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Biomedical subjects

R J Steele

Publications and source records attributed to R J Steele.

At least 55 records · Page 3Linked to original sources
PubMed1996

The involvement of dopamine in the striatum in passive avoidance training in the chick.

Quantitative receptor autoradiography was used to investigate the distribution of binding of [3H]SCH 23390 to dopamine (D1) and [3H]spiroperone to D2 receptors in regions of the forebrain of the one-day-old domestic chick (Gallus domesticus). High levels of specific binding of the D1 and D2 ligands were found in the striatal regions (paleostriatum augmentatum and lobus parolfactorius) of the one-day-old chick, as reported previously in the pigeon, turtle and rat, whilst binding levels were considerably lower in the pallidum (paleostriatum primitivum), hippocampus and hyperstriatum ventrale. The proportions of D1 and D2 receptor binding in the chick were relatively similar in the striatum and pallidum, apart from the paleostriatum augmentatum, where D2 receptors outnumber those of D1 by a factor of two. Binding of the D1 and D2 ligands to forebrain regions was also investigated 30 min after one-trial passive avoidance training of one-day-old chicks in which the aversive stimulus was a bead coated with a bitter tasting substance, methyl anthranilate. These experiments demonstrated a large and highly significant bilateral increase (compared to control birds) in binding to D1 (but not D2) receptors in the lobus parolfactorius. In this striatal region, equivalent to the caudate-putamen of mammals, previous studies have shown that synaptic and dendritic alterations occur following avoidance training. It is concluded that alterations in dopamine binding may be involved in processes that result in modification of the pecking response in chicks after avoidance training.

Animals↗
PubMed1996

Malignant ascites: a 2-year review from a teaching hospital.

In this retrospective review of 164 consecutive patients with malignant ascites it has been shown that ovarian ascites accounts for 28% of the total and is associated with a significantly improved survival compared with other groups (P<0.001). Non-ovarian ascites is associated with a very poor prognosis and many patients in this group are unsuitable for aggressive treatment. In 49% of patients, ascites will be the presenting feature requiring further investigation to ascertain the primary tumour. Thorough investigation of female patients should be performed in order to identify all patients with an ovarian primary so that appropriate chemotherapy can be given. However, thorough investigation in male patients is not justifiable.

Adult↗
PubMed1996

Therapeutic effect of the matrix metalloproteinase inhibitor, batimastat, in a human colorectal cancer ascites model.

The matrix metalloproteinase inhibitor batimastat was administered to a human colorectal cancer ascites model, which was initiated by injection of C170HM2 cells into the peritoneal cavity of SCID mice and resulted in solid tumour deposits and ascites formation. The cell line expressed both the 72 and 92 kDa forms of gelatinase by zymography. Batimastat administered from day 0 (40 mg kg-1) reduced the volume of ascites to 21% of control in mice treated from day 0 (P < 0.002) but not day 10. Formation of solid peritoneal deposits was significantly reduced to 77% of vehicle control when batimastat was administered from day 0 (P < 0.01) and 69% of control when administered from day 10 (P < 0.05). Thus, batimastat has the ability to reduce the volume of ascites forming in SCID mice injected intraperitoneally with the human colorectal cell line, C170HM2, when administered from day 0 but not from day 10. Solid peritoneal tumour deposits were significantly reduced in both treatment groups, highlighting the therapeutic potential of batimastat in this clinical condition.

Animals↗
PubMed1996

Anastomoses involving the colon and rectum: an 8-year experience.

From January 1987 to May 1995, 214 anastomoses involving the rectum or colon were fashioned using single-layer, interrupted serosubmucosal 3/0 braided polyamide. There were six deaths, one clinically evident anastomotic leak, and one wound infection. These results lend further support to the use of a single layer of serosubmucosal sutures for anastomoses involving the colon and rectum.

Adult↗
PubMed1996

Transanal endoscopic microsurgery--initial experience from three centres in the United Kingdom.

Over a 28-month period, 100 transanal endoscopic microsurgical excisions of rectal tumours were carried out in three centres. The histological diagnosis was benign adenoma in 77 and invasive adenocarcinoma in 23. Complete excision of the tumour with histological confirmation was achieved in 70 (91 per cent) of the adenomas and in all but one of the carcinomas. Of the carcinomas, 18 were recognized before operation and the remaining five were diagnosed on postoperative histology. Of the patients with carcinoma, one had immediate further surgery, nine had radiotherapy and 13 had no extra treatment. To date, four patients have had a recurrence of villous adenoma, and two of the patients treated for invasive carcinoma have had local recurrence. These initial results of transanal endoscopic microsurgery in the UK compare well with those of earlier reports, indicating that the technique has a useful place in the management of sessile adenomas of the mid and upper third of the rectum, and of some carefully selected carcinomas.

Adenocarcinoma↗
PubMed1995

Involvement of AMPA receptors in maintenance of memory for a passive avoidance task in day-old domestic chicks (Gallus domesticus).

Day-old chicks (Gallus domesticus) were trained on a one-trial passive avoidance task where the aversive stimulus was an unpleasant tasting substance, methyl anthranilate. Chicks were killed 6.5 h after training. The kinetic parameters of [3H] alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) binding were determined using quantitative receptor autoradiography and Scatchard analyses in 15 discrete forebrain regions of trained and control (water-trained) chicks, revealing two components of binding in each. KD values showed some regional variation, but were 22.2 +/- 1.1 nmol l-1 for the high-affinity component and 685 +/- 25 nmol l-1 for the low-affinity component of binding to whole forebrain sections from control chicks. Analyses also revealed that Hill coefficients were significantly less than 1 in all regions measured. A significant decrease in KD for the low-affinity component occurred bilaterally in the intermediate and medial hyperstriatum ventrale (IMHV; left, 34.8%; right, 33.3%), a region that has previously been shown to be implicated in the processes of memory formation, following passive avoidance training. A significant decrease in KD for the high-affinity component occurred in the right palaeostriatum augmentatum (19.5%). Significant decreases in Bmax accompanied the KD alterations in both cases. Additionally, bilateral intracerebral injections (administered 4.5-5.5 h after training) into the IMHV of 500 nmol l-1 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective antagonist of non-NMDA glutamate receptors (particularly AMPA receptors), resulted in amnesia for one-trial passive avoidance training in day-old chicks tested 6.5 h after training.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Anti-gastrin antibodies raised by gastrimmune inhibit growth of the human colorectal tumour AP5.

The neutralising ability of rabbit anti-gastrin-17 (G17) antiserum raised by Gastrimmune, an immunogen constructed of the N-terminal portion of human G17 conjugated to diptheria toxoid (DT), was evaluated. The anti-serum (denoted anti-G17: DT) was shown to displace 125[I] G17 from the gastrin receptors on AR42J cells. The therapeutic effect of the rabbit anti-G17:DT anti-serum was evaluated on a freshly derived human colorectal cancer cell line, AP5, which was shown to express both gastrin receptors and gastrin immunoreactivity as assessed by immunocytochemistry. Rabbit anti-G17:DT anti-serum was shown to block basal in vitro growth of AP5 cells when used at an antigen binding capacity of 3.75 x 10(-9) M. The same dilution of anti-serum completely reversed growth stimulated by human G17 at concentrations of 1 x 10(-10) and 1 x 10(-9) M but did not inhibit growth at 1 x 10(-8) M G17. When AP5 was grown as a xenograft in nude mice, the sensitivity to the proliferative effect of human G17 was maintained. In addition, the basal growth of AP5 xenografts was significantly reduced by i.v. infusion of rabbit anti-G17:DT anti-serum when compared to treatment with rabbit anti:DT control anti-serum. Thus anti-G17:DT antibodies raised by Gastrimmune may be of clinical value in gastrin-sensitive tumours.

3T3 Cells↗
PubMed1995

Increases in NMDA receptor binding are specifically related to memory formation for a passive avoidance task in the chick: a quantitative autoradiographic study.

One-day-old chicks (Gallus domesticus) were trained on a one-trial passive avoidance task in which the aversive stimulus was an unpleasant lasting substance, methylanthranilate (MeA). Control birds were presented with a water (W) coated bead. Five minutes after training a group of McA-trained chicks were given a brief sub-convulsive trans-cranial electric shock, which rendered half amnesic whilst the remainder were able to show recall for the aversive stimulus. Thirty minutes after training birds were killed and quantitative receptor autoradiography was used to determine NMDA sensitive [3H]L-glutamate binding in specific regions of the forebrain of: (i) MeA-trained chicks; (ii) water-control chicks; (iii) MeA-trained electroshocked chicks showing recall; and (iv) MeA-electroshocked chicks amnesic for the aversive stimulus. Increases (805 in the left lobus parolfactorius and 67% in the left intermediate medial hyperstriatum ventrale) in NMDA sensitive [3H]L-glutamate binding occurred in electro-shocked chicks which showed recall of the aversive experience but were absent in MeA-trained chicks rendered amnesic by electro-shock. The increased binding in electroshocked MeA-trained birds which showed recall was similar to that observed previously in MeA-trained birds (without electroshock), compared to water control birds, whereas binding levels in McA-trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly in MeA-trained electroshocked amnesic birds were not different from those of water control birds. These data argue strongly that alterations in binding to glutamate receptor sub-types are specific to memory formation for the passive avoidance task.

Animals↗
PubMed1995

Introduction of laparoscopic cholecystectomy in a large teaching hospital: independent audit of the first 3 years.

Commencing with the introduction of laparoscopic cholecystectomy, a detailed independent prospective audit of all cholecystectomies attributable to 12 general consultant surgeons has been carried out over a period of 3 years. Of 650 operations 502 were intended laparoscopic cholecystectomies. In the first year 58 per cent were intended laparoscopic cholecystectomies; this rose to 80 per cent in the second year and to 90 per cent in the third. The conversion rate was 21 per cent in the first year, 21 per cent in the second and 15 per cent in the third. The mean operating time for laparoscopic cholecystectomy was 133 min for year 1, 123 min for year 2 and 115 min for year 3, compared with 92, 101 and 95 min respectively for open cholecystectomy. The overall complication rate was 10 per cent for laparoscopic and 21 per cent for open cholecystectomy. This included six bile duct injuries (1.2 per cent) in the patients undergoing the laparoscopic procedure and one (0.7 per cent) in those having open cholecystectomy. This unselected audit of a group of general surgeons introducing laparoscopic cholecystectomy into their practice has revealed complication and conversion rates that are higher than those reported in most of the published literature, but may be representative of practice throughout the UK.

Cholangiopancreatography, Endoscopic Retrograde↗
PubMed1995

The Edinburgh randomized trial of axillary sampling or clearance after mastectomy.

Between January 1980 and October 1983, 417 patients were randomized for mastectomy followed by axillary node sampling or full axillary clearance. The aim of the study was to determine whether a standard 'four-node' axillary sample, followed by careful dissection of removed tissue, could accurately indicate the extent of local treatment required. Axillary radiotherapy was given only to patients with histological involvement of sampled nodes and not to any having axillary clearance. The incidence of involved nodes was similar for both groups, as were distant relapse and survival rates. Currently 62.6 percent are alive after clearance and 65.0 percent after sampling. A non-significant increase in the rate of locoregional relapse was observed for those treated by axillary node clearance, this being due mainly to increased relapse on the unirradiated chest wall (clearance 21 percent versus sampling 12 percent in patients with node-positive disease). There was only a minor difference in axillary relapse, favouring axillary clearance (3.0 versus 5.4 percent). In patients with operable breast cancer, mastectomy with axillary node sampling gives equal control to mastectomy with axillary node clearance but, as morbidity is greater, surgical clearance of the axilla is the preferred option.

Adult↗
PubMed1995

Gastrin sensitivity of primary human colorectal cancer: the effect of gastrin receptor antagonism.

The purpose of this study was to determine the effect of the gastrin receptor antagonist, CR2093, on basal and gastrin-stimulated growth of primary human colorectal adenocarcinomas and to relate this to gastrin receptor expression. Tumour cells, derived from surgical specimens by enzymatic disaggregation, were grown on matrices of type I collagen and irradiated fibroblasts. Gastrin receptor expression was measured by using a mouse monoclonal antibody directed against the gastrin receptor and an avidin-biotin immunocytochemical method. Increased growth in the presence of gastrin-17 (used at physiological concentrations and as assessed by [3H] thymidine uptake) was shown in 16/34 (47%) tumours. CR2093 significantly reversed this stimulated growth (P < 0.05, one way analysis of variance) in 9/16 (56.3%) of the tumours and inhibited the basal growth of 11/34 (32.4%). Basal growth inhibition was reversed by gastrin-17 in 82% (9/11) of tumours. Gastrin receptor expression was widespread, but was not related to the degree of growth response to gastrin, and there was no significant correlation between intensity of receptor expression and inhibition of basal growth by CR2093. In conclusion, both gastrin-stimulated and basal growth of primary human colorectal can be inhibited by gastrin receptor antagonism, but gastrin receptor expression does not predict the sensitivity of tumours to (i) the proliferative effects of gastrin or (ii) the inhibitory effects of a gastrin receptor antagonist on basal growth. Antigastrin agents may have clinical value in the treatment of gastrin-sensitive colorectal tumours, and gastrin receptor expression may be related to endogenous gastrin production by colorectal tumour cells.

Amino Acids↗
PubMed1995

Intragastric distribution of ion-exchange resins: a drug delivery system for the topical treatment of the gastric mucosa.

Previous studies by this group on freeze-dried oral dosage forms containing finely-divided ion-exchange resins revealed prolonged gastric residence and uniform distribution within the stomach. The present study was carried out to ascertain whether this was due to freeze-drying, properties of the radiolabelled ionic exchange resin, or the small dosing volume used. 99mTc-labelled cholestyramine resin was administered in two dosage forms, a freeze-dried tablet which dissolved in the oral cavity (orally dissolving tablet; ODT) and a 1.5 mL aqueous suspension. Two resin particle sizes (20-40 and 90-125 microns) were studied. Oesophageal transit and intragastric distribution and residence were followed by gamma scintigraphy. In a second study, in six subjects, gastric emptying of the water-soluble fraction of the ODT and 1.5 mL of water, was measured using 99mTc diethylenetriaminepentaacetic acid. Oesophageal transit of a water-soluble marker and resin in suspension was rapid, but the transit of the resin in the ODTs was significantly prolonged. Regardless of particle size or dosage form, the resin was evenly distributed throughout the stomach with 20-25% remaining for 5.5 h. In contrast, the water-soluble marker cleared from the stomach rapidly from both dosage forms. We suggest that oral dose forms containing finely-divided ion-exchange resins may form a useful system for topical treatment of the gastric mucosa, for example in targeting to Helicobacter pylori infection.

Adult↗
PubMed1995

Alkaline gastro-oesophageal reflux: dual probe pH monitoring.

Although the aetiology of Barrett's oesophagus or columnar line oesophagus (CLO), remains unknown, bile reflux has been implicated as a factor in its pathogenesis. This study aimed to detect alkaline reflux in gastro-oesophageal reflux patients using dual probe pH monitoring. Thirty patients with histologically diagnosed CLO, 15 age and sex matched patients with oesophagitis (grade 1-3), and 15 healthy volunteers were studied by dual probe, 18 hour pH monitoring and analysis of the bile acid content of oesophageal refluxate. Total acid exposure and acid exposure in the upright and supine postures were greater in CLO subjects than in oesophagitis patients and controls. Furthermore, the number of reflux episodes lasting more than five minutes and the duration of the longest reflux episode were significantly greater in the CLO subjects than the oesophagitis and control subjects. Nine subjects with CLO and oesophagitis, however, were not identified as refluxers, although six had a bile acid concentration in their oesophageal aspirate higher than the 95th centile value of the controls. There was no correlation between the oesophageal pH and the bile acid contents of refluxate. It is concluded that dual probe pH monitoring is not useful in detecting alkaline refluxers. pH monitoring, although the only subjective test available to identify acid refluxers, is not a sufficiently sensitive test with which to define alkaline reflux.

Barrett Esophagus↗
PubMed1994

Psychomotor skills of surgical trainees compared with those of different medical specialists.

Forty-eight trainees in surgery, psychiatry, anaesthetics and medicine underwent objective testing of manual dexterity (Mandex test), hand-eye coordination (Gibson spiral maze test) and visuospatial ability (embedded figures task). Surgical trainees performed significantly more quickly on the spiral maze test than psychiatrists (P = 0.03) but made more errors (P = 0.02). Combining male and female subjects across all groups, women were significantly more accurate than men. When men only were compared no psychomotor differences between specialty groups could be demonstrated. There were no differences in visuospatial ability by either sex or specialty. Self-selection on the basis of such skill is therefore unlikely.

Adult↗
PubMed1994

Taurolidine peritoneal lavage as prophylaxis against infection after elective colorectal surgery.

A total of 300 patients undergoing elective colorectal surgery over a 3-year period were randomly assigned to receive intraoperative peritoneal lavage with either taurolidine or saline. Culture swabs were taken from the region of surgery before and after lavage and the development of postoperative infection monitored. Of the positive culture swabs before lavage, a significantly higher proportion were negative after lavage with taurolidine than after that with saline. However, there was no difference in the incidence of postoperative infection between groups, suggesting that taurolidine intraoperative peritoneal lavage confers no clinical benefit over that with saline.

Anti-Infective Agents, Local↗