A randomized trial of the electronic Lung Cancer Symptom Scale for quality-of-life assessment in patients with advanced non-small-cell lung cancer.

Introduction: Improving health-related quality of life (hrqol) is a key goal of systemic therapy in advanced lung cancer, although routine assessment remains challenging. We analyzed the impact of a real-time electronic hrqol tool, the electronic Lung Cancer Symptom Scale (elcss-ql), on palliative care (pc) referral rates, patterns of chemotherapy treatment, and use of other supportive interventions in patients with advanced non-small-cell lung cancer (nsclc) receiving first-line chemotherapy. Methods: Patients with advanced nsclc starting first-line chemotherapy were randomized to their oncologist receiving or not receiving their elcss-ql data before each clinic visit. Patients completed the elcss-ql at baseline, before each chemotherapy cycle, and at subsequent follow-up visits until disease progression. Prospective data about the pc referral rate, hrqol, and use of other supportive interventions were collected. Results: For the 95 patients with advanced nsclc who participated, oncologists received real-time elcss-ql data for 44 (elcss-ql arm) and standard clinical assessment alone for 51 (standard arm). The primary endpoint, the pc referral rate, was numerically higher, but statistically similar, for patients in the elcss-ql and standard arms. The hrqol scores over time were not significantly different between the two study arms. Conclusions: The elcss-ql is feasible as a tool for use in routine clinical practice, although no statistically significant effect of its use was demonstrated in our study. Improving access to supportive care through the collection of patient-reported outcomes and hrqol should be an important component of care for patients with advanced lung cancer.

Effect of prior deformation on microstructural development and Laves phase precipitation in high-chromium stainless steel.

This study investigated the influence of deformation on precipitation behaviour and microstructure change during annealing. Here, the prior deformation of high-chromium stainless steel was tensile deformation of 3%, 6% and 10%, and the specimens were then annealed at 700˚C for 10 h. The specimens were subsequently analyzed using backscattered electron image and electron backscattering diffraction measurements with SEM. Compared with the deformation microstructure, the grains revealed no preferred orientation. The precipitates of TiN and NbC were formed homogenously in the grain interior and at grain boundaries after annealing. Fine Laves phase precipitates were observed in grains and along subgrain boundaries as the deformation increased. Furthermore, the volume fraction of Laves phase increased, but the average particle diameter of precipitate was reduced as the deformation increased.

Regorafenib-induced hyperammonemic encephalopathy.

WHAT IS KNOWN AND OBJECTIVE: Regorafenib improves progression-free survival as a late-line treatment for patients with metastatic gastrointestinal stromal tumour (GIST). As a multitargeted tyrosine kinase inhibitor (TKI), the expected adverse events of regorafenib are similar to those reported with imatinib, sunitinib or sorafenib. We report the first case of hyperammonemic encephalopathy related to regorafenib in a patient with metastatic GIST. CASE SUMMARY: A 61-year-old man maintained on regorafenib for metastatic GIST presented with acute confusion. Discontinuation of regorafenib led to complete resolution of confusion, which later recurred with hyperammonemia on recommencing regorafenib. Cessation of regorafenib and normalization of hyperammonemia then resulted in resolution of confusion. WHAT IS NEW AND CONCLUSIONS: Regorafenib withdrawal and recommencement had influenced the confusional state and hyperammonemia in this patient. There is a probable relationship between regorafenib and metabolic encephalopathy. There are case reports of similar encephalopathy thought to be induced by other multitargeted TKI, and, as such, a class effect could be postulated.

Treatment outcomes of rapid desensitisation protocols for chemotherapeutic agents and monoclonal antibodies following hypersensitivity reactions.

BACKGROUND: Hypersensitivity reactions (HSR) to chemotherapeutic agents and monoclonal antibodies are common and may limit further therapeutic options. Drug desensitisation aims to induce a temporary clinical unresponsiveness to drug antigens so the causative drugs of HSR can continue to be administered. Rapid desensitisation using standardised protocols has been conducted by the Department of Immunology at The Canberra Hospital for patients who developed HSR to chemotherapeutic agents and monoclonal antibodies. AIMS: This retrospective audit reviewed the safety and efficacy of the desensitisation protocols used for patients across the Capital Region Cancer Service (CRCS). METHODS: Patients across the CRCS who received rapid desensitisation were identified through a search of archived correspondence. Clinical files and pharmacy records were analysed to determine protocol safety and efficacy. RESULTS: From June 2006 to July 2013, 13 patients underwent rapid desensitisations to oxaliplatin, carboplatin, docetaxel or rituximab. A total of 25 desensitisations was conducted with 21 (84%) achieving full target dose without inducing recurrent HSR. As a result, nine patients were successfully desensitised and continued to receive treatment without any further HSR. Desensitisation was aborted in three patients because of recurrence of HSR, which was not of a greater severity than the initial HSR. After successful desensitisation, seven patients were able to resume the regular protocols without requiring additional supervision. CONCLUSION: Rapid desensitisation to various chemotherapeutic agents and monoclonal antibodies with standardised protocols used across CRCS is safe and effective; it provides a feasible treatment option enabling continuation of effective regimens in the setting of HSR.

Application of edge detection method based on image quality gradient for twin detection.

An image quality based method was applied to quantitatively analyse the contribution of electrodeposited copper twinning. This method, based on the image quality as obtained from electron backscattering diffraction, involves three processes: hexagonal edge detection, thinning algorithm and twin determination. The twin density determined by the new algorithm was 65.61% which is higher than the twin density, 57.44% as determined by the Orientation Imaging Microscopy (OIM) analysis. The newly developed algorithm provides an alternative to twin boundary detection.

Concentrations and antioxidative activity of anserine and carnosine in poultry meat extracts treated with demineralization and papain.

Anserine and carnosine found in animal skeletal muscle are capable of inhibiting the catalysis of lipid oxidation by heme and non-heme iron. A demineralization technique and a proteolytic enzyme (papain) were used in this research in order to reduce the levels of proxidants while maintaining high levels of anserine and camosine in poultry (chicken, duck and turkey) meat extracts. Undemineralized poultry meat extracts contained larger amounts of anserine, camosine, heme and non-heme iron (p < 0.05) than did demineralized poultry meat extracts. Both undemineralized and demineralized breast meat extracts of chicken, duck and turkey contained higher concentrations of anserine and camosine, but lower amounts of heme and non-heme iron than did thigh meat extracts. In chicken, duck and turkey meat (breast and thigh) extracts (undemineralized and demineralized), the anserine concentrations were greater (p < 0.05) than the camosine concentrations. The hydrogen-donating ability of undemineralized and demineralized chicken breast meat extracts was not significantly different (p > 0.05): however, demineralized chicken breast meat extracts showed higher (p < 0.05) ferrous chelating ability than did undemineralized meat extracts. The concentrations of anserine, camosine, heme and non-heme iron in chicken breast meat extracts increased (p < 0.05) with the addition of papain (1%) to the meat mixture before extraction. Heme and non-heme iron in the chicken breast meat extracts increased as the reaction time for papain increased from 30 to 120 min, but the concentrations of anserine and camosine were not significantly affected by the longer reaction time for papain. The hydrogen-donating ability and ferrous chelating ability of demineralized chicken breast meat extracts were not significantly affected by papain. The ratios of carnosine/anserine were very specific in the chicken, duck and turkey meat extracts (breast and thigh); and the turkey meat extracts had lower (p < 0.05) camosine/anserine ratios than did the chicken and duck meat extracts. The camosine/anserine ratios of undemineralized and demineralized poultry meat extracts were not significantly different (p > 0.05). This suggests that the carnosine/anserine ratios of undemineralized chicken (0.62 - 0.80), duck (0.75 - 0.77) and turkey (0.15 - 0.16) meat extracts could be used to estimate the single meat species in uncooked or cooked meat products.

ARL4, an ARF-like protein that is developmentally regulated and localized to nuclei and nucleoli.

ADP-ribosylation factors (ARFs) are highly conserved approximately 20-kDa guanine nucleotide-binding proteins that participate in both exocytic and endocytic vesicular transport pathways via mechanisms that are only partially understood. Although several ARF-like proteins (ARLs) are known, their biological functions remain unclear. To characterize its molecular properties, we cloned mouse and human ARL4 (mARL4 and hARL4) cDNA. The appearance of mouse ARL4 mRNA during embryonic development coincided temporally with the sequential formation of somites and the establishment of brain compartmentation. Using ARL4-specific antibody for immunofluorescence microscopy, we observed that endogenous mARL4 in cultured Sertoli and neuroblastoma cells was mainly concentrated in nuclei. When expressed in COS7 cells, ARL4-T34N mutant, predicted to exist with GDP bound, was concentrated in nucleoli. Yeast two-hybrid screening and in vitro protein-interaction assays showed that hARL4 interacted with importin-alpha through its C-terminal NLS region and that the interaction was not nucleotide-dependent. Like ARL2 and -3, recombinant hARL4 did not enhance cholera toxin-catalyzed auto-ADP-ribosylation. Its binding of guanosine 5'-O-(thiotriphosphate) was modified by phospholipid and detergent, and the N terminus of hARL4, like that of ARF, was myristoylated. Our findings suggest that ARL4, with its distinctive nuclear/nucleolar localization and pattern of developmental expression, may play a unique role(s) in neurogenesis and somitogenesis during embryonic development and in the early stages of spermatogenesis in adults.

Ultrasensitive reverse transcription-PCR assay for quantitation of human immunodeficiency virus type 1 RNA in plasma.

With the recent introduction of combination therapy, human immunodeficiency virus type 1 (HIV-1) RNA levels in plasma have been dramatically reduced, frequently to below the limit of quantitation (400 copies/ml of plasma) of the AMPLICOR HIV-1 MONITOR Test (Roche Diagnostic Systems). To achieve enhanced sensitivity of the AMPLICOR HIV-1 MONITOR Test, a modified specimen preparation procedure that allows input of RNA from 10-fold more plasma per amplification reaction was developed. This "ultrasensitive" method allows the accurate quantitation of plasma HIV-1 RNA levels as low as 50 copies/ml. A precision study yielded average within-run and between-run coefficients of variation (CV) of 24.8 and 9.6%, respectively. A multicenter reproducibility study demonstrated that the laboratory-to-laboratory reproducibility of this assay is good, with an average CV of 32%. The linear range of this test is between 50 and 50,000 copies/ml of plasma. RNA concentrations measured by the ultrasensitive and standard HIV-1 MONITOR tests exhibited good agreement within the shared linear range of the two methods. The two measurements were within a factor of 2 for 91% of the specimens tested, with the concentration measured by the ultrasensitive method being only slightly lower (median, 22% lower). Preliminary studies suggest that this assay will prove to be useful for predicting the stability of viral suppression in patients whose RNA levels drop below 400 copies/ml in response to highly active antiretroviral therapy.

The quality of ultrasonic root-end preparation: a quantitative study.

Ultrasonic root-end preparation techniques have recently been introduced and revolutionized the field of endodontic surgery. The purpose of this study was to compare quantitatively the quality of root-end preparation techniques prepared by a specially designed ultrasonic retrotip with those prepared in a traditional manner by a microhandpiece bur. Twenty roots with two canals and an isthmus from extracted maxillary human molars were selected for this study. After instrumentation, obturation, and root-end resection, root-end preparations were made using either an ultrasonic retrotip or a conventional microhandpiece bur. With the aid of the image processing and analysis system, the specimens were inspected under a stereomicroscope for further evaluation of the quality of the shape and size of preparation. The results of this investigation showed that the ultrasonic root-end preparations produced more conservative and less perforated cavities than those made with conventional microhandpiece bur preparations.

Scanning electron microscopic evaluation of the cleanliness of a new ultrasonic root end preparation.

Recently introduced ultrasonic instrumentation techniques for root end preparation have revolutionized the field of endodontic surgery. The specially designed tips offer improved access to the root end and create more conservative root and preparations while decreasing the amount of retained debris. This study compared the cleanliness of root end preparations made using ultrasonic instrumentation with that of those prepared in a traditional manner using a microhandpiece bur. We used 10 extracted maxillary human premolars and molars. After cleaning, shaping, and obturation of the root canals, a 3 mm root end resection perpendicular to the long axis of the root was performed with a carbide fissure bur. The roots were randomly divided into two groups and root end preparations were made using the two aforementioned techniques. The roots were longitudinally split and sputter-coated with gold for scanning electron microscopic study. Three independent dentists used a standardized grading system to evaluate the cleanliness of the root end preparations. The ultrasonic preparation had significantly less superficial debris and a thinner smear layer than the microhandpiece preparation (p < 0.05). There were no significant differences between the canal and isthmus portions of the root end preparations within each group in either superficial debris or smear layer. This indicates that cleaner surfaces for root end cavities are created using ultrasonic retrotips than using microhandpiece burs.

Long-term followup of and patient satisfaction with the Dynaflex self-contained inflatable penile prosthesis.

PURPOSE: We analyzed our experience with the Dynaflex* self-contained inflatable penile prosthesis to define specific complication rates and patient satisfaction in the long term. MATERIALS AND METHODS: From October 1990 through October 1994, 62 men underwent implantation of a Dynaflex prosthesis. Mean and median time since implantation was 50 and 53 months, respectively (minimum 24). In addition to standard followup and tabulation of complications, patients were contacted and interviewed regarding satisfaction with the prosthesis. RESULTS: Mechanical device failures occurred in 9.7% of cases with a mean time to failure of 40 months in 6 prostheses. An additional 16.1% of patients had an unsuccessful outcome due to dissatisfaction with the Dynaflex. Of the patients with a functional Dynaflex prosthesis contacted at the time of this review 88.1% expressed satisfaction. CONCLUSIONS: Mechanical failure rates for the Dynaflex prosthesis are comparable to those previously reported for multicomponent inflatable penile prostheses. Patient dissatisfaction, mainly due to difficulty in operating the Dynaflex inflation and deflation mechanisms, is much higher than for multicomponent inflatable penile prostheses. However, in patients who are successful in mastering operation of the Dynaflex satisfaction rates are high. Careful patient selection, and extended training and education efforts are the keys to maximizing successful outcomes with the Dynaflex prosthesis.

Optimization of the solubilization and renaturation of fish growth hormone produced by Escherichia coli.

Growth hormone (GH) enhances the growth rate of aquacultured fish and shellfish, but it is difficult to extract native GH from fish pituitary glands. However, fish recombinant GH (rGH) can be efficiently synthesized by Escherichia coli cells, although it exists in denatured form in inclusion bodies (IB). We studied the solubilization of IB and the renaturation of rGH to help facilitate the production of a large amount of biologically active rGH. A 100-ml sample of rGH-producing E. coli produced 73.43 +/- 5.47 mg IB (dry weight, n = 3) after 20 h induction by 1 mM isopropyl beta-o-thiogalactopyranoside. Interestingly, if the bacteria were induced by 0.1 mM beta-lactose, 95.3 +/- 3.43 mg of IB was obtained. The optimal conditions for denaturation and renaturation of rGH were when IB were solubilized in 6 M guanidine hydrochloride and then dialysed against pH 10 dialysis buffer (50 mM ammonium bicarbonate and 2 mM EDTA) containing 100 mM L-arginine, 2 mM oxidized glutathione and 2 mM reduced glutathione for 24 h at 4 degrees C in a volume ratio of 3 to 500. At least 20% of the denaturated rGH in IB was renatured. Juvenile black sea bream injected with 0.05 microgram/g resultant rGH once every 2 weeks exhibited significant increases (P < 0.05) in weight gain (84%) relative to fish in the control group over a 16-week period. This process is an economical and effective way to obtain an active form of rGH biosynthesized by a prokaryotic system.

Highly efficient expression of fish growth hormone by Escherichia coli cells.

A PCR product encoding the mature segment of fish pregrowth hormone (pre-GH) was inserted into an Escherichia coli expression vector, pET, in which the ori site was replaced by that of pUC19. The yield of recombinant GH (rGH) was as high as 44 to 47% of total protein. This rGH was immunoreactive to GH antibody. After renaturation, rGH was used to inject fish with 0.1 microgram of rGH per g once every 2 weeks, and this resulted in increases in weight (65%), percent weight gain (165%), and length (22%) relative to those of an untreated control group at week 16 and onward.

Buildup of steady-state picosecond pulses in an actively mode-locked laser-diode array.

We have studied experimentally the temporal and spectral characteristics of an actively mode-locked laserdiode array in an external cavity as it evolves to the steady state. It is found that the buildup time to steadystate picosecond pulses takes less than 45 round trips. The number of clusters of the longitudinal-mode spectrum reduces during the evolution and finally approaches a steady-state spectral distribution with the pulse energy mainly distributed among a few clusters near the line center.