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Biomedical subjects

L F Johnson

Publications and source records attributed to L F Johnson.

At least 163 records · Page 9Linked to original sources

Twenty-four-hour pH monitoring of esophageal function. Its use in evaluation in symptomatic patients after truncal vagotomy and gastric resection or drainage.

The incidence and character of gastrointestinal reflux after truncal vagotomy and gastric resection or drainage were studied prospectively in 42 symptomatic patients. Gastroesophageal reflux, proven by 24-hour pH monitoring, occurred in 31 patients. Initial symptoms of heartburn, regurgitation, or dysphagia were similar in patients with and without reflux. Eighteen patients had pure acid, nine had acid-alkaline, and four had pure alkaline reflux. Reflux occurred predominantly in the supine position. Esophagitis occurred only in patients with reflux and was not dependent on the pH of refluxed material. Reflux was eventually controlled by antireflux repair in 19 and by colon interposition in three patients. Twenty-four-hour esophageal pH monitoring is beneficial in evaluating symptoms after gastric surgery. It quantifies both acid and alkaline reflux, provides an objective assessment of the patient's subjective complaints, and gives a rational basis for management.

Drainage↗

Acid clearance during sleep in the pathogenesis of reflux esophagitis.

Impaired esophageal clearing of refluxed gastric contents during sleep has been implicated in the pathogenesis of reflux esophagitis. To more directly evaluate this hypothesis, 13 symptomatic patients with esophagitis and 13 normal controls had 15 ml of 0.1 N HCl instilled into the esophagus in the recumbent position while awake and during polygraphically monitored sleep. When sleep was maintained for the majority of the acid-clearing duration, the clearance times for both patients and controls were significantly prolonged when compared to those while awake (P less than 0.01). However, when sleep was maintained for less than 50% of the acid-clearing interval, the patients showed significantly longer acid clearance times. The swallowing rate did not differentiate the two groups under any condition. These data show that sleep impairs esophageal acid clearance. Acid clearance occurred predominantly in association with arousals from sleep. The defective acid clearance found in patients with esophagitis probably plays a major role in the pathogenesis of this disorder.

Adult↗

Esophageal hematoma. Four new cases, a review, and proposed etiology.

We report four cases of esophageal hematoma and emphasize that endoscopically and radiographically it may simulate a neoplasm. After a review of 26 cases, we found that patients with normal hemostasis often had esophageal hematoma occur distally after vomiting. Most of these hematomas probably originated from a Mallory-Weiss laceration. In contrast, patients with impaired hemostasis had esophageal hematoma occur proximally or at multiple sites. Many of these hematomas occurred spontaneously, without a history of vomiting, and probably resulted from impaired coagulation. Regardless of etiology most esophageal hematomas were associated with a benign course.

Adult↗

Evaluation of elevation of the head of the bed, bethanechol, and antacid form tablets on gastroesophageal reflux.

To ascertain how elevation of the head of the bed, bethanechol, and antacid foam tablets affect gastroesophageal reflux, we used prolonged intraesophageal pH monitoring in 55 symptomatic patients. Acid exposure was separated into reflux frequency and esophageal acid clearance time and recorded during the day in the upright posture and recumbent at night. Values before and during each therapy were compared to physiologic reflux in 15 asymptomatic controls. Ten patients slept with the head of the bed elevated and had a 67% improvement in the acid clearance time (P less than 0.025); however, the frequency of reflux episodes remained unchanged. Twelve patients given 25 mg of bethanechol 4 times a day had a 50% decrease in recumbent acid exposure only (P less than 0.05), due to a trend towards decreased reflux episodes and acid clearance in time. Bethanechol combined with head of bed elevation in 19 other patients decreased both reflux frequency (30%) and acid clearance time (53%, all P less than 0.05). Antacid foam tablets failed to significantly diminish acid exposure. Nocturnal reflux responded the best to those therapies tested.

Antacids↗

New concepts and methods in the study and treatment of gastroesophageal reflux disease.

This paper reviews progress in the use of 24-hour distal esophageal pH monitoring in the study of gastroesophageal reflux. This technique records acid exposure as numbers of reflux episodes and time required by the esophagus to return this acid juice to the stomach. These data afford an opportunity to conceptualize the pathophysiology of gastroesophageal reflux disease in relation to physiologic activities such as alimentation, sleep, and postural change. This knowledge will enable the clinician to critically focus attention on important issues of patient management and therapy as they relate to the pathophysiology of this disease.

Gastric Acid↗

Relationship of a hiatal hernia to the function of the body of the esophagus and the gastroesophageal junction.

One hundred two patients referred to our Esophageal Function Laboratory without endoscopic evidence of esophagitis were divided into two groups on the basis of the presence of a hiatal hernia on endoscopic examination. Fifty-three patients had a hiatal hernia and 49 did not. Both groups and 30 normal volunteer subjects had esophageal manometry and 24 hour esophageal pH monitoring. The incompetency of the cardia in patients with a hiatal hernia was dependent upon loss of components responsible for the antireflux mechanism, mainly a decrease in distal esophageal sphincter pressure and a decrease in the length of the sphincter exposed to the positive-pressure environment of the abdomen. These deficiencies were not related to the presence of a hiatal hernia and were similar to those of patients with an incompetent cardia without a hiatal hernia. Patients with a hiatal hernia and an incompetent cardia had significantly more esophageal exposure to refluxed acid than without a hiatal hernia. On the basis of the number of reflux episodes that lasted 5 minutes or longer and radioisotope transit studies, this increased acid exposure was due to both a loss of competency of the cardia and poor esophageal clearance secondary to the presence of a hiatal hernia. Reduction of the hernia and anchoring the distal esophagus into the abdomen not only may improve the antireflux mechanism, but corrects the clearance abnormality as well. The presence of a hiatal hernia has a detrimental effect on the clearance function of the body of the esophagus and may aggravate the effects of gastroesophageal reflux due to an incompetent cardia.

Adolescent↗

Cell cycle regulation of thymidylate synthetase gene expression in cultured mouse fibroblasts.

This study describes the regulation of thymidylate synthetase activity in mouse 3T6 fibroblasts during serum-induced transitions between the resting (G0) and growing state. The specific activity of thymidylate synthetase was about 17 times lower in resting 3T6 cells than in exponentially growing cells. When resting cells were serum-stimulated to re-enter the cell cycle, thymidylate synthetase activity remained at the level found in resting cells until 12 h following stimulation (G0-G1 phase), then increased sharply as the cells entered S phase. Enzyme activity increased about 20-fold over that of resting cells by 30 h following stimulation and continued to increase linearly for at least another 30 h. Studies with inhibitors of protein and RNA synthesis indicated that the increase in enzyme activity was due to de novo synthesis of the enzyme, and that the increase was controlled at the level of transcription. When cells were stimulated in the presence of inhibitors of DNA synthesis, thymidylate synthetase activity increased in the same manner as in control-stimulated cells. This indicated that the induction of gene expression was not directly coupled to DNA replication. When the serum stimulus was withdrawn during S phase (20 h following stimulation) the cells completed the cell cycle and divided, but then reverted back to the resting state. Thymidylate synthetase activity stopped increasing at about the same time the cells stopped synthesizing DNA, and decreased thereafter with a half-life of 20 to 25 h.

Animals↗

Absence of control of poly(A)(+) messenger RNA translation in growth-stimulated mouse 3T6 fibroblasts.

To better understand the mechanism by which the rate of protein synthesis is regulated in growth-stimulated mouse 3T6 fibroblasts, we have determined the proportion of cytoplasmic poly(A)(+) mRNA that is associated with polysomes. We found that this proportion is nearly the same (70-80%)in resting, serum-stimulatd, or exponentially growing cells. This indicates that the increase in the rate of protein synthesis following serum stimulation of 3T6 cells is regulated primarily by the increase in mRNA content rather than by an increase in the fraction of total mRNA engaged in protein synthesis. We also show that in detergent-lysed 3T6 cells, up to half of the subpolysomal poly(A)(+) mRNA is of mitochondrial origin. This conclusion is based on analysis of the size of the mRNA and its poly(A), its subcellular location and the inhibition of the labeling of this mRNA by ethidium bromide. The physical properties of subpolysomal mRNA of nuclear origin are similar to those of polysomal mRNA.

Animals↗

Cell cycle regulation of dihydrofolate reductase mRNA metabolism in mouse fibroblasts.

We have used the technique of DNA-excess filter hybridization to measure directly the content and metabolism of the mRNA for dihydrofolate reductase (DHFR; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3). The studies were conducted with a methotrexate-resistant derivative of mouse 3T6 fibroblasts (M50L3) that overproduces the enzyme and its mRNA by a factor of 300 but regulates the level of the enzyme during the cell cycle in the same manner as normal 3T6 cells. We found that, when resting (G0) M50L3 cells were serum-stimulated to reenter the cell cycle, the 10-fold increase in the rate of synthesis of DHFR that occurs at the beginning of S phase was the result of a corresponding increase in DHFR mRNA content. In pulse-labeling experiments, we found that there was a similar increase in the rate of production of the mRNA just prior to S phase. However, the half-life of the mRNA was the same (7.5 hr) in resting and exponentially growing cells. Therefore, the increase in DHFR mRNA content was due to an increase in the rate of production rather than an increase in the stability of the message. The delay between addition of [3H]-uridine to the culture medium and the emergence of DHFR mRNA from the nucleus was 15-20 min for both resting and growing M50L3 cells. A similar delay was observed for total mRNA. Therefore, the time required for the processing of newly synthesized DHFR heterogeneous nuclear RNA into DHFR mRNA is about the same as that for the average mRNA.

Animals↗

Hepatitis B in United States soldiers in Korea.

We studied US soldiers hospitalized in Korea during 1977 because of acute icteric hepatitis. The clinical characteristics of this illness were similar to those noted in previous studies of this population. In contrast to earlier reports, however, hepatitis B virus was shown to be the single most important cause. Of 139 patients with acute viral hepatitis, 76 (55%) had positive tests for hepatitis B surface antigen (HBsAg) and 63 (45%) were HBsAg-negative on a single determination by radioimmunoassay (AUSRIA II) approximately one week after the onset of symptoms. Nonparenteral transmission was the primary mechanism of hepatitis B infection in this sexually active population. Only one patient had evidence of parenteral drug use. Our increased recognition of hepatitis B virus in these patients can be explained entirely by increased sensitivity of the current radioimmunoassay methods for HBsAg. High rates of nonparenteral transmission of B virus within the populations of developing countries are well recognized. Our findings show that hepatitis B virus can be the major cause of nonparenterally acquired acute hepatitis among foreigners in contact with such a population.

Acute Disease↗

Liver injury with alcoholic hyaline after intestinal resection.

We describe a patient who developed liver injury with alcoholic hyaline after intestinal resection. Malnutrition appeared to be a dominant factor in the origin of his liver injury since no hepatotoxic drug, alcohol, or toxic bacterial product from a blind loop could be implicated.

Adult↗

"Melanosis" of the duodenum associated with a gastric ulcer and folic acid deficiency.

Melanosis involving the duodenum is extremely rare. We present endoscopic, microscopic, and histochemical studies of a patient with melanosis of the duodenum associated with a gastric ulcer and a folic acid deficiency. The pigment is similar to that observed in melanosis coli and histochemically does not stain like melanin or lipofuscin. The pigment disappeared with correction of the folate deficiency and healing of the gastric ulcer, suggesting a possible relationship with these entities.

Aged↗

Technique, indications, and clinical use of 24 hour esophageal pH monitoring.

The technique of 24 hour esophageal pH monitoring (24 hour pH test) is described. Experience with the 24 hour pH test in 393 patients with suspected esophageal disease has shown the clinical usefulness of the test in objectively determining the presence of gastroesophageal reflux. The test was effective in evaluating atypical symptoms of gastroesophageal reflux such as respiratory symptoms and chest pain and, in children, failure to thrive and recurrent pneumonia. The 24 hour pH test was particularly useful in evaluating patients who were referred with other abdominal or thoracic disease and had, in addition, symptoms suggestive of gastroesophageal reflux on history. The test helped to unsnarl the cause of recurrent symptoms after an esophageal myotomy for achalasia or an antireflux procedure. Of 179 patients with typical symptoms of gastroesophageal reflux, 27% had normal 24 hour test results and were subsequently diagnosed as having another cause for their symptoms. Of 146 patients who had normal findings on esophagoscopy, 54% were shown to have abnormal gastroesophageal reflux on 24 hour pH monitoring, indicating lack of sensitivity of endoscopy to detect reflux. In addition, the 24 hour pH test identified patterns of abnormal reflux and indicated those patients most at risk for development of stricture. The test is well tolerated by the patients, simple to use, and dependable when performed and read as described. The clinical use of the 24 hour pH test brings objectivity to the evaluation of exophageal disease that has hitherto not been available.

Aged↗