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Biomedical subjects

J G Moore

Publications and source records attributed to J G Moore.

At least 55 records · Page 3Linked to original sources

Intragastric pH and pharmacokinetics of intravenous ranitidine during sinusoidal and constant-rate infusions.

Six patients with healed duodenal ulcer completed two treatment periods with continuous i.v. infusion ranitidine. A 25-mg i.v. bolus was followed by a constant infusion at 6.25 mg/h or a sinusoidal infusion with infusion rates ranging from 3.125 to 9.375 mg/h. The sinusoidal infusion rate was designed to match the previously observed circadian changes in basal acid secretion. The peak infusion rate occurred at 19:30 h. A pharmacokinetic method was designed to predict the resultant plasma concentrations of ranitidine. Intragastric pH and plasma ranitidine concentration data were fit to a cosine function to evaluate circadian and ultradian rhythms. Plasma concentrations during the sinusoidal infusion exhibited a circadian rhythm according to model predictions. Cosinor analyses of the mean ranitidine plasma concentration data showed a mesor concentration of 237 ng/mL and amplitude of 76 ng/mL (coefficient of determination [CD] = 0.98). The acrophase in plasma concentration occurred at 2223 h, a delay of approximately 2.9 hours from the peak in the infusion rate. The constant-rate infusion resulted in a mean plasma concentration of 222 +/- 32 ng/mL. The 24-h mean intragastric pH values for the sinusoidal and constant regimens were 5.4 and 5.1, respectively (p = 0.170). The intragastric pH during the constant-rate infusion exhibited a significant circadian rhythm (CD = 0.52). The minimum pH (bathy-phase) occurred at 2031 h. No circadian rhythm was present during the sinusoidal-rate infusion (CD = 0.08). At the approximate time of the peak basal acid secretion, between 21:00 hours and midnight, the mean pH for the sinusoidal infusion was 5.77 versus 4.5 for the constant-rate infusion (p = 0.112). Sinusoidal infusions or alternate methods of increased doses at the times of peak acid output may improve around-the-clock control of intragastric pH.

Adult↗

13C-bicarbonate breath test as a measure of gastric emptying.

Radionuclide studies are widely used to estimate the gastric emptying rate of solids and liquids. Unfortunately, these methods carry the risk of radiation exposure and require expensive and complex equipment. Carbon-13, a stable, nonradioactive isotope, has been used successfully as a marker in the gastrointestinal tract for other purposes. A preliminary study using ingested NaH13CO3 and measuring 13CO2 breath excretion suggested that this test might be a simple, noninvasive, and inexpensive method for determining gastric emptying. To determine the efficacy of NaH13CO3 as a noninvasive marker for gastric emptying, the resulting 13CO2 breath excretion was determined simultaneously with standard radiolabeled meal measurements of gastric emptying of liquids and solids in 15 patients. 13CO2 breath excretion did not correlate with the gastric emptying of either solids or liquids, as determined by radionuclide techniques. These results suggest that NaH13CO3 is not a reliable indicator of gastric emptying. Factors other than gastric emptying may affect the rate of 13CO2 absorption and exhalation, rendering it unreliable as a measure of gastric emptying.

Adult↗

Confirmation of short solid-food lag phase by continuous monitoring of gastric emptying.

Reports on the existence of a lag phase before solid-food gastric emptying are conflicting. We studied solid-phase gastric emptying in ten normal-weight male subjects using two opposed cameras and continuous monitoring. Each ingested a 300-g meal containing 99mTc-labeled liver pate. Identical computer-interfaced cameras continuously monitored gastric activity from anterior and posterior projections. Lag phase was determined by three techniques: (1) inspection of the emptying curve; (2) time to a 2% decrease in stomach activity; and (3) the time of visual appearance of duodenal activity. A short lag phase time was found using all methods, averaging 8.6 min. We concluded that a short solid meal lag phase exists that can be missed with conventional radionuclide gastric emptying methods not employing continuous measurements.

Food↗

Exercise increases solid meal gastric emptying rates in men.

Gastric emptying rates of radiolabeled beef stew meals were measured in 10 healthy, young (median age = 27 years) male subjects on each of three randomly chosen study days. The subjects either (1) stood at rest, (2) walked on an exercise treadmill at 3.2 km/hr, or (3) at 6.4 km/hr during the study while gastric emptying was being monitored by externally positioned gamma cameras. Compared to the standing at rest study, exercise significantly increased gastric emptying (at rest emptying half-time (t1/2) = 72.6 +/- 7.6 (SEM) min; 3.2 km/hr t1/2 = 44.5 +/- 3.9 min, P = 0.0051; 6.4 km/hr t1/2 = 32.9 +/- 1.9 min, P = 0.0051). The 6.4 km/hr emptying time was significantly (P = 0.0249) faster than the 3.2 km/hr emptying time. Thus, the amount of exercise is a physiological factor that alters solid meal gastric emptying rates.

Adult↗

The impact of a quality assurance process on the frequency and confirmation rate of hysterectomy.

A criteria-based quality assurance process for hysterectomy was instituted at a large teaching hospital. After this process was initiated, the overall frequency of hysterectomy decreased by 24%, p less than 0.001. Significant reductions were seen in hysterectomy rates for the following indications: chronic pelvic pain (77%, p less than 0.0001), recurrent uterine bleeding (46%, p less than 0.001), preinvasive disease of the uterus (55%, p less than 0.005), and severe infection (70%, p less than 0.025). Adenomyosis was the single indication for which an increase in hysterectomy rate was observed. This increase, however, was completely reversed during the last 2 years of the study. This quality assurance process also resulted in a significant increase in the histologic verification rate (i.e., 82% vs 93%, p less than 0.001). These observations suggest that using such a criteria-based process can reduce the number of hysterectomies performed and improve the accuracy of the preoperative diagnosis.

California↗

Competitive titration in living sea urchin embryos of regulatory factors required for expression of the CyIIIa actin gene.

Previous studies have located some twenty distinct sites within the 2.3 kb 5' regulatory domain of the sea urchin CyIIIa cytoskeletal actin gene, where there occur in vitro high-specificity interactions with nuclear DNA-binding proteins of the embryo. This gene is activated in late cleavage, exclusively in cells of the aboral ectoderm cell lineages. In this study, we investigate the functional importance in vivo of these sites of DNA-protein interaction. Sea urchin eggs were coinjected with a fusion gene construct in which the bacterial chloramphenicol acetyltransferase (CAT) reporter gene is under the control of the entire CyIIIa regulatory domain, together with molar excesses of one of ten nonoverlapping competitor subfragments of this domain, each of which contains one or a few specific site(s) of interaction. The exogenous excess binding sites competitively titrate the available regulatory factors away from the respective sites associated with the CyIIIa.CAT reporter gene. This provides a method for detecting in vivo sites within the regulatory domain that are required for normal levels of expression, without disturbing the structure of the regulatory domain. We thus identify five nonoverlapping regions of the regulatory DNA that apparently function as binding sites for positively acting transcriptional regulatory factors. Competition with a subfragment bearing an octamer site results in embryonic lethality. We find that three other sites display no quantitative competitive interference with CyIIIa.CAT expression, though as shown in the accompanying paper, two of these sites are required for control of spatial expression. We conclude that the complex CyIIIa regulatory domain must assess the state of many distinct and individually necessary interactions in order to properly regulate CyIIIa transcriptional activity in development.

Actins↗

Achieving pH control in the critically ill patient: the role of continuous infusion of H2-receptor antagonists.

Stress-related gastric mucosal damage is a common occurrence in intensive care unit (ICU) patients. Because of the significant morbidity and mortality associated with this mucosal damage, many ICU patients routinely receive prophylactic therapy, usually with histamine H2-receptor antagonists (H2RAs). Gastric acid secretion occurs in a circadian pattern, with late afternoon and evening surges. H2RAs by continuous infusion may control this uneven pattern of secretion more effectively than H2RAs given by bolus injection. More studies are needed to identify the target ICU population for prophylactic treatment.

Cimetidine↗

Day and night esophageal motor function.

Circadian rhythmic variation has been documented in gastric, small bowel and colonic motility. Morning and evening studies of esophageal motility were performed to assess whether similar rhythmicity exists in esophageal function. Fifteen healthy male subjects were studied twice on separate study days. Esophageal manometry was performed either at 10 AM or 10 PM after a standardized meal given 10 h prior to each study. Lower esophageal sphincter pressures, distal esophageal contractile amplitudes, distal esophageal contractile durations, and the velocity of propagation of peristaltic waves in the proximal and distal esophagus were measured. No significant differences were detected in esophageal function between day and night studies. These findings suggest either 1) nocturnal slowing of gastrointestinal motility is not a generalized characteristic of the entire GI tract, or 2) a two time-point study is not adequate to detect a true circadian rhythm in esophageal motor function.

Adult↗

Pharmacodynamics of intravenous ranitidine after bolus and continuous infusion in patients with healed duodenal ulcers.

Fifteen adult men who had histories of duodenal ulcer disease were studied for 24 hours during treatment with varying intravenous doses of ranitidine (50 mg every 8 hours, 100 mg every 12 hours, 6.25 mg/hr continuous infusion, and 10 mg/hr continuous infusion) and placebo. Gastric pH was monitored under fasting conditions by means of an indwelling pH sensitive electrode. The continuous infusion regimens provided the most constant level of acid suppression. A "breakthrough" decrease in gastric pH began at approximately 6 PM at the 6.25 mg/hr dose level. The drop in pH at the 10 mg/hr dose level was less impressive. Ranitidine, 100 mg every 12 hours, resulted in better acid suppression than the regimen of 50 mg every 8 hours. A gastric pH greater than or equal to 4 was achieved 35 to 50 minutes after the start of administration for all regimens. The median effective concentration (EC50) of ranitidine was approximately 45 ng/ml. Continuous infusion regimens, with a dosage adjustment for the time of day, may be the optimal dosage regimen for patients requiring continuous protection from gastric damage by hydrochloric acid. Bolus loading doses are not required to speed the onset of effect in the clinical setting.

Adult↗

Validation of hysterectomy indications and the quality assurance process.

Hysterectomy is one of the most commonly performed major operations in the United States. Despite efforts to explain its high incidence, the perception remains that a significant number of hysterectomies are unjustified. More indications are listed for hysterectomy than for any other major operation. A quality assurance process is presented that requires the surgeon to select preoperatively one designated indication for each hysterectomy performed. The pathology report is expected to verify the surgical indication in 66% of the cases. The other 34% of hysterectomy specimens are not expected to show tissue pathology based on the listed indication. For these cases, predetermined validation criteria must be satisfied in the surgeon's preoperative note. Applying the process in this series of 584 consecutive hysterectomies, 93% (N = 396) of the "pathology expected" indications were verified by the pathology report and 98% (N = 188) of the "no pathology expected" indications were validated by the surgeon's preoperative note. The process of using a single designated indication and reviewing only two documents (the pathology report and the surgeon's preoperative note) has greatly simplified the quality assurance process. This system enables a quality assurance committee to monitor easily the appropriateness of hysterectomy indications for their institution. Information obtained from this process can influence changes regarding the acceptability of certain indications. As a result of this study, adenomyosis, because of its low (38%) verification rate, is no longer considered a reliable preoperative indication for hysterectomy at San Diego Naval Hospital.

California↗

NSAID-induced gastropathy in the elderly: understanding and avoidance.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant cause of gastric mucosal injury and bleeding, particularly in elderly patients. The mechanism of this injury appears to be, at least in part, a disruption of normal cytoprotective mechanisms by the inhibition of prostaglandin production. Acute injury results from the local effect of some drugs and may resolve with time. Chronic injury may occur with any NSAID and may often be asymptomatic until a complication occurs. Treatment of either lesion centers around NSAID withdrawal and standard ulcer therapy. Although routine prophylaxis of all patients is not indicated, those patients with a history of NSAID injury or other risk factors may need preventive measures if they are treated with NSAIDs. Oral prostaglandins, such as misoprostol, are effective in the prevention of NSAID-induced injury. The efficacy of sucralfate and H2-blockers in this setting appears promising but requires further study.

Age Factors↗

Elevated levels of GM-CSF and IL-1 in the serum, peritoneal and pleural cavities of GM-CSF transgenic mice.

Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the peritoneal and pleural cavity fluid of two lines of GM-CSF transgenic mice were abnormally high (up to 120,000 U/ml), often exceeded the elevated serum GM-CSF levels in these mice and correlated with the increased number of macrophages present. In the peritoneal fluid, the only significant elevations of IL-1 levels were seen in moribund male-line transgenic mice. In contrast, IL-1 levels in pleural cavity fluid of male-line transgenic mice were clearly higher than those in littermate control mice or female-line transgenic mice. In male-line transgenic mice, IL-1 levels in both peritoneal and pleural cavities correlated with local macrophage numbers. Endotoxin was detectable in the peritoneal cavity fluid from some mice of all types but did not correlate with elevated IL-1 levels. No correlation was observed between levels of GM-CSF or IL-1 in the peritoneal cavity and the development of fibrotic nodules in the peritoneal cavity or gut congestion, two lesions common in male-line GM-CSF transgenic mice. The data suggest that the elevated levels of IL-1 in GM-CSF transgenic mice may be the consequence of stimulation by GM-CSF of IL-1 production by the elevated numbers of macrophages in these mice.

Animals↗

Effect of body posture on radionuclide measurements of gastric emptying.

The purpose of this investigation was to compare the effect of body posture on gastric emptying measurements of radiolabeled meals. Eight healthy male subjects were studied on four separate days. During each study subjects were fed a standardized meal of beef stew labeled with technetium-99m sulfur colloid, and orange juice. Measurements of solid-phase gastric emptying rates were obtained by a gamma camera. Subjects were studied in the lying, sitting, standing, or combined sitting-standing postures. The results demonstrated that the lying position significantly slowed gastric emptying compared to all other positions. Conversely, a decrease in emptying times of 51% and 35% occurred in the combined sitting-standing position compared to the lying and sitting position. These results support a marked effect of body posture on the radionuclide measurement of gastric emptying.

Adult↗

The clinical implications of retroperitoneal endometriosis.

Over the past 10 years five patients with endometriosis involving only retroperitoneal structures in the pelvis without intraperitoneal involvement have been managed at the University of California-Los Angeles Hospital. These patients have presented difficult diagnostic and therapeutic problems. Moreover, this interesting but uncommon distribution of the disease has led to speculation concerning its pathogenesis. The substantial threat to the urinary tract and rectosigmoid colon is noted. Although a concurrent study at this hospital indicates a low incidence of endometriosis involving pelvic lymph nodes, it is quite apparent from the distribution of these instances of retroperitoneal involvement that its spread from the endometrium very likely takes place through pelvic lymphatics.

Adult↗

Divergent disease patterns in granulocyte-macrophage colony-stimulating factor transgenic mice associated with different transgene insertion sites.

A comparison was made of disease development in two lines of transgenic mice in which the granulocyte-macrophage colony-stimulating factor (GM-CSF) transgene was inserted in different chromosomal locations. Female-line mice (X chromosome insertion) had equivalent elevations of serum GM-CSF levels to those in male-line mice (autosomal insertion) but a shorter survival (median survival, 95 versus 145 days) and a significantly higher incidence of large inflammatory foci in skeletal muscle and gut congestion. Male-line transgenic mice had higher levels of cells in the peritoneal cavity and a higher frequency of spleen enlargement with excess erythropoiesis than female-line mice and uniquely developed fibrotic nodules in the abdominal and pleural cavities. The various diseases in GM-CSF transgenic mice are likely to have been induced by GM-CSF-stimulated products of macrophages, and in the two transgenic lines the macrophages exhibit characteristic differences in morphology and possibly functional activity.

Animals↗

AM and PM measurement of gastric potential difference and prostacyclin production in humans: effects of ranitidine.

It has been previously documented that aspirin induced gastric injury of healthy male volunteers was greater in the morning than in the evening. We have also reported that fasting gastric acid secretion rates and gastric retention times for solids were lower in the morning hours of the circadian cycle. We hypothesized, therefore, that defensive factors in the human stomach may exhibit circadian rhythmicity with greater vulnerability to noxious agents during the morning hours. It has also been hypothesized that an antisecretory agent, with reported protective effects, such as Ranitidine, would affect gastric defense mechanisms differently at different times in the circadian cycle. Transmural electrical potential difference (PD) and prostacyclin (PGI2) production by mucosal biopsy specimens were chosen as putative indicators of gastric defensive status. Accordingly, morning (1000) and evening (2200) studies were performed on 10 fasting healthy male subjects with and without oral Ranitidine (150 mg) given 3 hr before oro-gastric intubation for the measurement of PD and the removal of mucosal biopsy samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗