Magnetic resonance imaging (MRI) and diseases of the liver and biliary tract. Part 1. Basic principles, MRI in the assessment of diffuse and focal hepatic disease

Magnetic resonance imaging (MRI) relies on the physical properties of unpaired protons in tissues to generate images. Unpaired protons behave like tiny bar magnets and will align themselves in a magnetic field. Radiofrequency pulses will excite these aligned protons to higher energy states. As they return to their original state, they will release this energy as radio waves. The frequency of the radio waves depends on the local magnetic field and by varying this over a subject, it is possible to build the images we are familiar with. In general, MRI has not been sufficiently sensitive or specific in the assessment of diffuse liver disease for clinical use. However, because of the specific characteristics of fat and iron, it may be useful in the assessment of hepatic steatosis and iron overload. Magnetic resonance imaging is useful in the assessment of focal liver disease, particularly in conjunction with contrast agents. Haemangiomas have a characteristic bright appearance on T-2 weighted images because of the slow flowing blood in dilated sinusoids. Focal nodular hyperplasia (FNH) has a homogenous appearance, and enhances early in the arterial phase after gadolinium injection, while the central scar typically enhances late. Hepatic adenomas have a more heterogenous appearance and also enhance in the arterial phase, but less briskly than FNH. Hepatocellular carcinoma is similar to an adenoma, but typically occurs in a cirrhotic liver and has earlier washout of contrast. The appearance of metastases depends on the underlying primary malignancy. Overall, MRI appears more sensitive and specific than computed tomography with contrast for the detection and evaluation of malignant lesions. (C) 2000 Blackwell Science Asia Pty Ltd.

Magnetic resonance imaging and diseases of the liver and biliary tract. Part 2. Magnetic resonance cholangiography and angiography and conclusions

Magnetic resonance cholangiography (MRC) relies on the strong T-2 signal from stationary liquids, in this case bile, to generate images. No contrast agents are required, and the failure rate and risk of serious complications is lower than with endoscopic retrograde cholangiopancreatography (ERCP). Data from MRC can be summated to produce an image much like the cholangiogram obtained by using ERCP. In addition, MRC and conventional MRI can provide information about the biliary and other anatomy above and below a biliary obstruction. This provides information for therapeutic intervention that is probably most useful for hilar and intrahepatic biliary obstruction. Magnetic resonance cholangiography appears to be similar to ERCP with respect to sensitivity and specificity in detecting lesions causing biliary obstruction, and in the diagnosis of choledocholithiasis. It is also suited to the assessment of biliary anatomy (including the assessment of surgical bile-duct injuries) and intrahepatic biliary pathology. However, ERCP can be therapeutic as well as diagnostic, and MRC should be limited to situations where intervention is unlikely, where intrahepatic or hilar pathology is suspected, to delineate the biliary anatomy prior to other interventions, or after failed or inadequate ERCP. Magnetic resonance angiography (MRA) relies on the properties of flowing liquids to generate images. It is particularly suited to assessment of the hepatic vasculature and appears as good as conventional angiography. It has been shown to be useful in delineating vascular anatomy prior to liver transplantation or insertion of a transjugular intrahepatic portasystemic shunt. Magnetic resonance angiography may also be useful in predicting subsequent variceal haemorrhage in patients with oesophageal varices. (C) 2000 Blackwell Science Asia Pty Ltd.

Processing of urinary pheromones in Antechinus stuartii (Marsupialia: Dasyuridae): Functional magnetic resonance imaging of the brain

Little is known of the neural mechanisms of marsupial olfaction. However, functional magnetic resonance imaging (fMRI) has made it possible to visualize dynamic brain function in mammals without invasion. In this study, central processing of urinary pheromones was investigated in the brown antechinus, Antechinus stuartii, using fMRI. Images were obtained from 18 subjects (11 males, 7 females) in response to conspecific urinary olfactory stimuli. Significant indiscriminate activation occurred in the accessory olfactory bulb, entorhinal, frontal, and parietal cortices in response to both male and female urine. The paraventricular nucleus of hypothalamus, ventrolateral thalamic nucleus, and medial preoptic area were only activated in response to male urine. Results of this MRI study indicate that projections of accessory olfactory system are activated by chemo-sensory cues. Furthermore, it appears that, based on these experiments, urinary pheromones may act on the hypothalamo-pituitary-adrenocortical axis via the paraventricular nucleus of the hypothalamus and may play an important role in the unique life history pattern of A. stuartii. Finally, this study has demonstrated that fMRI may be a powerful tool for investigations of olfactory processes in mammals.

Experimental study of the deposition of combustion aerosols in the human respiratory tract

The total deposition of environmental tobacco smoke (ETS), diesel and petrol smoke in the respiratory tract of 14 non-smokers between the ages of 20 and 30 was determined experimentally. A scanning mobility particle sizer (SMPS) measuring a size range of 0.016-0.626 mu m was used to characterise the inhaled and exhaled aerosol during relaxed nasal breathing over a period of 10 min. The ETS, diesel, and petrol particles had average count median diameter (and geometric standard deviation) of 0.183 mu m (1.7), 0.125 mu m (1.7), and 0.069 mu m (1.7), respectively. The average total number deposition of ETS was 36% (standard deviation 10%), of diesel smoke 30% (standard deviation 9%), and of petrol smoke 41% (standard deviation 8%). The analysis of the deposition patterns as a function of particle size for the three aerosols in each individual showed that there is a significant difference between each aerosol for a majority of individuals (12 out of 14). This is an important result as it indicates that differences persist regardless of inter-subject variability. (C) 2005 Elsevier Ltd. All rights reserved.

Increased Transactivation Associated with SOX3 Polyalanine Tract Deletion in a Patient with Hypopituitarism

Backgound and Aims: Correct gene dosage of SOX3 is critical for the development of the hypothalamo-pituitary axis. Both overdosage of SOX3, as a result of gene duplication, and loss of function resulting from expansion of the first polyalanine (PA) tract are associated with variable degrees of hypopituitarism, with or without mental retardation. The aim of this study was to further investigate the contribution of SOX3 in the etiology of hypopituitarism and the mechanisms involved in the phenotypic variability. Methods: We screened 154 patients with congenital hypopituitarism and an undescended posterior pituitary for mutations in SOX3 and variability in the length of the first PA tract. In addition, 300 patients with variable septooptic dysplasia were screened for variability of the PA tract. Results: We report a novel 18-base pair deletion (p.A243_A248del6, del6PA) in a female patient with hypopituitarism resulting in a 2-fold increase in transcriptional activation in vitro, compared with wild-type SOX3. We also identified a previously reported seven-alanine expansion (p.A240_A241ins7, +7PA) in two male siblings with isolated GH deficiency and a distinct phenotype, in addition to the nonsynonymous variant p.R5Q in an unrelated individual; this appears to have no functional effect on the protein. In contrast to +7PA, del6PA maintained its ability to repress beta-catenin mediated transcription in vitro. Conclusion: This is the first study to report that PA tract deletions associated with hypopituitarism have functional consequences in vitro, possibly due to increased activation of SOX3 target genes. In addition, we have expanded the phenotypic spectrum associated with PA tract expansion (+7PA) mutations to include panhypopituitarism or isolated GH deficiency, with or without mental retardation. (J Clin Endocrinol Metab 96: E685-E690, 2011)

A prospective study evaluating the efficacy of the artificial sphincter AMS 800 for the treatment of postradical prostatectomy urinary incontinence and the correlation between preoperative urodynamic and surgical outcomes

OBJECTIVES We have evaluated prospectively the long-term efficacy of the artificial urinary sphincter (AUS) AMS 800 for the treatment postradical prostatectomy urinary incontinence (PRPUI) patients. We also evaluated the correlation between preoperative urodynamic findings and surgical outcomes. METHODS From May 1997 to April 2003, 40 consecutive patients with PRPUI caused by intrinsic sphincter deficiency (ISD) were treated with the AMS 800. Mean age was 68.3 +/- 6.3 years. Continence status was evaluated on the basis of pad count, impact of urinary incontinence on the quality of life, complications, and surgical revisions. Preoperative urodynamic findings were correlated with surgical outcomes. RESULTS Follow-up ranged from 27 to 132 months (mean = 53.4 +/- 21.4 months). There was a significant reduction in pad count from 4.0 +/- 0.9 to 0.62 +/- 1.07 diapers per day (P <0.001) leading to continence in 90%. There was a significant reduction on the impact of incontinence decreasing from 5.0 +/- 0.7 to 1.4 +/- 0.93 (P <0.001) in a visual analogue scale (VAS). Surgical revision rate was 20%. Preoperative urodynamics was useful to identify sphincter deficiency. Except by a tendency of worse results in patients with reduced bladder compliance (RBC), other urodynamic parameters did not correlate with a worse surgical outcome. CONCLUSIONS The AMS 800 offers good long-term continence to most PRPUI patients. Preoperative findings like detrusor hyperactivity (DH), impaired detrusor contraction (IDC), low Valsalva leak point pressure, bladder outlet obstruction (BOO), and mild RBC were not associated with worse surgical outcomes.

Urinary glycosaminoglycans as biomarker for urothelial injury: Is it possible to discriminate damage from recovery?

OBJECTIVES The glycosaminoglycan (GAG) layer is referred to as a bladder protective factor. We reproduced an experimental model of urothelial damage to assess GAG metabolism in the process of injury and recovery of the urothelium. METHODS Wistar female rats were bladder catheterized and instilled with either protamine sulfate (PS groups) or sterile saline (control groups). At different days after the procedure, 24-hour urine samples were obtained. The urinary levels of hyaluronic acid (HA) and sulfated glycosaminoglycan were determined in all groups and in nonmanipulated rats (day 0). Additionally, sulfated-GAG synthesis was assessed by the incorporation of [S-35]-inorganic sulfate. The bladders were analyzed by histochemical staining for HA and immunofluorescence for heparin sulfate and syndecan-4. RESULTS Urinary HA and sulfated-GAG were elevated after PS injection (P <0.05). A greater concentration of [S-35] -labeled GAG in the PS group animals on the fifth day and, especially, on the seventh day represented increased GAG synthesis at these periods (P <0.05). Bladder sections from the PS group animals on day 1 showed a greater amount of HA in the urothelium. PS instillation damaged the urothelium layer of heparin sulfate and syndecan-4 seen in the control animals. On day 5, patchy areas of a restored layer were seen, and, on day 7, this layer had completely regenerated. CONCLUSIONS Urinary GAG cannot differentiate urothelial damage from recovery. Elevated levels of urinary GAG can result from either desquamation of the surface cell GAG layer or increased GAG synthesis to regenerate the damaged urothelium.

Characterization of Superparamagnetic Iron Oxide Coated with Silicone Used as Contrast Agent for Magnetic Resonance Image for the Gastrointestinal Tract

The present work is a report of the characterization of superparamagnetic iron oxide nanoparticles coated with silicone used as a contrast agent in magnetic resonance imaging of the gastrointestinal tract. The hydrodynamic size of the contrast agent is 281.2 rim, where it was determined by transmission electron microscopy and a Fe(3)O(4) crystalline structure was identified by X-ray diffraction, also confirmed by Mossbauer Spectroscopy. The blocking temperature of 190 K was determined from magnetic measurements based on the Zero Field Cooled and Field Cooled methods. The hysteresis loops were measured at different temperatures below and above the blocking temperature. Ferromagnetic resonance analysis indicated the superparamagnetic nature of the nanoparticles and a strong temperature dependence of the peak-to-peak linewidth Delta H(pp), giromagnetic factor g, number of spins N(S) and relaxation time T(2) were observed. This behavior can be attributed to an increase in the superexchange interaction.

Model for Differential Nursing Diagnosis of Alterations in Urinary Elimination Based on Fuzzy Logic

Nursing diagnoses associated with alterations of urinary elimination require different interventions, Nurses, who are not specialists, require support to diagnose and manage patients with disturbances of urine elimination. The aim of this study was to present a model based on fuzzy logic for differential diagnosis of alterations in urinary elimination, considering nursing diagnosis approved by the North American Nursing Diagnosis Association, 2001-2002. Fuzzy relations and the maximum-minimum composition approach were used to develop the system. The model performance was evaluated with 195 cases from the database of a previous study, resulting in 79.0% of total concordance and 19.5% of partial concordance, when compared with the panel of experts. Total discordance was observed in only three cases (1.5%). The agreement between model and experts was excellent (kappa = 0.98, P < .0001) or substantial (kappa = 0.69, P < .0001) when considering the overestimative accordance (accordance was considered when at least one diagnosis was equal) and the underestimative discordance (discordance was considered when at least one diagnosis was different), respectively. The model herein presented showed good performance and a simple theoretical structure, therefore demanding few computational resources.

Effects of bilateral adrenalectomy on systemic kainate-induced activation of the nucleus of the solitary tract. Regulation of blood pressure and local neurotransmitters

Glutamatergic transmission through metabotropic and ionotropic receptors, including kainate receptors, plays an important role in the nucleus of the solitary tract (NTS) functions. Glutamate system may interact with several other neurotransmitter systems which might also be influenced by steroid hormones. In the present study we analyzed the ability of systemic kainate to stimulate rat NTS neurons, which was evaluated by c-Fos as a marker of neuronal activation, and also to change the levels of NTS neurotransmitters such as GABA, NPY, CGRP, GAL, NT and NO by means of quantitative immunohistichemistry combined with image analysis. The analysis was also performed in adrenalectomized and kainate stimulated rats in order to evaluate a possible role of adrenal hormones on NTS neurotransmission. Male Wistar rats (3 month-old) were used in the present study. A group of 15 rats was submitted either to bilateral adrenalectomy or sham operation. Forty-eight hours after the surgeries, adrenalectomized rats received a single intraperitoneal injection of kainate (12 mg/kg) and the sham-operated rats were injected either with saline or kainate and sacrificed 8 hours later. The same experimental design was applied in a group of rats in order to register the arterial blood pressure. Systemic kainate decreased the basal values of mean arterial blood pressure (35%) and heart rate (22%) of sham-operated rats, reduction that were maintained in adrenalectomized rats. Kainate triggered a marked elevation of c-Fos positive neurons in the NTS which was 54% counteracted by adrenalectomy. The kainate activated NTS showed changes in the immunoreactive levels of GABA (143% of elevation) and NPY (36% of decrease), which were not modified by previous ablation of adrenal glands. Modulation in the levels of CGRP, GAL and NT immunoreactivities were only observed after kainate in the adrenalectomized rats. Treatments did not alter NOS labeling. It is possible that modulatory function among neurotransmitter systems in the NTS might be influenced by steroid hormones and the implications for central regulation of blood pressure or other visceral regulatory mechanisms control should be further investigated.

TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America

Cancers of the upper aerodigestive tract [(UADT): oral cavity, pharynx, larynx and oesophagus] have high incidence rates in some parts of South America. Alterations in the TP53 gene are common in these cancers. In our study, we have estimated the prevalence and patterns of TP53 mutations (exons 4-10) in 236 UADT tumours from South America in relation to lifestyle risk factors, such as tobacco smoking and alcohol drinking. Moreover, we have conducted a pilot study of EGFR mutations (exons 18-21) in 45 tumours from the same population. TP53 mutation prevalence was high: 59% of tumours were found to carry mutant TP53. We found an association between TP53 mutations and tobacco smoking and alcohol drinking. The mutation rate increased from 38% in never-smokers to 66% in current smokers (P-value for trend = 0.09). G:C > T:A transversions were found only in smokers (15%). Alcohol drinkers carried more G:C > A:T transitions (P = 0.08). Non-exposed individuals were more probable to carry G:C > A:T transitions at CpG sites (P = 0.01 for never-smokers and P < 0.001 for never-drinkers). EGFR mutations were found in 4% of cases. Inactivation of TP53 by mutations is a crucial molecular event in the UADT carcinogenesis and it is closely related to exposure to lifestyle risk factors. EGFR mutations do not appear to be a common event in UADT carcinogenesis in this population.

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case-control study

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited. We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba. We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37-30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72-16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use. In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.

A Sex-Specific Association between a 15q25 Variant and Upper Aerodigestive Tract Cancers

Background: Sequence variants located at 15q25 have been associated with lung cancer and propensity to smoke. We recently reported an association between rs16969968 and risk of upper aerodigestive tract (UADT) cancers (oral cavity, oropharynx, hypopharynx, larynx, and esophagus) in women (OR = 1.24, P = 0.003) with little effect in men (OR = 1.04, P = 0.35). Methods: In a coordinated genotyping study within the International Head and Neck Cancer Epidemiology (INHANCE) consortium, we have sought to replicate these findings in an additional 4,604 cases and 6,239 controls from 10 independent UADT cancer case-control studies. Results: rs16969968 was again associated with UADT cancers in women (OR = 1.21, 95% CI = 1.08-1.36, P = 0.001) and a similar lack of observed effect in men [OR = 1.02, 95% CI = 0.95-1.09, P = 0.66; P-heterogeneity (P(het)) = 0.01]. In a pooled analysis of the original and current studies, totaling 8,572 UADT cancer cases and 11,558 controls, the association was observed among females (OR = 1.22, 95% CI = 1.12-1.34, P = 7 x 10(-6)) but not males (OR = 1.02, 95% CI = 0.97-1.08, P = 0.35; P(het) = 6 x 10(-4)). There was little evidence for a sex difference in the association between this variant and cigarettes smoked per day, with male and female rs16969968 variant carriers smoking approximately the same amount more in the 11,991 ever smokers in the pooled analysis of the 14 studies (P(het) = 0.86). Conclusions: This study has confirmed a sex difference in the association between the 15q25 variant rs16969968 and UADT cancers. Impact: Further research is warranted to elucidate the mechanisms underlying these observations. Cancer Epidemiol Biomarkers Prev; 20(4); 658-64. (C) 2011 AACR.

Acute increase in urinary 6-sulfatoximelatonin after clomipramine, as a predictive measure for emotional improvement

Nocturnal melatonin pineal output is triggered by sympathetic outflow. Antidepressants that block norepinephrine neuronal uptake should increase pineal function. This can be monitored by measuring 6-sulfatoximelatonin (aMT6s), the main melatonin metabolite, in the urine. In this study, we compared the excretion of aMT6s before (baseline), one, and 21 days after administration of clomipramine to healthy subjects (n = 32). At the end of treatment, subjects were divided into responders (n = 12) and non-responders (n = 20) according to the improvement in their emotional state in three out of four domains (interpersonal tolerance, efficiency, well-being and feeling different from the usual self). There was no difference in aMT6s before clomipramine between responders and non-responders in any of the time intervals analysed (06:00-12:00, 12:00-18:00, 18:00-24:00 and 24:00-06:00 hours). At day one, but not at day 21, the fraction of aMT6s excreted during the time interval 24:00-06:00, relative to the total amount excreted by each subject per day, was significantly higher (P = 0.0287) than baseline (0.57 +/- 0.04) in responders. No significant difference was observed in non-responders. The increase in pineal function induced by clomipramine was restricted to day one, indicating that long-lasting adaptation restores pineal function. In addition, the day one increase in aMT6s was significantly increased only in the responders group, raising the possibility that the blocking of neuronal uptake is predictive of emotional improvement.