CNR considerations for rapid real-time MRI tumor tracking in radiotherapy hybrid devices: Effects of B0 field strength.

PURPOSE: This work examines the subject of contrast-to-noise ratio (CNR), specifically between tumor and tissue background, and its dependence on the MRI field strength, B0. This examination is motivated by the recent interest and developments in MRI/radiotherapy hybrids where real-time imaging can be used to guide treatment beams. The ability to distinguish a tumor from background tissue is of primary importance in this field, and this work seeks to elucidate the complex relationship between the CNR and B0 that is too often assumed to be purely linear. METHODS: Experimentally based models of B0-dependant relaxation for various tumor and normal tissues from the literature were used in conjunction with signal equations for MR sequences suitable for rapid real-time imaging to develop field-dependent predictions for CNR. These CNR models were developed for liver, lung, breast, glioma, and kidney tumors for spoiled gradient-echo, balanced steady-state free precession (bSSFP), and single-shot half-Fourier fast spin echo sequences. RESULTS: Due to the pattern in which the relaxation properties of tissues are found to vary over B0 field (specifically the T1 time), there was always an improved CNR at lower fields compared to linear dependency. Further, in some tumor sites, the CNR at lower fields was found to be comparable to, or sometimes higher than those at higher fields (i.e., bSSFP CNR for glioma, kidney, and liver tumors). CONCLUSIONS: In terms of CNR, lower B0 fields have been shown to perform as well or better than higher fields for some tumor sites due to superior T1 contrast. In other sites this effect was less pronounced, reversing the CNR advantage. This complex relationship between CNR and B0 reveals both low and high magnetic fields as viable options for tumor tracking in MRI/radiotherapy hybrids.

Single-port hernia repair: a prospective cohort of 102 patients.

BACKGROUND: Single-port laparoscopic surgery (SPLS) for totally extraperitoneal (TEP) groin hernia repair is a novel procedure, ensuring safe and effective repairs. The aim of this study was to assess the intra-operative and post-operative outcome for 102 patients undergoing SPLS TEP inguinal hernia repair at the Royal Surrey County Hospital in Guildford, UK. This follows on from our previously published series of 16 patients, demonstrating the safety and feasibility of SPLS in our cohort (Agrawal et al. in Surg Endosc 24:952-956, 2010). METHODS: Between October 2008 and August 2010, we performed hernia repairs on 102 patients (98 men, 4 women) aged between 21 and 89 years (median 60). Patient demographics, type of hernia, incision length, operating time, complications, post-operative hospital stay, and recurrence were collected prospectively. Post-operative outcome was measured in terms of days to return to normal activities, work, and analgesia required. RESULTS: Sixty patients had unilateral and 39 bilateral hernias, with 2 femoral hernias and one lipoma of cord. Operating time was 15-120 min (median 35 for unilateral and 45 for bilateral repairs). The incision length ranged between 15 and 40 mm (median 25). There was 1 intra-operative complication (major peritoneal incursion) and 13 minor post-operative complications, with 8 urinary retentions. There were no mortalities and one recurrence at follow-up (up to 713 days). CONCLUSION: The authors' experience has shown that SPLS TEP groin hernia repair is a feasible and safe alternative to three-port laparoscopic hernia repairs in a large patient cohort. There were minimal post-operative complications and good post-operative outcome. Recurrence rate was 0.98 %. Further studies are required to assess the long-term outcome of SPLS hernia repairs in direct comparison with three-port technique.

SU-E-J-151: Evaluation of a Real Time Tumour Autocontouring Algorithm Using In-Vivo Lung MR Images with Various Contrast to Noise Ratios.

PURPOSE: To quantitatively evaluate a lung tumour autocontouring algorithm using in-vivo lung cancer patient MR images with varying contrast to noise ratios (CNR) simulating images acquired at various MR field strengths. METHODS: A non small cell lung cancer patient with posterior lung tumour is imaged (sagittal plane) in a 3T MRI using a dynamic bSSFP sequence (FOV: 40×40cm2 , voxel size: 3.1×3.1×20mm3 , TE = 1.1ms. TR = 2.2ms, 275ms per image) under free breathing for approximately 3 minutes (650 images). Gaussian random noise is added to the 3T images to approximately simulate the equivalent CNR in images acquired at 1.5T, 1.0T, 0.5T, 0.3T and 0.2T. The moving tumour in all 3T images is contoured by a physician for reference. The first 20 of these manual contours are used for the parameters optimization of auto-contouring algorithm. The automatic contours from the remaining images are quantitatively compared with the physician's contours using the centroid's displacement and the Dice's coefficient (DC). RESULTS: The oncologist's contours of the 3T images show a maximum S-I motion of 26mm. Compared to the oncologist's contours, automatic contours have an average centroid displacement of 1.37mm, and an average DC of 0.881. The autocontouring algorithm's performance with images in the range of 1.5T to 0.5T equivalent CNRs is similar to that of the 3T data. However, for the lowest CNR datasets (0.2, 0.3T) an increase in centroid displacement and decrease in DC is observed, with mean displacements of 1.56mm, 1.71mm and DCs of 0.870, 0.836 for the 0.3T and 0.2T dataset, respectivelyConclusions: With in-vivo MR images, the autocontouring algorithm generated lung tumour contours similar to ones drawn by a physician (DC 〉 0.83). In this patient, additional CNR from 〉0.5T MRIs does not provide statistically significant improvement in the accuracy of our autocontouring software. E.Yip is supported by the Canadian Institutes of Health Research as well as Alberta Innovates - Health Solutions.

Protocatechuic acid induces cell death in HepG2 hepatocellular carcinoma cells through a c-Jun N-terminal kinase-dependent mechanism.

Protocatechuic acid (PCA), chlorogenic acid (CA) and luteolin (LT) are plant phenols found in Chinese medicinal herbs such as Lonicera japonica. Cytotoxicity assays showed that PCA, CA and LT (at 100 micromol/L) effectively killed the HepG2 hepatocellular carcinoma cells. Among these three naturally occurring compounds, only PCA was capable of stimulating the c-Jun N-terminal kinase (JNK) and p38 subgroups of the mitogen-activated protein kinase (MAPK) family. Coincidently, PCA-induced cell death was rescued by specific inhibitors for JNK and p38, while the cytotoxicities of CA and LT were partially eliminated by the antioxidant effect of N-acetyl-L-cysteine (NAC). Further investigation demonstrated that the aqueous extract of Lonicera japonica also triggered HepG2 cell death in a JNK-dependent manner, but the amount of PCA alone in this herbal extract was insufficient to contribute the subsequent cytotoxic effect. Collectively, our results suggest that PCA is a naturally occurring compound capable of inducing JNK-dependent hepatocellular carcinoma cell death.

An aqueous extract of the popular Chinese nutraceutical Kwei Ling Ko (Tortoise shell-Rhizome jelly) activates the PPARgamma pathway and down-regulates the NFkappaB activity.

It is generally believed that the popular nutraceutical 'Kwei Ling Ko' (KLK; Tortoise shell-Rhizome jelly) has antiinflammatory effects, but the mechanism by which its effects are manifested remains unknown. Peroxisome proliferation-activated receptors (PPARs) are members of the nuclear hormone receptor/transcription factor superfamily with multiple roles in adipocyte differentiation, glucose homeostasis, immunomodulation and antiinflammatory regulation. As PPAR is required for adipocyte induction, we used adipogenesis as a possible screen for the activation of the PPAR pathway. Interestingly, an aqueous extract of KLK (sKLK) was able to induce the adipocyte differentiation of fibroblast cell lines. Adipogenesis was confirmed by flow cytometric analysis using a fluorescent lipid stain. Up-regulation of PPARgamma transcripts during adipogenesis was also demonstrated by reverse transcription-polymerase chain reaction (RT-PCR). The sKLK-induced adipogenesis was similar to that elicited by insulin. The activity of nuclear factor-kappaB (NFkappaB), a transcription factor responsible for the regulation of proinflammatory genes, was also down-regulated in response to sKLK. Luciferase reporter gene assays further demonstrated that sKLK inhibited both basal and tumor necrosis factor-alpha-stimulated NFkappaB activation. The activities reported in this study support an immunomodulatory effect for sKLK. As activation of PPAR pathway has a dual role in adipogenesis and anti-inflammation, our observations are consistent with the notion that KLK possesses antiinflammatory properties.

Volumetric evaluation of facial swelling utilizing a 3-D range camera.

Quantitative analysis of facial volume is important in the assessment of facial swelling. Previous research has demonstrated that the Fiore trade mark light-structured 3-D range camera is a rapid, non-invasive, and safe imaging technology for the quantitative analysis of facial morphology. The development of the Rugle-3D trade mark volumetric measurement software programme has allowed for the development of a powerful imaging and measurement system. This study aimed to determine the accuracy and reproducibility of Fiore trade mark by measuring simulated facial swelling. A model involving 20 human subjects was devised to simulate facial swelling for image acquisition and measurement in order to assess the accuracy and reproducibility of the device. A systematic error of 1.25% and reproducibility of 3.27% was determined for the imaging system. It is concluded that Fiore trade mark is an accurate and reproducible technology that is sensitive and would be applicable to clinical studies of facial swelling.

Bacterial formyl peptide mediated chemotaxis and extracellular acidification in shrimp haemocytes.

The bacterial formyl peptide N-formylmethionine-leucine-phenylalanine (fMLP) is a potent chemoattractant for mammalian neutrophils. In this study, we demonstrated the binding of fluorescent dye-conjugated-fMLP to haemocytes of the penaeid shrimp Penaeus penicillatus (Alcock), through the use of flow cytometry. Fluorescence microscopy with rhodamine-fMLP suggested that fMLP receptors are present only in sub-populations of the haemocytes: granulocytes and the semi-granular cells. In addition, fMLP dose-dependently mediated chemotaxis in sub-populations of haemocytes. Microphysiometry experiments demonstrated rapid extracellular acidification upon addition of fMLP, which is in agreement with the observation in neutrophils. t-BOC, the specific fMLP receptor antagonist, was able to block the binding, chemotaxis and extracellular acidification induced by the peptide. The ability of shrimp haemocytes to migrate toward fMLP in vitro suggests that this mechanism may be important for the accumulation of these cells in infected tissues of the shrimps.

Prevalence of latex hypersensitivity among health care workers in Malaysia.

Health care workers have been reported to constitute one of the few high-risk groups related to IgE-mediated hypersensitivity associated with the use of latex products. This paper describes the first ever study of prevalence carried out in Malaysia among these workers. One hundred and thirty health care personnel from Hospital Kuala Lumpur were skin tested. Extracts used were prepared from seven different brands of natural rubber latex gloves with varying levels of extractable protein (EPRRIM). Out of the 130 volunteers, 4 (3.1%) had positive skin test to latex with extracts with high levels of EPRRIM (> 0.7 mg/g). The prevalence among the Malaysian health care workers can be considered to be low in comparison to that of some consumer countries as the USA which reported a prevalence of as high as 16.9%.

Measurement of natural rubber latex allergen levels in medical gloves by allergen-specific IgE-ELISA inhibition, RAST inhibition, and skin prick test.

Exposure to natural rubber latex (NRL) medical gloves poses risks to patients sensitized to NRL and to users of protective gloves. Previous studies have shown that extractable allergen levels of the gloves vary widely. Since most of the available laboratory methods of NRL allergen measurement lack adequate validation, we wanted to evaluate the performance of a recently developed competitive IgE-ELISA-inhibition method in relation to the skin prick test (SPT) and RAST inhibition, as well as to extractable protein quantification and an immunochemical latex antigen assay (LEAP). Twenty samples of surgical (n = 14) and examination gloves (n = 6), covering > 90% of medical gloves marketed in Finland in 1994-5, were collected by the Finnish National Research and Development Centre for Welfare and Health, coded, extracted, and analyzed by the five methods. The IgE-ELISA inhibition correlated highly significantly with SPT (r = 0.94) and RAST inhibition (r = 0.96). Likewise, ELISA inhibition and RAST inhibition showed highly significant correlation (P = 0.96, P < 0.0001 in all three instances). Protein quantification by a modified Lowry method also correlated highly significantly with SPT (r = 0.80), RAST inhibition (r = 0.82), and ELISA inhibition (r = 0.81, P < 0.0001 in all three instances). Clearly weaker correlation, though statistically significant (r = 0.48, P = 0.03), was found between SPT and the LEAP assay. An NRL standard preparation was assigned an arbitrary content of 100,000 allergen units (AU) per ml. In relation to this standard, the NRL allergen level was considered low (< 10 AU/ml) in 11, moderate (10-100 AU/ml) in two, and high (> 100 AU/ml) in seven of the 20 glove brands analyzed. In conclusion, the results of a novel IgE-ELISA-inhibition method of measuring NRL allergen levels in medical gloves correlated highly significantly with those of SPT. The ELISA method was found to be sensitive, reproducible, technically easy, inexpensive, and suitable for the analysis of large numbers of NRL products. The results of extensive market surveys in 1994 and 1995, communicated to the medical community in Finland, appear to have had a clear effect in moving glove purchasing policies toward the use of low-allergen gloves.

Breast-feeding in neonatal intensive care.

OBJECTIVE: To determine the incidence of breast-feeding in very preterm babies while in neonatal intensive care. METHODOLOGY: A retrospective records analysis of all 151 babies with gestational age less than 35 weeks admitted to the neonatal intensive care unit (NICU) of a major teaching hospital in 1993. RESULTS: On discharge 64% of babies were having some breast milk (45% having breast milk alone, 19% both breast milk and formula), and 38% some breast-feeding (17% being solely breast-fed, the other 21% combining breast-feeding with either bottle-feeding or an intragastric tube [IGT]. Breast milk was the first milk for 41% of babies, with 83% having breast milk at some stage. Increasing gestational age was associated with a decreased likelihood of first milk being breast milk (73% of those less than 29 weeks compared to 21% of those aged 33-34 weeks, P < 0.001), but with increased rates of breast-feeding (23 compared to 59%, P = 0.01) and breast milk consumption (42 compared to 73%, P = 0.04). CONCLUSIONS: Breast-feeding rates in NICU are well below those found on discharge for full term babies. Both maternal and staff-related factors contribute to this. More and better education of mothers, doctors and nurses as well as changes to some unit practices could increase these rates.

Significance of rubber elongation factor as a latex allergen.

IgE-mediated hypersensitivity to proteins eluting from surgical gloves and other natural rubber products is a well-recognized allergic condition with special impact to health care workers and sensitized patients. Since rubber elongation factor (REF) has been suggested to be the major latex allergen (Hev b 1) we purified REF from rubber particles using electrophoresis and electroelution and reevaluated the occurrence of IgE antibodies to purified REF. The purified protein was subjected to tryptic digestion, peptide separation and amino acid sequencing. Amino acid sequences of 9 tryptic peptides from the purified 14-kD protein gave 100% homology to REF. In immunoblotting, sera from 4 of 6 latex-allergic children with spina bifida or other congenital anomalies exhibited IgE antibodies against REF whereas only 1 serum from the 30 other latex-allergic patients had similar antibodies. In IgE ELISA 8/45 (18%) latex-allergic patients had IgE antibodies to purified REF, whereas 30 (67%) of the same patients had IgE antibodies to purified prohevein, another rubber protein, recently shown to be a major natural rubber latex allergen. The observed overall low frequency of IgE antibodies to purified REF, as measured by two specific IgE assays, indicates that REF is one but not the most significant allergen among the natural rubber latex proteins.

Prohevein from the rubber tree (Hevea brasiliensis) is a major latex allergen.

BACKGROUND: There is general agreement that proteins eluting from different natural rubber latex products can cause immediate type hypersensitivity reactions in latex-allergic patients. However, there is as yet no consensus as to what are the most important allergens in natural rubber latex. OBJECTIVE: We wanted to purify and characterize at the primary structure level three natural latex proteins, suggested to represent significant allergens. METHODS: Proteins were purified from ultracentrifuged bottom fraction of natural rubber latex using high performance liquid chromatography gel filtration and reversed phase chromatography. Purified proteins were subjected to tryptic cleavage, peptide separation and amino acid sequencing. Immunoblotting was used to demonstrate IgE antibodies to the purified proteins in sera from latex-allergic patients. RESULTS: A 20 kDa protein was identified by amino acid sequencing as prohevein, a major protein in the rubber tree Hevea brasiliensis, and a 30 kDa natural rubber latex protein as hevamine, another essential rubber tree protein. A third, previously undescribed natural rubber latex protein, showed high homology to several plant endo-1,3-beta-glucosidases. In immunoblotting, the purified prohevein bound IgE antibodies from 24/29 (83%) sera of latex-allergic patients including positive results in 4/6 latex-allergic children with spina bifida or other congenital anomalies. The purified prohevein elicited positive skin-prick test reactions in all six latex-allergic patients showing IgE to prohevein. The purified 36 kDa protein bound IgE from 6/29 (21%) latex-allergic sera, and the purified hevamine from only 1/29 patient sera. CONCLUSION: The observed high frequency of IgE antibodies to prohevein suggests that this protein is a major natural rubber latex allergen.

Neurologists' use and interpretation of antiepileptic drug monitoring in the treatment of epilepsy.

Of the 150 local Ordinary Members of the Australian Association of Neurologists (AAN), 118 responded to a questionnaire on the use of AED level measurement in the management of epilepsy. AED level measurement is widely employed, but only phenytoin levels were accepted as being reliable by more than 90% of AAN members. Respondents questioned absolute reliance being placed on any of the other AED levels.

Clinical relevance of therapeutic drug level estimation with respect to clonazepam and carbamazepine: preliminary report.

This paper compares the results of plasma drug level estimations for 30 patients receiving clonazepam and 39 patients taking carbamazepine (assessing total and free carbamazepine concentrations together with carbamazepine epoxide levels) with the clinical features of seizure control. Owing to the small numbers of seizure-free patients, the power of the study was insufficient to justify absolute conclusions being drawn. However there appeared to be a trend which suggested that drug level estimations in both situations had virtually no clinical relevance. This causes one to question the growing reliance on plasma drug level estimation in the treatment of epilepsy and, because of the low power of the study, demands extension of the work to confirm its significance. This type of research in epilepsy, based exclusively on a secondary and tertiary referral source, has inherent difficulty in that a conspicuously low number of well controlled patients is included. Acknowledgement of this fact should lead one to appraise critically other papers giving dogmatic statements regarding therapeutic ranges of anticonvulsant plasma levels.

Persistence of EEG activity with prolonged induced hyperthermic fever.

Ten instances of deliberate systemic temperature elevation in the 41.5 degrees C to 42.2 degrees C range have been evaluated electroencephalographically, demonstrating decrease in predominant frequency and voltage. Persistence of electro-cerebral activity suggests that previous reports of electro-cerebral inactivity with elevated temperatures reflect indirect serious effects due to cardiovascular compromise with cerebral ischemia, rather than to a direct temperature-related loss of CNS electrical activity.