AF complained for more severe reactions than patients treated with CF. In 8 weeks after treatment completion patients treated with AF complained only for more severe pain on swallowing (P=0.027). In 4 months after treatment completion all types of toxicity except for skin teleangiectasia (P=0.001) were similar in the two groups. Loco-regional control: comparison between CF and AF showed no difference in terms of loco-regional control (P=0.37). CONCLUSIONS: The improvement in AF in terms of loco-regional control is estimated to be 3-5% in comparison with conventional regimen and is not significant. The intensity of reactions after 4 months was similar in both arms, what suggests the possibility of further shortening of the overall time by few days or enhancing the total dose within the limits of acceptable morbidity.

Aged↗
PubMed1985

The influence of overall treatment time on renal injury after multifraction irradiation.

The influence of overall treatment time on the radiation response of the mouse kidney was studied in an experiment in which 16 fractions were administered either evenly distributed over 20, 40 or 80 days, or as a split course (8 F/3 days; 74 days rest; 8 F/3 days). Urine output and an isotope assay of glomerular filtration were used to test the mice sequentially. The data were used both to obtain dose-response curves and also to determine the latent period before a chosen level of injury was expressed functionally. Prolonging the overall time from 20 to 80 days increased the isoeffect dose by 2-5 Gy (4-9%) for the isotope assay, and by 4-9 Gy (7-18%) for the urine output assay. This additional recovery as the interval between fractions was prolonged from 1 to 5 days is consistent with slow repair and can be expressed as a small "T" exponent of 0.02-0.12. (One analysis gave a result consistent with negative repair, but the errors on this result were unusually wide.) When the radiation was given as a split course, at the rate of 2 fractions per day, with a large gap of 10.5 weeks between courses, there was no additional sparing compared with 16 fractions over 20 days. This indicates that any sparing that might have resulted from slow repair or stimulated repopulation in the gap has been counterbalanced by having less time for repair of sublethal injury when intervals of 6-12 h are used instead of 24-48 h. Clearly no great increase in the tolerance dose for mouse kidney resulted from the split course.

Animals↗
PubMed1997

Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation.

PURPOSE: Accelerated repopulation of tumor cells during radiotherapy has been suggested as an important cause of treatment failure in squamous cell carcinoma of the head and neck. Due to tumor heterogeneity, not all tumors may benefit from accelerated radiotherapy at the expense of a lower total dose. This analysis evaluates the impact of histological differentiation on loco-regional control in relation to treatment duration. PATIENTS AND METHODS: A total of 501 patients with advanced supraglottic and pharyngeal squamous cell carcinoma with known histopathological grading were treated with planned split-course (191 patients) or continuous radiotherapy (310 patients) in two consecutive randomized controlled trials. Irradiation was given 2 Gy per fraction, 5 fractions per week to a dose of 66-68 Gy in 9.5 or 6.5 weeks, respectively. RESULTS: Overall, split-course and continuous treatment resulted in a 5-year loco-regional control of 30% and 41% (P = 0.007), respectively. However, the detrimental effects of split-course were only found in moderately and well-differentiated tumors, where the 5-year tumor controls were 38% and 21% after continuous and split-course treatment, respectively (P = 0.001). In contrast, in poorly differentiated tumors loco-regional control was obtained in 44% of the cases for continuous and 40% for split-course treatment (P = 0.63). CONCLUSIONS: It is suggested that the ability to accelerate repopulation may be lost by dedifferentiation, and that prolongation of the overall treatment time only lead to reduced loco-regional control in well to moderately differentiated tumors.

Carcinoma, Squamous Cell↗
PubMed1999

Impact of overall treatment time on local control of slow growing human GL squamous cell carcinoma in nude mice treated by fractionated irradiation.

BACKGROUND AND PURPOSE: The impact of overall treatment time of fractionated irradiation on local control of slow growing human GL squamous cell carcinoma (SCC) was determined. MATERIALS AND METHODS: Moderately well differentiated and keratinizing human GL SCC with a volume doubling time of 8 days were transplanted subcutaneously into the right hindleg of NMRI (nu/nu) mice and irradiated with 30 fractions under ambient conditions over 2, 3, 4.5, 6 and 10 weeks. Endpoint of the experiments was local tumor control at day 180 after end of treatment. RESULTS: The tumor control dose 50% (TCD50) increased from 40 to 57 Gy when the treatment time was extended from 2 to 10 weeks. The data can be well described by a linear increase in TCD50 with time. The recovered dose per day (D(r)) was 0.28 Gy (95% confidence interval 0.06; 0.48). The fit to the data was not significantly improved by assuming a biphasic (dog-leg) time course with constant TCD50 values in the initial part of treatment followed by a more rapid increase of TCD50 thereafter. CONCLUSIONS: D(r) in GL SCC was significantly less than the value of 1.0 Gy (0.7; 1.3) previously reported for poorly differentiated, non-keratinizing and fast growing human FaDu SCC (Baumann M, Liertz C, Baisch H, Wiegel T, Lorenzen J, Arps H. Impact of overall treatment time of fractionated irradiation on local control of human FaDu squamous cell carcinoma in nude mice. Radiother. Oncol. 1994:32:137-143), indicating important heterogeneity of the time factor between different tumors of the same histological type.

Algorithms↗