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Biomedical subjects

D Hutson

Publications and source records attributed to D Hutson.

35 records · Page 2Linked to original sources

Ionic transport mechanisms underlying fluid secretion by the pancreas.

The pancreas is a 'leaky' epithelium and secretes a juice in which sodium and potassium have concentrations similar to those of plasma. The characteristic features of the secretion are its isosmolality and its high bicarbonate concentration. It is the latter that has attracted considerable attention. Secretion in the isolated cat pancreas is directly proportional to the bicarbonate concentration in the nutrient fluid. The ability of the gland to secrete weak acids has led to the view that because of the very different chemical nature of the anions, it is most likely that it is a component common to all buffers, the proton, that is subject to active transport. This is supported by the decrease in pH and the increase in rho CO2 of the venous effluent when secretion occurs and the sensitivity of secretion to the pH of the nutritional extracellular fluid. It is proposed that the cellular mechanisms are as follows: CO2 diffuses into the cell and is hydrated to carbonic acid under the influence of carbonic anhydrase. The bicarbonate ion so formed diffused into the ductular lumen and the proton is transported backwards through the epithelium with a proton pump (Mg2+ -ATPase) provisionally located in the luminal membrane and a hydrogen-sodium exchange carrier located in the basolateral membrane. Energy for the latter process is derived from the sodium gradient between extracellular fluid and cell. This gradient is maintained by a (Na+ + K+)-ATPase also located in the basolateral membrane. Chloride appears to be transported partly through a chloride-bicarbonate exchange mechanism but largely passively together with a large sodium and potassium component through the paracellular pathway. Osmotic equilibrium is likely to occur in the small ductules.

Animals↗

Biliary excretion of moxalactam.

The biliary excretion of moxalactam was studied in 11 postsurgery patients who had indwelling T-tubes inserted in their common bile ducts. Peak levels of moxalactam in the bile reached mean levels of 33.7 +/- 11.1 and 173.7 +/- 67.0 micrograms/ml 2 h after intravenous administration of a single 500- or 2,000-mg dose, respectively. In 5 of the 10 patients given the 2,000-mg dose, peak moxalactam concentrations in the bile were 2 to 12 times higher than simultaneous serum levels, but considerable variation in the biliary excretion of moxalactam was observed among the individual patients.

Bile↗

Electrolyte secretion by the isolated cat pancreas during replacement of extracellular bicarbonate by organic anions and chloride by inorganic anions.

1. The effect of replacing extracellular bicarbonate and chloride by other anions on the volume and composition of secretin-stimulated pancreatic juice has been analysed in the isolated, perfused cat pancreas. 2. The anions of some aliphatic carboxylic acids were able partially to substitute for bicarbonate in sustaining pancreatic secretion. The order of effectiveness was: acetate greater than proprionate greater than butyrate greater than formate. 3. The rate of secretion in the presence of 25 mM-acetate was 42% of that achieved with 25 mM-bicarbonate. The concentration of acetate in the secretion varied with flow rate, reaching a maximum of 120 mM at high flow rates and declining at lower flow rates, with reciprocal changes in chloride concentration. Bicarbonate was always present in the secretion at a concentration of 5--7 mM. 4. Inorganic anions were able totally or partially to substitute for chloride in sustaining secretion. In relation to chloride, their degree of effectiveness was: chloride = bromide = or greater than nitrate greater than iodide greater than sulphate greater than methyl sulphate greater than isethionate. Those anions which had no effect on secretion rate (i.e. bromide and nitrate) also had no effect on the bicarbonate concentration of the secretion and themselves appeared in the secretion in place of chloride. Those anions which inhibited secretion increased the bicarbonate concentration in the secretion in proportion to the degree of inhibition they caused (i.e. the increase was greatest with isethionate). 5. When perfusate chloride was only partially replaced by bromide or iodide the ratios of chloride: bromide and chloride: iodide in the secretion were approximately equal to those in the perfusate. 6. The carbonic anhydrase inhibitor acetazolamide reduced secretory rate and bicarbonate concentration when added to normal perfusion fluid or chloride-substituted fluids, but had no effect following replacement of perfusate bicarbonate by acetate. 7. These observations illustrate that an extracellular source of permeant anions is required for optimal pancreatic bicarbonate secretion to occur. This may indicate the participation of an anion exchange carrier in the transport events responsible for this secretory process.

Acetazolamide↗

The permeability of the secretin stimulated exocrine pancreas to non-electrolytes.

1. A method of measuring the permeability of the pancreas by determining the apparent reflexion coefficient (sigmaA) is described, in the isolated pancreas secreting maximally under the influence of secretin. The principle is to add a non-electrolyte to the perfusate which will create an osmotic gradient (RTsigmadeltaC) counter to that of active transport and reduce the secretion rate. This is compared with the effect of an equal concentration (0.1 M) of sucrose (RTdeltaC; sigma = 1). The apparent reflection coefficient is obtained by dividing the percentage reduction in the secretion rate due to the test molecule with that due to sucrose. 2. Sucrose when added to the perfusate inhibits pancreatic secretion. For every 10 mM increase in sucrose concentration, the secretion rate was inhibited by 7.1%. It has been estimated that an osmotic gradient of 131 m-osmole/kg water will cause zero flow rate. This is a measure of the pressure required to counteract the local osmotic gradient set up by active transport, it is equivalent to about 3.4 atm. 3. Non-electrolytes with molecular volumes greater than about 85 cm3 mole-1 are relatively impermeable, below this value they enter the pancreatic juice with increasing ease as the molecular volume decreases. 4. SigmaA for a number of compounds has been measured: urea 0.17; ethanediol 0.27; thiourea 0.51; glycerol 0.69; creatinine 0.81; erythritol 0.91; arabinose 0.96; xylose 0.98; sorbitol 0.98. 5. The addition of non-electrolytes to the perfusate had effects on pancreatic secretion which were a function of sigmaA. For molecules with sigmaA lying between 0.81 and 1.0 an osmotic load of 0.1 M increased both the concentration of sodium plus potassium and the concentration of chloride plus bicarbonate by about 50 m-mole/l. Whereas the cation change is almost exclusively one of sodium that of the anions was preferentially an increase in chloride. For compounds with sigmaA lying between 0 and 0.81 the concentration of sodium plus potassium was proportional to sigmaA. 6. A number of compounds have been described which inhibit pancreatic secretion, other than by an osmotic effect. These include acetaldehyde, thioglycerol, nicotinamide, ribose, dihydroxyacetone, and glyceraldehyde. 7. It is concluded that the pancreas is more permeable than the gall-bladder of rabbit, fish and bullfrog, the proximal tubule of the kidney of rat and the small intestine of bullfrog, but is probably similar to that of small intestine of guinea-pig and man.

Animals↗

Fluoroscopically guided thin needle aspiration biopsy of the abdomen and retroperitoneum.

The results of 49 transabdominal and translumbar thin needle percutaneous aspiration biopsies in patients suspected of having malignant disease are reported. A correct diagnosis was obtained in 40 cases. Placement of the Chiba needle was accomplished by fluoroscopically controlled biplane radiography during constrast examinations. No complications were encountered. The technique allows cytologic diagnosis of malignancy without high risk exploratory surgery, prolonged hospitalization, or delay of treatment. Use of fluoroscopic needle guidance and biplane radiography for confirmation of position using various contrast examinations as markers is felt to be superior to either CT or ultrasound. The technique is readily available in all radiology departments.

Abdominal Neoplasms↗

New techniques for interruption of gastroesophageal venous blood flow.

Enlarged gastroesophageal veins were successfully obliterated in 41 patients using embolization with modified autogenous clots and/or Gelfoam, balloon occlusion, iatrogenic perivenous hematoma, sclerosing agents (Sotradecol and Keflin), or a combination of these methods. Thirteen patients were actively bleeding when studied, and the site of bleeding was detected in 4. Surgical exploration of 16 patients and autopsy study of 5 showed persistent obliteration ranging between three weeks and seven months. No major complications requiring reparative surgery were encountered. Gelfoam soaked with Sotradecol is the preferred agent because it provides persistent obliteration of the embolized veins. Patients who are acutely bleeding or have done so previously are candidates for selective obliteration of the gastroesophageal veins.

Catheterization↗

Transhepatic obliteration of gastroesophageal varices: results in acute and nonacute bleeders.

Seventy-three patients with hepatic cirrhosis and bleeding gastroesophageal varices underwent transhepatic portal vein catheterization and variceal obliteration. Gastroesophageal varices were successfully obliterated in 32 patients actively bleeding and in 35 patients with stabilized bleeding gastroesophageal varices. The remaining six were technical failures. Follow-up examinations in 10 patients from 1 month to 3 years later showed persistent obliteration of embolized veins. Recurrence of variceal bleeding occurred in nine patients. This method should be considered as a palliative, effective adjuvant to the medical treatment of patients with bleeding gastroesophageal varices.

Acute Disease↗

Hypothalamic inactivation of thyrotrophin-releasing hormone.

Following the demonstration of peptidases in the rat hypothalamus which inactivate thyrotrophin-releasing hormone (TRH), a sensitive and specific radioimmunoassay for the releasing hormone was used to investigate the presence of similar peptidases in the rabbit hypothalamus. TRH was found to be rapidly inactivated by supernatant and particulate hypothalamic fractions, with higher peptidase activity in the supernatant than in the particulate fraction. An optimum pH of 7.3 within physiological limits was obtained for the enzymes in both the fractions examined. The results obtained confirm that the rabbit hypothalamus contains enzymes capable of inactivating TRH, and since it has been found that such peptidases interfere with studies on TRH biosynthesis, it is possible that the peptidases may play a part in controlling the releasing hormone's production. The specificity of the antiserum used in the radioimmunoassay has also suggested that the peptidases may cleave the C-terminal-ProNH2,-NH2 or both from the TRH molecule to cause inactivation.

Animals↗

Percutaneous transhepatic cholangiography utilizing the Chiba University needle.

Percutaneous transhepatic cholangiography with the Chiba University needle has been performed in 42 patients with cholestasis. The examination was successful in 100% of patients with dilated intrahepatic bile ducts and in 89% of those with normal-size ducts. Complications were minimal. The results of this study suggest that PTC with the Chiba needle is superior to the current conventional methods. The patients with intrahepatic cholestasis, which often simulates extrahepatic biliary obstruction, were spared an unnecessary laparotomy.

Cholangiography↗

Visceral protothecosis mimicking sclerosing cholangitis in an immunocompetent host: successful antifungal therapy.

A healthy 39-year-old man who had clinical findings consistent with sclerosing cholangitis was found to have systemic protothecosis at surgery. Severe granulomatous inflammation and palpable nodules were found in the gallbladder, on the surface of the liver, and in the duodenum. Prototheca wickerhamii was detected in biopsied specimens and stool; the titer of indirect fluorescent antibody to this organism was 1:2,000. The patient recovered after a short course of treatment with amphotericin B and 3 months of oral therapy with ketoconazole. He had no other concurrent illness and had no abnormality in his immune system. This is the second reported human case of systemic protothecosis. An elevated IgG level, an elevated erythrocyte sedimentation rate, eosinophilia, and abnormal levels of enzymes in the liver were found in both cases. Protothecosis should be considered in the differential diagnosis of hepatic and biliary inflammatory diseases of uncertain etiology.

Adult↗