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Biomedical subjects

N Maynard

Publications and source records attributed to N Maynard.

7 recordsLinked to original sources

EpCAM and gpA33 are markers of Barrett's metaplasia.

AIMS: To characterise a specific and sensitive marker of Barrett's metaplasia (BM). METHODS: Cases of normal oesophageal squamous mucosa (11 fresh endoscopic biopsies and 10 formalin fixed, paraffin embedded tissue blocks), BM (11 biopsies and 11 tissue blocks), and normal gastric body mucosa (five biopsies and five tissue blocks) were analysed using reverse transcriptase PCR, Western blotting, and immunohistochemistry for EpCAM, and reverse transcriptase PCR for gpA33. RESULTS: Strong EpCAM mRNA expression was detected in all the BM cases, in contrast to weak expression in all the normal gastric mucosal samples and no expression in any of the normal oesophageal mucosal samples tested. Strong gpA33 mRNA expression was detected in all the BM cases, in contrast to weak expression in a quarter of the normal gastric mucosal samples and no expression in any of the normal oesophageal mucosal samples tested. Western blotting showed EpCAM protein expression in all the BM cases and in none of the normal gastric or oesophageal mucosal samples tested. Immunohistochemistry showed strong EpCAM protein expression in BM and complete absence of expression in normal oesophageal squamous epithelium. Scattered EpCAM expressing cells were found in the gland bases of normal gastric body mucosa. CONCLUSIONS: EpCAM protein and gpA33 mRNA expressions are specific and sensitive markers of BM.

Antigens, Neoplasm↗

CDX1 is an important molecular mediator of Barrett's metaplasia.

The molecular pathogenesis of Barrett's metaplasia (BM) of the esophagus is poorly understood. The change to an intestinal phenotype occurs on a background of esophagitis due to refluxing acid and bile. CDX1, an important regulator of normal intestinal development, was studied as a potential key molecule in the pathogenesis of BM. CDX1 mRNA and protein were universally expressed in all samples of BM tested but not in normal esophageal squamous or gastric body epithelia. This tissue-specific expression was attributable to the methylation status of the CDX1 promoter. Conjugated bile salts and the inflammatory cytokines TNF-alpha and IL-1beta were all found to increase CDX1 mRNA expression in vitro. These effects were primarily mediated by NF-kappaB signaling but only occurred when the CDX1 promoter was unmethylated or partially methylated. The data suggest that CDX1 is a key molecule linking etiological agents of BM to the development of an intestinal phenotype. Although the initial trigger for CDX1 promoter demethylation is not yet identified, it seems likely that demethylation of its promoter may be the key to the induction and maintenance of CDX1 expression and so of the BM phenotype.

Barrett Esophagus↗

Assessment of splanchnic oxygenation by gastric tonometry in patients with acute circulatory failure.

OBJECTIVE: To investigate the importance of splanchnic ischemia in patients with acute circulatory failure by comparing gastric intramucosal pH as measured by tonometry with conventional methods of assessing adequacy of tissue oxygenation. DESIGN: Prospective cohort of patients with acute circulatory failure in first 24 hours after admission to the intensive care unit. SETTING: Two general intensive care units in London, England. PATIENTS: Consecutive sample of 83 patients of varying diagnostic categories that required pulmonary artery catheterization. MAIN OUTCOME MEASURES: Gastric intramucosal pH and hemodynamic, oxygen transport, and metabolic variables were measured on admission and at 12 hours and 24 hours after admission. Prediction of outcome (death or survival) by each measurement was assessed by sensitivity, specificity, and logistic regression analysis. RESULTS: Mean 24-hour Acute Physiology and Chronic Health Evaluation (APACHE II) score was 20.3. There were significant differences in mean gastric intramucosal pH between survivors and nonsurvivors on admission and at 24 hours, (7.40 vs 7.28, 7.40 vs 7.24, respectively; P < .001). Admission heart rate was higher (116 vs 101 beats per minute; P < .003) and mean arterial pressure lower (82 vs 97 mm Hg; P < .01) in nonsurvivors. There were no consistent differences in cardiac index, oxygen delivery, and oxygen uptake between survivors and nonsurvivors. Admission arterial pH was significantly lower (7.3 vs 7.36; P < .003), base excess more negative (-5.3 vs -1.9; P < .001), and lactate concentration higher (3.14 vs 1.91 mmol/L; P < .03) in nonsurvivors. Gastric intramucosal pH had a sensitivity of 88% for predicting death and a likelihood ratio of 2.32, higher than for any other variable. Only gastric intramucosal pH at 24 hours independently predicted outcome. CONCLUSIONS: Gastric intramucosal pH was the most reliable indicator of adequacy of tissue oxygenation in this group of patients. Inadequate regional blood flow as detected by a reduction in gastric intramucosal pH, but not by systemic measures, is an important contributor to morbidity and mortality in intensive care units.

Aged↗

Post-myelogram headache--physiological or psychological?

Psychological aspects of post-lumbar puncture headache have hitherto received little attention. A hundred consecutive patients admitted for elective myelography were studied. Post-myelogram headache was assessed by an independent observer and found to be strongly associated with normality of the test (P less than 0.001). Psychological testing showed a trend between Hospital Anxiety Depression score and normality of myelogram as well as development of headache, although this did not achieve statistical significance. This study suggested that there is a large psychological as well as organic component to post-myelogram headache.

Adolescent↗

Feeding the critically ill patient.

Evidence for the active role of the gut in multiple organ failure has turned attention away from total parenteral nutrition back to enteral nutrition as the optimal nutritional support in the critically ill. With proper feeding protocols it is possible to feed enterally the most critically ill patients.

Decision Trees↗