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Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 235 records · Page 13Linked to original sources

Anaesthetic experience with cryotherapy for treatment of hepatic malignancy.

Hepatic cryotherapy is a relatively new technique, currently employed in the treatment of unresectable liver malignancy, which involves direct freezing of tumour deposits with liquid nitrogen. In a review of 26 patients undergoing this procedure, the anaesthetic considerations are defined. The total operation time ranged from 133 to 410 minutes. In spite of preventative measures, varying degrees of hypothermia occurred (range 33.7 degrees C to 36.5 degrees C), but no sequelae were encountered. Mean blood loss was 926 ml, and eleven patients required blood transfusion of between one and five units. There was a marked drop in platelet count associated with cryotherapy (mean fall of 123,000/mm3 by the second postoperative day). Following the procedure, fever and basal pulmonary atelectasis were common, while hypoglycaemia and renal impairment occurred on single occasions. Six patients underwent postoperative mechanical ventilation. Despite this, the mean hospital stay was under seven days.

Adult↗

Somatostatin receptors in human colorectal cancer.

We have previously reported that somatostatin may reduce tumour cellular proliferation in patients with colorectal carcinoma. However, it is not known what proportion of primary colorectal cancers express somatostatin receptors. We have therefore evaluated somatostatin receptor status in 50 primary colorectal cancers. Twelve (24%) of the cancers were shown to be somatostatin receptor positive. There was no correlation between receptor status and tumour stage or grade.

Autoradiography↗

Serum gastrin concentrations in colorectal cancer patients.

Fasting serum gastrin concentrations were shown to be elevated in colorectal cancer patients compared with controls (P = 0.0037), which was mainly accounted for by a subgroup of patients who had significantly elevated levels. In cancer patients there was no difference in gastrin concentrations in blood taken from a tumour-draining mesenteric vein and from a peripheral vein at the time of colonic resection. Serum gastrin concentrations were significantly lower after apparently curative resection for colorectal cancer (P = 0.028), suggesting that the elevated serum gastrin seen in these patients may be due, at least in part, to secretion of gastrin by the tumour.

Adult↗

Intracellular gastrin in human gastrointestinal tumor cells.

Flow cytometry and immunohistochemical analyses of the human gastric adenocarcinoma cell line MKN45G identified an intracellular peptide recognized by an anti-gastrin-17 (G17) antiserum but not by an anti-cholecystokinin-specific antiserum. Staining was not associated with the parental line MKN45, of which MKN45G is a clonal variant. The MKN45G cell line had elevated in vitro growth in serum-free medium in which the proliferation of MKN45G cells but not MKN45 cells was reduced to 58% of the control value by treatment with a rabbit anti-G17 antiserum. This inhibition of proliferation was reversed by preabsorbing the antiserum with excess G17. Disaggregated primary human gastric and colorectal tumors were screened for gastrin immunoreactivity by flow cytometry, and 6 of 28 colorectal and 8 of 22 gastric tumors had greater than 20% positively staining cells.

Adenocarcinoma↗

Changes in plasma lipid and lipoprotein cholesterol and weight prior to the diagnosis of cancer.

Changes in lipoprotein cholesterol, total plasma cholesterol, and weight prior to the diagnosis of cancer were examined in 103 men who developed cancer in a cohort of 3805 type IIa hyperlipidemic men aged 35-59 enrolled in the Lipid Research Clinics Coronary Primary Prevention Trial. Study measurements were made bimonthly. After adjusting for the effects of the trial intervention and other determinants of lipid levels, the cholesterol levels of the cases diagnosed with nonlocalized cancer dropped below the expected level approaching diagnosis when compared to the entire study population. The decrease averaged 9.3 mg/dl and began about 2 years prior to diagnosis. Weight levels dropped an average of 1.2 kg over the same period. Weight and cholesterol were significantly lower than expected within 8 months of diagnosis (P less than 0.05). No decrease was seen for those diagnosed with localized malignancies. Patterns for low-density lipoprotein cholesterol reflected those of total cholesterol. There was no clear relationship between cancer diagnosis and patterns of change for triglycerides and high-density lipoprotein cholesterol. In the future, investigations of any relationship between a host physiological state and cancer occurrence should account for the metabolic effects of preclinical disease demonstrated here. To protect against spurious conclusions, incident cases occurring within 2 years of measurement should be analyzed separately. In studies of cancer mortality, deaths occurring within 3.5 years of the base-line measurement should be analyzed separately.

Adult↗

Detection of colorectal liver metastases using intraoperative ultrasonography.

Intraoperative ultrasonography of the liver has been carried out in 99 patients undergoing surgery for colorectal cancer. Palpation of the liver, preoperative abdominal ultrasonography and computed tomography scanning were also performed in all patients. Metastases were identified in 26 of the 99 patients (26 per cent). Intraoperative ultrasonography diagnosed more metastases than palpation, abdominal ultrasonography or CT scanning, identifying metastases in 24 of the 26 patients, including six patients in whom the metastases were not detected by any other technique. Identification and localization of impalpable liver metastases is therefore possible using intraoperative ultrasonography.

Colorectal Neoplasms↗

Oestrogen receptor D5 antibody is an independent negative prognostic factor in gastric cancer.

Recent studies have demonstrated oestrogen receptors in tissues other than those considered to be sex hormone responsive, for instance in gastric cancer. In vitro experiments have shown oestradiol to be trophic to gastric cancer cell lines. The effect of D5 (an oestrogen receptor-related protein) status on survival was therefore studied in a group of 188 consecutive patients undergoing surgery for gastric cancer. Ninety-two patients (49 per cent) were positive for the D5 antibody. There were no differences between the D5-positive and D5-negative groups for age or adverse prognostic features such as high grade tumours or advanced stage. The D5-negative patients had a significant survival advantage over the D5-positive patients. The 95 per cent confidence interval for survival in the patients with D5-negative tumours was 63-101 weeks compared with 39-66 weeks for the patients with D5-positive tumours (Mantel-Cox statistic = 4.15, P = 0.042). Prognostic factor analysis with a Cox proportional hazards model showed tumour stage (P = 0.001) and D5 status (P = 0.003) to be significant independent factors in gastric cancer. Laurén type, grade and gender were not significant independent factors in this small series.

Aged↗

Use of the ultrathin choledochoscope in cholecystectomy.

Use of the ultrathin choledochoscope (2mm) was evaluated in 80 patients undergoing routine cholecystectomy. It was used successfully in 67 (84 per cent) patients. There were eight (12 per cent) explorations of the common bile duct and no negative explorations. The instrument was helpful in determining the nature of an equivocal on-table cholangiogram. The ultrathin choledochoscope may be useful in reducing the rate of negative common bile duct exploration.

Adult↗

High and prolonged pulmonary tissue concentrations of azithromycin following a single oral dose.

Antibiotic concentrations in pulmonary tissue samples and plasma were studied in this open investigation. Twenty-nine patients scheduled for elective pulmonary surgery received a single oral dose of 500 mg azithromycin 24, 72, 96 or 120 h prior to the operation; two patients received 250 mg b.i.d. Blood samples were taken before and at the time of resection, and tissue was obtained during surgery. Plasma and tissue concentrations of azithromycin were measured by high performance liquid chromatography (HPLC) and a microbiological bioassay. Only one patient had a detectable plasma concentration of azithromycin (0.13 micrograms/ml), measured 24 h post-dose by HPLC. However, high and sustained levels were found in lung tissue: mean concentrations measured by HPLC were 3.10 micrograms/g (SD +/- 2.17), 2.55 micrograms/g (SD +/- 1.36), 3.94 micrograms/g (SD +/- 2.40) and 3.13 micrograms/g (SD +/- 0.50) at 24, 72, 96 and 120 h, respectively. Bioassay results were similar to those for the HPLC assay. In summary, azithromycin levels in pulmonary tissue remained close to 3 micrograms/g for up to 5 days after a single oral 500 mg dose, in contrast to plasma levels which were much lower. The lung concentrations found are inhibitory for many sensitive respiratory pathogens and short-course azithromycin therapy is therefore a possibility.

Administration, Oral↗

Azithromycin levels in plasma and gastric tissue, juice and mucus.

Azithromycin is the first member of a new class called the azalides. Its distribution in gastric tissues was studied in 27 patients (mean age 66 years) with proven gastric cancer due to be resected. Five groups of patients received a single 500 mg oral dose of azithromycin 24, 48, 72, 96 or 120 h pre-operatively. Samples of blood, gastric juice, mucus and gastric tissue were taken and azithromycin assayed by high performance liquid chromatography. There was an increase in the level of azithromycin in gastric juice up to the 73-96 h period reaching a median peak of 0.20 micrograms/ml. There were higher levels of azithromycin in gastric mucus (approximately double the maximum attained in gastric juice) at each of the time periods to 120 h after the dose of azithromycin. Much higher levels were seen in the gastric tissue (median peak of 4.6 micrograms/g), which were statistically significant compared with gastric juice for the first two time periods (24-48 h, p = 0.005; 49-72 h, p = 0.012). Concentrations seen in the gastric tissue specimens were between five- and 10-fold greater than those seen in gastric mucus, and approximately 20-fold greater than the levels seen in gastric juice at each of the time periods after dosing. It is concluded that remarkably high levels of azithromycin are found in gastric tissue within 24 h of a 500 mg oral dose and that these levels persist over a five-day period. There exists a significant concentration gradient from gastric tissue to gastric juice. Such levels may be advantageous in the therapy of Helicobacter pylori infections.

Administration, Oral↗

Stereoselective effect of morphine on antinociception and endogenous opioid peptide levels in plasma but not cerebrospinal fluid of dogs.

Morphine releases endogenous opioids into the circulation of dogs. To test the stereospecificity of this effect, as well as to determine whether morphine also releases endogenous opioids centrally, which might be involved in its antinociceptive action, the effects of (-)-morphine sulfate (10 mg/kg, sc) or (+)-morphine hydrobromide on antinociception in a dog tail-flick test, on semi-quantified morphine-induced signs of salivation, emesis, defecation and ataxia, and on the plasma and cerebrospinal fluid (CSF) levels of endogenous opioid peptides were studied. Plasma and CSF levels of immunoreactive beta-endorphin (i-BE), met-enkephalin (i-ME), leu-enkephalin (i-LE), and dynorphin (i-DY) were quantified by radioimmunoassay in octadecylsilyl-silica cartridge extracts. Immunoreactive morphine (i-M) levels were measured in unextracted samples. (-)-Morphine treatment significantly increased antinociception, morphine-induced signs, i-M levels in plasma and CSF, and i-BE, i-ME, and i-LE levels in plasma, but not CSF. Levels of i-DY remained constant in plasma and CSF. (+)-Morphine treatment did not alter any of these parameters, indicating that the effects of morphine on nociception, behavioral signs, and plasma endogenous opioids in dogs were stereoselective. It is concluded that morphine does not cause an increase in immunoreactive endogenous opioid peptides in the CSF at the time of its peak antinociceptive effect.

Animals↗

A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update.

2,3,7,8-tetrachlorodibenzo-p-dioxin, more popularly called dioxin or TCDD and referred to in this review as 2,3,7,8-TCDD, is considered the prototype of the polychlorinated dibenzo-p-dioxins (PCDD). The PCDD are true contaminants and are formed primarily as byproducts in the manufacture of materials requiring the use of chlorinated phenols and during the combustion of chlorinated chemical products. From an environmental perspective, the PCDD have been most closely associated with the use of a number of phenolic herbicides, including Agent Orange, which is a 1:1 mixture of the butyl esters of 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). 2,3,7,8-TCDD and related PCDD are not produced commercially except in small amounts for research purposes and to date, have no known human benefit. 2,3,7,8-TCDD has been demonstrated to be the most potent and the most biologically active congener among the halogenated aromatic hydrocarbons (HAH), which include polychlorinated and polybrominated biphenyls (PCB and PBB, respectively) and the polychlorinated dibenzofurans (PCDF), in addition to the PCDD. An updated review on the effects of 2,3,7,8-TCDD on immunocompetence is timely from a number of perspectives. First, effects on immune function have been demonstrated to be among the earliest and most sensitive indicators of 2,3,7,8-TCDD-induced toxicity. Second, recent evidence indicates that exposure to 2,3,7,8-TCDD causes changes in innate immunity in addition to the changes in acquired immunity (i.e., which include effects on both cell-mediated and humoral immunity) previously shown to be associated with this chemical. Third, effects on immune function are almost universally observed among the animal species in which it has been evaluated, including some non-human primates. Fourth, effects of 2,3,7,8-TCDD on specific indicators of immune function have been correlated with changes in host resistance capabilities, which are often considered to be more holistic indicators of immunocompetence. Fifth, there are several reports which describe possible effects of 2,3,7,8-TCDD and related compounds (i.e., primarily PBB and PCB) on immune function in humans. It is important to emphasize at the onset that these studies have triggered much controversy, both political and scientific. However, it is equally important to speculate that at least part of the controversy associated with man's sensitivity to the immunological effects of 2,3,7,8-TCDD may be that the most appropriate approaches have heretofore not been applied. This possibility is discussed further in this review.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Co-stimulation of gastrointestinal tumour cell growth by gastrin, transforming growth factor alpha and insulin like growth factor-I.

Epidermal growth factor receptors and insulin like growth factor-I receptors were co-expressed on two gastric and three colorectal tumour cell lines. Previous studies have shown that gastrin receptors were also expressed at a low level or two of these cell lines. Both TGF alpha and IGF-I promoted cell growth in all of the cell lines tested. The cell doubling time of a colorectal cell line was reduced from 48 to 30-34 h. Furthermore the effects of the growth factors were additive. Each growth factor also increased the response of the cells to gastrin, but a combination of both growth factors and gastrin did not further increase growth.

Cell Division↗

The effect of long acting somatostatin analogue SMS 201.995 therapy on tumour kinetic measurements and serum tumour marker concentrations in primary rectal cancer.

Twelve patients with rectal carcinoma were treated for 2 weeks with the somatostatin analogue SMS 201.995. Effects of this therapy were assessed using serum marker concentration, Ki67 and gastrin-immunoreactivity of the primary tumour. In four out of 12 patients, a significant decrease in Ki67 immunoreactivity was seen during SMS 201.995 treatment while in the remaining eight patients there was no significant change in Ki67 expression. Four patients had elevated pretreatment serum carcinoembryonic antigen (CEA) levels. In two of these four patients, serum CEA levels fell modestly during SMS 201.995 therapy. This is the first clinical evidence that a somatostatin analogue can inhibit the growth of some colorectal cancers.

Adenocarcinoma↗

A priming effect of naloxone on in vitro LHRH release from the hypothalamus of mid-luteal ewes.

The possible involvement of endogenous opioid peptides (EOPs) in LHRH release from hypothalami of ewes during the breeding season was investigated using an in vitro perifusion system. Hypothalami were procured in December from ovariectomized (OVX; 62-65 days before the experiment; n = 6) and mid-luteal (ML; n = 7) Western White-Face ewes. Hypothalami were mid-sagitally sectioned into halves containing the preoptic area, mediobasal hypothalamus, and infundibulum (median eminence). The left half (treated) received two 30-min challenges (beginning at 130 and 250 min, respectively, after onset of perifusion) of 500 microM naloxone (NAL) followed by a 30-min 60-mM potassium (K) challenge (at 370 min after onset of perifusion). The right half served as the control, receiving only K at the same time as the treated tissue. Both NAL challenges elicited (p less than 0.05) LHRH release from tissues of both ML and OVX ewes. Release of LHRH by hypothalami from ML, but not from OVX, ewes was greater (p less than 0.01) after the second than after the first NAL challenge. These results are consistent with the view that an inhibitory opioid influence exists on LHRH release from ovine hypothalami. The release of LHRH in response to NAL was dependent on the ovarian status in vivo since the priming effect of NAL on subsequent NAL-induced LHRH release occurred only from the hypothalami of ML ewes. We suggest from these results that EOPs may modulate LHRH release from ovine hypothalami in an ovarian steroid-dependent and independent manner.

Animals↗

Effect of hepatic cryotherapy on serum CEA concentration in patients with multiple inoperable hepatic metastases from colorectal cancer.

Eleven patients with multiple hepatic metastases from colorectal cancer, all judged inoperable, were treated by cryotherapy using a probe through which liquid nitrogen was circulated using a single freeze thaw sequence. Localization of metastases, positioning of the probe and monitoring of ice ball size was by intra-operative ultrasound. Serum carcinoembryonic antigen (CEA) was measured in these patients: there was a postoperative fall in all but two. In all but one, there has been a subsequent rise. Speed and degree of rise of CEA varied between patients. Serial CEA may be an effective means of monitoring the effect of hepatic cryotherapy.

Carcinoembryonic Antigen↗