[Residents in supported housing and factors related to moving towards independent living]. / RIBW-bewoners en de factoren die samenhangen met een overgang naar een andere woonsituatie.

BACKGROUND: Few data are available on predictors for the transition of individuals with mental illness to more independent forms of housing.
AIM: To analyse which variables predict the transition of individuals with severe mental illness from supported housing within the Dutch community housing programs (CHP) to more independent ways of living.
METHOD: Data of 1569 participants were analysed using Cox regression analysis.
RESULTS: Individuals with a personality disorder, current alcohol misuse or who received ambulant care prior to admission in CHP had the highest probability of moving to a more independent way of living. Individuals who received clinical care prior to admission in CHP, individuals with admission in Supported Housing, and individuals with a history of substance dependency had the highest probability of clinical relapse.
CONCLUSION: The predictors found in this study can be used as a starting point both for hypotheses for additional aetiological research and for guidelines covering specific interventions.

Key role for CD4 T cells during mixed antibody-mediated rejection of renal allografts.

We utilized mouse models to elucidate the immunologic mechanisms of functional graft loss during mixed antibody-mediated rejection of renal allografts (mixed AMR), in which humoral and cellular responses to the graft occur concomitantly. Although the majority of T cells in the graft at the time of rejection were CD8 T cells with only a minor population of CD4 T cells, depletion of CD4 but not CD8 cells prevented acute graft loss during mixed AMR. CD4 depletion eliminated antidonor alloantibodies and conferred protection from destruction of renal allografts. ELISPOT revealed that CD4 T effectors responded to donor alloantigens by both the direct and indirect pathways of allorecognition. In transfer studies, CD4 T effectors primed to donor alloantigens were highly effective at promoting acute graft dysfunction, and exhibited the attributes of effector T cells. Laser capture microdissection and confirmatory immunostaining studies revealed that CD4 T cells infiltrating the graft produced effector molecules with graft destructive potential. Bioluminescent imaging confirmed that CD4 T effectors traffic to the graft site in immune replete hosts. These data document that host CD4 T cells can promote acute dysfunction of renal allografts by directly mediating graft injury in addition to facilitating antidonor alloantibody responses.

Facile characterization of translation initiation via nonsense codon suppression.

A new strategy for studying the mechanism of translation initiation in eukaryotes has been developed. The strategy involves the use of an in vitro translation system to incorporate a non-natural fluorescent amino acid into a protein from a suppressor tRNAPheCUA misacylated with that amino acid. It is thereby possible to monitor translation initiation efficiency at an AUG codon in different contexts; this is illustrated for three constructs encoding Escherichia coli dihydrofolate reductase mRNA with different translation initiation regions. Fluorescence measurements after in vitro translation of the mRNAs in rabbit reticulocyte lysate reflected differences in the position and efficiency of translation initiation and, therefore, can be used for characterization of the translation initiation process.

Prognostic indicators of the outcome of meningococcal disease: a study of 562 patients.

To assess prognostic indicators of a fatal outcome in patients with meningococcal disease, data from 562 patients with culture-proven meningococcal disease, reported in the Netherlands between 1 April 1989 and 30 April 1990, were collected prospectively by means of a questionnaire completed by the specialist in attendance. Analysis was done by the chi2 test and multiple logistic regression. During the study period 43 patients (7.7%) died. The risk of a fatal outcome was increased in patients aged 0-5 months, 10-19 years, and > or = 50 years, in female patients and in patients presenting with coma, temperature < or = 38.0 degrees C, mean arterial pressure < or = 70 mmHg, white blood cell count < or = 10 x 10(9)/L and platelet count < or = 100 x 10(9)/L. Predisposing factors and duration of disease before admission were significantly associated with outcome, but these associations disappeared in the multivariate analysis. Race, the administration of antibiotics prior to admission, seizures and haemorrhagic skin lesions were not associated with outcome. In conclusion age, gender, coma, temperature, mean arterial pressure, white blood cell count and platelet count were independent prognostic indicators of the outcome of meningococcal disease. The assessment of these characteristics may be helpful for the identification of high risk patients, whose prognosis might be improved by prompt transfer to an intensive care unit.

Functional morphology of the hindleg in two kangaroos Macropus giganteus and Aepyprymnus rufescens.

In this study the structures in the hindleg of the kangaroo which are potentially available for jumping were examined. Specimens of two species, Macropus giganteus and Aepyprymnus rufescens, were examined and are described and compared. The basic pattern of the jump of the two species is similar. This is reflected anatomically by the fact that in both species the extensors of the hip, knee and ankle as a percentage of the total weight of the hindleg are greater than the flexors of the same joints. An additional similarity is that the biceps femoris and adductor magnus have the greatest share in the weight of the hip extensors. Furthermore the estimated total force of the hip, knee and ankle extensors and total moment of the hip and ankle extensors are always greater than the flexors of the same joints. However, the percentage of the hip and knee extensors, the absolute forces and moments of both the extensors and flexors and the range of movement especially of the hip and knee are always greater in M. giganteus than in A. rufescens. As well as these differences, the long tibia and the position of the knee in view of the hip may be important factors for the longer jump achieved by M. giganteus. In comparison A. rufescens has a anatomical construction which seems to be a compromise between walking and jumping.

Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Alendronate has been described to have a bone-sparing effect in patients treated with moderate and high dosages of prednisone for heterogeneous diseases, however no data are available on groups of patients with the same underlying diseases who receive chronic low-dose prednisone treatment. The objective of the investigation reported here was, therefore, to study the effect of alendronate on bone mineral density (BMD) of the lumbar spine and hips in patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone treatment. METHODS: A total of 163 patients with RA, according to the ACR-criteria, were enrolled in a double-blind, placebo-controlled trial. The patients were treated with low-dose prednisone (

Muscle fatigue and efficiency in relation to interval duration of successive contractions.

The work output, energy consumption and efficiency during repetitive dynamic contractions were calculated for rat extensor digitorum longus muscle. The muscles performed 40 successive dynamic contractions at 37 degrees C (with occluded bloodflow) with interval durations of either 500, 250 or 167 ms. The muscle-tendon complexes were allowed to shorten at the velocity at which they could exert their highest power output (50 mm.s-1). Work output in the first contraction was the same among the three groups with different interval durations. The reduction in work output during the series of contractions differed among the groups, mainly in the last part of the exercise period. In the group with the longest interval duration, work output steadily decreased over the whole contraction period and at the end was approximately 72% of the output in the first contraction. In contrast, after the 30th contraction, work output decreased at a significantly higher rate of approximately 3% of each contraction in the groups with the intermediate and the shortest interval duration. After the last contraction, work output in these groups was approximately 52% of the work output in the first contraction. These differences in fatigue coincided with differences in the reduction in adenosine 5'-triphosphate and the production of inosine-5'-monophosphate. Total work output was not significantly different among the three groups with different interval durations, indicating that the different reductions in work output in the last contractions only had a minor influence on total work output of all 40 contractions. Also high-energy phosphate consumption and efficiency were not significantly different over these three exercise periods. Thus with the protocol used no interval dependent pattern of efficiency could be detected.

Effect of growth on efficiency and fatigue in extensor digitorum longus muscle of the rat.

The effect of growth on work output, energy consumption and efficiency during repetitive dynamic contractions was determined using extensor digitorum longus muscles of 40-, 60-, 120- and 700-day-old male Wistar rats. When work output of each contraction was normalized to the work output of the first contraction it was found that work output initially increased over the first 10-20 contractions by approximately 8% in each age group. Thereafter a faster decrease in work output was found in the youngest group (approximately 2% each contraction) compared to the older groups (approximately 0.7% each contraction). After 40 contractions the reduction in work output was significantly different only between the youngest group and the two oldest groups (-30% vs -5%). These differences in fatigue were not associated with differences in adenosine 5'-triphosphate and phosphocreatine concentrations or in lactate production. Total work output and high-energy phosphate consumption increased by approximately 555% and 380% from age 40 to 120 days, respectively. Consequently, efficiency was significantly higher (approximately 32%) in the older groups compared to 40-day-old animals. Normalized for muscle mass, mean rate of high-energy phosphate consumption was similar in all groups whereas mean power output was significantly lower in the youngest group (approximately 46%). Thus, the difference in efficiency between the young and the other groups may be attributed to a lower external power production in the youngest group rather than changes in energy turnover.

Age-related effects of fatigue and recovery from fatigue in rat medial gastrocnemius muscle.

Force-velocity, power-velocity and unloaded shortening data were obtained from in situ medial gastrocnemius muscle-tendon complexes (stimulated at 60 Hz) with intact circulation of mature male rats (approximately 125 days old). Measurements were carried out at the end of a long (15 s) contraction (fatigued muscles) or with a short (1 s) contraction either in the fresh state (fresh muscles) or in muscles which had recovered for 15 min after a long contraction. Compared to the fresh state fatigue reduced isometric force by 57%, maximal shortening velocity by approximately 40% and maximal power output by 81%. These reductions were similar to data previously obtained with younger rats (40 days old). However, the velocity data of the muscles which had recovered for 15 min after a long contraction showed a greater reduction in the mature rats. This difference between the two age groups together with a difference in the changes in the initial parts of the isometric force time curves suggest an age-dependent response of the fast-fatigable fibre population of these mixed muscles. In a separate series of experiments the underlying mechanism of the recovery from fatigue was studied in a group of young rats. Fatigue was induced with five long (15 s) contractions (each at 5 min intervals). The recovery of isometric force and power output was monitored with short contractions which indicated a plateau of recovery but the absolute values were still reduced after 60 min (85 and 71% of prefatigue values, respectively). Phosphocreatine concentration recovered rapidly, whereas the ATP concentration was still markedly reduced after 1 h of recovery. The time courses of recovery of inosine-5'-monophosphate (IMP) and lactate concentrations resembled those of force and power output. Thus it is possible that age-dependent differences in IMP and/or lactate production may play a role in fatigue and recovery from fatigue.

Effect of shortening velocity on work output and energy cost during repeated contractions of the rat EDL muscle.

The effect of shortening velocity on the reduction in work output, energy consumption and efficiency during repetitive contractions has been determined in rat extensor digitorum longus muscle. Muscles in situ (with occluded blood flow, 37 degrees C) were stimulated to perform 40 successive contractions (at 4 Hz) with a total duration of the exercise period of 10 s and shortening velocities of either 25, 50 or 75 mm.s-1 (whole muscle-tendon complex). Care was taken that work output during the shortening phase of the first contraction was the same for the different velocities used. Total work output of the 40 contractions was not significantly different between the three groups with different shortening velocities; nor was there a significant difference in the high-energy phosphate consumption over this 10-s exercise period. However, when the ratio of total work output and total energy consumption was calculated a significantly higher efficiency (25-30% in comparison with the efficiency of the other two velocities) was found with the shortening velocity of 50 mm.s-1. There was no significant difference in efficiency between shortening velocities of 25 and 75 mm.s-1. This suggests that with this protocol efficiency showed a velocity-dependent pattern that may have the same shape as the power/velocity curve. Whereas total work output during the 10-s exercise period was not significantly different between the velocities studied, the time course of the changes in work output was quite different. With shortening velocities of 50 and 75 mm.s-1 work output initially increased by maximally 6% and 12% respectively in contrast to a steady level in the contractions with a velocity of 25 mm.s-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of an active pre-stretch on fatigue of skeletal muscle.

In activities such as running, many muscles of the lower extremities appear to be actively stretched before they are allowed to shorten. In this study we investigated the effect of an active pre-stretch on the fatigability of muscles. Thus muscle contractions were compared in which shortening was preceded by an active isometric phase or by an active stretch. Rat medial gastrocnemius muscle-tendon complexes (with arrested blood flow) performed a series of ten repeated contractions (1.s-1) with either an active stretch or an isometric phase preceding the shortening. Contraction duration (0.45 s), and shortening duration (0.3 s), distance (6 mm) and velocity (20 mm.s-1) were the same in both types of contraction. Work output during the ten shortening phases was approximately 40% higher in the contractions with an active pre-stretch; in contrast, high-energy phosphate utilization was similar. Over the ten repeated contractions reduction of work output during the shortening phases of both types of contraction was similar in absolute terms (approx. 9.5 mJ). It is suggested that all the extra work performed during the shortening phases after a pre-stretch originated from sources other than cross-bridge cycling, which are hardly affected by fatigue. However, reduction of work output in relative terms, which is how the reduction is often expressed in voluntary exercise, was less after a pre-stretch (26% vs 32%), giving the impression of protection against fatigue by an active pre-stretch.

Changes in morphological and functional characteristics of male rat EDL muscle during growth.

Morphological and functional changes as well as changes in fibre-type composition were investigated in the left extensor digitorum longus (EDL) muscles of male Wistar rats of approximately 40, 60, 120 and 700 days old. A number of morphological changes occurred in the EDL muscle during growth. While from 40 to 120 days muscle mass and cross-sectional area (CSA) increased by 247 and 192%, changes in muscle and fibre lengths were much smaller (44 and 17%, respectively). Besides morphological changes tetanic force was also found to increase (approximately 307%) up to 120 days. Because this increase in force was greater than the increase in CSA, specific force increased by approximately 29% between 40 and 60 days. Thereafter, specific force stayed rather constant. From 40 until 60 days changes were also found in the force-frequency and force-velocity curve, which indicate a slowing of the muscles (until 60 days). Changes in fibre-type composition of the EDL muscle were found to occur later during growth between 60 and 120 days. In this period an increase in the relative total area of Type IIBd fibres and a decrease in the relative total area of Type IIBm fibres (corresponding to the Type 2X and IIB fibres, respectively), were found; this was apparently due to a conversion of many Type IIBm into Type IIBd fibres and not to a difference in cross-sectional growth between these fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical manifestations and course of meningococcal disease in 562 patients.

To describe the clinical manifestations and course of meningococcal disease (MD) data were collected on patients with culture-proven MD, reported in the Netherlands between April 1, 1989 and April 30, 1990 by means of a questionnaire completed by the specialist in attendance. During the study period, 562 patients (295 males, 267 females) were reported. The age of the patients ranged from 2 weeks to 88 years. Of the patients, 57.8% were classified as meningitic, 20.3% as bacteraemic and 21.9% as both meningitic and bacteraemic. In 4.6% of the patients a predisposing factor was present, and in 1.4% a previous episode of meningitis had occurred. A positive family history of meningitis was reported in 12.9% of the patients. On admission, 65.2% of the patients had haemorrhagic skin lesions, 7.9% coma and 4.2% seizures. During admission, 17.8% of the patients developed serious complications. The fatality rate was 7.7%. In 73.2% of the deceased, death occurred within 2 days after admission. Of the survivors, 8.5% recovered with serious sequelae. In conclusion, 16% of the patients with meningococcal disease either died or became severely disabled. Prevention of this putative life-threatening disease seems to be the only means of circumventing the problems caused by this serious condition.

Efficiency of rat medial gastrocnemius muscle in contractions with and without an active prestretch.

The efficiency of positive work was measured for rat medial gastrocnemius muscle at 25 degrees C during repeated contractions. Six muscles were stimulated to perform concentric contractions preceded by an active prestretch (PS contractions) and six muscles made to give concentric contractions from an isometric state (PI contractions). Both lengthening and shortening of the muscles (distance: 6 mm) occurred at a constant velocity of 20 mm s-1 (1.5 fibre lengths s-1). Stimulation was started 150 ms prior to the onset of concentric contraction for both types of contraction. For the PS contractions this meant that the active state was developed during the last 2.4 mm of the lengthening. Energy consumption (calculated from high-energy phosphate consumption) appeared to be equal for both types of contraction, although positive work output was 39.4% higher in the PS contractions than in the PI contractions. The efficiency of positive work was 36.8 +/- 3.5% in the PS contractions and 26 +/- 2.0% in the PI contractions. In contrast to results of previous studies, the positive work done by the muscle in the PS contractions was much larger than the negative work done on the muscle during stretch owing to the applied stimulation protocol which was intended to simulate in vivo conditions during running. The efficiency of positive work in the PS contractions is too low to explain the efficiencies of 40-70% reported for human and animal running.

Probing the S1/S1' substrate binding pocket geometry of HIV-1 protease with modified aspartic acid analogues.

Aspartates 25 and 125, the active site residues of HIV-1 protease, participate functionally in proteolysis by what is believed to be a general acid-general base mechanism. However, the structural role that these residues may play in the formation and maintenance of the neighboring S1/S1' substrate binding pockets remains largely unstudied. Because the active site aspartic acids are essential for catalysis, alteration of these residues to any other naturally occurring amino acid by conventional site-directed mutagenesis renders the protease inactive, and hence impossible to characterize functionally. To investigate whether Asp-25 and Asp-125 may also play a structural role that influences substrate processing, a series of active site protease mutants has been produced in a cell-free protein synthesizing system via readthrough of mRNA nonsense (UAG) codons by chemically misacylated suppressor tRNAs. The suppressor tRNAs were activated with the unnatural aspartic acid analogues erythro-beta-methylaspartic acid, threo-beta-methylaspartic acid, or beta,beta-dimethylaspartic acid. On the basis of the specific activity measurements of the mutants that were produced, the introduction of the beta-methyl moiety was found to alter protease function to varying extents depending upon its orientation. While a beta-methyl group in the erythro orientation was the least deleterious to the specific activity of the protease, a beta-methyl group in the threo orientation, present in the modified proteins containing threo-beta-methylaspartate and beta,beta-dimethylaspartate, resulted in specific activities between 0 and 45% of that of the wild type depending upon the substrate and the substituted active site position. Titration studies of pH versus specific activity and inactivation studies, using an aspartyl protease specific suicide inhibitor, demonstrated that the mutant proteases maintained bell-shaped pH profiles, as well as suicide-inhibitor susceptibilities that are characteristic of aspartyl proteases. A molecular dynamics simulation of the beta-substituted aspartates in position 25 of HIV-1 protease indicated that the threo-beta-methyl moiety may partially obstruct the adjacent S1' binding pocket, and also cause reorganization within the pocket, especially with regard to residues Val-82 and Ile-84. This finding, in conjunction with the biochemical studies, suggests that the active site aspartate residues are in proximity to the S1/S1' binding pocket and may be spatially influenced by the residues presented in these pockets upon substrate binding. It thus seems possible that the catalytic residues cooperatively interact with the residues that constitute the S1/S1' binding pockets and can be repositioned during substrate binding to orient the active site carboxylates with respect to the scissile amide bond, a process that likely affects the facility of proteolysis.

Hand cortical bone mass and its associations with radiographic joint damage and fractures in 50-70 year old female patients with rheumatoid arthritis: cross sectional Oslo-Truro-Amsterdam (OSTRA) collaborative study.

OBJECTIVE: To investigate the relationship between hand bone mineral density (BMD) and radiographic joint damage, and between hand BMD and fractures in 50-70 year old women with longstanding RA. METHODS: Demographic, clinical data, and imaging data on hand radiographs and Genants vertebral deformity score on spine radiographs were collected from 135 women with RA of > or =5 years, recruited from three European rheumatology clinics. Metacarpal hand BMD was measured by digital hand x ray radiogrammetry (DXR), and hip and lumbar spine BMD by dual x ray absorptiometry (DXA). Multiple regression analyses were used to examine associations between hand BMD and radiographic joint damage, and hand BMD and fractures. RESULTS: Hand BMD was strongly and independently associated with radiographic hand joint damage in a linear regression model adjusted for age, centre, BMI, disease duration, RF, 18 deformed joint count, ESR, and femoral neck BMD. In a multivariate logistic regression model adjusted for relevant variables, hand BMD and femoral neck BMD, but not spine BMD, were independently associated with vertebral deformities and with non-vertebral fractures. CONCLUSION: BMD measured by DXR on conventional hand radiographs in patients with RA may potentially be used as an indicator of joint damage and of vertebral and non-vertebral fracture risk.

Reproducibility of bone mineral density measurement in daily practice.

BACKGROUND: Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. OBJECTIVE: To examine the reproducibility of BMD by dual energy x ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in a group of postmenopausal women. METHODS: Ninety five women, mean age 59.9 years, underwent two subsequent BMD measurements of spine and hip. Reproducibility was expressed as smallest detectable difference (SDD), coefficient of variation (CV), and intraclass correlation coefficient (ICC). Sources of variation were investigated by multilevel analysis. RESULTS: The median interval between measurements was 0 days (range 0-45). The mean difference (SD) between the measurements (g/cm(2)) was -0.001 (0.02) and -0.0004 (0.02) at L1-4 and the total hip, respectively. At L1-4 and the total hip, SDD (g/cm(2)) was +/-0.05 and +/-0.04 and CV (%) was 1.92 and 1.59, respectively. The ICC at spine and hip was 0.99. CONCLUSIONS: Reproducibility in the postmenopausal women studied was good. In a repeated DXA scan a BMD change exceeding 2 radical 2CV (%), the least significant change (LSC), or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC (%) because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least +/-0.05 g/cm(2) at L1-4 and +/-0.04 g/cm(2) at the total hip should be considered significant.

Bone mineral density in patients with rheumatoid arthritis: relation between disease severity and low bone mineral density.

OBJECTIVE: To examine variables associated with bone mineral density (BMD) in patients with rheumatoid arthritis (RA). METHODS: We investigated 373 patients with low to moderately active RA. Patients with low disease activity were recruited from a cohort of patients in clinical remission. Patients with moderately active disease were included in a trial comparing the effects of long term high intensity exercise programme and conventional physical therapy. Demographic and clinical data were collected. Bone mineral density (BMD) was measured by means of dual x ray absorptiometry (DXA). Associations between demographic and clinical measurements on the one hand and BMD on the other were investigated in regression analyses. RESULTS: The patient group consisted of middle aged, mainly female, patients. The median (interquartile range) disease duration was 7 (4 to 13) years, the mean disease activity score (standard deviation) was 3.2 (1.4). Of the group, 66% was rheumatoid factor positive, and 83% (n = 304) had never used corticosteroids. The median Larsen score of hands and feet was 27 (5 to 61). Greater age and low body mass index were related to low BMD at the hip and spine. High Larsen score for hands and feet was significantly associated with low BMD at the hip. The use of corticosteroids was not independently associated with BMD. The results of the multiple regression analyses also applied to the subgroup of corticosteroid naive patients. CONCLUSION: BMD data of patients with low to moderately active RA demonstrated an association between high radiological RA damage and low BMD at the hip, which suggests an association between the severity of RA and the risk of generalised bone loss, which also occurred in corticosteroid naive patients.