Placental transfer and pharmacokinetics of allopurinol in late pregnant sows and their fetuses.

At present no standard pharmacological intervention strategy is available to reduce these adverse effects of birth asphyxia. In the present study we aimed to evaluate placental transfer of allopurinol, an inhibitor of XOR. For this purpose, fetal catheterization of the jugular vein was conducted in five late pregnant sows (one fetus per sow). At 24-48 h after surgery, sows received allopurinol (15 mg/kg body weight; i.v.) and pharmacokinetics of allopurinol and its active metabolite oxypurinol were measured in both late pregnant sows and fetuses. Maternal and fetal blood samples were collected during and after allopurinol administration. Maternal C(max) values averaged 41.90 microg/mL (allopurinol) and 3.68 microg/mL (oxypurinol). Allopurinol crossed the placental barrier as shown by the average fetal C(max) values of 5.05 microg/mL at 1.47 h after allopurinol administration to the sow. In only one fetus low plasma oxypurinol concentrations were found. Incubations of subcellular hepatic fractions of sows and 24-h-old piglets confirmed that allopurinol could be metabolized into oxypurinol. In conclusion, we demonstrated that allopurinol can cross the placental barrier, a prerequisite for further studies evaluating the use of allopurinol as a neuroprotective agent to reduce the adverse effects following birth asphyxia in neonatal piglets.

Umbilical cord clamping in term piglets: a useful model to study perinatal asphyxia?

Perinatal asphyxia results in tissue and cellular changes during the reperfusion period and clinical signs like perinatal mortality and decreased vitality at birth in newborn piglets. This study aimed to develop and validate a model of birth asphyxia, mimicking the evolvement of birth asphyxia in natural farrowings by conducting umbilical cord clamping (UCC) in term piglets during caesarean sections under general anaesthesia. In total 23 piglets were subjected to 5-8min of UCC and 24 piglets served as controls. Acid-base balance values and heart rates measured before UCC remained fairly constant throughout the surgical procedure, indicating nearly identical starting conditions of piglets within and between litters. UCC resulted in a significant, mild, mixed respiratory-metabolic acidosis (pH 7.22, pCO(2) 9.8kPa, BE(ecf) 2mmol/L, lactate 6.5mmol/L; controls: pH 7.31, pCO(2) 8.5kPa, BE(ecf) 5mmol/L, lactate 4mmol/L) at 10min after birth (defined as simultaneous cutting of the umbilical cord and removal of a plastic bag that had been placed over the head to avoid air intake). Heart rates were significantly decreased during UCC (range: 83-107beats/min versus 128-134beats/min in controls). Rectal temperatures and changes in body weight until 72h of life were not affected by UCC. Interestingly, four control and seven clamped piglets did not survive as no independent respiration could be attained. Birth weights and duration of UCC of these piglets did not differ significantly from those in surviving control and clamped piglets. In conclusion the mixed respiratory-metabolic acidosis arising in the surviving clamped piglets is not as severe as can be expected in highly asphyxiated, vaginally delivered newborn piglets. Repeatability of the model is compromised by considerable variation in the individual response to UCC.

Dietary specific antibodies in spray-dried immune plasma prevent enterotoxigenic Escherichia coli F4 (ETEC) post weaning diarrhoea in piglets.

In order to establish the mechanism of spray dried plasma powder (SDPP) in improving pig health and performance, a diet containing either 8% SDPP, spray dried immune plasma powder (SDIPP), or control protein (soybean and whey) ration was fed to piglets in an experimental model of enterotoxigenic Escherichia coli F4 (ETEC) post-weaning diarrhoea (PWD). SDIPP was obtained from pigs immunized with a vaccine containing ETEC fimbrial subunit F4 and heat-labile toxin (LT), and SDPP from non-immunized controls. Average daily growth (ADG) was determined, and daily samples of rectal faeces were assessed for diarrhoea (as percentage of dry matter), and ETEC excretion (in CFU/g). SDPP and SDIPP significantly (p<0.05) reduced diarrhoea, and SDIPP significantly reduced ETEC excretion. ADG was not significantly (p>0.05) affected. After the experiment, 30% of piglets tested F4 receptor positive (F4R+). A significant correlation between F4R status and morbidity was found. In F4R+ animals, SDIPP significantly improved diarrhoea and ADG, and decreased ETEC excretion, and SDPP significantly improved diarrhoea and ADG. Surprisingly, SDPP reduced diarrhoea in F4R+ animals without significant reduction of ETEC excretion, which is most likely related to the presence of anti-LT antibodies in SDPP. The results show that oral protection against ETEC by SDPP is attributable to spontaneous antibodies, in this case anti-LT antibodies. Furthermore, the results indicate that the combination of anti-LT and anti-F4 antibodies as in SDIPP is most effective in ETEC prevention. Finally, the F4R distribution in the herd should be taken into account to correctly assess efficacy.

Role of human leucocyte antigen DQ in the presentation of T cell epitopes in the major cow's milk allergen alphas1-casein.

BACKGROUND: Little is known about the association between human leucocyte antigen (HLA) and cow's milk allergy (CMA). The aim of the present study was to determine the HLA restriction of T cell clones (TCCs) specific to alphas1-casein, the most abundant milk protein, and to study possible HLA class II allele associations with CMA. METHODS: alphas1-Casein-specific TCCs were derived from 6 children with CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope specificity was defined by stimulation with overlapping peptides, spanning the alphas1-casein molecule. HLA restriction was determined in proliferation assays using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals. RESULTS: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA-DP. The sequence in alphas1-casein that was most immunogenic to T cells from children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401 and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than in non-atopic children, but this difference could not be confirmed in an additional group of subjects with and without CMA. CONCLUSIONS: HLA-DQ plays a substantial role in the presentation of T cell epitopes in alphas1-casein. However, HLA class II allele frequencies do not show major differences between cow's milk allergic, atopic and non-atopic subjects. T cell epitopes in the most immunogenic region are presented by various abundantly present HLA genotypes. Therefore, this sequence may be a suitable target for peptide immunotherapy.

Acid-base balance of umbilical artery blood of liveborn piglets at birth and its relation with factors affecting delivery of individual piglets.

In the limited number of studies that reported on the relation between factors affecting birth of individual piglets and acid-base balance values at birth, predominantly simple correlation coefficients have been used. The aim of the present study was to analyse the relation between factors affecting delivery of individual liveborn piglets and acid-base balance values (pH, PCO(2) , HCO(3)(-) and BE(ecf)) at birth. In total 201 piglets originating from 44 litters were used for the collection of blood samples from the umbilical artery immediately after birth, preferably in the period of apnea. Blood samples were analysed with the iStat Portable Clinical Analyser. Significantly lower pH, HCO(3)(-), BE(ecf) and significantly higher PCO(2) levels were found in posteriorly presented piglets, independently of the condition of the umbilical cord, birth weight and cumulative birth interval/rank. Independently of presentation, birth weight and rank, piglets born with ruptured umbilical cords showed significantly lower pH values. Next to that, increasing birth weights resulted in increasing HCO(3)(-) and BE(ecf) values at birth, independently of presentation, condition of the umbilical cord and cumulative birth interval/rank. Both an increase in cumulative birth interval and in rank was associated with a significant decrease of pH, HCO(3)(-), BE(ecf) and increase of PCO(2) levels in umbilical cord blood at birth. Together these results demonstrate for the first time that a clear relation exists between (factors affecting) the progress of delivery and acid-base balance values in a polytocous species like the pig.

Factors affecting duration of the expulsive stage of parturition and piglet birth intervals in sows with uncomplicated, spontaneous farrowings.

Modern pig farming is still confronted with high perinatal piglet losses which are mainly contributed to factors associated with the progress of piglet expulsion. Therefore the aim of this study was to identify sow- and piglet factors affecting the duration of the expulsive stage of farrowing and piglet birth intervals in spontaneous farrowing sows originating from five different breeds. In total 211 litters were investigated. Breed affected duration of the expulsive stage significantly: the shortest duration was found in Large White x Meishan F2 crossbred litters and the longest duration in Dutch Landrace litters. No effect of parity on the duration of the expulsive stage was found. An increase in littersize (P<0.01), an increase in number of stillborn piglets per litter (P<0.05) and a decrease of gestation length (P<0.05, independently of littersize) all resulted in an increased duration of the expulsive stage of farrowing. A curvilinear relationship between birth interval and rank (relative position in the birth order) of the piglets was found. Besides that, piglet birth intervals increased with an increasing birth weight (P<0.001). Stillborn (P<0.01) and posteriorly presented (P<0.05) piglets were delivered after significantly longer birth intervals than liveborn and anteriorly presented piglets. The results on sow- and piglet factors affecting duration of the expulsive stage and piglet birth intervals obtained in this study contribute to an increased insight into (patho) physiological aspects of perinatal mortality in pigs.

[Spray-dried plasma in diets for weaned piglets: influence on growth and underlying mechanisms]. / Gesproeidroogd bloedplasma in voeders voor gespeende biggen: invloed op groei en achterliggende mechanismen.

Spray-dried animal plasma (SDAP) is a by-product of slaughter plants. The plasma obtained from slaughtered pigs or ruminants is spray-dried and used for the production of human foodstuffs and animal feeds. SDAP added to the diet of weaned piglets has considerable positive effects on the growth performance of piglets. In a meta-analysis, it was calculated from 68 comparisons between SDAP-containing diets and control diets that the SDAP-induced change in average daily gain (ADG) and average daily feed intake (ADFI) in the first 2 weeks after weaning was +26.8% and +24.5%, respectively. Two experiments demonstrated that dietary SDAP can reduce post-weaning diarrhoea. The aim of the research described in this thesis was to learn more about the mechanisms underlying the growth- and health-promoting properties of SDAP in the diet of weaned piglets. Results showed that dietary SDPP has positive effects on the post-weaning growth performance and health of piglets. These effects are more pronounced in piglets kept under suboptimal conditions and/or high infection pressure, and in piglets fed on diets lacking anti-microbial growth promoters. SDAP acts by influencing the gastrointestinal microflora: it appears to affect pathogenic bacteria rather than exert a general anti-bacterial effect leading to nutrient sparing, as has been described for anti-microbial growth promoters. SDAP has great potential as treatment for immuno-compromised mammals, such as neonates, and for animals in which antibiotic treatment is not possible, for instance when there is a ban against antibiotics or when multi-resistant bacteria are involved.

Small intestinal morphology and disaccharidase activities in early-weaned piglets fed a diet containing spray-dried porcine plasma.

The purpose of this study was to test whether dietary spray-dried porcine plasma (SDPP) in early-weaned piglets prevents small intestinal villus atrophy by trophic or protective activity. Fifty-four weaned, 18-day-old piglets were used to determine the effect of dietary SDPP on small intestinal villus length, crypt depth, enterocyt mitotic activity and brush border enzyme activities during the first week after weaning. The piglets were offered a diet containing either 8% SDPP or 8% casein. At 2 and 7 days after weaning, piglets were anaesthetized to provide samples of the small intestinal wall and killed immediately afterwards. There were no differences in daily gain and daily feed intake between the two dietary treatments. At day 2 after weaning, all piglets showed a marked reduction in villus height when compared with baseline values. In all piglets, small intestinal enterocyte mitotic activity had decreased by day 2 and was increased again on day 7. There were no significant effects of dietary SDPP on small intestinal villus length, crypt depth and enterocyt mitotic activity. This indicates that SDPP has no trophic effect on the small intestinal mucosa and that it does not protect against the damaging effect on the small intestinal villi that is associated with the process of weaning. There was no effect of SDPP on lactase-, sucrase- or maltase-specific activities that are a measure of the digestive function of the small intestine. It can be concluded that SDPP versus casein has no effect on small intestinal morphology and disaccharidase activities in early weaned piglets kept under low infection pressure.

Transferrin toxin but not transferrin receptor immunotoxin is influenced by free transferrin and iron saturation.

BACKGROUND: Cytotoxic agents can be targeted successfully to cancer cells. The efficacy of such novel and potent anticancer strategies may be influenced by variables of iron metabolism. METHODS: The in vitro cytotoxicity against glioma cells of transferrin (Tf)-based targeted toxins was compared with that of alpha-transferrin receptor (TfR)-immunotoxin. RESULTS: Of four Tf-based targeted toxins, Tf-gelonin, Tf-pokeweed antiviral protein, Tf-momordin and Tf-saporin, inhibitory concentration 50% values against glioma-derived cell lines HS683 and U251, ranged from [4.8 +/- 1.5] x 10(-10) m for Tf-saporin to [26.9 +/- 15.3] x 10(-10) m for Tf-gelonin in [(3)H]-leucine incorporation assays. Tf-saporin and alpha-TfR-saporin-immunotoxin had similar efficacy, even in the more quantitative clonogenic assay (4-5 log kill with 1 x 10(-9) m) using the myeloma cell line RPMI 8226 and glioma cell line U251. However, on RPMI 8226, the efficacy of Tf-saporin 1 x 10(-9) m was reduced by 90% in the presence of 150 microg mL(-1)(=20% of normal plasma value) competing diferric transferrin, whereas the efficacy of the corresponding immunotoxin was affected only marginally. In addition, the efficacy of Tf-based conjugates will depend on their iron saturation state. Iron desaturation of Tf-saporin was demonstrated by [(59)Fe]-labelling, subsequent CM-Sepharose chromatography and SDS-PAGE. Desaturation led to virtually complete loss of affinity for the transferrin receptor, as determined by flow cytometry, which could be largely restored upon resaturation. CONCLUSION: Transferrin-based toxin conjugates are strongly influenced by the presence of free transferrin and the iron saturation state. The corresponding alpha-transferrin receptor-immunotoxin does not show these disadvantages, has similar efficacy and should be preferred for further experiments.

Growth performance and health status in weanling piglets fed spray-dried porcine plasma under typical Northern European conditions.

The effect of inclusion of spray-dried porcine plasma (SDPP) in diets for weanling piglets was studied. The objectives were to determine whether SDPP would have positive effects on post-weaning piglet performance and health under typical Northern European conditions. In experiment 1, 160 weanling piglets were assigned randomly to a control diet or a diet containing 3% SDPP, which was added at the expense of both fishmeal and dried skim milk. In experiment 2, 264 weanling piglets were assigned to a control diet containing whey protein, a diet without whey protein but with SDPP or a diet containing both whey protein and SDPP. In essence, SDPP was added to the test diets at the expense of either whey protein or fishmeal. Piglets were fed the diets for 3 weeks. In experiment 1, the piglets fed the SDPP diet had a 7% higher average daily gain (ADG) and a 4% lower feed conversion ratio (FCR) (p < 0.05) during the first 3 weeks after weaning than did those fed the control diet. There were no differences in leucocyte counts or gamma-globulin. In experiment 2 there were no significant differences in ADG and FCR among the dietary treatments. It is concluded that low amounts of SDPP in weanling diets can have positive effects on growth performance under Northern European conditions.

The effect of dietary spray-dried porcine plasma on clinical response in weaned piglets challenged with a pathogenic Escherichia coli.

Weaned piglets were used to determine the effect of dietary spray-dried porcine plasma (SDPP) on the clinical response to an infection with a pathogenic Escherichia coli (E. coli) O139:K82 LT(-). The piglets were divided into two groups of 10 animals each. One group was fed the control diet containing soybean(meal) plus whey powder. The test piglets were fed a diet with 8% SDPP. Piglets were orally infected with the challenge strain on days 6 and 7 after weaning. The experimental period lasted 14 days after which the piglets were euthanised and necropsied. Faecal samples were collected daily for bacteriological analysis. Segments of jejunum, caecum and rectum were removed for bacteriological analysis post mortem. Feed intake and weight gain, faecal and condition scores and body temperature were measured daily. In the control and SDPP groups, 6 and 7 piglets died from diarrhoea. The average daily feed intake (ADFI) and average daily gain (ADG) were substantially higher in the SDPP group than in the control group. SDPP-fed piglets generally had a more favourable faecal score and a healthier appearance than did the control piglets. The faecal excretion of E. coli O139:K82 was similar for control and test piglets. There were no diet effects on the E. coli O139:K82 counts at different sites of the intestine. In this experiment, the inclusion of SDPP at an economically acceptable percentage in the diet could not prevent piglet losses due to challenge with a pathogenic E. coli, but improvements of ADG, ADFI and faecal and condition scores were achieved.

Small intestinal morphology in weaned piglets fed a diet containing spray-dried porcine plasma.

The hypothesis tested in this study was that the reported beneficial effects of spray-dried porcine plasma (SDPP) on piglet post-weaning performance and health are associated with a trophic effect on small intestinal mucosa. At 24 days of age, the piglets of seven sows were assigned to one of three treatment groups. One group continued to be suckled. The other two groups were weaned and offered a diet containing either 15 per cent SDPP or casein. From each treatment group, one piglet was anaesthetised and samples were taken from the small intestinal wall at 26, 28 and 31 days of age. There were no significant effects of SDPP versus casein on villus length. On average, there was less mitotic activity in the SDPP -fed piglets than in those fed casein on days 4 and 7 after weaning. As less mitotic activity leads to less immature enterocytes, this may provide a mechanism for the reported beneficial effects of SDPP on performance and health.

In vitro evidence for differential involvement of CTGF, TGFbeta, and PDGF-BB in mesangial response to injury.

BACKGROUND: Connective tissue growth factor (CTGF) is a profibrotic growth factor, which is upregulated in wound healing and renal fibrosis, including anti-Thy-1.1 nephritis. The kinetics of CTGF mRNA expression in anti-Thy-1.1 nephritis suggested that CTGF regulation might contribute to glomerular response to injury downstream of transforming growth factor-beta (TGFbeta). In anti-Thy-1.1 nephritis the initial damage is followed by mesangial repair and limited sclerosis, which involves mesangial cell (MC) activation (alpha-smooth-muscle actin (alphaSMA) expression), proliferation, migration, and extracellular matrix production. The present in vitro study addresses the possible role of CTGF in these different aspects of mesangial response to injury, and how CTGF activity might relate to effects of TGFbeta and platelet-derived growth factor-BB (PDGF-BB). METHODS AND RESULTS: Immunostaining and ELISA showed that alphaSMA expression and transformation of MC into myofibroblast-like cells was induced by TGFbeta, but not affected by PDGF-BB, CTGF, or neutralizing anti-CTGF antibodies. [(3)H]thymidine incorporation and Ki67 staining demonstrated that, unlike PDGF-BB, neither CTGF nor TGFbeta induced the proliferation of MC. In contrast, both CTGF and TGFbeta induced MC migration, as evidenced by approximation of wound edges in scrape-wounded, non-proliferating rat MC monolayers. In addition, fibronectin expression was upregulated by both CTGF and TGFbeta, as measured by dot-blot analysis. Anti-CTGF completely blocked the effect of added CTGF. Moreover, anti-CTGF significantly reduced TGFbeta-induced increase in fibronectin. CONCLUSION: It thus appears that CTGF is specifically involved in a subset of the adaptive changes of MC involved in mesangial repair and sclerosis, which makes it an interesting candidate target for future intervention strategies.

Identification of human ccn2 (connective tissue growth factor) promoter polymorphisms.

BACKGROUND: Connective tissue growth factor (CCN2; CTGF) is a newly identified growth factor, which is involved in the regulation of wound repair and fibrosis. Because there is variation among individuals with respect to tissue response to injury, genetic factors might be involved in the final outcome of tissue repair or scarring. For example, polymorphisms in the promoter region of genes, such as those encoding transforming growth factor beta1 (TGF-beta1), interleukin 10 (IL-10), and tumour necrosis factor alpha (TNF-alpha), influence transcriptional responses and are thought to contribute to the dysregulation of these genes in pathological conditions. AIM: To investigate whether the promoter region of the ccn2 (ctgf) gene contains polymorphic sequences that might account for differential expression. MATERIALS/METHODS: Seventy seven human DNA samples were sequenced-45 were from healthy controls and 32 were from patients with ischaemic heart disease (IHD)-using M13 tailed sequence specific ccn2 (ctgf) primers for amplification of a 600 bp fragment upstream of the transcription start site. Amplicons were bidirectionally sequenced with a dye primer M13 forward and reverse sequencing kit. RESULTS: A C to G substitution was identified at position -132 in one of the patients with IHD. Moreover, in five of the 32 patients with IHD and in six of the 45 healthy controls, a G to C polymorphism was found at position -447. These substitutions at -132 and -447 are thought to lie within predicted binding domains for the transcription factors Pbx-1 and MZF1, respectively. In addition, insertions at position -43 (G), -47 (C), -71 (G) and a C to T substitution at position -198 were found in all DNA samples compared with the published ccn2 (ctgf) promoter sequence. These corrections do not involve sequences predicted to function as transcription factor binding sites. CONCLUSION: Sequence analysis of the ccn2 (ctgf) promoter of 77 human DNA samples has revealed corrections and polymorphic sites. The latter lie within putative regulatory elements.

Quality of life assessment: its integration in rehabilitation care through a model of daily living.

To integrate quality of life assessment with rehabilitation care, some correspondence is required between the concepts of quality of life and of rehabilitation. A notion of quality of life is presented in which quality is conceived as degree of goodness, and life as daily living. Rehabilitation is considered both a process of adaptation and assistance to that process. These notions of quality of life and of rehabilitation can together be operationalized through a model of daily living. An individual's appraisal of his own situation in relation to adaptation can be explained, assuming a hierarchy of internal standards. Explaining appraisal by others requires external standards. Both types of appraisal are important grounds for decisions regarding assistance. In addition, general ideas on justification of rehabilitation as assistance may influence such decisions. The model integrates both objective and subjective appraisal and ideas on justification into rehabilitation, thereby offering opportunities for theoretical underpinning of the practice.

Outcome of strategy training in stroke patients with apraxia: a phase II study.

OBJECTIVE: Evaluation of a therapy programme for stroke patients with apraxia. The programme is based on teaching patients strategies to compensate for the presence of apraxia. This programme was designed for assessment and treatment by occupational therapists. DESIGN: The outcome was studied in a pre-post test design. Measurements were conducted at baseline and 12 weeks later. SUBJECTS: Thirty-three stroke patients with apraxia were treated at occupational therapy departments n general hospitals, rehabilitation centres and nursing homes. MAIN OUTCOME MEASURES: The following measurements were conducted: an apraxia test, a motor functioning test, observation of activities of daily living (ADL), Barthel Index, and an ADL questionnaire for the therapist and the patient. RESULTS: The patients showed large improvements in ADL functioning on all measures and small improvements on the apraxia test and the motor functioning test. The effect sizes for the disabilities, ranging from 0.92 to 1.06, were large compared to the effect sizes for apraxia (0.34) and motor functioning (0.19). The significant effect of treatment is also seen when individual improvement and subjective improvement are considered. Measured with the Barthel Index for instance, 71% of the patients improved. CONCLUSIONS: These results suggest that the programme seems to be successful in teaching patients compensatory strategies that enable them to function more independently, despite the lasting presence of apraxia.

Life satisfaction of persons with spinal cord injury compared to a population group.

Life satisfaction is thought to be the subjective part of quality of life, i.e. the feelings of the persons concerned about their functioning and circumstances. In this study, life satisfaction of spinal cord-injured persons living in the community is compared to life satisfaction of a population group. Respondents were a nationwide sample of 318 persons with spinal cord injury (response 60%) and 507 inhabitants of a large city in The Netherlands (response 42%). Life satisfaction was measured using the Life Satisfaction Questionnaire, containing one question about general life satisfaction and eight questions about domain-specific life satisfaction. Mean scores of general life satisfaction and of satisfaction with self-care ability, leisure situation, vocational situation and sexual life were lower in persons with spinal cord injury than in the population group, but satisfaction with family life was higher. However, differences in general life satisfaction, satisfaction with leisure situation and with vocational situation could be attributed to differences in the composition of both groups. Satisfaction with self-care ability was lower in persons with tetraplegia than in persons with paraplegia, but we found no differences in other questions. Several relationships between life satisfaction and age and marital status existed, but they were more pronounced in the population group than in the group of persons with spinal cord injury. Time after injury and cause of injury were not related to life satisfaction variables. Uniformity in measurement instruments would facilitate comparisons between studies.

Predictors of health status and life satisfaction in spinal cord injury.

OBJECTIVE: To analyze relationships between injury-related variables, demographic variables, functional health status, and life satisfaction of people with spinal cord injury (SCI). DESIGN: Cross-sectional survey. SETTING: A community in the Netherlands. SUBJECTS: Three hundred eighteen people with SCI, aged 18 to 65 years. Mean age was 39.4 years and mean time after injury was 3.6 years. MAIN OUTCOME MEASURES: Health status was measured with the SIP68. Its six scales were aggregated to three dimensions, measuring physical, psychologic, and social functioning. Life satisfaction was measured with the Life Satisfaction Questionnaire. Data were analyzed by path analysis using LISREL V8. RESULTS: Obtained scores showed that respondents suffered from serious limitations in physical functioning and social functioning, had only a few limitations in psychologic functioning, and were satisfied with their lives in general and with most life domains. Physical functioning was accurately predicted by injury-related variables, but psychologic functioning was not. Next to level and completeness of the injury, the number of secondary complications turned out to be a predictor of functional health. In a path model that had a close fit with the data, injury-related variables were related to health status but not to life satisfaction. Social functioning (-.48), marital status (-.38), psychologic functioning (-.19), and age (-.16) were significant predictors of life satisfaction (total R2=.44). CONCLUSIONS: This study points out the high prevalence of secondary complications and their importance to the health status of people with SCI. Level of social and psychologic functioning are more important predictors of life satisfaction than the seriousness of the injury.

Services for spinal cord injured: availability and satisfaction.

This article discusses service delivery for Spinal Cord Injured (SCI) in the Netherlands. In this wealthy country, almost everyone has access to domestic adaptations and other equipment, regardless of income and with low, or without user contributions. However, satisfaction with this system of its products is rarely examined. Subjects in this research are 318 SCI individuals between 18 and 65 years of age, living in the community at a mean time of 3.6 years after injury. Availability of accessible housing, domestic adaptations, wheelchairs and outdoor transportation is investigated. Satisfaction with available services and satisfaction with service delivery procedures is measured by self-developed questionnaires. Relationships between these satisfaction scores and measures for functional health status (SIP68) and life satisfaction (LSQ) are analyzed. The presence of domestic adaptations is high, and 78.3% said their houses were sufficiently adapted at the time of the interview. Wheelchairs were generally available and most respondents had more than one. However, many users had complaints about their wheelchairs: 35.9% about their manual wheelchairs and 47.5% about their electric wheelchairs. Public transport was rarely used, 51.1% of respondents had an adapted car. Having an adapted car was significantly related to the ability to drive independently. Satisfaction with available services was acceptable, but satisfaction with service delivery procedures was very low. Satisfaction with available services did have a significant relationship with functional health status when the influence of the type of injury was taken into account. Satisfaction with available services also had a significant relationship with life satisfaction, after the influence of functional health status was taken into account. Further research on this topic is recommended.

B7-1 (CD80) as target for immunotoxin therapy for Hodgkin's disease.

In this preclinical study, the potential applicability of an anti-B7-1 immunotoxin (IT) for the treatment of Hodgkin's disease (HD) was investigated. Immunohistochemical analysis demonstrated strong expression of B7-1 on Hodgkin and Reed-Sternberg (R-S) cells and clear expression on dendritic cells, macrophages and some B-cells in tissues, but not on other tissue cells. Flow cytometric analysis demonstrated that B7-1 was expressed on a few monocytes, but not on CD34+ cells from bone marrow, resting T- or B-cells from peripheral blood or epithelial and endothelial cell lines. An anti-B7-1 immunotoxin containing the anti-B7-1 monoclonal antibody (MAb) B7-24 and saporin as toxin moiety was constructed and showed an affinity similar to that shown by the native MAb. It exhibited strong cytotoxicity against the B7-1+ B-cell line Raji (IC50 10(-11) M), R-S cell lines HDLM2, KM/H2 and L428 and also against a B7-1-transfected epithelial cell line, A431, whose parental line lacks expression of B7-1. In clonogenic assays with Raji cells or KM/H2 cells, a 3- or 4-log kill, respectively, was observed. No cytotoxicity was found against the B7-1- epithelial and endothelial cell lines or against haematopoietic progenitor cells. In conclusion, an anti-B7-1 immunotoxin was developed that had good cytotoxicity against R-S cell lines and that may be used in the elimination of R-S cells in vivo. A concomitant elimination of activated antigen-presenting cells may avoid development of antitoxin and anti-mouse Ig responses and allow repeated administration.