Usefulness of NMP22 as an adjunct to a typical urine cytology and low‐grade urothelial carcinoma

The usefulness of urine cytology combined with NMP22 was evaluated for the primary diagnosis of urothelial carcinoma. Of 53 clinically suspected patients, histopathological diagnoses were low‐grade urothelial carcinoma (25), high‐grade urothelial carcinoma (13), and inflammatory lesions (15). Cytology was positive in 25 and negative in 14 patients. Fourteen of 25 low‐grade urothelial carcinoma and 11/13 high‐grade urothelial carcinoma were diagnosed correctly on urine cytology. Atypical cells seen in 14 patients were categorized as inconclusive for malignancy. The overall sensitivity of urine cytology was 65.8%, whereas specificity was 100%. NMP22 was positive in 33 patients. Of these 30, 18 low‐grade and 12 high‐grade lesions were true positive. Of the 20 NMP22, eight negative cases were false‐negative. Ten of 15 with negative histopathology were also negative for NMP22, three were false‐positive, and two showed erratic results. Nine of 14 cases with atypical urine cytology were positive for NMP22. Eight of these showed low‐grade carcinoma on histopathology. The sensitivity of BladderChek NMP22 test was 79%, whereas specificity was 80%. NMP22 BladderChek test is a useful adjunct to urine cytology in atypical and low‐grade carcinoma. Diagn. Cytopathol. 2010;38:788–790. © 2009 Wiley‐Liss, Inc.     

Quantitation of urinary hydroxypyridinium cross-links from collagen by high-performance liquid chromatography.

Pyridinoline and deoxypyridinoline are intermolecular cross-links in mature collagen in bone and cartilage. The urinary excretion of the two compounds correlates well to bone turnover. A fast, sensitive, and accurate isocratic ion-pairing reverse-phase high-performance liquid chromatography method for measurement of pyridinoline and deoxypyridinoline in urine has been established. Intra- and inter-assay precision were 5-7% and 12-14%, respectively. Recovery for pyridinoline was 97.4% and for deoxypyridinoline 94.3%. The detection limit was 0.4 pmol. Pyridinoline:creatinine and deoxypyridinoline: creatinine ratios in healthy subjects, were 38.8 nmol:mmol and 13.0 nmol:mmol, respectively. Increased values of both cross-links were observed in children, in the age group 20-29 in both sexes, and in post-menopausal women.     

Biliary endogenous inorganic phosphate, D-glucose, IgA and transferrin are differentially altered by hydrostatic pressure.

Our objective was to determine the effects of hydrostatic biliary pressure on excretion patterns of endogenous solutes which reflect various pathways of bile formation. A stable in vivo model was developed using anesthetized rats intraduodenally infused with taurocholate to maintain bile flow. Bile was collected during a 2-h basal period, a 4-h pressure period where elevation of the bile duct cannula decreased bile flow to 1/3 the basal rate, and a 2-h period after release of hydrostatic biliary pressure. During pressure treatment, bile salt concentration gradually increased approximately 3-fold, biliary inorganic phosphate concentrations rapidly rose approximately 5-fold, and biliary glucose concentration progressively rose approximately 17-fold. Concentrations of proteins in bile were affected differently with extreme decreases in IgA, moderate decreases in total protein and leucine aminopeptidase, and minimal change in transferrin. By 2 h after pressure release, only the alterations in biliary glucose and IgA persisted. The observed striking and persisting increases in biliary glucose are tentatively explained as an impaired reabsorption of glucose by the biliary tract.     

Influence of left atrial and ventricular volumes on the relation between mitral valve annulus and coronary sinus

The aim of this study was to evaluate the anatomic relation between the coronary sinus (CS), mitral annulus, and coronary arteries using 64-multislice computed tomography (MSCT) in patients presenting with a wide range of atrial volumes and left ventricular functions to determine the potential clinical use for percutaneous mitral annuloplasty (PMA). The MSCT data of 165 patients (age 63.65 +/- 12.89 years, 67.3% men) were evaluated. The following variables were measured: CS length, CS ostium area, area of the section of CS when it becomes great cardiac vein, area between CS and atrioventricular groove assessed in volume-rendered 3-dimensional images, axial angle measured as the angle between CS and mitral annulus assessed in axial section, mitral valve annulus (MVA) area, left atrium volume, and left circumflex artery/marginal branch-CS relation referring to mitral annulus. The correlation was inversed between the reduction of the axial angle and all following variables: enlargement of both left ventricular end-systolic (r = -0.429, p <0.001) and end-diastolic (r = -0.428, p <0.001) volumes, left atrial volume (r = -0.361, p <0.001), and MVA (r = -0.324, p <0.001). Similarly, there was inverse correlation between the reduction of the area between CS and atrioventricular groove, and enlargement of both left ventricular end-systolic (r = -0.376, p <0.001) and end-diastolic (r = -0.291, p <0.001) volumes, left atrial volume (r = -0.221, p = 0.001), and MVA (r = -0.155, p = 0.019). Of note, circumflex artery was located between CS and MVA in 77% of the patients, but in patients with severe mitral regurgitation CS crossed circumflex/marginal branch artery more frequently (97% of cases). In conclusion, a close proximity of the CS to the mitral annulus but also to circumflex artery is more likely to occur with left atrial and ventricular enlargement. Thus, MSCT should be considered as part of the selection process of potential candidate to PMA to avoid external compression of circumflex artery/marginal branch by the device.     

The beneficial effect of azathioprine on maintenance of remission in severe ulcerative colitis

Background. The search is on to find more effective drug regimens for patients with severe ulcerative colitis, as conventional drugs such as sulfasalazine and its congeners fail to prevent relapse in a significant number of patients. Azathioprine has also been reported to be useful as a steroid-sparing drug in patients who suffer from frequent relapses. As these drugs when used individually fail to sustain remission in a significant number of patients, we evaluated the combination of these two drugs. Methods. Thirty-five newly diagnosed patients with severe ulcerative colitis were randomized into two groups; group A (combination therapy) received sulfasalazine and azathioprine, while group B (sulfasalazine monotherapy) received sulfasalazine and placebo. In addition, all the patients received steroids initially to achieve clinical remission. The patients were followed-up for a period of 1 year. The therapeutic outcome was measured by the number of patients who suffered relapse in each group. Results. All the patients completed the 1-year study period. While 4 patients (23.5%) in group A suffered relapse of disease, 10 (55.6%) in group B suffered relapse, the difference being statistically significant. The relapse-free period was also significantly longer in group A. Conclusions. Combination therapy (sulfasalazine and azathioprine) is more effective than sulfasalazine and placebo in the maintenance of remission in patients with severe ulcerative colitis. Received: November 20, 2000 / Accepted: September 14, 2001     

Aberrant methylation of multiple tumor suppressor genes in acute myeloid leukemia

Hypermethylator phenotype, a propensity of tumors to incur nonrandom concurrent methylation, has been described in several tumors, including acute myeloid leukemia (AML). More recent studies identified methylation of other tumor suppressor genes, DAP-kinase and SOCS1, singly in AML. We therefore assessed the methylation status of these genes concurrently with other known targets of methylation. We used methylation-specific PCR or COBRA to determine the extent of methylation of 10 genes in 28 AML samples from Turkey. In addition to DAP-kinase and SOCS1, we included ER, p15, and E-cadherin (reported to be frequently methylated) as well as p16, GSTP1, and HIC1 (reported as rarely methylated). We also included RARbeta and p73 for which only minimal data in AML is available. All samples were methylated at least in one locus and all except one demonstrated methylation of DAP-kinase, SOCS1, p15, and/or ER. DAP-kinase is the most frequently methylated gene in both pediatric (70%) and adult AML (55%). RARbeta is methylated in 18% and p73 in 10% of AMLs. Methylation of E-cadherin and RARbeta occurs preferentially in AMLs with high methylation index (MI), while epigenetic lesions in SOCS1, DAP-kinase, and p15 appear to be independent. MI may be age-dependent, with a peak in young adults. FAB M3 demonstrated a higher extent of methylation than M2/M4. This study provides an impetus for larger studies to define if the extent and pattern of methylation in subgroups of AML are clinically relevant.     

Role of substance P and the neurokinin 1 receptor in acute pancreatitis and pancreatitis-associated lung injury

Substance P, acting via the neurokinin 1 receptor (NK1R), plays an important role in mediating a variety of inflammatory processes. However, its role in acute pancreatitis has not been previously described. We have found that, in normal mice, substance P levels in the pancreas and pancreatic acinar cell expression of NK1R are both increased during secretagogue-induced experimental pancreatitis. To evaluate the role of substance P, pancreatitis was induced in mice that genetically lack NK1R by administration of 12 hourly injections of a supramaximally stimulating dose of the secretagogue caerulein. During pancreatitis, the magnitude of hyperamylasemia, hyperlipasemia, neutrophil sequestration in the pancreas, and pancreatic acinar cell necrosis were significantly reduced in NK1R−/− mice when compared with wild-type NK1R+/+ animals. Similarly, pancreatitis-associated lung injury, as characterized by intrapulmonary sequestration of neutrophils and increased pulmonary microvascular permeability, was reduced in NK1R−/− animals. These effects of NK1R deletion indicate that substance P, acting via NK1R, plays an important proinflammatory role in regulating the severity of acute pancreatitis and pancreatitis-associated lung injury.