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Biomedical subjects

H T Howat

Publications and source records attributed to H T Howat.

At least 19 recordsLinked to original sources

Pepsin secretion in anaesthetized cats stimulated by pentagastrin and gastrin II in the presence or absence of secretin.

1. In fasting anaesthetized cats pentagastrin and gastrin II, infused alone in doses which evoked a large acid response, did not stimulate the secretion of pepsin. However, peptic secretion increased significantly when either acid stimulant was infused simultaneously with a dose od Boots' secretin, in itself below the threshold for peptic stimulation. 2. The potentiation by pentagastrin and gastrin II of the peptic response to secretin was similar to the potentiation observed when caerulein, histamine and N-methyl histamine are given with secretin, an effect we have attributed to a non-specific increase of gastric mucosal blood flow which accompanies the infusion of these acid stimulants and effectively increases the concentration of secretin delivered at the site of the chief cell in the gastric mucous membrane.

Animals↗

A clinical evaluation of isotope scanning, ultrasonography and computed tomography in pancreatic disease.

In a prospective study of 46 patients with suspected pancreatic disease the provisional diagnoses arrived at independently by isotope scanning (IS), ultrasonography (USS) and computed tomography (CT) have been compared. In the control group, IS and CT were associated with a higher false positive rate than USS; The isotope scan was abnormal in most patients with proven chronic pancreatitis and cancer. The results from USS and CT were similar when structural changes were present. USS was superior in diagnosing pancreatic carcinoma and was a convenient means to follow the progression of acute pancreatitis to final resolution or the development of a pseudocyst. CT proved especially useful in accurately delineating cysts, pseudocysts and calculi prior to planning surgery and in assessing disease in contiguous viscera.

Evaluation Studies as Topic↗

Ultrasonic scanning in pancreatic disease.

We have analysed retrospectively the pancreatic ultrasound scans (using a bistable machine) in 138 consecutive patients, and have related the results to the clinical status and the final diagnosis in each case. The scans were read without knowledge of the patient's clinical state. When technically unsatisfactory scans were excluded from consideration, the overall diagnostic accuracy of ultrasonography proved to be 82%, with a false positive rate of 8%. The scan was abnormal in all 10 patients with cancer of the pancreas: a positive diagnosis of cancer was made in six. All patients with chronic pancreatitis in relapse had abnormal scans, but in 53% the scans were normal in patients in whom the disease was in clinical remission. In seven patients with chronic pancreatitis who suffered relentless pain, the head of the pancreas was swollen and contained cystic areas or emitted abnormal echoes. In acute pancreatitis ultrasonic scanning proved useful in following the progression of the disease to final resolution, or to development of complicating pseudocyst, abscess, or ascites. Random echoes in the early stages of acute pancreatitis are features of haemorrhagic necrosis. In alcoholic relapsing pancreatitis the persistence of abnormal echoes, disposed linearly along the axis of major ducts, suggests the presence of chronic pancreatitis.

Acute Disease↗

Computed tomography in pancreatic disease.

Computed tomography (CT) of the pancreas has been evaluated in 50 patients with established exocrine pancreatic disease and 20 patients without pancreatic disease. Increase in size, irregularity in outline and heterogeneity of composition of the pancreas implied disease but were in no way specific to any particular disease entity. In acute pancreatitis, following complete resolution, the pancreas appeared normal whereas incomplete resolution was associated with non-specific swelling and heterogeneity of density. The extent and location of pseudocysts could be accurately delineated. In chronic pancreatitis, duct calculi, duct dilatation and large intrapancreatic cysts aided the differentiation between focal enlargement due to chronic pancreatitis and expansion due to cancer. Hepatic metastases and abnormalities of the biliary system seen in association with cancer further aided this differentiation.

Ampulla of Vater↗

A comparison of the pepsin stimulating effects of secretin preparations.

1. The peptic responses to Boots, GIH and synthetic secretins have been compared in fasting anaesthetized cats in which the pylorus and bile duct were occluded to prevent the release of duodenal hormones by acid and bile salts. A quantity of dilute acid introduced into the stomach at regular intervals ensured the total recovery of viscid secretions and preserved peptic activity. 2. The mean peak outputs of pepsin obtained in response to Boots secretin were significantly greater than the mean peak outputs of pepsin stimulated by equipotent doses of GIH secretin (4 Crick-Harper-Raper units of Boots secretin have been shown to stimulate a flow of juice and bicarbonate from the pancreas equal to that produced by 1 clinical unit of GIH secretin). The maximum output of pepsin stimulated by Boots secretin, 16 C.H.R. u./kg hr was 3 times the observed maximum output in response to the 4 times more potent dose of GIH secretin, 16 c.u./kg hr. The slopes of the log dose-response lines were significantly different for these two products indicating that their modes of action in stimulating pepsin may not be identical. 3. The outputs of pepsin following GIH and synthetic secretin were similar. Both these secretins stimulated the secretion of pepsin when infused in doses which stimulated the pancreas supramaximally. The less pure product Boots secretin evoked significantly higher peptic responses at doses submaximal for pancreatic stimulation, suggesting that a substance other than secretin exists in Boots preparations which contributes significantly to the overall output of pepsin in response to this product. The peptic response which was accompanied by a slight increase in acid output, but without any increase in pancreatic lipolytic activity, was not inhibited by atropine. This substance which is not present in highly purified GIH secretin does not appear to be cholic acid, gastrin, pancreozymin, glucagon or insulin. 4. The possibility that a vasodilator substance is present in Boots secretin which by expanding the splanchnic bed increases the concentration of secretin at target sites in the stomach and pancreas seems unlikely, as the flow of pancreatic juice does not increase proportionately with the vast increase in pepsin. A vasodilator substance which specifically affects the gastric vasculature remains a theoretical but unlikely explanation for our observation.

Animals↗

The interaction of secretin and stimulants of gastric acid secretion in anaesthetized cats.

1. In fasting anaesthetized cats in which the pylorus and common bile duct were occluded, acid secretion in response to caerulein, desulphated caerulein, histamine and N methyl histamine given singly and combined with Boots secretin 4 C.H.R. u./kg hr has been studied. 2. Eight separate estimates of the calculated maximal response of acid (four acid stimulants given with and without secretin) did not differ significantly from one another. In the presence of secretin the E.D.50 of each acid stimulant was lowered. 3. Outputs of acid in response to the smallest doses of desulphated caerulein, histamine and N methyl histamine increased significantly when secretin was infused (P less than 0-05). 4. On a weight basis caerulein was 23, 474 and 95 times more potent than desulphated caerulein, histamine and N methyl histamine respectively. 5. When secretin was infused simultaneously caerulein was 8, 171 and 165 times more potent than desulphated caerulein, histamine and N methyl histamine respectively. 6. N methyl histamine was 5-6 times more potent than histamine on a weight basis when infused on its own; and 1-16 times more potent than histamine when given in the presence of secretin.

Animals↗

Pancreatitis--a retrospective study.

A retrospective study has been made of all adult patients admitted to Manchester Royal Infirmary with exocrine pancreatic disease between 1968 and 1974, in order to define the factors which influence the variable mortality and morbidity rates in published accounts of patients with acute pancreatitis. The most plausible explanation is that some series with low mortality rates include a variable number of patients with relapsing acute pancreatitis and acute exacerbations of chronic pancreatitis. Both these pathological entities have a negligible mortality and morbidity rate compared with single attacks of acute pancreatitis. The difficulties encountered by the clinician in determining the prognosis of acute pancreatitis at the time of admission to hospital are discussed. Attention is drawn to the differing role of alcohol as an aetiological factor in relapsing chronic pancreatitis and acute pancreatitis.

Acute Disease↗

The influence of secretin on the secretion of pepsin in response to acid stimulants in the anaesthetized cat.

Peptic secretion was studied in fasting anaesthetized cats in which the pylorus and common bile duct had been occluded to prevent the release of duodenal hormones which might stimulate or inhibit gastric secretion. Dilute acid was instilled into the stomach at intervals to aid recovery of gastric secretion and to preserve peptic activity. 2. Caerulein, histamine and N-methyl histamine did not increase the output of pepsin when given on their own. Desulphated caerulein was a weak peptic stimulant. 3. Two C.H.R. u./kg per hour secretin initiated pancreatic secretion, the volume of which increased progressively as the dose was increased by stages to 32 C.H.R. u./kg per hour. 4. Four C.H.R. u./kg per hour secretin did not increase the output of pepsin. Peptic secretion was stimulated by 8 C.H.R. u./kg per hour. A maximal output of approximately 2000 u. pepsin/15 min was obtained when 16 C.H.R. u./kg per hour was infused. 5. When each acid stimulant was infused along with 4 C.H.R. u./kg per hour secretin the output of pepsin increased significantly. The peak output, which usually occurred between 15 and 30 min after stimulation, did not exceed 1000 u. pepsin/15 min. 6. The proposed explanation for the potentiation of the peptic response when an acid stimulant is infused along with a dose of secretin, in itself below the threshold of peptic stimulation, is that each acid stimulant increases gastric mucosal blood flow, approximately doubling the effective concentration of secretin delivered to the peptic cell.

Animals↗

The relative potency of the Crick-Harper-Raper unit and the GIH clinical unit of secretin.

A reinvestigation of the relationship between the Crick-Harper-Raper (CHR) and the GIH clinical units (CU) of secretin has been undertaken in anaesthetized cats with the knowledge that for some time before 1970 the CHR standard used by The Boots Company to assay secretin had lost some specific activity. One clinical unit of GIH secretin (batch no. 17421) is 3-8 times more potent than 1 Crick-Harper-Raper unit of restandardized Boots secretin (batch no. 142) in increasing the flow rate of pancreatic juice, and four times more potent in increasing the amount of bicarbonate.

Animals↗

An evaluation of 75 Se selenomethionine scanning as a test of pancreatic function compared with the secretin-pancreozymin test.

The uptake of (75)Se Selenomethionine by the pancreas has been evaluated in 102 patients and compared with the secretin-pancreozymin test of pancreatic function. In groups of patients with chronic pancreatitis and cancer of the pancreas abnormal scans closely parallel the diminished exocrine secretion, especially bicarbonate output, following a submaximal dose of secretin. Thirty per cent of the group with no pancreatic abnormality have abnormal scans, though the secretinpancreozymin test is normal. Though a normal scan excludes the presence of chronic pancreatitis and cancer of the pancreas with a probability greater than 90%, an abnormal scan is found so frequently in normal subjects that it does not provide a reliable index of impaired pancreatic function.

Bicarbonates↗