Integrin αvß6 sets the stage for colorectal cancer metastasis.

The ß6 subunit of the αvß6 integrin heterodimer has long been an enigma in cancer biology though recent research has provided many new insights into its biology. Collectively, these findings include discovery of the transcriptional, translational and cell biological mechanisms by which ß6 acts, the identification of the cellular influences ß6 exerts upon the cell proteome, the characterisation of multiple ß6-centric pro-metastatic signalling systems and the search for pharmacological therapies (industry and academia) targeted against ß6. Once expressional restriction is overcome in early colorectal cancer (CRC), epithelial cell surface restricted αvß6 can physically interact with, and activate, known oncoproteins, and has the potential to enable the cross-talk through non-canonical signal transduction pathways, resulting in the adoption of an invasive/metastatic phenotype. This recent research has identified numerous interconnections and potential feedback loops, highlighting the fact that the expression of the ß6 subunit may initiate a cascade of downstream effects on the CRC cell rather than acting through a single mechanism. We here review these recent studies and postulate that the existence of a cell surface uPAR/αvß6/TGFß "metastasome" interactome in/on a proportion of colorectal cancer cells, where ß6 expression sequesters and activates multiple systems at the invasive front of tumour lesions, promoting cancer metastasis and hence explaining why ß6 has been correlated with reduced patient survival in CRC.

Jejunal perfusion of simple and conjugated folates in celiac sprue.

The intestinal absorption of [3H]-pteroylmonoglutamate (simple folic acid) and pteroyl-micron[14C]glutamyl-gamma-hexaglutamate ([14C]PG-7, conjugated folic acid) was assessed by the method of jejunal perfusion in five patients with proven celiac sprue who were studied after a gluten-containing or a gluten-free diet, and in nine normal subjects. The luminal disappearance of each folate was markedly impaired after exposure of the patients to dietary gluten and improved by gluten restriction, but not to within the range found in the normal subjects. The luminal disappearance of each folate was markedly impaired after exposure of the patients to dietary gluten and improved by gluten restriction, but not to within the range found in the normal subjects. In each experiment, column chromatography of the luminal aspirates revealed similar spectra of hydrolytic products of [14C]PG-7, whereas the fraction of the distal aspirate chromatogram appearing as pteroyl-micron[14C]glutamyl-gamma-monoglutamate ([14C]-PG-1) was similar in all three groups. By accounting for the variable effects of absorption on the luminal appearance of [14C]PG-1 and by correcting for mucosal hydrolysis which was not followed by release of [14C]PG-1 to the luminal contents, the calculated rate of in vivo hydrolysis of [14C]PG-7 to [14C]PG-1 was found impaired in both celiac sprue groups, with significant improvement on treatment. In mucosal biopsies from the sprue patients, the in vitro activity of folate conjugase in whole homogenates was higher and the activity of disaccharidase lower than in a group of 12 normal mucosal biopsies. These in vitro data suggest that the predominant cellular location of mucosal folate conjugase is different from that of disaccharidase, whereas comparison with the results of in vivo hydrolysis suggests that measurement of the enzyme in whole mucosal homogenates overestimates its significant digestive activity. The present studies indicate that (a) the mucosal lesion of celiac sprue significantly limits the intestinal absorption of both simple and conjugated folate, and (b) malabsorption of conjugated folate results from a combination of impaired hydrolysis and decreased mucosal uptake of hydrolytic product.

Comprehensive predictions of outcome in closed head-injured patients. The development of prognostic equations.

A comprehensive diagnostic evaluation was administered to 162 closed head-injured patients within 1 to 21 days (mean, 7.5 days) after injury. Each evaluation consisted of (1) power spectral analyses of electroencephalogram (EEG) recorded from 19 scalp locations referenced to age-matched norms, (2) brainstem auditory evoked potentials, (3) computed tomography (CT)-scan, and (4) Glasgow Coma Score (GCS) at time of admission (GCS-A) and at time of EEG test (GCS-T). Functional outcome at one year following injury was assessed using the Rappaport Disability Rating Scale (DRS), which measures the level of disability in the six diagnostic categories of (1) eye opening, (2) best verbal response, (3) best motor response, (4) self-care ability for feeding, grooming, and toileting, (5) level of cognitive functioning, and (6) employability. The ability of the different diagnostic measures to predict outcome at one year following injury was assessed using stepwise discriminant analyses to identify patients in the extreme outcome categories of complete recovery versus death and multivariate regression analyses to predict patients with intermediate outcome scores. The best combination of predictor variables was EEG and GCS-T, which accounted for 74.6% of the variance in the multivariate regression analysis of intermediate outcome scores and 95.8% discriminant accuracy between good outcome and death. The best single predictors of outcome in both the discriminant analyses and the regression analyses were EEG coherence and phase. A gradient of prognostic strength of diagnostic measures was EEG phase greater than EEG coherence greater than GCS-T greater than CT-scan greater than EEG relative power. The value of EEG coherence and phase in the assessment of diffuse axonal injury was discussed.

A method of masking oxytocin infusion rates.

BACKGROUND: Controversy exists as to the optimum infusion rate of oxytocin during labor. A system is described to mask infusion rates, and this may help eliminate bias in the study of oxytocin infusion. METHOD: The hardware consists of a commercially available infusion pump that has the capability to receive and send computer messages and a laptop computer. The pump and a programmed computer are attached to a portable stand for bedside use. The display on the pump may be masked while the computer displays the level for any one of three actual rates. EXPERIENCE: Masked and unmasked simulations were performed without human subjects, followed by unmasked bedside testing in 45 patients. The simulation and bedside testing confirmed the system had the ability to maintain designated flow rates in all manner of increases, decreases, stoppages, and restarts. CONCLUSION: This system is a computer-controlled infusion pump with the ability to mask infusion rates. This may allow investigators to compare oxytocin infusion rates objectively in the induction and augmentation of labor.

Computerized EEG analyses of autistic children.

Electroencephalographic measures of the neurophysiological dysfunction underlying autism have been nonspecific and incomplete. Studies using electroencephalographic methods have been fraught with subject sampling bias, a lack of standardized techniques and measures, and a lack of appropriate control groups. Low-functioning autistic children with age-matched normals, age-matched mentally handicapped, and mentally age-matched normal toddlers were tested using a computerized electroencephalographic technique. The autistic children showed significantly more slow wave activity and less alpha, as well as less inter- and intrahemispheric asymmetry than either normal or mentally handicapped children. In general, electroencephalographic features of autistic children closely resembled those of the toddlers, supporting a model of maturational lag as the key descriptor for autistic CNS functioning. A model of diminished cortical differentiation is proposed to account for the low level of intellectual functioning.

Ingestion of carbohydrates varying in complexity produce differential brain responses.

Variations in the complexity of carbohydrate substances were studied with respect to their differential effects on brain function. Glucose, sucrose, fructose and corn starch were each administered as part of an oral carbohydrate tolerance test during 17 test trials. Brain EEG changes and blood glucose levels were monitored concurrently throughout a 5 hour period. The glucose solution produced more substantial EEG effects than the other three carbohydrate solutions. Absolute blood glucose level was the primary determinant of electrocortical changes found predominantly in the left parietal-occipital and left temporal cortical regions. Implications for the study and evaluation of cognitive function were discussed.

Primary mesothelioma. A practical tutorial review.

TARGET AUDIENCE: Gastroenterologists, internists, and surgeons LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand the main diagnostic features of this disease and the differential diagnosis with other entities that have a more benign outcome. The lack of acceptable treatment is explained.

There is an inverse relationship between the presence of significant endoscopic findings and the amount of diazepam required to obtain adequate sedation in upper endoscopy.

A retrospective study was done in order to validate our observation that patients who require large doses of diazepam for sedation for upper endoscopy usually have less significant pathological findings than those who receive smaller, most of the patients (70%) who had significant endoscopic findings required 20 mg of diazepam or less. This was in contrast to patients requiring large doses of diazepam greater than 20 mg, who only had significant findings in 26.7% of the cases.

Perforation of the cecum, as a complication of pleural biopsy.

A case of a rupture of the cecum following pleural biopsy in a patient with lung carcinoma complicated by inappropriate secretion of antidiuretic hormone is reported. We hypothesized that this unusual complication was caused by a neurogenic effect caused by the trauma of the biopsy causing an imbalance in the autonomic nervous system producing a sympathetic predominance leading to adynamic ileus and subsequent perforation.

Observer variability in upper gastrointestinal endoscopy.

An analysis of the observer variation between 4 endoscopists was made assessing the frequency of visual interpretative discrepancies in the areas of the esophagus, stomach and duodenum. The observer variation in relation to the experience of the endoscopist was compared. The trial was carried out in 104 patients. Two observers were staff members with a minimum of 5 years experience in endoscopy. The other two were fellows with one year experience in endoscopy. The procedure was carried out by one endoscopist while the other observed the procedure through the teaching attachment. The findings were immediately recorded on a protocol. Discrepancies observed were classified in two categories: "Major" and "Minor" discrepancies. Results were evaluated in subgroups according to the different endoscopist's training (staff vs fellow, staff vs staff, fellow vs fellow). An analysis of the lesions where discrepancies occurred was made. The minor discrepancies per case was 2.18 +/- 1.32. Major discrepancies were reduced to 1.19 +/- 1.08. There was a significantly decreased incidence of minor and major discrepancies in the comparison of the staff vs staff as opposed to cases performed by fellow vs fellow (p less than 0.01 and p less than 0.005). The diagnoses where discrepancies occurred most often in order of decreasing frequency included. Esophagitis, hiatal hernia, gastritis, gastric ulcer, erosions and duodenal mucosal lesions.

A reappraisal of percutaneous liver biopsy in clinical practice.

The diagnostic yield of 101 consecutive percutaneous liver biopsies was assessed. Adequate tissue was obtained in most specimens. Even in the presence of an adequate specimen, other procedures were often necessary to rule out other diagnostic possibilities not explained nor completely ruled out by percutaneous liver biopsy alone. With the current diagnostic procedures available to the clinician which have low morbidity and low mortality, the use of blind percutaneous liver biopsy as an initial diagnostic step in certain types of liver disease should be reassessed.