992 resultados para 03091030 TM-6
Resumo:
The title compound, C24H24N2O3S, exhibits antifungal and antibacterial properties. The compound crystallizes with two molecules in the asymmetric unit, with one molecule exhibiting 'orientational disorder' in the crystal structure with respect to the cyclohexene ring. The o-toluidine groups in both molecules are noncoplanar with the respective cyclohexene-fused thiophene ring. In both molecules, there is an intramolecular N-H...N hydrogen bond forming a pseudo-six-membered ring which locks the molecular conformation and eliminates conformational flexibility. The crystal structure is stabilized by O-H...O hydrogen bonds; both molecules in the asymmetric unit form independent chains, each such chain consisting of alternating 'ordered' and 'disordered' molecules in the crystal lattice.
Resumo:
In the molecule of the title compound, C20H23NO3, the bulky methoxyphenyl substituents at the equatorial 2,6-positions crowd the vicinity of the equatorial amino H atom and prevent it from forming intermolecular hydrogen bonds. The piperidine ring adopts a distorted chair conformation.
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The quinolinyl fused-ring of the title compound, C11H8ClNO, is almost planar (r.m.s. deviation = 0.013 Å); the formyl group is slightly bent out of the plane of the fused ring system [C-C-C-O torsion angle = 13.5 (4)°].
Resumo:
In the title compound, C17H10Br2O5, the chromene ring is almost planar with minimal puckering [total puckering amplitude = 0.067 (4) angstrom]. The dihedral angle between chromeme ring system and phenyl ring is 3.7 (2)degrees. The crystal structure is stabilized by intermolecular C-H center dot center dot center dot O interactions and an intramolecular O-H center dot center dot center dot O hydrogen bond also occurs.
Resumo:
The Jorvi Bipolar Study (JoBS) is a collaborative ongoing bipolar research project between the Department of Mental Health and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital (HUCH), Espoo, Finland. The JoBS is a prospective, naturalistic cohort study of secondary level care psychiatric out-and inpatients with a new episode of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) bipolar disorder (BD). Altogether, 1630 patients (aged 18-59) years were screened using the Mood Disorder Questionnaire (MDQ) for a possible new episode of DSM-IV BD. 490 patients were interviewed with semi-structured interview [the Structured Clinical Interview for DSM-IV Disorders, research version with Psychotic Screen (SCID-I/P)]. 191 patients with new episode of DSM-IV BD were included in the bipolar cohort study. Psychiatric comorbidity was evaluated using semi-structured interviews. At 6- and 18-month follow-up, the interviews were repeated and life-chart methodology was used to integrate all available information about nature and duration of all different phases. Suicidal behaviour was examined both at intake and follow-up by psychometric scale [Scale for Suicidal Ideation (SSI)], interviewer s questions and medical and psychiatric records. The aim of this thesis was to evaluate prevalence of suicidal behaviour and incidence of suicide attempts, and examine the wide range of risk factors for attempted suicide both, at intake and follow-up, in representative secondary-level sample of psychiatric in- and outpatients with BD. In this study suicidal behaviour was common among psychiatric patients with BD. During the episode when patients were included into cohort study (index episode), 20% of the patients had attempted suicide and 61% had suicidal ideation. Severity of depressive episode and hopelessness were independent risk factors for suicidal ideation, whereas hopelessness, comorbid personality disorder and previous suicide attempt predicted suicide attempts during the index episode. There were no differences in prevalence of suicidal behaviour between bipolar I and II disorder; the risk factors were overlapping but not identical. During the index episode, suicide attempts took place during depressive, mixed and depressive mixed phases. Furthermore, there were marked differences regarding level of suicidal ideation during different phases, with the highest levels during the mixed phases of the illness. Hopelessness was independently associated with suicidal behaviour during the depressive phase. A subjective rating of severity of depression (Beck Depression Inventory) and younger age predicted suicide attempts during mixed phases. During the 18-month follow-up 20% of patients attempted suicide. Previous suicide attempts, hopelessness, depressive phase at index episode and younger age at intake were independent risk factors for suicide attempts during follow-up. Taken altogether, 55% patients attempted suicide before index episode, during index episode or during follow-up. The incidence of suicide attempts was 37-fold during combined mixed and depressive mixed states and 18-fold during major depressive phase as compared with other phases. Prior suicide attempt and time spent in combined mixed phases - mixed and depressive mixed - and depressive phases independently predicted the suicide attempt during follow-up. More than half of the patients have attempted suicide during their lifetime, a finding which highlights the public health importance of suicidal behaviour in bipolar disorder. Clinically, it is crucial to recognize BD and manage the mixed and depressive phases of bipolar patients fast and effectively, as time spent in depressive and mixed phases involves a remarkably high risk of suicide attempts.
Resumo:
Three-dimensional (3D) hierarchical nanoscale architectures comprised of building blocks, with specifically engineered morphologies, are expected to play important roles in the fabrication of 'next generation' microelectronic and optoelectronic devices due to their high surface-to-volume ratio as well as opto-electronic properties. Herein, a series of well-defined 3D hierarchical rutile TiO2 architectures (HRT) were successfully prepared using a facile hydrothermal method without any surfactant or template, simply by changing the concentration of hydrochloric acid used in the synthesis. The production of these materials provides, to the best of our knowledge, the first identified example of a ledgewise growth mechanism in a rutile TiO2 structure. Also for the first time, a Dye-sensitized Solar Cell (DSC) combining a HRT is reported in conjunction with a high-extinction-coefficient metal-free organic sensitizer (D149), achieving a conversion efficiency of 5.5%, which is superior to ones employing P25 (4.5%), comparable to state-of-the-art commercial transparent titania anatase paste (5.8%). Further to this, an overall conversion efficiency 8.6% was achieved when HRT was used as the light scattering layer, a considerable improvement over the commercial transparent/reflector titania anatase paste (7.6%), a significantly smaller gap in performance than has been seen previously.
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The outcome of the successfully resuscitated patient is mainly determined by the extent of hypoxic-ischemic cerebral injury, and hypothermia has multiple mechanisms of action in mitigating such injury. The present study was undertaken from 1997 to 2001 in Helsinki as a part of the European multicenter study Hypothermia after cardiac arrest (HACA) to test the neuroprotective effect of therapeutic hypothermia in patients resuscitated from out-of-hospital ventricular fibrillation (VF) cardiac arrest (CA). The aim of this substudy was to examine the neurological and cardiological outcome of these patients, and especially to study and develop methods for prediction of outcome in the hypothermia-treated patients. A total of 275 patients were randomized to the HACA trial in Europe. In Helsinki, 70 patients were enrolled in the study according to the inclusion criteria. Those randomized to hypothermia were actively cooled externally to a core temperature 33 ± 1ºC for 24 hours with a cooling device. Serum markers of ischemic neuronal injury, NSE and S-100B, were sampled at 24, 36, and 48 hours after CA. Somatosensory and brain stem auditory evoked potentials (SEPs and BAEPs) were recorded 24 to 28 hours after CA; 24-hour ambulatory electrocardiography recordings were performed three times during the first two weeks and arrhythmias and heart rate variability (HRV) were analyzed from the tapes. The clinical outcome was assessed 3 and 6 months after CA. Neuropsychological examinations were performed on the conscious survivors 3 months after the CA. Quantitative electroencephalography (Q-EEG) and auditory P300 event-related potentials were studied at the same time-point. Therapeutic hypothermia of 33ºC for 24 hours led to an increased chance of good neurological outcome and survival after out-of-hospital VF CA. In the HACA study, 55% of hypothermia-treated patients and 39% of normothermia-treated patients reached a good neurological outcome (p=0.009) at 6 months after CA. Use of therapeutic hypothermia was not associated with any increase in clinically significant arrhythmias. The levels of serum NSE, but not the levels of S-100B, were lower in hypothermia- than in normothermia-treated patients. A decrease in NSE values between 24 and 48 hours was associated with good outcome at 6 months after CA. Decreasing levels of serum NSE but not of S-100B over time may indicate selective attenuation of delayed neuronal death by therapeutic hypothermia, and the time-course of serum NSE between 24 and 48 hours after CA may help in clinical decision-making. In SEP recordings bilaterally absent N20 responses predicted permanent coma with a specificity of 100% in both treatment arms. Recording of BAEPs provided no additional benefit in outcome prediction. Preserved 24- to 48-hour HRV may be a predictor of favorable outcome in CA patients treated with hypothermia. At 3 months after CA, no differences appeared in any cognitive functions between the two groups: 67% of patients in the hypothermia and 44% patients in the normothermia group were cognitively intact or had only very mild impairment. No significant differences emerged in any of the Q-EEG parameters between the two groups. The amplitude of P300 potential was significantly higher in the hypothermia-treated group. These results give further support to the use of therapeutic hypothermia in patients with sudden out-of-hospital CA.
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Soy-derived phytoestrogen genistein and 17β-estradiol (E2), the principal endogenous estrogen in women, are also potent antioxidants protecting LDL and HDL lipoproteins against oxidation. This protection is enhanced by esterification with fatty acids, resulting in lipophilic molecules that accumulate in lipoproteins or fatty tissues. The aims were to investigate, whether genistein becomes esterified with fatty acids in human plasma accumulating in lipoproteins, and to develop a method for their quantitation; to study the antioxidant activity of different natural and synthetic estrogens in LDL and HDL; and to determine the E2 esters in visceral and subcutaneous fat in late pregnancy and in pre- and postmenopause. Human plasma was incubated with [3H]genistein and its esters were analyzed from lipoprotein fractions. Time-resolved fluoroimmunoassay (TR-FIA) was used to quantitate genistein esters in monkey plasma after subcutaneous and oral administration. The E2 esters in women s serum and adipose tissue were also quantitated using TR-FIA. The antioxidant activity of estrogen derivatives (n=43) on LDL and HDL was assessed by monitoring the copper induced formation of conjugated dienes. Human plasma was shown to produce lipoprotein-bound genistein fatty acid esters, providing a possible explanation for the previously reported increased oxidation resistance of LDL particles during intake of soybean phytoestrogens. Genistein esters were introduced into blood by subcutaneous administration. The antioxidant effect of estrogens on lipoproteins is highly structure-dependent. LDL and HDL were protected against oxidation by many unesterified, yet lipophilic derivatives. The strongest antioxidants had an unsubstituted A-ring phenolic hydroxyl group with one or two adjacent methoxy groups. E2 ester levels were high during late pregnancy. The median concentration of E2 esters in pregnancy serum was 0.42 nmol/l (n=13) and in pre- (n=8) and postmenopause (n=6) 0.07 and 0.06 nmol/l, respectively. In pregnancy visceral fat the concentration of E2 esters was 4.24 nmol/l and in pre- and postmenopause 0.82 and 0.74 nmol/l. The results from subcutaneous fat were similar. In serum and fat during pregnancy, E2 esters constituted about 0.5 and 10% of the free E2. In non-pregnant women most of the E2 in fat was esterified (the ester/free ratio 150 - 490%). In postmenopause, E2 levels in fat highly exceeded those in serum, the majority being esterified. The pathways for fatty acid esterification of steroid hormones are found in organisms ranging from invertebrates to vertebrates. The evolutionary preservation and relative abundance of E2 esters, especially in fat tissue, suggest a biological function, most likely in providing a readily available source of E2. The body s own estrogen reservoir could be used as a source of E2 by pharmacologically regulating the E2 esterification or hydrolysis.
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In this paper, we present an algebraic method to study and design spatial parallel manipulators that demonstrate isotropy in the force and moment distributions. We use the force and moment transformation matrices separately, and derive conditions for their isotropy individually as well as in combination. The isotropy conditions are derived in closed-form in terms of the invariants of the quadratic forms associated with these matrices. The formulation is applied to a class of Stewart platform manipulator, and a multi-parameter family of isotropic manipulators is identified analytically. We show that it is impossible to obtain a spatially isotropic configuration within this family. We also compute the isotropic configurations of an existing manipulator and demonstrate a procedure for designing the manipulator for isotropy at a given configuration. (C) 2008 Elsevier Ltd. All rights reserved.
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Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is rapidly increasing disease with a pathophysiology connected to oxidative stress. Exact pre-treatment clinical staging is essential for optimal care of this lethal malignancy. The cost-effectiviness of treatment is increasingly important. We measured oxidative metabolism in the distal and proximal esophagus by myeloperoxidase activity (MPA), glutathione content (GSH), and superoxide dismutase (SOD) in 20 patients operated on with Nissen fundoplication and 9 controls during a 4-year follow-up. Further, we assessed the oxidative damage of DNA by 8-hydroxydeoxyguanosine (8-OHdG) in esophageal samples of subjects (13 Barrett s metaplasia, 6 Barrett s esophagus with high-grade dysplasia, 18 adenocarcinoma of the distal esophagus/GEJ, and 14 normal controls). We estimated the accuracy (42 patients) and preoperative prognostic value (55 patients) of PET compared with computed tomography (CT) and endoscopic ultrasound (EUS) in patients with adenocarcinoma of the esophagus/GEJ. Finally, we clarified the specialty-related costs and the utility of either radical (30 patients) or palliative (23 patients) treatment of esophageal/GEJ carcinoma by the 15 D health-related quality-of-life (HRQoL) questionnaire and the survival rate. The cost-utility of radical treatment of esophageal/GEJ carcinoma was investigated using a decision tree analysis model comparing radical, palliative, and hypothetical new treatment. We found elevated oxidative stress ( measured by MPA) and decreased antioxidant defense (measured by GSH) after antireflux surgery. This indicates that antireflux surgery is not a perfect solution for oxidative stress of the esophageal mucosa. Elevated oxidative stress in turn may partly explain why adenocarcinoma of the distal esophagus is found even after successful fundoplication. In GERD patients, proximal esophageal mucosal anti-oxidative defense seems to be defective before and even years after successful antireflux surgery. In addition, antireflux surgery apparently does not change the level of oxidative stress in the proximal esophagus, suggesting that defective mucosal anti-oxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD. In the malignant transformation of Barrett s esophagus an important component appears to be oxidative stress. DNA damage may be mediated by 8-OHdG, which we found to be increased in Barrett s epithelium and in high-grade dysplasia as well as in adenocarcinoma of the esophagus/GEJ compared with controls. The entire esophagus of Barrett s patients suffers from increased oxidative stress ( measured by 8-OhdG). PET is a useful tool in the staging and prognostication of adenocarcinoma of the esophagus/GEJ detecting organ metastases better than CT, although its accuracy in staging of paratumoral and distant lymph nodes is limited. Radical surgery for esophageal/GEJ carcinoma provides the greatest benefit in terms of survival, and its cost-utility appears to be the best of currently available treatments.
Resumo:
The Molecular Adsorbent Recirculating System (MARS) is an extracorporeal albumin dialysis device which is used in the treatment of liver failure patients. This treatment was first utilized in Finland in 2001, and since then, over 200 patients have been treated. The aim of this thesis was to evaluate the impact of the MARS treatment on patient outcome, the clinical and biochemical variables, as well as on the psychological and economic aspects of the treatment in Finland. This thesis encompasses 195 MARS-treated patients (including patients with acute liver failure (ALF), acute-on-chronic liver failure (AOCLF) and graft failure), and a historical control group of 46 ALF patients who did not undergo MARS. All patients received a similar standard medical therapy at the same intensive care unit. The baseline data (demographics, laboratory and clinical variables) and MARS treatment-related and health-related quality-of-life data were recorded before and after treatment. The direct medical costs were determined for a period of 3.5 years.Additionally, the outcome of patients (survival, native liver recovery and need for liver transplantation) and survival predicting factors were investigated. In the outcome analysis, for the MARS-treated ALF patients, their 6-month survival (75% vs. 61%, P=0.07) and their native liver recovery rate (49% vs. 17%, P<0.001) were higher, and their need for transplantations was lower (29% vs. 57%, P= 0.001) than for the historical controls. However, the etiological distribution of the ALF patients referred to our unit has changed considerably over the past decade and the percentage of patients with a more favorable prognosis has increased. The etiology of liver failure was the most important predictor of the outcome. Other survival predicting factors in ALF included hepatic encephalopathy, the coagulation factors and the liver enzyme levels prior to MARS treatment. In terms of prognosis, the MARS treatment of the cirrhotic AOCLF patient seems meaningful only when the patient is eligible for transplantation. The MARS treatment appears to halt the progression of encephalopathy and reduce the blood concentration of neuroactive amino acids, albumin-bound and water-soluble toxins. In general, the effects of the MARS treatment seem to stabilize the patients, thus allowing additional time either for the native liver to recover, or for the patients to endure the prolonged waiting for transplantation. Furthermore, for the ALF patients, the MARS treatment appeared to be less costly and more cost-efficient than the standard medical therapy alone. In conclusion, the MARS treatment appears to have a beneficial effect on the patient outcome in ALF and in those AOCLF patients who can be bridged to transplantation.
Resumo:
Pitfalls in the treatment of persons with dementia Persons with dementia require high-quality health care, rehabilitation and sufficient social services to support their autonomy and to postpone permanent institutionalization. This study sought to investigate possible pitfalls in the care of patients with dementia: hip fracture rehabilitation, use of inappropriate or antipsychotic medication, social and medicolegal services offered to dementia caregiving families. Three different Finnish samples were used from years 1999-2005, mean age 78 to 86 years. After hip fracture operation, the weight-bearing restriction especially in group of patients with dementia, was associated with a longer rehabilitation period (73.5 days vs. 45.5 days, p=0.03) and the inability to learn to walk after six weeks (p<0.001). Almost half (44%) of the pre-surgery home-dwellers with dementia in our sample required permanent hospitalization after hip fracture. Potentially inappropriate medication was used among 36.2% of nursing home and hospital patients. The most common PIDs in Finland were temazepam over 15 mg/day, oxybutynin, and dipyridamole. However, PID use failed to predict mortality or the use of health services. Nearly half (48.4%) of the nursing home and hospital patients with dementia used antipsychotic medication. The two-year mortality did not differ among the users of conventional or atypical antipsychotics or the non-users (45.3% vs.32.1% vs.49.6%, p=0.195). The mean number of hospital admissions was highest among non-users (p=0.029). A high number of medications (HR 1.12, p<0.001) and the use of physical restraints (HR 1.72, p=0.034) predicted higher mortality at two years, while the use of atypical antipsychotics (HR 0.49, p=0.047) showed a protective effect, if any. The services most often offered to caregiving families of persons with Alzheimer s disease (AD) included financial support from the community (36%), technical devices (33%), physiotherapy (32%), and respite care in nursing homes (31%). Those services most often needed included physiotherapy for the spouse with dementia (56%), financial support (50%), house cleaning (41%), and home respite (40%). Only a third of the caregivers were satisfied with these services, and 69% felt unable to influence the range of services offered. The use of legal guardians was quite rare (only 4.3%), while the use of financial powers of attorney was 37.8%. Almost half (47.9%) of the couples expressed an unmet need for discussion with their doctor about medico-legal issues, while only 9.9% stated that their doctor had informed them of such matters. Although we already have many practical methods to develop the medical and social care of persons with AD, these patients and their families require better planning and tailoring of such services. In this way, society could offer these elderly persons better quality of life while economizing on its financial resources. This study was supported by Social Insurance Institution of Finland and part of it made in cooperation with the The Central Union of the Welfare for the Aged, Finland.
Resumo:
In the title compound, C19H16ClNO2, the quinoline ring system is planar (r.m.s. deviation = 0.008 angstrom). The phenyl group and the -CO2 fragment of the ester unit form dihedral angles of 60.0 (1) and 60.5 (1)degrees, respectively, with the quinoline ring system.
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Eighty-five new cases of conjunctival melanoma (CM) were diagnosed in Finland between 1967 and 2000. The annual crude incidence of CM was 0.51 per million inhabitants. The average age-adjusted incidence of 0.54 doubled during the study period, analogous to the increase in the incidence of cutaneous malignant melanoma during this period, suggesting a possible role for ultraviolet radiation in its pathogenesis. Nonlimbal tumors were more likely than limbal ones to recur and they were associated with decreased survival. Increasing tumor thickness and recurrence of the primary tumor were other clinical factors related to death from CM. The histopathologic specimens of 85 patients with CM melanoma were studied for cell type, mitotic count, tumor-infiltrating lymphocytes and macrophages, mean vascular density, extravascular matrix loops and networks, and mean diameter of the ten largest nucleoli (MLN). The absence of epithelioid cells, increasing mitotic count and small MLN were associated with shorter time to recurrence according to the Cox univariate regression. None of the histopathologic variables was associated with mortality from CM. Four (5%) patients had a CM limited to the cornea without evidence of a tumor other than primary acquired melanosis of the conjunctiva. Because there are no melanocytes in the cornea, the origin of these melanomas most likely is the limbal conjunctiva. All four corneally displaced CM were limited to the epithelium, and none of the patients developed metastases. An anatomic sub-classification based on my patients and world literature was developed for corneally displaced CM. In 20 patients the metastatic pattern could be determined. Ten patients had initial systemic metastases detected, nine had initial regional metastases, and in one case the two types were detected simultaneously. The patients most likely to develop either type of initial metastases were those with nonlimbal conjunctival melanoma, those with a primary tumor more than 2 mm thick, and those with a recurrent conjunctival melanoma. Approximately two thirds of the patients had limbal CM, a location associated with good prognosis. One third, however, had a primary CM originating outside the limbus. In these patients the chance of developing local recurrences as well as systemic metastases was significantly higher than in patients with limbal CM. Each recurrence accompanies an increased risk of developing metastases, and recurrences contribute to death along with increasing tumor thickness and nonlimbal tumor location. In my data, an equal number of patients with initial locoregional and systemic metastasis existed. Patients with limbal primary tumors less than 2 mm in thickness rarely experienced metastases, unless the tumor recurred. Consequently, the patients most likely to benefit from sentinel lymph node biopsy are those who have nonlimbal tumors, CM that are over 2 mm thick, or recurrent CM. The histopathology of CM differs from that of uveal melanoma. Microvascular factors did not prove to be of prognostic importance, possibly due to the fact that CM at least as often disseminates first to the regional lymph nodes, unlike uveal melanoma that almost always disseminates hematogenously.
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Acute renal failure (ARF) is a clinical syndrome characterized by rapidly decreasing glomerular filtration rate, which results in disturbances in electrolyte- and acid-base homeostasis, derangement of extracellular fluid volume, and retention of nitrogenous waste products, and is often associated with decreased urine output. ARF affects about 5-25% of patients admitted to intensive care units (ICUs), and is linked to high mortality and morbidity rates. In this thesis outcome of critically ill patients with ARF and factors related to outcome were evaluated. A total of 1662 patients from two ICUs and one acute dialysis unit in Helsinki University Hospital were included. In study I the prevalence of ARF was calculated and classified according to two ARF-specific scoring methods, the RIFLE classification and the classification created by Bellomo et al. (2001). Study II evaluated monocyte human histocompatibility leukocyte antigen-DR (HLA-DR) expression and plasma levels of one proinflammatory (interleukin (IL) 6) and two anti-inflammatory (IL-8 and IL-10) cytokines in predicting survival of critically ill ARF patients. Study III investigated serum cystatin C as a marker of renal function in ARF and its power in predicting survival of critically ill ARF patients. Study IV evaluated the effect of intermittent hemodiafiltration (HDF) on myoglobin elimination from plasma in severe rhabdomyolysis. Study V assessed long-term survival and health-related quality of life (HRQoL) in ARF patients. Neither of the ARF-specific scoring methods presented good discriminative power regarding hospital mortality. The maximum RIFLE score for the first three days in the ICU was an independent predictor of hospital mortality. As a marker of renal dysfunction, serum cystatin C failed to show benefit compared with plasma creatinine in detecting ARF or predicting patient survival. Neither cystatin C nor plasma concentrations of IL-6, IL-8, and IL-10, nor monocyte HLA-DR expression were clinically useful in predicting mortality in ARF patients. HDF may be used to clear myoglobin from plasma in rhabdomyolysis, especially if the alkalization of diuresis does not succeed. The long-term survival of patients with ARF was found to be poor. The HRQoL of those who survive is lower than that of the age- and gender-matched general population.