Plasma trypsin in chronic pancreatitis and pancreatic adenocarcinoma.

We have used a simple and precise radioimmunoassay to measure trypsin in human plasma. Fasting plasma trypsin concentrations were extremely low in patients with chronic pancreatitis with steatorrhoea (5 +/- 2 ng/ml) when compared to healthy controls (86 +/- 7 ng/ml, p less than 0.001). In patients with chronic pancreatitis but no steatorrhoea basal plasma trypsin levels were similar to those of the normal controls (99 +/- 25 ng/ml). A small but significant postprandial rise in plasma trypsin concentrations was observed in normal subjects (mean increment 15 +/- 4%, p less than 0.005, paired t test) but was absent in patients with chronic pancreatitis with steatorrhoea. In contrast to exocrine deficient chronic pancreatitis, other malabsorptive conditions associated with steatorrhoea (active coeliac disease and acute tropical sprue) demonstrated mean fasting trypsin concentrations similar to controls. Patients with adenocarcinoma of the pancreas had basal trypsin concentrations similar to healthy subjects as did patients with adenocarcinoma of the stomach, colon, rectum, brochus, and breast. In some cases measurement of plasma trypsin may be of help in the differential diagnosis of steatorrhoea.

3H-cimetidine and the H2-receptor.

The H2-antagonist cimetidine is widely employed in biochemical and pharmacological studies of the H2-receptor. These studies include the use of 3H-cimetidine in radioligand binding experiments. Confirming our previous finding as to the unsuitability of this ligand in these types of investigations, we now report data showing the lack of correlation between the displacement of specific 3H-cimetidine binding and histamine stimulated adenylate cyclase activity, and the displacement of specific binding by imidazoles devoid of H2-receptor activity. Results are also presented which question the use of copper ions in 3H-cimetidine binding studies. Our conclusions are discussed in relation to the work carried out by a number of laboratories where 3H-cimetidine is reported to label the H2-receptor.

Radioimmunoassay of trypsin. A new aid in the assessment of pancreatic function.

This review describes the development and application of a novel test to determine levels of human immunoreactive trypsin, an enzyme produced solely by the pancreas, in biological fluids. Being organ-specific, the assay of immunoreactive trypsin should be an ideal marker of pancreatic function, and this is supported by the results of a number of clinical and research investigations. Use of this assay in studies of chronic pancreatitis, juvenile-onset diabetes, and cystic fibrosis has yielded much valuable data, and it is expected that further research will lead to an improved understanding of these and other conditions associated with the pancreas in health and disease.

An assessment of the value of spleen scanning in the staging of Hodgkin's disease.

The value of non-invasive spleen scanning with 51Cr-chromate heat damaged red cells has been assessed in 68 patients with histologically proved Hodgkin's disease in whom pre-treatment laparotomy with splenectomy was performed. The scans were reported independently by two observers. Following this, the uptake pattern of the radioactive tracer and size of organ on the scan were compared with the post-operative weight and pathology of the spleen. From these results it is concluded that this method of spleen scanning is an unreliable technique in staging Hodgkin's disease.

The use of an in vitro binding assay to predict histamine H2-antagonist activity.

Thirty-seven compounds were evaluated for their ability to inhibit histamine stimulated adenylate cyclase and to inhibit 3H-tiotidine binding. The compounds examined included a number of known H2-antagonists and a number of potential H2-antagonists of diverse chemical structure. The correlation between the Ki values from the binding assay and from the inhibition of adenylate cyclase was calculated to be r = 0.99, p less than 0.001. Thus 3H-tiotidine binding in guinea-pig cerebral cortex can be used to give a valid assessment of histamine H2-receptor activity.

Specific binding of 3H-tiotidine to histamine H2 receptors in guinea pig cerebral cortex.

Although the H2 subclass of histamine receptor has been revealed by classical pharmacological approaches, the direct identification of this adenylate cyclase-linked receptor has, despite much effort, remained elusive. Initial studies using 3H-metiamide and 3H-histamine and, subsequently, work from our own laboratory and others using 3H-cimetidine and 3H-ranitidine in various tissues, has shown the unsuitability of these ligands for labelling the H2 receptor. We report here our results using 3H-tiotidine, a more potent H2-antagonist than either cimetidine or ranitidine, and show that this ligand meets the criteria for labeling the H2 receptor in guinea pig cerebral cortex membranes.