Search PubMed⌕ Search

Biomedical subjects

M L Allen

Publications and source records attributed to M L Allen.

At least 37 records · Page 2Linked to original sources

Gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin administration.

OBJECTIVES: The purpose of this study was to assess gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin. METHODS: A total of 47 healthy volunteers participated in randomized, controlled acute and chronic trials. Seventeen participated in a repeated measures acute trial, and 30 participated in an independent sample chronic trial. Gastrointestinal blood loss was determined by obtaining 72-hour stool collections and quantitating Chromium-51 labeled erythrocytes. RESULTS: Acute phase trials: gastrointestinal blood loss during base line was 0.47 (+/- 0.11) mL/day, 0.96 (+/- 0.12) mL/day with enteric-coated aspirin (p < 0.0006), and 1.82 (+/- 0.35) mL/day with plain aspirin (p < 0.0001 vs. base line, p = 0.0476 vs. enteric-coated aspirin). Chronic phase trials: gastrointestinal blood loss was 1.12 (+/- 0.31) mL/day with enteric-coated aspirin (p = 0.0024 vs. control) and 2.60 (+/- 0.68) with plain aspirin (p < 0.0001 vs. control, p = 0.0364 vs. enteric-coated aspirin). CONCLUSIONS: During acute and chronic ingestion, plain aspirin at a dose of 325 mg/day significantly increased gastrointestinal blood loss when compared to control or enteric-coated aspirin values, although enteric-coated aspirin values were also significantly increased compared to control. Gastric adaptation does not decrease blood loss with low dose aspirin consumption.

Adaptation, Physiological↗

Properties of voltage-gated K+ currents expressed in Xenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1.

Two similar mouse Shaker-like K+ channel genes, mKv1.1 and mKv1.2, have been shown to form heteromultimers in vivo. The predicted amino acid sequence of each channel is nearly identical in mice, rats and humans, suggesting that each has been highly conserved evolutionarily. Here we report the biophysical and pharmacological properties of each channel when expressed alone or when coexpressed in Xenopus oocytes. The voltage sensitivities of activation were similar for both, but the voltages at which the K+ conductances were half-maximal (V1/2) were -37 mV and -27 mV for mKv1.1 and mKv1.2 respectively. Both displayed voltage-dependent, but incomplete, inactivation following a prepulse with mKv1.2 showing the greater degree of inactivation. For mKv1.1, the onset and recovery from inactivation could be described by single, slow time constants (2-4 s), whereas for mKv1.2 the onset and recovery from inactivation displayed a second, faster time constant (< 400 ms). Using a mutant mKv1.1 that is 100-fold less sensitive to dendrotoxin-I than mKv1.1, we demonstrate that this mutant mKv1.1 and wild-type mKv1.2 subunits can form heteromultimeric channels. With some exceptions, of unknown significance, the biophysical properties of the heteromultimeric channels formed by wild-type mKv1.1 and mKv1.2 subunits were intermediate between those of mKv1.1 and mKv1.2 homomultimers, but quantitatively more similar to the more abundant subunit.

Animals↗

Fecal Clostridium difficile carriage among medical housestaff.

Housestaff, physician assistants, and hospitalized patients at a teaching hospital were tested for fecal carriage of Clostridium difficile. The test results showed that fecal carriage of C. difficile may not be important in the epidemiology of hospital-acquired diarrhea.

Carrier State↗

The pattern of nocturnal and diurnal esophageal acid exposure in the pathogenesis of erosive mucosal damage.

OBJECTIVES: The primary objective of the present investigation was to determine from variables obtained from 24-h esophageal pH monitoring significant discriminators between patients with and without erosive esophageal mucosal damage. METHODS: Data obtained from this study were from 24-h esophageal pH monitoring and the results of upper gastrointestinal endoscopy. Statistical methods included the use of multivariate discriminant analysis. RESULTS: The results revealed that the single best measure which discriminated patients with erosive and nonerosive esophagitis was the number of recumbent reflux episodes lasting greater than 5 min. CONCLUSIONS: We conclude from these data that 1) specific evaluation of recumbent reflux and acid exposure can add substantially to the interpretation of 24-h esophageal pH studies, particularly with regard to identifying patients at risk for the development of erosive esophagitis or other potential complications; 2) esophageal mucosal erosions are associated with an increase in percent acid contact time in both the upright and supine positions, but the pattern of reflux, particularly during the nocturnal interval in terms of the number of episodes greater than 5 min, adds significant predictive value in discriminating patients with erosive mucosal damage.

Adult↗

Intrapleural streptokinase in experimental empyema.

Intrapleural streptokinase has been used in multiloculated empyemas to enhance pleural space drainage, presumably by causing fibrinolysis of the interlocular septae. We evaluated the efficacy and safety of daily administration of 10,000 U intrapleural streptokinase or equal volumes of saline to enhance resolution of experimental empyema in the rabbit pleural space. Seventy-two hours after intrapleural turpentine, 10(8) colony-forming units each of Escherichia coli, Peptostreptococcus anaerobius, and Bacteroides fragilis were injected into the sterile pleural effusion of all animals. Immediately after bacterial inoculation, and daily for 3 days, animals received 10,000 U streptokinase or saline intrapleurally. Animals that achieved a pleural fluid pH < 7.30 and either glucose < 50 mg/dl or LDH > 500 IU/L were included for data analysis. At Day 4 after bacterial inoculation, the streptokinase-treated empyemic rabbits had more pleural fluid (18.8 +/- 5.1 ml) (mean +/- SEM) than did saline-treated control animals (4.8 +/- 1.7 ml) (p = 0.015), fewer interpleural adhesions (8.2 +/- 2.7) than did saline-treated control animals (25.1 +/- 3.6) (p = 0.002), and comparable amounts of visceral and parietal pleural plaque than did saline-treated control animals (p = NS). No evidence of systemic fibrinolysis was observed at 1 h after intrapleural streptokinase administration. We conclude that intrapleural streptokinase decreases interpleural adhesion numbers but fails to reduce the amount of pleural plaque observed in experimental empyema in rabbits. The increases in pleural fluid volume observed after streptokinase administration may be due to mechanisms other than fibrinolytic activity.

Animals↗

A comparison of rotation and nonrotation in tetracycline pleurodesis.

Previously, we have shown rapid and complete dispersion of tetracycline hydrochloride in the pleural space following chest tube instillation. To assess the clinical relevance of this observation, we randomized patients with symptomatic pleural effusions to rotation (R) (n = 19) and nonrotation (NR) (n = 21) groups following administration of tetracycline hydrochloride, 20 mg/kg (n = 30); 300 mg of minocycline hydrochloride (n = 6); and 500 mg of doxycycline hydrochloride (n = 4) through a chest tube. Patients in the R group were maneuvered through six positions for the 2 h that the chest tube remained clamped. The NR patients remained supine for 2 h. Rotation and nonrotation groups were similar in demographics, source of pleural effusion, symptoms, and serum and pleural fluid analyses (all p = NS). A chest radiograph was scored based on pleural fluid recurrence throughout survival or up to 12 months. Survival, duration of chest tube instillation, and success of pleurodesis assessed by radiographic pleural fluid reaccumulation (73.7 vs 61.9 percent; R vs NR) were similar (p = NS). Rotational maneuvers appear to offer no benefit to the success of pleural symphysis after intrapleural instillation of tetracycline class agents.

Aged↗

Using quality focus teams in the diagnostic imaging department.

Quality Focus Teams (QFTs) have become a very effective and popular tool used to address quality issues and improve service. With the recent movement toward total quality management (TQM), or continuous quality improvement (CQI), these teams can play an important role in patient care and the quality of service provided by your department. While teams are not a new concept, they have gained a new popularity in the healthcare field by focusing on service quality. Such teams have been referred to in the past as quality circles or management teams, and were used primarily by manufacturers to address quality issues and implement improvements. They were usually brought together to address a specific problem or crisis. QFTs, on the other hand, usually go a step further by addressing ways of continually improving service or care, even in the absence of a crisis or obvious problem. With the increasingly competitive environment in healthcare and the demands to maintain the highest level of quality possible, QFTs should be a part of every department. This article will provide radiology managers with the basic information needed to begin developing, using and benefitting from QFTs.

Management Quality Circles↗

PKA-dependent regulation of mKv1.1, a mouse Shaker-like potassium channel gene, when stably expressed in CHO cells.

Potassium (K) channels are important regulators of cellular physiology and can themselves be modulated by phosphorylation. We have investigated the potential protein kinase A (PKA) regulation of mKv1.1, a mouse Shaker-like K channel gene, when it is expressed in stably transfected Chinese hamster ovary (CHO) cell lines. Whole-cell patch-clamp records show that expression of mKv1.1 gives rise to a rapidly activating, sustained K+ current, referred to classically as a delayed rectifier-type current. In order to study the effects of PKA, we compared cell lines transfected with mKv1.1 alone with lines cotransfected with both mKv1.1 and a plasmid encoding a dominant negative mutation in the regulatory subunit of PKA. These mutant regulatory subunits bind to endogenous catalytic subunits of PKA but do not respond to cAMP, thereby causing a chronic reduction in the basal PKA activity in these cells. We found that mKv1.1 current kinetics are unaltered but current density is 3.4-fold higher in the cell lines expressing mutant regulatory subunit than in lines expressing only mKv1.1. RNase protection assays indicate that levels of the specific RNA for mKv1.1 are increased almost twofold in the lines expressing mutant regulatory subunit over the lines expressing mKv1.1 only. Further, the levels of mKv1.1 protein, assayed using an mKv1.1 channel-specific antibody, are increased by almost a factor of 3 between the two types of cell lines. These results suggest that PKA can regulate mKv1.1 channel expression by changing steady-state levels of RNA and by other posttranscriptional mechanisms.

Animals↗

Premature lower esophageal sphincter closure as a cause of dysphagia.

Impaired lower esophageal sphincter (LES) relaxation is highly correlated with dysphagia. A variation of the impaired relaxation of the LES of achalasia has been described, characterized by premature closure after normal relaxation. With a microtransducer system, standard manometric testing followed by food ingestion identified 33 patients (12 male, 21 female, 18-79 yr old) who exhibited premature LES closure. Twenty-three (70%) of these patients had a presenting complaint of dysphagia. Of these, seven (30%) experienced dysphagia during food ingestion. Manometry documented a concurrent motor abnormality in the esophageal body in 28 (85%) patients. Of the five remaining patients who did not have a concurrent motor abnormality, all had a presenting complaint of dysphagia, and three (60%) experienced dysphagia during food ingestion. The incidence of dysphagia during testing reported by patients with premature LES closure is comparable to that reported by patients with achalasia (45%) or diffuse esophageal spasm (38%) who have been studied during food ingestion in our laboratory.

Adolescent↗

Isolation and sequence of the cDNAs encoding the subunits of the isozyme form of wheat protein synthesis initiation factor 4F.

The nucleotide sequences of the cDNAs for the two subunits, p82 and p28, of the isozyme form of wheat germ eukaryotic initiation factor 4F (eIF-(iso)4F) were determined. The cDNA for the p82 subunit encodes a polypeptide of 86,514 Da. The deduced amino acid sequence of p82 contains possible motifs for ATP binding, metal binding, and phosphorylation. The cDNA sequence for the small subunit, p28, which is a m7G cap-binding protein, encodes a polypeptide of 23,524 Da. The deduced amino acid sequence of p28 is similar (approximately 38%) to cap-binding proteins from yeast and mammals. The p28 of wheat eIF-(iso)4F does not contain a serine or threonine in the vicinity of the serine (Ser53) of mammalian cap-binding protein which is phosphorylated and shown to affect activity in mammalian cells.

Amino Acid Sequence↗

Sequence of a cDNA encoding the alpha-subunit of wheat translation elongation factor 1.

A cDNA encoding the alpha-subunit of wheat protein synthesis elongation factor 1 (EF-1 alpha) was isolated from a wheat cDNA expression library and sequenced. The deduced amino acid sequence is compared to EF-1 alpha from other species and to elongation factor Tu (EF-Tu) from Escherichia coli. Putative GTP-binding sites are identified.

Amino Acid Sequence↗

Manometry during food ingestion aids in the diagnosis of diffuse esophageal spasm.

It has been shown that food ingestion can provoke esophageal motor abnormalities in patients with otherwise normal manometry. Such motor abnormalities are usually nonspecific in character. We now report water swallow and food ingestion data on 12 patients with a history of dysphagia and/or chest pain who satisfied strict manometric diagnostic requirements for diffuse esophageal spasm. Three of these patients had normal water swallow manometry, yet, during food ingestion, showed manometric evidence of diffuse esophageal spasm. In the other nine patients, the occurrence of nonperistaltic contractions was greater, and there was a greater incidence of nonperistaltic contractions of 100 mm Hg or more after ingestion of food. We conclude that food ingestion increases the diagnostic yield of manometric testing for diffuse esophageal spasm and, not infrequently, magnifies an abnormality seen during standard water-swallow testing.

Adult↗

Effect of different doses of omeprazole on 24-hour oesophageal acid exposure in patients with gastro-oesophageal reflux.

To define the optimum doses of omeprazole appropriate for acute and long-term therapy of patients with gastro-oesophageal reflux disease, 24-h oesophageal pH was measured in 12 patients with symptomatic reflux and an abnormal 24-h oesophageal acid exposure time (greater than 6%) in a randomized, double-blind, four-way crossover study comparing the effects of omeprazole 10, 20, or 40 mg/day and placebo. Total reflux time over 24 hours, number of reflux episodes per hour, and the number of reflux episodes lasting greater than 5 minutes were measured by ambulatory 24-h oesophageal pH monitoring. All doses of omeprazole were superior to placebo in decreasing gastro-oesophageal reflux as measured by each index. With placebo, oesophageal acid exposure was 16.3% of the 24 hours, 10 mg omeprazole/day reduced that to 6.3%, 20 mg/day lowered acid exposure to 0.9%, and 40 mg/day to 0.6%. Thus only the 20 and 40 mg doses reduced acid exposure to within the normal range. Similar results were obtained with the other indices of reflux. These data suggest that a rational dose regimen for reflux oesophagitis is 20 mg/day, a regimen that has proved effective in clinical trials. The present study indicates that 24-hour oesophageal pH monitoring is a practical approach to the determination of drug dosage in patients with gastro-oesophageal reflux.

Adult↗

Prevalence of gastroesophageal reflux in elderly patients in a primary care setting.

Despite the aging of our population, there remains a paucity of information about gastroesophageal reflux (GER) in the elderly. To assess the prevalence and characteristics of GER within this patient population, questionnaires evaluating symptoms associated with GER were administered to 313 consecutive patients 62 yr old or older from a primary care setting. Fourteen percent of these patients reported having at least weekly heartburn. Ambulatory 24-h esophageal pH monitoring was accomplished in 54 of the 313 patients surveyed. Twenty percent (11/54) of this subgroup exhibited increased acid contact time (pH less than 4 for more than 6% of the monitoring period). Twenty-two percent (12/54) complained of heartburn, yet only six individuals (11%) exhibited both symptomatic and objective indications of acid reflux. Surprisingly, 31% (17/54) of the patients studied exhibited significant alkalinity within the distal esophagus (pH greater than 8 for greater than 1.5% of the monitoring period). Whereas 29% of these patients (5/17) reported heartburn, 40% of those reporting heartburn (2/5) had acid GER as well as excessive alkalinity. In contrast to patients with acid GER--none of whom reported pulmonary symptoms--24% (4/17) of these patients with esophageal alkalinity reported wheezing, nocturnal cough, or paroxysmal nocturnal dyspnea. Of the four patients with significant distal esophageal exposure to both acid and alkali, two reported heartburn and a third reported dysphagia. In addition to the somewhat higher prevalence of acid reflux than anticipated, a surprisingly high prevalence of esophageal alkalinity was observed.

Aged↗

Esophageal motility, heartburn, and gastroesophageal reflux: variations in clinical presentation of esophageal dysphagia.

Dysphagia is a potentially important symptom, often leading to the finding of an anatomical or motility disorder of the esophagus. Dysphagia and heartburn represent two of the most common symptoms associated with esophageal motility disorders. To explore the relationship of symptomatic esophageal dysphagia and heartburn and their association with primary esophageal motor disorders, we have performed a retrospective assessment of 1035 patient evaluations performed at our gastrointestinal laboratory. A clear statistical association of symptomatic dysphagia and heartburn was established; however, no pattern diagnostic of a specific motility disorder was discernible. A sizable fraction of our patient population with dysphagia demonstrated normal esophageal motility. A significant portion of dyspeptic patients exhibited both normal motility and acid exposure. The differences observed between the incidence of subjective symptoms and objective dysfunction may be explained in part by an altered or increased esophageal sensitivity of these patients.

Adult↗

Healing or amelioration of esophagitis does not result in increased lower esophageal sphincter or esophageal contractile pressure.

There is conflicting evidence regarding whether lower esophageal sphincter and esophageal contractile pressures are affected by changes in the severity of gastroesophageal reflux disease. We compared the manometric and endoscopic findings from 30 patients before and after treatment for esophagitis. Before treatment, the grade of esophagitis (I-III) was significantly correlated (r = -0.37; p less than 0.05) with lower esophageal sphincter pressure, but not with esophageal contractile pressure. After treatment, the grade of esophagitis did not change or became worse in 15 patients, and became better in 15 patients. Of these, seven healed. The group that showed no endoscopic improvement demonstrated no change in lower esophageal sphincter or esophageal contractile pressures. The group that did show endoscopic improvement also demonstrated no increase in lower esophageal sphincter or esophageal contractile pressures, and this was particularly evident in those whose esophagitis healed. These data suggest that healing of esophagitis does not result in improvement of esophageal motor function.

Adult↗