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Biomedical subjects

D M McCarthy

Publications and source records attributed to D M McCarthy.

161 records · Page 9Linked to original sources
PubMed1974

The responses of rat intestinal brush border and cytosol peptide hydrolase activities to variation in dietary protein content: dietary regulation of intestinal peptide hydrolases.

The effects of variation in dietary protein content on small intestinal brush border and cytosol peptide hydrolase activities have been investigated. One group of rats was fed a high protein diet (55% casein) and another group was fed a low protein diet (10% casein). After 1 wk, brush border peptide hydrolase activity (L-leucyl-beta-naphthylamide as substrate) and cytosol peptide hydrolase activity (L-prolyl-L-leucine as substrate) were determined in mucosae taken from the proximal, middle, and distal small intestine. As judged by several parameters, brush border peptide hydrolase activity was significantly greater in rats fed the high protein diet when data for corresponding segments were compared. In contrast, no significant difference was seen in cytosol peptide hydrolase activity. IN A SECOND STUDY, BRUSH BORDER AND CYTOSOL PEPTIDE HYDROLASE ACTIVITIES WERE DETERMINED IN THE PROXIMAL INTESTINE BY UTILIZING AN ADDITIONAL THREE PEPTIDE SUBSTRATES: L-leucyl-L-alanine, L-phenylalanylglycine, and glycyl-L-phenylalanine. Sucrase, maltase, and alkaline phosphatase activities were also determined. As before, brush border peptide hydrolase activities were significantly greater in rats fed the high protein diet. However, activities of the nonproteolytic brush border enzymes did not vary significantly with diet. In contrast to the results obtained with L-prolyl-L-leucine as substrate for the cytosol enzymes, cytosol activity against the three additional peptide substrates was greater in rats fed the high protein diet. It is suggested that the brush border peptide hydrolase response to variation in dietary protein content represents a functional adaptation analogous to the regulation of intestinal disaccharidases by dietary carbohydrates. The implication of the differential responses of the cytosol peptide hydrolases is uncertain, since little is known of the functional role of these nonorgan-specific enzymes.

Animals↗
PubMed1973

Changes in sucrase, enterokinase, and peptide hydrolase after intestinal resection. The association of cellular hyperplasia and adaptation.

In a study of changes in digestive enzymes after massive intestinal resection and the mechanisms by which such changes occur, rats were sacrified 4 wk after removal of the proximal two-thirds of the small intestine. Alterations in the mucosal levels of sucrase, enterokinase, and dipeptide hydrolase (L-leucyl-L-alanine substrate) were examined in the light of associated changes in protein. DNA and wet mucosal weight, measured in standardized gut segments from various regions of intestine. Metabolic studies showed that normal growth patterns were reestablished after the operation but significant elevations in stool weight and fecal nitrogen occurred in the second postoperative week, falling towards normal by the 4th wk. In standard gut segments wet weight of mucosa, protein, and DNA rose, especially in distal segments, DNA increasing disproportionately. Mucosal levels of the proximally distributed and membrane-bound enzymes, sucrase and enterokinase, showed similar patterns of change: when enzyme activity was expressed in terms of the total per segment, proximally there were considerable increases in both enzymes, but, expressed in terms of specific activity, that of sucrase fell and that of enterokinase was unaltered. By contrast, the largely soluble and more distally distributed dipeptide hydrolase increased more in distal segments and the increases in total activity were accompanied by lesser increases in specific activity. However, in spite of increases in total activity, enzyme activity per milligram DNA fell by over 50% in postanastomotic segments. Subcellular distribution studies showed no change in the percentage of the total activity which was membrane-bound and zymograms confirmed that no new dipeptide hydrolase had appeared after resection. It is concluded that increases in the segmental totals of various enzymes seen after resection are achieved by disproportinate increases in the number of mucosal cells per segment and that the greatest change in a particular enzyme occurs in the region where the enzyme is normally found in highest concentration.

Animals↗
PubMed1972

75 Se-selenomethionine scanning in the diagnosis of tumours of the pancreas and adjacent viscera: the use of the test and its impact on survival.

The results of pancreatic scanning with (75)Se-selenomethionine in 393 carefully documented patients over a two-year period are presented. On follow up 50 patients had operatively proven malignant tumours in the gland and a further 22 had similar tumours in adjacent organs, clinically mimicking carcinoma of the pancreas and in many cases causing scan abnormalities. Five patients had pancreatic adenomata. Remote tumours rarely affected the scan. Examination of the role of scanning in patients with neoplastic disease revealed that the test was effective in screening and in detection; false negative diagnoses were rare. By contrast, survival following diagnosis was extremely poor with only 8% of pancreatic tumours resectable and 50% metastasized at the time of surgery. Causes of pancreatic dysfunction, other than pancreatitis or carcinoma, which were associated with abnormalities on the scan are described and general aspects of reporting on the scan are discussed. The patterns seen in abnormal scans, while non-specific with regard to aetiology, were anatomically meaningful and useful adjuncts to the diagnosis of pancreatic disease. A normal scan excluded pancreatic cancer with a probability greater than 95%.

Adenoma↗
PubMed1969

Measurement of duodenal tryptic activity and 75Se-selenomethionine pancreatic scanning compared as tests of pancreatic function.

The results of a subjective assessment of pancreatic function, based on the appearance of a (75)Se-pancreatic scan, were compared with measurements of the tryptic activity of duodenal aspirates in 16 normal and 38 abnormal subjects. In normals and in abnormals whose scans showed a generalized rather than a localized abnormality there was close agreement between the results of the two sets. In patients with a localized abnormality of the pancreatic head on scanning the tryptic activity of the aspirate was useful in differentiating carcinoma of the pancreas from that of the common bile duct. In general the scan was the more discriminative test though otherwise the places of the two tests in diagnosis are rather similar. The particular situations in which each test is valuable, or in which one or other test can be omitted, are discussed.

Clinical Enzyme Tests↗
PubMed1969

Value of hypotonic duodenography as an adjunct to pancreatic scanning.

A technique has been developed which allows the position of the upper gastrointestinal tract, as determined radiographically, to be superimposed on the pancreatic photoscan, performed after an injection of (75)Se-selenomethionine. Results of the technique applied to 27 ;abnormal' and 23 ;normal' subjects are described. The importance of the additional information gained by the combined technique is discussed in terms of normal variation and increased diagnostic yield, and the situations in which it was found most useful are described. The addition of correlated duodenography rendered scan reporting more objective in 50% of cases.

Barium Sulfate↗
PubMedDate not supplied

Early changes in thallium distribution. Effect on quantitative analysis.

Thirty-two patients with coronary artery disease and an abnormality on an initial anterior view thallium scan had repeat images obtained after delays of 30 and 240 minutes. Scans were analyzed by quantitative criteria. Comparison of the initial stress study with the 30-minute redistribution scan showed no significant change in 11 patients, defects becoming smaller in 13 patients, and defects becoming larger in eight patients. When comparing the stress or the early redistribution images with the late redistribution scans, the diagnosis (eg, scar vs. ischemia) would have been affected in 14 cases. Analysis of the sources of variability showed that all the apparent worsening but only part of the defect resolution could be explained by variability inherent to repositioning the patient. Thus, the size of an initial defect is very sensitive to the time between the end of exercise and the onset of data collection and the nature of changes in scan appearance is complex.

Adult↗
PubMedDate not supplied

Assessing physicians' estimates of the probability of coronary artery disease: the influence of patient characteristics.

The authors assessed physicians' probability estimates of coronary artery disease (CAD) in 250 patients undergoing a screening exercise stress test. True likelihood of disease (prevalence) was derived from the literature. Discrimination and calibration were assessed by comparing physicians' probability estimates and prevalence using pairwise comparisons, rank correlation, and linear regression. There were differences in the discriminative abilities of the physicians based on patient characteristics. For example, the physicians had better discriminative ability for patients with typical cardiac chest pain compared with atypical chest pain. The physicians were able to predict the prevalence of CAD in broad groups of patients. However, they overestimated probabilities for patients with low prevalence of disease and underestimated probabilities for patients with high prevalence of disease. The authors conclude that physicians make consistent errors in the use of probability estimates. The quality of these estimates depends on patient characteristics such as type of chest pain and true likelihood of disease.

Angiography↗
PubMedDate not supplied

Digoxin toxicity secondary to clarithromycin therapy.

OBJECTIVE: To report a case of digoxin toxicity thought to be secondary to clarithromycin therapy. CASE SUMMARY: A 78-year-old white woman with congestive heart failure taking digoxin 0.25 mg po qd presented to our hospital with nausea, vomiting, and diarrhea. She had taken clarithromycin 500 mg po bid for 3 days, and a serum digoxin concentration obtained the day of admission was 4.4 mug/L. An electrocardiogram (ECG) done on admission revealed ST segment changes consistent with digoxin effect and later asymptomatic, nonsustained ventricular tachycardia (NSVT). Clarithromycin was discontinued and digoxin was withheld at admission, resulting in the resolution of symptoms, ECG abnormalities, and NSVT on day 3 of hospitalization. On day 5 her serum digoxin concentration was 1.5 micrograms/L and digoxin therapy was reinstituted at a dose of 0.125 mg/d po. DISCUSSION: This is the fourth published case implicating clarithromycin as the cause of digoxin toxicity. This interaction is most likely due to clarithromycin eradication of digoxin-metabolizing gut flora, thereby increasing digoxin bioavailability. CONCLUSIONS: Approximately 10% of patients are thought to be extensive presystemic metabolizers of digoxin and may therefore be most susceptible to a drug interaction with clarithromycin. Serum digoxin concentrations in such patients should be monitored closely during clarithromycin therapy.

Aged↗
PubMedDate not supplied

Ultrasonic investigation of pancreatic islet cell tumors.

Ultrasonographic imaging was performed on 49 patients who had pancreatic islet cell tumors, including examples of all six known tumor varieties. In beta cell insulinomas, ultrasonography was of little value for tumor visualization, because these tumors tend to be small and the patients frequently are obese. On the other hand, ultrasonography was very effective for evaluating the nonbeta cell tumors, detecting both primary pancreatic neoplasms and hepatic metastases in patients with glucagonomas, somatostatinoma, non-functioning tumors, and the WDHA syndrome. In detection of the Zollinger-Ellison syndrome, ultrasonography compares favorably with previously reported gastrinoma detection by angiography and CT scanning.

Adenoma, Islet Cell↗
PubMedDate not supplied

Helicobacter pylori and non-steroidal anti-inflammatory drugs: does infection affect the outcome of NSAID therapy?

1. H. pylori gastritis appears to increase the likelihood of developing dyspeptic symptoms on NSAID therapy. 2. There is preliminary evidence that the histologic severity of H. pylori gastritis may be adversely affected by NSAID therapy, with a consequent increase in the risk of developing a peptic ulcer, possibly with complications. Whether this results from an effect on the inflammatory process or results from a quantitative increase in H. pylori colonization is unknown. In these respects, ASA may differ from other NSAIDs. 3. Ulcers are more likely to develop during the course of NSAID therapy in those infected with H. pylori; eradication of the infection reduces ulcer recurrence in the face of continued NSAID therapy, and it seems likely that this must reduce but not abolish the risk of GI bleeding in those using NSAIDs. Eradication also reduces the damage (and possibly risks) of low-dose aspirin therapy. 4. While H. pylori and NSAID use are independent risk factors for GI bleeding, whether or not they are interactive remains unresolved. 5. The effect of H. pylori infection on the risk of perforation during NSAID therapy, or conversely, the contribution of NSAID therapy to the risk of perforation in H. pylori-infected subjects, is also unclear at the present time. 6. Only large outcome studies of accurately diagnosed patients (with regard to H. pylori gastritis), and with much more specific detail as to the type of NSAID, dose and duration of therapy, employing only well-defined end-points, such as significant hemorrhage, perforation or death, and avoiding all surrogate markers short of these end points can hope to unravel this tangled web.

Aged↗