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D L Morris

Publications and source records attributed to D L Morris.

At least 127 records · Page 7Linked to original sources
PubMed1997

Pilot study--cimetidine enhances lymphocyte infiltration of human colorectal carcinoma: results of a small randomized control trial.

BACKGROUND: Cimetidine preserves postoperative immune function and inhibits the growth of some cancers. In this study, the effect of cimetidine on the local immune response to colorectal carcinoma was investigated. METHODS: Forty-two patients scheduled for elective resection of colorectal carcinoma were randomized either to receive cimetidine for 1 week perioperatively or to act as controls. A lymphocyte density of 50 cells per high-power field (approximately 50% of the tumor/tissue interface) was considered a positive response. Patient survival was determined by Kaplan-Meier life table analysis. The effects of histamine and cimetidine on normal subject lymphocyte function was determined in a mitogen-stimulated proliferation assay. RESULTS: A positive lymphocyte response was observed in 5 of 24 control carcinoma patients (21%) and 10 of 18 cimetidine-treated carcinoma patients (56%) (P = 0.03). The presence of a lymphocyte response correlated with a better survival (P = 0.02). Histamine had an inhibitory effect on lymphocyte proliferation with a median effective dose of 5 x 10(-7) M. Cimetidine antagonized this effect with a negative logarithm of the cimetidine molar concentration required to reduce the effect of histamine in half of 6.55. CONCLUSIONS: Histamine inhibits normal lymphocyte function, antagonized by cimetidine at a histamine type 2 receptor. Cimetidine increases lymphocyte infiltration of primary colorectal carcinoma, possibly by overcoming the immunosuppressive effects of high local histamine concentrations. The presence of a local lymphocyte response correlates with an improved 3-year survival.

Aged↗
PubMed1997

A comparative laboratory study of liquid nitrogen and argon gas cryosurgery systems.

Cryotherapy can now be applied using a variety of delivery systems and cryogens. We compared the Cryotech LCS 3000 liquid nitrogen system (Spembly, Andover, UK) with the CRYOcare argon gas-based system (Irvine, CA, U.S.A.) using three different 3-mm cryoprobes: an old liquid nitrogen probe (N-probe), a new N-probe featuring gas bypass and an argon gas probe. Each probe was tested in two models: (i) fresh sheep liver at 20 degrees C--the probe was inserted to a depth of 1.5 cm; the rate of ice ball formation was monitored by recording radial temperatures every 15 s at 5, 10, 15, and 20 mm from the cryoprobe, and the ice-ball diameter was measured every 2.5 min. After 10 min, the probe was warmed and the time taken until it could be extracted from the liver was recorded. (ii) Warm water bath--the probe was immersed in warm water (42 degrees C) for 15 min and the ice-ball diameter was measured at 5-min intervals. Radial temperatures in liver declined more rapidly (P < 0.001) and time to probe extraction was less (P < 0.01) when the argon gas system was used. The new N-probe performed better than its older counterpart, but was still slower than the argon gas system. In liver (20 degrees C), ice-ball diameters were similar after 10 min, but in warm water, they were larger when the new N-probe was used (P < 0.02). It would appear that the argon gas system is initially faster, but it does not achieve as large an ice ball in a warm environment as the liquid nitrogen system.

Animals↗
PubMed1997

Bile duct warmer in hepatic cryosurgery--a pig liver model.

Freezing of the common bile duct resulted in injury, stenosis, or perforation of the bile duct in a dog model. Biliary cutaneous fistulas and bile leaks are reported as complications of hepatic cryosurgery in man. In an ex vivo pig liver model we compared freezing close to the bile duct with and without warming the bile duct with warmed saline solution via an inserted catheter ("bile duct warmer"). The recorded temperatures at the outer wall of the bile duct were -50 degrees C after 10 min of freezing without and 5. 8 degrees C with the use of the warmer (P < 0.001, two-way ANOVA). The bile duct warmer system may be a simple and inexpensive device in reducing perioperative morbidity after hepatic cryosurgery of hepatic liver lesions close to a bile duct.

Animals↗
PubMed1997

Vitamin D3 analog, EB1089, inhibits growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model.

PURPOSE: In this study, we investigated the effect of the vitamin D3 analog, EB1089, on the growth of subcutaneous xenografts of the human colon cancer cell line, LoVo, in a nude mouse model. METHODS: BALB/c Nu/Nu nude mice were inoculated subcutaneously with 10(6) LoVo cells. EB1089 dissolved in isopropanol was administered intraperitoneally and orally on alternate days at doses of 0.1, 0.5, and 2.5 microg/kg/day. Control animals received isopropanol alone. Tumor volumes estimated using the formula 0.5 X length X (width)2. The tumor kinetic index was determined by immunohistochemical detection of proliferating cell nuclear antigen. RESULTS: Significant dose-dependent inhibition of tumor growth was seen. After 20 days of treatment with 0.1 microg/kg/day EB1089, mean tumor volume in treated mice was 41 to 49 percent less than that in control animals (P < 0.01). Significant inhibition of tumor growth was also seen with 0.5 microg/kg/day EB1089 after 22 days of treatment (51 percent of control P < 0.01). Treatment with 2.5 microg/kg/day resulted in weight loss that required termination of this group; these mice were subsequently found to be hypercalcemic. The tumor kinetic index was significantly lower in tumors treated with 0.1 microg/kg/day EB1089 compared with that for control tumors (8 vs. 30 percent in controls). CONCLUSION: These findings suggest that the vitamin D3 analog, EB1089, is a potent antiproliferative agent for some human colon cancers.

Animals↗
PubMed1997

Characterization of the role played by antigen challenge in the suppression of in vivo humoral immunity by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The goal of these studies was to characterize the role played by antigen challenge in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunosuppression. The effects of single exposure to TCDD (4.2, 14, and 42 microg/kg) in B6C3F1 mice on the reverse plaque assay (RPA; no sensitization) and the sheep red blood cell (SRBC) antibody response were compared. While the RPA was suppressed in a dose-dependent fashion with significance at the two highest doses, a much more dramatic effect was noted with the primary anti-SRBC response: a suppression was noted at the lowest dose, which was comparable to that observed with the highest dose in the RPA. Subsequent studies compared the RPA in B6C3F1 (Ah-high responder) and DBA/2 (Ah-low responder) mice after both single and repeated exposure to identical cumulative doses of TCDD (4.2, 14, and 42 microg/kg). The repeated exposures consisted of 14 consecutive daily treatments of 0.3, 1.0, and 3.0 microg/kg. The results indicated only a slight difference in the effects of TCDD in the two strains after single exposure, and even less difference after repeated exposure. Moreover, administering TCDD on different days relative to the SRBC challenge indicated a suppression in both strains when given 1, 2, or 3 days before antigen challenge, on the day of antigen challenge, or 1 or 2 days after antigen challenge. The only day of administration where the suppression was attenuated was 3 days after antigen challenge. These results confirm an important relationship between antigen challenge and TCDD exposure on immunosuppression.

Animals↗
PubMed1997

Histamine content in colorectal cancer. Are there sufficient levels of histamine to affect lymphocyte function?

Histamine has been found to stimulate growth of colorectal cancer in vitro and in vivo. Histamine has also been found to inhibit lymphocyte activity in vitro at concentrations greater than 10(-7) M. The aim of our study was to determine if the histamine concentrations in human colorectal cancer were sufficient to achieve these effects. We measured the histamine content in 31 colorectal cancer specimens using a radioenzymatic assay. Results were expressed as microgram histamine per gram of fresh tissue weight. Recovery and reproducibility studies were also carried out. The median histamine concentration in colorectal cancer tissue was 8.4 micrograms/g [7.6 x 10(-5)M], ranging from 0.3 microgram/g to 20.6 micrograms/g. The high concentration of histamine in colon cancer is enough to be locally immunosuppressive.

Adult↗
PubMed1997

Immunophenotyping analysis of peripheral blood, splenic, and thymic lymphocytes in male and female rats.

A flow cytometry method was used to characterize lymphoid tissue-associated lymphocyte subsets in the Sprague-Dawley rat. Mononuclear leukocytes from peripheral blood, spleen, and thymus of male and female rats were labeled with a panel of fluorescently tagged monoclonal and polyclonal antibodies directed against specific cell-surface proteins. The differential expression of these marker proteins was used to phenotypically distinguish one subpopulation of lymphocytes from another when analyzed via flow cytometry. This method was used to determine the relative percentages and absolute number of total B cells (CD45RA+; sIgM+), total T cells (CD3+; pan-T+), helper T cells (CD3 + CD4+), cytotoxic/ suppressor T cells (CD3 + CD8+), and the CD4:CD8 ratio in each of these lymphoid tissues. Additionally, all subsets of differentiating T cells in the thymus (i.e., CD4 + CD8-, CD4-CD8+, CD4 + CD8+, and CD4-CD8-cells) were distinguished using dual parameter analyses. Results of this study demonstrate that 1) the selected panel of antibodies used in this study can identify all lymphocyte subsets present in blood, spleen, and thymus of the rat and 2) male and female Sprague-Dawley rats show slight, but not statistically significant, differences in the proportions of some lymphocyte subsets present in select lymphoid tissues. This flow cytometry method can be used to accurately assess the potential immunotoxic or immunomodulatory effect of xenobiotic agents as characterized by changes in the phenotypic expression patterns or alterations in the quantity of lymphocyte subpopulations in the rat.

Animals↗
PubMed1997

TNF-alpha release from human peripheral blood mononuclear cells to predict the proinflammatory activity of cytokines and growth factors.

Therapeutic applications of novel growth factors and cytokines can be limited due to the oftentimes severe inflammatory reactions that are encountered in patients following parenteral administration. These inflammatory responses, hallmarked by fever, headache, and chills are mediated by the release of inflammatory cytokines following administration of protein-based therapeutics. TNF-alpha appears to be one of the most potent and pleiotropic inflammatory cytokines released during the early stages of an inflammatory response. In the present study, we have explored the use of an in vitro assay system to determine whether the release of TNF-alpha from human PBMC could be correlated with documented inflammatory activity in humans. The cytokines tested included rhGM-CSF, rhIL-2, rhIL-3, and rhIFN-gamma, rhG-CSF, which has been shown to lack substantial proinflammatory activity in humans, was also tested. The potent macrophage activator and inflammatory agent, LPS, was used as a positive control. Results of this study demonstrate and confirm an association between the inflammatory activity of cytokines observed in patients and the stimulation of TNF-alpha release from PBMC in vitro. This assay system can be used as a predictive tool in determining the inflammatory potential of novel growth factors and cytokines.

Cytokines↗
PubMed1997

The in vitro effect of vitamin D3 analogue EB-1089 on a human prostate cancer cell line (PC-3).

OBJECTIVE: To determine the effect of vitamin D3 analogue (EB-1089) on the growth and proliferation of a prostate cancer cell line (PC-3). MATERIALS AND METHODS: PC-3 cells (10(4) cells per well) were plated into 24-well tissue culture plates. After 24 h, the culture medium was replaced with one containing the vitamin D3 analogue EB-1089; a control treatment using only replacement medium was conducted in parallel. Cell proliferation was measured by the incorporation of 3H-thymidine 7 and 12 days after the addition of the vitamin D3 analogue. Cells were precipitated with 5% trichloroacetic acid and the radioactivity determined using a scintillation counter. Each experiment was performed at least five times. RESULTS: There was a significant dose-dependent inhibition of cell growth after 7 and 12 days of treatment with EB-1089, varying from 40 to 70% of the 3H-thymidine incorporation by controls, respectively. The maximum inhibition occurred with 0.1 micromol/L EB-1089 on day 7 and day 12 (both P < 0.01). Longer incubation times appeared to have a greater effect when higher concentrations of EB-1089 were used. CONCLUSION: These in vitro studies have shown that the vitamin D3 analogue EB-1089 can significantly reduce the growth rate of the prostate cancer cell line PC-3. This would support the hypothesis that deficiency of vitamin D increases the risk of prostate cancer and further in vivo testing of vitamin D is warranted for its potential role in active therapy.

Antineoplastic Agents↗
PubMed1997

Previous intravenous chemotherapy does not alter response rate or survival time of patients with hepatic metastases from colorectal cancer treated by hepatic artery chemotherapy.

BACKGROUND: The present paper addressed the issue of whether pretreatment with intravenous (i.v.) chemotherapy affects response rate or survival in patients receiving hepatic artery chemotherapy (HAC). METHODS: Case note reviews of 164 patients treated in a teaching hospital from June 1990 to July 1996 were carried out. RESULTS: The response rate and carcino-embryonic antigen (CEA) fall in the two groups was almost identical. There was a nonsignificant survival advantage in the non-pretreatment group. CONCLUSIONS: Previous administration of i.v. chemotherapy did not affect the CEA response of patients receiving HAC.

Antidotes↗
PubMed1997

Elderly persons' interpretation of a bodily change as an illness symptom.

Based on a community random sample of 406 elderly, factors that persuade an elderly person to interpret a bodily change as a symptom of illness are described. Three measures of such illness interpretation among 27 different bodily changes are used in analysis: giving an illness label to the change, consulting a physician for it, and/or using self-care for treatment. The three types of representations across all 27 bodily changes taken together, as well as among five typical complaints most commonly experienced, are reported. The findings show that the perceived seriousness of the bodily change and the general health context of the older person in which it has occurred are conducive to interpreting a bodily change as an illness symptom.

Aged↗
PubMed1997

Cryosurgery.

The in situ destruction of malignant tissue by freezing is a relatively new addition to the list of treatment options for patients with cancer in solid organs. Although skin cancers have long been treated by cryosurgery, the lack of suitable equipment for both delivering and monitoring the freezing process hindered further development of the treatment of more inaccessible lesions until the 1960s. At this time, Cooperz developed cryosurgical machines which enabled the destruction of CNS lesions in patients with Parkinson's disease and stimulated renewed interest in the application of cryosurgery to the treatment of cancer.

Journal Article↗
PubMed1997

Renal cryotherapy in a sheep model; a feasibility study.

PURPOSE: This study was designed to evaluate the safety and efficacy of renal cryotherapy as a possible treatment of renal malignancy with preservation of renal parenchyma. MATERIALS AND METHODS: Ten Merino sheep were anaesthetised and the right kidney was exposed through a retro-peritoneal approach. A 5 mm. cryotherapy probe (LCS 3000 Cryotec UK) was inserted into the lower pole of the kidney and freezing was undertaken to form an iceball 5 cm. in diameter. RESULTS: There was no mortality and no complications were observed. A transient rise in creatinine was observed post-operatively. The sheep were euthenased at 4 weeks and at necropsy macroscopic examination revealed a contracted, fibrotic wedge shaped lesion of 3 cm in diameter. Histological examination of the "cryolesion" revealed a central area of coagulative necrosis and a 5 mm rim of partial necrosis with preservation of renal tubules. CONCLUSION: We conclude that renal cryotherapy is safe and can achieve effective renal necrosis in the sheep model.

Animals↗
PubMed1997

Computed tomography changes following cryotherapy for hepatic cancer.

Encouraging survival and tumour marker results have been described in patients where the focally destructive technique, hepatic cryotherapy, is used to treat primary and secondary hepatic malignancy. Radiology allows assessment of the cryotherapy procedure and follow-up treatment. This paper aims to review and describe the appearance of hepatic cryotherapy by CT.

Cryosurgery↗
PubMed1997

Long-term results of the Angelchik prosthesis for gastro-oesophageal reflux.

INTRODUCTION: Between 1982 and 1989, 46 patients had insertion of an Angelchik prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent) subsequently had the prosthesis removed, all but one for intractable dysphagia. METHODS: Thirty-six of the original patients were followed by questionnaire, and 32 of these had a barium marshmallow swallow investigation. RESULTS: A high proportion of patients (20 of 26) with a prosthesis in situ had symptoms of dysphagia. On objective evaluation by marshmallow swallow, the transit time was significantly slower than that of an age-matched control group (P < 0.01), but showed no significant deterioration with time compared with previous postinsertion studies. CONCLUSION: The Angelchik prosthesis causes long-term dysphagia in a high proportion of patients, severe enough in one-quarter to necessitate its removal. Its continued use cannot, therefore, be recommended.

Adult↗