Biglycan neo-epitope (BGN262), a novel biomarker for screening early changes in equine osteoarthritic subchondral bone.

OBJECTIVE: Native biglycan (BGN), which can undergo proteolytic cleavage in pathological conditions, is well known to be involved in bone formation and mineralization. This study aimed to delineate the specific cleavage fragment, a neo-epitope for BGN (BGN262), in synovial fluid (SF) from young racehorses in training, osteoarthritic (OA) joints with subchondral bone sclerosis (SCBS), and chip fracture joints. DESIGN: A custom-made inhibition ELISA was developed to quantify BGN262 in SF. Cohort 1: A longitudinal study comprising 10 racehorses undergoing long-term training. Cohort 2: A cross-sectional study comprising joints from horses (N = 69) with different stages of OA and radiographically classified SCBS. Cohort 3: A cross-sectional study comprising horses (N = 9) with chip fractures. Receiver operating characteristic (ROC) curve analysis was performed (healthy joints vs chip joints) to evaluate BGN262 robustness. RESULTS: Cohort 1: SF BGN262 levels from racehorses showed a statistical increase during the first 6 months of the training period. Cohort 2: BGN262 levels were significantly higher in the SF from severe SCBS joints. Cohort 3: SF BGN262 levels in chip fracture joints showed a significant increase compared to normal joints. The ROC analysis showed an AUC of 0.957 (95% C.I 0.868-1.046), indicating good separation between the groups. CONCLUSIONS: The data presented show that BGN262 levels increase in SF in correlation with the initiation of training, severity of SCBS, and presence of chip fractures. This suggests that BGN262 is a potential predictor and a novel biomarker for early changes in subchondral bone (SCB), aiming to prevent catastrophic injuries in racehorses.

Patients' experiences of different care settings and a new life situation after allogeneic haematopoietic stem cell transplantation.

Over the past 20 years, considerable healthcare resources have shifted from an inpatient to an outpatient setting. To be in an outpatient setting or at home after allogeneic haematopoietic stem cell transplantation (allo-HSCT) has been shown to be medically safe and beneficial to the patient. In this study we describe patients' experiences of different care settings (hospital or home) and a new life situation during the acute post-transplant phase after HSCT. Semi-structured interviews were conducted with 15 patients (six women and nine men) 29-120 days after HSCT. An inductive qualitative content analysis was performed to analyse the data. The analysis resulted in four categories: To be in a safe place, To have a supportive network, My way of taking control, and My uncertain return to normality. The findings showed that patients undergoing HSCT felt medically safe regardless of the care setting. The importance of a supportive network (i.e. the healthcare team, family and friends) was evident for all patients. Both emotional and problem-focused strategies were used to cope with an uncertain future. Being at home had some positive advantages, including freedom, having the potential for more physical activity, and being with family members. The study highlights some key areas thought to provide more personalised care after HSCT.

Family members' life situation and experiences of different caring organisations during allogeneic haematopoietic stem cells transplantation-A qualitative study.

The aim of this study was to describe family members' life situation and experiences of care in two different care settings, the patient's home or in hospital during the acute post-transplantation phase after allogeneic haematopoietic stem cell transplantation (HSCT). Data were collected through semi-structured interviews with 14 family members (seven women and seven men). An inductive qualitative content analysis was used to analyse the data. The majority of the family members' (n = 10) had experiences from home care. The findings show the family members' voice of the uncertainty in different ways, related with the unknown prognosis of the HSCT, presented as Being me being us in an uncertain time. The data are classified into; To meet a caring organisation, To be in different care settings, To be a family member and To have a caring relationship. Positive experiences such as freedom and security from home care were identified. The competence and support from the healthcare professionals was profound. Different strategies such as adjusting, having hope and live in the present used to balance to live in an uncertain time. The healthcare professionals need to identify psychosocial problems, and integrate the psychosocial support for the family to alleviate or decrease anxiety during HSCT, regardless of the care setting.

Neutral Silicon-Vacancy Center in Diamond: Spin Polarization and Lifetimes.

We demonstrate optical spin polarization of the neutrally charged silicon-vacancy defect in diamond (SiV^{0}), an S=1 defect which emits with a zero-phonon line at 946 nm. The spin polarization is found to be most efficient under resonant excitation, but nonzero at below-resonant energies. We measure an ensemble spin coherence time T_{2}>100 µs at low-temperature, and a spin relaxation limit of T_{1}>25 s. Optical spin-state initialization around 946 nm allows independent initialization of SiV^{0} and NV^{-} within the same optically addressed volume, and SiV^{0} emits within the telecoms down-conversion band to 1550 nm: when combined with its high Debye-Waller factor, our initial results suggest that SiV^{0} is a promising candidate for a long-range quantum communication technology.

Fear-avoidance beliefs about physical activity in adults with rheumatoid arthritis.

OBJECTIVES: The aim of this study was to describe fear-avoidance beliefs about physical activity and explore how these beliefs correlate with sociodemographic, disease-specific, and psychosocial factors in adults with rheumatoid arthritis (RA). METHOD: This cross-sectional study is part of the Physical Activity in Rheumatoid Arthritis (PARA) 2010 study. The study participants (n = 2351) were identified through the Swedish Rheumatology Quality (SRQ) registries from six rheumatology clinics in Sweden. Univariate and backwards stepwise logistic regressions were performed. RESULTS: Stepwise logistic regressions showed that male gender [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.26-1.91] and having a below average income (OR 1.35, 95% CI 1.12-1.63) were associated with an increased risk of high scores on the modified Fear Avoidance-Belief Questionnaire (mFABQ). The two disease-specific factors most indicative of high mFABQ scores were high level of pain (OR 1.99, 95% CI 1.40-2.84) and poor health (OR 1.59, 95% CI 1.10-2.29). With regard to psychosocial factors, low health-related quality of life (HRQoL; OR 0.44, 95% CI 0.35-0.55) and a low score on the Exercise Self-Efficacy Scale (ESES; OR 0.66, 95% CI 0.52-0.82) were significantly associated with a high mFABQ score. The model fit was 0.27 (Nagelkerke's R(2)). CONCLUSIONS: High fear-avoidance beliefs about physical activity in patients with RA were found to be associated with being male and having a below average income, a high level of pain, poor health, a low HRQoL, and low ESES score. Additional research is warranted for adults with RA to capture the multiple potential correlates to fear-avoidance beliefs about physical activity.

Does head CT scan pathology predict outcome after mild traumatic brain injury?

BACKGROUND AND PURPOSE: More evidence is needed to forward our understanding of the key determinants of poor outcome after mild traumatic brain injury (MTBI). A large, prospective, national cohort of patients was studied to analyse the effect of head CT scan pathology on the outcome. METHODS: One-thousand two-hundred and sixty-two patients with MTBI (Glasgow Coma Scale score 15) at 39 emergency departments completed a study protocol including acute head CT scan examination and follow-up by the Rivermead Post Concussion Symptoms Questionnaire and the Glasgow Outcome Scale Extended (GOSE) at 3 months after MTBI. Binary logistic regression was used for the assessment of prediction ability. RESULTS: In 751 men (60%) and 511 women (40%), with a mean age of 30 years (median 21, range 6-94), we observed relevant or suspect relevant pathologic findings on acute CT scan in 52 patients (4%). Patients aged below 30 years reported better outcome both with respect to symptoms and GOSE as compared to patients in older age groups. Men reported better outcome than women as regards symptoms (OR 0.64, CI 0.49-0.85 for ≥3 symptoms) and global function (OR 0.60, CI 0.39-0.92 for GOSE 1-6). CONCLUSIONS: Pathology on acute CT scan examination had no effect on self-reported symptoms or global function at 3 months after MTBI. Female gender and older age predicted a less favourable outcome. The findings support the view that other factors than brain injury deserve attention to minimize long-term complaints after MTBI.

Fear of hypoglycaemia in adults with Type 1 diabetes.

AIMS: The aim of this study was to examine the fear of hypoglycaemia and its association with demographic and disease-specific variables in a large and unselective population of adult patients with Type 1 diabetes. METHODS: Questionnaires were sent by post to all patients with Type 1 diabetes who were identified in the local diabetes registries of two hospitals in Stockholm, Sweden (n=1387). Fear of hypoglycaemia was measured using the Swedish Hypoglycaemia Fear Survey, the Worry subscale and the Aloneness subscale. Demographic variables and disease-specific factors were collected from patients' self reports and medical records. Univariate analysis and multiple stepwise linear regression analysis were used in the statistical analyses of the data. RESULTS: Seven hundred and sixty-four (55%) patients participated in the study (mean age 43.3 years and mean HbA(1c) 7.0%, normal <5.0%). The Hypoglycaemia Fear Survey - Worry subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, hypoglycaemic symptoms during hyperglycaemia and hypoglycaemic unawareness. The Hypoglycaemia Fear Survey - Aloneness subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, frequency of mild hypoglycaemia, HbA(1c) , hypoglycaemic unawareness and visits to the emergency room because of severe hypoglycaemia. Fear of hypoglycaemia proved to be more prevalent in females and indicated a different pattern between genders in relation to factors associated with fear of hypoglycaemia. CONCLUSIONS: This study identifies the frequency of severe hypoglycaemia as the most important factor associated with fear of hypoglycaemia. Moreover, for the first time, we document gender differences in fear of hypoglycaemia, suggesting that females are more affected by fear of hypoglycaemia than men.

Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) lacking expression of steroid receptors and human epidermal growth factor receptor 2, having chemotherapy as the only therapeutic option, is characterised by early relapses and poor outcome. We investigated intratumoural (i.t.) levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF) and survival in patients with TNBC compared with non-TNBC. PATIENTS AND METHODS: VEGF levels were determined by an enzyme immunosorbent assay in a retrospective series consisting of 679 consecutive primary breast cancer patients. RESULTS: Eighty-seven patients (13%) were classified as TNBC and had significantly higher VEGF levels; median value in TNBC was 8.2 pg/microg DNA compared with 2.7 pg/microg DNA in non-TNBC (P < 0.001). Patients with TNBC had statistically significant shorter recurrence-free survival [hazard ratio (HR) = 1.8; P = 0.0023], breast cancer-corrected survival (HR = 2.2; P = 0.004) and overall survival (HR = 1.8; P = 0.005) compared with non-TNBC. Patients with TNBC relapsed earlier than non-TNBC; mean time from diagnosis to first relapse was 18.8 and 30.7 months, respectively. The time between first relapse and death was also shorter in TNBC: 7.5 months versus 17.5 months in non-TNBC (P = 0.087). CONCLUSIONS: Our results show that TNBC have higher i.t. VEGF levels compared with non-TNBC. Ongoing clinical trials will answer if therapy directed towards angiogenesis may be an alternative way to improve outcome in this poor prognosis group.

Author Correction: Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer.

As breast volume may be associated with heart cancer risk, we studied the relationship between breast volume, CYP1A2*1F and coffee intake. Among healthy premenopausal non-hormone users, 3+ cups per day was associated with lower volume only in C-allele carriers (P(interaction)=0.02), which is consistent with reports that coffee protects only C-allele carriers against breast cancer.

Electrospun nerve guide conduits have the potential to bridge peripheral nerve injuries in vivo.

Electrospinning can be used to mimic the architecture of an acellular nerve graft, combining microfibers for guidance, and pores for cellular infiltration. We made electrospun nerve guides, from polycaprolactone (PCL) or poly-L-lactic acid (PLLA), with aligned fibers along the insides of the channels and random fibers around them. We bridged a 10 mm rat sciatic nerve defect with the guides, and, in selected groups, added a cell transplant derived from autologous stromal vascular fraction (SVF). For control, we compared to hollow silicone tubes; or autologous nerve grafts. PCL nerve guides had a high degree of autotomy (8/43 rats), a negative indicator with respect to future usefulness, while PLLA supported axonal regeneration, but did not outperform autologous nerve grafts. Transplanted cells survived in the PLLA nerve guides, but axonal regeneration was not enhanced as compared to nerve guides alone. The inflammatory response was partially enhanced by the transplanted cells in PLLA nerve grafts; Schwann cells were poorly distributed compared to nerve guide without cells. Tailor-made electrospun nerve guides support axonal regeneration in vivo, and can act as vehicles for co-transplanted cells. Our results motivate further studies exploring novel nerve guides and the effect of stromal cell-derived factors on nerve generation.

A morning dose of insulin glargine prevents nocturnal ketosis after postprandial interruption of continuous subcutaneous insulin infusion with insulin lispro.

AIM: The aim of this crossover trial was to evaluate the potential of partial substitution of basal insulin with glargine, administered once daily in the morning, to protect against nocturnal ketosis after postprandial interruption of continuous subcutaneous insulin infusion (CSII). METHODS: Seven patients with type 1 diabetes received 4 weeks of treatment with insulin lispro, administered by CSII, and 4 weeks of treatment with CSII and a partial basal replacement dose of insulin glargine administered in the morning. On day 28 of each treatment phase, patients were admitted to the research unit where dinner was served and their usual dinner insulin bolus dose given, after which CSII was discontinued at 7 pm. Plasma (p) beta-hydroxybutyrate and p glucose were measured every hour for 12 h thereafter. RESULTS: Plasma beta-hydroxybutyrate at 7 pm was 0.16+/-0.05 and 0.13+/-0.07 mmol/l with and without glargine, respectively, and increased to 0.17+/-0.10 and 0.60+/-0.3 mmol/l within 6 h (P=0.02). Plasma glucose increased without glargine, from 8.6+/-2.9 to 21.1+/-3.0 mmol/l (P=0.003), but did not rise significantly following glargine (13.6+/-4.7 vs. 12.6+/-5.6 mmol/l; P=0.65). CONCLUSIONS: Partial replacement with a morning dose of insulin glargine protects against the development of ketosis for as much as 12 h after postprandial interruption of CSII. This treatment strategy could, therefore, be useful for patients who are prone to ketosis but, for other reasons, are deemed suitable for CSII.

Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen is being increasingly used for the treatment of breast cancer and is undergoing study for the primary prevention of breast cancer. However, concerns have been raised that the drug may increase the incidence of new primary malignancies, such as endometrial, liver, and colorectal cancers. PURPOSE: Our goal was to assess the carcinogenic risks associated with long-term use of tamoxifen in women with early stage breast cancer. METHODS: The incidence of new primary cancers among 2729 women participants of the Stockholm Trial was determined at a median follow-up of 9 years. In this trial, after primary surgery, postmenopausal patients aged less than 71 years with unilateral invasive breast cancer were randomly allocated to receive either 2 years of adjuvant tamoxifen (40 mg daily) or no adjuvant endocrine therapy. Information on second cancers was obtained by retrospective linkage to the Swedish Cancer Registry. To increase statistical power, a joint analysis of the incidence of endometrial and gastrointestinal cancers was performed in the following three major studies in Scandinavia evaluating adjuvant tamoxifen therapy: the Stockholm Trial, the Danish Breast Cancer Group Trial, and the South-Swedish Trial. These studies included a total of 4914 patients with a median follow-up of 8-9 years. All P values were calculated from two-tailed tests of statistical significance. RESULTS: In the Stockholm Trial, there was a statistically significant (P = .008) reduction in the incidence of second primary cancers in the contralateral breast among the tamoxifen-treated patients. However, there was a nearly sixfold increase in endometrial cancers (P < .001) and a threefold increase in gastrointestinal cancers in the tamoxifen-treated patients. The results of the joint studies showed a statistically significant increase in endometrial cancers among the tamoxifen-treated patients (relative risk [RR] = 4.1; 95% confidence interval [CI] = 1.9-8.9). There was also an excess of gastrointestinal cancers associated with tamoxifen. Most of this excess involved colorectal cancers (RR = 1.9; 95% CI = 1.1-3.3) and stomach cancer (RR = 3.2; 95% CI = 0.9-11.7). There was no substantial increase in any other type of gastrointestinal cancer (e.g., liver cancer) among the tamoxifen-treated patients. CONCLUSION: The endometrium and gastrointestinal organs may be target sites for tamoxifen-induced carcinogenesis in humans. IMPLICATIONS: The increased incidence of colorectal and stomach cancers reported here should be regarded as tentative until supported by long-term data from a larger number of tamoxifen trials. Also, appropriate surveillance of cancer incidence is warranted for the protection of participants enrolled in current tamoxifen chemoprevention trials.

Key factors for human islet isolation and clinical transplantation.

BACKGROUND: To further improve the outcome of clinical islet transplantation analysis of the impact of donor- and process-related factors could be of great importance. MATERIALS AND METHODS: Thirty-eight consecutive clinical islet transplantations were performed with consecutive islet isolations. Univariate analysis for donor- and isolation-related variables were correlated with recipient C-peptide levels at 2 and 4 weeks after transplantation. "Warm ischemia time" was defined as the time from start of University of Wisconsin solution perfusion in the donor until the pancreas was removed to the back table. RESULTS: Short "warm ischemia time" (WIT), low expression of tissue factor (TF) in pancreatic tissue, and high creatinine levels in the donor were variables related to high C-peptide values after islet transplantation. Furthermore, hospitalization length longer than 4 days was associated with low C-peptide levels. The number of islet equivalents (IEQ) did not correlate with the clinical outcome, possibly due to the fact that IEQ number was included in the release criteria for clinical islet transplantation CONCLUSIONS: Successful clinical islet transplantation is strongly correlated with donor and pancreas procurement factors rather than isolation process-related variables. "WIT" may induce TF expression in the pancreatic tissues. TF has been identified as the main trigger of the instant blood-mediated-inflammatory reaction in clinical islet transplantation. Therefore, assay of TF expression in pancreatic tissues could be applied as useful screening tool to identify "good" pancreata for clinical transplantation.

Coordinated care planning for elderly patients using videoconferencing.

We studied the transfer of information during coordinated care planning between a university hospital and a local health care centre/social welfare department about 35 km away. During a seven-month study period, 10 sessions were conducted by videoconferencing and seven sessions were conducted by face-to-face conferencing. Videoconferencing reduced the time required for each coordinated care-planning session from an average of 60 to 45 min. There was also an increase in the number of participating professional categories. Travel time for the staff in the face-to-face group was 60-180 min each. Use of a care-planning report during the sessions resulted in improved quality of documentation, which contributed to better care following discharge. The technical problems that occurred did not detract from the beneficial experience of participating. Interviews with next of kin showed that they had been able to influence the content of the care during the care-planning sessions. Videoconferencing proved useful in coordinated care planning. It resulted in time saved due to reduced travel time, participation by more staff categories and an enhancement of the documentation quality.

Effects of ROCK inhibitor Y27632 and EGFR inhibitor PD168393 on human neural precursors co-cultured with rat auditory brainstem explant.

Hearing function lost by degeneration of inner ear spiral ganglion neurons (SGNs) in the auditory nervous system could potentially be compensated by cellular replacement using suitable donor cells. Donor cell-derived neuronal development with functional synaptic formation with auditory neurons of the cochlear nucleus (CN) in the brainstem is a prerequisite for a successful transplantation. Here a rat auditory brainstem explant culture system was used as a screening platform for donor cells. The explants were co-cultured with human neural precursor cells (HNPCs) to determine HNPCs developmental potential in the presence of environmental cues characteristic for the auditory brainstem region in vitro. We explored effects of pharmacological inhibition of GTPase Rho with its effector Rho-associated kinase (ROCK) and epidermal growth factor receptor (EGFR) signaling on the co-cultures. Pharmacological agents ROCK inhibitor Y27632 and EGFR blocker PD168393 were tested. Effect of the treatment on explant penetration by green fluorescent protein (GFP)-labeled HNPCs was evaluated based on the following criteria: number of GFP-HNPCs located within the explant; distance migrated by the GFP-HNPCs deep into the explant; length of the GFP+/neuronal class III ß-tubulin (TUJ1)+ processes developed and phenotypes displayed. In a short 2-week co-culture both inhibitors had growth-promoting effects on HNPCs, prominent in neurite extension elongation. Significant enhancement of migration and in-growth of HNPCs into the brain slice tissue was only observed in Y27632-treated co-cultures. Difference between Y27632- and PD168393-treated HNPCs acquiring neuronal fate was significant, though not different from the fates acquired in control co-culture. Our data suggest the presence of inhibitory mechanisms in the graft-host environment of the auditory brainstem slice co-culture system with neurite growth arresting properties which can be modulated by administration of signaling pathways antagonists. Therefore the co-culture system can be utilized for screens of donor cells and compounds regulating neuronal fate determination.

Lysosomal release of cathepsin D precedes relocation of cytochrome c and loss of mitochondrial transmembrane potential during apoptosis induced by oxidative stress.

Apoptosis was induced in human foreskin fibroblasts by the redox-cycling quinone naphthazarin (5,8-dihydroxy-1,4-naphthoquinone). Most of the cells displayed ultrastructure typical of apoptosis after 8 h of exposure to naphthazarin. Apoptosis was inhibited in fibroblasts pretreated with the cathepsin D inhibitor pepstatin A. Immunofluorescence analysis of the intracellular distribution of cathepsin D revealed a distinct granular pattern in control cells, whereas cells treated with naphthazarin for 30 min exhibited more diffuse staining that corresponded to release of the enzyme from lysosomes to the cytosol. After 2 h, release of cytochrome c from mitochondria to the cytosol was indicated by immunofluorescence. The membrane-potential-sensitive probe JC-1 and flow cytometry did not detect a permanent decrease in mitochondrial transmembrane potential (delta psi(m)) until after 5 h of naphthazarin treatment. Our findings show that, during naphthazarin-induced apoptosis, lysosomal destabilization (measured as release of cathepsin D) precedes release of cytochrome c, loss of delta psi(m), and morphologic alterations. Moreover, apoptosis could be inhibited by pretreatment with pepstatin A.

Lipofuscin-induced autofluorescence of living neonatal rat cardiomyocytes in culture.

Lipofuscin-specific autofluorescence of living, cultured rat neonatal myocardial myocytes was studied with respect to intensity and spectral characteristics. The autofluorescence emission spectrum changed over time indicating continuously ongoing intramolecular reorganisation of the pigment. Moreover, as compared with formaldehyde-fixed material native lipofuscin produced a considerable red-shifted autofluorescence, indicating formaldehyde-induced molecular modification or quenching of certain parts of the spectrum. The relationship between oxidative stress and lipofuscinogenesis was confirmed because the rate of lipofuscin accumulation was increased when cells were grown at increasing ambient oxygen concentrations.

Monoclonal antibodies towards the fast inhibitor of tissue plasminogen activator from human plasma and serum.

Hybridoma cells were produced by fusing mouse myeloma cells (SP 2/0-Ag 14) with spleen cells from a Balb/c mouse, previously immunized with the partially purified complex between tissue plasminogen activator (t-PA) and its fast inhibitor from human plasma (serum). Screening with a radioimmunoassay revealed a number of hybridomas secreting antibodies directed towards the complex. Of these, about 1/3 reacted both with the complex and t-PA, whereas about 2/3 reacted only with the complex. Three of the latter hybridomas, producing antibodies directed towards the inhibitor-moiety in the complex have been cloned and the antibodies were studied in detail. PA-inhibitor activity in plasma or serum and t-PA/PA-inhibitor complex could be specifically adsorbed on all three insolubilized monoclonal antibodies (MC1, MC2 and MC3). None of the antibodies seems to be directed against structures of vital importance for the functional activity of the PA-inhibitor. In accordance with this finding the antibody with the highest avidity (MC1) reacts equally well with the PA-inhibitor alone or in complex with t-PA. A radioimmunoassay was developed with this antibody and significant displacement was obtained with samples with PA-inhibitor concentrations above 2 AU/mL. In 13 plasma samples with different levels of PA-inhibitory activity a significant correlation was obtained when comparing this activity with the PA-inhibitor antigen as measured with the radioimmunoassay (r = 0.88).

Desensitization by terbutaline of beta-adrenoceptors in the guinea-pig soleus muscle: biochemical alterations associated with functional changes.

1 The effects of adrenaline and terbutaline on cyclic adenosine 3',5'-monophosphate (cyclic AMP) content, 22Na-efflux, 42K-influx and subtetanic contractions have been assessed in soleus muscles isolated from guniea-pigs which had been maintained on food with or without terbutaline for 5 days. 2 Terbutaline and adrenaline increased cyclic AMP content and suppressed subtetanic contractions, and regression analysis indicates a statistically significant correlation between these two effects (P less than 0.01). 3 In muscles obtained from terbutaline-treated animals, the effects of terbutaline and adrenaline on cyclic AMP content, active Na-K-transport and subtetanic contractions were all considerably suppressed, but insulin stimulated 22Na-efflux and affected subtetanic contractions to the same extent as in the muscles obtained from the control group. 4 The results suggest that terbutaline treatment leads to a reduction in the number of beta 2-adrenoceptors in skeletal muscle or an impairment of their function. 5 The results provide further support for the idea that the effect of adrenaline or insulin on skeletal muscle contractions is the outcome of stimulation of active Na-K-transport.