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D L Morris

Publications and source records attributed to D L Morris.

At least 73 records · Page 4Linked to original sources
PubMed2000

Prehospital and emergency department delays after acute stroke: the Genentech Stroke Presentation Survey.

BACKGROUND AND PURPOSE: Patient delays in seeking treatment for stroke and delays within the Emergency Department (ED) are major factors in the lack of use of thrombolytic therapy for stroke. The Genentech Stroke Presentation Survey was a multicentered prospective registry of patients with acute stroke. The study was designed to characterize prehospital delays and delays within the ED. METHODS: Patients with stroke symptoms presenting to 48 EDs participating in a clinical trial of acute stroke therapy were enrolled prospectively. A 1-page data form was completed from patient interviews and medical records. RESULTS: A total of 1207 subjects were entered into the study. Ninety-four percent of the 721 subjects with complete data had a diagnosis of stroke or transient ischemic attack, 13% were black, 50% were female, and 67% were aged >65 years. The median time from symptom onset to ED arrival was 2.6 (interquartile range 1.2 to 6.3) hours. The median time from ED arrival until CT scan completion was 1.1 (0.7 to 1.8) hours, and the total delay time (symptom onset until CT scan completion) had a median of 4.0 (2.3 to 8.3) hours. Patients who arrived by emergency medical services had significantly shorter prehospital delay times and times to CT scan. Age, race, sex, and educational level did not appear to affect prehospital delay times. CONCLUSIONS: Despite its limitations, this large geographically diverse study strongly suggests that the use of emergency medical services is an important modifiable determinant of delay time for the treatment of acute stroke.

Acute Disease↗
PubMed2000

Determinants of use of emergency medical services in a population with stroke symptoms: the Second Delay in Accessing Stroke Healthcare (DASH II) Study.

BACKGROUND AND PURPOSE: With the advent of time-dependent thrombolytic therapy for ischemic stroke, it has become increasingly important for stroke patients to arrive at the hospital quickly. This study investigates the association between the use of emergency medical services (EMS) and delay time among individuals with stroke symptoms and examines the predictors of EMS use. METHODS: The Second Delay in Accessing Stroke Healthcare Study (DASH II) was a prospective study of 617 individuals arriving at emergency departments in Denver, Colo, Chapel Hill, NC, and Greenville, SC, with stroke symptoms. RESULTS: EMS use was associated with decreased prehospital and in-hospital delay. Those who used EMS had a median prehospital delay time of 2.85 hours compared with 4.03 hours for those who did not use EMS (P:=0.002). Older individuals were more likely to use EMS (odds ratio [OR] 1.21 for each 5-year increase, 95% CI 1.14 to 1.29), as were individuals who expressed a high sense of urgency about their symptoms (OR 1.69, 95% CI 1.09 to 2.62). Knowledge of stroke symptoms was not associated with increased EMS use (OR 0.63, 95% CI 0.40 to 0.98). Patients were more likely to use EMS if someone other than the patient first identified that there was a problem (OR 2.35, 95% CI 1.61 to 3.44). CONCLUSIONS: Interventions aimed at increasing EMS use among stroke patients need to stress the urgency of stroke symptoms and the importance of calling 911 and need to be broad-based, encompassing not only those at high risk for stroke but also their friends and family.

Age Factors↗
PubMed2000

Bovine abortions associated with Bacteroides fragilis fetal infection.

Two Santa Gertrudis cattle from a herd of 105 aborted within a 24-hour period. Bacteroides fragilis was isolated from tissues of each aborted fetus. Histopathologic lesions included placentitis and bronchopneumonia in which gram-negative, rod-shaped organisms were visible. The diagnostic workup failed to reveal other causes of abortion. Anaerobes are rarely implicated in bovine abortions, and no other report was found that described abortion in cattle due to B. fragilis.

Abortion, Veterinary↗
PubMed2000

Automated assay for HER-2/neu in serum.

BACKGROUND: The extracellular domain of the HER-2/neu oncogene product is increased in sera of some patients with epithelial cancers. Our aim was to develop an automated serum assay for the extracellular domain of the HER-2/neu protein. METHODS: We used a monoclonal antibody labeled with fluorescein for capture and a monoclonal Fab' fragment labeled with alkaline phosphatase for detection. Separation of bound and free detection conjugate was performed with magnetizable particles coated with monoclonal antibody to fluorescein. Alkaline phosphatase activity was measured kinetically at 405 or 450 nm. RESULTS: The assay was linear from 0.1 to 250 microg/L. No hook effect was evident up to 10 000 microg/L. Within-run imprecision (CV) was 0.8-1.2%, and total imprecision was 1.1-1.7%. Cross-reactivity with human epidermal growth factor receptor, which has extensive homology with HER-2/neu extracellular domain, was <0.6%. Human anti-mouse antibodies, heterophilic antibodies, and rheumatoid factor did not interfere, nor did the therapeutic monoclonal antibody Herceptin((R)). In 51 healthy females, the mean value was 9.3 microg/L with a range of 6.4-14.0 microg/L. No reagent lot-to-lot variability was detected over four lots of reagents tested. CONCLUSION: The Bayer Immuno 1(TM) assay for HER-2/neu was precise and resistant to interferences, characteristics that are essential for longitudinal monitoring of cancer patients.

Antibodies, Monoclonal↗
PubMed2000

Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer.

PURPOSE: Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. MATERIALS AND METHODS: Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. RESULTS: Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. CONCLUSIONS: The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.

Humans↗
PubMed2000

Effect of marimastat on serum tumour markers in patients with colorectal cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of enzymes that break down extra cellular matrix proteins during tissue formation. Tumours have been shown to over-express certain matrix metalloproteinases relative to normal tissue. Matrix metalloproteinases are associated with the disruption of tissue architecture in the growth of tumours and they are also important in the development of metastases. Pre-clinical studies have shown that inhibitors of matrix metalloproteinases (MMPIs) can restrict malignant growth and block the process of tumour neovascularisation. Marimastat is a synthetic MMPI which has been investigated in clinical studies of patients with advanced cancers. OBJECTIVE: The aim of this open study is to describe the change in serum CEA in eight patients with advanced colorectal metastatic disease treated with Marimastat. RESULTS: The mean percentage change in serum CEA level of the patients before commencing Marimastat treatment was 35.6 (SD 25.7) with a mean percentage change in serum CEA of 6.8 (SD 18.3) during the first month of treatment. The average percentage change in serum CEA after one month of treatment with Marimastat was 20 percent. CONCLUSIONS: Although the study sample is small, there is a significant difference in serum CEA change prior to and post commencement of marimastat treatment. It is important to note that the observation period was short for most patients due to their advanced disease.

Adult↗
PubMed2000

Low preoperative serum carcinoembryonic antigen concentration is a marker of good prognosis in patients undergoing cryotherapy for low volume hepatic metastases from colorectal cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) is of prognostic value in colorectal cancer and has been shown to be related to the ability of colorectal cancer cells to implant and to metastasise and to have an effect on immune function. This study attempts to separate the prognostic effects of serum CEA level and volume of hepatic metastases following cryotherapy for liver metastases from colorectal cancer. METHODS: Out of 195 patients undergoing cryotherapy for liver tumour between 4/90 and 5/97 we identified 94 patients who had cryoablation of colorectal liver metastases with known volume of metastases and preoperative serum CEA. Survival was estimated using the Kaplan-Meier method and the log-rank test was used to test for significant differences in survival of subgroups with different tumour volumes and preoperative serum CEA. RESULTS: Tumour volume was prognostic, with patients with low volume-disease having a significantly better outcome than patients with medium or high volume disease. There was clearly no effect of preoperative serum CEA level on survival in patients with high volume disease. However, in the medium and low volume group the patients with low serum CEA preoperatively have a significantly better survival than patients with a high preoperative serum CEA. CONCLUSIONS: We believe that the data supports the belief that CEA has a biological effect which significantly worsens survival following hepatic cryotherapy in patients with low volume and medium hepatic metastases from colorectal cancer. Therapeutic approaches to this phenomenon may be of value both in primary and secondary colorectal cancer.

Biomarkers, Tumor↗
PubMed1999

Randomized trial of preoperative cimetidine in patients with colorectal carcinoma with quantitative assessment of tumor-associated lymphocytes.

BACKGROUND: Previous studies have suggested that cimetidine, a histamine-2 receptor antagonist with immunostimulatory effects, may improve survival in patients with colorectal carcinoma. This effect may be apparent by an increase in the number of peritumoral lymphocytes. A prospective, double blind, randomized, placebo-controlled trial of a short course of preoperative treatment with cimetidine in patients with colorectal carcinoma was performed to assess the effect of cimetidine on survival and on the number of peritumoral lymphocytes. METHODS: One hundred and twenty-five patients who were scheduled to undergo elective colon or rectal excision for carcinoma were randomized to receive either placebo or cimetidine preoperatively for 5 days. In addition to standard histopathology, immunohistochemistry and computer video image analysis were used to assess the number of peritumoral lymphocytes in an objective manner. Interim survival analysis according to the Kaplan-Meier method was performed. RESULTS: A trend toward a survival advantage in the group of patients receiving cimetidine (800 mg twice daily) compared with the placebo group was observed (P = 0.20, log rank test) that was most marked in patients with replication error negative tumors (P = 0.04). Similarly, in these two groups there was a trend toward an increase in the number of patients with a conspicuous lymphocytic infiltration (P = 0.10, chi-square test). However, there was no difference in the number of peritumoral lymphocytes as measured by image analysis. CONCLUSIONS: Based on the results of the current study, a short course of preoperative treatment with cimetidine does appear to have an effect on patient survival; however, the exact mechanism is unknown. The failure of this study to demonstrate a clear increase in the local lymphocyte response does not exclude an immunologic mechanism of action.

Adjuvants, Immunologic↗
PubMed1999

Pretreatment echogenicity of colorectal liver metastases predicts survival after hepatic cryotherapy.

PURPOSE: There is currently no knowledge of the prognostic value of echogenicity of colorectal liver metastases in patients receiving no treatment, hepatic cryotherapy, or any other treatment modality. We sought to determine whether differences in echogenicity of colorectal liver metastases predict prognosis after hepatic cryotherapy. METHODS: Between April 1990 and May 1997 the echogenicity of liver metastases was assessed intraoperatively in 48 patients undergoing cryotherapy for in situ destruction of colorectal liver metastases, with use of an Aloka machine with a 5-MHz scanner. Survival time was calculated by the Kaplan-Meier method, and the prognostic value of echogenicity and several other possible prognostic factors was tested with the log-rank test. RESULTS: Thirty-three patients were found to have hyperechoic metastases. These patients had a favorable outcome, with a median survival time of 50 months, as compared with a median survival time of 24 months in the 15 patients with hypoechoic metastases (P = 0.0074). Regarding the remaining prognostic factors that were tested, only age less than 51 years, absence of involved nodes at primary resection, small diameter of liver metastases, and low preoperative serum carcinoembryonic antigen levels were associated with a favorable outcome. CONCLUSION: We believe that this is an original description of the prognostic importance of echogenicity of colorectal liver metastases. Differences in echogenicity may be related to tumor biology. This will be addressed in further studies.

Adult↗
PubMed1999

World survey on the complications of hepatic and prostate cryotherapy.

Cryotherapy is used as a treatment for nonresectable liver tumors and adenocarcinoma of the prostate. Morbidity and mortality following cryotherapy are generally considered to be infrequent, but a syndrome of multiorgan failure, severe coagulopathy, and disseminated intravascular coagulation following hepatic cryotherapy has been described and referred to as the cryoshock phenomenon. In this study we aimed to assess and describe the incidence and clinical features of the cryoshock phenomenon following cryosurgery from the surveyed experience of a large number of clinical centers and to relate the data to the overall mortality and morbidity of this treatment. A questionnaire was sent to all cryotherapy users (n = 299) of whom we were aware. We requested information on the number of patients treated, the occurrence, and the clinical features of cryoshock and mortality and morbidity following cryotherapy of the prostate or liver. Altogether 134 completed questionnaires were returned (44.8%). Seventy-two centers had experience with hepatic cryotherapy and 62 with prostate cryotherapy. Following hepatic cryotherapy, the phenomenon of cryoshock was observed in 21 of 2173 patients (1%) and was responsible for 6 of 33 perioperative deaths (18.2%). Cryoshock was rare following prostate cryotherapy (2 of 5432 patients, 0.04%) and did not contribute to the overall mortality of 0.06%. Hepatic and prostate cryotherapy are safe. Cryoshock is rare after prostate cryotherapy but occurs in 1% of patients following hepatic cryotherapy. Cryoshock is associated with a high risk of death, being responsible for 18.2% of deaths in this survey. Research regarding the mechanism and possible avoidance of cryoshock is required.

Acute Kidney Injury↗
PubMed1999

Interleukin-6 and tumor necrosis factor-alpha levels following hepatic cryotherapy: association with volume and duration of freezing.

Although morbidity following cryotherapy is usually minor, a syndrome of multiorgan failure and disseminated intravascular coagulation (DIC) has been described and referred to as the cryoshock phenomenon. We hypothesized that mediators similar to those in septic shock may be involved in this syndrome. In this study we aimed to assess the plasma concentrations of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) following hepatic cryotherapy and to relate them to the duration and volume of freezing and to hepatocellular injury. Between April and December 1997 blood samples were taken preoperatively and at different times postoperatively from patients undergoing hepatic artery catheter-insertion (HAC) (n = 15), cryotherapy (n = 5), liver resection (n = 9), liver resection and edge cryotherapy (n = 7), or liver resection and cryotherapy of additional lesions (n = 9). They were analyzed for serum aspartate transaminase (AST) and plasma TNF-alpha and IL-6 levels. There was a significant association (Pearson correlation) of serum AST levels 1 hour postoperatively with plasma TNF-alpha and IL-6 levels at the end of the procedure. In patients undergoing cryotherapy or resection with cryotherapy of additional lesions (n = 14), the volume and duration of hepatic freezing were significantly associated with postoperative serum AST and plasma TNF-alpha and IL-6 levels at various postoperative times. Hepatic cryotherapy is followed by cytokine release, with postoperative plasma TNF-alpha and IL-6 levels associated with the degree of hepatic cryotrauma. These mediators may be involved in the occurrence of cryoshock following large-volume hepatic freezing.

Aspartate Aminotransferases↗
PubMed1999

Analysis of cytochrome P450 and phase II conjugating enzyme expression in adult male rat hepatocytes.

The induction of cytochrome P450 (CYP450) and Phase II conjugating enzymes by prototypical hepatic enzyme inducers was studied in adult male rat hepatocytes. Hepatocytes were suspended and cultured in diluted Matrigel in a basal serum-free Dulbecco's modified Eagle medium and exposed to the prototypical liver enzyme inducers, 3-methylcholanthrene, phenobarbital, hydrocortisone, and clofibrate for 48 h. Total RNA and microsomes were isolated and prepared, respectively, at 72 h. The expression of CYP1A1, CYP1A2, CYP2B1, CYP2C11, CYP2E1, CYP3A1, CYP3A2, CYP4A1, fatty acyl-CoA oxidase, uridine diphosphate-glucuronosyltransferase, glutathione-S-transferase, and sulfotransferase was determined at the mRNA level with reverse transcriptase polymerase chain reaction (RT-PCR). The expression of CYP1A1, CYP2B1, CYP2C11, CYP2E1, and CYP4A1 was also measured at the apoprotein level by Western immunoblotting. Using these culture and expression analysis techniques, we have found that the expression of these metabolic enzymes can be maintained in culture for up to 7 d at the mRNA and apoprotein levels. In addition, hepatocytes were found to respond to chemical enzyme inducers with marked increases in enzyme expression at either the mRNA or protein level and in a concentration-related fashion. Cells were responsive to enzyme induction as early as 24 h after initial plating. The results obtained from this investigation indicate that the presence of diluted Matrigel (at a concentration of 0.35 mg/ml), the use of low concentrations of insulin (1 microM), hydrocortisone (0.1 microM), and serum-free culture medium can maintain the differentiated phenotype and responsiveness of cultured hepatocytes to chemical-induced metabolic enzyme expression. Under the conditions used in this study, enzyme induction in adult male rat hepatocytes shows close agreement with enzyme induction observed in the livers of rats exposed to these or similar prototypical enzyme inducers. Rat hepatocytes cultured in the presence of diluted Matrigel coupled with enzyme mRNA expression analysis with RT-PCR are proven to be a valuable and important in vitro toxicological approach to assess the chemical-induced changes in expression of liver CYP450 and Phase II conjugating enzymes.

Acyl-CoA Oxidase↗
PubMed1999

Paramyxovirus infections in childhood and subsequent inflammatory bowel disease.

BACKGROUND & AIMS: Measles virus has been implicated in the etiology of both inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis. Subacute sclerosing panencephalitis (SSPE) is caused by atypical measles infection. This study investigated the patterns of infection that are risks for SSPE, early infection and a close temporal relationship between measles and another infection, as potential risks for IBD. METHODS: The data are from 7019 members of a nationally representative 1970 British Cohort Study. The ages of five childhood infections were recorded before onset of IBD symptoms. Diagnoses of IBD and insulin-dependent diabetes mellitus (IDDM), as a control disease, were identified by age 26 years. RESULTS: Mumps infection before age 2 years was a risk for ulcerative colitis (odds ratio, 25.12; 95% confidence interval, 6. 35-99.36). Measles and mumps infections in the same year of life were significantly associated with ulcerative colitis and Crohn's disease, with odds ratios of 7.47 (2.42-23.06) and 4.27 (1.24-14.46), but not with IDDM. These relationships are independent of each other as well as sex, social class at birth, household crowding in childhood, and family history of IBD. CONCLUSIONS: Atypical paramyxovirus infections in childhood may be risk factors for later IBD.

Adult↗
PubMed1999

Metal binding properties of thiols; complexes with horse liver alcohol dehydrogenase.

The metal binding properties of thiols were investigated fluorimetrically and spectrophotometrically using horse liver alcohol dehydrogenase as a model metalloenzyme. The steady-state kinetics revealed that in the presence of the coenzyme the primary interaction of a thiol with the enzyme is by thiolate competing with alcohol for the active zinc site. The experiments with 2-mercaptoethanol and ethanethiol showed that at physiological pH it is enzyme-NAD-thiol complexes which are kinetically important with enzyme-thiol complexes only significant at higher pH. The dissociation constants for the binding of thiols in the ternary enzyme-NAD-thiol complexes showed tighter binding as the pH increases, with dithiols binding more tightly than monothiols. The primary binding to zinc was less dependent on the pKa value of each thiol than on mutual stabilization of zinc bound thiolate by the positive charge on the pyridinium ring of NAD, and by monodentate binding and with some dithiols perhaps bidentate binding. The tighter binding to the enzyme of the thiol when it is more hydrophobic or less polar indicates that the thiols interact not only with the active zinc site but also with a neighboring hydrophobic site. This is important for tight binding thiols which are rigidly held by multivalent binding through being anchored hydrophobically and to positively charged centers like zinc.

Alcohol Dehydrogenase↗
PubMed1999

Crystal structure of the MHC class I homolog MIC-A, a gammadelta T cell ligand.

The major histocompatibility complex (MHC) class I homolog MIC-A functions as a stress-inducible antigen that is recognized by a subset of gammadelta T cells independent of beta2-microglobulin and bound peptides. Its crystal structure reveals a dramatically altered MHC class I fold, both in detail and overall domain organization. The only remnant of a peptide-binding groove is a small cavity formed as the result of disordering a large section of one of the groove-defining helices. Loss of beta2-microglobulin binding is due to a restructuring of the interaction interfaces. Structural mapping of sequence variation suggests potential receptor binding sites on the underside of the platform on the side opposite of the surface recognized by alphabeta T cell receptors on MHC class I-peptide complexes.

Crystallography, X-Ray↗
PubMed1999

Indicators of recurrence following cryotherapy for hepatic metastases from colorectal cancer.

BACKGROUND: This retrospective review aimed to assess the incidence of local recurrence at the cryosite, hepatic and extrahepatic recurrence and the corresponding disease-free intervals. Prognostic indicators following hepatic cryotherapy were also identified. METHODS: Eighty-five patients underwent complete cryotreatment of colorectal liver metastases between April 1990 and May 1997. Possible prognostic indicators were tested for their impact on the disease-free interval at the cryosite, liver disease-free survival and overall disease-free survival with univariate and multivariate analysis. RESULTS: At a median follow-up of 22 months 66 patients developed tumour recurrence: 18 in the liver only; 15 in the liver and lung; 22 in the liver and extrapulmonary areas; and 11 at extrahepatic sites only. Local recurrence at the cryosite occurred in 28 patients. Cryotreated metastases larger than 3 cm were associated with a shorter disease-free interval at the cryosite and liver disease-free survival; persistently raised serum carcinoembryonic antigen (CEA) levels after operation were associated with shorter liver disease-free and overall disease-free intervals in multivariate analysis. CONCLUSION: Improvements in probe placement and monitoring of the freezing process are required to allow successful treatment of large liver metastases. A failure in complete postoperative CEA response indicates that hepatic or extrahepatic disease was not detected before operation, which may be avoided with better staging procedures.

Adult↗
PubMed1999

Peritonectomy and intraperitoneal chemotherapy in appendiceal and colorectal cancer.

BACKGROUND: Peritoneal spread of gastrointestinal malignancies has been regarded as an incurable disease, and treatment has been aimed at short-term palliation. The use of cytoreductive surgery, including peritonectomy procedures and intraperitoneal chemotherapy, has been proposed with the intention of prolonging survival, and perhaps curing patients with peritoneal carcinomatosis from appendiceal and possibly colon cancers. A series of eight patients who have undergone this procedure at St George Hospital is presented, and the results obtained by other groups are reviewed. METHOD: Eight patients fitted the criteria for peritoneal carcinomatosis between January 1996 and November 1998. In seven patients this was secondary to appendiceal or colon cancer. and one patient had signet ring cancer of the uterus. The surgical treatment involved removing all macroscopic evidence of disease, and this was followed by early postoperative intraperitoneal chemotherapy. RESULTS: The eight patients (seven female, one male) ranged in age from 25 to 67 years. There were seven complications, including two patients with pelvic abscesses, and one patient who developed Tenchkoff catheter occlusion. There were three deaths, one due to pelvic sepsis after 30 days, and the other two were due to metastatic disease. Of the remaining five patients, two have developed recurrence and three remain disease-free. CONCLUSION: The results of peritonectomy and intraperitoneal chemotherapy for appendiceal tumours are encouraging. The role in colorectal cancer is less clear, although there are some reports that suggest a benefit.

Abscess↗