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Biomedical subjects

P Keeling

Publications and source records attributed to P Keeling.

At least 37 records · Page 2Linked to original sources

Experimental columnar metaplasia in the canine oesophagus.

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.

Animals↗

Implication of duodenogastric reflux in the pathogenesis of Barrett's oesophagus.

Fasting and postprandial intragastric bile acid concentrations have been estimated and compared in patients with complications of Barrett's oesophagus, patients with Barrett's oesophagus without complications, patients with oesophagitis and a group of normal subjects who acted as controls. There was no significant difference in fasting intragastric bile acid concentrations between the groups. Postprandial bile acid concentrations were significantly greater in the patients with complications of Barrett's than in the remaining groups at 60, 90 and 120 min. Significant concentrations of bile acids were seen in gastric juice of unaltered pH and may be undetected on intra-oesophageal pH monitoring. Duodenogastric reflux may be implicated in the pathogenesis of complications of Barrett's oesophagus.

Adult↗

Esophageal scintigraphy: applications and limitations in the study of esophageal disorders.

This study examines the scintigraphic transit pattern in a variety of esophageal disorders. Scintigraphy was performed with a semi solid bolus and the patient in an upright position. Condensed esophageal images were obtained from which we derived the esophageal transit time. The pattern of bolus transit was graded by the duration of transit and by the presence of hold up or retrograde motion. Scintigrams were performed in 11 volunteers and 88 patients whose esophageal function had been confirmed by conventional gastroesophageal techniques. Esophageal disorders examined included achalasia (20), scleroderma (9), esophageal carcinoma (8), Barrett esophagus (5), and reflux esophagitis (27). We also examined the effects of gastroesophageal surgery on esophageal function. Transit times distinguished grossly abnormal esophageal function from normal but did not distinguish between different esophageal disorders. Graded transit patterns were a more sensitive indicator of esophageal function and permitted some differentiation between esophageal disorders and allowed evaluation of the effects of gastroesophageal surgery.

Esophageal Diseases↗

Oesophageal resection in the elderly.

The outcome of transthoracic resection for carcinoma of the oesophagus and cardia was compared in seventy six patients over seventy years of age with that of 179 patients under seventy. A resectability rate of 89% was achieved in the over 70 group and 91% in the under seventy group. Hospital mortality at 3 months was 21% in the elderly group and 14% in the younger age group (P = NS). Postoperative pulmonary infection and cardiac arrhythmias were more frequent in the elderly but postoperative hospital stay was almost identical in both groups. There were three fatal anastomotic leaks in the over seventy group and six in the under seventies. Survival figures at one and five years showed no significant difference between the groups. We conclude that age alone is not a contraindication to surgical resection of carcinoma of the oesophagus and cardia.

Adult↗

Barrett's oesophagus: pH profile.

Twenty-four patients with a columnar-lined (Barrett's) oesophagus underwent oesophageal manometry and 24 h ambulatory oesophageal pH monitoring. The results were compared with 25 patients with oesophagitis studied in the same fashion. No significant difference in lower oesophageal sphincter pressure was demonstrated between the two groups. The Barrett's patients demonstrated significantly greater acid exposure in the distal oesophagus than oesophagitis patients. Clearance or refluxed acid was poorer in Barrett's patients than oesophagitis patients. Twelve of the Barrett's patients presented with complications of the condition, i.e. ulceration or stricture. No significant difference in acid exposure was demonstrated between Barrett's patients with or without complications. These results suggest that patients with columnar-lined (Barrett's) oesophagus have greater acid exposure than patients with oesophagitis. The development of complications of a Barrett's oesophagus may not be dependent on acid reflux alone.

Adult↗

Blunt injury of the neck of the pancreas: a report of nine patients.

Nine patients with injury of the neck of the pancreas following blunt abdominal injury are reported. Eight were sustained in road traffic accidents and only two victims had used seatbelts. Serious associated injuries were present in four patients and the pancreatic injury was missed in two patients. The diagnosis of this injury was made at laparotomy in six, while one patient had the diagnosis confirmed at endoscopic retrograde pancreatography (ERP). The neck of the pancreas was the site of injury in all nine cases. Pancreatic drainage (3), suture repair (1) and distal resection with splenectomy (2) were the operative procedures performed. Pseudocyst of the pancreas (2), pancreatic fistulas (2), pancreatitis (1) and ascites (1), which necessitated a further laparotomy, accounted for postoperative morbidity. There was one postoperative death from haemorrhage due to stress ulceration. This study emphasizes that the neck of the pancreas is at special risk following blunt abdominal injury.

Accidents, Traffic↗

Adenocarcinoma of the esophagus and cardia.

Two hundred thirty-nine patients with carcinoma of the esophagus and cardia were seen between 1971 and 1985. Of 128 adenocarcinomas, 108 (84%) were resected. There were 111 squamous cell tumors, of which 104 (94%) were resected. Hospital mortality rate (3 months) was 19.4% in patients with adenocarcinoma and 14.4% in those with squamous cell carcinoma. It was significantly higher in the over 70 age group in both series. The 1 year survival rate in the adenocarcinoma group (52.3%) was lower than in the squamous group (59.1%), which reflects the higher operative mortality rate in the former. The 5 year survival rate was 18% in the adenocarcinoma group and 18.7% in the squamous cell group. With one exception, all patients who survived for 5 years had a Stage I tumor. Although the operative mortality was higher in the adenocarcinoma group, the prognosis was similar to that of the squamous cell carcinoma group.

Actuarial Analysis↗

Arrangement of MP26 in lens junctional membranes: analysis with proteases and antibodies.

The major membrane protein of the bovine lens fiber cell is a 26-kilodalton (kD) protein (MP26), which appears to be a component of the extensive junctional specializations found in these cells. To examine the arrangement of MP26 within the junctional membranes, various proteases were incubated with fiber cell membranes that had been isolated with or without urea and/or detergents. These membranes were analyzed with electron microscopy and SDS-PAGE to determine whether the junctional specializations or the proteins were altered by proteolysis. Microscopy revealed no obvious structural changes. Electrophoresis showed that chymotrypsin, papain, and trypsin degraded MP26 to 21-22 kD species. A variety of protease treatments, including overnight digestions, failed to generate additional proteolysis. Regions on MP26 which were sensitive to these three proteases overlapped. Smaller peptides were cleaved from MP26 with V8 protease and carboxypeptidases A and B. Protein domains cleaved by these proteases also overlapped with regions sensitive to chymotrypsin, papain, and trypsin. Specific inhibition of the carboxypeptidases suggested that cleavage obtained with these preparations was not likely due to contaminating endoproteases. Since antibodies are not thought to readily penetrate the 2-3 nm extracellular gap in the fiber cell junctions, antibodies to MP26 were used to analyze the location of the protease-sensitive domains. Antisera were applied to control (26 kD) and proteolyzed (22 kD) membranes, with binding being evaluated by means of ELISA reactions on intact membranes. Antibody labeling was also done following SDS-PAGE and transfer to derivatized paper. Both assays showed a significant decrease in binding following proteolysis, with the 22 kD product showing no reaction with the anti-MP26 sera. These investigations suggest that MP26 is arranged with approximately four-fifths of the primary sequence "protected" by the lipid bilayer and the narrow extracellular gap. One-fifth of the molecule, including the C-terminus, appears to be exposed on the cytoplasmic side of the membrane.

Animals↗

Longitudinal assay of lymphocyte responsiveness in patients with major burns.

Serial blast transformation in vitro was measured in peripheral lymphocytes from 38 patients with major thermal injury. Lymphocytes were tested with the antigens streptokinase-streptodornase (SKSD), mumps and purified protein derivative (PPD), the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA), and in the one-way mixed lymphocyte reaction. Statistically significant suppression by the burn injury was noticed in all measurements except response to PHA. One-time measurements were not significantly different between the patients who survived and the patients who did not survive their burn injuries. However, serial determinations of responsiveness to the three natural antigens SKSD, mumps and PPD, as well as the mixed lymphocyte reaction accurately reflected prognosis.

Adolescent↗

Immunomodulation in major burns: an in vitro system for assaying the effect of modulators.

The restoration of normal immune responses is a clinical goal in the severely immunosuppressed burn-trauma patient. The recently documented emergence of the suppressor system following major burns, however, dictates caution in the use of agents which stimulate immunologically competent cells. We describe an in vitro system, utilizing human peripheral lymphocytes, which accurately reflects the degree of immunosuppression of burned patients, and which can be used to predict the effect of immunologically active agents. Of a group of synthetic polyribonucleotides tested in this system, Poly I:C produced a significant favorable modulation in doses of 3.7 micrograms/ml. The most marked effect was noted in the subgroup of patients who eventually succumbed and in whom clinical modulation would be most advantageous.

Adjuvants, Immunologic↗

Acromegaly secondary to growth hormone releasing hormone secretion.

BACKGROUND: Acromegaly secondary to growth hormone releasing hormone (GHRH) secretion is exceptionally rare. AIM: To report a case of acromegaly diagnosed in 1984 and assumed to be pituitary in origin. Sixteen years later, the cause was found to be a GHRH secreting neuroendocrine pancreatic tumour. METHOD: A case report. CONCLUSION: Although ectopic GHRH production is very rare, endocrinologists should be aware of this possibility in acromegaly patients if a pituitary tumour was not detected using pituitary imaging.

Acromegaly↗