La tomografía por emisión de positrones (pet) y pet-tac en riñón,vías urinarias y próstata: actualización

PET has demonstrated its utility in management decisions in several types of tumors. In urologic tract tumors and prostate cancer its diagnostic performance has been lower due to the urinary excretion of the radiotracer, which can mask the presence of lesions. However, specific protocols must be applied that improve the diagnostic performance of PET with 18FFDG in the evaluation of pelvic lesions. Furthermore, prostate cancer is a low-grade tumor with low avidity for 18F-FDG. In spite of these limitations, with PET new and interesting possibilities have been presented. The availability of PET-CT systems has improved its diagnostic performance. On the other hand, the development of new radiotracers that allow targeting other molecular processes and that are metabolized by pathways different to the urinary tract signifies an important advantage compared to 18F-FDG and has evidenced interesting results.     

Rectal hyposensitivity: pathophysiological mechanisms

Abstract Rectal hyposensitivity (RH) relates to a diminished perception of rectal distension. It may occur due to afferent nerve dysfunction and/or secondary to abnormal structural or biomechanical properties of the rectum. The aim of this study was to determine the contribution of these underlying pathophysiological mechanisms by systematically evaluating rectal diameter, compliance and afferent nerve sensitivity in patients with RH, using methodology employed in clinical practice. The study population comprised 45 (33 women; median age 48, range 25–72 years) constipated patients (Rome II criteria) with RH and 20 with normal rectal sensitivity on balloon distension and 20 healthy volunteers. Rectal diameter was measured at minimum distending pressure during isobaric distension under fluoroscopic screening. Rectal compliance was assessed during phasic isobaric distension by measuring the slope of the pressure–volume curve. Electrical stimulation of the rectal mucosa was employed to determine afferent nerve function. Values were compared to normal ranges established in healthy volunteers. The upper limits of normal for rectal diameter, compliance and electrosensitivity were 6.3 cm, 17.9 mL mmHg^?1 and 21.3 mA respectively. Among patients with RH, rectal diameter, but not compliance, was increased above the normal range (megarectum) in seven patients (16%), two of whom had elevated electrosensitivity thresholds. Rectal diameter and compliance were elevated in 23 patients (51%), nine of whom had elevated electrosensitivity thresholds. The remaining 15 patients (33%) with RH had normal rectal compliance and diameter, all of whom had elevated electrosensitivity thresholds. Two‐third of the patients with RH on simple balloon distension have elevated rectal compliance and/or diameter, suggesting that impaired perception of rectal distension is due to inadequate stimulation of the rectal afferent pathway. However, a proportion of such patients also appear to have impaired nerve function. In the remaining one‐third of the patients, rectal diameter and compliance are normal, while electrosensitivity thresholds are elevated, suggestive of true impaired afferent nerve function. Identification of these subgroups of patients with RH may have implications regarding their management.     

Increased mucosal nitric oxide production in ulcerative colitis is mediated in part by the enteroglial-derived S100B protein

Abstract  In the central nervous system glial-derived S100B protein has been associated with inflammation via nitric oxide (NO) production. As the role of enteroglial cells in inflammatory bowel disease has been poorly investigated in humans, we evaluated the association of S100B and NO production in ulcerative colitis (UC). S100B mRNA and protein expression, inducible NO synthase (iNOS) expression, and NO production were evaluated in rectal biopsies from 30 controls and 35 UC patients. To verify the correlation between S100B and NO production, biopsies were exposed to S100B, in the presence or absence of specific receptor for advanced glycation end-products (RAGE) blocking antibody, to measure iNOS expression and nitrite production. S100B and iNOS expression were evaluated after incubation of biopsies with lipopolysaccharides (LPS) + interferon-gamma (IFN-γ) in the presence of anti-RAGE or anti-S100B antibodies or budesonide. S100B mRNA and protein expression, iNOS expression and NO production were significantly higher in the rectal mucosa of patients compared to that of controls. Exogenous S100B induced a significant increase in both iNOS expression and NO production in controls and UC patients; this increase was inhibited by specific anti-RAGE blocking antibody. Incubation with LPS + IFN-γ induced a significant increase in S100B mRNA and protein expression, together with increased iNOS expression and NO production. LPS + IFN-γ-induced S100B up-regulation was not affected by budesonide, while iNOS expression and NO production were significantly inhibited by both specific anti-RAGE and anti-S100B blocking antibodies. Enteroglial-derived S100B up-regulation in UC participates in NO production, involving RAGE in a steroid insensitive pathway.     

The nitric oxide synthase inhibitor, Ng-nitro-l-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans

Abstract The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N^g‐nitro‐l ‐arginine‐methyl‐ester (l ‐NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four‐way randomized crossover (hyperglycaemia vs euglycaemia; l ‐NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 ± 3.8 years; body mass index (BMI) 23.6 ± 1.2 kg m^?2] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L^?1 using a glucose/insulin clamp. An intravenous infusion of l ‐NAME (180 μg kg^?1 h^?1) or placebo (0.9% saline) was commenced (T = ?30 min) and continued for 150 min. At T = ?2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by l ‐NAME. l ‐NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 ± 0.8 (hyperglycaemia) vs 6.5 ± 0.6 (euglycaemia); P < 0.01]; l ‐NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 (l ‐NAME) vs 5.1 ± 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of l ‐NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.     

Spatio-temporal analysis reveals aberrant linkage among sequential propagating pressure wave sequences in patients with symptomatically defined obstructed defecation

Abstract  Available evidence implicates abnormal colonic contractility in patients suffering from constipation. Traditional analysis of colonic manometry focuses on the frequency, extent and amplitude of propagating sequences (PS). We tested the hypotheses that the spatio-temporal linkage among sequential PSs exists throughout the healthy human colon and is disrupted during constipation. In eight patients with severe constipation and eight healthy volunteers, we recorded colonic pressures from 16 regions (caecum–rectum) for 24 h. Sequential PSs were regionally linked if the two PSs originated from different colonic regions but the segments of colon traversed by each PS overlapped. In order to determine whether this linkage occurred by chance, a computer program was used to randomly rearrange all PSs in time. Data were re-analysed to compare regional linkage between randomly re-ordered PSs (expected) and the natural distribution of PSs (observed). In controls the observed regional linkage (82.5 ± 9.0%) was significantly greater than the expected value (60.5 ± 4.3%; P  = 0.0001). In patients the observed and expected regional linkage did not differ. The (observed − expected) delta value of regional linkage in controls was significantly greater than in patients (21.7 ± 8.5% vs −2.3 ± 7.0%; P  = 0.01). Regional linkage among sequential PSs in the healthy colon appears to be a real phenomenon and this linkage is lost in patients with constipation. Regional linkage may be important for normal colonic transit and loss of linkage might have pathophysiological relevance to and provide a useful biomarker of severe constipation.     

Does acute psychological stress increase perception of oesophageal acid?

Abstract Gastro‐oesophageal reflux disease (GORD) patients often report an increase in their reflux symptoms during stressful situations. The aim of this study was to assess the influence of acute psychological stress on oesophageal acid perception. In 15 healthy volunteers and 10 GORD patients with a positive symptom–reflux association an oesophageal acid perfusion test was performed, once with and once without the presence of an acute psychological stressor (IQ test). The order of the measurements was randomized. The time from onset of the acid infusion to first acid perception, discomfort and pain was noted. Blood pressure was measured to assess the effect of the stress task. In healthy volunteers, the time to first perception (control task: 617 ± 174 s vs stress task: 561 ± 162 s), discomfort (control task: 969 ± 158 s vs stress task: 940 ± 151 s) or pain (control task: 1393 ± 122 s vs stress task: 1366 ± 121 s) did not differ significantly between both measurements. In GORD patients, no significant differences between both measurements were found either in time to first perception (control task: 63 ± 26 s vs stress task: 43 ± 15 s), discomfort (control task: 153 ± 44 s vs stress task: 249 ± 62 s) or pain (control task: 558 ± 139 s vs stress task: 633 ± 118 s). Systolic blood pressure rose significantly during the stress task in both the healthy volunteers (6 ± 1 mmHg) and the GORD patients (9 ± 2 mmHg). Neither in the healthy volunteers nor in the GORD patients, the acute psychological stress induced by an IQ test increased oesophageal acid perception. The observed increase in systolic blood pressure shows that the experimental stressors were effective.     

Selective lack of tolerance to delayed gastric emptying after daily administration of WIN 55,212-2 in the rat

Abstract  The use of cannabinoids to treat gastrointestinal (GI) motor disorders has considerable potential. However, it is not clear if tolerance to their actions develops peripherally, as it does centrally. The aim of this study was to examine the chronic effects of the cannabinoid agonist WIN 55,212-2 (WIN) on GI motility, as well as those in the central nervous and cardiovascular systems. WIN was administered for 14 days, at either non-psychoactive or psychoactive doses. Cardiovascular parameters were measured in anaesthetized rats, whereas central effects and alterations in GI motor function were assessed in conscious animals using the cannabinoid tetrad and non-invasive radiographic methods, respectively. Tests were performed after first (acute effects) and last (chronic effects) administration of WIN, and 1 week after discontinuing treatment (residual effects). Food intake and body weight were also recorded throughout treatment. Blood pressure and heart rate remained unchanged after acute or chronic administration of WIN. Central activity and GI motility were acutely depressed at psychoactive doses, whereas non-psychoactive doses only slightly reduced intestinal transit. Most effects were reduced after the last administration. However, delayed gastric emptying was not and could, at least partially, account for a concomitant reduction in food intake and body weight gain. The remaining effects of WIN administration in GI motility were blocked by the CB1 antagonist AM 251, which slightly accelerated motility when administered alone. No residual effects were found 1 week after discontinuing cannabinoid treatment. The different systems show differential sensitivity to cannabinoids and tolerance developed at different rates, with delayed gastric emptying being particularly resistant to attenuation upon chronic treatment.