Upper gastrointestinal pH in seventy-nine healthy, elderly, North American men and women.

Gastric and duodenal pH levels were measured in 79 healthy, elderly men and women (mean +/- SD = 71 +/- 5 years) under both fasted and fed conditions using the Heidelberg capsule technique. The pH was recorded for 1 hr in the fasted state, a standard liquid and solid meal of 1000 cal was given over 30 min, then the pH was measured for 4 hr postprandially. Results are given as medians and interquartile ranges: fasted gastric pH, 1.3 (1.1-1.6); gastric pH during the meal, 4.9 (3.9-5.5); fasted duodenal pH, 6.5 (6.2-6.7); and duodenal pH during the meal, 6.5 (6.4-6.7). Although fasted gastric pH, fasted duodenal pH, and duodenal pH during the meal differ statistically from those observed in young subjects, the differences are not expected to be clinically significant in terms of drug absorption for the majority of elderly subjects. Following a meal, gastric pH decreased from a peak pH of 6.2 (5.8-6.7) to pH 2.0 within 4 hr in most subjects. This rate of return was considerably slower than in young, healthy subjects. Nine subjects (11%) had a median fasted gastric pH > 5.0, and in five of these subjects the median pH remained > 5.0 postprandially. In this group, drugs and dosage forms which require an acidic environment for dissolution or release may be poorly assimilated.

Effects of preoperative electrical stimulability and historical factors on performance with multichannel cochlear implant.

We investigated the relationship between results of preoperative transtympanic electrical promontory stimulation, duration of deafness, postoperative implanted psychophysical results, and postoperative speech and speech sound recognition as indicated by a battery of five tests. Our subjects were 10 patients implanted with the Cochlear Corporation multielectrode implant, 1 year postimplantation, with a minimum of 17 active electrodes programmed in the bipolar + 1 mode. The results indicated that preoperative promontory thresholds, the slope of the threshold function, and the duration of auditory deprivation are excellent predictors of postoperative speech and speech sound recognition in the auditory (processor alone) mode. These results have significant implications for patient selection and counseling.

Short-term changes in renal function, blood pressure, and electrolyte levels in patients receiving cyclosporine for dermatologic disorders.

We compared the changes in renal function, blood pressure (BP), and concentrations of serum potassium, magnesium, and urate (uric acid) in two groups of patients not given transplants. Group 1, comprising 21 psoriatic patients, was treated with 14 mg/kg per day of oral cyclosporine for 4 weeks in a prospective, placebo-controlled study; group 2, comprising 28 patients with diverse cutaneous diseases, was given 6 mg/kg per day of oral cyclosporine for 1 to 3 months in a prospective, open-labeled study. Renal function (determined by serum urea nitrogen [SUN] and creatinine levels and urinalysis), BP, serum electrolyte levels (potassium and magnesium), and urate level were measured weekly for the first 4 weeks in both groups, and then, after 2 and 3 months of therapy, in group 2 only. During the first 4 weeks in group 1 patients, there were significant increases in values of SUN, creatinine, BP, potassium, and urate, and a significant decrease in the serum magnesium value. When data for the two groups were combined, the changes from pretherapy values in each of the above measures (except systolic BP) during the first 4 weeks correlated significantly with cyclosporine trough levels. In group 2, the changes that occurred in the first 4 weeks in the SUN value, SUN/creatinine ratio, and BP were magnified over the subsequent 8 weeks of treatment. In the combined group for the first 4 weeks of therapy, duration of therapy, independent of cyclosporine trough levels, correlated with changes in SUN, creatinine, and urate levels, but not with changes in the potassium or magnesium level or in BP. We conclude that the cyclosporine blood level was a better discriminant than cyclosporine dosage in the analysis of renal dysfunction and hypertension in these patients.

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck.

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.

Upper gastrointestinal (GI) pH in young, healthy men and women.

The pH in the upper gastrointestinal tract of young, healthy men and women was measured in the fasting state and after administration of a standard solid and liquid meal. Calibrated Heidelberg capsules were used to record the pH continuously over the study period of approximately 6 hr. In the fasted state, the median gastric pH was 1.7 and the median duodenal pH was 6.1. When the meal was administered the gastric pH climbed briefly to a median peak value of 6.7, then declined gradually back to the fasted state value over a period of less than 2 hr. In contrast to the pH behavior in the stomach, feeding a meal caused a reduction in the median duodenal pH to 5.4. In addition, there was considerable fluctuation in the postprandial duodenal pH on an intrasubject basis. The pH in the duodenum did not return to fasted state values within the 4-hr postprandial observation period. There was no tendency for the duodenal pH to be related to the gastric pH in either the fed or fasted phases of the study. Furthermore, pH in the upper GI tract of young, healthy subjects appears to be independent of gender. The differences in upper GI pH between the fasted and the fed state are discussed in terms of dosage form performance and absorption for orally administered drugs.

Adenosine triphosphate turnover in humans. Decreased degradation during relative hyperphosphatemia.

The regulation of ATP metabolism by inorganic phosphate (Pi) was examined in five normal volunteers through measurements of ATP degradation during relative Pi depletion and repletion states. Relative Pi depletion was achieved through dietary restriction and phosphate binders, whereas a Pi-repleted state was produced by oral Pi supplementation. ATP was radioactively labeled by the infusion of [8(14)C]adenine. Fructose infusion was used to produce rapid ATP degradation during Pi depletion and repletion states. Baseline measurements indicated a significant decrease of Pi levels during phosphate depletion and no change in serum or urinary purines. Serum values of Pi declined 20 to 26% within 15 min after fructose infusion in all states. Urine measurements of ATP degradation products showed an eightfold increase within 15 min after fructose infusion in both Pi-depleted and -supplemented states. Urinary radioactive ATP degradation products were fourfold higher and urinary purine specific activity was more than threefold higher during Pi depletion as compared with Pi repletion. Our data indicate that there is decreased ATP degradation to purine end products during a relative phosphate repletion state as compared to a relative phosphate depletion state. These data show that ATP metabolism can be altered through manipulation of the relative Pi state in humans.