The cost of callbacks: return visits for diagnostic imaging discrepancies in a pediatric emergency department.

PURPOSE: Diagnostic imaging has mirrored the steady growth of healthcare utilization in the USA. This has created greater opportunity for diagnostic errors, which can be costly in terms of morbidity and mortality as well as dollars and cents. The purposes of this study were to describe all return visits to a tertiary care urban pediatric emergency department (PED) resulting from diagnostic imaging discrepancies and to calculate the costs of these return visits. METHODS: From July 2014 to February 2015, all children who underwent a diagnostic imaging study during an ED visit were assembled. Analysis was performed on all children who were called back and returned to the ED following a discrepant read. Direct and indirect costs to the patient, family, hospital, and society for these return visits were calculated. RESULTS: During the study period, 8310 diagnostic imaging studies were performed, with 207 (2.5%) discrepant reads. Among the discrepant reads, 37 (0.4% of total, 17.9% of discrepant) patients had a return visit to the ED for further management. Including ED charges, time and travel costs to the family, and costs of radiation exposure, return visits for radiologic discrepancies over this 8-month period cost a total of $84,686.47, averaging $2288.82 per patient. CONCLUSIONS: Though the overall diagnostic imaging discrepancy rate among our study population was low, the clinically significant discrepancies requiring return ED visits were potentially high risk, and costly for the patient, family, and healthcare system.

Cancer Incidence and Mortality due to Excess Body Weight in Ireland: An Analysis of 10-year data.

Excess body weight (EBW) increases the risk of specific cancers. The prevalence of EBW has risen significantly in Ireland over recent decades. To highlight the impact on cancer, and to inform future policies, we calculated the proportion of cancers in Ireland that were attributable to EBW using the Population Attributable Fraction (PAF). This fraction was then applied to Irish incidence and mortality data for specific cancers from 2003-2012 to estimate the number of new cancers and cancer deaths attributable to EBW. We found that each year in Ireland, approximately 800 new cancers and 300 cancer deaths are attributable to EBW. The greatest attributable risk of cancer was seen for the upper digestive tract and endometrium, whilst breast and colorectal have the greatest numbers of attributable cancers. EBW is a major cause of cancer, responsible for 4.5% of all cancers in Ireland. Public awareness of this significant preventable risk must improve.

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

BACKGROUND: Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, ß tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. RESULTS: Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and ß tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. CONCLUSION: Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection.

War and Marriage: Assortative Mating and the World War II GI Bill.

World War II and its subsequent GI Bill have been widely credited with playing a transformative role in American society, but there have been few quantitative analyses of these historical events' broad social effects. We exploit between-cohort variation in the probability of military service to investigate how WWII and the GI Bill altered the structure of marriage, and find that it had important spillover effects beyond its direct effect on men's educational attainment. Our results suggest that the additional education received by returning veterans caused them to "sort" into wives with significantly higher levels of education. This suggests an important mechanism by which socioeconomic status may be passed on to the next generation.

Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD.

BACKGROUND: Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to fluoxetine on binding of [(11)C]DASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with [(11)C]MRB (a NET ligand) and [(11)C]AFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys. METHODS: Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01-0.12mg/kg/h and 0.045-1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated. RESULTS: ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0-1.8mg/kg, approx. 300-600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates. CONCLUSION: Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET.

Migratory history of the threespine stickleback Gasterosteus aculeatus in western Ireland.

Microchemical analysis of trace elements in otoliths and bio-mineralised earstones of teleost fishes is an emerging approach to analysing the environmental migratoryand life histories of fish species. The migration history of the three-spine stickleback (Gasterosteus aculeatus) collected in western Ireland was examined using calcium (Ca) and strontium (Sr) concentrations in otoliths. The otolith Sr:Ca values fluctuated with the habitat. The habitat use and migration history of G. aculeatus can be categorised into two types, as determined by the mean value and life history transect of the otolith Sr:Ca; that is, freshwater and estuarine residents, whereas there were no anadromous sticklebacks which is believed to be a typical migration pattern in the species. The otolith Sr:Ca profiles of the freshwater resident fishes exhibited constantly low Sr:Ca values, averaging 0.41-0.58 × 10-3 from the core towards the edge. However, the otolith Sr:Ca profiles of the estuarine resident fishes exhibited constantly high Sr:Ca values from the core towards the edge without a clear transition point from low to high Sr:Ca values, as found in the anadromous fish, averaging 1.82-4.26 × 10-3. The present study is the first published confirmation that 100 % of sticklebacks living in coastal habitats in Ireland > have an estuarine resident migratory pattern, constantly residing in marine environments or brackish water throughout their lifespan and not in freshwater environments in Ireland.

Cancer incidence and mortality due to alcohol: an analysis of 10-year data.

Alcohol consumption is causally related to cancer of the upper aero-digestive tract, liver, colon, rectum, female breast and pancreas. The dose response relationship varies for each site. We calculated Ireland's cancer incidence and mortality attributable to alcohol over a 10-year period. Between 2001 and 2010, 4,585 (4.7%) male and 4,593 (4.2%) female invasive cancer diagnoses were attributable to alcohol. The greatest risk was for the upper aero-digestive tract where 2,961 (52.9%) of these cancers in males and 866 (35.2%) in females were attributable to alcohol. Between 2001 and 2010, 2,823 (6.7%) of male cancer deaths and 1,700 (4.6%) of female cancer deaths were attributable to alcohol. Every year approximately 900 new cancers and 500 cancer deaths are attributable to alcohol. Alcohol is a major cause of cancer after smoking, obesity and physical inactivity. Public awareness of risk must improve. Over half of alcohol related cancers are preventable by adhering to Department of Health alcohol consumption guidelines.

Ability of non-invasive intermittent blood pressure monitoring and a continuous non-invasive arterial pressure monitor (CNAP™) to provide new readings in each 1-min interval during elective caesarean section under spinal anaesthesia.

We compared the ability of automated non-invasive intermittent oscillometric blood pressure monitoring with a new device, CNAP(TM) (continuous non-invasive arterial pressure) to provide a new blood pressure reading in each 1-min interval between spinal anaesthesia and delivery during caesarean section. We also compared the accuracy of continuous non-invasive arterial pressure readings with non-invasive blood pressure measurements before spinal anaesthesia. Fifty-nine women participated. The non-invasive and continuous non-invasive monitors displayed new blood pressure readings in a mean of 82% (11%) and 83% (13%) (p = 0.97) of the one-minute intervals between spinal anaesthesia and delivery, respectively. Continuous non-invasive arterial pressure was more likely to fail on two or more consecutive minutes (p=0.001). From the pre-spinal readings, the mean bias, defined as non-invasive-continuous non-invasive arterial pressure, and limits of agreement (±2SD mean bias) for systolic, diastolic and mean blood pressure respectively were +1.3 (±26.0), -2.9 (±21.8) and +2.6 (±20.4) mmHg. The new monitor has disadvantages compared with conventional non-invasive intermittent blood pressure monitoring.

Characterization of the bovine innate immune response in milk somatic cells following intramammary infection with Streptococcus dysgalactiae subspecies dysgalactiae.

The innate immune response of milk somatic cells in cows to Streptococcus dysgalactiae ssp. dysgalactiae was investigated by deliberate intramammary challenge. Cows were challenged with 2,500 colony-forming units of Strep. dysgalactiae DPC 5435, previously isolated from a clinical mastitis case. Eight of the 9 cows treated showed clinical signs of mastitis (swollen udders, increased somatic cell score, and clotted milk) within 1 wk of challenge. Messenger RNA levels of IL-1ß and toll-like receptor 4 (TLR4) in milk somatic cells increased approximately 40 fold within 48 h of infusion, whereas tumor necrosis factor α increased 16 fold within the same time frame. Interestingly, cows homozygous for the G allele of the C-X-C chemokine receptor type 1 (CXCR1)-777 polymorphism had higher IL-8 and CXCR1 transcript abundance at 24h postinfusion compared with cows homozygous for the C allele. The difference in expression of these genes at this critical time point may influence the severity of disease within different genotypes.

Experience of women on the Irish National Gestational Trophoblastic Disease Registry.

OBJECTIVE: Gestational Trophoblastic Disease (GTD) is a rare pregnancy related disorder and the most curable of all gynaecological malignancies. GTD comprises the premalignant conditions of complete or partial hydatidiform mole known as molar pregnancy and a spectrum of malignant disorders termed gestational trophoblastic neoplasia. Clinical management and treatment in specialist centres is essential to achieve high cure rates and clinical guidelines recommend registration with a GTD centre as a minimum standard of care. National GTD registries are valuable repositories of epidemiological data and facilitate clinical audit, centralised pathology review and human chorionic gonadotropin (hCG) monitoring. This study sought the opinion of women enrolled on the Irish National GTD registry to inform future service development and establish a knowledge base for molar pregnancy in Ireland. STUDY DESIGN: A cross-sectional survey using an anonymised questionnaire was distributed by post to all women on the GTD registry. The questionnaire was designed by a multidisciplinary team and consisted of twenty-five closed-ended questions and two open-ended questions to facilitate feedback. Data collected in the survey included information on the patient experience of registration, knowledge of molar pregnancy, diagnosis at their local hospital, hCG monitoring and overall satisfaction with the service. RESULTS: The survey had a successful participation rate of 42.6% (215/504). Forty-nine percent (n = 106) of respondents rated a rapid hCG result as their top priority. Forty percent (n = 84) of women had concerns about future pregnancies but acknowledged that these were largely addressed by the GTD specialist nurses. A quarter of respondents reported that other medical professionals with whom they interacted during follow-up treatment did not understand their condition. Many women commented on the emotional stress of attending their local maternity unit for phlebotomy while dealing with pregnancy loss. CONCLUSION: This study is unique in being the first survey of women on the Irish National GTD registry. It highlights the specific needs of women with molar pregnancy in terms of psychological support, bereavement counselling and peer support groups. It reveals a knowledge gap in molar pregnancy amongst healthcare professionals which should be considered in future planning of medical and nursing curricula.

Psychological adjustment to Type 2 diabetes and relationship quality.

AIMS: To examine the associations between psychological adjustment to Type 2 diabetes and the reported quality and type of relationships with partners. METHODS: All participants (n=88) completed a number of questionnaires, including two measures of relationship quality: the Dyadic Adjustment Scale and the Personal Assessment of Intimacy in Relationships Scale, the Diabetes Quality of Life Scale and the ATT-19 (which assesses personal integration of diabetes). Additionally, HbA(1c) levels were obtained from medical notes. RESULTS: Measures of relationship quality significantly contributed to the explanation of two outcomes: personal integration of diabetes and satisfaction with the burden of self-management behaviours. More specifically, the findings demonstrate that a specific aspect of relationship quality--intimacy in recreational activities--is positively associated with the outcomes mentioned above. CONCLUSIONS: People with Type 2 diabetes who are not taking insulin, who share engagement in physical activities with their partner are more likely to be psychologically well-adjusted to their diagnosis of diabetes.

Depth distribution and biological characteristics of the European eel Anguilla anguilla in Lough Ennell, Ireland.

Using a longline survey, a total of 196 European eels Anguilla anguilla were collected at different depths in Lough Ennell (maximum depth 30 m), central Ireland. The catch per unit of effort of A. anguilla that were caught from 1 to 25 m depths was lowest at 0.5-5.0 m and greatest at the deepest depth range (22.5-25.0 m). Sub-samples of A. anguilla from depths of <15 m showed little or no difference in size, sex ratio, age, growth rate, condition factor, length-mass relationship, gonado-somatic index, fin index or eye index with fish from depths of >15 m. All fish examined were female yellow-phase A. anguilla that had ages from 7 to 20 years (mean +/-s.d. = 10.3 +/- 2.9 years), with growth rates from 24.0-60.8 mm year(-1) (mean +/-s.d. = 40.7 +/- 8.5 mm year(-1)). Variations in the growth rates were greater in the shallow group than that of the deep group. This study suggested that deeper regions are important feeding habitats for A. anguilla and that fish in this lake were growing moderately fast compared to similar habitats and areas in the species' range.

Effects of basic fibroblast growth factor on bone formation in vitro.

Basic fibroblast growth factor (bFGF) was studied for its effects on bone formation in cultured rat calvariae. bFGF at 0.1-100 ng/ml stimulated [3H]thymidine incorporation into DNA by up to 4.4-fold. bFGF also increased the number of colcemid-induced metaphase arrested cells and the DNA content. Transient (24 h) treatment with bFGF enhanced [3H]-proline incorporation into collagen 24-48 h after the factor was removed; this effect was DNA synthesis dependent and blocked by hydroxyurea. The collagen stimulated by bFGF was type I, and this effect was observed primarily in the periosteum-free bone. In contrast, continuous treatment with bFGF for 24-96 h inhibited [3H]proline incorporation into type I collagen. bFGF did not alter collagen degradation. In conclusion, bFGF stimulates calvarial DNA synthesis, which causes an increased number of collagen-synthesizing cells, but bFGF has a direct inhibitory effect on collagen synthesis.

Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis.

RA is a heterogeneous group of disorders characterized by variations in clinical manifestations, disease course, and probably response to therapeutic interventions. We have addressed the question whether genetically and potentially etiologically more homogeneous subgroups of RA patients can be defined based upon the expression of the RA-linked sequence motif in the third hypervariable region of the HLA-DRB1 gene. Genetic comparison of patients classified upon clinical manifestation and disease course demonstrated that patients with mild disease were genetically distinct from those progressing to severe and destructive disease. Specifically, rheumatoid factor (RF) negative patients preferentially expressed RA-linked HLA-DRB1 alleles with an arginine substitution in position 71, whereas the alleles with a lysine substitution in position 71 accumulated in RF+ patients. RF- patients were further subdivided based on clinical markers (time of onset of erosive disease and requirement for aggressive therapy). Clinical heterogeneity correlated with genetic heterogeneity. Patients with early erosive disease and patients requiring aggressive therapy frequently typed HLA-DRB1*04+. Patients with late erosive/nonerosive disease or a benign disease course manageable with nonaggressive treatment preferentially expressed HLA-DRB1*01 or lacked an RA-linked haplotype. These data indicate that the heterogeneity of RA reflects genetic differences. Sequence variations within the disease-linked sequence motif, as well as polymorphisms surrounding the candidate genetic element, affect pattern, course, and treatment response of RA. Amino acid position 71 in the HLA-DRB1 gene has a unique role, the understanding of which may provide important clues to disease etiology.

Insulin-like growth factor I mediates selective anabolic effects of parathyroid hormone in bone cultures.

PTH was studied for its effects on bone formation in cultured rat calvariae. 0.01-10 nM PTH stimulated [3H]thymidine incorporation into DNA by up to 4.8-fold. Although continuous treatment with PTH for 24-72 h inhibited [3H]proline incorporation into collagen, transient (24 h) treatment enhanced [3H]proline incorporation into collagen 24-48 h after the hormone was removed. The collagen stimulated by PTH was type I and the effect was observed in the periosteum-free bone and was not blocked by hydroxyurea. Furthermore, treatment with 1-100 nM PTH for 24 h increased insulin-like growth factor (IGF) I concentrations by two to fourfold, and an IGF I antibody prevented the PTH stimulation of collagen synthesis, but not its mitogenic effect. In conclusion, continuous treatment with PTH inhibits calvarial collagen, whereas transient treatment stimulates collagen synthesis, and the stimulatory effect is mediated by local production of IGF I.

Isoform-specific regulation of platelet-derived growth factor activity and binding in osteoblast-enriched cultures from fetal rat bone.

In osteoblast-enriched cultures from fetal rat bone, the A-chain homodimer of platelet-derived growth factor (PDGF-AA) is less potent than the PDGF isoforms containing B chain subunits (PDGF-AB and PDGF-BB), but normal osteoblasts appear to synthesize only PDGF-A subunit mRNA and polypeptide. However, other agents may regulate PDGF-AA activity in skeletal tissue. Pretreatment of osteoblast-enriched cultures with interleukin 1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF-alpha) synergistically enhanced the mitogenic effect of PDGF-AA coincident with increased binding site occupancy, but neither factor augmented PDGF-BB activity or binding. Polyacrylamide gel analysis showed 125I-PDGF-AA binding complexes predominantly at greater than 200 kD and faint labeling at 185 kD. After IL-1 alpha or TNF-alpha pretreatment, PDGF-AA binding increased at both sites, but this effect was more striking at 185 kD, which co-migrated with 125I-PDGF-BB-labeled complexes. PDGF-AA binding sites were rapidly lost by comparison to those for PDGF-BB in cycloheximide-treated cultures, but they remained relatively enhanced by IL-1 alpha and TNF-alpha pretreatment. These studies indicate that IL-alpha and TNF-alpha increase PDGF-AA binding and activity for osteoblasts by mechanisms that are at least in part independent of new receptor synthesis, and suggest regulatory events that could control how PDGF binding sites specifically recognize different ligands.

Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis.

Microvascular endothelial cells (RFCs) cultured in two-dimensional (2D) cultures proliferate rapidly and exhibit an undifferentiated phenotype. Addition of transforming growth factor beta1 (TGFbeta1) increases fibronectin expression and inhibits proliferation. RFCs cultured in three-dimensional (3D) type I collagen gels proliferate slowly and are refractory to the anti-proliferative effects of TGF beta1. TGF beta1 promotes tube formation in 3D cultures. TGF beta1 increases fibronectin expression and urokinase plasminogen activator (uPA) activity and plasminogen activator inhibitor-1 (PAI-1) levels in 3D cultures. Since the TGF beta type I and II receptors have been reported to regulate different activities induced by TGF beta1, we compared the TGF beta receptor profiles on cells in 2D and 3D cultures. RFCs in 3D cultures exhibited a significant loss of cell surface type II receptor compared with cells in 2D cultures. The inhibitory effect of TGF beta1 on proliferation is suppressed in transfected 2D cultures expressing a truncated form of the type II receptor, while its stimulatory effect on fibronectin production is reduced in both 2D and 3D transfected cultures expressing a truncated form of the type I receptor. These data suggest that the type II receptor mediates the antiproliferative effect of TGF beta1 while the type I receptor mediates the matrix response of RFCs to TGF beta1 and demonstrate that changes in the matrix environment can modulate the surface expression of TGF beta receptors, altering the responsiveness of RFCs to TGF beta1.

Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis.

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods. RESULTS: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.

Activin-A binding and biochemical effects in osteoblast-enriched cultures from fetal-rat parietal bone.

Activin, a disulfide-linked polypeptide dimer first isolated from gonadal tissue extracts, has amino acid sequence and structural homology with transforming growth factor beta (TGF beta). Along with other activities, TGF beta regulates replication and differentiation and interacts with a defined set of binding sites on isolated bone cells. To determine if activin shares these properties, recombinant human activin-A (A-chain homodimer) was examined in osteoblast-enriched cultures obtained from fetal-rat parietal bone. After 23 h of treatment, 60 to 6,000 pM activin-A increased the rate of [3H]thymidine incorporation into DNA 1.5- to 4.0-fold, and at 600 to 6,000 pM, it enhanced the rate of [3H]proline incorporation into collagen and noncollagen protein by up to 1.7-fold. Like earlier studies with TGF beta in primary osteoblast-enriched cultures, the stimulatory effects of activin-A on DNA and protein synthesis were opposed by parathyroid hormone, and the influence of activin-A on collagen synthesis was independent of cell replication. Binding studies with 125I-activin-A indicated approximately 8,000 high-affinity (Kd = 0.4 nM) and 300,000 low-affinity (Kd = 40 to 50 nM) binding sites per cell. Polyacrylamide gel analysis revealed 125I-activin-A-binding complexes of Mr greater than 200,000 and 73,000 which did not appear to correspond to primary TGF beta-binding sites. These results indicate that activin-A produces TGF beta-like effects in bone and that some of these effects may be mediated, at least in part, by distinct activin receptors on bone cells.