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Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 163 records · Page 9Linked to original sources
PubMed1996

Laparoscopic hepatic cryotherapy: a study of safety in rabbits.

Hepatic cryotherapy is used to treat unresectable liver tumors and could potentially be undertaken laparoscopically; however, the risk of gas embolism during laparoscopic hepatic cryotherapy has not been studied. Eight New Zealand White rabbits underwent laparoscopic hepatic cryotherapy with continuous precordial ultrasound monitoring for gas embolism. No episodes of gas embolism were detected, and at postmortem no intracardiac gas was found in any rabbit. In conclusion, this study found no evidence that gas embolism is any more likely to occur during laparoscopic than in open hepatic cryotherapy.

Animals↗
PubMed1996

Australian experience of cryoablation of liver tumors: metastases.

The authors' clinical experience of treating almost exclusively inoperable liver malignancy in 149 patients by cryotherapy is reviewed. There was only one 30-day death; morbidity was modest. Postoperative carcinoembryonic antigen (CEA) changes were extremely predictive of outcome in patients with liver metastases from colorectal cancer. For the group in which CEA levels returned to the normal range, median survival exceeded 1000 days. In addition, the authors reported encouraging results with cryotherapy as an adjunct to resection.

Australia↗
PubMed1995

Octreotide reduces the kinetic index, proliferating cell nuclear antigen-maximum proliferative index, in patients with colorectal cancer.

BACKGROUND: Somatostatin has been shown to inhibit in vitro and xenograft growth of human colon cancer. The kinetic index, proliferating cell nuclear antigen (PCNA), has previously been used to measure the effects of manipulation of growth of normal rectal epithelium. METHODS: Twenty-five patients with distal colorectal cancer were considered for entry in a presurgical study of Sandostatin (Sandoz, East Hanover, NJ) 1 mg every 8 hours. Biopsies were performed pretreatment, during treatment (14 days), and day of surgical resection (2 days off treatment). A control series of 16 patients underwent endoscopic and subsequent surgical biopsy. A kinetic index was created called PCNA-maximum proliferative index (PCNA-MPI), which was reproducible within one biopsy and between two separate biopsies. Multiple biopsies were taken from the growing edge of tumors, the most cellular and best-stained fields selected, and the highest 6 of 10 separate counted fields were used to produce PCNA-MPI. RESULTS: A significant decline in PCNA-MPI was observed in 6 of the 10 treated patients for whom all three biopsies were available, followed by a significant elevation on withdrawal of treatment. Changes in PCNA-MPI in the control group were less frequent and smaller. CONCLUSIONS: Sandostatin causes a reduction in PCNA-MPI in patients with human colorectal cancer.

Antineoplastic Agents, Hormonal↗
PubMed1995

Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors.

BACKGROUND: Liver metastases from neuroendocrine tumors often present with disabling symptoms due to syndromes of hormonal excess. A locally destructive technique such as hepatic cryotherapy not only alleviates symptoms but may improve survival in this group of patients. METHODS: Six patients with metastatic neuroendocrine tumors were treated with hepatic cryotherapy. Four patients were symptomatic and three of these had elevated tumor markers from ectopic hormone production. RESULTS: All patients are alive and asymptomatic, with a median follow-up of 24 months (range, 6 months to 6 years). All have had a complete radiologic response. All with elevated preoperative markers have had a greater than 89% decrease in tumor markers. Coagulopathy occurred in two patients necessitating additional surgery, but there was no other morbidity attributable to the cryotherapy. CONCLUSION: To the authors' knowledge, this study demonstrates for the first time that hepatic cryotherapy offers supportive treatment for patients with neuroendocrine tumors metastatic to the liver. Cryotherapy alleviates symptoms and may improve survival.

Adenoma, Islet Cell↗
PubMed1995

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice.

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type-specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.

Animals↗
PubMed1995

Constitutive and inducible levels of egr-1 and c-myc early growth response gene expression in self-renewing B-1 lymphocytes.

B-1 lymphocytes constitute a mature B cell population that differs from conventional B cells in signaling requirements for cell cycle progression, being unusually responsive to PKC agonism but refractory to antigen receptor stimulation. Further, B-1 cells are self-renewing and derive from surface immunoglobulin-positive precursors. A previous report on clonally derived B-1 cells suggested that increased levels of expression of c-myc might underlie these unusual growth characteristics. This issue has now been reexamined using primary B-1 cells. The possible role of egr-1, in addition to c-myc, in specifying the responsiveness of B-1 cells was evaluated by determining levels of gene expression at baseline and after mitogenic treatment. Expression of the two genes was similar in B-1 and B-2 cells prior to stimulation. Subsequently, B-1 cells responded with higher levels of gene expression than B-2 cells regardless of ultimate cell cycle progression, with the exception of stimulation by anti-Ig. Overall, there was no apparent direct correlation between stimulated levels of expression of egr-1 or c-myc and mitogen-induced S phase entry, nor were B-1 cells characterized by constitutively elevated levels of either proto-oncogene that might explain their capacity for self-renewal.

Animals↗
PubMed1995

Hepatic cryotherapy: double-freeze cycles achieve greater hepatocellular injury in man.

Hepatic cryotherapy is a relatively new technique used to treat both primary and secondary tumors. This paper concerns the changes in serum aspartate transaminase (AST) in 45 patients following both single and double freeze with partial thaw cycles. There was considerable elevation in serum AST, greatest on the day of operation, and there was a significantly higher peak AST following the double-freeze cycles (1159; SE, 117.5) compared with single-freeze/thaw procedures (437; SE, 61.7). This finding indicates greater hepatocellular disruption which may be important both in planning clinical hepatic cryosurgery to achieve adequate destruction and also to avoid the morbidity of the cryoshock phenomenon.

Aspartate Aminotransferases↗
PubMed1995

SMS 201.995 (Sandostatin) enhances in-vitro effects of 5-fluorouracil in colorectal cancer.

5-fluorouracil (5-FU) is still the most effective cytotoxic agent for the treatment of human colorectal cancer. Response rates, however, vary between 5-20%. One attempt to improve the effect of 5-FU is through biomodulation. We have previously found the somatostatin analogue, SMS 201.995 (Sandostatin, Sandoz), to inhibit both the in-vitro and in-vivo growth of some human colon cancer cell lines. It may act specifically by means of receptors on the surface of tumour cells, or by reducing the concentration of some growth factors. We report that, when 5-FU at 0.125 and 0.25 micrograms/ml was combined with SMS 201.995 at 10(-12) x 2 to 10(-8) x 2M, an enhanced inhibition of in-vitro growth of two human colorectal cancer cell lines (C170 and LIM 1215) was achieved. Effects were measured using [3H]-thymidine uptake and by a colorimetric assay of cellular respiration (MTT, Promega, Sydney). SMS 201.995 alone has minimal inhibitory effects, whilst 5-FU alone shows inhibition as low as 39.6% of control. When 5-FU was then combined with SMS 201.995, a 10-30% inhibition occurred compared to the 5-FU control. The combination of 5-FU and SMS 201.995 may be a useful method of improving response to human colorectal cancer therapy.

Adenocarcinoma↗
PubMed1995

A randomized trial of cimetidine with 5-fluorouracil and folinic acid in metastatic colorectal cancer.

Cimetidine has demonstrated a survival benefit in a randomized trial as adjuvant therapy for gastric cancer. We have demonstrated expression of histamine receptors on colon cancer cell lines and inhibition of their growth with cimetidine. Cimetidine also activates suppressor T cells and stimulates cell-mediated immunity. We therefore performed a randomized controlled clinical trial to determine the effect of cimetidine 400 mg given twice daily in conjunction with chemotherapy vs chemotherapy alone. Thirty-eight patients were randomized and 35 patients were eligible for further analysis. Both groups were well matched for pre-treatment characteristics. There was no difference in overall response. There was, however, a significantly increased rate of CEA response in the cimetidine group. Four of 11 patients (36%) in the cimetidine group had a CEA response compared to none of eight in the control. Meaningful comparisons of overall survival cannot yet be made. This study demonstrates that cimetidine has encouraging activity in increasing CEA response in patients with metastatic colorectal cancer treated with chemotherapy. This observation needs to be extended in a larger randomized study, which is currently underway.

Adult↗
PubMed1995

Changes in dietary fat intake preceding the diagnosis of cancer.

We studied changes in dietary fat intake preceding the diagnosis of cancer in 96 men diagnosed with cancer during the Coronary Primary Prevention Trial and Post-trial Follow-up. Diet was assessed semiannually by 24-hour recall for the duration of the trial. Dietary fat intake was elevated in the interval 12-24 months before diagnosis compared with the interval 24-36 months before diagnosis [6.9 gm per day; 95% confidence interval (CI) = 0.04-13.7]. The percentage of calories as fat was also elevated (1.9%; 95% CI = 0.34-3.4). Fat consumption decreased in the 0- to 12-month prediagnostic interval. The basis for the elevation is unclear, but it may have been due to the metabolic effects of cancer before its diagnosis. Case-control studies of long-term diet may overestimate positive associations between dietary fat and cancer risk if the cases' recall includes the prediagnostic period, during which fat intake is elevated. In analyses of prospective studies of dietary fat and cancer, data from within the first 2-3 years of baseline should be examined separately to evaluate the potential for bias introduced by the inclusion of measurements representing transient elevations in dietary fat intake.

Adult↗
PubMed1995

Hepatic artery chemotherapy for colorectal liver metastases.

Fifty per cent of patients with colorectal cancer develop hepatic metastases but only a minority are candidates for potentially curative surgical resection. Hepatic artery chemotherapy (HAC) has been used to treat patients with non-resectable metastases confined to the liver. Although response rates to HAC have been shown to be higher than response rates to systemic chemotherapy, the advantage in terms of survival has been debated. Furthermore, HAC requires surgical catheter placement which adds to the cost and morbidity of treatment. There have now been eight prospective randomized trials of HAC vs intravenous chemotherapy and/or supportive therapy. The present paper analyses the results of these trials with particular reference to survival. Surgical morbidity, treatment-related toxicity and cost are also discussed.

Antineoplastic Agents↗
PubMed1995

Cryotherapy of liver tumours--a practical guide.

The use of cryotherapy for the treatment of some unresectable liver tumours has been clearly established as a therapeutic option. Intra-operative ultrasound has enhanced the process by enabling the surgeon to identify hepatic lesions and to allow visualisation of the freezing process to ensure that the cryolesion will include the tumour mass. The purpose of this paper is to provide a practical guide to surgeons who wish to perform cryotherapy of liver tumours. Patient selection and anaesthetic considerations are important. The surgeon should be able to deal with the complications of cryotherapy, particularly the intra-operative haemorrhage which may arise from cracking of the hepatic parenchyma as the iceball thaws. Follow-up is based on tumour marker assay and imaging of the liver and repeat cryotherapy can be considered for selected cases.

Cryosurgery↗
PubMed1995

An experimental study of optimal parameters for bipolar electrocoagulation.

The role of artery diameter, probe force application (94, 250 or 491 g), coagulation time (2, 10, or 20 secs) and BICAP generator output (5, 10) were studied in rabbit arteries of 3 to 5 mm hemicircumference. Arterial welds were then tested to destruction by increasing intraluminal pressure. The best arterial welds were achieved by the highest force and coagulation time; high generator output did not improve weld strength. These in vitro experiments suggest that when treating a bleeding peptic ulcer, BICAP therapy should be done with a low generator output of 5 or less, for at least 20 seconds per site, and with as great a compression force as possible.

Animals↗