The development of evidence-informed physical activity guidelines for adults with spinal cord injury.

OBJECTIVES: To systematically develop evidence-informed physical activity guidelines to improve physical fitness in people with spinal cord injury (SCI). SETTING: This study was conducted in Canada. METHODS: The Appraisal of Guidelines, Research and Evaluation II guideline development protocol was used to develop exercise guidelines to improve physical capacity and muscular strength. The evidence base for the guideline development process consisted of a systematic review and quality appraisal of research examining the effects of exercise on physical fitness among people with SCI. A multidisciplinary expert panel deliberated the evidence and generated the guidelines. Pilot testing led to refinement of the wording and presentation of the guidelines. RESULTS: The expert panel generated the following guidelines: for important fitness benefits, adults with a SCI should engage in (a) at least 20 min of moderate to vigorous intensity aerobic activity two times per week and (b) strength training exercises two times per week, consisting of three sets of 8-10 repetitions of each exercise for each major muscle group. CONCLUSION: People with SCI, clinicians, researchers and fitness programmers are encouraged to adopt these rigorously developed guidelines.

Secondary complications and subjective well-being in individuals with chronic spinal cord injury: associations with self-reported adiposity.

STUDY DESIGN: This is a cross-sectional study. OBJECTIVES: To examine the associations between adiposity, secondary complications and subjective well-being (SWB) in individuals with spinal cord injury (SCI). SETTING: Parkwood Hospital (London); Hamilton Health Sciences-Chedoke Site and McMaster University (Hamilton); Toronto Rehabilitation Institute, Lyndhurst Centre (Toronto); and St Mary's of the Lake Hospital and Queen's University (Kingston), Ontario, Canada. METHODS: A total of 531 men and 164 women (N=695) enrolled in the Study of Health and Activity in People with Spinal Cord Injury (SHAPE-SCI) completed the Secondary Health Complications Survey, SF-36 pain subscale, Satisfaction with Life Scale (SWLS) and the Patient Health Questionnaire-9 (PHQ) during a telephone interview. Body mass index (BMI) measurements were obtained from a subsample of the SHAPE-SCI participants (n=73) during a home visit. RESULTS: Controlling for covariates, individuals who reported being overweight were more likely to have a history of overuse injuries and fatigue, experienced a greater impact of overuse injuries and fatigue, had greater pain and depressive symptoms, and had lower satisfaction with life than individuals who did not report being overweight. BMI was only associated with an increased likelihood of reporting spasticity. CONCLUSION: Self-reported overweight status was associated with an increased prevalence of certain secondary complications and lower SWB. Future prospective studies should examine whether reductions in adiposity are associated with changes in the prevalence and the impact of secondary complications and SWB.

Planning, leisure-time physical activity, and coping self-efficacy in persons with spinal cord injury: a randomized controlled trial.

UNLABELLED: Arbour-Nicitopoulos KP, Martin Ginis KA, Latimer AE. Planning, leisure-time physical activity, and coping self-efficacy in persons with spinal cord injury: a randomized controlled trial. OBJECTIVE: To examine the effects of action and coping planning (ACP) on leisure-time physical activity (LTPA) and coping self-efficacy in exercise initiates living with spinal cord injury (SCI). DESIGN: Ten-week, single-blind randomized controlled trial. SETTING: General community. PARTICIPANTS: Adults (N=44) with SCI (mean age +/- SD, 49.70+/-12.71y) were randomly assigned to either an action planning only (APO; n=22) or an ACP (n=22) condition. INTERVENTION: Participants in the APO condition formed action plans for LTPA at weeks 1 and 5, and self-monitored their LTPA behavior. Those in the ACP condition formed coping plans for managing self-identified activity barriers, in addition to forming action plans and self-monitoring. MAIN OUTCOME MEASURES: Measures of intentions, coping self-efficacy, and behavior were assessed at weeks 1, 5, and 10. RESULTS: Intention-to-treat analyses indicated that persons in the ACP condition reported significantly greater LTPA, scheduling, and general barriers self-efficacy at weeks 5 and 10, in comparison with those in the APO condition. Scheduling self-efficacy mediated the effects of the intervention on LTPA, accounting for 38% of the total effect of the intervention on week 5 LTPA. CONCLUSIONS: These findings illustrate the effectiveness of supplementing action plans with coping plans for enhancing LTPA and coping self-efficacy beliefs among exercise initiates living with SCI.

Hierarchical models facilitate spatial analysis of large data sets: a case study on invasive plant species in the northeastern United States.

Many critical ecological issues require the analysis of large spatial point data sets - for example, modelling species distributions, abundance and spread from survey data. But modelling spatial relationships, especially in large point data sets, presents major computational challenges. We use a novel Bayesian hierarchical statistical approach, 'spatial predictive process' modelling, to predict the distribution of a major invasive plant species, Celastrus orbiculatus, in the northeastern USA. The model runs orders of magnitude faster than traditional geostatistical models on a large data set of c. 4000 points, and performs better than generalized linear models, generalized additive models and geographically weighted regression in cross-validation. We also use this approach to model simultaneously the distributions of a set of four major invasive species in a spatially explicit multivariate model. This multispecies analysis demonstrates that some pairs of species exhibit negative residual spatial covariation, suggesting potential competitive interaction or divergent responses to unmeasured factors.

Activities of daily living performed by individuals with SCI: relationships with physical fitness and leisure time physical activity.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To examine patterns of participation in activities of daily living (ADL) and fitness-related factors associated with these patterns among individuals with spinal cord injury (SCI). SETTING: Centre for Health Promotion and Rehabilitation at McMaster University, School of Kinesiology and Health Studies at Queen's University. METHODS: Forty-eight participants completed the Physical Activity Recall Assessment for People with Spinal Cord Injury (PARA-SCI) and a fitness test assessing cardiovascular fitness (VO(2max) and peak power output (Po)). The most commonly reported ADL were extracted from the PARA-SCI data for analysis. RESULTS: Women tended to spend more time participating in domestic and personal care ADL than men. Compared to individuals with tetraplegia, individuals with paraplegia tended to spend more time transferring, cleaning and preparing food and less time wheeling, toileting and dressing. Fitness and participation in leisure time physical activity (LTPA) were associated with certain ADL. Participants with higher levels of fitness spent more time partaking in ADL wheeling and cleaning. Moreover, greater time spent participating in moderate- and heavy-intensity LTPA was positively correlated with time spent engaged in certain ADL. CONCLUSION: By identifying common ADL performed by individuals with SCI, the study findings begin to provide direction for developing strategies to optimize ADL participation. Future research should examine fitness as a way to help individuals with SCI optimize their ADL participation.

Establishing evidence-based physical activity guidelines: methods for the Study of Health and Activity in People with Spinal Cord Injury (SHAPE SCI).

STUDY DESIGN: Prospective, observational cohort study. OBJECTIVES: This paper describes the rationale and methodology for the Study of Health and Activity in People with Spinal Cord Injury (SHAPE SCI). The study aims to (1) describe physical activity levels of people with different injury levels and completeness, (2) examine the relationship between physical activity, risk and/or presence of secondary health complications and risk of chronic disease, and (3) identify determinants of physical activity in the SCI population. SETTING: Ontario, Canada. METHODS: Seven hundred and twenty men and women who have incurred a traumatic SCI complete self-report measures of physical activity, physical activity determinants, secondary health problems and subjective well-being during a telephone interview. A representative subsample (n=81) participate in chronic disease risk factor testing for obesity, insulin resistance and coronary heart disease. Measures are taken at baseline, 6 and 18 months. CONCLUSION: SHAPE SCI will provide much-needed epidemiological information on physical activity patterns, determinants and health in people with SCI. This information will provide a foundation for the establishment of evidence-based physical activity guidelines and interventions tailored to the SCI community.

The effects of single bouts of body-weight supported treadmill training on the feeling states of people with spinal cord injury.

STUDY DESIGN: Pre-test, post-test study of the relationship between exercise-related changes in feeling states and pain among persons with chronic incomplete spinal cord injury (SCI) who performed three separate exercise sessions consisting of body-weight supported treadmill training (BWSTT). OBJECTIVES: To determine whether exercise-related changes in feeling states are related to exercise-related changes in pain and in-task pain. SETTING: Hamilton, Ontario, Canada. METHODS: A total of 14 men and women with chronic, incomplete SCI (ASIA B and C) performed three exercise sessions of BWSTT. Measures of pain and feeling states were administered before and after each session along with a measure of pain experienced while exercising. RESULTS: Participants who experienced greater decreases in pain from pre- to post-exercise also experienced greater improvements in feeling states. Pain experienced during exercise was unrelated to changes in feeling states. CONCLUSION: Among persons with SCI, exercise-related changes in pain can influence the effects of individual exercise bouts on feeling states.

Long-term body-weight-supported treadmill training and subsequent follow-up in persons with chronic SCI: effects on functional walking ability and measures of subjective well-being.

STUDY DESIGN: Longitudinal, prospective within-subject design. OBJECTIVES: (1) To determine the effects of long-term body-weight-supported treadmill training (BWSTT) on functional walking ability and perceived quality of life in persons with chronic incomplete spinal cord injury (SCI), and (2) to investigate whether training adaptations are maintained following cessation of the BWSTT programme. SETTING: Hamilton, Ontario, Canada. METHODS: A group of 14 individuals with chronic (mean 7.4 years postinjury) incomplete SCI (ASIA B & C) participated in thrice-weekly sessions of BWSTT for a period of approximately 12 months (144 sessions). Functional walking ability and indices of subjective well-being were evaluated during the training programme and over an 8-month follow-up. RESULTS: In total, 13 subjects successfully completed the 144 training sessions in the required study period (max. 15 months). Adherence to the thrice-weekly training frequency was 78.8%. All subjects improved in treadmill walking ability (54% reduction in required external body-weight support (BWS), 180% increase in treadmill walking speed, 335% increase in distance walked/session), and six subjects improved their capacity to walk over ground. There were accompanying increases in satisfaction with life and satisfaction with physical function, both of which were significantly correlated with improvements in treadmill walking ability. All but one subject returned for follow-up assessment 8 months post-training; while there was a slight decline in treadmill walking performance, over ground walking scores remained relatively stable. The only change in subjective well-being in the follow-up was a slight decrease in satisfaction with physical function. CONCLUSION: Thrice-weekly BWSTT for 12 months was an effective stimulus to improve treadmill walking ability and indices of subjective well-being in persons with chronic incomplete SCI, and most of these improvements were maintained for up to 8 months following the cessation of training.

Maintenance of exercise participation in individuals with spinal cord injury: effects on quality of life, stress and pain.

STUDY DESIGN: Follow-up study of seven individuals with spinal cord injury (SCI) who completed a 9-month randomized control trial (RCT) of exercise training. OBJECTIVE: In a 9-month RCT conducted in our lab, individuals with SCI who participated in a twice-weekly supervised exercise training reported greater perceived quality of life (PQOL), and less stress and pain than a nonexercising control cohort. The present follow-up study examined the voluntary continuation of exercise training after the study ended and the persistence of the accrued psychosocial benefits. SETTING: Centre for Health Promotion and Rehabilitation, McMaster University, Hamilton, Ontario, Canada. METHODS: Five men and two women (age 42.3+/-3.6 years) with SCI (C5-T12; ASIA A-D 12.7+/-8.2 years postinjury) were invited to continue supervised exercise training twice weekly at the completion of the 9-month RCT. Exercise adherence, PQOL, stress and bodily pain were measured at a 3-month follow-up and were compared to values obtained at baseline, and at 3, 6 and 9 months during the intervention. RESULTS: There was a significant decrease in adherence at the 3-month follow-up compared to the overall 9-month adherence rate (42.7 versus 80.6%, respectively; P<0.01). There was also a significant decrease in PQOL (P<0.05) and a trend for increased pain (P=0.07) and stress (P=0.12), at follow-up compared to the end of the 9-month trial. Finally, there was a significant negative correlation between pain at the conclusion of the RCT and exercise adherence over the 3-month follow-up period (r=-0.91; P<0.01). CONCLUSIONS: These findings emphasize the importance of continued exercise adherence to the maintenance of exercise-related increases in psychological well-being among individuals with SCI.

Long-term exercise training in persons with spinal cord injury: effects on strength, arm ergometry performance and psychological well-being.

STUDY DESIGN: Randomized controlled trial of exercise training in persons with spinal cord injury. OBJECTIVE: The purpose of this study was to examine the effects of 9 months of twice-weekly exercise training on strength, arm ergometry performance, and indices of psychological well-being and quality of life. SETTING: Centre for Health Promotion and Rehabilitation, McMaster University, Hamilton, Ontario, Canada. METHODS: Thirty-four men and women (aged 19-65 years) with traumatic spinal cord injury (C4-L1; ASIA A-D) of 1-24 years duration volunteered to participate, and were randomized into exercise (EX; n=21) and control (CON; n=13) groups. Twenty-three subjects (11 EX; 12 CON) successfully completed the 9-month study. Subjects were assessed for one repetition maximum (1RM) strength, arm ergometry performance, and several indices of quality of life and psychological well-being at baseline, 3, 6, and 9 months. RESULTS: At baseline, there were no significant differences between groups in age, submaximal arm ergometry performance, muscle strength, or psychological well-being. Following training, the EX group had significant increases in submaximal arm ergometry power output (81%; P<0.05), and significant increases in upper body muscle strength (19-34%; P<0.05); no significant changes occurred in CON. Participants in EX reported significantly less pain, stress and depression after training, and scored higher than CON in indices of satisfaction with physical function, level of perceived health and overall quality of life (P<0.05). Exercise adherence (per cent of prescribed sessions attended) in those subjects who completed the 9 months of training was 82.5%. CONCLUSIONS: These results demonstrate that long-term twice-weekly exercise training in this population is feasible, and results in significant gains in both physical and psychological well-being.

Insulin-like growth factor I mediates high-fat diet-induced adipogenesis in Osborne-Mendel rats.

To determine if high-fat (HF) diet-induced changes in adipose tissue cellularity are associated with the presence of paracrine growth factor(s) that alter preadipocyte proliferation, Osborne-Mendel rats were fed either a HF (76% energy) or a low-fat (LF, 12% energy) diet for 85 days. HF-fed rats had greater (P < 0.05) fat pad size, total fat cell number, number of small (30-70 microm) and large (80-140 microm) adipocytes, and percentage of 100- to 140-microm adipocytes compared with LF-fed rats. Preadipocytes in primary cell culture treated with inguinal adipose tissue conditioned medium (ATCM) prepared from HF-fed rats had greater (P < 0.05) proliferation compared with cultures treated with ATCM from LF-fed rats. Proliferative capacity of ATCM prepared from HF-fed rats was attenuated after the stripping of the medium of insulin-like growth factor I using an immunomagnetic bead separation system. These data are consistent with the concept that insulin-like growth factor I is involved in the paracrine regulation of adipogenesis.

Toxicology and pharmacokinetics of DTGM, a fusion toxin consisting of a truncated diphtheria toxin (DT388) linked to human granulocyte-macrophage colony-stimulating factor, in cynomolgus monkeys.

We developed a fusion toxin consisting of the catalytic and translocation domains of diphtheria toxin linked to human granulocyte-macrophage colony-stimulating factor (GM-CSF) (DTGM) for the treatment of patients with acute myeloid leukemia (AML). Our goal in this study was to determine the toxicity and pharmacokinetics of DTGM in cynomolgus monkeys (Macacca fascicularis), which possess cross-reactive GM-CSF receptors. Four groups of young adult monkeys (6 males and 12 females) were treated with five daily bolus iv infusions of 1, 5, 7.5, and 10 microgram/kg DTGM. Monkeys (2 males and 2 females) treated at 1 microgram/kg/day showed no significant side effects. Monkeys (2 males and 2 females) treated at 5 microgram/kg/day showed Grade 1-2 thrombopenia (NCI common toxicity criteria) on day 9. In contrast, monkeys (6 females) treated at 7.5 microgram/kg/day developed Grade 3 neutropenia, Grade 1-2 thrombopenia, Grade 1-3 anemia, and Grade 1-3 hypoalbuminemia. The neutropenia developed by day 4 in the 7.5 microgram/kg/day monkeys and by day 3 or 5 in the 10 microgram/kg/day monkeys and resolved in both groups by day 9, but the thrombopenia, anemia, and hypoalbuminemia persisted until day 16. Monkeys (2 male and 2 female) treated with 10 microgram/kg/day showed Grade 4 neutropenia that resolved by day 8 and Grade 2-3 anemia, hypoalbuminemia, and thrombopenia. Three of the animals developed sepsis. DTGM plasma half-life was 30 min with a peak concentration of 0.1 microgram/mL or 2 nM (1000-fold higher than the IC50 in vitro for AML blasts). Immune responses were minimal in all animals tested at 14 and 28 days with anti-DTGM levels <1 microgram/mL. All four animals at 10 microgram/kg died or were euthanized, and necropsies were performed. Animals necropsied on days 4 and 6 showed marked apoptosis and hypoplasia in the marrow, which was completely resolved for animals necropsied on day 9. No injury to other organs, including kidney, heart, liver, central nervous system, or lung, was seen. The drug was selectively toxic to malignant or differentiated myeloid cells with little toxicity to myeloid progenitors or other organs. Minimal effects in nontarget tissues make DTGM a promising candidate chemotherapeutic agent.

High-level expression and purification of the recombinant diphtheria fusion toxin DTGM for PHASE I clinical trials.

A genetically engineered fusion toxin targeted to acute myeloid leukemic (AML) blasts was designed with the first 388 amino acid residues of diphtheria toxin with an H-M linker fused to human granulocyte-macrophage colony-stimulating factor. The cDNA was subcloned in the pRK bacterial expression plasmid and used to transform BL21 (DE3) Escherichia coli harboring pUBS500 plasmid. Transformants were grown in Superbroth and induced with IPTG. Inclusion bodies were isolated, washed, and denatured in guanidine hydrochloride with dithioerythritol. Recombinant protein was refolded by diluting 100-fold in cold buffer with arginine and oxidized glutathione. After dialysis, purified protein was obtained after anion-exchange, size exclusion on FPLC, and polymixin B affinity chromatography. The final material was filter sterilized, aseptically vialed, and stored at -80 degrees C. Fifty-four 3-liter bacterial culture preparations were made and pooled into 27 batches. The final product was characterized by Coomassie Plus protein assay, Coomassie-stained SDS-PAGE, limulus amebocyte lysate endotoxin assay, human AML HL60 cell cytotoxicity assay, HPLC TSK3000, N-terminal sequencing, E. coli DNA contamination, C57BL6 mouse toxicity, and immunohistochemistry. Yields were 23 mg/liter bacterial culture of denatured fusion toxin. After refolding and chromatography, final yields were 24 +/- 4% or 5 mg/liter. Vialed product was sterile and 1.7 +/- 0.4 mg/ml in PBS. Purity by SDS-PAGE was 99 +/- 1%. Aggregates by HPLC were <1%. Potency revealed a 24-h IC50 of 2.7 +/- 0.5 pM on HL60 cells. Endotoxin levels were 1 eu/mg. The N-terminal sequence was confirmed, and E. coli DNA was <113 pg/mg. The LD10 in mice was 110 microg/kg/day x5. There was no evidence of loss of solubility, proteolysis, aggregation, or loss of potency over 3 months at -80 and -20 degrees C. Further, the drug was stable at 4, 25, and 37 degrees C in human serum for 48 h. Drug reacted only with human monocytes, granulocytes, and myeloid precursors in frozen human tissue sections by immunohistochemistry. The synthesis of this protein drug should be useful for production for clinical phase I/II clinical trials and may be suitable for other diphtheria fusion toxins indicated for clinical development. This is the first report of the scaleup of a recombinant fusion toxin for clinical trials.

Activation of particulate guanylyl cyclase by endothelins in cultured SV-40 transformed cat iris sphincter smooth muscle cells.

We investigated the effects of endothelins (ETs) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ET-3 increased cGMP formation in a concentration-dependent manner (EC50 = 98nM), which was 2.5 times higher than that of ET-1. The ET(B)receptor agonists sarafotoxin-S6c and IRL 1620 also increased cGMP production, mimicking the effects of the ETs. The ET(B) receptor antagonist BQ 788, but not the ET(A) receptor antagonist BQ610, dose-dependently blocked ET-3-stimulated cGMP formation (IC50=10nM). The phorbol ester, Phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylyl cyclase in smooth muscle, dose-dependently inhibited ET-3-stimulated cGMP accumulation (IC50=66nM). LY83583 and ODQ, inhibitors of soluble guanylyl cyclases, as well as inhibitors of the nitric oxide cascade and of intracellular Ca2+ elevation had no appreciable effect on ET-3-induced cGMP production. ET-3 markedly inhibited carbachol-induced intracellular Ca2+ mobilization. We conclude that ET-3 increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ET(B) receptor subtype and subsequent stimulation of the membrane-bound guanylyl cyclase. Elevation of cGMP by ET and the subsequent inhibition of muscarinic stimulation of intracellular Ca2+ mobilization by the cyclic nucleotide could serve to modulate the contractile effects of Ca2+-mobilizing agonists in the iris sphincter smooth muscle.

The effects of thyroxine on serum and tissue concentrations of insulin-like growth factors (IGF-I and -II) and IGF-binding proteins in the fetal pig.

We have extensively studied the effect of hypophysectomy on the growth and development of tissues in the fetal pig. However, little is known about the effect of hypophysectomy on tissue levels of insulin-like growth factors I and II (IGF-I and -II) and how these growth factors are affected by T4 replacement. Fetal pigs were hypophysectomized (Hypox) at 70 days of gestation, and pellets containing 15 mg T4 were implanted into the lateral musculature of the hind limb at either 70 or 90 days of gestation. Fetuses were removed at either 90 or 105 days of gestation, respectively. Control (non-Hypox), Hypox, and T4 (Hypox-T4) fetal weights were similar at 90 days, but Hypox-T4 weighted less than control and Hypox fetuses at 105 days. Hypophysectomy decreased levels of serum T4, LH, cortisol, and IGF-I (105 days) when compared with controls. Heart and liver (105 days and 90 days) and fat, muscle, and kidney (90 days) IGF-I levels were lower in Hypox fetuses when compared with controls. Hypophysectomy decreased concentrations of IGF-II in only 105-day fetal kidneys. Hypophysectomy decreased serum levels of IGF binding protein 1 (IGFBP-1) (90 days) and IGFBP-2 (105 days) and increased IGFBP-4 (105 days) in comparison with control. T4 treatment of Hypox fetuses increased serum concentrations of T4 and IGF-I over Hypox levels at both 90 and 105 days gestation. Cortisol levels remained decreased in the T4-treated fetuses. Levels of IGF-I in the heart (90 and 105 days) and liver (90 days) of Hypox fetuses were increased by T4 treatment. T4 did not effect tissue IGF-II levels when compared with Hypox. T4 increased serum IGFBP-1, -2, and -4 levels over Hypox values. We suggest that T4 enhances production of IGF-I (as opposed to IGF-II), which in turn mediates some of T4's capability to enhance tissue development in the fetal pig.

The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus.

Late term fetuses from genetically obese dams have slightly larger fat cells, greater adipose tissue lipoprotein lipase (LPL) activities, elevated levels of thyroid hormones, and depressed growth hormone (GH) levels when compared to fetuses from lean dams. We have investigated the influence of thyroid hormone and GH status per se on these and other adipose tissue traits by chronically treating hypophysectomized (hypox) fetuses (day 70) between day 90 and 105 of gestation with either thyroxine (T4) or human GH. Treatment with T4 decreased body weights (P<.05), increased serum T4 levels (P<.05), and enhanced skin and hair development (P<.05). Quantitative analysis of sections of perirenal and subcutaneous adipose tissue indicated that T4 increased LPL activity (P<.05), slightly increased fat cell size, and more than doubled (P<.05) lipid accretion. A hypox induced deficit in fat cell cluster number in the outer layer of subcutaneous tissue was normalized by T4 (P<.05). Conversely, human GH (hGH) treatment had no influence on body weight, increased serum hGH levels, decreased fat cell size (P<.05) and LPL activity (P<.05) but had no influence on lipid accretion. Quantitative analysis of adipose tissue sections provided direct and indirect evidence of a "critical" or "sensitive" period between 90 and 105 days, since fetal hypox at day 70 severely impeded preadipocyte recruitment/replication during this period. Furthermore, T4 but not GH effectively normalized this hypox-induced deficiency in preadipocyte development. Therefore, T4 may have a major role in preadipocyte recruitment/replication during late fetal life.

Alterations of serum insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) in swine infected with the protozoan parasite Sarcocystis miescheriana.

The effects of a Sarcocystis miescheriana infection on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were investigated to determine possible mechanisms of growth retardation in growing pigs. Sixteen pigs averaging 14 kg body weight were divided into 4 groups of 4 pigs each and infected either with 0.5, 1.0, or 3.0 x 10(6) sporocysts of S. miescheriana. Four pigs were retained as non-infected controls; however, they became serologically positive during the course of the infection. Effects also were investigated in 2 groups of 3 pregnant sows. One group was infected with 0.5 x 10(6) sporocysts and the other group was retained as uninfected controls. Body weights of infected growing pigs were depressed as compared to controls following the acute phase 15 d after infection (dai). Serum concentrations of IGF-I dropped significantly (p < 0.05) during the acute phase of infection in all infected groups of growing pigs. Conversely, the amounts of unsaturated serum IGFBPs were elevated significantly (p < 0.05) during the acute phase of infection. Specifically, serum concentrations of IGFBP-1, IGFBP-2, and IGFBP-4 were elevated at this time, as determined by ligand blot analysis. There was no association between growth factor alterations and tissue damage as measured by serum creatinine kinase and aspartate aminotransferase levels. The extent of effects in growing pigs was related to the amount of the original parasite inoculum. During the acute phase of infection 2 of 3 pregnant sows aborted. The third sow went to term, but piglets were stillborn or died within 24 hr. Compared to uninfected controls, serum concentrations of IGF-I in infected pregnant sows were depressed during and after the acute phase of the infection. Levels of unsaturated serum IGFBPs in pregnant sows were not affected. These data suggest that decreased IGF-I levels and/or elevated levels of specific forms of IGFBPs may be a mechanism by which growth is affected in feeder pigs infected with S. miescheriana.

Intraluminal irradiation for inoperable obstructing endobronchial carcinoma of the lung.

Between April 1, 1987 and August 31, 1988, 31 patients with inoperable symptomatic obstructing carcinoma of the lung underwent 79 intraluminal irradiation sessions in an effort to re-establish patency of the airway. Palliation was excellent, 74% of the patients had complete relief of atelectasis, while two patients with extensive tracheal disease experienced little objective response. There was little morbidity, other than that associated with bronchoscopy. Overall, survival at 6 months was 55% with 22% of patients at risk for 18 months surviving. This compares favorably with the more complicated technique of laser resection for relieving malignant airway obstruction.