bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychological and behavioural factors associated with sexual risk behaviour among Slovak students
Authors: Kalina Ondrej , Geckova Andrea M , Jarcuska Pavol , Orosova Olga , van Dijk Jitse P , Reijneveld Sijmen A
Published: January 2009

Background

Knowledge about the prevalence of sexual risk behaviour (SRB) in adolescence is needed to prevent unwanted health consequences. Studies on SRB among adolescents in Central Europe are rare and mostly rely on a single indicator for SRB. This study aims to assess the association of behavioural and psychological factors with three types of SRB in adolescents in Central Europe.

Methods

We obtained data on behavioural factors (having been drunk during previous month, smoking during previous week, early sexual initiation), psychological factors (self-esteem, well-being, extroversion, neuroticism, religiousness), and SRB (intercourse under risky conditions, multiple sexual partners, and inconsistent condom use) in 832 Slovak university students (response 94.3%).

Results

Among those with sexual experience (62%), inconsistent condom use was the most prevalent risk behaviour (81% in females, 72% in males). With the exception of having been drunk in males, no factor was associated with inconsistent condom use. Regarding the other types of SRB, early sexual initiation was most strongly associated. In addition, other, mostly behavioural, factors were associated, in particular having been drunk.

Conclusion

Results suggest that behavioural factors are more closely related to SRB than psychological factors. Associations differ by type of SRB and gender but offer few clues to target risk groups for inconsistent condom use. Results show a high need for health-promotion programmes in early adolescence that target SRB in conjunction with other health risk behaviours such as alcohol abuse.
Procedural confidence in hospital based practitioners: implications for the training and practice of doctors at all grades
Authors: Connick Rona M , Connick Peter , Klotsas Angelos E , Tsagkaraki Petroula A , Gkrania-Klotsas Effrossyni
Published: January 2009

Background

Medical doctors routinely undertake a number of practical procedures and these should be performed competently. The UK Postgraduate Medical Education and Training Board (PMETB) curriculum lists the procedures trainees should be competent in. We aimed to describe medical practitioner's confidence in their procedural skills, and to define which practical procedures are important in current medical practice.

Methods

A cross sectional observational study was performed measuring procedural confidence in 181 hospital practitioners at all grades from 2 centres in East Anglia, England.

Results

Both trainees and consultants provide significant service provision. SpR level doctors perform the widest range and the highest median number of procedures per year. Most consultants perform few if any procedures, however some perform a narrow range at high volume. Cumulative confidence for the procedures tested peaks in the SpR grade. Five key procedures (central line insertion, lumbar puncture, pleural aspiration, ascitic aspiration, and intercostal drain insertion) are the most commonly performed, are seen as important generic skills, and correspond to the total number of procedures for which confidence can be maintained. Key determinants of confidence are gender, number of procedures performed in the previous year and total number of procedures performed.

Conclusion

The highest volume of service requirement is for six procedures. The procedural confidence is dependent upon gender, number of procedures performed in the previous year and total number of procedures performed. This has implications for those designing the training curriculum and with regards the move to shorten the duration of training.
The first-year growth response to growth hormone treatment predicts the long-term prepubertal growth response in children
Authors: Kriström Berit , Dahlgren Jovanna , Niklasson Aimon , Nierop Andreas FM , Albertsson-Wikland Kerstin
Published: January 2009

Background

Pretreatment auxological variables, such as birth size and parental heights, are important predictors of the growth response to GH treatment. For children with missing pretreatment data, published prediction models cannot be used.

The objective was to construct and validate a prediction model for children with missing background data based on the observed first-year growth response to GH. The accuracy and reliability of the model should be comparable with our previously published prediction model relying on pretreatment data. The design used was mathematical curve fitting on observed growth response data from children treated with a GH dose of 33 μg/kg/d.

Methods

Growth response data from 162 prepubertal children born at term were used to construct the model; the group comprised of 19% girls, 80% GH-deficient and 23% born SGA. For validation, data from 205 other children fulfilling the same inclusion and treatment criteria as the model group were used. The model was also tested on data from children born prematurely, children from other continents and children receiving a GH dose of 67 μg/kg/d.

Results

The GH response curve was similar for all children, but with an individual amplitude. The curve SD score depends on an individual factor combining the effect of dose and growth, the 'Response Score', and time on treatment, making prediction possible when the first-year growth response is known. The prediction interval (± 2 SDres) was ± 0.34 SDS for the second treatment year growth response, corresponding to ± 1.2 cm for a 3-year-old child and ± 1.8 cm for a 7-year-old child. For the 1–4-year prediction, the SDres was 0.13 SDS/year and for the 1–7-year prediction it was 0.57 SDS (i.e. < 0.1 SDS/year).

Conclusion

The model based on the observed first-year growth response on GH is valid worldwide for the prediction of up to 7 years of prepubertal growth in children with GHD/ISS, born AGA/SGA and born preterm/term, and can be used as an aid in medical decision making.
Isolation and characterisation of polychlorinated biphenyl (PCB) degrading fungi from a historically contaminated soil
Authors: Tigini Valeria , Prigione Valeria , Di Toro Sara , Fava Fabio , Varese Giovanna C
Published: January 2009

Background

Polychlorinated biphenyls (PCBs) are widespread toxic pollutants. Bioremediation might be an effective, cost competitive and environment-friendly solution for remediating environmental matrices contaminated by PCBs but it is still unsatisfactory, mostly for the limited biodegradation potential of bacteria involved in the processes. Very little is known about mitosporic fungi potential in PCB bioremediation and their occurrence in actual site historically contaminated soils. In the present study, we characterised the native mycoflora of an aged dump site soil contaminated by about 0.9 g kg-1of Aroclor 1260 PCBs and its changing after aerobic biotreatment with a commercial complex source of bacteria and fungi. Fungi isolated from the soil resulting from 120 days of treatment were screened for their ability to adsorb or metabolise 3 target PCBs.

Results

The original contaminated soil contained low loads of few fungal species mostly belonging to the Scedosporium, Penicillium and Aspergillus genera. The fungal load and biodiversity generally decreased throughout the aerobic treatment. None of the 21 strains isolated from the treated soil were able to grow on biphenyl (200 mg L-1) or a mixture of 2-chlorobiphenyl, 4,4'-dichlorobiphenyl and 2,2',5,5'-tetrachlorobiphenyl (20 mg L-1each) as sole carbon sources. However, 16 of them grew in a mineral medium containing the same PCBs mixture and glucose (10 g L-1). Five of the 6 isolates, which displayed the faster and more extensive growth under the latter conditions, were found to degrade the 3 PCBs apparently without the involvement of ligninolytic enzymes; they were identified as Penicillium chrysogenum, Scedosporium apiospermum, Penicillium digitatum and Fusarium solani. They are the first PCB degrading strains of such species reported so far in the literature.

Conclusion

The native mycoflora of the actual site aged heavily contaminated soil was mainly constituted by genera often reported as able to biodegrade organopollutants. It was generally remarkably reduced after the biotreatment, which however resulted in the selection of few mitosporic fungal species able to biodegrade PCBs. This is the first study in which an extensive characterisation of the cultivable indigenous mycoflora of an actual site aged PCB contaminated soil, as well as its changes upon soil bioremediation treatment, was conducted. Moreover, this is the first paper in which 5 strains ascribable to 4 mitosporic species able to biodegrade PCB are reported in the literature.
Advantage of vacuum assisted closure on healing of wound associated with omentoplasty after abdominoperineal excision: a case report
Authors: Cresti Silvia , Ouaïssi Mehdi , Sielezneff Igor , Chaix Jean-Baptiste , Pirro Nicolas , Berthet Bruno , Consentino Bernard , Sastre Bernard
Published: January 2009

Background

Primary closure of the perineum with drainage after abdominoperineal excision of the rectum for carcinoma, is widely accepted. However hematoma, perineal abscess and re-operation are significantly more frequent after primary closure than after packing of the perineal cavity. Those complications are frequently related to the patients' clinical antecedent (i.e radiotherapy, diabetes, smoking).

Case presentation

In the present report, vacuum assisted drainage was used after abdominoperineal excision for carcinoma in the very first step due to intraoperative gross septic contamination during tumor resection. The first case: A 57-years old man with a 30-years history of peri-anal Crohn's disease, the adenocarcinoma of the lowest part of the rectum and Crohn colitis with multiple area of severe dysplasia required panproctocolectomy with a perineal resection. The VAC system was used during 12 days (changed every 3 days). We observed complete healing 18 days after surgery. The second case: A 51-year-old man, with AIDS. An abdominoperineal resection was performed for recurrence epidermoid anal cancer. The patient was discharged at day 25 and complete healing was achieved 30 days later after surgery.

Conclusion

The satisfactory results showed in the present report appear to be favored by association of omentoplasty and VAC system. Those findings led us to favor VAC system in the case of pelvic exenteration associated with high risk of infection.
Can urinary exosomes act as treatment response markers in prostate cancer?
Authors: Mitchell Paul J , Welton Joanne , Staffurth John , Court Jacquelyn , Mason Malcolm D , Tabi Zsuzsanna , Clayton Aled
Published: January 2009

Background

Recently, nanometer sized vesicles (termed exosomes) have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy.

Methods

Ten patients (with locally advanced PCa) provided spot urine specimens at three time points during standard therapy. Patients received 3–6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA) and tumour-associated marker 5T4 was examined.

Results

The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8) patient.

Conclusion

Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide clinically useful information.
Human cyclin T1 expression ameliorates a T-cell-specific transcriptional limitation for HIV in transgenic rats, but is not sufficient for a spreading infection of prototypic R5 HIV-1 strains ex vivo
Authors: Michel Nico , Goffinet Christine , Ganter Kerstin , Allespach Ina , KewalRamani Vineet N , Saifuddin Mohammed , Littman Dan R , Greene Warner C , Goldsmith Mark A , Keppler Oliver T
Published: January 2009

Background

Cells derived from native rodents have limits at distinct steps of HIV replication. Rat primary CD4 T-cells, but not macrophages, display a profound transcriptional deficit that is ameliorated by transient trans-complementation with the human Tat-interacting protein Cyclin T1 (hCycT1).

Results

Here, we generated transgenic rats that selectively express hCycT1 in CD4 T-cells and macrophages. hCycT1 expression in rat T-cells boosted early HIV gene expression to levels approaching those in infected primary human T-cells. hCycT1 expression was necessary, but not sufficient, to enhance HIV transcription in T-cells from individual transgenic animals, indicating that endogenous cellular factors are critical co-regulators of HIV gene expression in rats. T-cells from hCD4/hCCR5/hCycT1-transgenic rats did not support productive infection of prototypic wild-type R5 HIV-1 strains ex vivo, suggesting one or more significant limitation in the late phase of the replication cycle in this primary rodent cell type. Remarkably, we identify a replication-competent HIV-1 GFP reporter strain (R7/3 YU-2 Env) that displays characteristics of a spreading, primarily cell-to-cell-mediated infection in primary T-cells from hCD4/hCCR5-transgenic rats. Moreover, the replication of this recombinant HIV-1 strain was significantly enhanced by hCycT1 transgenesis. The viral determinants of this so far unique replicative ability are currently unknown.

Conclusion

Thus, hCycT1 expression is beneficial to de novo HIV infection in a transgenic rat model, but additional genetic manipulations of the host or virus are required to achieve full permissivity.
Glycine Receptor in Rat Hippocampal and Spinal Cord Neurons as a Molecular Target for Rapid Actions of 17-β-Estradiol
Authors: Jiang Peng , Kong Yan , Zhang Xiao-Bing , Wang Wei , Liu Chun-Feng , Xu Tian-Le
Published: January 2009

Glycine receptors (GlyRs) play important roles in regulating hippocampal neural network activity and spinal nociception. Here we show that, in cultured rat hippocampal (HIP) and spinal dorsal horn (SDH) neurons, 17-β-estradiol (E2) rapidly and reversibly reduced the peak amplitude of whole-cell glycine-activated currents ( IGly). In outside-out membrane patches from HIP neurons devoid of nuclei, E2 similarly inhibited IGly, suggesting a non-genomic characteristic. Moreover, the E2 effect on IGly persisted in the presence of the calcium chelator BAPTA, the protein kinase inhibitor staurosporine, the classical ER (i.e. ERα and ERβ) antagonist tamoxifen, or the G-protein modulators, favoring a direct action of E2 on GlyRs. In HEK293 cells expressing various combinations of GlyR subunits, E2 only affected the IGly in cells expressing α2, α2β or α3β subunits, suggesting that either α2-containing or α3β-GlyRs mediate the E2 effect observed in neurons. Furthermore, E2 inhibited the GlyR-mediated tonic current in pyramidal neurons of HIP CA1 region, where abundant GlyR α2 subunit is expressed. We suggest that the neuronal GlyR is a novel molecular target of E2 which directly inhibits the function of GlyRs in the HIP and SDH regions. This finding may shed new light on premenstrual dysphoric disorder and the gender differences in pain sensation at the CNS level.
Visual impairment from fibrous dysplasia in a middle-aged African man: a case report
Authors: Bekibele Charles O , Fasola Olubayo A , Okojie Vickie N , Komolafe Opeyemi O , Oluwasola Olayiwola A , Emejulu Jude K , Ajaiyeoba Ayotunde I , Baiyeroju Aderonke M
Published: January 2009

Introduction

Fibrous dysplasia is a benign tumour of the bones and is a disease of unknown aetiology. This report discusses a case of proptosis and visual deterioration with associated bony mass involving the right orbit.

Case presentation

A 32-year-old Nigerian man of Yoruba ethnic origin presented to the eye clinic of our hospital with right-eye proptosis and visual deterioration of 7-year duration. Presentation was preceded by a history of trauma. Proptosis was preceded by trauma but was non-pulsatile with no thrill or bruit but was associated with bony orbital mass. The patient reported no weight loss. Examination of his right eye showed visual acuity of 6/60 with relative afferent pupillary defect. Fundal examination revealed optic atrophy. Computed tomography showed an expansile bony mass involving all the walls of the orbit. The bony orbital mass was diagnosed histologically as fibrous dysplasia. Treatment included orbital exploration and orbital shaping to create room for the globe and relieve pressure on the optic nerve.

Conclusion

Fibrous dysplasia should be considered in the differential diagnosis of slowly developing proptosis with associated visual loss in young adults.
RPS2: a novel therapeutic target in prostate cancer
Authors: Wang Min , Hu Youji , Stearns Mark E
Published: January 2009

Background

A number of studies have previously shown that the over expression of different ribosomal proteins might play an important role in cancer (i.e. S3a, L10, L16). We have previously reported that RPS2, a 33 Kda ribosomal protein was over expressed in malignant prostate cancer cell lines and in archived tumor specimens. Thus, RPS2 or other aberrantly over-expressed ribosomal proteins might promote cancer and be excellent therapeutic targets for treatment of the disease.

Methods

Western blotting and RT-PCR have been used to measure and compare the levels of expression of RPS2 in a variety of malignant prostate cancer cell lines, plus normal and benign cells lines. We have developed a 'ribozyme-like' DNAZYM-1P '10–23' motif oligonucleotide and examined whether it targets RPS2 in different cell lines by RT-PCR and Western blots. Growth and apoptosis assays were carried out to measure whether DNAZYM-1P 'knock-down' of RPS2 influenced cell proliferation or survival. We have also developed a SCID mouse tumor model with PC-3ML cells to determine whether DNAZYM-1P targeting of RPS2 compromised tumor growth and mouse survival rates in vivo.

Results

Western blots showed that PC-3ML, LNCaP, CPTX-1532, and pBABE-cmyc stably transfected IBC-10a cells all over-expressed RPS2, whereas IBC-10a parent, NPTX-1532, and BPH-1 cells or mouse NIH-3T3 cells expressed barely detectable levels of RPS2. RT-PCR assays showed that DNAZYM-1P, which targeted RPS2, 'knocked-down' RPS2 expression in the malignant cells (i.e. PC-3ML cells) in vitro. The DNAZYM-1P also inhibited cell growth and induced apoptosis in the malignant prostate cells, but had little effect on the normal IBC-10a or NPTX-1532 cell lines. Finally, SCID mouse tumor modeling studies showed that DNAZYM-1P blocked tumor growth and metastasis by PC-3ML cells and eventually eradicated tumors following localized or systemic i.v. delivery. Mouse survival studies revealed that there was a dosage dependent increase in disease free survival rates in mice treated systemically with DNAZYM-1P (i.e. mouse survival increased from 0% to 100%).

Conclusion

In sum, we have shown for the first time that therapeutic targeting of RPS2 is an excellent approach for the eradication of prostate cancer in preclinical tumor modeling studies.
Semi-invasive pulmonary aspergillosis in an immunosuppressed patient: a case report
Authors: Cabral Fernanda C , Marchiori Edson , Zanetti Gláucia , Takayassu Tatiana C , Mano Claudia M
Published: January 2009

Background

The authors present the high-resolution computed tomography findings of an immunosuppressed patient with semi-invasive pulmonary aspergillosis.

Case presentation

The main finding consisted of irregular, thick-walled cavity in the right upper lobe and a mass with soft-tissue attenuation within it and thickening of adjacent pleura. Additional findings were bronchial wall thickening associated with a 'tree-in-bud' pattern. Following the clinical, laboratorial and imaging criteria, the diagnosis of semi-invasive pulmonary aspergillosis was defined and antifungical treatment was introduced.

Conclusion

The patient responded well to the treatment with improvement in his systemic symptoms and regression of the pulmonary lesions.
Solitary large hepatic metastasis in an elderly patient with anaplastic thyroid carcinoma: a case report
Authors: Adamidou Alexandra , Kotsaftis Panagiotis , Vlachou Maria , Haritanti Afroditi , Xanthakis Ioannis , Zantidis Anestis , Ntaios George
Published: January 2009

Background

We present the case of a patient who presented with anaplastic thyroid carcinoma with a solitary large liver metastasis. Hepatic metastases are extremely rare in anaplastic thyroid carcinoma.

Case presentation

We report the case of a 78-year old Greek man who presented with voice hoarseness, dyspnoea and a large mass on the anterior surface of the cervical region (neck), as well as constitutional symptoms such as anorexia, weight loss and malaise. On physical examination, the thyroid was hard and tender on palpation and a liver mass was palpable. Routine biochemistry yielded normal results except increased C-reactive protein, alkaline phosphatase and γ-glutaryl transferase. Other biochemical tests including tumor markers, thyroid hormones, antithyroid antibodies, hepatitis B and hepatitis C antibodies were negative. Imaging methods revealed enlargement of the left thyroid lobe extending to the anterior mediastinum and compressing the trachea, metastatic bilateral pulmonary lesions and a large, nodular, contrast-enhanced mass-occupying lesion in the right hepatic lobe. The findings of fine-needle aspiration biopsy of the thyroid were consistent with anaplastic carcinoma. Liver biopsy showed infiltrations by poorly differentiated anaplastic cells, few of which were slightly positive for thyroglobulin. These findings were suggestive of a hepatic metastasis originating from anaplastic thyroid carcinoma. During his hospitalization, the patient suffered progressive obstruction of the trachea due to rapid increase of the thyroid gland mass. The tumor was considered unresectable due to its advanced stage, as well as the presence of extrathyroid metastatic lesions. The patient was irradiated on cervical region (neck) and upper mediastinum with a daily dose of 300 cGy for 10 days which resulted in mild improvement of obstructive phenomena. However, his clinical condition deteriorated rapidly and he died within a few days.

Conclusion

Solitary, large hepatic metastasis may constitute a rare complication in anaplastic thyroid carcinoma.
Serum concentrations of cortisol, interleukin 6, leptin and adiponectin predict stress induced insulin resistance in acute inflammatory reactions
Authors: Lehrke Michael , Broedl Uli C , Biller-Friedmann Ingeborg M , Vogeser Michael , Henschel Volkmar , Nassau Kirsten , Göke Burkhard , Kilger Erich , Parhofer Klaus G
Published: January 2009

Introduction

Inflammatory stimuli are causative for insulin resistance in obesity as well as in acute inflammatory reactions. Ongoing research has identified a variety of secreted proteins that are released from immune cells and adipocytes as mediators of insulin resistance; however, knowledge about their relevance for acute inflammatory insulin resistance remains limited. In this study we aimed for a clarification of the relevance of different insulin resistance mediating factors in an acute inflammatory situation.

Methods

Insulin resistance was measured in a cohort of 37 non-diabetic patients undergoing cardiac surgery by assessment of insulin requirement to maintain euglycaemia and repeated measurements of an insulin glycaemic index. The kinetics of cortisol, interleukin 6 (IL6), tumour necrosis factor α (TNFα), resistin, leptin and adiponectin were assessed by repeated measurements in a period of 48 h.

Results

Insulin resistance increased during the observation period and peaked 22 h after the beginning of the operation. IL6 and TNFα displayed an early increase with peak concentrations at the 4-h time point. Serum levels of cortisol, resistin and leptin increased more slowly and peaked at the 22-h time point, while adiponectin declined, reaching a base at the 22-h time point. Model assessment identified cortisol as the best predictor of insulin resistance, followed by IL6, leptin and adiponectin. No additional information was gained by modelling for TNFα, resistin, catecholamine infusion rate, sex, age, body mass index (BMI), operation time or medication.

Conclusions

Serum cortisol levels are the best predictor for inflammatory insulin resistance followed by IL6, leptin and adiponectin. TNFα, and resistin have minor relevance as predictors of stress dependent insulin resistance.
Complex differentiation tools for geophysical inversion
Authors: Abokhodair Abdulwahab A.
Published: January 2009

I propose a method for derivative approximation, virtually unknown in the geophysical literature but is rapidly gaining recognition in other areas of computational science. The technique, called the complex-step derivative (CSD), is based on the theory of complex variables and approximates first-order derivatives of real-valued functions that are analytic in the complex plane. I extend the CSD technique to second-order derivatives, while preserving the robustness of the first-order formula. Thus the formulas together provide a complete differentiation system (referred to as semiautomatic differentiation, or SD) that allows efficient and accurate approximation of gradients, Jacobians and Hessians, as well as 2D and 3D partial and cross-partial spatial derivatives. Performance evaluation tests indicate that in comparison with ordinary finite-difference schemes (FD), the SD scheme is six to eight orders of magnitude more accurate, numerically highly stable, and step-size insensitive, which are major advantages over FD. The method shares with FD its attractive feature of ease of implementation. The SD scheme is implemented in a MATLAB toolkit. The validity of the CSD method depends critically on the requirement that the target function of differentiation be analytic in the complex plane. Therefore, prior to using the CSD method, one must ensure that all functions in the complex library are defined so that they satisfy this requirement. Specialized complex-function libraries that resolve this and other technical issues for CSD applications are available in the public domain.
Randomized Phase III Study of 1 Month Versus 1 Year of Adjuvant High-Dose Interferon Alfa-2b in Patients With Resected High-Risk Melanoma
Authors: Pectasides Dimitrios , Dafni Urania , Bafaloukos Dimitrios , Skarlos Dimosthenis , Polyzos Aristidis , Tsoutsos Dimosthenis , Kalofonos Haralambos , Fountzilas George , Panagiotou Petros , Kokkalis George , Papadopoulos Othon , Castana Ourania , Papadopoulos Stefanos , Stavrinidis Elias , Vourli Georgia , Ioannovich John , Gogas Helen
Published: January 2009

Purpose

A high-dose interferon alfa (IFN-α) regimen as reported in E1684 was unique for the incorporation of an induction phase of maximally tolerated dosages of intravenous (IV) therapy for the initial 4 weeks. This is the only trial that has shown prolongation of overall survival and relapse-free survival (RFS) in comparison with observation. Analysis of the hazard curves for RFS and overall survival (OS) in E1684 revealed separation of the high-dose and observation arms, suggesting that the induction phase may represent a critical component of this regimen, although this has not been tested prospectively.

Patients and Methods

We conducted a prospective randomized study of IV induction therapy versus a full year of high-dose IFN, with primary end points of RFS and OS for patients with stage IIB, IIC, and III melanoma, within 56 days of curative surgery. Patients were randomly assigned to receive IFN-α-2b 15 × 106 U/m2 IV × 5/7 days weekly × 4 weeks (arm A) versus the same regimen followed by IFN-α-2b 10 × 106 U (flat dose) administered subcutaneously three times a week for 48 weeks (arm B).

Results

Between 1998 and 2004, 364 patients were enrolled (353 eligible: arm A, n = 177; arm B, n = 176). At a median follow-up of 63 months (95% CI, 58.1 to 67.7), the median RFS was 24.1 months versus 27.9 months (P = .9) and the median OS was 64.4 months versus 65.3 months (P = .49). Patients in arm B had more grade 1 to 2 hepatotoxicity, nausea/vomiting, alopecia, and neurologic toxicity.

Conclusion

There were no significant differences in OS and RFS between the regimens of 1 month and 1 year of treatment.
Phase III Comparison of Preoperative Chemotherapy Compared With Chemoradiotherapy in Patients With Locally Advanced Adenocarcinoma of the Esophagogastric Junction
Authors: Stahl Michael , Walz Martin K. , Stuschke Martin , Lehmann Nils , Meyer Hans-Joachim , Riera-Knorrenschild Jorge , Langer Peter , Engenhart-Cabillic Rita , Bitzer Michael , Königsrainer Alfred , Budach Wilfried , Wilke Hansjochen
Published: January 2009

Purpose

Preoperative chemotherapy is an accepted standard in the treatment of localized esophagogastric adenocarcinoma. Adding radiation therapy to preoperative chemotherapy appears promising, but its definitive value remains unknown.

Patients and Methods

Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival time. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% to 35% by addition of radiation therapy. The study was prematurely closed due to low accrual.

Results

The median observation time was 46 months. A total of 126 patients were randomly assigned and 119 eligible patients were evaluated. The number of patients undergoing complete tumor resection was not different between treatment groups (69.5% v 71.5%). Patients in arm B had a significant higher probability of showing pathologic complete response (15.6% v 2.0%) or tumor-free lymph nodes (64.4% v 37.7%) at resection. Preoperative radiation therapy improved 3-year survival rate from 27.7% to 47.4% (log-rank P = .07, hazard ratio adjusted for randomization strata variables 0.67, 95% CI, 0.41 to 1.07). Postoperative mortality was nonsignificantly increased in the chemoradiotherapy group (10.2% v 3.8%; P = .26).

Conclusion

Although the study was closed early and statistical significance was not achieved, results point to a survival advantage for preoperative chemoradiotherapy compared with preoperative chemotherapy in adenocarcinomas of the esophagogastric junction.
Physical Activity and Quality of Life in Adult Survivors of Non-Hodgkin's Lymphoma
Authors: Bellizzi Keith M. , Rowland Julia H. , Arora Neeraj K. , Hamilton Ann S. , Miller Melissa Farmer , Aziz Noreen M.
Published: January 2009

Purpose

To examine the prevalence and correlates of physical activity in adult survivors of aggressive non-Hodgkin's Lymphoma (NHL) and to explore the association between physical activity level and health-related quality of life (HRQOL).

Patients and Methods

Physical activity and HRQOL data from 319 survivors of NHL (mean age, 59.8 years, standard deviation, ±14.8) who were diagnosed in Los Angeles County approximately 2 to 5 years before the study was analyzed.

Results

One quarter of survivors of NHL met public health guidelines of 150 minutes or more of moderate to vigorous exercise per week. More than half (53%) reported some activity but less than 150 minutes per week, whereas 20% reported no physical activity. Females, those with lower perceived health competence, and individuals with more comorbid limitations were at increased risk for inactivity. Individuals who met public health guidelines reported better HRQOL than those who were sedentary. Interestingly, our findings suggest a significant positive association between HRQOL and those who get at least some exercise.

Conclusion

The effort to promote physical activity among cancer survivors, who are at risk for poor quality of life as a result of treatment, is of great importance to the health of this growing population. As NHL, similar to other cancers, becomes a disease that people live with as opposed to one that people die as a result of, oncologists and primary care physicians will be increasingly challenged to provide evidence-based guidance for the long-term management of the patient's health. Consideration should be given to how clinicians frame exercise-promoting messages to cancer survivors, especially to those who are sedentary.
Delivery of Survivorship Care by Primary Care Physicians: The Perspective of Breast Cancer Patients
Authors: Mao Jun J. , Bowman Marjorie A. , Stricker Carrie T. , DeMichele Angela , Jacobs Linda , Chan Dingyun , Armstrong Katrina
Published: January 2009

Purpose

Most of the 182,460 women diagnosed with breast cancer in the United States this year will become long-term survivors. Helping these women transition from active treatment to survivorship is a challenge that involves both oncologists and primary care physicians (PCPs). This study aims to describe postmenopausal breast cancer survivors' (BCS) perceptions of PCP-related survivorship care.

Patients and Methods

We conducted a cross-sectional survey of 300 BCSs seen in an outpatient breast oncology clinic at a large university hospital. The primary outcome measure was a seven-item self-reported measure on perceived survivorship care (Cronbach's α = .89). Multivariate regression analyses were used to identify factors associated with perceived care delivery.

Results

Overall, BCSs rated PCP-related survivorship care as 65 out of 100 (standard deviation = 17). The areas of PCP-related care most strongly endorsed were general care (78%), psychosocial support (73%), and health promotion (73%). Fewer BCSs perceived their PCPs as knowledgeable about cancer follow-up (50%), late effects of cancer therapies (59%), or treating symptoms related to cancer or cancer therapies (41%). Only 28% felt that their PCPs and oncologists communicated well. In a multivariate regression analysis, nonwhite race and level of trust in the PCP were significantly associated with higher perceived level of PCP-related survivorship care (P = .001 for both).

Conclusion

Although BCSs perceived high quality of general care provided by their PCPs, they were not as confident with their PCPs' ability to deliver cancer-specific survivorship care. Interventions need to be tested to improve oncology-primary care communication and PCP knowledge of cancer-specific survivorship care.
Prolonged Survival of Dendritic Cell–Vaccinated Melanoma Patients Correlates With Tumor-Specific Delayed Type IV Hypersensitivity Response and Reduction of Tumor Growth Factor β-Expressing T Cells
Authors: López Mercedes N. , Pereda Cristian , Segal Gabriela , Muñoz Leonel , Aguilera Raquel , González Fermín E. , Escobar Alejandro , Ginesta Alexandra , Reyes Diego , González Rodrigo , Mendoza-Naranjo Ariadna , Larrondo Milton , Compán Alvaro , Ferrada Carlos , Salazar-Onfray Flavio
Published: January 2009

Purpose

The aim of this work was to assess immunologic response, disease progression, and post-treatment survival of melanoma patients vaccinated with autologous dendritic cells (DCs) pulsed with a novel allogeneic cell lysate (TRIMEL) derived from three melanoma cell lines.

Patients and Methods

Forty-three stage IV and seven stage III patients were vaccinated four times with TRIMEL/DC vaccine. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and regulatory T-cell populations were determined. Overall survival and disease progression rates were analyzed using Kaplan-Meier curves and compared with historical records.

Results

The overall survival for stage IV patients was 15 months. More than 60% of patients showed DTH-positive reaction against the TRIMEL. Stage IV/DTH-positive patients displayed a median survival of 33 months compared with 11 months observed for DTH-negative patients (P = .0014). All stage III treated patients were DTH positive and remained alive and tumor free for a median follow-up period of 48 months (range, 33 to 64 months). DTH-positive patients showed a marked reduction in the proportion of CD4+ transforming growth factor (TGF) β+ regulatory T cells compared to DTH-negative patients (1.54% v 5.78%; P < .0001).

Conclusion

Our findings strongly suggest that TRIMEL-pulsed DCs provide a standardized and widely applicable source of melanoma antigens, very effective in evoking antimelanoma immune response. To our knowledge, this is the first report describing a correlation between vaccine-induced reduction of CD4+TGFβ+ regulatory T cells and in vivo antimelanoma immune response associated to improved patient survival and disease stability.
Gene Expression Profiling Reveals a New Classification of Adrenocortical Tumors and Identifies Molecular Predictors of Malignancy and Survival
Authors: de Reyniès Aurélien , Assié Guillaume , Rickman David S. , Tissier Frédérique , Groussin Lionel , René-Corail Fernande , Dousset Bertrand , Bertagna Xavier , Clauser Eric , Bertherat Jérôme
Published: January 2009

Purpose

Adrenocortical tumors, especially cancers, remain challenging both for their diagnosis and prognosis assessment. The aim of this article is to identify molecular predictors of malignancy and of survival.

Patients and Methods

One hundred fifty-three unilateral adrenocortical tumors were studied by microarray (n = 92) or reverse transcription quantitative polymerase chain reaction (n = 148). A two-gene predictor of malignancy was built using the disease-free survival as the end point in a training cohort (n = 47), then validated in an independent validation cohort (n = 104). The best candidate genes were selected using Cox models, and the best gene combination was validated using the log-rank test. Similarly, for malignant tumors, a two-gene predictor of survival was built using the overall survival as the end point in a training cohort (n = 23), then tested in an independent validation cohort (n = 35).

Results

Unsupervised clustering analysis discriminated robustly the malignant and benign tumors, and identified two groups of malignant tumors with very different outcome. The combined expression of DLG7 and PINK1 was the best predictor of disease-free survival (log-rank P ≈ 10−12), could overcome the uncertainties of intermediate pathological Weiss scores, and remained significant after adjustment to the Weiss score (P < 1.3 × 10−2). Among the malignant tumors, the combined expression of BUB1B and PINK1 was the best predictor of overall survival (P < 2 × 10−6), and remained significant after adjusting for MacFarlane staging (P < .005).

Conclusion

Gene expression analysis unravels two distinct groups of adrenocortical carcinomas. The molecular predictors of malignancy and of survival are reliable and provide valuable independent information in addition to pathology and tumor staging. These original tools should provide important improvements for adrenal tumors management.
Early and Late Mortality After Diagnosis of Wilms Tumor
Authors: Cotton Cecilia A. , Peterson Susan , Norkool Patricia A. , Takashima Janice , Grigoriev Yevgeny , Green Daniel M. , Breslow Norman E.
Published: January 2009

Purpose

To assess rates and causes of mortality in patients with Wilms tumor (WT).

Methods

Through 2002, 6,185 patients enrolled onto the National Wilms Tumor Study between 1969 and 1995 were actively observed. Deaths were classified on the basis of medical records as the result of original disease, late effects (including second malignant neoplasms [SMNs], cardiac causes, pulmonary disease, and renal failure), or other causes. Standardized mortality ratios (SMRs) and Cox regression were used to assess the effects of sex, age, and calendar period of diagnosis on mortality.

Results

Within 5 years of WT diagnosis, 819 deaths occurred, and 159 deaths occurred among 4,972 known 5-year survivors. The SMR was 24.3 (95% CI, 22.6 to 26.0) for the first 5 years, was 12.6 (95% CI, 10.0 to 15.7) for the next 5 years, and remained greater than 3.0 thereafter. For deaths in the first 5 years, the mortality risk decreased by 5-year calendar period of diagnosis (rate ratio [RR] = 0.78 per period). No such trend occurred for later deaths. Among 5-year survivors, 62 deaths were attributed to late effects of treatment or disease, including 27 to SMNs. A trend of decreased risk with calendar period of diagnosis was observed for late-effects mortality (RR = 0.86; 95% CI, 0.67 to 1.10) and for SMN mortality (RR = 0.82; 95% CI, 0.55 to 1.21).

Conclusion

Although the survival outlook for WT patients has improved greatly over time, survivors remain at elevated risk for death many years after their original diagnosis.
Phase II Trial of Bevacizumab in the Treatment of Persistent or Recurrent Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study
Authors: Monk Bradley J. , Sill Michael W. , Burger Robert A. , Gray Heidi J. , Buekers Thomas E. , Roman Lynda D.
Published: January 2009

Purpose

Vascular endothelial growth factor is a key promoter of tumor progression in cervical carcinoma. The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of bevacizumab, a recombinant humanized anti–vascular endothelial growth factor monoclonal antibody.

Patients and Methods

Eligible patients had recurrent cervical cancer, measurable disease, and GOG performance status ≤ 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and toxicity.

Results

Forty-six patients were enrolled (median age, 46 years); 38 patients (82.6%) received prior radiation as well as either one (n = 34, 73.9%) or two (n = 12, 26.1%) prior cytotoxic regimens for recurrent disease. Grade 3 or 4 adverse events at least possibly related to bevacizumab included hypertension (n = 7), thrombo-embolism (n = 5), GI (n = 4), anemia (n = 2), other cardiovascular (n = 2), vaginal bleeding (n = 1), neutropenia (n = 1), and fistula (n = 1). One grade 5 infection was observed. Eleven patients (23.9%; two-sided 90% CI, 14% to 37%) survived progression free for at least 6 months, and five patients (10.9%; two-sided 90% CI, 4% to 22%) had partial responses. The median response duration was 6.21 months (range, 2.83 to 8.28 months). The median PFS and overall survival times were 3.40 months (95% CI, 2.53 to 4.53 months) and 7.29 months (95% CI, 6.11 to 10.41 months), respectively. This compared favorably with historical phase II GOG trials in this setting.

Conclusion

Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer and merits phase III investigation.
Association Between Hyperglycemia and Survival in Patients With Newly Diagnosed Glioblastoma
Authors: Derr Rachel L. , Ye Xiaobu , Islas Melissa U. , Desideri Serena , Saudek Christopher D. , Grossman Stuart A.
Published: January 2009

Purpose

Hyperglycemia has been associated with poor outcomes in many disease states. This retrospective study assessed the association between hyperglycemia and survival in patients with newly diagnosed glioblastoma multiforme (GBM).

Patients and Methods

Between 1999 and 2004, before the standard use of temozolomide, 191 patients were accrued onto New Approaches to Brain Tumor Therapy CNS Consortium trials with similar eligibility criteria. Time-weighted mean glucose and mean glucocorticoid dose were calculated for each patient using all values collected regularly in follow-up. The primary outcome was survival.

Results

Mean glucose levels ranged between 65 and 459 mg/dL. These were divided into quartiles: quartile one (< 94 mg/dL), quartile two (94 to 109 mg/dL), quartile three (110 to 137 mg/dL), and quartile four (> 137 mg/dL). Median survival times for patients in quartiles one, two, three, and four were 14.5, 11.6, 11.6, and 9.1 months, respectively. The association between higher mean glucose and shorter survival persisted after adjustment for mean daily glucocorticoid dose, age, and baseline Karnofsky performance score (KPS). Compared with patients in the lowest mean glucose quartile, those in quartile two (adjusted hazard ratio [HR], 1.29; 95% CI, 0.85 to 1.96), quartile three (adjusted HR, 1.35; 95% CI, 0.89 to 2.06), and quartile four (adjusted HR, 1.57; 95% CI, 1.02 to 2.40) were at progressively higher risk of dying (P = .041 for trend).

Conclusion

In these patients with newly diagnosed GBM and good baseline KPS, hyperglycemia was associated with shorter survival, after controlling for glucocorticoid dose and other confounders. The effect of intensive management of glucocorticoid-related hyperglycemia on survival deserves additional study in patients with GBM.
Phase I/II Trial of Tremelimumab in Patients With Metastatic Melanoma
Authors: Camacho Luis H. , Antonia Scott , Sosman Jeffrey , Kirkwood John M. , Gajewski Thomas F. , Redman Bruce , Pavlov Dmitri , Bulanhagui Cecile , Bozon Viviana A. , Gomez-Navarro Jesus , Ribas Antoni
Published: January 2009

Purpose

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with tremelimumab (CP-675,206), a fully human anti-CTLA4 monoclonal antibody, was tolerated and demonstrated antitumor activity in a single dose, dose-escalation phase I trial in patients with solid tumors. This phase I/II trial was conducted to examine safety of multiple doses of tremelimumab, to further assess efficacy, and to identify an appropriate dosing regimen for further development.

Patients and Methods

Twenty-eight patients with metastatic melanoma received monthly intravenous infusions of tremelimumab at 3, 6, or 10 mg/kg for up to 1 year to determine recommended monthly phase II dose. During phase II, 89 patients received tremelimumab 10 mg/kg once every month or 15 mg/kg every 3 months.

Results

No dose-limiting toxicity was observed in phase I once every month dosing. In phase II, 8 (10%) of 84 response-assessable patients attained objective antitumor responses; best overall objective response was one complete response and three partial responses in each dosing regimen. Most responses were durable (range, 3 to 30+ months). Most frequent treatment-related adverse events (AEs) were diarrhea, rash, and pruritus. Frequency of grade 3/4 AEs was 13% in the 15 mg/kg every 3 months arm and 27% in the 10 mg/kg once every month. Serious AEs were also less frequent in the 15 mg/kg once every 3 months cohort (9% v 23% in 10 mg/kg arm).

Conclusion

Multiple infusions of tremelimumab were generally tolerable and demonstrated single-agent antitumor activity. Both phase II regimens generated durable tumor responses. Based on its more favorable safety profile, 15 mg/kg every 3 months was selected for further clinical testing.