The administration of the opioid buprenorphine decreases motivational error signals.

While opioid addiction has reached pandemic proportions, we still lack a good understanding of how the administration of opioids interacts with cognitive functions. Error processing - the ability to detect erroneous actions and correct one's behaviour afterwards - is one such cognitive function that might be susceptible to opioidergic influences. Errors are hypothesised to induce aversive negative arousal, while opioids have been suggested to reduce aversive arousal induced by unpleasant and stressful stimuli. Thus, this study investigated whether the acute administration of an opioid would affect error processing. In a double-blind between-subject study, 42 male volunteers were recruited and received either 0.2 mg buprenorphine (a partial µ-opioid receptor agonist and κ-opioid receptor antagonist) or a placebo pill before they performed a stimulus-response task provoking errors. Electroencephalograms (EEG) were recorded while participants performed the task. We observed no group differences in terms of reaction times, error rates, and affective state ratings during the task between buprenorphine and control participants. Additional measures of adaptive control, however, showed interfering effects of buprenorphine administration. On the neural level, decreased Pe (Error Positivity) amplitudes were found in buprenorphine compared to control participants following error commission. Further, frontal delta oscillations were decreased in the buprenorphine group after all responses. Our neural results jointly demonstrate a general reduction in error processing in those participants who received an opioid before task completion, thereby suggesting that opioids might have indeed the potential to dampen motivational error signals. Importantly, the effects of the opioid were evident in more elaborate error processing stages, thereby impacting on processes of conscious error appraisal and evidence accumulation.

[The German keratomycosis registry : Initial results of a multicenter survey]. / Das Deutsche Pilz-Keratitis-Register : Erste Ergebnisse einer multizentrischen Erhebung.

BACKGROUND AND PURPOSE: Mycotic keratitis is a serious but relatively rare disease. No targeted data collection in Germany existed until the foundation of the German Pilz-Keratitis Register in 2015. PATIENTS AND METHODS: The inclusion of retrospective and prospective patients was carried out. INCLUSION CRITERIA: diagnosis confirmed by the polymerase chain reaction (PCR), culture, histology or confocal microscopy (IVCM). Collected parameters: date of symptom onset, date and method of diagnosis, risk factors, visual acuity and findings at admission and at follow-up, conservative and surgical treatment. RESULTS: By January 2018, a total of 102 eyes from the years 2000-2017 were reported from 16 centers (64.3% female, mean age 52 years, range 18-95 years). The initial diagnosis was made correctly in only 20.6% of cases. The mean time to correct diagnosis was 31.7 ±â€¯46.9 (0-296) days. The diagnosis was confirmed in cultures in 74.5%, histologically in 30.4%, by PCR in 38.2% and IVCM in 27.4%. Fungal species identified were: 36.7% Fusarium spp., 35.8% Candida spp., 6.4% Aspergillus spp. and 21.1% other. The most important risk factor was the use of contact lenses. The most commonly used antifungal agent was voriconazole (64.7%) followed by amphotericin B (37.2%). Penetrating keratoplasty was performed in 65.7% of the cases and 8.8% of the affected eyes had to be enucleated. The visual acuity of the entire study population increased from the initial 0.16 ±â€¯0.25 (0.001-1.0) decimal to 0.28 ±â€¯0.34 (0-1.0) decimal. CONCLUSION: The correct diagnosis of fungal keratitis is often significantly delayed. The treatment can be very difficult and keratoplasty is often necessary. In order to gain a better understanding of this disease, to recognize previously unknown risk factors and, if necessary, a change in the spectrum of pathogens and to identify approaches to treatment optimization, the fungal keratitis registry will be continued.

Effect of divalent versus monovalent cations on the MS2 retention capacity of amino-functionalized ceramic filters.

Ceramic capillary membranes conditioned for virus filtration via functionalization with n-(3-trimethoxysilylpropyl)diethylenetriamine (TPDA) are analyzed with respect to their virus retention capacity when using feed solutions based on monovalent and divalent salts (NaCl, MgCl2). The log reduction value (LRV) by operating in dead-end mode using the model bacteriophage MS2 with a diameter of 25 nm and an IEP of 3.9 is as high as 9.6 when using feeds containing MgCl2. In contrast, a lesser LRV of 6.4 is observed for feed solutions based on NaCl. The TPDA functionalized surface is simulated at the atomistic scale using explicit-solvent molecular dynamics in the presence of either Na+ or Mg2+ ions. Computational prediction of the binding free energy reveals that the Mg2+ ions remain preferentially adsorbed at the surface, whereas Na+ ions form a weakly bound dissolved ionic layer. The charge shielding between surface and amino groups by the adsorbed Mg2+ ions leads to an upright orientation of the TPDA molecules as opposed to a more tilted orientation in the presence of Na+ ions. The resulting better accessibility of the TPDA molecules is very likely responsible for the enhanced virus retention capacity using a feed solution with Mg2+ ions.

Global sensitivity analysis of an in-sewer process model for the study of sulfide-induced corrosion of concrete.

The presence of high concentrations of hydrogen sulfide in the sewer system can result in corrosion of the concrete sewer pipes. The formation and fate of hydrogen sulfide in the sewer system is governed by a complex system of biological, chemical and physical processes. Therefore, mechanistic models have been developed to describe the underlying processes. In this work, global sensitivity analysis was applied to an in-sewer process model (aqua3S) to determine the most important model input factors with regard to sulfide formation in rising mains and the concrete corrosion rate downstream of a rising main. The results of the sensitivity analysis revealed the most influential model parameters, but also the importance of the characteristics of the organic matter, the alkalinity of the concrete and the movement of the sewer gas phase.

Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance.

BACKGROUND: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy. METHODS: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy. RESULTS: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å(2)) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively. CONCLUSION: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer.

An adaptive framework to differentiate receiving water quality impacts on a multi-scale level.

The paradigm shift in recent years towards sustainable and coherent water resources management on a river basin scale has changed the subject of investigations to a multi-scale problem representing a great challenge for all actors participating in the management process. In this regard, planning engineers often face an inherent conflict to provide reliable decision support for complex questions with a minimum of effort. This trend inevitably increases the risk to base decisions upon uncertain and unverified conclusions. This paper proposes an adaptive framework for integral planning that combines several concepts (flow balancing, water quality monitoring, process modelling, multi-objective assessment) to systematically evaluate management strategies for water quality improvement. As key element, an S/P matrix is introduced to structure the differentiation of relevant 'pressures' in affected regions, i.e. 'spatial units', which helps in handling complexity. The framework is applied to a small, but typical, catchment in Flanders, Belgium. The application to the real-life case shows: (1) the proposed approach is adaptive, covers problems of different spatial and temporal scale, efficiently reduces complexity and finally leads to a transparent solution; and (2) water quality and emission-based performance evaluation must be done jointly as an emission-based performance improvement does not necessarily lead to an improved water quality status, and an assessment solely focusing on water quality criteria may mask non-compliance with emission-based standards. Recommendations derived from the theoretical analysis have been put into practice.

Storage and recall of weak coherent optical pulses with an efficiency of 25%.

We demonstrate experimentally an efficient coherent rephasing scheme for the storage and recall of weak coherent light pulses in an inhomogeneously broadened optical transition in a Pr(3+):YSO crystal at 2.1 K. Precise optical pumping using a frequency stable (≈1 kHz linewidth) laser is employed to create a highly controllable atomic frequency comb structure. We report single photon level storage and retrieval efficiencies of 25%, based on coherent photon-echo-type reemission in the forward direction. The high efficiency is mainly a product of our highly controllable and precise ensemble-shaping technique. The coherence property of the quantum memory is proved through interference between a super-Gaussian pulse and the emitted echo.

Optical and electrical interfacing technologies for living cell bio-chips.

Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by micro-system-technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such whole-cell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the micro-electronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.

Understanding laser stabilization using spectral hole burning.

There have recently been several studies of the performance of laser frequency stabilization using spectral holes in solids, instead of an external cavity, as a frequency reference. Here an analytical theory for Pound-Drever-Hall laser frequency stabilization using spectral hole-burning is developed. The interaction between the atomic medium and the phase modulated light is described using a linearized model of the Maxwell-Bloch equations. The interplay between the carrier and modulation sidebands reveals significant differences from the case of locking to a cavity. These include a different optimum modulation index, an optimum sample absorption, and the possibility to lock the laser in an inherent linear frequency drift mode. Spectral holes in solids can be permanent or transient. For the materials normally used, the dynamics and time scales of transient holes often depend on population relaxation processes between ground state hyperfine levels. These relaxation rates can be very different for different solid state materials. We demonstrate, using radio-frequency pumping, that the hyperfine population dynamics may be controlled and tailored to give optimum frequency stabilization performance. In this way also materials with initially non-optimum performance can be used for stabilization. The theoretical predictions regarding the inherent linear frequency drift is compared to experimental data from a dye laser stabilized to a spectral hole in a Pr(3+)3+:Y(2)SiO(5) crystal.

Remote laser-induced breakdown spectroscopy for the detection and removal of salt on metal and polymeric surfaces.

The detection of contamination such as salt in outdoor high-voltage insulator systems and its subsequent removal are vital for a reliable transmission of electric power. Remote detection of salt on a copper metal surface was carried out by using a mobile laser-induced breakdown spectroscopy (LIBS) Lidar system with a laser wavelength of 355 nm. Detection of salt on a polymeric high-voltage insulator was obtained when an additional lens was inserted into the beam path, and the number of photons that was detected could be calculated by using a calibrated white light source. Ablative cleaning could readily be carried out with LIBS and was verified by observing the disappearance of the sodium D-line emission.

Fungus covered insulator materials studied with laser-induced fluorescence and principal component analysis.

A method combining laser-induced fluorescence and principal component analysis to detect and discriminate between algal and fungal growth on insulator materials has been studied. Eight fungal cultures and four insulator materials have been analyzed. Multivariate classifications were utilized to characterize the insulator material, and fungal growth could readily be distinguished from a clean surface. The results of the principal component analyses make it possible to distinguish between algae infected, fungi infected, and clean silicone rubber materials. The experiments were performed in the laboratory using a fiber-optic fluorosensor that consisted of a nitrogen laser and an optical multi-channel analyzer system.

Monitoring of hematological, inflammatory and oxidative reactions to acute oral iron exposure in human volunteers: preliminary screening for selection of potentially-responsive biomarkers.

BACKGROUND: Iron is an essential micronutrient but also a major catalyst of oxidative and inflammatory reactions. OBJECTIVE: To evaluate the potential utility of selected biomarkers in blood or urine to indicate in vivo oxidative or inflammatory response to oral iron intake at pharmacological doses. METHODS: Three healthy volunteers provided morning, fasting samples of blood and urine on up to 13 study days--3 before, 7 during and 3 following a 7-consecutive-day period of receiving 120 mg of iron per day as ferrous sulfate in commercially available syrup. A series of 23 biomarkers were measured on each collection of biological fluids to monitor iron-responsive changes in biomarkers related to hematological or iron status, inflammation and in vivo oxidation. RESULTS: Among the inflammatory biomarkers measured, white blood cells, serum CRP and urinary neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL-4) and TNF-alpha had abnormal responses with a time association to the oral iron intake. Among the oxidative biomarkers, expression of blood superoxide dismutase (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid reactive substances (TBARS), total oxidative capacity and carbonyl proteins were stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to ingestion of the iron challenge. Serum hepcidin concentration increased dramatically in all three subjects after only the first 120 mg dose of iron, and remained elevated even 9 days after cessation of the iron intervention. CONCLUSIONS: Most of the candidate biomarkers show very limited promise as response-indicators to oral iron dosing at the 120 mg dosages or lower, but circulating IL-4, TNF-alpha as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine and isoprostanes showed potential utility as reliable indicators of oxidative and inflammatory response to oral ferrous sulfate.

Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. PATIENTS AND METHODS: A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 x 10(9)/L). Forty of 41 patients received both infusions. RESULTS: Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. CONCLUSION: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.

Complete reconstruction of the quantum state of a single-photon wave packet absorbed by a Doppler-broadened transition.

An idea for how to reconstruct the quantum state of a nonstationary single-photon wave packet absorbed in a macroscopic medium with inhomogeneously broadened lines is presented. An analytical treatment of the problem is performed and the requirements on the proposed scheme for complete recovery of the recorded nonstationary quantum state with a probability close to unity is described. The physical nature of the present scheme is also discussed.

Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas.

PURPOSE: To evaluate the efficacy and safety of tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, Seattle, WA, and GlaxoSmithKline, Philadelphia, PA) in patients with chemotherapy-refractory low-grade or transformed low-grade non-Hodgkin's lymphoma (NHL) and to compare its efficacy to the patients' last qualifying chemotherapy (LQC) regimens. PATIENTS AND METHODS: Sixty patients who had been treated with at least two protocol-specified qualifying chemotherapy regimens and had not responded or progressed within 6 months after their LQC were treated with a single course of iodine I 131 tositumomab. RESULTS: Patients had received a median of four prior chemotherapy regimens. A partial or complete response (CR) was observed in 39 patients (65%) after iodine I 131 tositumomab, compared with 17 patients (28%) after their LQC (P <.001). The median duration of response (MDR) was 6.5 months after iodine I 131 tositumomab, compared with 3.4 months after the LQC (P <.001). Two patients (3%) had a CR after their LQC, compared with 12 (20%) after iodine I 131 tositumomab (P <.001). The MDR for CR was 6.1 months after the LQC and had not been reached with follow-up of more than 47 months after iodine I 131 tositumomab. An independent review panel verified that 32 (74%) of the 43 patients with nonequivalent durations of response (> 30 days difference) had a longer duration of response after iodine I 131 tositumomab (P <.001). Only one patient was hospitalized for neutropenic fever. Five patients (8%) developed human antimurine antibodies, and one (2%) developed an elevated TSH level after treatment. Myelodysplasia was diagnosed in four patients in follow-up. CONCLUSION: A single course of iodine I 131 tositumomab was significantly more efficacious than the LQC received by extensively pretreated patients with chemotherapy-refractory, low-grade, or transformed low-grade NHL and had an acceptable safety profile.

The carboxyl-terminal domain of the granulocyte colony-stimulating factor receptor uncouples ribosomal biogenesis from cell cycle progression in differentiating 32D myeloid cells.

Translational regulation plays an important role in development. In terminally differentiating cells a decrease in translation rate is common, although the regulatory mechanisms are unknown. We utilized 32Dcl3 myeloblast cells to investigate translational regulation during granulocyte colony-stimulating factor (G-CSF)-induced differentiation. G-CSF causes a significant decrease in translation rate compared with interleukin-3, which is a mitogen for these cells. Although these two cytokines exhibit modest differences in their effect on translation factor phosphorylation, they exhibit dramatic differences in their effect on ribosomal abundance and ribosomal DNA transcription. However, because both cytokines stimulate cell cycling, G-CSF induces a dissociation of ribosomal biogenesis from cell cycle progression. This uncoupling of ribosomal biogenesis from cell cycle progression appears to be closely related to the transmission of a differentiation signal, because it is not observed in cells expressing a carboxyl-terminally truncated G-CSF receptor, which supports proliferation but not differentiation of these cells. Because a similar event occurs early in differentiation of murine erythroleukemic cells, this suggests that ribosomal content is a common target of differentiating agents.

Reconstructive management of contralateral breast cancer in patients who previously underwent unilateral breast reconstruction.

When a patient who has had unilateral breast reconstruction presents with a new cancer on the opposite side, the reconstructive management of the second breast can be unclear. This study was performed to determine whether reconstruction of the second breast is oncologically reasonable and to evaluate the reconstructive options available to these patients. Patients who had mastectomy with unilateral breast reconstruction between 1988 and 1994 and who had a minimal follow-up of 5 years from the initial breast cancer were reviewed. Of 469 patients reviewed, 18 patients (4 percent) were identified who developed contralateral breast cancer. Mean age at the initial breast cancer presentation was 43 years (range, 26 to 57 years), and mean age at presentation with contralateral breast cancer was 48 years (range, 36 to 67). The mean interval between the initial and contralateral breast cancer presentations was 5 years (range, 1 to 10 years). Mean follow-up from the time of contralateral breast cancer was 5 years (range, 1 to 9 years). In most cases, contralateral breast cancer presented at an early stage (13 of 18 patients; 72 percent), and a shift to an earlier stage at presentation of the contralateral cancer was evident compared with the initial breast cancer. Of the 18 patients who developed contralateral breast cancer, 16 (89 percent) had no evidence of disease, one was alive with disease, and one died. Reconstructive management after the initial mastectomy included 16 transverse rectus abdominis myocutaneous flaps (seven free and nine pedicled), one latissimus dorsi myocutaneous flap with implant, and one superior gluteal free flap. Surgical management of the second breast after contralateral breast cancer included breast conservation in two patients, mastectomy without reconstruction in four, and mastectomy with reconstruction in 12. Reconstruction of the second breast included one free transverse rectus abdominis myocutaneous flap, three extended latissimus dorsi flaps, two latissimus dorsi myocutaneous flaps with implants, three implants alone, two Rubens flaps, and one superior gluteal free flap. No major complications were noted after the reconstruction of the second breast. The best symmetry was obtained when similar methods and tissues were used on both sides. The incidence of contralateral breast cancer after mastectomy and unilateral breast reconstruction is low. In most cases, contralateral breast cancer presents at an earlier stage compared with the initial breast cancer, and the prognosis is good. In patients who develop a contralateral breast cancer after mastectomy and unilateral breast reconstruction, the reconstruction of the second breast after mastectomy is oncologically reasonable and should be offered to provide optimal breast symmetry and a better quality of life. The best result is obtained when similar methods and tissues are used on both sides.

Aesthetically successful mandibular reconstruction with a single reconstruction plate.

Aesthetically successful mandibular reconstruction can be performed with free fibular flaps and with a single low-profile reconstruction plate. The keys to aesthetic success are accurate bending of the reconstruction plate, accurate alignment of the bone, and maintenance of the lower border of the mandible. If only the mandible and overlying oral lining are missing, the results can be indistinguishable from normal. In massive defects that include other structures besides the mandible, however, excellent aesthetic results can be difficult or impossible. Massive soft tissue deficits and heavy doses of postoperative radiation therapy can impact severely the aesthetic quality of the result. Patients should be aware of these limitations and have appropriately realistic expectations.

Thrombolytic therapy: what is its role in free flap salvage?

Thrombolytic agents have been demonstrated to improve free flap salvage in animal models. However, clinical evidence regarding their efficacy has been scant. The authors reviewed their experience with flap salvage using thrombolytic therapy in 1,733 free flaps from February 1990 to July 1998. Patients with intraoperative pedicle thrombosis were excluded from this review. Forty-one of the 55 free flaps that were reexplored emergently were identified as having pedicle thrombosis. Of these 41 flaps, 28 free flaps were salvaged (flap salvage group, 68%) and 13 free flaps failed (flap failure group, 32%). Thrombolytic therapy (urokinase in 7 patients, tissue plasminogen activator in 1 patient) was used in six flaps in the flap salvage group and two flaps in the flap failure group. Statistical analysis demonstrated no difference between the two groups with regard to thrombolytic therapy. There was also no difference between the two groups with regard to use of systemic heparin (100-500 U per hour) at the time of pedicle thrombosis or with regard to whether Fogarty catheters were used. Smoking, preoperative radiotherapy, and the use of interpositional vein grafts during initial flap reconstruction had no impact on the outcome of flap salvage. The flap salvage group was reexplored at a mean of 1.5 days compared with the flap failure group, which was reexplored at a mean of 4.2 days (p = 0.007). Early detection of pedicle thrombosis remains the most important factor in the salvage of free flaps. Although these numbers are small and definitive statements cannot be made, the role of thrombolytic agents in free flap salvage requires further clinical evaluation.

Comparison of immediate and delayed free TRAM flap breast reconstruction in patients receiving postmastectomy radiation therapy.

Tumor pathologic features and the extent of nodal involvement dictate whether radiation therapy is given after mastectomy for breast cancer. It is generally well accepted that radiation negatively influences the outcome of implant-based breast reconstruction. However, the long-term effect of radiation therapy on the outcome of breast reconstruction with the free transverse rectus abdominis myocutaneous (TRAM) flap is still unclear. For patients who need postmastectomy radiation therapy, the optimal timing of TRAM flap reconstruction is controversial. This study compares the outcome of immediate and delayed free TRAM flap breast reconstruction in patients who received postmastectomy radiation therapy. All patients at The University of Texas M. D. Anderson Cancer Center who received postmastectomy radiation therapy and who also underwent free TRAM flap breast reconstruction between January of 1988 and December of 1998 were included in the study. Patients who received radiation therapy before delayed TRAM flap reconstruction were compared with patients who underwent immediate TRAM flap reconstruction before radiation therapy. Early and late complications were compared between the two groups. Early complications included vessel thrombosis, partial or total flap loss, mastectomy skin flap necrosis, and local wound-healing problems, whereas late complications included fat necrosis, volume loss, and flap contracture of free TRAM breast mounds. Late complications were evaluated at least 1 year after the completion of radiation therapy for patients who had delayed reconstruction and at least 1 year after reconstruction for patients who had immediate reconstruction. During the study period, 32 patients had immediate TRAM flap reconstruction before radiation therapy and 70 patients had radiation therapy before TRAM flap reconstruction. Mean follow-up times for the immediate reconstruction and delayed reconstruction groups were 3 and 5 years, respectively. The mean radiation dose was 50 Gy in the immediate reconstruction group and 51 Gy in the delayed reconstruction group. One complete flap loss occurred in the delayed reconstruction group, and no flap loss occurred in the immediate reconstruction group. The incidence of early complications did not differ significantly between the two groups. However, the incidence of late complications was significantly higher in the immediate reconstruction group than in the delayed reconstruction group (87.5 percent versus 8.6 percent; p = 0.000). Nine patients (28 percent) in the immediate reconstruction group required an additional flap to correct the distorted contour from flap shrinkage and severe flap contraction. These findings indicate that, in patients who are candidates for free TRAM flap breast reconstruction and need postmastectomy radiation therapy, reconstruction should be delayed until radiation therapy is complete.