Detection of oxidative DNA damage in oesophageal biopsies of patients with reflux symptoms and normal pH monitoring.

BACKGROUND: Gastro-oesophageal reflux has been shown to induce oxidative DNA damage. AIM: To determine whether oxidative DNA damage, detected in oesophageal biopsies by simple immunohistochemical staining, correlates with gastro-oesophageal reflux disease as determined by pH monitoring. METHODS: The study included 47 patients with reflux symptoms who had oesophageal biopsy and 24-h pH monitoring studies performed within 3 months of each other with no variation in treatment in the time between the two procedures. Sections of formalin-fixed and paraffin-embedded oesophageal biopsies were stained for 8-hydroxy-2'-deoxyguanosine using the standard immunoperoxidase method. Positive nuclear immunoreactivity was considered to indicate oxidative DNA damage. RESULTS: Seven (33%) of the 21 cases with normal 24-h pH monitoring results were negative for oxidative DNA damage, compared with only two (8%) of the 26 cases with abnormal 24-h pH results (P=0.058, two-sided Fisher's exact test). Five of the patients with normal 24-h pH results had oesophageal biopsies performed within 24 h of the monitoring procedure and, of these, four (80%) were positive for oxidative DNA damage, including a case in which both biopsy and 24-h pH monitoring were performed on the same day whilst the patient was on proton pump inhibitor therapy. All cases with normal 24-h pH results and positive oxidative DNA damage showed features of reflux on routine morphological evaluation. CONCLUSIONS: Oxidative DNA damage can occur in the absence of acid reflux and despite adequate antisecretory therapy. This may indicate that other agents, such as bile, can induce oxidative DNA damage in an acid-suppressed environment. The significant discordance between oxidative DNA damage and 24-h pH results makes the determination of oxidative DNA damage a poor surrogate marker for 24-h pH monitoring.

Heterotopic bone formation in rectal carcinoma. Case report and literature review.

A case of heterotopic bone formation in a primary rectal adenocarcinoma was recently observed in a 54-year-old woman. This unusual finding was present both in the diagnostic biopsy and in the subsequently resected bowel. Pertinent gross and microscopic features are presented. This report represents the twelfth case in the literature of heterotopic bone formation in a primary rectal adenocarcinoma and the first such finding in a colonic biopsy from one of these malignancies. The average age of these patients was 56 years (range 32-72) and the male-to-female ratio was 5:7. The rectum is the most common site of ossification in the gastrointestinal tract. The exact mechanism of heterotopic ossification is unknown, but it is probably the result of metaplasia of fibroblasts. Adenocarcinoma has been associated with 12 of the 16 reported cases of rectal glandular tumors with heterotopic bone.

Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings.

To determine the accuracy of echocardiographic left ventricular (LV) dimension and mass measurements for detection and quantification of LV hypertrophy, results of blindly read antemortem echocardiograms were compared with LV mass measurements made at necropsy in 55 patients. LV mass was calculated using M-mode LV measurements by Penn and American Society of Echocardiography (ASE) conventions and cube function and volume correction formulas in 52 patients. Penn-cube LV mass correlated closely with necropsy LV mass (r = 0.92, p less than 0.001) and overestimated it by only 6%; sensitivity in 18 patients with LV hypertrophy (necropsy LV mass more than 215 g) was 100% (18 of 18 patients) and specificity was 86% (29 of 34 patients). ASE-cube LV mass correlated similarly to necropsy LV mass (r = 0.90, p less than 0.001), but systematically overestimated it (by a mean of 25%); the overestimation could be corrected by the equation: LV mass = 0.80 (ASE-cube LV mass) + 0.6 g. Use of ASE measurements in the volume correction formula systematically underestimated necropsy LV mass (by a mean of 30%). In a subset of 9 patients, 3 of whom had technically inadequate M-mode echocardiograms, 2-dimensional echocardiographic (echo) LV mass by 2 methods was also significantly related to necropsy LV mass (r = 0.68, p less than 0.05 and r = 0.82, p less than 0.01). Among other indexes of LV anatomy, only measurement of myocardial cross-sectional area was acceptably accurate for quantitation of LV mass (r = 0.80, p less than 0.001) or diagnosis of LV hypertrophy (sensitivity = 72%, specificity = 94%).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of hemodynamic load to left ventricular hypertrophy and performance in hypertension.

Left ventricular hypertrophy and dysfunction in patients with hypertension are often poorly related to the level of blood pressure. To evaluate the reasons for this, 100 untreated patients (44 +/- 14 years) with essential hypertension were studied using cuff blood pressure and quantitative echocardiography to measure left ventricular mass index and end-diastolic relative wall thickness as 2 indexes of left ventricular hypertrophy. Left ventricular hypertrophy, as measured by either left ventricular mass index or end-diastolic relative wall thickness, correlated weakly with all indexes of blood pressure including systolic, diastolic, and mean blood pressure (r = 0.16 to 0.32). In contrast, end-diastolic relative wall thickness, an index which assesses the severity of concentric hypertrophy, showed a closer direct relation with total peripheral resistance (r = 0.52 p less than 0.001) and a significant inverse relation with cardiac index (r = -0.47, p less than 0.001). Left ventricular performance as assessed by fractional systolic shortening of left ventricular internal dimensions was not significantly related to left ventricular mass index, blood pressure, or peak systolic wall stress, but declined significantly with increasing mean systolic wall stress (r = -0.42, p less than 0.001) and even more with increasing end-systolic wall stress (r = -0.71, p less than 0.001). It is concluded that in patients with hypertension (1) left ventricular hypertrophy is correlated only modestly with measurements of resting blood pressure; and (2) the classic pattern of concentric left ventricular hypertrophy, as measured by relative wall thickness, is more closely related to the "typical" hypertensive abnormality of elevated peripheral resistance, suggesting that these anatomic and hemodynamic changes may be pathophysiologically interdependent. Furthermore, left ventricular performance declines when the pressure overload in hypertension is not offset by compensating hypertrophy, allowing wall stresses to increase.

Inheritance of mitral valve prolapse: effect of age and sex on gene expression.

To ascertain if mitral valve prolapse is inherited we studied 45 probands and 179 first-degree relatives. Echocardiographic mitral prolapse was present in 54 of 179 first-degree relatives (30%); at least one first-degree relative was affected in 29 families, including members of two generations in 23 families. The number of affected persons in the 54 sibships fell within the range predicted for autosomal dominant inheritance. The familial prevalence of prolapse was similar whether or not the proband had characteristic symptoms, auscultatory abnormalities, electrocardiographic findings, thoracic bony abnormalities, or coexistent heart disease. Mitral prolapse occurred in 37 of 90 women (41%) but 17 of 89 men (19%; p less than 0.005), and in 51 of 143 adults (35%) but only 3 of 36 children aged 1 to 15 (p less than 0.005). Mitral valve prolapse is an inherited autosomal dominant condition irrespective of clinical findings, and the mitral prolapse gene shows age and sex dependent expression. Mitral valve prolapse appears to be the commonest mendelian cardiovascular abnormality in humans.

Scanning electron microscopy of spore germination in Dictyostelium discoideum.

The ellipsoidal dormant spores of Dictyostelium dicoideum prepared by freeze-drying had a uniform, compact appearance with fine wrinkles or ridges on the surface. Swollen spores were uneven in appearance, without fine wrinkles but with a seemingly expanded surface covering. The surfaces of the postgermination spore husks appeared unaltered except for a single straight exit slit along the longitudinal plane.