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Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 55 records · Page 3Linked to original sources

Analysis of the Albumin Cobalt Binding (ACB) test as an adjunct to cardiac troponin I for the early detection of acute myocardial infarction.

Human albumin has the ability to bind cobalt at the N-terminus. The exposure of circulating albumin to ischemic tissue alters the ability of albumin to bind cobalt, probably through a mechanism involving free-radical production. The Albumin Cobalt Binding (ACB) test measures the alteration in albumin metal binding, and elevation of the ACB test is thought to be an early indicator of myocardial ischemia. In a previous multicenter study of chest pain patients presenting to the emergency department (ED), this test demonstrated high negative predictive value and sensitivity in the sample collected at presentation for predicting cardiac troponin I (cTnI)-negative or cTnI-positive results 6-24 h later. Since the completion of that report, the European Society of Cardiology (ESC) and the American College of Cardiology (ACC) have redefined the criteria for the diagnosis of acute myocardial infarction (AMI). The data from the multicenter ACB study were re-examined using the new diagnostic criteria for AMI to determine if combining the ACB test with troponin improved the sensitivity of either assay used alone for early diagnosis of AMI. Assay values were compared to either the final discharge diagnosis made at each site or to a diagnosis of AMI using the strict application of the ESC/ACC guidelines. Using the criterion of physician's discharge diagnosis and using blood collected at ED presentation, the cTnI test alone had a sensitivity of 23.9%, and the ACB test alone had a sensitivity of 39.1%, but the sensitivity significantly increased to 55.9% (p < 0.001 over cTnI alone) when both tests were used in combination. The sensitivity of the combination of ACB and cTnI tests at the 1- to 6-h time-point was 86.7% and at the >6- to 12-h time-point was 93.5%, but they were not significantly improved over the cTnI test alone. In conclusion, using the new ESC/ACC criteria, the combination also resulted in a statistically significant higher diagnostic sensitivity on blood collected at presentation. These data indicate a possible role of the ACB test in the early triage of patients with chest pain.

Albumins↗

Characteristics of an Albumin Cobalt Binding Test for assessment of acute coronary syndrome patients: a multicenter study.

BACKGROUND: The ability of the N-terminal region of human albumin to bind cobalt is diminished by myocardial ischemia. The characteristics of an assay based on albumin cobalt binding were assessed in suspected acute coronary syndrome patients and in a control reference population. The ability of the Albumin Cobalt Binding (ACB) Test measurement at presentation to predict troponin-positive or -negative results 6-24 h later was also examined. METHODS: We enrolled 256 acute coronary syndrome patients at four medical centers. Blood specimens were collected at presentation and then 6-24 h later. The dichotomous decision limit and performance characteristics of the ACB Test for predicting troponin-positive or -negative status 6 h-24 h later were determined using ROC curve analysis. Results for 32 patients could not be used because the time of onset of ischemia appeared to have been >3 h before presentation or was uncertain. The reference interval was determined by parametric analysis to estimate the upper 95th percentile of a reference population (n = 109) of ostensibly healthy individuals. RESULTS: Increased cTnI was found in 35 of 224 patients. The ROC curve area for the ACB Test was 0.78 [95% confidence interval (CI), 0.70-0.86]. At the optimum decision point of 75 units/mL, the sensitivity and specificity of the ACB Test were 83% (95% CI, 66-93%) and 69% (95% CI, 62-76%). The negative predictive value was 96% (95% CI, 91-98%), and the positive predictive value was 33% (95% CI, 24-44%). The within-run CV of the ACB Test was 7.3%. Results for the reference population were normally distributed; the one-sided parametric 95th percentile was 80.2 units/mL. CONCLUSIONS: This exploratory study suggests that the ACB Test has high negative predictive value and sensitivity in the presentation sample for predicting troponin-negative or -positive results 6-24 h later.

Acute Disease↗

In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3.

Inhibitory effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the proliferation of a variety of cancer cell lines have been extensively reported. We have studied the effect of 1,25-(OH)2D3 (10(-11)-10(-6) M) on the proliferation of a number of human and rat liver cancer cell lines. Additionally, the effect of 1,25-(OH)2D3 (0.02-0.5 microg/kg per day) on the rate of growth of liver cancer cell line xenografts in nude mice was also investigated. In vitro, proliferation of Hep-3B, PLC/PRF/5, and SKHEP-1 cells was significantly inhibited by 1,25-(OH)2D3, while HTC and Novikoff cells were more resistant to the inhibitory effects of the drug. In vivo, treatment of SKHEP-1 tumor bearing nude mice with different doses of 1,25-(OH)2D3 significantly retarded tumor growth without the development of hypercalcemia.

Animals↗

Echogenicity of liver metastases is an independent prognostic factor after potentially curative treatment.

HYPOTHESIS: Intraoperative echogenic appearance of liver metastases from colorectal cancer is a prognostic factor of outcome after curative treatment. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Department of Surgery at a university hospital. PATIENTS: One hundred forty-three consecutive patients with hepatic metastases from colorectal cancer who underwent liver resection with curative intent between 1992 and 1998. INTERVENTION: Curative treatment was achieved by liver resection alone, liver resection plus edge cryotherapy, or liver resection plus cryotherapy to lesions not amenable to further resection. In patients with more than 2 lesions, a hepatic artery catheter was placed for regional chemotherapy. MAIN OUTCOME MEASURES: The echogenic appearance of the liver metastases was assessed by intraoperative ultrasound by a single person throughout the study using a 5-MHz ultrasound probe. The findings were prospectively entered into the database. RESULTS: Fifty-four percent of patients had hyperechoic metastases. This group had significantly longer overall (log rank, P<.001) and recurrence-free survival (log rank, P =.004) compared with patients who had hypoechoic metastases (36%). A significantly higher percentage of mucin-secreting tumors were found in the hypoechoic patient group (chi(2), P =.001). Dukes stage of the primary tumor (P =.02), echogenicity of the liver secondaries (P =.04), and diameter of the largest resected metastasis (P =.01) were independent prognostic factors for recurrence-free survival in the Cox regression model. CONCLUSION: These results support the hypothesis that echogenicity of liver metastases from colorectal cancer is an independent prognostic factor of outcome after curative resection.

Colorectal Neoplasms↗

H2-antagonists in the treatment of colon and breast cancer.

Several clinical trials have now been carried out with histamine type 2 receptor antagonists in cancer patients often as an adjunct to surgical resection of the primary tumour While promising results have been obtained in some groups of patients with gastrointestinal cancer, with increased survival and evidence of increased immunological recognition of tumour, results are less encouraging for breast cancer. This may be due to differences in the levels of histamine or the role of histamine in growth of these different tumour types.

Adjuvants, Immunologic↗

Palliation of hilar biliary obstruction from colorectal metastases by endoscopic stent insertion.

BACKGROUND: In patients with hepatic metastases from colorectal carcinoma there is a distinct subgroup in whom jaundice is not due to hepatic replacement but rather biliary obstruction. We reviewed our experience with stent insertion in patients with malignant proximal biliary obstruction from metastatic colorectal carcinoma. METHODS: Thirty-three patients were treated between July 1992 and December 1996. Placement of a single stent was attempted at initial endoscopic retrograde cholangiopancreatography. Hilar biliary obstruction was classified according to Bismuth's classification. RESULTS: Successful stent placement was possible in 94% overall and at initial endoscopic retrograde cholangiopancreatography in 39% of patients. Successful stent placement occurred significantly more often in patients with a type I stricture. Cholangitis was the principal complication occurring in 24% of patients. The 30-day mortality rate was 24%, with death occurring significantly less often in patients with a type I or II stricture. Overall, 45% of patients had a 30% fall in bilirubin at 1 week. The median survival was 81 days, with significantly longer survival seen in patients with a type I or II stricture. CONCLUSIONS: Endoscopic stent placement offers effective palliation in most patients with hilar obstruction from colorectal metastases. A subset of patients with type III strictures and greater than 3 intrahepatic metastases often do not benefit from stent insertion.

Adenocarcinoma↗

Immunotherapy.

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Dose-Response Relationship, Immunologic↗

The initial care of newborn infants and subsequent hay fever.

BACKGROUND: Patterns of neonatal exposure to microorganisms have changed substantially over the last 100 years, and it has been suggested that this has influenced the risk of immune-mediated disease. Using a proxy measure, we tested the hypothesis that the initial handling of newborn infants, which is known to affect the pattern of exposure to microorganisms, may alter the risk of developing subsequent atopy, as indicated by hay fever. METHODS: Analysis was performed on 5,519 members of the 1970 British Cohort Study, a nationally representative birth cohort. Cohort members with hay fever were identified at intervals up to the age of 26 years. Details of neonatal care and childhood circumstances were recorded prospectively. Those who had spent their first night away from their mother in the communal infant nursery were selected as likely to have experienced atypical exposure compared with infants who remained with their mother. Adjustment was made for potential confounding factors in infancy and childhood by multiple logistic regression analysis. RESULTS: Unadjusted relative odds (with 95% CI) for developing hay fever among those spending the first night in the communal nursery, when compared with other infants who remained with the mother, were 1.48 (1.23-1.77), P<0.001. Comprehensive adjustment for the potential confounding factors, including feeding practices on the first day of life, markers of social and material circumstances, and region, did not substantially alter this relationship, with adjusted relative odds of 1.31 (1.08-1.59), P=0.005. CONCLUSIONS: While our proxy measure is associated with an increased risk of hay fever, further research is required to confirm that this is due to the pattern of infectious exposure in very early life. The results are consistent with the hypothesis that the first challenges are particularly important in the development of the newborn infant's immune system.

Adult↗

Resection with cryotherapy of colorectal hepatic metastases has the same survival as hepatic resection alone.

BACKGROUND: Hepatic resection is well established as a potentially curative treatment for hepatic colorectal cancer metastases. However, only a small proportion of patients with liver metastases are suitable for resection because they either have extrahepatic disease, or the extent and/or the distribution of their hepatic disease would make excision impossible. We have previously described the use of cryotherapy for inadequate resection margins and lesions in the remaining lobe of the liver. Combining such cryodestructive techniques with resection offers the possibility of increasing the proportion of patients to whom potentially curative treatment can be offered. The aim of this study was to compare survival in patients treated with resection and cryotherapy against those of patients treated with resection alone. Potential prognostic variables were also examined. METHOD: Patients undergoing a hepatic resection with or without cryotherapy at our unit between April 1990 and July 1997 were identified from our database and their notes reviewed. Survival was estimated using the Kaplan-Meier method and compared using the Log rank test. RESULTS: One hundred and seven patients were treated in total: 32 underwent resection alone, and 75 underwent resection combined with cryotherapy. There was no significant difference between the survival of patients treated with resection alone and those treated with resection and cryotherapy. CONCLUSIONS: Edge and contralobe cryotherapy can be combined with hepatic resection to allow a greater proportion of patients with hepatic colorectal metastases to be offered treatment, and results in similar survival figures comparable to hepatic resection for at least 3 years.

Adult↗

Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect?

Endogenous histamine has been shown to effect growth mechanisms in experimental mammary carcinomas via H2 membrane receptors (Cricco et al, 1994). Both H1 and H2 binding sites are present in human mammary glands but only 75% malignant carcinomas express H2 receptors (Lemos et al, 1995). The presence of mast cells around tumour tissue raises questions concerning the source of histamine in breast tumour tissue. While cimetidine, an H2 antagonist, has been shown to influence the presence of tumour infiltrating lymphocytes (TIL) in colorectal cancer (Adams and Morris, 1994, 1997) that was not found to be the case in breast cancer (Ng et al, 1995). In recent studies tumour cell proliferation, as measured by Ki-67 antibody labelling, has been seen as an additional prognostic indicator in breast cancer (Railo et al, 1993, 1997; Ferno, 1998; Schauer et al, 1998). We investigated the possibility that cimetidine may influence tumour proliferation by blocking the growth-promoting effects of histamine. No relationship between preoperative cimetidine administration and tumour cell proliferation was seen overall. A weak correlation was seen between tissue histamine content and mast cell count which was not influenced by cimetidine. Tumour cell proliferation correlated well with other prognostic indicators such as grade and differentiation.

Adult↗

Endothelin-stimulated Ca(2+)signaling and endothelin receptor expression are decreased by parathyroid hormone treatment in UMR-106 osteoblastic osteosarcoma cells.

Modulation of endothelin (ET-1)-induced [Ca(2+)](i)transients and receptor expression by parathyroid hormone (PTH) was studied in UMR-106 osteoblastic osteosarcoma cells. Ca(2+)signaling was assessed with Fura-2, and ET receptor mRNA expression was determined using ET(A)- and ET(B)-specific primers and RT-PCR amplification. ET-1 binding in UMR-106 cell membranes was also measured. PTH pretreatment for 8 h decreased the [Ca(2+)](i)transients elicited by ET-1 and by the ET(B)-selective agonist sarafotoxin 6c (S6c). When ET(B)receptors were desensitized by pretreatment with S6c or blocked with the ET(B)-selective antagonist BQ-788, the remaining ET(A)component of the signal was also decreased by PTH pretreatment. In contrast, [Ca(2+)](i)transients elicited by PGF(2alpha)and ionomycin were increased following PTH pretreatment, indicating that the effect of PTH to decrease ET-1-stimulated transients was selective. PTH pretreatment also decreased [(125)I]ET-1 binding and ET(A)and ET(B)mRNA, with maximal effects at approximately 8 h. ET-1 was not detectable in medium from either control or PTH treated UMR-106 cultures, suggesting that the decreased expression of ET receptors was not due to enhanced ET production and subsequent homologous desensitization. The downregulation of ET receptors in osteoblasts by PTH pretreatment may serve as a homeostatic mechanism in bone.

Bone Neoplasms↗

Measles vaccination and inflammatory bowel disease: a national British Cohort Study.

OBJECTIVE: Measles vaccination has been suggested as a risk for inflammatory bowel disease. Atypical age of measles infection has also been associated with Crohn's disease. This study was designed to examine the relationship of measles vaccination and age of measles vaccination with later inflammatory bowel disease. METHODS: A prospective population-based national birth cohort was used, of those born in 1 wk in April 1970 in Great Britain. The data are from 7616 responding members of the 1970 British Cohort Study with complete vaccination data, who were traced at age 26 yr. A diagnosis of Crohn's disease, ulcerative colitis, and diabetes mellitus (a control disease) was obtained by survey at age 26 yr, and confirmed by physicians. Vaccination data were from survey at age 5 yr. Measles and mumps infection data were obtained from the survey at age 10 yr. Adjustment was made for sex, household crowding in childhood, and father's social class at birth. RESULTS: No statistically significant association was found between measles vaccination status at 5 yr and Crohn's disease (adjusted odds ratio [OR] 0.67, 95% confidence interval [CI] 0.27-1.63), ulcerative colitis (adjusted OR 0.57, 95% CI 0.20-1.61), or diabetes (adjusted OR 0.75, 95% CI 0.33-1.74). There was a statistically significant trend (p = 0.040) with increasing age of measles vaccination for risk of Crohn' s disease, although this was based on very few cases vaccinated after age 2 yr. CONCLUSIONS: In this cohort, monovalent measles vaccination status is not associated with inflammatory bowel disease by age 26 yr. Older age at measles vaccination needs to be examined in other studies to confirm whether it is a genuine risk for Crohn's disease.

Adult↗