Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study.

BACKGROUND: Cough may be a manifestation of gastro-oesophageal reflux disease (GERD). The utility of acid suppression in GERD-related cough is uncertain. AIM: To assess the impact of high-dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. METHODS: Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24-h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough-Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. RESULTS: Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. CONCLUSION: In subjects with chronic cough and rare or no heartburn, high-dose proton pump inhibitor does not improve cough-related quality of life or symptoms.

Use of computed tomography in the assessment of mandibular invasion in carcinoma of the retromolar trigone.

Carcinomas originating in the retromolar trigone (RMT) are uncommon and characterized by early spread. Determination of mandibular invasion is significant for planning therapy and determining prognosis. For oral cavity cancers in general, CT is reasonably accurate in assessing bone invasion. However, there is a paucity of information specifically addressing the value of CT in the RMT. In this study, the records of patients with biopsy-proven RMT carcinomas treated between 1984 and 1998 were reviewed with attention to preoperative CT scans and histopathologic findings during surgery. Half of the patients who were treated with primary resection had mandibular invasion. Bone invasion was not identified radiographically in 27% of patients with preoperative CT scans. The sensitivity of CT for bone involvement in RMT cancers was 50%, with a negative predictive value of 61.1%. The positive predictive value was 91.1%. These findings suggest that CT is a useful, but potentially inaccurate, predictor of bone invasion in the RMT.

Biologic and biochemical analyses of p16(INK4a) mutations from primary tumors.

BACKGROUND: Point mutations in the tumor suppressor gene p16(INK4a) (also known as p16, CDKN2, MTS1, and INK4a) are found in many tumor types. Because the function of the products of these naturally occurring mutants has not been fully explored, we investigated the functional activities of a wide range of naturally occurring p16 mutant proteins. METHODS: Sixteen cancer-associated p16 mutant proteins, resulting from missense mutations, were characterized for their ability to bind and inhibit the cyclin-dependent kinases (CDK4 and CDK6) and to induce cell cycle arrest in G(1) phase. RESULTS/CONCLUSIONS: Among 16 mutants analyzed, nine had detectable functional defects. Three mutants (D84V, D84G, and R87P) had defects in CDK binding, kinase inhibition, and cell cycle arrest. The corresponding mutations are located in the third ankyrin repeat in a highly conserved region believed to form the CDK binding cleft. Three mutants (P48L, D74N, and R87L) had defects in kinase inhibition and cell cycle arrest. Among the 10 mutants with normal CDK binding and inhibitory activity, three mutants (N71S, R80L, and H83Y) had defects only in their ability to induce cell cycle arrest. Thus, p16 mutant proteins that retain CDK4 and CDK6 binding may have more subtle functional defects. All nine mutations leading to functional impairments mapped to the central portion of the p16 protein. Ankyrin repeats II and III appear more critical to p16 function, and mutations in ankyrin repeats I and IV are less likely to disrupt p16 function.

Physiological assessment of coronary artery disease and myocardial viability in ischemic syndromes using adenosine echocardiography.

We hypothesized that it would be feasible and safe to use adenosine echocardiography to assess the physiological significance of coronary stenoses, detect ischemic myocardium, and assess myocardial viability in a high risk group of patients with coronary artery disease (CAD). Therefore, in 40 patients with either unstable angina, non-Q myocardial infarction, or myocardial infarction treated with thrombolytic therapy, we performed adenosine echocardiography (140 mug/kg per min for 5 mins with a 16 segment model for analysis) and compared the findings with quantitative planar thallium-201 scintigraphy, and (in 26 patients) coronary angiography. The technique was safe, and there were no serious complications. Adenosine resulted in a significant increase in heart rate and decrease in blood pressure. The sensitivity of adenosine echocardiography and thallium scintigraphy were 96% and 88%, respectively, for detecting greater than 75% stenosis. The change in echo score from baseline during adenosine infusion was significantly higher with more severe coronary disease (single vessel right coronary artery {RCA} or left circumflex {LCX} disease = 0.125 +/- 0.15, proximal left anterior descending coronary artery {LAD} disease = 0.23 +/- 0.15, RCA and LCX disease = 0.30 +/- 0.14, LAD and RCA and/or LCX disease = 0.62 +/- 0.13). Likewise, the echo score during adenosine infusion was significantly higher in patients with high risk thallium scans (low risk = 1.29 +/- 0.26, medium risk = 1.74 +/- 0.22, and high risk = 2.21 +/- 0.37). In 13 patients receiving thrombolytic therapy, adenosine echocardiography identified 12 with viable myocardium as defined by quantitative thallium criteria. Furthermore, the wall-motion response of the viable segment was indicative of the degree of stenosis of the artery subtending the segment. Regional function deteriorated in patients with high grade (95 +/- 2%) stenoses and improved in those with nonflow limiting stenoses (66 +/- 25%, P = 0.03). Therefore, we conclude that adenosine echocardiography can detect significant coronary stenoses, has a high degree of concordance with thallium in detecting cardiac perfusion abnormalities, and can assess myocardial viability following thrombolytic therapy.