Newspaper framing of food and beverage corporations' sponsorship of sport: a content analysis.

BACKGROUND: Unhealthy diets are a leading contributor to obesity, disability and death worldwide. One factor cited as contributing to rises in obesity rates is the pervasive and ubiquitous marketing of unhealthy foods and beverages (F&Bs) across a variety of mediums, such as sport sponsorship at both professional and amateur levels. Despite increased academic attention on the detrimental impacts of sport sponsorship within the obesogenic environment, this has not been matched by legislative action. One explanation may be the way that F&B corporations' sport sponsorship is framed within policy debates. Framing is the deliberate ways in which (often contested) issues are presented in communication. This paper examines how sport sponsorship by F&B corporations is framed through media reports. METHODS: This study employed a mixed methods content and framing analysis. First, we conducted a quantitative newsprint content analysis (n = 234). This then informed and directed a thematic framing analysis of a sub-set of articles (n = 54) that specifically associated sport sponsorship by F&B corporations with obesity and childhood obesity. RESULTS: The findings suggest that two competing frames are evident within newspaper coverage: 1) public health and 2) industry. The public health frame rejects the sponsorship of sport by High in Fat Sugar and Salt (HFSS) product corporations in particular, calling for such sponsorship to be restricted or banned. The industry frame characterises sponsorship of sport as a form of corporate social responsibility, positioning industry as good moral actors and part of the solution to childhood and adult obesity. These frames are evident across other Unhealthy Commodity Industries (UCIs) policy debates. However, the prominence of industry actors within the sample is potentially indicative of their discursive power within this space, particularly with their emphasis on the financial maintenance of sport as well as encouraging physical activity, contributing to the lack of regulatory development of sport sponsorship by F&B corporations. CONCLUSIONS: The findings of this study are particularly useful for public health organisations who seek regulatory change, as it may provide further insight into countering industry framing practices, raising the salience of regulation of sport sponsorship and thus increasing the likelihood of regulatory development that seeks to improve population health.

3D-Printed Franz cells - update on optimization of manufacture and evaluation.

OBJECTIVES: Laboratory in vitro permeation processes require the use of modified Franz type diffusion cells which are conventionally fabricated from glass. Fragility and high cost are frequently associated with this type of laboratory apparatus. The purpose of our present research was to develop a simple, economical and versatile approach to manufacture Franz type cells using additive manufacturing (AM). METHODS: Graphical Franz diffusion cell designs were reproduced with a stereolithography (SLA) 3D printer and assessed over a minimum period of 24 h. The surface morphology of AM printouts was analysed before and after compatibility studies using scanning electron microscopy (SEM). Comparative permeation studies in both glass and AM Franz type diffusion cells were conducted using a caffeine solution (1.5 mg mL-1 ), applied to a model silicone membrane. RESULTS: Testing of the 3D printed scaffolds confirmed similar recovery of the permeant when compared to glass cells: 1.49 ± 0.01 and 1.50 ± 0.01 mg mL-1 , respectively, after 72 h. No significant differences were visible from the SEM micrographs demonstrating consistent, smooth and non-porous surfaces of the AM Franz cells' core structure. Permeation studies using transparent 3D printed constructs resulted in 12.85 ± 0.53 µg cm-2 caffeine recovery in the receptor solution after 180 min with comparable permeant recovery, 11.49 ± 1.04 µg cm-2 , for the glass homologues. CONCLUSION: AM constructs can be considered as viable alternatives to the use of conventional glass apparatus offering a simple, reproducible and cost-effective method of replicating specialised laboratory glassware. A wider range of permeants will be investigated in future studies with these novel 3D printed Franz diffusion cells.

OBJECTIF: les processus de perméation in vitro en laboratoire nécessitent l'utilisation de cellules de diffusion de type Franz modifiées, fabriquées traditionnellement en verre. La fragilité et un coût élevé sont fréquemment associés à ce type d'appareil de laboratoire. L'objectif de nos travaux de recherche actuels était de développer une approche simple, économique et polyvalente pour fabriquer des cellules de type Franz à l'aide de la fabrication additive (FA). MÉTHODES: les conceptions des cellules de diffusion Franz graphiques ont été reproduites avec une imprimante 3D stéréolithographie (SLA) et évaluées sur une période minimum de 24 h. La morphologie de surface des impressions FA a été analysée avant et après des études de compatibilité à l'aide de la microscopie électronique à balayage (MEB). Des études comparatives de perméation des cellules de diffusion de type Franz en verre et FA ont été réalisées à l'aide d'une solution de caféine (1,5 mg ml-1 ) appliquée à un modèle de membrane en silicone. RÉSULTATS: les tests des supports imprimés 3D ont confirmé une récupération similaire du perméant par rapport aux cellules de verre : 1,49 ± 0,01 et 1,50 ± 0,01 mg ml-1 , respectivement, après 72 h. Aucune différence significative n'a été observée sur les micrographiques MEB, montrant des surfaces cohérentes, lisses et non poreuses de la structure centrale des cellules Franz FA. Les études de perméation utilisant des constructions transparentes imprimées en 3D ont conduit à une récupération de la caféine de 12,85 ± 0,53 µg cm-2 dans la solution de récepteur après 180 min avec une récupération de perméant comparable, 11,49 ± 1,04 µg cm-2 , pour les homologues de verre. CONCLUSION: les constructions FA peuvent être considérées comme des alternatives viables à l'utilisation d'appareils de verre conventionnels offrant une méthode simple, reproductible et rentable de réplication de la verrerie de laboratoire spécialisée. Une gamme plus large de perméants sera étudiée dans de futures études avec ces nouvelles cellules de diffusion Franz imprimées en 3D.

Investigations into in situ Enterococcus faecalis biofilm removal by passive and active sodium hypochlorite irrigation delivered into the lateral canal of a simulated root canal model.

AIM: To investigate in situ Enterococcus faecalis biofilm removal from the lateral canal of a simulated root canal system using passive or active irrigation protocols. METHODOLOGY: Root canal models (n = 43) were manufactured from transparent resin materials using 3D printing. Each canal was created with an 18 mm length, apical size 30, a .06 taper and a lateral canal of 3 mm length, with 0.3 mm diameter. Biofilms were grown in the lateral canal and apical 3 mm of the main canal for 10 days. Three models from each group were examined for residual biofilm using SEM. The other forty models were divided into four groups (n = 10). The models were observed under a fluorescence microscope. Following 60 s of 9 mL of 2.5% NaOCl irrigation using syringe and needle, the irrigant was either left stagnant in the canal or activated using gutta-percha, sonic or ultrasonic methods for 30 s. Images were then captured every second using an external camera. The residual biofilm percentages were measured using image analysis software. The data were analysed using generalized linear mixed models. A significance level of 0.05 was used throughout. RESULTS: The greatest level of biofilm removal was obtained with ultrasonic agitation (66.76%) followed by sonic (45.49%), manual agitation (43.97%) and passive irrigation groups (38.67%), respectively. The differences were significant between the residual biofilm in the passive irrigation and both sonic and ultrasonic groups (P = 0.001). CONCLUSION: Agitation resulted in better penetration of 2.5% NaOCl into the lateral canal of an artificial root canal model. Ultrasonic agitation of NaOCl improved the removal of biofilm.

3D-printed Franz type diffusion cells.

OBJECTIVE: Franz cells are routinely used to measure in vitro skin permeation of actives and must be inert to the permeant under study. The aim of the present work was to develop and manufacture transparent Franz-type diffusion cells using 3D printing. Printouts were then tested using a range of model active compounds. The study also aims to identify the critical 3D-printing parameters necessary for the process, including object design, choice of printing resin, printout curing and post-curing settings and introduction of model coatings. METHODS: Transparent Franz cells were constructed using an online computer aided design program and reproduced with different stereolithography 3D printers. The two acrylate-based resins used for the fabrication process were a commercially available product and a polymer synthesised in-house. Comparative studies between glass and 3D-printed Franz cells were conducted with selected model actives: terbinafine hydrochloride (TBF), niacinamide (NIA), diclofenac free acid (DFA) and n-methyl paraben (MPB). In preliminary studies, MPB showed the lowest recovery when exposed to the receptor compartment of 3D printed cells. Consequently, in vitro permeation studies were carried out using only MPB with polydimethylsiloxane (PDMS) membrane. RESULTS: A decrease in the amounts of selected compounds was observed for transparent 3D-printed Franz cells compared to glass cells. MPB showed the lowest recovery (53.8 ± 13.1%) when compared with NIA (74.9 ± 4.0%), TBF (81.5 ± 12.0%) and DFA (90.2 ± 12.9%) after 72 h. Permeation studies conducted using 3D-printed transparent cells with PDMS membrane also showed a decrease in MPB recovery of 51.4 ± 3.7% for the commercial resin and 94.4 ± 3.5% for the polymer synthesised in-house, when compared to glass cells. Although hydrophobic coatings were subsequently applied to the 3D-printed cells, the same reduction in MPB concentration was observed in the receptor solution. CONCLUSION: Transparent Franz cells were successfully prepared using 3D printing and were observed to be robust and leak-proof. There are few resins currently available for preparation of transparent materials and incompatibilities between the actives investigated and the 3D-printed cells were evident. Hydrophobic coatings applied as barriers to the printed materials did not prevent these interactions.

Short communication: Influence of pulsed light treatment on the quality and sensory characteristics of Cheddar cheese.

The objective of this study was to examine the effect of pulsed light (PL) treatment on the color, oxidative stability, and onset of molding of Cheddar cheese. Slices of sharp white Cheddar cheese of 2.5 × 5 cm were treated on one side with PL doses from 1.02 to 12.29 J/cm2, sealed in polyethylene bags, and stored at 6°C for up to 1 mo. Peroxide value, color parameters, and the onset of molding were evaluated. No significant changes in color or peroxide value were observed for PL-treated samples compared with the untreated controls. Pulsed light was able to significantly delay surface molding during refrigerated storage, with a PL dose of 9.22 J/cm2 delaying the onset of molding by 7 d. The effect of PL on the taste, appearance, and acceptability of Cheddar cheese slices treated with a PL dose of 9.22 J/cm2 on each side was assessed. In triangle tests, 60 untrained panelists were unable to detect significant differences between the control and PL-treated samples, although PL had a significant effect on overall liking, flavor, and appearance. These findings suggest that although PL can be effective for surface decontamination of cheese, it may have some detrimental effects on sensory properties.

Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as a screening method for the prevention of colorectal cancer.

BACKGROUND: Colorectal cancer is a significant cause of death. Removal of precancerous adenomas, and early detection and treatment of cancer, has been shown to reduce the risk of death. The aim of this review and meta-analysis was to determine whether flexible sigmoidoscopy (FS) is an effective population screening method for reducing mortality from colorectal cancer. METHODS: MEDLINE (1946 to December 2012) and Embase (1980-2012, week 15) were searched for randomized clinical trials in which FS was used to screen non-symptomatic adults from a general population, and FS was compared with either no screening or any other alternative screening methods. Meta-analysis was carried out using a random-effects Mantel-Haenzsel model. RESULTS: Twenty-four papers met the inclusion criteria, reporting results from 14 trials. Uptake of FS was usually lower than that for stool-based tests, although FS was more effective at detecting advanced adenoma and carcinoma. FS reduced the incidence of colorectal cancer after screening, and long-term mortality from colorectal cancer, compared with no screening in a selected population. Compared with stool-based tests in a general population, FS was associated with fewer interval cancers. CONCLUSION: FS is efficacious at reducing colorectal cancer mortality compared with no screening. It is more effective at detecting advanced adenoma and carcinoma than stool-based tests. FS may be compromised by poorer uptake. Introduction of FS as a screening method should be done on a pilot basis in populations in which it is not currently used, and close attention should be paid to maximizing uptake. The relative risk of adverse events with FS compared with stool-based tests should be quantified, and its real-world effectiveness evaluated against the most effective stool-based tests.

Bar workers' health and environmental tobacco smoke exposure (BHETSE): symptomatic improvement in bar staff following smoke-free legislation in Scotland.

OBJECTIVE: To examine changes in the health of bar workers after smoke-free legislation was introduced. DESIGN: Longitudinal study following bar workers from before legislation introduction, at 2 months after introduction and at 1 year to control for seasonal differences. SETTING: Bars across a range of socio-economic settings in Scotland. PARTICIPANTS: 371 bar workers recruited from 72 bars. INTERVENTION: Introduction of smoke-free legislation prohibiting smoking in enclosed public places, including bars. MAIN OUTCOMES MEASURES: Change in prevalence of self-reported respiratory and sensory symptoms. RESULTS: Of the 191 (51%) workers seen at 1-year follow-up, the percentage reporting any respiratory symptom fell from 69% to 57% (p = 0.02) and for sensory symptoms from 75% to 64% (p = 0.02) following reductions in exposure, effects being greater at 2 months, probably partly due to seasonal effects. Excluding respondents who reported having a cold at either baseline or 1 year, the reduction in respiratory symptoms was similar although greater for "any" sensory symptom (69% falling to 54%, p = 0.011). For non-smokers (n = 57) the reductions in reported symptoms were significant for phlegm production (32% to 14%, p = 0.011) and red/irritated eyes (44% to 18%, p = 0.001). Wheeze (48% to 31%, p = 0.006) and breathlessness (42% to 29%, p = 0.038) improved significantly in smokers. There was no relationship between change in salivary cotinine levels and change in symptoms. CONCLUSIONS: Bar workers in Scotland reported significantly fewer respiratory and sensory symptoms 1 year after their working environment became smoke free. As these improvements, controlled for seasonal variations, were seen in both non-smokers and smokers, smoke-free working environments may have potentially important benefits even for smokers.

Infections presenting for clinical care in early life and later risk of hay fever in two UK birth cohorts.

BACKGROUND: The 'hygiene hypothesis' proposes that infections in infancy protect against hay fever (HF). We investigated infections during infancy in relation to HF, including rarer ones not previously researched in this context, while examining the role of potential confounding variables. METHODS: From birth cohorts derived within the General Practice Research Database (GPRD) and Doctors Independent Network (DIN) database of computerized patient records from UK general practice, we selected 3549 case-control pairs, matched for practice, age, sex and control follow-up to case diagnosis. Conditional logistic regressions were fitted for each of 30 infections; behavioural problems (BP) acted as a control condition unrelated to HF. Odds ratios (OR), adjusted for consultation frequency were pooled across the databases using fixed effect models. We also adjusted for sibship size in GPRD and a socioeconomic marker in DIN. RESULTS: Upper respiratory tract infections, diarrhoea and vomiting and acute otitis media in infancy were each related with a moderately increased risk of HF in both databases, as were BP. These associations were lost on adjustment for consultation frequency. Only bronchiolitis was significantly associated with a reduced pooled risk of HF after adjustment for consultations (OR = 0.8). Adjustment for sibship size in GPRD and a socioeconomic marker in DIN had little impact on the OR. CONCLUSIONS: Of 30 infectious illnesses investigated, none had strong or consistent associations with HF after adjustment for consultation frequency. Except for bronchiolitis, possibly a chance finding, none of the clinically apparent infections considered appear to have an important role in allergy prevention.

Media framing and construction of childhood obesity: a content analysis of Swedish newspapers.

Objective: Despite lower prevalence than most European countries, childhood obesity is a Swedish public health priority due to its lasting health impacts and socioeconomic patterning. Mass media content influences public and political perceptions of health issues, and media framing of childhood obesity may influence perceptions of its solutions. This study examines framing of childhood obesity in Swedish morning and evening newspapers from 1996 to 2014. Methods: Content analysis of 726 articles about childhood obesity published in the five most-circulated Swedish newspapers. Article content coded quantitatively and subjected to statistical analysis, describing relationships between themes and trends over time. Results: Childhood obesity was consistently problematised, primarily in health terms, and linked to socio-economic and geographical factors. The yearly frequency of articles peaked in 2004, followed by a decline, corresponding with evidence about prevalence. Childhood obesity was framed as being driven by individual behaviours more frequently than structural or environmental factors. Structural framings increased over time, but constructions of the problem as driven by individual behaviours, particularly parenting, remained prominent. Conclusions: A relative growth in structural framings of causes and solutions over time, combined with prominent coverage of socio-economic inequalities, might be indicative of public and political amenability towards societal-level solutions, but individual behaviours remain prominent in framing of the issue. Health advocates might incorporate these insights into media engagement.

Content analysis of UK newspaper and online news representations of women's and men's 'binge' drinking: a challenge for communicating evidence-based messages about single-episodic drinking?

OBJECTIVES: In the UK, men's alcohol-related morbidity and mortality still greatly exceeds women's, despite an increase in women's alcohol consumption in recent decades. New UK alcohol guidelines introduce gender-neutral low-risk alcohol consumption guidance. This study explores how UK newspaper and online news represent women's and men's 'binge' drinking to identify opportunities to better align reporting of harmful drinking with evidence. DESIGN: Quantitative and qualitative content analysis of 308 articles published in 7 UK national newspapers and the BBC News website between 1 January 2012 and 31 December 2013. RESULTS: Articles associated women with 'binge' drinking more frequently than men, and presented women's drinking as more problematic. Men were more frequently characterised as violent or disorderly, while women were characterised as out of control, putting themselves in danger, harming their physical appearance and burdening men. Descriptions of female 'binge' drinkers' clothing and appearance were typically moralistic. CONCLUSIONS: The UK news media's disproportionate focus on women's 'binge' drinking is at odds with epidemiological evidence, may reproduce harmful gender stereotypes and may obstruct public understandings of the gender-neutral weekly consumption limits in newly proposed alcohol guidelines. In order to better align reporting of harmful drinking with current evidence, public health advocates may engage with the media with a view to shifting media framing of 'binge' drinking away from specific groups (young people; women) and contexts (public drinking) and towards the health risks of specific drinking behaviours, which affect all groups regardless of context.

UV-curable gels as topical nail medicines:In vivo residence, anti-fungal efficacy and influence of gel components on their properties.

UV-curable gels, used as nail cosmetics for their in vivo durability, were reported to be promising as topical nail medicines. Our first aim was thus to investigate whether such durability applies to drug-loaded formulations. This was found to be true. However, ethanol inclusion in the pharmaceutical formulation (to enable drug loading) reduced the in vivo residence. The second aim was therefore to determine any other effects of ethanol, and if ethanol could be avoided by the choice of monomers. Thus, three methacrylate monomers, ethyl methacrylate, isobornyl methacrylate and 2-hydroxyethyl methacrylate (HEMA) were selected, and their influence on the formulation properties were determined. Ethanol and the methacrylate monomer influenced some (but not all) of the formulation properties. The most significant was that HEMA could dissolve drug and enable the preparation of ethanol-free, drug-loaded formulations, which would benefit in vivo residence. The absence of ethanol reduced drug loading, release and ungual flux, but had no negative impact on the in vitro anti-fungal efficacy. Thus, judicious selection of gel components enabled the exclusion of ethanol. The long in vivo residence, little residual monomers, sufficient ungual permeation and in vitro anti-fungal activity of the gels indicates their potential as anti-onychomycotic topical medicines.

Phase I evaluation of sequential doxorubicin gemcitabine then ifosfamide paclitaxel cisplatin for patients with unresectable or metastatic transitional-cell carcinoma of the urothelial tract.

PURPOSE: This phase I trial sought to evaluate the toxicity of and determine the maximum-tolerated dose (MTD) for the two-drug regimen doxorubicin and gemcitabine (AG) followed by the three-drug regimen of ifosfamide, paclitaxel, and cisplatin (ITP) in patients with unresectable or metastatic transitional-cell carcinoma. PATIENTS AND METHODS: Patients received AG every other week for six cycles followed by ITP every 3 weeks for four cycles. Five AG dose levels were investigated, up to doxorubicin 50 mg/m(2) and gemcitabine 2, 000 mg/m(2), to determine the MTD of the regimen. The dose and schedule of ITP were constant: ifosfamide 1,500 mg/m(2) (days 1 to 3); paclitaxel 200 mg/m(2) (day 1); and cisplatin 70 mg/m(2) (day 1). Granulocyte colony-stimulating factor was given between all cycles of therapy. RESULTS: Fifteen patients enrolled onto this phase I trial. AG was well tolerated at all dose levels, with no grade 3 or 4 myelosuppression. Toxicity experienced with ITP included grade 3 and 4 granulocytopenia in four patients and grade 3 nausea/vomiting in three patients. No grade 3 and 4 neurotoxicity was observed. Eight of 14 assessable patients experienced a major response to AG, including five of six patients treated at the two highest AG dose levels. After completion of AG-ITP, nine of 14 assessable patients had a major response (three complete responses and six partial responses). CONCLUSION: AG is a well-tolerated and active regimen. Sequential chemotherapy with AG-ITP is also well tolerated, and phase II investigation at the highest dose level is ongoing.

Phase II randomized trial of gallium nitrate plus fluorouracil versus methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced transitional-cell carcinoma.

PURPOSE: A phase II randomized trial of gallium nitrate/fluorouracil (5-FU) versus dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was performed in poor-risk patients with advanced urothelial tract tumors. The efficacy and toxicity of these regimens were compared. Assessment of dose-intense M-VAC as salvage treatment in patients who failed to respond to the gallium nitrate/5-FU regimen was also performed. PATIENTS AND METHODS: Thirty-four patients who had not received prior systemic chemotherapy were randomized to either arm of the study. All patients had one or more clinical features predicting a low likelihood of durable complete response to standard chemotherapy, ie, weight loss, visceral metastases, and low performance status. Gallium nitrate and 5-FU were each administered by continuous 5-day infusions every 28 days. M-VAC was recycled every 21 days, with prophylactic recombinant human granulocyte colony-stimulating factor (rh-G-CSF). RESULTS: Two of 17 patients (12%; 95% confidence interval [CI], 1.4% to 36.4%) had a major response to gallium nitrate/5-FU. Sixteen of 17 patients treated with M-VAC (94%; 95% CI, 71.3% to 99.8%) demonstrated a major response. Five of 12 patients who failed to respond to the gallium nitrate/5-FU combination responded to M-VAC as second-line therapy (42%; 95% CI, 15.2% to 72.3%). Median survival for the gallium nitrate and 5-FU arm was 19 versus 17 months for the M-VAC arm, with a median follow-up duration of 35 months (range, 2 to 51) for all patients. Dose-intense M-VAC was associated with a greater incidence of neutropenia and thrombocytopenia. CONCLUSION: Dose-intense M-VAC is superior to gallium nitrate/5-FU in poor-risk patients (P < .0001). Despite the overall high response rate, the median survival for patients with M-VAC remained unsatisfactory. Similar survival distributions were observed for patients who received investigational therapy followed by cisplatin-based therapy and patients treated with initial cisplatin-based therapy.

Phase II trial of docetaxel in patients with advanced or metastatic transitional-cell carcinoma.

PURPOSE: A phase II trial of docetaxel was conducted to assess its efficacy and toxicity in patients with advanced transitional-cell carcinoma (TCC) who had failed to respond to prior cisplatin-based therapy. PATIENTS AND METHODS: Thirty assessable patients who had failed to respond to or relapsed after one prior cisplatin-containing regimen were treated with docetaxel 100 mg/m2 over 1 hour, every 21 days. All patients were premedicated with dexamethasone and diphenhydramine to reduce allergic reactions. Reductions of subsequent doses were made for severe hematologic toxicity. Prophylactic hematopoietic growth factors were not used. RESULTS: Four of 30 patients (13.3%; 95% confidence interval [CI], 3.8% to 30.7%) demonstrated a partial response (PR), with durations of response ranging from 3 to 8 months. The estimated median survival duration for all patients is 9 months (95% CI, 6 to 12 months) with a median follow-up time of 14 months (range, 1 to 27). Hematologic toxicity included anemia, thrombocytopenia, neutropenia, and febrile neutropenia. Nonhematologic toxicity included alopecia and mucositis. Fluid retention was not observed and cutaneous toxicity was mild and infrequent. Dose reductions were necessary for adverse events in 18 patients (60%). CONCLUSION: Docetaxel is an active single agent in previously treated patients with TCC of the urothelial tract. Therapy was well tolerated in this patient population but myelosuppression was frequent. Further study in previously untreated patients, both alone and in combination, is warranted.

Treatment of patients with transitional-cell carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial.

PURPOSE: A phase II trial of ifosfamide, paclitaxel, and cisplatin (ITP) was conducted in previously untreated patients with advanced transitional-cell carcinoma (TCC) to assess its efficacy and toxicity. PATIENTS AND METHODS: Thirty patients with metastatic or unresectable TCC were treated with ifosfamide 1.5 g/m2/d for 3 days with paclitaxel 200 mg/m2 over 3 hours and cisplatin 70 mg/m2 on day 1 of each 28-day treatment cycle. Therapy was continued for a maximum of six cycles. Prophylactic hematopoietic growth factor (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) was given on days 6 to 17 of each cycle. RESULTS: Twenty-three of 29 assessable patients (79%; 95% confidence interval [CI], 60% to 92%) demonstrated a major response (six complete [CR] and 17 partial [PR]) with response durations that ranged from 5 to 24+ months. Five patients with T4 bladder primary tumors had a major response, two with pathologic CR. At a median follow-up duration of 17.9 months, nine (31%) patients remain disease-free (range, 10+ to 24+). Hematologic toxicity included anemia, thrombocytopenia, and neutropenia; febrile neutropenia was observed in 17% of patients and 4% of cycles. No grade 4 nonhematologic toxicity was observed. Grade 3 nonhematologic toxicity included alopecia, allergy (3%), renal insufficiency (13%), and neuropathy (10%). Dose reductions or drug omissions were necessary for adverse events in seven (23%) patients. CONCLUSION: ITP is an active, well-tolerated regimen in previously untreated patients with TCC of the urothelial tract. Further study of this regimen in patients with both TCC and non-transitional-cell urothelial tumors is ongoing.

Preferential depletion of host over donor T cells through in vivo decay of active rabbit-anti-thymocyte globulin levels during reduced intensity conditioning.

Inadequate T-cell chimerism following reduced-intensity conditioning transplantation may contribute to graft rejection and disease relapse. Anti-thymocyte globulin (ATG) enhances early donor T-cell chimerism, but may also deplete donor T cells, increasing risks of infection and relapse. We prospectively tested administration of rabbit ATG (rATG) ⩾14 days before the infusion of the graft, followed by in vivo decay of active rATG levels, to selectively deplete host T cells. Twenty-three patients received rATG total dose 4.5 mg/kg on days -16 and -15, fludarabine 30 mg/m(2) per day on day -7 through -3, IV busulfan 130 mg/m(2) per day on days -4 and -3 and cyclophosphamide 1500 mg/m(2) on day -2. rATG levels were therapeutic in all patients on day -14, but were sub-therapeutic (<1 µg/mL) by day 0 in 82% of patients. Median donor T-cell chimerisms on days 30 and 180 were 100% (75-100%) and 100% (90-100%), respectively. Non-relapse mortality and relapse/progression at 48 months were 17 and 30%. Cumulative incidences of acute GvHD grades II-IV and III-IV were 39 and 9%. Median follow-up is 64 months (46-79 months). Survival and disease-free survival at 48 months were 70 and 52%. These data suggest that selective depletion of host T cells using this regimen is a feasible and effective strategy.

Imaging of renal cell carcinoma.

Today, a large proportion of patients diagnosed with renal cancer are those with small tumors discovered incidentally on imaging studies. Radiologic studies should be tailored to enable further characterization of renal masses, so that nonmalignant lesions can be differentiated from malignant ones. Intravenous urography (IVU) is often obtained as the first imaging study to evaluate the urinary tract in patients with symptoms that may indicate the presence of renal cell carcinoma Ultrasound scanning, computed tomography (CT), magnetic resonance imaging (MRI), and imaging-guided percutaneous biopsy techniques should be used appropriately to achieve maximum accuracy in the detection and staging of renal carcinoma. Diagnostic angiography, largely supplanted by less invasive radiologic techniques, may be useful in selected situations. After surgical removal of renal cell carcinoma, follow-up imaging is especially important in the first 2 years, when recurrence is most likely, especially in patients with stage III or IV tumors. The clinical presentation will determine choices of specific imaging "algorithms" for detection and staging of renal cell cancer.

Percutaneous transluminal dilation in renal transplant arterial stenosis.

Twelve hypertensive patients underwent percutaneous transluminal dilation (PTD) for relief of arterial stenosis complicating renal allotransplantation. Two patients underwent repeat PTD for recurrent stenosis and hypertension. Six patients had end to end anastomosis of the donor renal artery to the recipient hypogastric artery; four of six PTDs were successful. Six patients had end to side anastomosis of the donor renal artery to the recipient external iliac artery; seven of eight PTDs, including one of two repeat PTDs, were successful. Prior to PTD, all patients were using several antihypertensive medications. Following successful PTD, the mean blood pressure dropped from 184 +/- 15/118 +/- 9 to 133 +/- 13/89 +/- 11 mm Hg (P < 0.001) and remained at that level for up to 15 months (average followup 9 months) with decreased or no antihypertensive medications. Since surgical correction of arterial stenosis occurring after renal transplantation is difficult and may endanger the graft, PTD should be the first interventional therapy.

Clinical validation of SPECT and CT/MRI image registration in radiolabeled monoclonal antibody studies of colorectal carcinoma.

UNLABELLED: Registration methods combine the anatomic localizing ability of CT or MRI with SPECT images of radiolabeled monoclonal antibodies (Mabs), allowing the accurate staging of patients prior to surgery or following treatment. METHODS: Twenty-four patients (15 males and 9 females, mean age 55 yr, range 29-70 yr) were studied with this technique. Ten patients had suspected colorectal cancer recurrence and were infused with 10 mCi of 131I-CC49 prior to staging laparotomy. Fourteen patients treated in a Phase I radioimmunotherapy study with 131I-CC49 were also studied. All patients underwent SPECT imaging of the abdomen and pelvis 5-7 days following infusion of Mab. RESULTS: Phantom studies demonstrated a 3.6-mm surface fitting mean accuracy of datasets for the liver and 1.8 mm for an intrahepatic tumor. In the presurgical group, SPECT and CT/MRI registration allowed more accurate identification of uptake abnormal sites. Areas of metastatic disease > 1 cm confirmed at surgery were found in six of nine patients with liver lesions and in two patients with extrahepatic (including one patient with pelvic) disease. In patients imaged following radioimmunotherapy, all lesions > 1.5 cm seen on CT/MRI were identified, and activity distribution in tumor and normal tissue could be more accurately assessed. CONCLUSIONS: Routine registration of SPECT and CT/MRI images is feasible and allows more accurate anatomic assessment of sites of abnormal uptake in radiolabeled Mab studies.

Phase I radioimmunotherapy trial with iodine-131-CC49 in metastatic colon carcinoma.

UNLABELLED: CC49 is a murine monoclonal antibody (MAb) that reacts against the TAG-72 antigen. We carried out a Phase I study with escalating doses of 131I-CC49 in patients with advanced colorectal cancer expressing the TAG-72 antigen to determine the dose-limiting toxicity and therapeutic efficacy, if any, of the radioimmunoconjugate. METHODS: Twenty-four patients with TAG-72- expressing colorectal cancer were treated with escalating doses of 131I-CC49 starting at 15 mCi/m2 and going up to 90 mCi/m2 of 131I labeled to 20 mg MAb CC49. Patients were selected if TAG-72 was expressed in > or = 50% of cells in previously resected tumor and at least one metastasis was demonstratable on standard imaging such as CT. All patients had failed conventional chemotherapy and had not received prior radiotherapy or murine MAb. Patients were under radiation isolation precautions until whole-body radioactivity decreased to < or = 5 mR/hr at 1 m. Whole-body scintigrams were obtained prior to discharge and 1 and 2 wk after infusion in all patients. SPECT imaging was carried out at least once in all patients. RESULTS: All patients had excellent targeting of radioactivity to known tumor sites. There was no nonhematologic toxicity. Hematologic toxicity was more pronounced in those patients who had received extensive prior chemotherapy. There were no major responses. All patients developed an immune response (HAMA) within 4 wk of therapy. CONCLUSION: Radioimmunotherapy with 131I-CC49 is safe and there is significant therapeutic efficacy in this Phase I trial at the doses studied. There is excellent targeting of radioactivity to antigen-positive tumors. Dose-limiting toxicity is hematopoietic, with the maximum tolerated dose in this group of heavily pretreated patients being 75 mCi/m2.