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Investigation into the early hydration of Portland cement was performed by in situX-ray diffraction (XRD). Technical white cement was used for the XRD analysis on a D5000 diffractometer (Siemens). All diffraction patterns of the in situmeasurement which were recorded up to 22 h of hydration at defined temperatures were analyzed by Rietveld refinement. The resulting phase composition was transformed with respect to free water and C-S-H leading to the total composition of the cement paste. The hydration reactions can be observed by dissolution of clinker phases as well as by the formation of the hydrate phases ettringite and portlandite. With increasing temperatures the reactions proceed faster. The formation of ettringite is directly influenced by the rate of dissolution of anhydrite and tricalcium aluminate (C3A). The beginning of the main period of hydration is marked by the start of portlandite formation. The experiments point out that a quantitative phase analysis of the cement hydration is feasible with standard laboratory diffractometers.

Genetic variation in drug targets (e.g. receptors) can have pronounced effects on clinical responses to endogenous and exogenous agonists. Polymorphisms in the gene encoding the β2-adrenergic receptor (β2-AR) have been associated with altered expression, down-regulation, and altered cell signaling in vitro. Because β2-ARs play a crucial role in the regulation of the cardiovascular system, the functional importance of genetic variation in the β2-AR on cardiovascular responses to physiological or pharmacological stimuli has gained widespread attention. The objective of this review is to characterize these intermediate cardiovascular phenotypes and their influence on cardiovascular disease and adrenergic drug responses. Two common single nucleotide polymorphisms, encoded at codon 46 (Gly16Arg) and 79 (Gln27Glu) of the β2-AR gene, have been studied intensively. They have been shown to be associated with altered vasodilator responses to regional and systemic administration of β2-agonists, altered cardiovascular responses to sympathoexcitatory maneuvers, and altered myocardial function. Importantly, these intermediate physiological patterns may influence the development of and the outcomes associated with hypertension and other cardiovascular diseases. As recently reported, β2-AR gene variation can risk-stratify patients receiving β-blocker therapy and may predict β-blocker efficacy in patients post acute coronary syndrome or in patients with heart failure. Further studies will advance our understanding of the link between β2-AR genotypes, intermediate cardiovascular phenotypes, and clinical phenotypes. In the long term, reassessment of the benefits of β-blocker-therapy within genotype groups should be carried out with the ultimate goal to design the optimal therapeutic regimen for the individual patient.

This work presents a study of the influence of both Bi content and Sb/Bi ratio on the electrical characteristics of a commercial-type ZnO varistor. In contrast to previous studies two nonlinear coefficients, the breakdown fields and energy absorption abilities were measured after sintering at 970°C or 930°C. The Bi-content was varied from 0.9 to 1.8 at% while the Sb/Bi ratio was varied from 0.8 to 1.5, leading to values of up to 104 for the nonlinear coefficient α1, 1100 V mm−1for the breakdown field and 1137 J cm−3for the energy absorption ability. The highest α value was measured for the highest Bi-content and the lowest Sb/Bi ratio and vice versa. The breakdown field EVincreased with lower sintering temperature, increased Sb/Bi ratio (at a given Bi-content) and increased Bi-content (at a given Sb/Bi ratio). The energy absorption coefficient increased at the higher sinter temperature and with lower Sb and Bi concentrations. The observed effects were related to the amount of spinel phase (Zn7Sb2O12) formed during the sintering process and the amount of liquid phase present during early stages of the sintering process.

We studied the multifunctional protein clusterin (apolipoprotein J, SGP-2, SP-40,40) in brain tissue using quantitative Western blotting and immunohistochemistry. The material included postmortem brains from 19 patients with Alzheimer's disease (AD), 6 with vascular dementia (VAD), and 7 age-matched control subjects. Intense clusterin staining was found in the soma of both neuronal and astroglial cells. In addition, positive staining was found in a portion of senile plaques (SP) in AD brains. Quantitative analysis showed that clusterin levels were significantly increased in AD, both in frontal cortex (150% of the control value,P=0.002) and in the hippocampus (179% of the control value,P<0.001), while normal clusterin levels were found in cerebellum (104% of the control value). No significant changes were found in VAD. Within the AD group, there was a significant negative correlation between clusterin levels in hippocampus and severity of dementia (r=−0.40), while no such correlation was found in frontal cortex (r=0.12). No significant correlations were found between clusterin levels and the number of SP or neurofibrillary tangles. No significant differences in clusterin levels were found in any brain region between AD patients possessing different numbers of the ApoE4 allele. The increased clusterin levels in AD brain, together with the absence of a correlation between SP counts and clusterin levels, and the finding that clusterin is only found in a smaller portion of SP do not suggest a link between clusterin and β-amyloid dependence. Instead we hypothesize that the increase is part of a regional response in AD brain.

Both mycophenolate mofetil (MMF) and azathioprine (AZA) are immunosuppressive drugs that inhibit purine synthesis. In theory, MMF selectively inhibits lymphocyte proliferation, while AZA has well-known effects on red blood cells and thrombocytes as well. In renal transplant recipients we replaced CsA therapy by MMF in an attempt to reduce the immunosuppressive load 1 year after kidney transplantation. During this study we observed the effect of MMF on haematological parameters such as haemoglobin (Hb), leukocytes, and thrombocytes.

Triple drug treatment consisting of mycophenolate mofetil (MMF), in a standard dose of 2 g daily, combined with cyclosporine (CsA) and prednisone, has become the standard immunosuppressive regimen after kidney transplantation in many centers. The need for therapeutic drug monitoring of mycophenolic acid (MPA) has not yet been established. Several drug interactions with MMF are known. We investigated the influence of CsA withdrawal on MPA trough levels in renal transplant patients.

24 heart transplant recipients were treated with OKT3 together with azathioprine for 7 days as a rejection prophylaxis. The plasma OKT3 concentration ranged from 280 to 1600 ng/ml. During treatment the T cells in peripheral blood disappeared but returned modulated without TcR‐α/β‐chains and with low CD3 expression. Antimurine antibodies were induced and median IgG antimurine antibody concentrations increased from 9.6 mg/l pretransplant to 52.1 mg/l as measured by ELISA. In 13 out of 24 patients, anti‐idiotypic antibodies were present at a level that caused over 50% inhibition of OKT3 binding to T cells. The extent of inhibition was positively correlated with the increase in IgG antimurine antibody levels, both in relative (> 3 times pre‐transplant level, p < 0.05) and in absolute terms (more than 50 mg/l, p < 0.001). In 9 patients, who received two prophylactic courses of OKT3, we found a decrease in anti‐OKT3 antibody levels after the second course of OKT3 which can be caused by the additional cyclosporin A (CsA) immune suppression. The second course also resulted in a rapid depletion of circulating functional T cells despite the presence of anti‐OKT3 antibodies generated after the first course.

Abstract:  Stereoselectivity in the oxidation of ferrocenyl sulphides with several species of microorganisms such as Corynebacterium equi was reversed between (methylthiomethyl)ferrocene and (t-butylthiomethyl)ferrocene, indicating that the size of the side chain could control the stereochemical course of the biooxidation. The size seems to be effective within some limit, because the more bulky compound, (phenylthiomethyl)ferrocene, was a poor substrate. On the other hand, the microbial oxidation of (methylthiomethyl)ruthenocene and -osmocene with Mortierella isabellina and that of (t-butylthiomethyl)ruthenocene and -osmocene with C. equi gave levorotatory sulphoxides (85–97% e.e.), which were all found to have R absolute configuration. These stereoselectivities were the same as those for the corresponding ferrocenyl sulphides. Thus, the central atom of the metallocenic sulphides seems not to affect the stereoselectivity in the biooxidation. The microbial oxidation is a useful method to prepare several kinds of chiral metallocenic sulphoxides with high optical purity.

Drugs with a short elimination half-life should display fewer side effects than longer acting drugs in the treatment of sleep disturbances due to their smaller tendency to accumulate, especially in the elderly. This hypothesis could be confirmed in a double blind study of zopiclone versus flurazepam.

The Quartz Hill molybdenum prospect, with an estimated tailings disposal rate of up to 80,000 tons per day, was developed through preliminary engineering design, environmental impact assessments, and permit applications during the 1970s and 1980s. The intent was to meet the stringent environmental requirements of several federal and state regulatory agencies. The case history of mine development, extending over two decades, provides a unique set of details usable by future large-scale coastal and island mine prospects in the U.S. and elsewhere. Two fjords provided options for submarine tailings disposal (STD) with conventional deaeration and seawater mix chamber. An outfall was designed, and would be located, to produce a density current descending to fjord bottom. Innovative modeling of near-field and far-field tailings dispersal, and resuspension potential, was developed and applied. Of about $102,000,000 invested on the development, approximately $31,000,000 was given to environmentally related work. From the assessments, it was agreed that land disposal of tailings would cause more environmental damage than STD. There was disagreement, however, between regulatory agencies over the preferred site for STD. Discharge permits were drafted, but the applications were finally denied by the Environmental Protection Agency (EPA) in 1990. In 1991 the developer sold its interest in the prospect to another company.

In Rotterdam 304 heart transplants have been performed since 1984. End-stage renal failure, necessitating renal replacement therapy, has developed in 24 patients (8%) after an interval of 25-121 months (median 79 months). After starting renal replacement therapy one-year survival was only 60%. Overall survival after heart transplantation, however, was favourable: 5 and 10 year survival rates of 79% and 50% respectively.

In order to elucidate the reaction scheme of the oscillatory malonic acid-KBrO3system in sulphuric acid the products extracted from the reaction system by ether are analysed by gas chromatography and mass spectrometry. After 2 hours reaction time implying approx. 80 to 100 cycles malonic acid, monobromomalonic acid and dibromoacetic acid are identified in a relative ratio of about 1.0, 0.14 and 0.023.

Summary A multidimensional concept of diagnosis and treatment of mental disorders is presented. Major contributions to basic research come from pharmacological experiments. Clinical outcome in treatment of endogenous depression can be assessed by rating scales and psychophysiological tests and correlated with the serum level of the drug. In the case of maprotiline there seems to be a correlation between serum level and clinical outcome.

Sixteen kidney transplant recipients received the IgG2a anti-CD3 monoclonal antibody OKT3 and azathioprine as rejection prophylaxis during the first two postoperative weeks. Concomitant immunosuppression consisted of low dose steroids while cyclosporine A therapy was instituted on day 12. Side effects included fever, bronchospasm, hypotension and diarrhoea. OKT3 caused T cell modulation resulting in CD3 dim +, CD4+ or CD8+, CD5+, WT31− and 11F2−cells. Anti-OKT3 antibodies were found in approximately 50% of the patients. The protocol induced a 100% patient and graft survival and a 81% actuarial freedom of rejection at 18 months. It prevented CsA associated nephrotoxicity in the direct postoperative phase.

We studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37 male/21 female) consecutive renal allograft recipients were entered in this trial. Treatment results were compared with 56 patients treated with intravenous cyclosporin (CyA). In all patients concomitant medication consisted of steroids and azathioprine, followed by oral CyA. Following rabbit ATG, T cells (WT31) quickly disappeared from the peripheral blood and a return to greater than 100/mm3 was observed at a median of 7 (range 3–21) days. Graft survival was the same in both groups, as was the incidence of primary nonfunction. The rate of acute rejection was significantly lower in the rabbit ATG-treated patients (12% vs 50%). We conclude that a single shot of rabbit ATG is an attractive, easy, and cost-effective induction scheme with a low incidence of delayed graft function and acute rejection episodes. A relatively high incidence of vascular thrombosis of the graft, however, warrants further study before this treatment regimen can be generally applied.

We investigated blood-brain barrier (BBB) function in relation to Alzheimer's disease (AD) and vascular dementia (VAD) in the very elderly. Sixty-five 85-year-old persons from a population-based sample were followed for 3 years; 29 were demented at age 85 (13 with AD, 14 with VAD, and 2 with other dementias), 7 developed dementia during follow-up, and 29 remained nondemented. CSF/serum albumin ratio was used as as a measure of BBB function. Dementia was defined according to the DSM-III-R, AD according to the NINCDS-ADRDA criteria, and VAD according to the NINDS-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria. Mean CSF/serum albumin ratio was higher in all dementias (8.5± 4.3; p= 0.007) and in the subtypes AD (8.9 ± 5.3; p= 0.046) and VAD (8.7 ± 3.5; p= 0.002) than in nondemented individuals (versus 6.5 ± 2.0), but it was not related to dementia severity. Nondemented women at age 85 (n = 3) who developed dementia during the follow-up had a higher CSF/serum albumin ratio than those not developing dementia (10.4 ± 2.0 versus 6.0 ± 1.9; p= 0.007). Nondemented individuals lacking the apolipoprotein E 3 allele (n = 4) had a higher CSF/serum albumin ratio (9.3 ± 0.8 versus 6.6 ± 2.1; p= 0.029) than other individuals. A relative BBB dysfunction is associated with both AD and VAD among very elderly individuals. This finding is possibly found early in the disease before the onset of clinical dementia.

Four different immunoassays were used to measure cyclosporine A (CsA) plasma (20°C) levels in heart and kidney transplant recipients. Two radioimmunoassays (RIAs) (Sandimmune and Cyclotrac) and the fluorescence polarization immunoassay (FPIA) were based on polyclonal antibodies, whereas the fourth (Cyclotrac-SP) used a CsA-specific mouse monoclonal antibody. We found considerable differences in measured CsA concentrations, which were dependent on the method used and the clinical situation of the patient. Correlation coefficients between the nonspecific assays ranged from 0.899 to 0.901 with plasma values increasing in the order Sandimmune < Cyclotrac < FPIA. In the CsA-specific RIA, values were lower, and the correlation with the nonspecific assays ranged from 0.761 to 0.795. In the first 21 days posttransplantation, the heart transplant group showed a higher ratio of nonspecific/specific CsA (mean 4.0) compared with the subsequent period (mean 2.3) or with renal transplant recipients (mean 2.4). The TDX method showed the best assay characteristics. In heart transplant patients with specific and nonspecific 125I-RIA methods, mean CsA levels were 25 lower during rejection periods compared with periods without signs of rejection.

In a double-blind, randomized, placebo-controlled trial, BT563, a murine IgGt anti-IL-2R antibody, was given as a rejection prophylaxis after kidney transplantation. Drug-related side effects were not observed. During the 10-day course of BT563, no rejections (0/27) were found, whereas a rejection episode occurred in 7 patients (7/29) (P=0.01) during placebo treatment. Within the first 4 postoperative weeks, freedom from rejection in the BT563 group and in the placebo group was 96 vs. 76 (P=0.05). Due to rejection in the placebo group, 2 grafts were lost. At 3 months, an overall rejection incidence in the BT563 and placebo group was found of 3/27 (11) vs. 8/29 (28) patients (P=0.18). Infectious complications were distributed equally between the 2 groups. CMV disease, found in 3 placebo-treated patients, occurred after rejection treatment (2/3). Within the BT563 group, 1 patient lost his graft due to renal artery thrombosis, 2 grafts were lost as a result of technical failure, and 2 patients had a squamous cell carcinoma that could be treated curatively. We conclude that the use of the anti-IL-2R mAb BT563 effectively prevents rejection after kidney transplantation without increasing infectious complications.

Alzheimer's disease (AD) is the most common form of dementia, and is characterized by a degeneration of neurones and their synapses, and a higher number of senile plaques (SP) and neurofibrillary tangles (NFT) compared with that found in non-demented individuals of the same age. NFT are composed of a hyperphosphorylated and ubiquitinated form of tau protein. Previous studies have found that in the cerebrospinal fluid (CSF) both tau and ubiquitin are increased in AD. We examined CSF-tau and CSF-ubiquitin in a population based sample of 85-year-olds, 26 demented (11 with probable Alzheimer's disease (AD), 13 with probable vascular dementia (VAD) and 2 with mixed (AD/VAD) type of dementia) and 35 non-demented individuals. CSF-tau was significantly higher both in the probable AD group (254±113 pg/mL;P<0.01), and in the probable VAD group (247±75 pg/mL;P<0.005), than in the non- demented group (171±78 pg/mL), but did not significantly differ between the probable AD and probable VAD groups. In contrast, CSF-ubiquitin did not significantly differ between the probable AD (100±24 ng/mL), probable VAD (102±16 ng/mL), and non-demented (97±27 ng/mL) groups. CSF-tau increased with increasing severity of dementia (P<0.001), though no such relation was found for CSF-ubiquitin. Neither CSF-tau nor CSF-ubiquitin differed between patients with or without the apolipoprotein E E4 isoform. Higher CSF-tau and CSF-ubiquitin levels were also associated with increasing degree of cortical and central brain atrophy as measured by computerized tomography. The relationships between CSF-tau and severity of dementia and to brain atrophy suggest that CSF-tau may be used as a measure of neuronal/ axonal degeneration in patients with dementia. We have previously shown a marked increase in both CSF-tau and CSF-ubiquitin in younger patients with AD and VAD. The less pronounced increase in CSF-tau and the lack of difference in CSF-ubiquitin in older patients suggest that the severity of the degenerative process is less in older than in younger demented patients.

Abstract The TNF-α system is thought to play a central role in the reduced immunity of haemodialysis patients. The imbalance between the high levels of soluble TNF receptors R 1 and R 2 and the low levels of immunoactive TNF-α results in an increased TNF-α buffering capacity leading to reduced immune responses. Apart from impaired renal clearance of the receptors, inefficient TNF-α production as a result of the uraemia may also contribute to the imbalance between this cytokine and its receptors. In patients receiving a living-related kidney transplant, renal function is nearly normalized in a very short period. This restoration of renal function may result in a state of better immunocompetence, either as a result of improved clearance of the receptors or as a result of reversal of the uraemic state. To differentiate between these two possibilities, we measured TNF-α protein, mRNA and the soluble TNF receptors R 1 and R 2 before and after successful renal transplantation. TNF-α mRNA was not affected by transplantation, indicating constant TNF-α production. The imbalance in the TNF-α system was markedly improved after transplantation, although normal values of the soluble receptors were not reached. One year after transplantation in stable kidney transplant recipients there was still an imbalance in the TNF-α system caused by persistently elevated levels of the soluble TNF-receptors. These results suggest that even after successful kidney transplantation the TNF-α system remains activated. However, despite immunosuppressive therapy, recipients of a living-related kidney do have a better balanced TNF-α system compared to haemodialysis patients.

A simple and reliable method for the determination of piracetam in serum and brain homogenates is presented.

AbstractThe δ13C value of bacterial carbon is an important parameter in microbial ecology for studying the carbon flow within a microbial community and for the identification of ecological important strains involved in the mineralization of certain carbon pools in the environment. In our study, biomarkers were isolated from bacteria from a microbial consortium derived from two chemostats and δ13C values were measured. Similar isotope ratios between biomarkers such as fatty acids and outer membrane protein, biomass and substrate were observed. The δ13C analyses of outer membrane protein F of Pseudomonasand biomarker fatty acids were combined to follow bacterial assimilation of 13C labelled 4-chlorocatechol. This new approach was also used in the environment where soil samples were cultivated with different 13C traced substrates.The isotopic analyses of bacterial biomarkers indicated that carbons of histidine were widely incorporated into bacterial biomarkers, in contrast to 4-chlorocatechol which was less often used as a substrate. Results indicate that by isolating bacterial biomarkers and measuring their δ13C values, activities of microbial communities in a complex environmental sample can be determined. This new method has the potential to elucidate individual carbon sources for individual bacterial taxa in microbial ecology.

Objectives Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Pitea River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease. Methods Participants: Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year. Main outcome measures Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism. Results CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia. Conclusions The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease.

Objectives To study the association of apoE genotypes with dementia and cerebrovascular disorders in a population based sample of 85 year old people. Methods A representative sample of 85 year old people (303 non-demented, 109 demented) were given a neuropsychiatric and a medical examination and head CT. The apoE isoforms were determined. Dementia was diagnosed according to DSM-III-R. Results At the age of 85, carriers of the apoE ε4 allele had an increased odds ratio (OR) for dementia (1.9; p&lt;0.01) and its subtypes Alzheimer's disease (1.9; p&lt;0.05) and vascular dementia (2.0; p&lt;0.05). Among those categorised as having vascular dementia, the apoE ε4 allele was associated with mixed Alzheimer's disease-multi-infarct dementia (OR 6.5; p&lt;0.05), but not with pure multi-infarct dementia (OR 1.5; NS). Only carriers of the apoE ε4 allele who also had ischaemic white matter lesions on CT of the head had an increased OR for dementia (OR 6.1; p=0.00003), and its main subtypes Alzheimer's disease (OR 6.8; p=0.002) and vascular dementia (OR 5.6; p=0.0007), whereas carriers of the apoE ε4 allele without white matter lesions had an OR for dementia of 1.0 (OR for Alzheimer's disease 1.8; NS and for vascular dementia 0.6; NS) and non-carriers of the apoE ε4 allele with white matter lesions had an OR for dementia of 2.2; NS (OR for Alzheimer's disease 2.7; NS and for vascular dementia 1.6; NS). The apoE allele variants were not related to mortality or incidence of dementia between the ages of 85 and 88. The ε2 allele was related to a higher prevalence of stroke or transient ischaemic attack at the age of 85 (OR 2.1; p&lt;0.05) and a higher incidence of multi-infarct dementia during the follow up (OR 2.9; p&lt;0.05). Conclusions Neither the apoE ε4 allele nor white matter lesions are sufficient risk factors by themselves for dementia at very old ages, whereas possession of both these entities increases the risk for Alzheimer's disease and vascular dementia substantially.

The impact of continuous hemofiltration (CHF) using a polyacrylonitrile membrane on the kinetics of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-lβ), and their inhibitors (soluble TNF receptors [sTNFrl, sTNFrII], interleukin-1 receptor antagonist [IL-1Ra]) was assessed in nine oliguric patients suffering from systemic inflammatory response syndrome. Blood and plasma flow (Qb, Qp), sieving coefficient (SC), plasma and ultrafiltrate clearances (Kp, Kuf), and plasma extraction rates (ERp) were calculated at different time points using standard formulas. No significant improvement of hemodynamics or gas exchange was noted following HF but a significant increase in serum bicarbonate occurred after 24 h (P < 0.05). TNFα was detected in plasma from all patients (153 ± 2.3 pg/mL [mean ± SEM]). None of the patients had detectable IL-1β levels. High levels of the TNF receptors (sTNFrl 20.338 ± 2.431 pg/mL; sTNFrII 17.839 ± 2.630 pg/mL) and IL-1Ra (19.775 ± 3.943 pg/mL) were found in all patients. Upon initiation of hemofiltration (HF), the mean individual sTNFrl/TNFα. ratio amounted to 269 ± 84.6 and the sTNFrII/TNFα ratio to 249 ± 91.8. Mean ultrafiltrate volume (Vuf) was 11.8 ± 0.4 L/day. Appreciable sieving of IL-1Ra (SC 0.45 ± 0.10), but not of the other cytokines, was noted (SC TNFα, sTNFrI, sTNFrII < 0.09). Despite minimal Kuf of TNFα, sTNFrI, and STNFrII (Kuf < 0.8 mL/min), appreciable Kp was noted, suggesting that membrane adsorption occurs (Kp ≈ 8 mL/min). There was a nonsignificant increase of the ratios between both TNF receptors and TNFα across the filter (sTNFrI/TNFα ratio [pre] 231 ± 37.9 versus [post] 312 ± 75.3); sTNFrII/TNFα ratio [pre] 211 ± 42.1 versus [post] 291 ± 79.3). Appreciable Kp of IL-1Ra was noted (Kp 17.3 ± 1.61 mL/min), which was only in part due to Kuf(4.0 ± 0.86 mL/min). There was a significant decrease of IL-1Ra levels across the membrane, both overall ([pre] 20.223 ± 2.282 versus [post] 16.637 ± 2.039 pg/mL; P < 0.01) and at different time points (P < 0.01). Only for IL-1Ra was significant extraction from plasma noted (ERp 26 ± 6.0%). Plasma levels of TNFα, sTNFrI, sTNFrII, and IL-1Ra were not altered by 24 h of CHF. In conclusion, both cytokines and cytokine inhibitors can be removed from the circulation, either by convective transport or by membrane adsorption. Using low-volume HF (Vuf 12 L/day), no impact on cytokine plasma levels nor the patients hemodynamics or gas exchange was noted. The appreciable SC of IL-1Ra (0.45), however, suggests that HF with high(er) UF volumes (>50 L/day) may be able to achieve reductions in plasma levels of some peptide (anti)mediators. However, whether this aspecific elimination of both mediators and antimediators may alter the clinical course in critically ill patients remains to be investigated.

The first-passage problem is considered for the process [image omitted]  where V(s) is an Ornstein-Uhlenbeck process with an additive constant term μ friction parameter β, and variance σ2 starting from V(O)=μ+μ Global explicit analytic approximations to the first-passage density are derived for the case of a one-sided fixed barrier at distance x from X (0). By a series of simulations the quality of these approximations is studied for varies χ,ν,β,μ,σ2. We also consider an application to stochastic models for particle sedimentation in fluids where the first-passage problem of an integrated Ornstein-Uhlenbeck process naturally arises.

The γ radiolysis of carbon tetrachloride at 77 K results in the formation of free radicals which are stable at 185 K and have been identified as ĊCl3. These radicals trapped in crystallites of CCl4 or at 'boundaries' give very different E.S.R. spectra. Their a13C coupling constants are practically identical (117 G et 114 G). The structure of ĊCl3 radicals has been determined: it is nonplanar and the [image omitted] angle has a value of 116°. The action of O2 on the ĊCl3 radicals leads to the CCl3[image omitted]2 peroxide radicals whose a13C coupling at 200 K is 6·15 G.Après irradiation γ à 77 K du tétrachlorure de carbone, le seul radical stable à 185 K est le radical ĊCl3. Le radical ĊCl3, suivant qu'il est piégé au sein des cristallites de CCl4 ou aux joints de grains, donne un spectre R.P.E. très différent.Pour les deux types de radicaux, les constantes de couplage a13C sont voisines (117 G et 114 G). On peut ainsi en déduire que le radical CCl3 est non plan avec une valeur de 116° pour l'angle [image omitted]. Par action de l'oxygène sur le radical ĊCl3, on a observé à 200 K le radical CCl3[image omitted]2 dont la constante de couplage a13C est 6,15 G.

Le radical tert-butyle obtenu par irradiation γ à 77°k du chlorure de tertiobutyle peut se présenter sous deux structures différentes. Une forme pyramidale, ayant pour origine les contraintes exercées par le réseau cristallin, et pour laquelle le couplage a13C avec le carbone central est une fonction décroissante de la température. Une forme plane pour laquelle a13C croît avec la température. L'étude du radical plan a permis de séparer les contributions relatives des vibrations, a13Cv, et de la polarisation des électrons des couches internes et des liaisons, a13Cpol, à la valeur du couplage a13C. Le résultat obtenu confirme la relative insensibilité de a13CPol, par rapport aux détails des substituants du carbone central, prévue par les calculs de Melchior.

Abstract Twenty-seven stable kidney transplant recipients treated with cyclosporine and prednisone were converted to mycophenolate mofetil (MMF) and prednisone 1 year after transplantation. After conversion the patients were treated with a standard daily dose of 1 g MMF b. i. d. and 10 mg prednisone for 4 months. Thereafter, two MMF dose reductions were performed with a 4-month interval. Mycophenolic acid (MPA) trough levels were measured at regular intervals. A relation was found between MPA trough levels and MMF dose. The median MPA trough level for patients treated with 1 g MMF b. i. d. was 4.3 μg/ml (0.95–15.5) and 3.0 μg/ml (0.73–7.8) for patients treated with 750 mg b. i. d. (P = 0.0002). The MPA trough levels further decreased from 3.0 to 2.3 μg/ml (0.6–6.63) in patients treated with 500 mg MMF b. i. d. (P = 0.01). Dose reduction of MMF from 1 g to 750 mg b. i. d. could be performed without acute rejections. A further dose reduction to 500 mg b. i. d. elicited 3 rejections. Patients experiencing an acute rejection had a median MPA trough level of 2.3 μg/ml (1.26–3.38) compared to 3.8 μg/ml (1.48–6.52) in patients without an acute rejection (P = 0.25). We conclude that there is a significant relation between MPA trough levels and MMF dose. MPA trough levels were not predictive of rejection in the present study.

Combining cyclosporin (CsA) and prednisone with mycophenolate mofetil (MMF) results in a significant reduction in the rate of biopsy-proven acute rejection after kidney transplantation. This is achieved with a standard daily MMF dosage of 2 or 3 g. Whether monitoring of the pharmacologically active metabolite mycophenolic acid (MPA) will lead to improved safety and efficacy is unclear.