DNA methylation status is more reliable than gene expression at detecting cancer in prostate biopsy.

BACKGROUND: We analysed critically the potential usefulness of RNA- and DNA-based biomarkers in supporting conventional histological diagnostic tests for prostate carcinoma (PCa) detection. METHODS: Microarray profiling of gene expression and DNA methylation was performed on 16 benign prostatic hyperplasia (BPH) and 32 cancerous and non-cancerous prostate samples extracted by radical prostatectomy. The predictive value of the selected biomarkers was validated by qPCR-based methods using tissue samples extracted from the 58 prostates and, separately, using 227 prostate core biopsies. RESULTS: HOXC6, AMACR and PCA3 expression showed the best discrimination between PCa and BPH. All three genes were previously reported as the most promising mRNA-based markers for distinguishing cancerous lesions from benign prostate lesions; however, none were sufficiently sensitive and specific to meet the criteria for a PCa diagnostic biomarker. By contrast, DNA methylation levels of the APC, TACC2, RARB, DGKZ and HES5 promoter regions achieved high discriminating sensitivity and specificity, with area under the curve (AUCs) reaching 0.95-1.0. Only a small overlap was detected between the DNA methylation levels of PCa-positive and PCa-negative needle biopsies, with AUCs ranging between 0.854 and 0.899. CONCLUSIONS: DNA methylation-based biomarkers reflect the prostate malignancy and might be useful in supporting clinical decisions for suspected PCa following an initial negative prostate biopsy.

Identification of p53 as a sequence-specific DNA-binding protein.

The tumor-suppressor gene p53 is altered by missense mutation in numerous human malignancies. However, the biochemical properties of p53 and the effect of mutation on these properties are unclear. A human DNA sequence was identified that binds specifically to wild-type human p53 protein in vitro. As few as 33 base pairs were sufficient to confer specific binding. Certain guanines within this 33-base pair region were critical, as methylation of these guanines or their substitution with thymine-abrogated binding. Human p53 proteins containing either of two missense mutations commonly found in human tumors were unable to bind significantly to this sequence. These data suggest that a function of p53 may be mediated by its ability to bind to specific DNA sequences in the human genome, and that this activity is altered by mutations that occur in human tumors.

Diagnostic yield and safety of endoscopic ultrasound-guided trucut [corrected] biopsy in patients with gastric submucosal tumors: a prospective study.

BACKGROUND AND STUDY AIMS: Endoscopic-ultrasound-guided trucut needle biopsy (EUS-TCB) has not been adequately evaluated in patients with submucosal tumors (SMTs). PATIENTS AND METHODS: This prospective, uncontrolled study involving 49 consecutive patients with hypoechoic gastric SMTs (> or = 20 mm) evaluated diagnostic yield and 30-day morbidity of EUS-TCB, factors related to the success of EUS-TCB, and agreement between EUS-TCB and the surgical pathology diagnosis. Seventy-three percent of tumors were gastrointestinal stromal tumors (GIST). RESULTS: Tumor tissue adequate for diagnosis was obtained by EUS-TCB in 31 patients (63 %; 95 %CI 49 % to 75 %). In the remaining cases, EUS-TCB provided no tissue (n = 11) or an insufficient amount (n = 7). Logistic regression analysis showed that tumor location on the lesser curvature of the stomach was the only independent predictor of obtaining diagnostic material [odds ratio (OR) 7.4; 95 %CI 1.9 to 28; P = 0.004]. The experience of the endosonographer, the size of the tumor, and the location of the tumor relative to the long axis of the stomach were not related to the success of the biopsy. Agreement between EUS-TCB and surgical pathology specimens in respect of the diagnosis and CD117 status was high (0.9, standard error 0.31; and 0.95, standard error 0.16, respectively); however, there was no correlation between the mitotic index as determined on EUS-TCB and that determined on the surgical pathology specimen (correlation coefficient, 0.08). There were two severe septic complications in 52 procedures (3.9 %; 95 %CI 0.3 % to 14 %). CONCLUSIONS: The diagnostic yield of EUS-TCB in patients with gastric SMTs was moderate. Tissue samples were too small to reliably determine the mitotic index. Antibiotic prophylaxis should be considered because of possible septic complications.

Abundant Acceptor Emission from Nitrogen-Doped ZnO Films Prepared by Atomic Layer Deposition under Oxygen-Rich Conditions.

Nitrogen-doped and undoped ZnO films were grown by thermal atomic layer deposition (ALD) under oxygen-rich conditions. Low-temperature photoluminescence spectra reveal a dominant donor-related emission at 3.36 eV and characteristic acceptor-related emissions at 3.302 and 3.318 eV. Annealing at 800 °C in oxygen atmosphere leads to conversion of conductivity from n- to p-type, which is reflected in photoluminescence spectra. Annealing does not increase any acceptor-related emission in the undoped sample, while in the ZnO:N it leads to a considerable enhancement of the photoluminescence at 3.302 eV. The high resolution cathodoluminescence cross-section images show different spatial distribution of the donor-related and the acceptor-related emissions, which complementarily contribute to the overall luminescence of the annealed ZnO:N material. Similar area of both emissions indicates that the acceptor luminescence comes neither from the grain boundaries nor from stacking faults. Moreover, in ZnO:N the acceptor-emission regions are located along the columns of growth, which shows a perspective to achieve a ZnO:N material with homogeneous acceptor conductivity at least at the micrometer scale.

Increased total mortality as a function of 24-h pulse pressure dipping.

Elevated pulse pressure (PP) as a difference between systolic and diastolic blood pressure is a significant risk factor of cardiovascular (CV) diseases. The goal of our study was to determine the association between PP and major adverse CV events (MACEs), and all-cause and CV mortality in the different age groups of patients with coronary artery disease (CAD) confirmed by angiography. To the PROGNOSIS study, finally there were included 891 subjects with CAD. An analysis of the receiver operating characteristic was used for predicting PP dipping among the age groups of patients. A COX proportional hazards model was used to examine the association between PP and PP dipping and risk of MACE, revascularization, CV and total mortality after adjusting for sex, diabetes, smoking and low-density lipoprotein cholesterol. The median follow-up period was 8.3 years (interquartile range: 5.3-9.0 years). There were 245 (27%) all-cause deaths including 114 (13%) CV deaths during the follow-up period. MACE occurred in 442 (50%) subjects, but coronary artery interventions (percutaneous coronary intervention or coronary artery bypass grafting) were performed in 578 subjects (65%). A Cox proportional regression analysis confirmed the relationship between PP dipping as well as PP dipping thresholds points and risk of MACE and total mortality only in the group of the oldest subjects. In contrast to younger CAD patients, PP dipping is related to MACE, CV and total mortality in very elderly CAD subjects. Nocturnal PP values tend to be higher than diurnal PP values in the oldest CAD individuals. In conclusion, in contrast to younger CAD patients, PP dipping is related to MACE, CV and total mortality in very elderly CAD subjects. Nocturnal PP values tend to be higher than diurnal PP values in the oldest CAD individuals.

Elevated levels of pro-cathepsin-d in the plasma of breast-cancer patients.

Changes in the expression and processing of cathepsin D (CD) have been shown to be associated with cancer invasion and metastasis. However, the value of CD as a prognostic marker remains controversial. Most studies have used immunological methods to measure the mature form of CD, although it is the precursor (pro-CD) that appears to be abnormally secreted by breast cancer cells. A sandwich-type ELISA has been developed that is specific for pro-CD. The assay employs a monoclonal antibody to mature CD as the capture reagent and a rabbit polyclonal to the pro fragment as the detector. The assay is specific for pro-CD and capable of quantitating this antigen in biological samples. Pro-CD levels were measured in plasma samples from 76 breast cancer patients and compared with 36 samples from normal control individuals. The plasmas of breast cancer patients showed elevated levels of pro-CD; 12% were more than two standard deviations above the mean for the normal samples. Immunoblots of the plasma samples using a CD monoclonal antibody revealed a band at the appropriate size for pro-CD that corresponded in intensity with the ELISA results. Affinity adsorption of breast cancer plasmas with pepstatin agarose followed by immunoblot analysis revealed a single protein band that correlated with pro-CD. Only trace amounts were detected in the normal control plasmas. These results demonstrate that cathepsin D is present in the plasma of breast cancer patients primarily in its precursor form and that it may be a useful prognostic indicator.

Diffuse filiform polyposis of the colon in Crohn's disease. Case report.

A case of giant diffuse filiform polyposis of the entire colon with pathological features of Crohn's disease in a 30-year-old man is presented. The most important aspects and difficulties with differential diagnosis of filiform polyposis are discussed.

Treatment of hypertension in a managed care setting.

BACKGROUND: Based on recommendations of the Fifth and Sixth Reports of the Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, Health Care Plan (now Univera Healthcare) Buffalo, NY, developed a clinical guideline to improve the management of patients with hypertension. To increase awareness and utilization, the guideline was distributed as hard copy reports and made available through our electronic information system. OBJECTIVE: To determine blood pressure (BP) control rates and adherence to guideline recommendations. STUDY DESIGN: Retrospective chart review. PATIENTS AND METHODS: We randomly sampled hypertensive patients seen during 1998 to evaluate hypertension management. Computerized medical and pharmacy records were reviewed for patient demographics, antihypertensive medications, comorbid conditions, and BP readings. Patient assessment was based on antihypertensive regimen and achievement of target BP according to the recommendations of the guidelines (< 140/90 mm Hg for the general population and < 130/85 mm Hg for special populations). In addition, we assessed control rates using traditional Health Plan Employer Data and Information Set (HEDIS) measures (< 140/90 mm Hg). RESULTS: Overall, 35% of patients achieved target BP and 68% were treated with agents recommended by our JNC-based guideline. In contrast, using traditional HEDIS measures, 41% of patients achieved BP control. Of 39 patients with compelling indications (primarily diabetic patients), 13% achieved BP target and 67% were treated with recommended agents. CONCLUSIONS: The impact of our clinical guideline is reflected through the relatively high utilization of recommended drugs. However, optimal BP control continues to be problematic. In particular, patients with diabetes warrant focused attention.

Functional and structural changes of isolated rat parietal cells during membrane potential modulation.

The present experiments were undertaken to extent our earlier observations (J Physiol Pharmacol 1991, 42, 367-79) relating membrane potential with membrane recycling of parietal cells. Studies were performed in vitro using gastric glands that were isolated through the use of rat stomachs transformed into "everted sacs" and filled with hyperosmolar NaCl-EDTA solution. Acid production was indirectly determined by accumulation of 14C-aminopyrine (AP) and its translocation by measurement of acridine orange fluorescence. H+/K(+)-ATPase activity was assayed by measurement of K(+)-stimulated p-nitrophenylphosphatase (pNPPase) of the proton pump. Morphologic state of parietal cells in relation to their functional activity was observed using electron microscopy. Changes in the membrane potential were obtained by the treatment of gastric glands with protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) in the incubation media of different pH. CCCP caused time-dependent decrease in AP accumulation by parietal cells from the medium of pH 6.6 but not that of pH 7.8. pNPPase activity increased in aplical and decreased in tubulovesical membrances prepared from CCCP treated glands which were incubated in the medium being more acidic than cell cytoplasm. Electron microscopic assessment showed morphological transformation of resting parietal cells treated with CCCP in pH 6.6 from nonsecreting to secreting state. CCCP acting in acidic incubation medium also caused the decrease in acridine orange fluorescence in the cytoplasm of parietal cells with some temporary increase of its fluorescence in the lumen o gastric glands. These findings support our hypothesis that changes in parietal cell membrane potential by protonophore CCCP may translocate HCl from tubulovesicles to secretory canaliculi. While the above explanation is suggestive, the exact mechanisms controlling a membrane recycling during the secretory response of parietal cells in vitro remain to be elucidated.

Liver vitamin A concentration in patients who died of cancer.

The concentrations of vitamin A in liver samples obtained at autopsy of patients who died of cancer was investigated. It was found that liver vitamin A levels in cancer patients were significantly lower than in controls. Although our recent results have suggested that the decreased serum retinol level in cancer patients reflects rather a functional impairment of vitamin A release from the liver, the results of this study suggest that this phenomenon can also indicate a true vitamin A deficiency in patients with neoplastic process.

Managing serious dog bite injuries in children.

Mammalian bites account for 1% of all emergency department visits and dogs are common perpetrators. School-aged children are the most vulnerable and experience the majority of this type of trauma. Most of the cases involve a known dog and many of the attacks involve the family pet. When a child presents with a severe dog bite, the injury should be managed using appropriate assessment and intervention techniques. In some cases, conscious sedation can be used to provide amnesia, analgesia and sedation during the surgical repair. Proper preparation of the wound prior to repair will decrease infection rates. The need for tetanus and rabies prophylaxis must be evaluated in all dog bites. Facial injuries may require complex repair and reconstruction with appropriate surgical referral. Thorough discharge instructions are an important aspect of the nursing role.

Pediatric spinal cord injuries: a case presentation.

Spinal cord injuries (SCIs) in the pediatric population present a unique challenge to the caregiver in that both the physical injury and the growth and development issues need to be addressed simultaneously. Different types of injuries are anticipated than those seen in adults because of the developmental phases of the pediatric spinal cord. This article will review the differences between the pediatric and adult spinal cords, growth and development, and the types of injuries incurred by this population, followed by a case presentation.

[Value of cytologic examination in diagnosis of focal lesions to the liver and pancreas]. / Wartosc badania cytologicznego w diagnostyce zmian ogniskowych w watrobie i trzustce.

Four hundred fifty three percutaneous fine-needle biopsies (FNB) guided ultrasonically of the focal lesions to the liver and 418 to the pancreas were subjected to retrospective analysis. Biopsies were performed with the aid of real time ultrasound equipment ALOKA SSD-280. The needles of 0.7 and 0.8 mm in outer diameter were used for the aspiration. Smears were fixed with alcohol and stained with hematoxylin and eosin, and examined under light microscope. Specimens suitable for the examination were obtained in 97% of liver biopsies and 90% of pancreatic biopsies. Sensitivity of FNB in the diagnosis of hepatic and pancreatic carcinoma was 97% and 91%, respectively. Its specificity was 100%. ENB efficiency in the diagnosis of the focal lesions to the liver was 98% and in case of the focal lesions to pancreas -95%.

Chronohygienic and chronosocial aspects of industrial accidents.

A series of 2,772 accidents has been analyzed in two plants. The following aspects were considered: 1) environmental circumstances, 2) accident causes as given by witnesses or victims, and 3) time of day. Activity of the plants or particular groups of workers was assessed by supervisors on a 10-point scale. A circadian rhythm of accidents has been shown. It was determined to be governed by the interrelationships between the following endogenous and exogenous rhythmic factors: human factors, such as fatigue and circadian fluctuation of biological functions; and multiple hygienic and social components, which either promote human performance or suppress it, e.g., high environmental temperature, overcrowding, and noise. The rate of accidents depends on the particular combinations of these factors, all of which change around the clock. In both plants, the circadian rhythm of accidents was approximately parallel to the circadian rhythm of activity of the plant as a whole rather than to the activity of shift workers only, with a peak around 1100 hr. The lowest number of accidents was noted during night shifts; some increase was observed after midnight, however, in spite of the lowest level of plant activity at that time.

Malignant transformation of benign epithelial gastric polyps.

OBJECTIVES: To compare the malignant potential of hyperplastic polyps and adenomas in relation to different histological classifications and to try to follow the natural history of the BEGP-carcinoma sequence. METHODS: During a 13-yr period (1981-1993), 811 BEGP were discovered in 432 patients in consecutive esophagogastroscopic examinations in our department. Adequate endoscopic biopsies or polypectomy specimens were histologically diagnosed as hyperplastic polyp in 751 (92.6%) and adenoma in 60 (7.4%) of the lesions, according to WHO classification. Hyperplastic lesions were further divided into two subgroups: 268 were polypoid foveolar hyperplasia (FH) and 483 were typical hyperplastic polyps (HP), according to Elster's classification. Special attention was paid to focal malignancy at the first examination or malignant transformation of BEGP during follow-up. Ninety-six patients with 220 BEGP were followed for 1-11 yr, with an average of 2 yr and 8 months. RESULTS: According to Elster's classification, there were 10/483 (2.1%) HP and 6/60 (10.0%) adenomas with focal carcinoma. Moreover, in 19/265 patients (7.1%) with HP and in 4/30 patients (13.3%) with adenomas, carcinoma was found elsewhere in the stomach. During our follow-up, 5/131 HP showed different steps of histological transformation: focal intestinal metaplasia in two, focal dysplasia in one, and focal carcinoma in two of them, which is 1.6%, 0.8%, and 1.6%, respectively. In 1/23 adenomas, focal carcinoma developed after 1 yr of observation (4.3%). Separate gastric carcinomas developed outside polyps during follow-up in 2/58 (3.5%) patients with hyperplastic polyps only. None of those with FH had focal carcinoma either at primary biopsy or during long-term observation. All proportions concerning gradual transformation of hyperplastic polyps classified as only one group according to WHO were lower. CONCLUSIONS: In contrast to hitherto existing opinions, our results give support to the idea that gastric HP, like adenomas, are susceptible to malignant transformation. It seems sensible to separate a subgroup of FH from HP, since FH have no malignant potential until they change their histology to HP. The treatment of FH and HP as one group is the main reason why the malignant potential of hyperplastic polyps is still underestimated.

Diving injuries: a preventable catastrophe.

During a 5-year period from January 1987 through January 1992, 58 patients were admitted to the Allegheny General Hospital trauma center for non-scuba, non-suicidal diving injuries. There were 46 men and 12 women (mean age, 23 years). Forty-five patients were injured in swimming pools. Twenty-two patients had blood alcohol levels > 100 mg/dL. Cervical spine injury was the most common pathologic entity encountered in this group of patients. Closed head injury, pelvic fracture, thoracic vertebral fracture, and rib fractures were other injuries identified. Some patients had multiple organ failure syndrome. Aquatic recreational activities carry a risk for injury that is preventable. The mechanism, clinical data, and complications of 58 patients are presented and the importance of prevention is discussed.

Squamous cell papillomas of the esophagus: report of 20 cases and literature review.

A series of 20 patients with 24 squamous cell papillomas of the esophagus are presented. Nonspecific symptoms not directly connected with esophageal disorders were the reason for esophagoscopy. Clinical findings, treatment, and follow-up of the patients in the context of the world literature review of 141 cases reported to date, are discussed.