Enhanced selectivity for the hydrolysis of block copoly(2-oxazoline)s in ethanol-water resulting in linear poly(ethylene imine) copolymers.

The ability of merging the properties of poly(2-oxazoline)s and poly(ethylene imine) is of high interest for various biomedical applications, including gene delivery, biosensors, and switchable surfaces and nanoparticles. In the present research, a methodology for the controlled and selective hydrolysis of (co)poly(2-oxazoline)s is developed in an ethanol-water solvent mixture, opening the path toward a wide range of block poly(2-oxazoline-co-ethylene imine) (POx-PEI) copolymers with tunable properties. The unexpected influence of the selected ethanol-water binary solvent mixture on the hydrolysis kinetics and selectivity is highlighted in the pursue of well-defined POx-PEI block copolymers.

Thrombotic thrombocytopenic purpura precipitated by acute pancreatitis.

A 20 year old woman, admitted with acute pancreatitis, subsequently developed microangiopathic haemolytic anaemia, thrombocytopenia and mild neurological compromise. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made, and she was treated with plasma exchange leading to complete resolution of this condition. TTP is a rare multisystem disorder which may be life threatening if not treated promptly. The increasing recognition of acute pancreatitis as a potential aetiological factor offers new insights into the pathogenesis, diagnosis and treatment of TTP.

Synthesis and crystal structures of multifunctional tosylates as basis for star-shaped poly(2-ethyl-2-oxazoline)s.

The synthesis of well-defined polymer architectures is of major importance for the development of complex functional materials. In this contribution, we discuss the synthesis of a range of multifunctional star-shaped tosylates as potential initiators for the living cationic ring-opening polymerization (CROP) of 2-oxazolines resulting in star-shaped polymers. The synthesis of the tosylates was performed by esterification of the corresponding alcohols with tosyl chloride. Recrystallization of these tosylate compounds afforded single crystals, and the X-ray crystal structures of di-, tetra- and hexa-tosylates are reported. The use of tetra- and hexa-tosylates, based on (di)pentaerythritol as initiators for the CROP of 2-ethyl-2-oxazoline, resulted in very slow initiation and ill-defined polymers, which is most likely caused by steric hindrance in these initiators. As a consequence, a porphyrin-cored tetra-tosylate initiator was prepared, which yielded a well-defined star-shaped poly(2-ethyl-2-oxazoline) by CROP as demonstrated by SEC with RI, UV and diode-array detectors, as well as by ¹H NMR spectroscopy.

Head-to-head comparison of the hybrid tracer indocyanine green-99mTc-nanocolloid with 99mTc-Senti-Scint using sentinel node lymphoscintigraphy and single-photon emission computed tomography combined with computer tomography in melanoma.

OBJECTIVE: The hybrid tracer indocyanine green (ICG)-Tc-nanocolloid has been introduced for sentinel node imaging. However, until now, a comparison of this tracer with other radiocolloids with a larger particle size has not been effectuated. Based on a head-to-head evaluation in patients with melanoma, we have compared ICG-Tc-nanocolloid (particle size 5-80 nm) with Tc-Senti-Scint (particle size 100-600 nm) to establish differences in drainage pattern and sentinel node localization using lymphoscintigraphy and single-photon emission computed tomography combined with computer tomography (SPECT-CT) in melanoma patients scheduled for sentinel node biopsy. METHODS: Twenty-five patients (mean age: 56.9 years, range: 25-79 years) with a melanoma scheduled for SLN biopsy prior to (re)excision of the primary lesion (scar) were prospectively included following a two-day procedure. The first day, after Tc-Senti-Scint injection in four intradermal depots around the primary lesion or scar, early/delayed lymphoscintigraphy and SPECT-CT images were acquired. The injection sites were marked. The second day, after assessing lymph node radioactivity using planar scintigraphy, ICG-Tc-nanocolloid was injected at the previously marked skin points and imaging was performed. The paired planar and SPECT-CT images of both tracers were evaluated with respect to drainage patterns, SLN visualization and non-SLN appearing. RESULTS: Twenty-four out of 25 patients were evaluable. SLN visualization on a patient basis was 100% for ICG-Tc-nanocolloid and 96% for Tc-Senti-Scint, whereas uptake in non-SLNs was found in, respectively, 71% (17/24) and 61% (14/23). Concordance in drainage to 45 lymph node basins was 91%. Discordant drainage was found for two melanomas in the head-and-neck and one in the clavicular area. Unique lymph node basins were seen in 44/45 (98%) for ICG-Tc-nanocolloid and 42/45 (93%) for Tc-Senti-Scint. Concerning identified SLNs, the number was similar for both tracers (n = 58); however, more non-SLNs (65 vs 50) were visualized with ICG-Tc-nanocolloid than with Tc-Senti-Scint. CONCLUSION: A slightly higher SLN visualization accompanied by a tendency to depict more non-SLNs was found for ICG-Tc-nanocolloid. Excepting the head and neck area, an overall high concordance in drainage was found for both radiotracers. With an additional value for the hybrid tracer due to the combination of preoperative imaging and the additional visual signal in the operation room, added by the fluorescent component of the hybrid tracer, there was a preference for ICG-Tc-nanocolloid.

Star-Shaped Polyacrylates: Highly Functionalized Architectures via CuAAC Click Conjugation.

Well-defined functional star-shaped polymer structures with up to 29 arms have been successfully synthesized by the combination of atom transfer radical polymerization (ATRP) and click chemistry. First, azide end-functionalized poly(isobornyl acrylate) (PiBA) star-shaped polymers were prepared by successive ATRP and bromine substitution. Subsequently, alkyne end-functionalized molecules and polymers were introduced onto the star-shaped PiBA bearing pendant azide moieties by copper-catalyzed azide-alkyne cycloaddition (CuAAC). The possibilities and limits for the CuAAC on such highly branched polyacrylates are described.

Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group.

PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.

Concurrent and adjuvant chemotherapy for nasopharyngeal carcinoma: a factorial study.

PURPOSE: To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B. RESULTS: Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009). CONCLUSION: An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.

Total body potassium in aging humans: a longitudinal study.

Total body potassium (TBK) data calculated from longitudinal measurements over 18 y of 40K by whole-body counting of 564 male and 61 female healthy humans in a 2-pi liquid scintillation counter show little change in females younger than 50 y compared with males of those ages. Males show less TBK from 41 y onward as they age, with most rapid rate of loss between 41 and 60 y. Females have a rapid loss of TBK when they are older than 60 y; the loss is at a greater rate than that of males. Percent total body fat calculated from total body weight and lean body mass (LBM) derived from TBK document greater adiposity in females at all ages except ages 51-60 y when females are similar to males in change in percent fat per year per centimeter.

A randomized trial of intracavitary bleomycin and Corynebacterium parvum in the control of malignant pleural effusions.

Fifty-eight patients with malignant pleural effusions were entered into a prospectively randomized clinical trial comparing the efficacy of a local instillation of bleomycin or corynebacterium parvum (C. parvum) in controlling fluid reaccumulation after simple needle aspiration (thoracentesis). The response was assessed at 30 days by chest X-ray and clinical examination. There were 44 evaluable patients; 18 of 25 (72%) of those receiving bleomycin and 9/19 (47%) of those who had C. parvum gained a complete or partial response. This difference in response rate was not statistically significant (p = 0.13). The majority of patients had an effusion from a primary breast carcinoma and the response in this group was almost statistically significant (p = 0.06) with 74% of bleomycin patients and 43% of C. parvum patients responding. Fever following instillation was more common with C. parvum (53% of patients compared with 24% after bleomycin, p = 0.02), whereas nausea was more common after bleomycin (28% vs. 10.5%, p = 0.16). Local chest pain after aspiration occurred in 52% of the bleomycin group and 47% of the C. parvum subjects. There was no significant difference between the groups in age, sex, tumour type, presenting symptoms, volume of aspirate, systemic therapy or number of previous aspirations. Both of these agents appeared to be active in the control of malignant pleural effusions although the response rate was higher with bleomycin and overall, both have acceptable levels of toxicity.

A randomised cross-over trial comparing low-dose metoclopramide and chlorpromazine with high-dose metoclopramide in Chinese patients with advanced cancer receiving cisplatinum and 5-fluorouracil.

Nineteen Chinese patients receiving chemotherapy for advanced cancer were studied for chemotherapy-induced acute nausea and vomiting. The chemotherapy consisted of cisplatinum 100 mg/m2 i.v. infusion over 4 h on day 1 and 5-fluorouracil (5-FU) 1000 mg/m2 120-h continuous infusion from day 2 to day 6, repeated every 3 weeks. At the first course of chemotherapy the patients were randomized to receive either low-dose metoclopramide and chlorpromazine or high-dose metoclopramide, and then crossed over for the second course. In the high-dose metoclopramide group there was a suggestion of an earlier onset of emesis, with slightly more frequent retching and vomiting and less food consumed. However, the duration of emesis was shorter in the high-dose group. These differences were not statistically significant. There were no major side effects. Mild salutary drowsiness was noticed in patients receiving low-dose metoclopramide and chlorpromazine. This trial suggests that, in the dosage, route and schedule described, high-dose metoclopramide is no more effective than low-dose metoclopramide together with chlorpromazine in preventing cisplatinum-induced nausea and vomiting. The low-dose scheme is more economic and suitable for patients with advanced cancer.

Adjuvant chemotherapy in the treatment of breast cancer: results of a multicentre study.

248 patients with locally radically treated early breast cancer (196 node-positive) were randomized post-operatively between 6 courses of a 'CMF like' chemotherapy and no further treatment. Results (with a minimum of 5 years follow-up on every patient) favour chemotherapy with a significant increase in the median time to recurrence from 31 to 50 months for all patients (P = 0.04) and from 26 to 49 months for node-positive patients (P = 0.023). No significant effect on survival is seen although there is a trend towards longer survival in the treated group. The regimen used was relatively non-toxic when compared to the traditional CMF with 34% of patients experiencing mild nausea and vomiting immediately post-injection and only 11% complaining of more severe nausea and vomiting. Because of this lower toxicity the treatment was found to be amenable to administration in both regional hospitals and specialized centres.

Long custom-made plastic tracheostomy tube in severe tracheomalacia.

Tracheomalacia occasionally occurs after repair of esophageal atresia and distal tracheoesophageal fistula. It is usually mild, and tracheostomy is rarely necessary. In severe cases of tracheomalacia after repair of esophageal atresia and distal tracheoesophageal fistula, the tracheomalacia may extend below the tip of a regular plastic tracheostomy tube. A patient with just such a problem is presented. A custom-made long plastic tracheostomy tube was designed. A method of gluing the upper portion of a standard plastic tracheostomy tube to an uncuffed thin-walled polyvinyl chloride endotracheal tube was discovered and the technique is described in detail. The literature is reviewed concerning custom-made long plastic tracheostomy tubes and tracheomalacia in relation to esophageal atresia and distal tracheoesophageal fistula.

Radiation myelopathy in patients treated for carcinoma of bronchus using a six fraction regime of radiotherapy.

The adoption of a six-fraction regime of radiotherapy for patients with locally advanced carcinoma of the bronchus was followed by the appearance of radiation myelitis in eight cases. These were among a group of 130 patients given radiotherapy with anterior and posterior treatment fields, without shielding of the spinal cord. Radiation myelitis was found only in those where the calculated spinal-cord dose exceeded 3350 cGy (rad). The possible precipitating factors in the eight patients who suffered myelopathy were compared with those in the remaining 62 patients who also received spinal-cord doses calculated to be greater than 3350 cGy (rad). Only one difference was found--the haemoglobin concentration was significantly higher in those who suffered neuropathy compared with those who did not (P = 0.05).

The comedo skin reaction to radiotherapy.

A 50-year-old man had a maxillectomy and post-operative radiotherapy for squamous carcinoma of the maxilla. The acute skin reaction merged at 2 months into a chronic comedo-type acneiform skin reaction in the irradiated area. Previous literature on this reaction to radiation is reviewed. The reaction is rare and occurs mostly in the head and neck area, more commonly in patients who have received acneigenic drugs, and with a latent period of between 2 weeks and 6 months from completion of radiotherapy. The pathogenesis of acne is discussed and a mechanism of post-irradiation acne is suggested.

Composition of pork carcasses by potassium-40 liquid scintillation detection: estimation and validation.

Liquid scintillation detection of potassium-40 was used to estimate pork carcass composition of 124 boars, barrows and gilts. Pigs were fed to five live weights (23, 45, 68, 91 and 114 kg) and 40K emissions were determined on live pigs in a whole body counter (WBC) equipped with a two-pi liquid scintillation detector. Then, pigs were slaughtered conventionally and the right side of each carcass was weighed, 40K emissions of this carcass side was determined in the WBC and total grams of potassium were calculated. The right side of each carcass was ground, sampled and analyzed for fat, protein, moisture and potassium. Fat, protein, moisture and overall potassium percentage means were 23.9 +/- 7.2, 16.5 +/- .94, 57.0 +/- 6.5 and .25 +/- .02, respectively. Whole body counter carcass potassium was highly correlated (P less than .01) to chemically determined carcass potassium (r = .70). Percentage of fat, protein and moisture prediction equations were formed by stepwise regression using the linear, quadratic and interactive effects of live animal and carcass side weight. Whole body counter live animal and carcass potassium and sex were utilized as independent variables. Carcass weight and 40K determined potassium of the carcass explained more of the variation in carcass composition than did live animal weight and 40K determined potassium of the live animal.

Ewing's sarcoma: fifteen years' experience at Angau Memorial Hospital.

A retrospective study was carried out on Ewing's sarcoma as seen between 1973 and 1987 at the Cancer Treatment Centre, Angau Memorial Hospital, Lae, Papua New Guinea. Some striking differences were observed in the epidemiological indices and the clinical picture of this disease here, when compared with other centres in the world. Most notably, Ewing's sarcoma, hitherto a rare tumour in this country, seems to be on the increase. In addition, among the flat bones, involvement of the scapula was disproportionately high. The early response to treatment was similar to findings elsewhere, although the long-term patient follow-up in this series was not satisfactory enough to allow proper estimates of long-term survival rates. The most recently advocated approach to the management of Ewing's sarcoma, which emphasizes surgery in preference to radiotherapy for local disease control, and adjuvant chemotherapy for micrometastases, is outlined.

Target volume definition for intensity-modulated radiotherapy after induction chemotherapy and patterns of treatment failure after sequential chemoradiotherapy in locoregionally advanced oropharyngeal squamous cell carcinoma.

AIMS: To validate our approach to target volume definition for intensity-modulated radiotherapy (IMRT) after induction chemotherapy and to analyse the pattern of treatment failure in patients with locoregionally advanced oropharyngeal squamous cell carcinoma (SCC) after sequential chemoradiotherapy (SCRT). MATERIALS AND METHODS: We studied all patients with locoregionally advanced oropharyngeal SCC treated with SCRT, definitive IMRT and no prior surgery between December 2004 and February 2010. SCRT consisted of three cycles of induction chemotherapy followed by IMRT with concurrent weekly chemotherapy. Our approach to IMRT tumour volume definition after induction chemotherapy was similar to recommendations from published clinical practice guidelines. Volumetric expansion was used to create the high-dose clinical target volume with a margin of 10 mm. The high-dose planning target volume (PTV) was treated to 65 Gy, whereas the prophylactic-dose PTV received 54 Gy over 30 fractions using the simultaneous integrated boost technique. The location and extent of each treatment failure was recorded, reconstructed on the planning computed tomography images and analysed using the dose distribution of the IMRT plan. RESULTS: Fifty-two patients were included. The median follow-up was 32.2 months (range 5.0-67.1 months). There were seven local failures, no regional recurrences and one with distant disease. None of the patients required post-treatment neck dissection. All local failures were in-field and occurred within the high-dose PTV. There were no marginal recurrences. Actuarial recurrence-free, disease-specific and overall survival rates at 3 years were 83.9, 85.9 and 79.7%, respectively. CONCLUSIONS: The absence of marginal recurrences validated the approach to IMRT target volume definition after induction chemotherapy proposed by clinical practice guidelines and practised at our institution. It suggested a lack of benefit with the use of larger geometric margins and additional anatomical expansion for the high-dose clinical target volume. SCRT resulted in excellent regional and distant disease control in patients with locoregionally advanced oropharyngeal SCC.

Lymphatic drainage of melanomas located on the manubrium sterni to cervical lymph nodes: a case series assessed by SPECT/CT.

The lymphatic drainage of cutaneous melanomas located on the upper trunk is often complex and sometimes follows an unexpected pattern. Occasionally, even direct drainage to cervical lymph nodes is seen. In this case series, 3 patients with lymphatic drainage to the neck derived from melanomas located over the manubrium sterni are described. There appears to be a restricted area that involves the manubrium sterni from which lymphatic drainage to different cervical node basins appears more frequent. SPECT/CT was helpful in visualizing these patterns and for the localization of the sentinel nodes.

Interobserver variation in parotid gland delineation: a study of its impact on intensity-modulated radiotherapy solutions with a systematic review of the literature.

OBJECTIVES: This study evaluates the interobserver variation in parotid gland delineation and its impact on intensity-modulated radiotherapy (IMRT) solutions. METHODS: The CT volumetric data sets of 10 patients with oropharyngeal squamous cell carcinoma who had been treated with parotid-sparing IMRT were used. Four radiation oncologists and three radiologists delineated the parotid gland that had been spared using IMRT. The dose-volume histogram (DVH) for each study contour was calculated using the IMRT plan actually delivered for that patient. This was compared with the original DVH obtained when the plan was used clinically. RESULTS: 70 study contours were analysed. The mean parotid dose achieved during the actual treatment was within 10% of 24 Gy for all cases. Using the study contours, the mean parotid dose obtained was within 10% of 24 Gy for only 53% of volumes by radiation oncologists and 55% of volumes by radiologists. The parotid DVHs of 46% of the study contours were sufficiently different from those used clinically, such that a different IMRT plan would have been produced. CONCLUSION: Interobserver variation in parotid gland delineation is significant. Further studies are required to determine ways of improving the interobserver consistency in parotid gland definition.

Multidisciplinary collaborative gross tumour volume definition for lung cancer radiotherapy: a prospective study.

Variability in gross tumour volume (GTV) definition is a major source of systematic error in conformal radiotherapy. This prospective study assesses the role of multidisciplinary collaboration between oncologists and radiologists in defining lung cancer volumes. Twenty patients with non-small cell lung cancer due to receive three-dimensional conformal radiotherapy formed the study population. GTVs were defined by a radiologist (GTVrad) and an oncologist (GTVonc) using available clinical information and imaging. A collaborative meeting was then held to agree on a final, common GTV (GTVfin) to be used for treatment planning, and differences analysed. The collaboration changed the GTV in 19/20 patients with a total of 50 regions being edited. Changes made were categorized as (a) differentiation of tumour from atelectasis or ground glass shadowing, (b) separation of tumour from vasculature, and (c) defining mediastinal extent of tumour. Oncologists were more confident in the GTVfin than the GTVonc. The radiologist took longer to define the GTV than the oncologist. Real-time collaborative GTV definition by a radiologist and oncologist is practical and feasible. This approach allows specific areas of uncertainty to be categorized and focussed on, reducing systematic error in GTV definition. The physician's approach to risk and decision making for each patient may also play a role.