Association of lymphovascular invasion with metastasis (loco-regional lymph node or distant) among adult Filipino patients with papillary thyroid carcinoma: A case control study

Background/Objective@#Papillary thyroid carcinoma is the most common type of thyroid cancer. Treatment includes surgery and remnant ablation with radioactive iodine theraphy while follow-up monitoring includes I- 131 whole body scans land thyroglobulin monitoring. Lymphovascular invasion (LVI) has been used as a predictor of metastasis in different cancers. Therefore, it might be useful in predicting metastasis in patients with papillary thyroid carcinoma since metastasis in this type of carcinoma travels via the lymphatic route. The purpose of this study was to determine the association of LVI with metastasis among patients with papillary thyroid carcinoma@*Methodology@#Records of patients with papillary thyroid carcinoma (histopathologic reports, thyroglobulin levevls and I-131 whole body scans) were reviewed. Univariate and multivariate anlyses were performed. @*Results@#A total of 108 subjects were recruited for this study, 47 (43.5%) of which had LVI. There was no association found between LVI and metastasis on baseline (p=0.72) and follow-up scans (p=0.07). However, there was an association between metastasis resolution on follow-up scans and high-dose radioactive treatment (p=0.02) regarless of presence or absence of LVI.@*Conclusion@#There was a significant association of the presence of LVI with elevated thyroglobulin levels (p-value<0.0001). A significant association was also seen with LVI and dose of activity with resolution of thyroid remnant, locoregional lymph node and distant metastasis (p=0.02). Even though no association jwas seen between LVI and metastasis, a robust percentage of patients with LVI were positive for metastasis on whole body scans.

Outcome and economic implications of proteomic test-guided second- or third-line treatment for advanced non-small cell lung cancer: extended analysis of the PROSE trial.

OBJECTIVES: Lung cancer accounts for a significant number of new cancer cases and deaths, with the majority of patients presenting with non-small cell lung cancer (NSCLC). Although epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors are recommended as an alternative to chemotherapy for certain patients, challenges exist for clinical utilization. The objective of this analysis was to assess the outcome and economic implications of a clinically validated serum-based proteomic test to guide treatment decisions in patients with advanced NSCLC, who are EGFR-negative or status unknown, and have progressed following at least one chemotherapy regimen. METHODS: This analysis was conducted from a US payer perspective. Clinical outcomes were evaluated over the lifetime of a patient, based on data from randomized trials and clinical studies. The clinical endpoints included treatment utilization, adverse events, survival, and a composite measure of length and quality of life, referred to as the quality-adjusted life year (QALY). Costs for testing, treatment, surveillance, and management of adverse events were analyzed based on publicly available costs of the related procedures. The economic endpoints were cumulative lifetime direct medical costs and cost per QALY gained. RESULTS: In the base case, treatment recommendation for 27.3% of the patient population changed from erlotinib to chemotherapy after using the proteomic test. Overall survival increased by 0.091 year and QALYs increased by 0.050 year. The total lifetime direct medical cost per patient decreased by $135 with test-guided treatment. The findings were robust over a wide range of variation in the input parameters. CONCLUSION: The serum-based proteomic test informed treatment selection for patients with advanced NSCLC who failed previous chemotherapy regimen(s), improving QALYs and saving costs.

Analysis of petroleum contaminated soils by spectral modeling and pure response profile recovery of n-hexane.

This pilot study compared penalized spline regression (PSR) and random forest (RF) regression using visible and near-infrared diffuse reflectance spectroscopy (VisNIR DRS) derived spectra of 164 petroleum contaminated soils after two different spectral pretreatments [first derivative (FD) and standard normal variate (SNV) followed by detrending] for rapid quantification of soil petroleum contamination. Additionally, a new analytical approach was proposed for the recovery of the pure spectral and concentration profiles of n-hexane present in the unresolved mixture of petroleum contaminated soils using multivariate curve resolution alternating least squares (MCR-ALS). The PSR model using FD spectra (r(2) = 0.87, RMSE = 0.580 log10 mg kg(-1), and residual prediction deviation = 2.78) outperformed all other models tested. Quantitative results obtained by MCR-ALS for n-hexane in presence of interferences (r(2) = 0.65 and RMSE 0.261 log10 mg kg(-1)) were comparable to those obtained using FD (PSR) model. Furthermore, MCR ALS was able to recover pure spectra of n-hexane.

Bio-effects of non-ionizing electromagnetic fields in context of cancer therapy.

Bio-effects mediated by non-ionizing electromagnetic fields (EMF) have become a hot topic of research in the last decades. This interest has been triggered by a growing public concern about the rapid expansion of telecommunication devices and possible consequences of their use on human health. Despite a feasibility study of potential negative impacts, the therapeutic advantages of EMF could be effectively harnessed for the treatment of cancer and other diseases. This review aims to examine recent findings relating to the mechanisms of action underlying the bio-effects induced by non-ionizing EMF. The potential of non-thermal and thermal effects is discussed in the context of possible applications for the induction of apoptosis, formation of reactive oxygen species, and increase of membrane permeability in malignant cells. A special emphasis has been put on the combination of EMF with magnetic nano-particles and ultrasound for cancer treatment. The review encompasses both human and animal studies.

Acaricidal properties of Ricinus communis leaf extracts against organophosphate and pyrethroids resistant Rhipicephalus (Boophilus) microplus.

Indian cattle ticks have developed resistance to commonly used acaricides and an attempt has been made to formulate an ecofriendly herbal preparation for the control of acaricide resistant ticks. A 95% ethanolic extract of Ricinus communis was used to test the efficacy against reference acaricide resistant lines by in vitro assay. In in vitro assay, the extract significantly affects the mortality rate of ticks in dose-dependent manner ranging from 35.0 ± 5.0 to 95.0 ± 5.0% with an additional effect on reproductive physiology of ticks by inhibiting 36.4-63.1% of oviposition. The leaf extract was found effective in killing 48.0, 56.7 and 60.0% diazinon, deltamethrin and multi-acaricide resistant ticks, respectively. However, the cidal and oviposition limiting properties of the extract were separated when the extract was fractionated with hexane, chloroform, n-butanol and water. The HPTLC finger printing profile of R. communis leaf extract under λ(max.) - 254 showed presence of quercetin, gallic acid, flavone and kaempferol which seemed to have synergistic acaricidal action. In vivo experiment resulted in 59.9% efficacy on Ist challenge, however, following 2nd challenge the efficacy was reduced to 48.5%. The results indicated that the 95% ethanolic leaf extract of R. communis can be used effectively in integrated format for the control of acaricide resistant ticks.

Molecular epidemiology of Staphylococcus aureus mastitis in dairy heifers.

The specific purpose was to investigate the possible interrelationships of genotypes of Staphylococcus aureus found in mammary glands, horn flies, and extramammary sites on 3 southeastern US dairies. A total of 1,228 samples were obtained from various sources on the 3 dairy herds, each of which had a history of Staph. aureus mastitis. Dairy herds studied had access to pasture, and samples were collected during the summer when horn flies (Haematobia irritans) were active. Samples collected included milk samples from all lactating herd cows, colostrum samples from heifers calving during the study period, heifer body sites (mouth, nostrils, and teats), the heifer environment (water, feed, and soil/vegetation/pasture), horn flies, and humans (hands and nostrils). Isolation of Staph. aureus was attempted from all samples, with isolates subjected to genotypic analysis using pulsed-field gel electrophoresis. A total of 244/1228 (or 19.9%) of all samples were positive for Staph. aureus. For milk samples, 52/383 (or 13.6%) of samples were Staph. aureus positive, and 70/411 (or 17.0%) of heifer quarter colostrum samples were positive. Horn fly samples were frequently positive, with over one-half (29/52, or 55.8%) of samples positive for Staph. aureus. Staphylococcus aureus obtained during the study comprised isolates from 12 different genotype groups as defined in this study. Identical genotypes were obtained from horn flies, heifer colostrum samples, and cow milk samples. Group B genotypes were shared among flies, heifer colostrum samples, body sites, and cow milk samples, whereas group A genotypes were common to the same sample locations and body sites but rarely (once) found in horn flies. We conclude, based upon the finding of identical pulsed-field gel electrophoresis genotypes in flies, heifer body sites, and heifer colostrum samples, that flies and heifer body sites could be important sources of Staph. aureus for heifer intramammary infections.

In vitro and in vivo efficacy of Acorus calamus extract against Rhipicephalus (Boophilus) microplus.

To develop a environment friendly control measure against cattle tick, Rhipicephalus (Boophilus) microplus, medicinally important plants were identified and extracts were prepared. Twelve 95% ethanolic, thirteen 50% hydroethanolic and nine hot water extracts were prepared and tested against laboratory reared homogenous colony of R. (B.) microplus. Amongst the 34 extracts, 26 extracts showed no mortality within 72 h of application while 12.0 ± 4.9% to 35.0 ± 9.6% mortality of treated ticks was recorded in other extracts. Of the effective extracts, the extract prepared from rhizome of Acorus calamus proved highly efficacious and 100% final mortality within 14 DPT was recorded. The LC85 value of the extract was determined as 11.26. In vivo experiments confirmed the efficacy of the extract up to 42%, and repeat application was required after 7 DPT. The extract was found safe and no reaction was observed when animals were treated with 50% of the concentration, which was five times of the concentration used for in vivo studies. The possibility of using the extract for the control of cattle tick is discussed.

Effect of the UK postcode lottery on survival of patients with metastatic renal cancer: an audit of outcomes in patients with metastatic renal cancer suitable for treatment with tyrosine kinase inhibitors.

AIMS: To determine whether primary care trusts' agreement or refusal to fund sorafenib or sunitinib affects outcomes for patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: This retrospective audit was conducted in a tertiary referral centre for urological cancer. Requests to prescribe drugs not approved by the National Institute for Health and Clinical Excellence are recorded on a trust database. We obtained details of all requests made for sunitinib and sorafenib for patients with renal cell carcinoma since licence in 2006. Outcome measures analysed were overall survival measured from the date of request for funding and hospital resource use as measured from Payment by Results data. Known prognostic factors and the patient's Index of Multiple Deprivation score were assessed at baseline as potential confounders of survival difference. RESULTS: Seventy-nine patients were identified. The groups were similar with respect to prognostic factors and Index of Multiple Deprivation scores. Thirty-seven and eight patients had funding approved for sunitinib and sorafenib, respectively; 21 and 13 were turned down. Seven patients who were denied funding received one or other of these drugs by self-funding treatment. Survival was longer for patients who received treatment with a drug for which they had applied for funding than for those who did not (hazards ratio 0.46; 95% confidence interval 0.21-1.01; chi(2)=3.80; 1 d.f.; P=0.05); the advantage was similar for patients receiving sunitinib (hazards ratio=0.49; 95% confidence interval 0.18-1.36; chi(2)=1.86; 1 d.f.; P=0.17) and sorafenib (hazard ratio=0.44; 95% confidence interval 0.11-1.69; chi(2)=1.58; 1 d.f.; P=0.21). Overall National Health Service resource use apart from funding for the renal cancer drugs was similar for both groups. CONCLUSIONS: Compared with patients receiving treatment, patients denied access to sunitinib and sorafenib had substantially worse survival outcomes, despite receiving treatment from the same clinical team. Access to the new drugs did not have an effect on overall use of National Health Service resources by funded patients. Modern treatments for advanced renal cancer should be available to all National Health Service patients with the disease.

Presence of 25(OH)D deficiency and its effect on vitamin D receptor mRNA expression.

BACKGROUND AND OBJECTIVES: Vitamin D and its metabolites act through vitamin D receptor (VDR). We hypothesized that subjects with low serum 25(OH)D levels but normal PTH might have increased VDR expression. DESIGN AND METHODS: VDRmRNA expression was assessed by real time PCR in duodenal mucosa and PBMC (peripheral blood mononuclear cells) in 45 subjects with normal duodenoscopy and in PBMC alone in 48 healthy volunteers with hypovitaminosis D. 25(OH)D, PTH and VDRmRNA expression in PBMC was reassessed after 8 weeks of oral cholecalciferol (60 000 IU per week) in a subset (n=23) of healthy volunteers. RESULTS AND CONCLUSIONS: The VDRmRNA expressions in the duodenum and PBMC were significantly correlated (r=0.42), but the expression was 13 times higher in the former than the latter. The mean VDRmRNA expression was similar in 25(OH)D-deficient subjects with or without PTH elevation, both in the duodenum and PBMC. The PBMC VDRmRNA expression showed no significant change after cholecalciferol supplementation. A weak correlation coefficient between duodenal mucosa and PBMC VDRmRNA suggests that caution needs to be exercised while using the latter as a surrogate for other sites.

Dysarthria in traumatic brain injury: a breath group and intonational analysis.

Prosodic abnormality is a common feature in the dysarthrias associated with traumatic brain injury (TBI), but very few analytic studies have been reported on the nature of the prosodic disturbances. This study, based on analyses of conversational and sentence speech samples, reports on breath group structure and its temporal and intonational components for 12 subjects with TBI and 8 healthy controls. It introduces the method of f0 close-copy stylization to the study of intonational patterns in dysarthria. The subjects with TBI had reduced mean length and variation of breath groups along with frequent inappropriate locations of breath pause and lengthy and variable breath pauses. Prosodic features that were preserved in the subjects with TBI were phrase final lengthening, f0 downtrend and a relatively normal f0 distribution. However, these subjects had reduced speaking and articulation rates, reduced f0 movement and reduced f0 slope. The phrase final lengthening and f0 downtrend phenomena, which can serve as prosodic cues of syntactic boundary, appear to be robust features of speech production, but the dynamic features of f0 control were more vulnerable to the neurological damage. This study indicates the importance of breath group management in TBI-induced dysarthria and the need to use methods such as those used in this study for large-scale investigations that examine cognitive, linguistic and motoric factors that conspire to reduce communicative efficiency.

Plasticity of the spinal neural circuitry after injury.

Motor function is severely disrupted following spinal cord injury (SCI). The spinal circuitry, however, exhibits a great degree of automaticity and plasticity after an injury. Automaticity implies that the spinal circuits have some capacity to perform complex motor tasks following the disruption of supraspinal input, and evidence for plasticity suggests that biochemical changes at the cellular level in the spinal cord can be induced in an activity-dependent manner that correlates with sensorimotor recovery. These characteristics should be strongly considered as advantageous in developing therapeutic strategies to assist in the recovery of locomotor function following SCI. Rehabilitative efforts combining locomotor training pharmacological means and/or spinal cord electrical stimulation paradigms will most likely result in more effective methods of recovery than using only one intervention.

Relationship between the development of autoimmunity and sensorimotor gating in MRL-lpr mice with reduced IL-2 production.

MRL-lpr mice develop systemic lupus-like autoimmune disease associated with changes in emotional reactivity and spatial learning and memory. Although the major immunological deficit in MRL-lpr mice is uncontrolled lymphoproliferation associated with a Fas gene mutation, these mice have a marked deficit in interleukin-2 (IL-2) production which, when treated, can prevent the development of autoimmune disease. Moreover, both MRL-lpr and IL-2 knockout mice manifest alterations in hippocampal cytoarchitecture and cognitive behavior. We found previously that IL-2 knockout mice have alterations in prepulse inhibition (PPI), a measure of sensorimotor gating. Thus, the present study sought to test the hypothesis that that PPI would be altered in MRL-lpr mice. Compared to MRL(+/+) control mice, MRL-lpr mice exhibited different patterns of PPI during development. Whereas 7 and 12-week MRL-lpr mice with evidence of autoimmune disease (the onset and early stages, respectively) showed increased PPI, 5 week predisease MRL-lpr mice did not. MRL-lpr mice also exhibited increased acoustic startle reactivity that was independent of autoimmune disease. These behavioral changes were not associated with increased brain expression of the proinflammatory cytokines genes, IL-1alpha and IL-6, CD3, or c-myc-associated apoptosis.

Insecticidal and vertebrate toxicity associated with ethnobotanicals used as post-harvest protectants in Ghana.

Six plant species (Cassia sophera, Chamaecrista nigricans, Mitragyna inermis, Ocimum americanum, Securidaca longepedunculata and Synedrella nodiflora) traditionally used in Ghana to control insect pests of stored grain and legumes were screened in the laboratory at three concentrations (0.5, 1 and 5%, w/w) against four common storage pests (Rhyzopertha dominica, Callosobruchus maculatus, Sitophilus zeamais and Prostephanus truncatus). All the plants showed some ability to control all or some of the test insect species. Levels of efficacy varied according to test concentration with the highest concentration tested providing the best control. The S. longepedunculata plant induced the highest percent mortality and was the best at reducing emergence of the F(1) generation. The six plants were also incorporated into standard rat diet at two concentrations (1 and 5%, w/w) and fed to rats over a 6-week period to assess potential deleterious effects against vertebrates. None of the plants demonstrated any neurotoxicological or neurobehavioural effects to the rats over the course of the trial. However, S. longepedunculata and C. nigricans caused a significant reduction in rat growth rate when incorporated at 5% in the diet, induced cell hyperplasia in the liver, and reduced the mean weight of the liver and kidneys, compared to the control group of rats. Kidney pathology was affected only by the 5% concentration of S. longepedunculata which caused a reduced accumulation of alpha2mu-globulin. The implications of these results are discussed in the context of farmer usage of insecticidal plants for stored product protection.

Performance of the Baxter Flo-Gard 6201 volumetric infusion pump for monoplace chamber applications.

For non-hyperbaric purposes, the Baxter Flo-Gard 6201 volumetric pump is capable of infusing multiple types of fluids at rates of 1-1,999 ml x h(-1). We designed a study to determine flow accuracy of this pump at variable rates, fluid viscosities, and volumes over a range of chamber pressures. For hyperbaric use, the pump pressure sensor was adjusted. Sodium chloride solution 0.9% (NS), enteral formula, and packed red blood cells (PRBC) were infused at varying rates from 86.1 to 304 kPa (0.85 to 3.0 atm abs). For NS, measured compared to set flow rates ranged from 12.5% to -7.5% at settings of 1 and 5 ml x h(-1) from 86.1 to 304 kPa (0.85 to 3.0 atm abs) pressures, respectively. For NS infusions at a set rate of 100 ml x h(-1), the measured flow was identical to the set rate at all pressures. At flow settings of 1,999 ml x h(-1), the measured flow varied from the set flow by +/-4.9% Enteral infusion at 100 ml x h(-1) showed approximately a 3% increase in the measured vs. set flow rate. PRBC measured flow rates ranged from -0.4 to 6% of the set rate. During chamber compression and decompression, with set flow rates from 1 to 10 ml x h(-1), the measured flow was considerably less than expected during compression and more than expected during decompression. In conclusion, the Baxter Flo-Gard 6201 infusion pump demonstrated acceptable performance for infusing saline, enteral formula, and PRBC at low and high infusion rates into the pressurized monoplace hyperbaric chamber up to 304 kPa (3 atm abs), with the exception of low rates during compression and decompression.

Functional/metabolic modulation of the brain stem lesions caused by 1,3-dinitrobenzene in the rat.

To determine whether neuronal activity plays a role in the localisation of brain stem lesions in 1,3-dinitrobenzene intoxication we produced asymmetrical changes in auditory input by rupturing the left tympanic membrane in Fischer rats. This raised the auditory threshold on that side from 57-63 dB to 104-122 dB. It also decreased glucose utilisation in the ipsilateral cochlear nucleus and significantly increased utilisation in the contralateral nucleus, resulting in a relative deficit of 72 +/- 6%. Similarly, tympanic membrane rupture led to decreased glucose utilisation in the contralateral and increased utilisation in the ipsilateral inferior colliculus. Additional exposure to "white noise" prevented the decrease in glucose utilisation in the contralateral inferior colliculus. Dosing with dinitrobenzene (10 mg/kg in 4 doses over 48 hr) to otherwise normal rats produces symmetrical vasculonecrotic lesions in these regions, but in animals with left tympanic membrane rupture the severity of morphological changes in the ipsilateral cochlear nucleus and the contralateral inferior colliculus were substantially reduced. Additional exposure to "white noise" increased the degree of damage in the ipsilateral cochlear nucleus and contralateral inferior colliculus. These findings indicate that altered auditory function in rats, with its associated metabolic consequences exercises a significant role in the development of brain stem damage in auditory pathways following dinitrobenzene intoxication.

Effect of adrenaline on plasma concentrations of bupivacaine following lower limb nerve block.

Twenty-two patients undergoing total knee arthroplasty received combined sciatic plus femoral "3 in 1" blocks as adjuncts to general anaesthesia. Eleven patients received 0.375% bupivacaine 45 ml (168.75 mg) with adrenaline 1 in 200,000 and the remaining 11 received plain solution according to a previously prepared, randomized list. The mean maximum plasma bupivacaine concentration was significantly greater with plain solution than when adrenaline was added (1.66 micrograms ml-1 compared with 0.98 micrograms ml-1) (P less than 0.05). Bupivacaine concentrations were greater at all times in the plain group compared with the group receiving adrenaline. These differences were statistically significant at 10, 15 and 20 min (P less than 0.05). The greatest peak concentration recorded was 3.13 micrograms ml-1 in one patient receiving plain bupivacaine. No patient developed signs of systemic toxic effects. Peak plasma concentrations were related inversely to body weight in patients receiving solution containing adrenaline (P less than 0.005), but no relationship existed in patients who received plain solution.

The role of basal forebrain in the primary cholinergic vasodilation in rat neocortex produced by systemic administration of cismethrin.

The pyrethroid insecticide cismethrin (9 mumol/kg) causes a large blood flow increase in cerebral cortex, without a parallel increase in metabolism. A unilateral lesion of the basal forebrain attenuated the blood flow increase in the cortex ipsilateral to the lesion but augmented that in the contralateral cortex. Cortical choline acetyltransferase was similarly affected. Atropine sulphate substantially reduced the flow increase and was additive to the lesion effects. Systemic cismethrin is thus capable of activating a cholinergic vasodilation in the cortex and, in the parietal cortex at least, a substantial proportion of the flow increase is mediated by extrinsic projections from the basal forebrain.

Hypothermia produced by tributyl S,S,S-phosphorotrithioate (DEF).

Tributyl S,S,S-phosphorotrithioate (DEF) produces profound hypothermia in rats, mice and guinea pigs by inhibition of thermogenesis. Its actions on heat conservation and motor control are, however, minimal. It is effective against both shivering and non-shivering thermogenesis and completely blocks the increase in body temperature evoked by anterior hypothalamic stimulation. A number of other measures indicated that this is unlikely to be due to a lack of peripheral thermogenic capacity: thus plasma concentrations of glucose, free fatty acids, and ketone bodies remained normal or rose after DEF, and in vitro noradrenaline-stimulated lipolysis was normal in the presence of DEF. The metabolic response to the uncoupler, 2,4-dinitrophenol was unchanged by DEF, and the increase in temperature of brown fat evoked in vivo by nerve stimulation or noradrenaline was also unaffected. It is suggested that DEF (or more likely a DEF metabolite) acts selectively on a central thermogenic control process.