Inclusion of supine period in short-duration pH monitoring is essential in diagnosis of gastroesophageal reflux disease

Prolonged esophageal pH monitoring is the most accurate method for detecting abnormal gastroesophageal reflux (GER) in patients with gastroesophageal reflux disease (GERD). However, some investigators have found that short-duration postprandial pH monitoring in the upright position is also useful, while others have failed to find such results. Therefore, we have compared a 6-hr period of pH monitoring (3-hr postprandial period after daytime meal and 3-hr supine period) with a total 24-hr period in detecting abnormal gastroesophageal reflux. Sixty-five patients (44 men, mean age 41.3 years) with GERD and 16 healthy volunteers (11 men, mean age 34.3 years) underwent 24-hr pH monitoring according to a standard protocol. Various reflux parameters during 24-hr pH monitoring were compared with reflux parameters during the 6-hr period. Abnormal GER was detected in 56 patients presenting with typical symptoms of GERD (sensitivity 86.2%). These patients could be further divided into upright (N=18), supine (N=15), and combined (N=23) refluxers, depending on the posture in which abnormal reflux occurred. Esophageal pH monitoring during the 3-hr postprandial upright period showed abnormal reflux in only 35 patients (sensitivity 53.8%;P<0.00005, compared with the 24-hr pH monitoring period). Abnormal GER was identified in 13 of 18 upright, 19 of 23 combined, and only one of 15 supine refluxers, as well as in two of nine patients with normal 24-hr pH-metry. However, inclusion of the 3-hr supine monitoring period in the 3-hr postprandial upright period improved detection of abnormal GER to 78.5% (51 patients;P=NS compared with 24-hr pH monitoring period). This was related mainly to improved detection of abnormal GER in supine refluxers (11 of 15; 73.3%). Esophageal acid exposure time correlated significantly with severity of esophagitis only during the total and supine periods of both the 24- and 6-hr periods and not during the upright period. Esophageal acid clearance correlated significantly with increasing grades of esophagitis for the supine and total periods only. We conclude that 3-hr postprandial pH monitoring, as has been conventionally practiced, is not appropriate in the detection of abnormal GER; inclusion of a supine period in the short-duration pH monitoring schedule increases the detection of pathological reflux. We therefore recommend that a supine period should be included in short-duration pH monitoring schedules. We also found that supine reflux was the most important factor in the development of esophagitis.     

Preload reduction with right ventricular pacing: Effects on left ventricular hemodynamics and contractile pattern

Studies were performed in 32 patients to evaluate left ventricular pressure-volume changes and contractile pattern during right ventricular pacing as compared to normal sinus rhythm. Coronary artery disease was present in 27 patients, while 5 patients (control group) had no evidence of coronary artery or left ventricular disease. Studies were performed during both normal sinus rhythm and right ventricular pacing at comparable heart rates, utilizing angiographic methods to determine heart volumes. Right ventricular pacing in all patients resulted in decreased left ventricular systolic (p< 0.01) and diastolic (p< 0.01) pressures and decreased stroke work (p< 0.001). In the control group, right ventricular pacing caused a decrease in left ventricular end-diastolic volume (p< 0.01) and stroke volume (p< 0.01), with no change in ejection fraction. The patients with coronary artery disease were divided into four groups, dependent on the left ventricular contractile pattern during normal sinus rhythm and the percentage of change in hemiaxis shortening during right ventricular pacing. In group A (six patients with asynergy) and group B (seven patients with asynergy), there was no significant change in the percentage of hemiaxis shortening during right ventricular pacing when compared to normal sinus rhythm. Ventricular volume studies in these patients (groups A and B) were similar to the control groups and no change in contractile pattern was observed during pacing. In group C, twelve patients had asynergy and a 10% increase in percentage of hemiaxis shortening during right ventricular pacing when compared to normal sinus rhythm. Right ventricular pacing resulted in decreased end-diastolic pressure (p< 0.01) and end-diastolic volume (p< 0.001), no change in stroke volume, and an increased ejection fraction (p< 0.01). Contractile patterns improved in all patients in group C during pacing. Group D consisted of two patients with asynergy and a 10% decrease in percentage of hemiaxis shortening during pacing, associated with a decrease in end-diastolic volume and ejection fraction with deterioration of left ventricular contractile pattern. These results indicate that right ventricular pacing in patients with coronary artery disease decreases preload, which may be accompanied by improved left ventricular contractile pattern (11/27) and in some patients (2/27) deterioration of left ventricular function.     

Sleep disordered breathing – a new component of syndrome x?

Sleep disordered breathing (SDB) is a complication of obesity estimated to occur in about 4–6% of overweight individuals. These respiratory disturbances during sleep incorporate a number of conditions including snoring, upper airway resistance syndrome and obstructive sleep apnoea syndrome (OSAS). It is thought that as well as having deleterious effects on sleep quality these conditions may also promote cardiovascular and hormonal changes leading to an elevated blood pressure and an increased incidence of cardiovascular morbidity. Evidence reviewed here points to an alteration in sympathovagal balance, baroreceptor sensitivity, insulin resistance and leptin, growth hormone and lipid levels. Whether these changes are a consequence of the associated obesity or the SDB itself remains to be proven.     

Role of bacterial toxins,bile acids,and free fatty acids in colonic water malabsorption in tropical sprue

Colonic perfusion studies in 10 southern Indian patients with tropical sprue and nine matched healthy adults revealed a defect of water and sodium absorption from the colon in sprue. Heat-labile and heat-stable enterotoxin production was not detected in coliforms cultured from the feces of any of the 19 subjects. The 24-hr fecal bile acid output was increased in patients with sprue, but fecal aqueous bile acid concentrations remained within normal limits, and these did not correlate with defects in colonic water and sodium absorption. Fecal free fatty acid excretion was markedly increased in sprue. There was a negative correlation between fecal excretion of unsaturated free fatty acids and colonic water and sodium absorption.     

Platelets modulate the proteolysis of factor VIII:C protein by plasmin

Factor VIII coagulant protein (VIII:C) functions as a critical cofactor with factor IXa, calcium ions, and phospholipid during the activation of factor X. In the course of this reaction, the activity of VIII:C is first increased and then is destroyed by one or more serine proteases that are part of the coagulation sequence. In this study, we have investigated the influence of platelets on the inactivation of VIII:C by plasmin. Platelets were separated from plasma proteins in the presence of granule release inhibitors and were incubated with plasmin and isolated VIII:C or the complex of purified VIII:C/von Willebrand factor (vWF); VIII:C activity and antigen levels were assessed over time. In the presence of platelets, the isolated VIII:C showed an initial increase in VIII:C activity that was not present when platelets were absent, and the VIII:C/vWF showed an increase in VIII:C activity over that seen when platelets were absent. In addition, platelets stabilized VIII:C activity over a one-hour time course when compared with buffer. The VIII:C antigen did not increase and decreased slowly whether platelets were present or absent. Preincubating the platelets with ristocetin, collagen, or plasmin did not alter the results, and experiments using platelets from a patient with severe von Willebrand's disease also showed a pattern similar to that seen with normal platelets. Experiments using fixed platelets or phospholipid vesicles showed that they did not support the activation reaction or delay the inactivation reaction. These studies demonstrate that platelets modulate the activation and inactivation of VIII:C by plasmin, apparently by a mechanism that is independent of the platelet release reaction.