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Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 145 records · Page 8Linked to original sources
PubMed1997

High serum carcinoembryonic antigen concentration in patients with colorectal liver metastases is associated with poor cell-mediated immunity, which is predictive of survival.

BACKGROUND: Carcinoembryonic antigen (CEA) inhibits lymphocyte function and patients with cancer have lower cell-mediated immunity (CMI) than the normal population. To test this association an investigation was made of the relationship between CMI score, CEA level and survival. METHODS: CEA level, CMI score and other variables were compared with the survival time of 109 patients with colorectal liver metastases using Cox regression analysis. RESULTS: There was a significant association between CMI and CEA categories (P = 0.04, chi 2 test). The odds of patients with normal CMI having a CEA level in the upper quartile observed for all patients were 22 per cent of those of patients with depressed CMI (odds ratio 0.22 (95 per cent confidence interval (c.i.) 0.03-0.90), mid-P corrected). The median survival time of patients with normal CMI scores was 943 days compared with 488 days for those with depressed CMI (P = 0.03, log rank test; P = 0.04, Peto). The mortality risk of patients with normal CMI at entry to the study was, in the first 2 years of treatment, 40 per cent of that of patients with depressed CMI (95 per cent c.i. for relative risk 0.20-0.82, Cox regression). CONCLUSION: In patients with colorectal hepatic metastases, CMI is predictive of survival and a raised serum CEA level is associated with depressed CMI.

Adult↗
PubMed1996

Analysis of rat cytochrome P450 isoenzyme expression using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

A method was developed using reverse transcriptase-polymerase chain reaction (RT-PCR) to selectively detect and qualitatively determine the levels of mRNA expression of the major isoenzymes of cytochrome P450 (P450 1A1, 1A2, 2B1/2, 2C11, 2E1, 3A1, 3A2, and 4A1) and fatty acyl-CoA oxidase (FACO) in the rat. Total liver RNA was isolated from male Sprague-Dawley rats treated with various inducers of cytochrome P450 (P450) and analyzed for the presence and relative quantities of each P450 isoenzyme mRNA using this technique. The specificity of the oligonucleotide primers used in the detection of each P450 mRNA was tested and confirmed through the simultaneous analysis of liver microsomal protein preparations for the presence of constitutive or inducible P450 apoprotein and enzyme activities using western immunoblotting and specific enzyme activity measures, respectively. This method of P450 expression analysis is proven to be highly specific and readily applicable for the assessment of P450 enzyme induction and down-regulation in the rat during routine toxicology studies when expression of the gene product is regulated by transcriptional activation and/or mRNA stabilization.

Animals↗
PubMed1996

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elevates basal B-cell intracellular calcium concentration and suppresses surface Ig- but not CD40-induced antibody secretion.

Humoral immune responses to either T-independent or T-dependent antigens have previously been shown to be suppressed by the halogenated aromatic hydrocarbon environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) through direct action on B-lymphocytes. To better understand the molecular nature of the TCDD-induced suppression of B-cell differentiation, we studied the effects of TCDD using in vitro models of T-independent (antibody directed against surface IgM) and T-dependent [activated T-helper (TH) cells bearing CD40 ligand] B-cell maturation. We report here that TCDD suppresses murine B-cell IgM secretion induced by either soluble or insolubilized anti-IgM plus lymphokines but does not affect IgM secretion stimulated by activated T(H)-cells and lymphokines. Because soluble or insolubilized anti-IgM but not fixed, activated TH-cells was found to trigger increases in intracellular ionized calcium in isolated B-cells, the effect of TCDD exposure on B-cell intracellular calcium concentration and mobilization was examined. In comparison to the endoplasmic reticulum calcium ATPase inhibitor thapsigargin, which induces an immediate rise in resting [Ca2+]i of up to four- to fivefold, TCDD treatment did not produce a rapid increase in [Ca2+]i but did result in an elevation of basal levels of nearly the same magnitude 18 hr postexposure. However, anti-IgM-induced calcium transients were similar in the presence or absence of TCDD. TCDD exposure also produced instability of the calcium concentration curve, with the observed elevation of basal intracellular calcium occurring after both in vitro and in vivo treatment paradigms. The immunomodulatory profiles of activity of TCDD and thapsigargin on the B-cell proliferative response to PMA plus ionomycin differ, suggesting that the kinetics of calcium release by these compounds dictates the overall effect on the responding B-cell. Taken together, the data indicate that TCDD elevates resting intracellular calcium levels in murine B-cells and may selectively inhibit calcium-dependent signaling pathways linked to surface Ig.

Animals↗
PubMed1996

Primary resection and synchronous regional hepatic chemotherapy or cryotherapy for colorectal cancer with liver metastases.

Twenty-two patients with colorectal cancer and synchronous unresectable hepatic metastases were treated by resection the primary tumour with concurrent insertion of an Infusaid infusaport system for regional chemoperfusion (hepatic arterial 20, portal venous 2). Four patients in addition had cryotherapy the liver metastases. Morbidity from the synchronous procedures was minimal. Median survival was 10 months. Four patients with poorly-differentiated tumours had a poor response, with a median survival of 3.75 months.

Aged↗
PubMed1996

Ranitidine and cimetidine differ in their in vitro and in vivo effects on human colonic cancer growth.

Histamine has recently been shown to be a growth factor for some gastric and colorectal cancer cells. Previous studies have shown that cimetidine blocks in vitro and in vivo histamine-stimulated growth and cAMP release from the human colonic cancer cell line, C170. In this study, ranitidine, another H2 receptor antagonist, did not affect either basal or histamine-stimulated in vitro proliferation of C170, and failed to prevent cAMP release in vitro. Ranitidine did not inhibit in vivo growth of C170 at a dose of 1, 10, 25, 50 or 100 mg/kg, in contrast to 50 mg/kg/day cimetidine, which produced 39.3% inhibition of tumour volume (p<0.01) after 23 days' treatment. Ranitidine did not inhibit in vivo histamine-stimulated growth of C170 cells . LIM2412, another colonic cancer cell line, was significantly stimulated by both cimetidine and ranitidine in vivo. Ranitidine had no effect on in vitro cell proliferation.

Adenocarcinoma↗
PubMed1996

In vitro and in vivo assessment of urethral warming catheters for the transperineal cryoablation of prostatic carcinoma.

OBJECTIVE: To evaluate the two most common urethral warming catheters currently available for their effectiveness in preventing urethral injury in an animal model and thus during transperineal cryosurgery for the treatment of prostate cancer. PATIENTS, MATERIALS AND METHODS: The warming efficiency of the variable-diameter thin latex-balloon catheter (Cook, Australia) and the fixed-diameter PVC catheter (Candela, USA) were evaluated in a water-bath. A sheep model was then used for subsequent experiments to further evaluate the better catheter. The technique used for the insertion of the Cook catheter in a series of 33 patients treated with prostate cryosurgery is also described. RESULTS: In vitro, the Cook catheter was more effective (P < 0.01) than the Candela catheter in preventing localized cooling. In vivo, results in five animals showed that the urethral epithelium was viable in all sections that had been protected by the catheter and focally denuded or necrotic in those sections not protected, with each animal used as its own control (P < 0.01 Fisher's exact test). The 33 patients treated while using the Cook catheter had no subsequent complications. CONCLUSION: The urethral warming catheter currently in use for prostatic cryosurgery in Australia is more effective in vitro than its competitor and is effective in preventing urethral injury in vivo.

Catheterization↗
PubMed1996

Critical temperature for in vivo cryoablation of human prostate cancer in a xenograft model.

OBJECTIVES: To assess the in vivo sensitivity of human prostate cancer cells (PC3) to cryoablation and thus define the minimum temperature needed to prevent the recurrence of cancer after percutaneous transperineal radical prostatic cryoablation. MATERIALS AND METHODS: Twenty-five male nu/nu mice were inoculated by a subcutaneous injection with 5 x 10(5) PC3 cells. After 3 weeks the tumours (mean area 60.4 mm2, SEM 5.7) were frozen using a 3 mm cryotherapy probe (LCS 3000 Cryotech UK) to temperatures ranging from 0 degrees to -40 degrees C. RESULTS: No tumours recurred in seven mice which had tumours frozen to < -15 degrees C. There were eight recurrences in 15 mice which had tumours frozen to between 0 degree and -15 degrees C, and all were confirmed histologically. CONCLUSIONS: The minimum temperature required to prevent recurrence of tumours from human prostate cancer cells was < -15 degrees C in this in vivo mouse model.

Animals↗
PubMed1996

In vitro effect of histamine and histamine H1 and H2 receptor antagonists on cellular proliferation of human malignant melanoma cell lines.

Histamine is an established growth factor for gastric and colorectal cancer. Contradictory data for response of melanoma to histamine have been reported. Our aims were to determine the effect of histamine and H1 and H2 receptor antagonists on cell growth and cyclic AMP production. Four human melanoma cell lines were cultured with a range of concentrations of histamine, and with the H2 receptor antagonists cimetidine, ranitidine or famotidine, or the H1 receptor antagonist diphenhydramine. Cellular proliferation was measured by the uptake of [3H]-thymidine. Cyclic AMP production was also measured to determine the receptor status of the cell lines. Histamine significantly stimulated growth in two of four cell lines, with maximal stimulation at 1 x 10(-8) M. This effect was inhibited by all four antagonists in a dose-dependent manner. Histamine [10(-7) to 10(-4) M] also induced a dose-dependent increase in cyclic AMP production in the two histamine-responsive cell lines, suggesting that these cell lines express H2 receptors. We conclude that there may be a role for histamine receptor antagonists in melanoma treatment and that further investigation is warranted.

Cell Division↗
PubMed1996

Dose dependent in vivo inhibition of human colorectal cancer (LoVo) by the gastrin receptor antagonist, CI-988.

1. The dose-response relationship of a new, potent and selective cholecystokinin B receptor antagonist, CI-988, on the growth of LoVo, a human colon cancer cell line, was studied in vivo. 2. We have previously shown the growth of LoVo to be inhibited both in vitro and in vivo by CI-988. 3. LoVo was grown for 10 days in nude mice that were then treated with CI-988 at 1, 5, 10, 25 and 50 mg/kg per day orally for 20 days. 4. CI-988 significantly inhibited the growth of xenografts at all concentrations except the highest concentration of 50 mg/kg per day (P < 0.00001; ANOVA). The largest inhibitory activity was caused by the 10 mg/kg per day dose, causing a 47% inhibition at day 29 (P = 0.00003: Newman-Keul's test). 5. CI-988 may be of use in inhibiting the growth of colorectal cancer.

Animals↗
PubMed1996

Major upper gastrointestinal haemorrhage associated with hepatic arterial chemoperfusion.

BACKGROUND: The present study reviews the nature of upper gastrointestinal complications of hepatic arterial chemoperfusion at a tertiary referral centre for the treatment of hepatic malignancy. METHODS: The patients involved in the present study all had major upper gastrointestinal (GI) haemorrhage and were undergoing hepatic arterial chemoperfusion. RESULTS: Eight patients had major upper GI haemorrhage. Three of these patients were not referred for surgical management, and all three patients died. The five patients who were admitted or transferred to our unit and who underwent surgery all survived. CONCLUSIONS: These complications are probably caused by extravasation of 5-fluorouracil (5-FU) following thrombosis of the gastroduodenal artery. The resulting cavity may perforate into the hepatic artery, portal vein, duodenum or biliary tree. Surgeons and oncologists should be aware of these complications. If upper abdominal pain occurs, chemoperfusion should cease immediately and an urgent investigation, which may include catheter angiography, gastroscopy and computed tomography (CT) scanning, should be carried out to exclude an hepatic artery pseudo-aneurysm.

Aged↗
PubMed1996

Gastrin receptor antagonist CI-988 inhibits growth of human colon cancer in vivo and in vitro.

BACKGROUND: Whilst gastrin has been found to be trophic for some colorectal cancer cell lines, and gastrin receptor antagonists are able to block this phenomenon, their potency has been modest. METHODS: The effect of a new, potent and selective CCK B receptor antagonist, CI-988 on the growth of LoVo, a human colon cancer cell line both in vitro and in vivo was instigated. RESULTS: Basal growth of LoVo in vitro was inhibited by up to 58.93 +/- 7.30% with concentrations of CI-988 as low as 1 X 10(-11) mol/L whereas the addition of gastrin (G17) at 0.5 nmol/L had no effect. LoVo was also grown in vivo for 10 days in nude mice subsequently treated with CI-988 at 10 mg/kg per day orally for 20 days. CI-988 inhibited the growth of xenografts by 53%. CONCLUSION: This was the first study in cancer with this potent gastrin receptor antagonist, CI-988. The results suggest that CI-988 may be of use in inhibiting the growth of colorectal cancer.

Administration, Oral↗
PubMed1996

Two cases of spontaneous liver rupture and literature review.

Spontaneous liver rupture is uncommon, difficult to diagnose and carries a universally high mortality. It has been well documented to occur as a complication of primary or secondary hepatic malignancy. Similarly, there are 28 cases of ruptured haemangiomata described in the world literature. It is also well described in severe pregnancy-induced hypertension and is said to carry a mortality of 18% for patients treated by packing and drainage of the haematoma and 75% for patients treated with liver resection. Two female patients aged 60 and 61 presented to our accident and emergency department. One had a history of hypertension only and the other a history of a bleeding diathesis from the lupus anticoagulant. Both presented with hypotension and abdominal pain and both were diagnosed by abdominal CT scan. One was treated with hepatic artery ligation and tamponade and the other with liver resection and correction of the coagulopathy. Neither had any evidence of a ruptured hemangioma or tumor at laparotomy or on histological examination, and both are alive and well. The conclusions to be drawn from this review and our own recent experience is that the treatment of choice for ruptured haemangiomata is liver resection and, for rupture during pregnancy, is tamponade with packs and evacuation of the haematoma. Hepatic arteriography and embolisation, if possible, is a useful adjunct. Correction of any coagulopathy is essential. We can only speculate that the aetiology in our patients was uncontrolled hypertension in one and coagulopathy in the other.

Female↗
PubMed1996

Laparoscopic vs open ultrasound of the liver: an in vitro study.

Intra-operative contact ultrasound is a sensitive method of detecting liver tumours. The aim of this study was to compare the sensitivity of open contact ultrasound (OUS) of the liver with laparoscopic contact ultrasound (LUS). Hypoechoic "lesions" were created in 5 fresh pig livers by inserting 28 grapes via small incisions in the inferior surface. The size (range 8-25 mm) and location of each grape was recorded. Scanning was undertaken in random order by two experienced independent observers with no knowledge of the size, number or position of the lesions, using an Aloka 650 series scanner and 7.5 MHz probes. The crude sensitivity with OUS was 96% and 100% respectively for the two observers, and 92% for each with LUS. One grape was interpreted as 2 separate grapes on LUS by one observer. Absolute sensitivity (grapes identified in the correct location) was 86% and 93% respectively with OUS and 79% for each observer with LUS. LUS was almost as sensitive as OUS in this model of hepatic metastases.

Animals↗