Commentary: Caution needed in introducing warfarin treatment.
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Atrial Fibrillation↗
Biomedical subjects
R J Steele
Publications and source records attributed to R J Steele.
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↗
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↗
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↗
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↗
Current views on the pathophysiology of acute biliary pancreatitis.
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Acute Disease↗
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↗
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↗
Prediction of recurrent bleeding after endoscopic haemostasis in non-variceal upper gastrointestinal haemorrhage.
Endoscopic haemostasis by injection of adrenaline was attempted in 135 consecutive patients with active upper gastrointestinal bleeding. Initial haemostasis was obtained in 127 patients following injection of 5-15 ml 1:10,000 adrenaline; eight patients in whom haemostasis was not achieved underwent immediate laparotomy. There was further haemorrhage in 25 patients, which was successfully treated by further injection of adrenaline in ten. Fifteen patients had major rebleeding requiring emergency surgery. Stepwise logistic regression analysis identified three factors that, taken together, were highly predictive of the need for surgery: pulse rate on admission, the position of the ulcer and whether the patient was obese. A scoring system was derived from the logistic analysis equation that was found to predict correctly the need for emergency surgery in 84 per cent of patients. In patients with a high probability of rebleeding surgery should be considered after initial endoscopic haemostasis and stabilization. In the majority of patients endoscopic treatment alone is sufficient for permanent haemostasis.
Adolescent↗
Inhibitory effects of the gastrin receptor antagonist CR2093 on basal, gastrin-stimulated and growth factor-stimulated growth of the rat pancreatic cell line AR42J.
AR42J, a rat pancreatic cell line expressing receptors for both gastrin and epidermal growth factor (EGF), has been used to examine the effect of the gastrin receptor antagonist CR2093 on basal, gastrin-17 (G17), EGF and transforming growth factor (TGF)-alpha stimulated growth in vitro. In serum-free conditions, CR2093 reduced the basal growth of AR42J at a concentration known to displace physiological levels of G17 from gastrin receptors and this effect was reversed by G17 at 1 x 10(-9) M. Alone, G17 had little effect on growth, but EGF and TGF-alpha stimulated growth to 181 and 176% of control values, respectively, and marked synergy was observed when G17 was used in combination with both EGF (212%) and TGF-alpha (259%). When CR2093 was added, the synergistic effects of the G17/EGF and G17/TGF-alpha combinations were reduced to basal levels. In addition, CR2093 inhibited the growth stimulation induced by EGF and TGF-alpha alone. When the ability of CR2093 to bind to EGF receptors was assessed in a ligand binding assay, it was found that the antagonist displaced up to 23% of labeled EGF. Thus CR2093 has potent inhibitory effects on the basal growth of AR42J which can be reversed by G17. It can also inhibit type 1 growth factor-stimulated growth, but although this action may in part be related to the antagonist's ability to inhibit binding to the EGF receptor, other mechanisms may be involved.
Amino Acids↗
Graded exercises for basic training in laparoscopic surgery.
A series of graded exercises for use in laparoscopic simulation is described. These exercises are designed to introduce the basic skills required for laparoscopic surgery, and have been found to be useful both for the training of junior surgeons and in workshops.
Education, Medical, Continuing↗
Predeposit autologous blood transfusion in patients with colorectal cancer: a feasibility study.
Over a 2-year period, a predeposit autologous blood transfusion service was provided for all patients undergoing elective surgery for left-sided colonic or rectal cancer in one hospital. Of 129 such patients, 28 were suitable for autologous donation. Eight of these received autologous blood only, 13 required no transfusion, and seven needed additional homologous blood. Thus, although predeposit autologous transfusion for patients with colorectal cancer is possible, only a very small proportion are likely to derive any benefit which it might confer.
Aged↗
Psychomotor testing and the ability to perform an anastomosis in junior surgical trainees.
Ten junior surgical trainees underwent objective testing of manual dexterity and visuospatial ability and were required to carry out five consecutive anastomoses on fresh porcine jejunum. Anastomoses were scored by a single observer and a cumulative error score (CES) derived for each procedure. In the first anastomosis there was little correlation between the psychomotor test results and the anastomosis scores. In subsequent trials there were significant negative correlations between aspects of manual dexterity and the CES. Over the five anastomoses there were significant negative correlations between improvement and manual dexterity, but there was a positive correlation between improvement and visuospatial ability (rs = 0.76, P < 0.005). Visuospatial skills are more important than pure motor ability in predicting the capacity to perform an anastomosis and tests of manual dexterity may be misleading in this context.
Adult↗
The early diagnosis of oesophageal adenocarcinoma by endoscopic screening.
Oesophageal carcinoma has a very poor prognosis unless detected at a pre-symptomatic stage. This can only be done by screening and patients with Barrett's columnar lined epithelium of the oesophagus (CLO) are high risk candidates for an endoscopic screening programme. Surveillance studies in CLO patients, when reviewed, showed that the incidence of adenocarcinoma was between 1 in 52 and 1 in 81 patient years, with a mean of 1 in 76. This paper describes the Nottingham experience with an endoscopic screening programme that was established in 1976. To date it has detected four adenocarcinomas at a mean cost similar to that of detecting breast cancer by screening.
Adenocarcinoma↗
Assessment of proliferation of squamous, Barrett's and gastric mucosa in patients with columnar lined Barrett's oesophagus.
There is no satisfactory biomarker yet available for predicting the likelihood of premalignant changes or carcinoma developing in Barrett's or columnar lined oesophagus. In this study we have evaluated the proliferation of squamous epithelium, columnar epithelium from columnar lined oesophagus and gastric columnar epithelium from 23 Barrett's patients using positive immunoreactivity with the mouse monoclonal antibody Ki67 (which recognises an antigen associated with proliferative cells) with a view to using this parameter as a biomarker. Squamous epithelium had significantly higher Ki67 immunostaining as compared with columnar epithelium from columnar lined oesophagus (when examining the tissue with greater than 15% cells staining positive for Ki67, Fisher's exact test p = 0.004) but there was no difference found between the epithelium from the columnar lined oesophagus and gastric columnar epithelium. There was no correlation between histological inflammation and Ki67 immunoreactivity of Barrett's mucosa, and the Ki67 immunostaining of two patients with dysplasia was no different from the rest of the group. There was, however, a significant correlation between the Ki67 immunoreactivity of columnar epithelium from columnar lined oesophagus and columnar epithelium from the stomach (correlation coefficient = 0.44, p = 0.03) suggesting that epithelium from columnar lined oesophagus behaves in a similar fashion to gastric epithelium.
Adult↗
Length of Barrett's oesophagus: an important factor in the development of dysplasia and adenocarcinoma.
In a 15 year prospective study of endoscopic surveillance of columnar lined oesophagus, 102 patients with a mean follow up of 54 (12.5) months and total follow up of 462 years have been evaluated. Of all the sets of biopsies taken, 59 in 21 patients were found to exhibit dysplasia or carcinoma. Four male patients had carcinoma of the oesophagus, indicating a 30 times increased risk of development of adenocarcinoma in columnar lined oesophagus. The length of columnar lined oesophagus in subjects with dysplasia was significantly longer as compared with the whole group (p = 0.01) and when compared with the patients without dysplasia (p = 0.005). None of the patients with dysplasia had a columnar lined oesophagus of less than 8 cm. Length of columnar lined oesophagus therefore seems to be a significant risk factor in the development of dysplasia and subsequent carcinoma and intensive follow up of patients with columnar lined oesophagus greater than 8 cm in length is recommended.
Adenocarcinoma↗
Chronic giardiasis of the stomach.
Two cases of chronic giardiasis of the stomach diagnosed from gastric mucosal biopsy specimens are reported. The first case was associated with an acute-on-chronic gastritis and Helicobacter-like organisms, and the second with an adenocarcinoma of the stomach. In both cases the trophozoites had been missed in earlier biopsy specimens. As far as is known this is the first report of giardiasis of the stomach.
Aged↗
Epidermal growth factor receptor expression in Barrett's esophagus.
Six cases of known Barrett's esophagus were examined immunohistochemically for the presence of epidermal growth factor receptor. All cases showed expression of epidermal growth factor receptor in intestinal metaplastic Barrett's epithelium, the most common form of Barrett's change. Expression of epidermal growth factor receptor may be important in neoplastic transformation in Barrett's esophagus, possibly by an autocrine mechanism. Alternatively, epidermal growth factor receptor expression in intestinal metaplastic Barrett's epithelium may represent a nonneoplastic regenerative phenomenon as seen at other sites within the gastrointestinal tract. Further larger studies are required to assess the clinical significance of these findings.
Barrett Esophagus↗