A multi-analyte serum test for the detection of non-small cell lung cancer.

BACKGROUND: In this study, we appraised a wide assortment of biomarkers previously shown to have diagnostic or prognostic value for non-small cell lung cancer (NSCLC) with the intent of establishing a multi-analyte serum test capable of identifying patients with lung cancer. METHODS: Circulating levels of 47 biomarkers were evaluated against patient cohorts consisting of 90 NSCLC and 43 non-cancer controls using commercial immunoassays. Multivariate statistical methods were used on all biomarkers achieving statistical relevance to define an optimised panel of diagnostic biomarkers for NSCLC. The resulting biomarkers were fashioned into a classification algorithm and validated against serum from a second patient cohort. RESULTS: A total of 14 analytes achieved statistical relevance upon evaluation. Multivariate statistical methods then identified a panel of six biomarkers (tumour necrosis factor-α, CYFRA 21-1, interleukin-1ra, matrix metalloproteinase-2, monocyte chemotactic protein-1 and sE-selectin) as being the most efficacious for diagnosing early stage NSCLC. When tested against a second patient cohort, the panel successfully classified 75 of 88 patients. CONCLUSIONS: Here, we report the development of a serum algorithm with high specificity for classifying patients with NSCLC against cohorts of various 'high-risk' individuals. A high rate of false positives was observed within the cohort in which patients had non-neoplastic lung nodules, possibly as a consequence of the inflammatory nature of these conditions.

A 74-year-old man with an enlarging pleural-based mass that was not a mesothelioma.

Soft tissue sarcomas of the chest wall, also known as primary malignant mesenchymal tumors, may be mistaken for a malignant mesothelioma because of their histologic similarities. Reports of primary pleural sarcomas are exceedingly uncommon. We present an unusual case of a primary pleural sarcoma with unique clinical and histological features not previously seen in any other subtype of pulmonary sarcoma.

PAH, PCB, TPH and mercury in surface sediments of the Delaware River Estuary and Delmarva Peninsula, USA.

Surface sediment concentrations of polycyclic aromatic hydrocarbons (PAH) and polychlorinated biphenyls (PCB), total petroleum hydrocarbons (TPH) and mercury, were compared from two areas with contrasting land use history, the industrial Delaware Estuary and the rural Delmarva Peninsula (USA). TPH in the Delaware (38-616mg/kg) and saturate/aromatic fractions suggested petroleum/industrial sources compared to biogenic sources in the Delmarva coastal control (<34-159mg/kg). Within the Delaware the ∑PAH18 ranged from 3749 to 22,324µg/kg with isomeric ratios indicative of petroleum combustion source/s, conversely, those in the Delmarva (5-2139µg/kg) also yielded relatively higher perylene that were consistent with natural background levels derived from vegetation/coal combustion source/s. ∑PCB(tri-hepta) concentrations in the Delmarva (0.6-6.5µg/kg) were less than the threshold effect concentration (TEC), whereas the Delaware had received much higher PCB loading (18.1-136.8µg/kg) as evidenced by a significantly higher amounts in some samples (>TEC).

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in sediments from the Mersey Estuary, U.K.

Sediments from the Mersey Estuary were analysed for polycylic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). Total PAH concentrations ranged from 626 to 3766 microg/kg and total PCB concentrations ranged from 36 to 1409 microg/kg. These concentrations are intermediate in comparison to other U.K estuaries with similar histories of industrialisation and urbanisation. The distribution of individual PAHs were consistent throughout the Mersey Estuary, this together with molecular indices suggests mainly pyrolitic inputs, augmented by a variety of industrial petrogenic sources. Comparison of tri-to-hepta PCB congeners revealed multiple sources and inputs throughout the estuary. A sediment core collected in close proximity to Garston Docks revealed the take-off, peak pollutant input and recent decline of PCB pollution. However, a second depth profile of sediments at Ellesmere Port showed little change in total or individual PCB concentrations due to extensive sediment reworking and mixing.

The significance of colloids in the transport of pesticides through Chalk.

Agrochemical contamination in groundwater poses a significant long term threat to water quality and is of concern for legislators, water utilities and consumers alike. In the dual porosity, dual permeability aquifers such as the Chalk aquifer, movement of pesticides and their metabolites through the unsaturated zone to groundwater is generally considered to be through one of two pathways; a rapid by-pass flow and a slower 'piston-flow' route via the rock matrix. However, the dissolved form or 'colloidal species' in which pesticides move within the water body is poorly understood. Following heavy rainfall, very high peaks in pesticide concentration have been observed in shallow Chalk aquifers. These concentrations might be well explained by colloidal transport of pesticides. We have sampled a Chalk groundwater beneath a deep (30 m) unsaturated zone known to be contaminated with the pesticide diuron. Using a tangential flow filtration technique we have produced colloidal fractions from 0.45 microm to 1 kDa. In addition, we have applied agricultural grade diuron to a typical Chalk soil and created a soil water suspension which was also subsequently fractionated using the same filtration system. The deep groundwater sample showed no evidence of association between colloidal material and pesticide concentration. In comparison, despite some evidence of particle trapping or sorption to the filters, the soil water clearly showed an association between the <0.45 microm and <0.1 microm colloidal fractions which displayed significantly higher pesticide concentrations than the unfiltered sample. Degradation products were also observed and found to behave in a similar manner to the parent compound. Although relatively large colloids can be generated in the Chalk soil zone, it appears transport to depth in a colloidal-bound form does not occur. Comparison with other field and monitoring studies suggests that rapid by-pass flow is unlikely to occur beneath 4-5 m. Therefore, shallow groundwaters are most at risk from rapid transport of high concentrations of pesticide-colloidal complexes. The presence of a deep unsaturated zone will mean that most of the colloidal-complexes will be filtered by the narrow Chalk pores and the majority of pesticide transport will occur in a 'dissolved' form through the more gradual 'piston-flow' route.

"What if I do nothing?" The natural history of operable cancer of the alimentary tract.

INTRODUCTION: "Natural history", or anticipated survival without treatment, is critical for patients weighing risks and benefits of cancer surgery. Current estimates concerning the natural history of cancer includes patients whose poor health precludes treatment; a cohort whose fate is likely distinctly worse than those eligible for surgery ("operable"). The study objective was to evaluate survival among patients recommended for cancer surgery but went untreated, to determine the natural history of "operable" alimentary tract cancer. METHODS: The NCDB was queried for untreated patients with clinical stage I-III esophageal, gastric, colon, and rectal cancer diagnosed between 2003 and 2009. Untreated patients who were recommended for surgery were considered "operable," while patients coded as surgically ineligible for health reasons were "inoperable." RESULTS: 5-year survival of untreated, "operable" alimentary tract cancers varied by clinical stage: esophageal cI = 10.0%, cII = 9.8%, cIII = 4.6%; gastric cI = 9.2%, cII = 5.8%, cIII = 4.3%; colon cI = 18.4%, cII = 5.0%, cIII = 10.4; and rectal cI = 17.1%, cII = 14.0%, cIII = 19.9%. At every timepoint, stage-specific survival of "operable" patients was superior to inoperable patients (p < 0.05). Additionally, median survival among "operable" patients at least doubled "inoperable" patients for each tumor. CONCLUSION: Natural history of patients with "operable" alimentary tract cancer is superior to that of "inoperable" patients. Preoperative counseling should be refined to reflect this distinction.

Syndrome simulating pseudotumor cerebri caused by partial transverse venous sinus obstruction in metastatic prostate cancer.

PURPOSE: To report a case of partial transverse venous sinus obstruction causing a syndrome resembling pseudotumor cerebri. METHOD: Case report. A 61-year-old man developed decreased vision, bilateral papilledema, and a highly increased cerebrospinal fluid opening pressure. Brain magnetic resonance imaging (MRI) disclosed a small, extra-axial mass near the torcula, which was dismissed as an incidental meningioma because cerebral angiography showed sinus patency. RESULTS: The patient's vision worsened. Biopsy of the enlarging mass disclosed metastatic prostate cancer. After radiation therapy, the mass shrank, magnetic resonance angiography disclosed reopening of the transverse sinuses, and papilledema resolved, but visual fields remained severely compromised. CONCLUSION: Partial blockage of the dural venous sinus by a small mass near the torcula can cause a sufficient increase in intracranial pressure to produce vision-threatening papilledema.

Pancreatic epithelial cyst in an adult treated by central pancreatectomy.

The infrequent occurrence of benign epithelial cysts of the pancreas is the reason why little is known regarding their clinical relevance and surgical management. We report the case of a 38-year-old woman with a benign epithelial cyst that was resected by the rarely performed central pancreatectomy. The presentation, evaluation, and differences between this and other cystic lesions of the pancreas are discussed. The benefits of central pancreatectomy for this benign lesion are reviewed.

Selective muscle activation following rapid varus/valgus perturbations at the knee.

Knee muscles are generally divided into groups based on their function as flexors or extensors. In this study we sought to determine if muscles were selectively activated according to their potential roles as varus or valgus stabilizers following rapid loads to the knee. While subjects were supine, varus or valgus moments were applied to the knees of 10 human subjects using a servomotor-driven perturbation device. During the experiments, electromyograms (EMG) were recorded from seven muscles, four of which had medial moment arms relative to the knee center, and three of which had lateral moment arms. It was observed that, for all medial muscles, a statistically significant increase in muscle activation followed valgus loads as compared with varus loads. All lateral muscles except the vastus lateralis showed the opposite response (as expected). These results suggest that muscles can be reflexively activated independent of their roles as flexors or extensors to provide stability to the human knee during varus or valgus loads. The timing of the reflex is consistent with that arising from joint mechanoreceptors, although polysynaptic stretch reflex may also be involved.

Orbital extension of a frontal sinus osteoma in a thirteen-year-old girl.

Osteomas are uncommon, slow-growing, benign osteogenic neoplasms that arise most frequently in the craniofacial skeleton. (1,2) Osteoma is the most common benign tumor of the nose and paranasal sinuses and the most common neoplasm of the frontal sinus. (3-5) Paranasal sinus osteomas originate in the sinus wall, fill the lumen with well-defined mature osseous tissue, and occasionally extend into the orbit where they give rise to orbital signs and symptoms. Osteomas most commonly become symptomatic in the second to fifth decade in life, but orbital involvement has rarely been reported in patients aged 18 years and younger. (2,6-10) We report a case of a frontal sinus osteoma with orbital extension in a 13-year-old girl.

Microcosm studies of microbial degradation in a coal tar distillate plume.

Investigation of a groundwater plume containing up to 24 g l(-1) phenolic compounds suggested that over a period of nearly 50 years, little degradation had occurred despite the presence of a microbial community and electron acceptors within the core of the plume. In order to study the effect of contaminant concentration on degradation behaviour, laboratory microcosm experiments were performed under aerobic and anaerobic conditions at four different concentrations obtained by diluting contaminated with uncontaminated groundwater. The microcosms contained groundwater with total phenols at ca. 200, 250, 660 and 5000 mg l(-1), and aquifer sediment that had been acclimatised within the plume for several months. The microcosms were operated for a period of 390-400 days along with sterile controls to ascertain whether degradation was microbially mediated or abiotic. Under aerobic conditions, degradation only occurred at concentrations up to 660 mg l(-1) total phenols. At phenol concentrations below 250 mg l(-1) a benzoquinone intermediate, thought to originate from the degradation of 2,5-dimethylphenol, was isolated and identified. This suggested an unusual degradative pathway for this compound; its aerobic degradation more commonly proceeding via catecholic intermediates. Under anaerobic conditions, degradation only occurred in the most dilute microcosm (total phenols 195 mg l(-1)) with a loss of p-cresol accompanied by a nonstoichiometric decrease in nitrate and sulphate. By inference, iron(III) from the sediment may also have been used as a terminal electron acceptor, in which case the amount of biologically available iron released was calculated as 1.07 mg Fe(III)/g of sediment. The study shows that natural attenuation is likely to be stimulated by dilution of the plume.

Chemical signatures of the Anthropocene in the Clyde estuary, UK: sediment-hosted Pb, (207/206)Pb, total petroleum hydrocarbon, polyaromatic hydrocarbon and polychlorinated biphenyl pollution records.

The sediment concentrations of total petroleum hydrocarbons (TPHs), polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), Pb and (207/206)Pb isotope ratios were measured in seven cores from the middle Clyde estuary (Scotland, UK) with an aim of tracking the late Anthropocene. Concentrations of TPHs ranged from 34 to 4386 mg kg(-1), total PAHs from 19 to 16,163 µg kg(-1) and total PCBs between less than 4.3 to 1217 µg kg(-1). Inventories, distributions and isomeric ratios of the organic pollutants were used to reconstruct pollutant histories. Pre-Industrial Revolution and modern non-polluted sediments were characterized by low TPH and PAH values as well as high relative abundance of biogenic-sourced phenanthrene and naphthalene. The increasing industrialization of the Clyde gave rise to elevated PAH concentrations and PAH isomeric ratios characteristic of both grass/wood/coal and petroleum and combustion (specifically petroleum combustion). Overall, PAHs had the longest history of any of the organic contaminants. Increasing TPH concentrations and a concomitant decline in PAHs mirrored the lessening of coal use and increasing reliance on petroleum fuels from about the 1950s. Thereafter, declining hydrocarbon pollution was followed by the onset (1950s), peak (1965-1977) and decline (post-1980s) in total PCB concentrations. Lead concentrations ranged from 6 to 631 mg kg(-1), while (207/206)Pb isotope ratios spanned 0.838-0.876, indicative of various proportions of 'background', British ore/coal and Broken Hill type petrol/industrial lead. A chronology was established using published Pb isotope data for aerosol-derived Pb and applied to the cores.

Sedimentary records of sewage pollution using faecal markers in contrasting peri-urban shallow lakes.

Sewage contamination in shallow lake sediments is of concern because the pathogens, organic matter and nutrients contribute to the deterioration of the water-bodies' health and ecology. Sediment cores from three shallow lakes (Coneries, Church and Clifton Ponds) within Attenborough nature reserve located downstream of sewage treatment works were analysed for TOC, C/N, δ(13)C, δ(15)N, bacterial coliforms and faecal sterols. (210)Pb and (137)Cs activities were used to date the sediments. Elemental analysis suggests that the source of organic matter was algal and down profile changes in δ(13)C indicate a possible decrease in productivity with time which could be due to improvements in sewage treatment. δ(15)N for Coneries Pond are slightly higher than those observed in Church or Clifton and are consistent with a sewage-derived nitrate source which has been diluted by non-sewage sources of N. The similarity in δ(15)N values (+12 ‰ to +10 ‰) indicates that the three ponds were not entirely hydrologically isolated. Analysis by gas chromatography/mass spectrometry (GC/MS) reveals that Coneries Pond had sterol concentrations in the range 20 to 30 µg/g (dry wt.), whereas, those from Clifton and Church Ponds were lower. The highest concentrations of the human-sourced sewage marker 5ß-coprostanol were observed in the top 40 cm of Coneries Pond with values up to 2.2 µg/g. In contrast, Church and Clifton Pond sediments contain only trace amounts throughout. Down-profile comparison of 5ß-coprostanol/cholesterol, 5ß-coprostanol/(5ß-coprostanol+5α-cholestanol) and 5ß-epicoprostanol/coprostanol as well as 5α-cholestanol/cholesterol suggests that Coneries Pond has received appreciable amounts of faecal contamination. Examination of 5ß-stigmastanol (marker for herbivorous/ruminant animals) down core concentrations suggests a recent decrease in manure slurry input to Coneries Pond. The greater concentration of ß-sitosterol in sediments from Church and Clifton Ponds as compared to Coneries is attributed in part to their greater diversity and extent of aquatic plants and avian faeces.

Arteriovenous communication in the orbit.

Arteriovenous malformations (AVMs) are anomalous communications between arterial and venous systems without interposed capillaries. These lesions are rarely entirely intraorbital. A case of an arteriovenous communication between branches of the internal and external carotid arterial circulations and the ophthalmic veins located within the orbit is reported. Treatment with embolization resulted in a branch retinal artery occlusion. Attempted direct arterial occlusion of a dural-based fistula of the eye is a risky procedure. If embolized, AVMs should probably be approached from the venous side, if at all.

Selective muscle activation following electrical stimulation of the collateral ligaments of the human knee joint.

The objective of this study was to establish the presence of a local neurosensory reflex are from mechanoreceptors in human collateral ligaments and joint capsule to knee muscles and to determine if these muscles could be selectively activated as varus or valgus stabilizers using randomized trials. All studies were performed in the research department laboratories. Eleven subjects were recruited from the university staff and students based on no prior history of knee ailments. Subjects laid supine on an experimentation table as a current-modulated electrical stimulation was provided through the medial (MCL) or lateral collateral (LCL) knee ligaments. Latency of activation was measured for seven muscles, four by surface electrodes (semitendinosus, biceps femoris long head, vastus medialis, and lateralis), and three by intramuscular electrodes (sartorius, gracilis, tensor fascia lata). In the protocol, selective activation was defined as the relative increase in the activity of four muscles with medial moment arms following MCL stimulation compared with corresponding activity following LCL stimulation. For lateral muscles, the opposite was assumed (ie, that more activity would follow LCL than MCL stimulation). Monte Carlo simulations were performed on the data to determine significant selective muscle activation (p < .05). Statistically significant increases in activation were observed, most consistently, in the vastus medialis following MCL stimulation and in the vastus lateralis following LCL stimulation. These results suggest that a neurosensory reflex are from ligament mechanoreceptors may provide varus and valgus stabilization and knee muscles may be selectively activated to counter varus or valgus loads.

Mucin Hypersecreting Intraductal Papillary Neoplasm of the pancreas.

Mucin Hypersecreting Intraductal Papillary Neoplasm is a rare neoplasm that arises from ductal epithelial cells. This entity is distinct from the more commonly known Mucinous Cystadenoma or Mucinous Cystadenocarcinoma. Despite this distinction, it has been erroneously categorized with these more common cystic neoplasms. Characteristic clinical presentation, radiographic, and endoscopic findings help distinguish this neoplasm from the cystadenomas and cystadenocarcinomas. Histopathologic identification is not crucial to the preoperative diagnosis. This neoplasm is considered to represent a premalignant condition and, therefore, surgical resection is warranted. Prognosis, following resection, is felt to be curative for the majority of patients. We present two cases of Mucin Hypersecreting Intraductal Papillary Neoplasm and discuss their diagnosis and surgical therapy.