The association of the N-terminal pro-brain-type natriuretic peptide response to exercise with disease severity in therapy-naive pulmonary arterial hypertension: a cohort study.

BACKGROUND: While the N-terminal pro-brain-type natriuretic peptide (NT-proBNP) at rest is known to be associated with prognosis in pulmonary arterial hypertension (PAH), it is unclear if the NT-proBNP response to exercise (ΔNT-proBNP) can contribute to a better assessment of disease severity. METHODS: We investigated the association of NT-proBNP values at rest and during peak exercise with hemodynamics and cardiopulmonary exercise testing parameters in 63 therapy-naive PAH patients. RESULTS: The median NT-proBNP increases from 1414 at rest to 1500 pg/ml at peak exercise. The ΔNT-proBNP is baseline-dependent in PAH. Both, NT-proBNP at rest and NT-proBNP at peak exercise, are significantly correlated with hemodynamics and functional capacity. However, neither NT-proBNP at peak exercise nor ΔNT-proBNP correlated better with surrogate markers of disease severity than NT-proBNP at rest. CONCLUSION: The ΔNT-proBNP does not contribute to a better assessment of disease severity in PAH.

The association of N-terminal pro-brain-type natriuretic peptide with hemodynamics and functional capacity in therapy-naive precapillary pulmonary hypertension: results from a cohort study.

BACKGROUND: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used as a surrogate marker for disease severity in pulmonary hypertension (PH). However, NT-proBNP tends to have a high variability and may insufficiently correlate with hemodynamics and exercise capacity. METHODS: To investigate the association of NT-proBNP with hemodynamics and cardio-pulmonary exercise testing (CPET) in 84 therapy-naive patients with precapillary PH. RESULTS: NT-proBNP levels were significantly correlated with hemodynamics and CPET parameters except for cardiac index, diffusion capacity, PaO2 at peak exercise, and peak minute ventilation. NT-proBNP correlated best with hemodynamics and CPET in women and patients >65 years. NT-proBNP correlated better with CPET in pulmonary arterial hypertension compared to chronic thromboembolic PH (CTEPH). CONCLUSION: NT-proBNP is associated with disease severity in precapillary PH. The association might be age- and gender-dependent. NT-proBNP may insufficiently correlate with disease severity in CTEPH, possibly due to comorbidity.

The prognostic value of tumour regression grade following neoadjuvant chemoradiation therapy for rectal cancer.

AIM: To date, there is no uniform consensus on whether tumour regression grade (TRG) is predictive of outcome in rectal cancer. Furthermore, the lack of standardization of TRG grading is a major source of variability in published studies. The aim of this study was to evaluate the prognostic impact of TRG in a cohort of patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation therapy (CRT). In addition to the Mandard TRG, we utilized four TRG systems modified from the Mandard TRG system and applied them to the cohort to assess which TRG system is most informative. METHOD: One-hundred and fifty-three patients with a T3/T4 and/or a node-positive rectal cancer underwent neoadjuvant 5-fluorouracil-based CRT followed by surgical resection. RESULTS: Thirty-six (23.5%) patients achieving complete pathological response (ypCR) had a 5-year disease-free survival (DFS) rate of 100% compared with a DFS rate of 74% for 117 (76.5%) patients without ypCR (P = 0.003). The Royal College of Pathologists (RCPath) TRG best condenses the Mandard five-point TRG by stratifying patients into three groups with distinct 5-year DFS rates of 100%, 86% and 67%, respectively (P = 0.001). In multivariate analysis, pathological nodal status and circumferential resection margin (CRM) status, but not TRG, remained significant predictors of DFS (P = 0.002, P = 0.035 and P = 0.310, respectively). CONCLUSION: Our findings support the notion that ypCR status, nodal status after neoadjuvant CRT and CRM status, but not TRG, are predictors of long-term survival in patients with locally advanced rectal cancer.

Allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and pulmonary mucormycosis.

Mucormycosis is a serious invasive fungal infection in immunocompromised patients. Patients undergoing treatment for hematologic malignancies are predominantly prone to the pulmonary manifestation of mucormycosis. Historically, allogeneic hematopoietic cell transplantation (HCT) in patients suffering from pulmonary mucormycosis (PM) was considered contraindicated owing to mortality rates up to 90%. We present 3 patients with acute myeloid leukemia and PM who were treated with radical surgical debridement combined with high-dose liposomal amphotericin B (LAB), and subsequently underwent successful allogeneic HCT. To date, all 3 patients are in complete remission and show no signs of mucormycosis. Allogeneic HCT in patients with PM seems feasible provided that the infectious focus is completely removed surgically and adequate antifungal pharmacotherapy, such as high-dose LAB or posaconazole, is established.

"Hands off hand hygiene training": Implementation of a COVID safe auditor training program.

Optimal hand hygiene practices reduce the risk of healthcare-associated infections, especially in high-risk settings of immunocompromised patients. In 2020, face-to-face learning was disallowed in the environment of coronavirus disease 2019 transmission. We developed a revised learning program for hand hygiene auditors for our cancer care facility. The learning package resulted in a 2-fold increase in the number of participants, with effective promotion by managers, due in part to reduced time and resources for training, and flexibility for staff.

Differentiation- and stress-dependent nuclear cytoplasmic redistribution of myopodin, a novel actin-bundling protein.

We report the cloning and functional characterization of myopodin, the second member of the synaptopodin gene family. Myopodin shows no significant homology to any known protein except synaptopodin. Northern blot analysis resulted in a 3.6-kb transcript for mouse skeletal and heart muscle. Western blots showed an 80-kD signal for skeletal and a 95-kD signal for heart muscle. Myopodin contains one PPXY motif and multiple PXXP motifs. Myopodin colocalizes with alpha-actinin and is found at the Z-disc as shown by immunogold electron microscopy. In myoblasts, myopodin shows preferential nuclear localization. During myotube differentiation, myopodin binds to stress fibers in a punctuated pattern before incorporation into the Z-disc. Myopodin can directly bind to actin and contains a novel actin binding site in the center of the protein. Myopodin has actin-bundling activity as shown by formation of latrunculin-A-sensitive cytosolic actin bundles and nuclear actin loops in transfected cells expressing green fluorescent protein-myopodin. Under stress conditions, myopodin accumulates in the nucleus and is depleted from the cytoplasm. Nuclear export of myopodin is sensitive to leptomycin B, despite the absence of a classical nuclear export sequence. We propose a dual role for myopodin as a structural protein also participating in signaling pathways between the Z-disc and the nucleus.

Retrospective single center analysis of outcome, risk factors and therapy in steroid refractory graft-versus-host disease after allogeneic hematopoietic cell transplantation.

Acute and chronic graft-vs.-host disease (aGvHD and cGvHD) are major complications after allogeneic hematopoietic cell transplantation (HCT) leading to substantial morbidity and mortality. This retrospective single-center study analyzes incidence, therapy, and outcome of GvHD in n = 721 patients ≥18 years having received allogeneic HCT 2004-2013 with a special focus on steroid refractory GvHD. Acute (n = 355/49.2%) and chronic (n = 269/37.3%) GvHD were mainly treated by steroids in first-line therapy. The proportion of steroid refractory aGvHD and cGvHD was 35.7% and 31.4%, respectively. As there is no standard therapy for steroid refractory GvHD, a range of different agents was used. In aGvHD, the overall response rate (ORR) of steroid refractory GvHD to second-line treatment was 27.4%. Mycophenolate mofetil (MMF) and mTOR inhibitors led to superior response rates (ORR 50.0% and 53.3%, respectively). In steroid refractory cGvHD therapy, ORR was 44.4%. Use of calcineurin inhibitors (CNI; n = 11/45.5%), MMF (n = 18/50.0%), mTOR inhibitors (n = 10/60.0%), and extracorporeal photophoresis (ECP; n = 16/56.3%) showed ORR above average. Targeted therapies lead to responses in 7.7% (n = 13). This data may help to improve the design of future prospective clinical studies in GvHD.

SMPDL3b modulates insulin receptor signaling in diabetic kidney disease.

Sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is a lipid raft enzyme that regulates plasma membrane (PM) fluidity. Here we report that SMPDL3b excess, as observed in podocytes in diabetic kidney disease (DKD), impairs insulin receptor isoform B-dependent pro-survival insulin signaling by interfering with insulin receptor isoforms binding to caveolin-1 in the PM. SMPDL3b excess affects the production of active sphingolipids resulting in decreased ceramide-1-phosphate (C1P) content as observed in human podocytes in vitro and in kidney cortexes of diabetic db/db mice in vivo. Podocyte-specific Smpdl3b deficiency in db/db mice is sufficient to restore kidney cortex C1P content and to protect from DKD. Exogenous administration of C1P restores IR signaling in vitro and prevents established DKD progression in vivo. Taken together, we identify SMPDL3b as a modulator of insulin signaling and demonstrate that supplementation with exogenous C1P may represent a lipid therapeutic strategy to treat diabetic complications such as DKD.

Computed tomography findings of human polyomavirus BK (BKV)-associated cystitis in allogeneic hematopoietic stem cell transplant recipients.

BACKGROUND: Over 70% of the general population worldwide is positive for antibodies against polyomavirus hominis type 1 (BKV). Polyomavirus can be reactivated in immunocompromised patients and thereby induce urogenital tract infection, including cystitis. PURPOSE: To describe the computed tomography (CT) findings of human polyomavirus-induced cystitis in adult patients after allogeneic hematopoietic stem cell transplantation (allogeneic HCT). MATERIAL AND METHODS: The study population was a retrospective cohort of 11 consecutive adult patients (eight men, three women; age range 22-59 years, mean 42.9 years) who received allogeneic HCT between December 2003 and December 2007 and were tested positive for urinary BKV infection. All CT scans were evaluated with regard to bladder wall thickness, mucosal enhancement, distinct layering of thickened bladder wall, and presence of intravesical clots, perivesical stranding as well as attenuation values of intravesical urine. Clinical data concerning transplant and conditioning regimen variables and laboratory parameters were correlated with degree and extent of imaging findings. RESULTS: All patients had clinical signs of cystitis with different degrees of thickening of the urinary bladder wall. Well-delineated urinary bladder layers were present in six patients. Thickening of the urinary bladder wall was continuous in nine of 11 patients. Increased attenuation of intravesical urine was found in seven patients with hemorrhagic cystitis. Four patients had intraluminal clots. Perivesical stranding was not a major CT finding, occurring in a mild fashion in three of 11 patients. The clinical classification of hemorrhagic cystitis did not correlate with the analyzed imaging parameters. Patient outcome was not influenced by this infectious complication. CONCLUSION: CT findings in patients with polyomavirus BK cystitis consist of different degrees of bladder wall thickening usually with good delineation of all mural layers and increased mucosal enhancement. These findings are not specific for BKV cystitis, but awareness of this differential diagnosis should help in the early diagnosis and correct management of this infectious complication.

Electroactive Amphiphiles for Addressable Supramolecular Nanostructures.

In this focus review we aim to highlight an exciting class of materials, electroactive amphiphiles (EAAs). This class of functional amphiphilic molecules has been the subject of sporadic investigations over the last few decades, but little attempt has been made to date to gather or organise these investigations into a logical fashion. Here we attempted to gather the most important contributions, provide a framework in which to discuss them, and, more importantly, point towards the areas where we believe these EAAs will contribute to solving wider scientific problems and open new opportunities. Our discussions cover materials based on low molecular weight ferrocenes, viologens and anilines, as well as examples of polymeric and supramolecular EAAs. With the advances of modern analytical techniques and new tools for modelling and understanding optoelectronic properties, we believe that this area of research is ready for further exploration and exploitation.

Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin.

NPHS2 was recently identified as a gene whose mutations cause autosomal recessive steroid-resistant nephrotic syndrome. Its product, podocin, is a new member of the stomatin family, which consists of hairpin-like integral membrane proteins with intracellular NH(2)- and COOH-termini. Podocin is expressed in glomerular podocytes, but its subcellular distribution and interaction with other proteins are unknown. Here we show, by immunoelectron microscopy, that podocin localizes to the podocyte foot process membrane, at the insertion site of the slit diaphragm. Podocin accumulates in an oligomeric form in lipid rafts of the slit diaphragm. Moreover, GST pull-down experiments reveal that podocin associates via its COOH-terminal domain with CD2AP, a cytoplasmic binding partner of nephrin, and with nephrin itself. That podocin interacts with CD2AP and nephrin in vivo is shown by coimmunoprecipitation of these proteins from glomerular extracts. Furthermore, in vitro studies reveal direct interaction of podocin and CD2AP. Hence, as with the erythrocyte lipid raft protein stomatin, podocin is present in high-order oligomers and may serve a scaffolding function. We postulate that podocin serves in the structural organization of the slit diaphragm and the regulation of its filtration function.

Photoinduction of optical anisotropy in an azobenzene-containing ionic self-assembly liquid-crystalline material.

Liquid-crystalline (LC) phase behavior and photoinduction of optical anisotropy in the ionic self-assembly complex 4-(4-diethylaminophenylazo) benzenesulfonate-dimethyldidodecylammonium (EO-C12D) has been investigated by polarized light microscopy, differential scanning calorimetry (DSC), x-ray scattering, null-ellipsometry, and UV-visible absorbance techniques. The complex exists in a bilayer smectic- A (smA{2}) LC phase at elevated temperatures (65-160 degrees C) and in a rectangular columnar (Col{r}) LC phase in the temperature range of -5-65 degrees C . Hysteresis in the transition from the smectic to the columnar LC phase was observed. Detailed experimental investigations of the phase behavior, film-forming properties, and induction of optical anisotropy were performed. High values of photoinduced anisotropy (dichroic ratio of approximately 50) were detected when thin films of the complex were irradiated with linearly polarized light ( Ar+ laser, lambda=488 nm ). It was shown that the azobenzene units align perpendicular to the polarization of the exciting light causing an alignment of the columns parallel to the light electric field vector. On the basis of all experimental results a model of the photoinduced alignment of the photochromic complex is proposed in which photoalignment of the material is connected to the reorientation of domains.

Obstructive sleep apnea might trigger acute pulmonary embolism: results from a cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) might be an independent risk factor for acute pulmonary embolism (APE). AIM OF THE STUDY: A prospective cohort study was conducted to investigate if APE is sleep-related in untreated OSA syndrome or not. METHODS: 206 APE patients were evaluated by portable monitoring and polysomnography. APE symptoms which caused an arousal from sleep or occurred within the first hour after wake-up were considered to be sleep-related. RESULTS: APE manifestation is significantly more often sleep-related in patients with moderate or severe OSA compared to subjects with an apnea-hypopnea index ≤15/h (p < 0.001). The relative risk of sleep-related APE increases with the severity of OSA. CONCLUSIONS: OSA might trigger APE, possibly reflecting a pathophysiological relationship between these two conditions.

Na(+)/H(+) exchange inhibition with HOE642 improves postischemic recovery due to attenuation of Ca(2+) overload and prolonged acidosis on reperfusion.

BACKGROUND: Na(+)/H(+) exchange inhibition with HOE642 (cariporide) improves postischemic recovery of cardiac function, but the mechanisms of action remain speculative. Because Na(+)/H(+) exchange is activated on reperfusion, it was hypothesized that its inhibition delays realkalinization and decreases intracellular Na(+) and, via Na(+)/Ca(2+) exchange, Ca(2+) overload. Attenuated Ca(2+) overload and prolonged acidosis are known to be cardioprotective. METHODS AND RESULTS: Left ventricular developed and end-diastolic pressures were measured in isolated buffer-perfused rat hearts subjected to 30 minutes of no-flow ischemia and 30 minutes of reperfusion (37 degrees C) with or without 1 micromol/L HOE642 added to the perfusate 15 minutes before ischemia. Intracellular Ca(2+) concentration ([Ca(2+)](i)) and pH(i) were measured with aequorin (n=10 per group) and (31)P NMR spectroscopy (n=6 per group), respectively. HOE642 did not affect preischemic mechanical function, [Ca(2+)](i), or pH(i). Mechanical recovery after 30 minutes of reperfusion was substantially improved with HOE642: left ventricular developed pressure (in percent of preischemic values) was 92+/-3 versus 49+/-7 and left ventricular end-diastolic pressure was 16+/-3 versus 46+/-5 mm Hg (P<0.05 for HOE642-treated versus untreated hearts). End-ischemic [Ca(2+)](i) was significantly lower in HOE642-treated than in untreated hearts (1.04+/-0.06 versus 1.84+/-0. 02 micromol/L, P<0.05). Maximal intracellular Ca(2+) overload during the first 60 seconds of reperfusion was attenuated with HOE642 compared with untreated hearts: 2.0+/-0.3 versus 3.2+/-0.3 micromol/L (P<0.05). pH(i) was not different at end ischemia ( approximately 5.9+/-0.05). Realkalinization was similar in the first 90 seconds of reperfusion and significantly delayed in the next 3 minutes (eg, 6.8+/-0.07 in HOE642-treated hearts compared with 7. 2+/-0.07 in untreated hearts; P<0.05). CONCLUSIONS: HOE642 improves postischemic recovery by reducing Ca(2+) overload during ischemia and early reperfusion and by prolonging postischemic acidosis.

Platelet prostacyclin binding in coronary artery disease.

Reduced responsiveness of platelets to prostacyclin, reported in vitro in patients with coronary artery disease, has been thought to be a factor predisposing toward coronary thrombosis and vasospasm as a result of enhanced in vivo release of cyclic endoperoxides and thromboxane A2 by the platelets. In this study, specific binding of prostacyclin to intact platelets was determined in patients with coronary artery disease by direct binding studies using 9-3H-prostacyclin sodium salt. In addition, the inhibitory effect of prostacyclin on primary aggregation induced by adenosine diphosphate and cyclic adenosine monophosphate (cyclic AMP) accumulation stimulated by prostacyclin was examined. Twenty patients with angiographically documented coronary artery disease and stable angina, 8 patients with acute myocardial infarction, 14 healthy volunteers and 10 patients with normal angiograms were studied. In patients with stable angina, binding capacity and affinity of platelet prostacyclin binding sites and prostacyclin-induced cyclic AMP accumulation were not different from those of control subjects. In patients with acute myocardial infarction, however, binding capacity of platelet prostacyclin receptors was significantly reduced (0.69 +/- 0.45 versus 1.35 +/- 0.37 pmol/10(9) platelets, p = 0.001) and the postreceptor response, represented by platelet responsiveness to prostacyclin and prostacyclin-induced cyclic AMP synthesis, was impaired. Because all patients with myocardial infarction were receiving intravenous heparin and nitroglycerin, which might interfere with platelet prostacyclin binding, competition experiments were performed in vitro. Neither heparin (3 to 250 IU/ml) nor nitroglycerin (0.8 to 22 microM) displaced specifically bound 9-3H-prostacyclin. L-Epinephrine in concentrations up to 10 microM also exhibited no competition with specific platelet prostacyclin binding.(ABSTRACT TRUNCATED AT 250 WORDS)

The adhesion molecule E-cadherin and a surface antigen recognized by the antibody 9C4 are selectively expressed on erythroid cells of defined maturational stages.

The antigen expression of immature erythroid bone marrow cells was studied using two recently generated monoclonal antibodies (mAb), mAb 67A4 and 9C4, with specificities for the epithelial cell adhesion molecule E-cadherin (E-cad; mAb 67A4), and a novel 110 kDa differentiation antigen (mAb 9C4) with unknown molecular structure. Pappenheim staining of FACS-purified cells labeled with mAb 9C4 and anti-glycophorin A (GA) revealed that the majority of the 9C4+GA- and 9C4+GA+ cells consisted of erythroblasts. In contrast, the E-cad-positive population comprised normoblasts and erythroblasts. While the E-cad+GA- fraction contained mainly erythroblasts and basophilic normoblasts, the E-Cad+GA+ population was enriched in orthochromatic and polychromatophilic normoblasts. By colony assays of affinity column-purified cells it could be shown that erythroid colony forming units (CFU-E) were enriched and erythroid burst forming units (BFU-E) were depleted in the 9C4- and E-cad-positive fractions. Flow cytometric analysis of bone marrow cells double-labeled with mAb 67A4 and anti-CD71, anti-CD117, anti-CD34, or anti-GA revealed that about 90% of the E-cad-positive cells coexpressed CD71, about 70% were positive for CD117, about 50% for GA, and only about 5% coexpressed CD34. The expression pattern of 9C4 antigen was similar to that of E-Cad with the exception that only a minority of the 9C4-positive cells coexpressed GA. Lymphoid and myeloid markers were negative on both the E-Cad- and 9C4-positive populations. In these studies we describe the identification of a new mAb-defined antigen which is specifically expressed on erythroblasts and CFU-E(9C4) and demonstrate that E-Cad is not only expressed on epithelial cells but also on erythropoietic cells of defined maturational stages.

Highly ordered monodomain ionic self-assembled liquid-crystalline materials.

Liquid-crystalline properties of the ionic self assembled complex benzenehexacarboxylic- (didodecyltrimethylammonium)6 [BHC- (C12D)6] were investigated by polarizing microscopy, differential scanning calorimetry (DSC), x-ray analysis, null ellipsometry, UV and IR spectroscopy. The complex exhibits a bilayer smectic Sm- A2 liquid-crystalline phase and aligns spontaneously. Alignment properties do not depend on the hydrophobic or hydrophilic treatment of the surfaces. The aligned complex possesses a negative (delta n=-0.02) homeotropically oriented optical axis, with layers aligned parallel to the surface. X-ray analysis of the aligned sample revealed a lamellar structure with a d spacing of 3.15 nm, consisting of sublayers of thicknesses d1 = 1.41 and d2 = 1.74 nm . This was confirmed by simple geometrical calculations and detailed temperature-dependent investigations, revealing that the first layer contains the BHC molecules and oppositely charged groups of the surfactants, and the second the alkyl tails of the surfactant. Changes in the order parameters (as calculated from the IR investigations) are correlated with the phase transitions as found by DSC. The properties of the complex are strongly influenced by the ionic interactions within the complex. The presence of these groups slows down the dynamics within the material sufficiently to allow for crystallization of the complex from an aligned LC phase into a single crystal domain, as well as restricting the transition to the isotropic phase.

Influence of age on outcome after allogeneic hematopoietic cell transplantation: a single center study in patients aged ⩾60.

Reduced intensity conditioning regimens lead to an increasing use of allogeneic hematopoietic cell transplantation (HCT) in elderly patients. We retrospectively analyzed 151 patients aged ⩾60 receiving allogeneic HCT 2000-2012 at our center. Median age was 66 years. Kaplan-Meier estimated 3-year OS was 42% with a median follow-up of 38 months. Cumulative incidences of progression and non-relapse mortality after 3 years were 38 and 24%. OS was better in the group of patients >65 years with a Kaplan-Meier estimated OS of 50% vs 34%, P=0.060. We observed a significant influence of donor age (<50 years: 53% vs >50 years: 30%, P=0.017) and gender match (matched: 57% vs mismatched: 32%, P=0.007) on outcome. The use of a matched related donor was inferior compared with a matched or mismatched unrelated donor (19% vs 47%, P=0.015). On multivariate analysis there was an increased hazard ratio for a non-gender-matched HLA-matched-related donor (hazard ratio 3.23, 95% confidence interval 1.55-6.74, P=0.002). Age had no significant impact on OS (P=0.414). In conclusion, the data suggest that older age alone has no negative impact on the outcome of allogeneic HCT. Transplant decision should be tailored to disease risk and patient performance status rather than age.

Concurrent sequencing of full-dose CMF chemotherapy and radiation therapy in early breast cancer has no effect on treatment delivery.

With the increasing use of breast-conserving therapy plus systemic chemotherapy for the treatment of early breast cancer, the optimal sequencing of radiation therapy and chemotherapy remains controversial. Sequencing of therapy may influence not only treatment delivery, but control rates, complications and cosmesis. The aim of this study was to evaluate whether concurrent sequencing of standard doses of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) and adjuvant radiation therapy for early breast cancer impacted on optimum treatment delivery. As both an intravenous (i.v.) 3-week regimen and classic (standard) CMF were utilised in this study, both types of CMF were compared. The effect of sequencing on complications and treatment delays were also assessed. 116 patients treated with CMF chemotherapy and adjuvant tangent breast radiation were studied. 73 patients were treated prospectively with concurrent therapy and were retrospectively compared with a matched group of 40 patients treated with sequential or sandwich therapy. All patients had stage 1 or 2 cancers. There were no planned dose reductions introduced for either treatment modality. Concurrent sequencing had no impact on the ability to deliver optimum radiation or chemotherapy doses. There was no significant difference in acute Radiation Therapy Oncology Group (RTOG) skin reactions or complications between the two groups. Although small, there was a significant delay (1.32 days (0-15 versus 0.36 (0-7)) in the concurrent group (P=0.03) in the delivery of radiation therapy. Sequencing had no significant effect on haematological parameters. 'Standard' CMF had a more profound effect on treatment delivery than i.v. CMF (Radiation delay 2.2 days versus 0.26, P=0.002, % chemotherapy delivered 93% versus 99% P=0.000004). At a mean follow-up of 2.6 years, there was no difference in the cosmetic scores between the two groups. Both local and distant control rates were excellent. This study has shown that standard radiation therapy can be delivered safely concurrently with CMF chemotherapy. Whether this approach may lead to better control rates in the future needs further study.