4%] with diffuse disease; 136 [70.5%] with limited disease, 31 [16.1%] with limited involvement and 4 unknown), the observed overall crude prevalence of SSc was 105.4 cases per million adult inhabitants (95% confidence interval [CI]: 91.0; 121.4). With the capture-recapture method, the estimated selleck number of SSc cases was 233 (95%

CI: 217.3; 260.0), so an estimated 40 cases were not identified by the three sources. The estimated overall prevalence was 132.2 cases per million adult inhabitants (95% CI: 115.8; 154.0).

Conclusions: Our study provides the first estimate of SSc prevalence in the Lorraine region. The capture-recapture method allowed us to estimate an additional

21% of unobserved cases and is a good alternative to the community-based Staurosporine cell line study design for estimating the prevalence of rare diseases. (C) 2013 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 42:530-538″
“Guidelines vary regarding the safety of administering intravenous immunoglobulin (IVIG) during infections, although evidence for this advice is lacking and is based on expert opinion.

We retrospectively studied patients with common variable immunodeficiency who reacted during IVIG therapy as to whether routinely obtained markers of infection such as C-reactive protein (CRP) were elevated.

19 patients on replacement IVIG therapy in a hospital-based infusion unit were studied. CRP levels obtained were normalized to baseline levels without reactions (defined as 100).

8 of 19 patients had 16 reactions over a total of 107 infusions. Normalized CRP levels during reactions were higher [mean (+/- SD) of 258

(+/- 215)] than during infusions with no reaction [mean 100 (+/- 54.9), p = 0.017], and higher than in patients who did not react [mean 100 (+/- 79.7), p = 0.017].

Some patients with IVIG reactions had elevated CRP levels suggesting that concurrent infection may have caused the reaction. Pre-emptive antibiotic therapy and delaying infusion could prevent unnecessary morbidity.”
“Background: Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of TPCA-1 inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated.

Methods: Complete Freund’s adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant.

The antifungal compound was identified as phenyllactic acid (PLA), and it was found to have a minimum inhibitory concentration on Phytophthora drechsleri Tucker of 18 mg/mL. Bio-control activity tests indicated that PLA has a wide spectrum of antagonistic effects against Fusarium oxysporum, Botrytis cinerea, Glomerella cingulata, Penicillium citrinum, Penicillium digitatum, particularly against F. oxysporum. PLA is the most notable antimicrobial compound with broad and effective antimicrobial activity against both bacteria and fungi that has been

isolated and identified to date. These results indicate that B. coagulans TQ33 has the potential for application in biological pesticides.”
“Introduction: In vivo brain receptor occupancy has been the key assay in driving preclinical drug discovery SRT1720 solubility dmso program and there is a need to hasten this screening step. Radiolabeled methods, which are time consuming and expensive, are most widely employed to measure receptor occupancy. Thus we sought to develop and validate an alternative novel approach for measuring rat brain alpha(4)beta(2) neuronal nicotinic acetylcholine receptor occupancy using high performance liquid chromatography combined with tandem mass spectrometric detector (LC-MS/MS).

Methods: Tracer optimization studies like in vivo dose and time dependent brain regional distribution;

saturation binding and blocking study with nicotine and atropine were carried out GDC-0994 cost for ZW-104 in rats. Assay validity was tested by pretreatment with potent alpha(4)beta(2) ligands; TC-1734, cytisine, ABT-089, ABT-594 and A-366833. Receptor occupancy along with plasma and brain exposure levels of alpha(4)beta(2) ligand was measured in the same set of animals.

Results: The regional distribution of ZW-104 in rat was found to be, thalamus > frontal cortex > striatum > hippocampus > cerebellum, and is in accordance with the distribution and regional densities of alpha(4)beta(2)

nAChRs measured using [F-18]ZW-104 in mice and baboons. Pretreatment with nicotine ARS-1620 mouse and alpha(4)beta(2) ligands dose dependently reduced the binding of ZW-104 in the thalamus. Non-nicotinic antagonist atropine did not alter the binding of ZW-104 in the thalamus, indicating the tracer specificity. The ED50 values calculated for occupancy were found to be 3.01, 0.83, 14.81, 0.001 and 0.11 mg/kg for TC-1734, cytisine, ABT-089, ABT-594, and A-366833, respectively.

Discussion: These findings demonstrate that non-radiolabeled ZW-104 is suitable for determining the alpha(4)beta(2) receptor occupancy in rat brain. The LC-MS/MS based receptor occupancy assay is a rapid method and allows the generation of occupancy data along with the brain and plasma concentration in the same group of animals. (C) 2012 Elsevier Inc. All rights reserved.

While the natural history of vaginal haemangioendothelioma is uncertain, as a group, they have a propensity for local recurrence. To our knowledge this is the third reported case of a vaginal haemangioendothelioma.

Management of this tumour is challenging given the paucity of literature on this tumour. There is a need to add rare tumours to our “”knowledge bank”" to guide management of these unusual tumours.”
“Objectives: To discuss the use of molecular mutation analysis in the surgical management of pediatric thyroid nodules.

Methods: This study is a case series with retrospective chart review performed buy BAY 73-4506 at a tertiary children’s hospital. Pediatric patients who presented to the Children’s Hospital of Pittsburgh of UPMC with a thyroid nodule and had subsequent fine needle aspiration with positive molecular mutation between November 2009 and February 2012 were identified and charts were reviewed. Patient demographics, presenting signs, lab results, pathologic Selleckchem BMS-777607 findings, and surgical outcomes were collected.

Results: 5 pediatric patients with positive molecular mutation studies on preoperative FNA were identified. FNA results were categorized as follows: suspicious for follicular neoplasm (n = 2), suspicious for malignant cells (n = 1), and positive for malignant cells (n = 2). The following molecular

mutations were identified: BRAF (V600E) (n = 2), PAX8/PPAR gamma (n = 1), HRAS (n = 1), and RET/PTC (n = 1). A total thyroidectomy was performed on each patient. In all cases the final pathology was positive for malignancy (papillary thyroid carcinoma (PTC), n = 3; follicular variant of PTC, n = 2). Three of five patients had transient postsurgical hypocalcemia. There were no other postoperative complications.

Conclusions: This series provides evidence that preoperative FNA with reflex JQ-EZ-05 price molecular testing in pediatric thyroid nodules can help guide surgical decision

making, reduce the need for repeat surgeries, and diminish the risk of complications from a staged procedure. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“New hydrophilic polymer sorbents comprising reactionary sites which are complementary to a molecule of antibiotic erythromycin were synthesized by the method of molecular imprinting. A series of similar sorbents without reactionary sites was used for comparison of sorption characteristics. Sorption of erythromycin on both types of polymer sorbents synthesized was studied in a wide range of pH and ionic strength. Selectivity of erythromycin sorption on molecularly imprinted cross-linked polymers was shown to depend on the specific interaction of target molecule with polymer matrix. This type of sorbent is perspective for the development of antibiotic purification directly from a culture medium Saccharopolyspora erythreus. DOI: 10.1134/S0003683811060056″
“Lymphoedema can present with an array of distressing symptoms, which can pose significant management dilemmas.

Physical examination was remarkable for markedly red skin flushing, not unlike that seen during histamine fish poisoning. R. ornithinolytica is a histamine-producing bacterium recently elucidated as a major cause of histamine fish poisoning. Only 2 other cases of human infection by R. ornithinolytica have been reported.”
“The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and see more formalin tests.

The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive ACY-241 nmr effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition

in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.”
“The stability, electronic, and optical properties of two dimensional hydrogenated few atomic layer silicon (H-FLSi) are systematically

studied with density functional theory calculations. The formation energy of H-FLSi decreases with increasing layer thickness and approaches zero at the thickness of double layer, Selleck BAY 11-7082 suggesting that this material is energetically favorable and thus its experimentally synthesizing is feasible. Its bandgap decreases with the increase of the thickness and eventually approaches the value of bulk silicon. More interestingly, the bandgap of hydrogenated silicon films can be tuned by external electric field and even becomes metal. Importantly, the light absorption threshold and absorption peak of the H-Si mono-and bilayer locate in different energy regions and both move toward higher energy region as compared with those of the bulk silicon. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3553838]“
“The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice.

Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved. Semin Arthritis Rheum 40:447-454″
“Imiquimod 5% cream is currently approved for treatment of nonfacial, superficial basal cell carcinomas (BCCs). Topical imiquimod might be a reasonable candidate for adjunctive therapy of nodular, nasal BCCs before Mohs surgery.

To observe the effectiveness of imiquimod 5% cream in reducing the number of Mohs stages, defect size, cost of Mohs surgery, and reconstruction.

Patients applied the study medication nightly for 6 weeks with occlusion followed by a 4-week rest period before Mohs surgery was performed.

No differences were demonstrated

in the number of Mohs stages, defect sizes, Cyclosporin A order or costs between the two groups, possibly because of our small sample size. Only five of 12 patients (42%) in the treatment group were found histologically clear of tumor (complete responders).

Imiquimod 5% cream was not helpful as an adjunctive treatment of nodular, nasal BCCs before Mohs surgery, but a larger study might show a benefit. Clearance of nodular, nasal BCCs treated with imiquimod prior PHA-739358 datasheet to Mohs surgery was less than described in previous studies. Nasal BCCs may be more resistant to imiquimod treatment. Local inflammatory reactions limit imiquimod’s usefulness in this setting. Histologic assessment of nasal BCCs treated with imiquimod is recommended.

Grants

were provided by the Scott and White Research and Education Division and the pharmaceutical industry (3M and Graceway Pharmaceuticals).”
“Objective:

To establish if first or second trimester biometry is a useful adjunct in the prediction of adverse perinatal outcome in twin pregnancy.

Methods: A consecutive cohort of 1028 twin pregnancies was enrolled for the Evaluation of Sonographic Predictors of Restricted growth in Twins (ESPRiT) study, a prospective study conducted at eight academic centers. Outcome data was recorded for 1001 twin pairs that completed the study. Ultrasound biometry was available for 960 pregnancies. Biometric data obtained between 11 and 22 weeks were evaluated as predictors of a composite of adverse perinatal outcome (mortality, hypoxic ischemic encephalopathy, periventricular leukomalacia, necrotizing enterocolitis, CHIR98014 datasheet respiratory distress, or sepsis), preterm delivery (PTD) and birthweight discordance greater than 18% (18% BW). Outcomes were adjusted for chorionicity and gestational age using Cox Proportional Hazards regression.

Results: Differences in crown-rump length (CRL) were not predictive of adverse perinatal outcome. Between 14 and 22 weeks, a difference in abdominal circumference (AC) of more than 10% was the most useful predictor of adverse outcome, PTD and 18% or more BW discordance in all twins. Overall the strongest correlation was observed for intertwin differences in biometry between 18 and 22 weeks.

Conclusion: Biometry in the early second trimester can successfully identify twin pregnancies at increased risk.

The structure, morphology, mechanical NVP-LDE225 manufacturer properties, and thermal stability of these hybrid materials were investigated by FTIR, SEM, tensile shear test (TSS), and TG. FTIR spectra indicated that the multiple reactive functional silanol group Si-OH on the surface of SiO(2) particles reacted with PVA and PF. Compared with pure PF, the composite 50-50-3% exhibited the maximum shear strength which increased by 158%, whereas the elongation at break increased by 63%. Morphological results agreed well with the mechanical properties. The TG results suggested that the composite material 50-50-3% and pure PF had almost the same thermal stability because silica sol and PVA had opposite effects

on the heat resistance of the hybrid materials. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 744-751, 2011″
“Microscopic two-level systems (TLSs) are known to contribute to loss in resonant superconducting microwave circuits. This loss increases at low power and temperatures as the TLSs become unsaturated. We find that the loss is dependent on both the substrate-superconductor interface and the roughness of the surfaces. A native, oxide-free interface reduced the loss due to TLSs. However, a rough

surface in the CPW gap did not cause more TLS loss, but the overall loss was significantly increased for the roughest IWR-1-endo surfaces. [doi:10.1063/1.3499608]“
“Humoral hypercalcemia of malignancy is an important cause of hypercalcemia associated with malignancies and has been rarely reported because of vulvar cancer.

A 65-year-old woman performed modified radical BTK inhibitor molecular weight vulvectomy and bilateral lymph node dissection because of vulvar cancer was referred to our clinic with fatigue and somnolence 4 months after her operation. Calcium level was 15.9 mg/dL. There was no bone metastasis,

and hypercalcemia was thought as paraneoplastic syndrome because of distant recurrence of the primary vulvar cancer.

Vulvar cancer and hypercalcemia can be seen together very rarely. However, recurrence should be kept in mind in patients with symptoms and signs of hypercalcemia.”
“This work investigates the effect of polycarbonate (PC) and montmorillonite (MMT) content on the properties and morphology of epoxy resin (EP). Izod impact strength (IS), flexural strength and critical stress intensity factor (KC) were estimated as function of modifiers content. The values of IS and KC parameters increased by respectively 150% and 90% with the addition of 5 wt % PC. Hybrid compositions containing 1 wt % MMT and 5 wt % PC exhibited the best mechanical properties. Indeed, the addition of 1 wt % MMT to EP modified with 5 wt % PC caused enhancement of IS values by 100% in comparison with neat EP. SEM micrographs revealed that the enhancement mechanism of mechanical properties might be due to extensive yielding of EP associated with the formation of stratified elongated structures.

Longer time to union was seen in association with older fractures, displaced fractures, proximal fractures, and fractures in patients with osteonecrosis. The union rate following surgery Idasanutlin supplier was 96.5% (109 of 113). Increased time to union was seen in association with open physes,

fracture displacement, proximal fracture, the type of screw used for surgical fixation, and the use of bone graft at the time of surgery.

Discussion: With changes in patient characteristics and activities, scaphoid fracture patterns in children and adolescents are now similar to the published patterns in adults. While 90% of acute nondisplaced fractures heal with nonoperative treatment, three months of cast immobilization or more may be required for more proximal injuries. Almost one-third of pediatric patients with scaphoid fractures will present late with chronic nonunions; in these instances, surgical reduction and internal fixation should be considered the primary treatment option.”
“In this

study, we applied a transcranial magnetic stimulation (TMS) to investigate the temporal aspect for the functional processing of visual attention. Selleckchem AS1842856 Although it has been known that right posterior parietal cortex (PPC) in the brain has a role in certain visual search tasks, there is little knowledge about the temporal aspect of this area. Three visual search tasks that have different difficulties of task execution individually were carried out. These three visual search tasks are the “”easy feature task,”" the “”hard feature task,”" and the “” conjunction task.”" To investigate the temporal aspect

Ro-3306 manufacturer of the PPC involved in the visual search, we applied various stimulus onset asynchronies (SOAs) and measured the reaction time of the visual search. The magnetic stimulation was applied on the right PPC or the left PPC by the figure-eight coil. The results show that the reaction times of the hard feature task are longer than those of the easy feature task. When SOA = 150 ms, compared with no-TMS condition, there was a significant increase in target-present reaction time when TMS pulses were applied. We considered that the right PPC was involved in the visual search at about SOA = 150 ms after visual stimulus presentation. The magnetic stimulation to the right PPC disturbed the processing of the visual search. However, the magnetic stimulation to the left PPC gives no effect on the processing of the visual search. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3061845]“
“Patients with hepatitis C virus-related decompensated cirrhosis can benefit frominterferonbased antiviral therapy, but the common complication of cytopenia is a contraindication for this treatment. Splenectomy prior to interferon therapy may alleviate this problem.

We believe that further efforts must be directed at preoperative diagnosis of mild bleeding disorders CX-4945 datasheet to ensure safer surgeries. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“Jjustification of Repeated Animal Experiments and Determination of the Required Number of Animals According to the German Animal Protection Act The repetition of animal experiments requires justification according to the German Animal Protection Act (Tierschutzgesetz). On the other hand, repetition of experiments is considered

necessary for the improvement of the precision and reliability of the results. In this paper it is shown that such improvement is not achieved by a repetition of the experiment but by repeated inclusion of animals into the experiment. The more animals are included, the SRT2104 cost more precisely and reliably the results can be

generalized to further situations. The number of animals necessary for a proposed precision can be determined with statistical methods. The basic ideas are explained in the paper and demonstrated with two examples. In long term experiments the precision can he improved, if all experimental conditions are applied within temporally homogenous blocks to few animals and the blocks are repeated till the necessary number of animals is reached (block experiments). By sequential interim analyses, where at each analysis on the basis of all available data a decision on continuation or conclusion of the experiment is drawn, a further reduction of the number of animals can be achieved. These methods are discussed in the paper. Repetitions of total animal experiments are justified, if there exist legitimate doubts on the soundness of the published results or if in so called ring-experiments the variability of the results between different laboratories should be investigated.”
“This

review summarizes analytical determinations using bismuth screen-printed electrodes (Bi-SPEs). We emphasize fundamental understanding of the design and the fabrication of learn more these economical disposable sensors that are environment friendly. The methods of coating the Bi on the working surface and their potential modifications are used to classify the types of Bi-SPE. We present tables with the most significant information from the accessible literature. (C) 2013 Elsevier Ltd. All rights reserved.”
“Juvenile xanthogranuloma (JXG) is a histiocytic inflammatory disorder that can present different histologic patterns. Classic JXG consists of sheets of foamy histiocytes and numerous multinucleated Touton giant cells. Nonlipidized JXG (NJXG) is one of the unusual variants of JXG, consisting of a diffuse monomorphic infiltrate of mononuclear histiocytes, suggesting an aggressive or malignant tumor due the high mitotic index. However, NJXG behaves clinically as classic JXG. We present an unusual case of a 6-year-old boy who presented an exophytic ulcerated nodule on the lower lip diagnosed as NJXG.

6%. In 522 patients, bulbar urethroplasty using nontransecting techniques (nontransecting anastomotic urethroplasty and simple oral grafting techniques) provided approximately the same success rate, ranging from 81.8 to 100%.

Summary

Future studies, including

more homogenous series of patients and subjective evaluation of urinary and sexual complications after repair, are necessary to surely establish the gold standard of treatment for nontraumatic strictures located in the proximal bulbar urethra.”
“Depending on the reactant ratio, dithiooxamide (ethanedithioamide) reacted as N-nucleophile or N,N’-binucleophile with highly electrophilic aldimines, N-(2,2,2-trichloroethylidene)- and N-(2,2-dichloro-2-phenylethylidene)arenesulfonamides, to give the corresponding mono- or bis-adducts, N-[2-polychloro-1-(arylsulfonylamino) Dinaciclib ethyl]ethanedithioamides or N,N’-bis[2-polychloro-1-(arylsulfonylamino)ethyl]ethanedithioamides, in good yield.”
“We have studied the influence of pre-training psychological stress on the expression www.selleckchem.com/products/AZD1152-HQPA.html of c-fos mRNA following long-term spatial memory retrieval. Rats were trained to learn the location of a hidden escape platform in the radial-arm water maze, and then

their memory for the platform location was assessed 24 h later. Rat brains were extracted 30 min after the 24-h memory test trial for analysis of c-fos mRNA. Four groups were tested: (1) Rats given standard training (Standard); (2) Rats given cat exposure (Predator Stress) 30 min prior to training (Pre-Training Stress); (3) Rats given water exposure only

(Water Yoked); and (4) Rats given no water exposure (Home Cage). The Standard trained group find more exhibited excellent 24 h memory which was accompanied by increased c-fos mRNA in the dorsal hippocampus and basolateral amygdala (BLA). The Water Yoked group exhibited no increase in c-fos mRNA in any brain region. Rats in the Pre-Training Stress group were classified into two subgroups: good and bad memory performers. Neither of the two Pre-Training Stress subgroups exhibited a significant change in c-fos mRNA expression in the dorsal hippocampus or BLA. Instead, stressed rats with good memory exhibited significantly greater c-fos mRNA expression in the dorsolateral striatum (DLS) compared to stressed rats with bad memory. This finding suggests that stressed rats with good memory used their DLS to generate a non-spatial (cue-based) strategy to learn and subsequently retrieve the memory of the platform location. Collectively, these findings provide evidence at a molecular level for the involvement of the hippocampus and BLA in the retrieval of spatial memory and contribute novel observations on the influence of pre-training stress in activating the DLS in response to long-term memory retrieval.”
“Prevalence rates of food allergy have increased rapidly in recent decades.

The growth of the lungs of the infant with BPD through childhood remains poorly characterized.

Summary

Recent experiences in neonatology suggest that combining less invasive care strategies that avoid excessive oxygen and ventilation, decrease postnatal infections, and optimize nutrition may decrease the incidence and severity

of BPD.”
“The use of two antidepressants from the initiation of treatment in major depressive disorder has been investigated in several recent studies and forms a paradigm shift in the pharmacotherapy of the condition. Several, but not all, trials have claimed improved response and remission rates with the combinations as opposed to monotherapy. buy Nutlin-3 The use of folate preparations (folic and folinic acid and L-methylfolate) have shown effective augmentation of antidepressant response in a variety of controlled and open-label settings in patients with normo- and hypofolatemic status. Several recent trials using L-methylfolate, the active and more bioavailable form of folic acid, have shown promising adjunctive use with a well-tolerated adverse event profile.”
“Impairment of the health-related quality of life (HRQOL) of patients with end-stage A-1331852 concentration renal disease (ESRD) is now well documented. These impairments involve a wide variety of domains and can be assessed using an array of well-validated instruments.

Incorporation of at least some of these instruments into routine patient care is important in order to measure the physical and psychological impact of a disease and its treatment on the HRQOL of patients. How this implementation can be achieved in a practical way is, however, a challenge. As more research focuses on improving the HRQOL of patients with ESRD, the selleck chemicals llc systematic evaluation

of HRQOL and incorporation into patient care is becoming increasingly important. Whether strategies to improve the HRQOL of patients will translate into improved patient outcomes-as evidenced by reduced mortality and hospitalizations-and lower costs, remains to be determined.”
“Background and Purpose: At present, open retroperitoneal lymph node dissection (RPLND) remains the preferred approach at many high-volume centers for the surgical treatment of patients with low-stage testis cancer. Despite the potential advantages of a minimally invasive approach, including improved cosmesis and shorter recovery times, there remain concerns over the quality of dissection and oncologic control offered through a minimally invasive approach. Our objective was to critically evaluate the safety and intermediate-term oncologic efficacy of laparoscopic RPLND (L-RPLND).

Patients and Methods: A retrospective chart review was performed, evaluating all patients who underwent L-RPLND between 2003 and 2009. Patient records were updated by telephone interview.

Results: A total of 59 patients underwent L-RPLND during the study period, of which 13 had previously undergone chemotherapy.