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Biomedical subjects

J E Hartley

Publications and source records attributed to J E Hartley.

32 records · Page 2Linked to original sources

Primary inguinal hernia repair: how audit changed a surgeon's practice.

Over 10 years one senior consultant surgeon performed 114 standard plication darn herniorraphies on 92 patients with primary inguinal hernias. These patients were contacted and were reviewed if there was any suspicion of recurrence. Four recurrences were detected, giving an overall recurrence rate of about 3.5%. According to actuarial life-table analysis the risks of recurrence at 1 year, 5 years and 10 years were 0.94%, 3.02% and 9%. This level of recurrence is unacceptable in modern practice and, as a result of the audit, the surgeon changed his technique of primary inguinal hernia repair.

Female↗

Artificial neural networks applied to outcome prediction for colorectal cancer patients in separate institutions.

BACKGROUND: Artificial neural networks are computer programs that can be used to discover complex relations within data sets. They permit the recognition of patterns in complex biological data sets that cannot be detected with conventional linear statistical analysis. One such complex problem is the prediction of outcome for individual patients treated for colorectal cancer. Predictions of outcome in such patients have traditionally been based on population statistics. However, these predictions have little meaning for the individual patient. We report the training of neural networks to predict outcome for individual patients from one institution and their predictive performance on data from a different institution in another region. METHODS: 5-year follow-up data from 334 patients treated for colorectal cancer were used to train and validate six neural networks designed for the prediction of death within 9, 12, 15, 18, 21, and 24 months. The previously trained 12-month neural network was then applied to 2-year follow-up data from patients from a second institution; outcome was concealed. No further training of the neural network was undertaken. The network's predictions were compared with those of two consultant colorectal surgeons supplied with the same data. FINDINGS: All six neural networks were able to achieve overall accuracy greater than 80% for the prediction of death for individual patients at institution 1 within 9, 12, 15, 18, 21, and 24 months. The mean sensitivity and specificity were 60% and 88%. When the neural network trained to predict death within 12 months was applied to data from the second institution, overall accuracy of 90% (95% CI 84-96) was achieved, compared with the overall accuracy of the colorectal surgeons of 79% (71-87) and 75% (66-84). INTERPRETATION: The neural networks were able to predict outcome for individual patients with colorectal cancer much more accurately than the currently available clinicopathological methods. Once trained on data from one institution, the neural networks were able to predict outcome for patients from an unrelated institution.

Bias↗

Barium peritonitis: a rare complication of upper gastrointestinal contrast investigation.

Contrast examination of the gastrointestinal tract is rarely complicated by perforation. The colon and rectum are most commonly affected, with many perforations limited to the retroperitoneum. Generalised peritonitis is therefore rare, but is life-threatening and difficult to treat. We present two analogous cases in which extravasation of barium sulphate complicated contrast meal investigation. These cases illustrate important aspects in the management of this unusual occurrence.

Adult↗

Randomized trial of blunt-tipped versus cutting needles to reduce glove puncture during mass closure of the abdomen.

Eighty-five consecutive patients were randomized to undergo mass closure of the abdomen with no. 1 polydioxanone mounted on either a blunt-tipped (n = 46) or cutting (n = 39) needle. Gloves were changed before closure and tested for perforation afterwards using standard air or water techniques. Fourteen pairs of gloves were punctured when using a cutting needle, and three pairs when a blunt-tipped needle was used. The majority of punctures were to the non-dominant glove. The surgeon was aware of the puncture in eight of the 14 instances involving a sharp needle and in one of the three involving a blunt-tipped needle. Blunt-tipped needles, while not eliminating the risk, significantly reduced the incidence of surgical glove puncture (P < 0.001, Fisher's exact test). The use of cutting needles for abdominal closure should be abandoned.

Abdomen↗

Electrophysiological, biochemical, neurohormonal and behavioural studies with WAY-100635, a potent, selective and silent 5-HT1A receptor antagonist.

Although considerable progress has been made in characterising the 5-HT1A receptor using agonists, partial agonists or non-selective antagonists, further studies of 5-HT1A receptor function have been hindered by the lack of highly selective antagonists. The term 'silent' antagonist has been used for such compounds in order to distinguish them unequivocally from several 5-HT1A receptor partial agonists which were initially designated 'antagonists'. In this report we provide a comprehensive review of the biochemical, pharmacological and behavioural properties of the first potent, selective and silent 5-HT1A receptor antagonist, WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride). WAY-100635 had an IC50 (displacement of specific [3H]8-OH-DPAT binding to 5-HT1A receptors in the rat hippocampus) of 1.35 nM and was > 100-fold selective for the 5-HT1A site relative to a range of other CNS receptors. [3H]WAY-100635 was also characterised as the first 5-HT1A antagonist radioligand, displaying the same regional distribution of binding sites as [3H]8-OH-DPAT in rat brain. As would be expected for the binding of an antagonist to a G-protein-coupled receptor, the Bmax of [3H]WAY-100635 specific binding was consistently 50-60% greater than that of the agonist radioligand, [3H]8-OH-DPAT. Mn2+, but not guanine nucleotides, inhibited [3H]WAY-100635-specific binding. [3H]WAY-100635 was also shown to bind selectively to brain 5-HT1A receptors in vivo, following intravenous administration to mice. In vitro electrophysiological studies demonstrated that WAY-100635 had no 5-HT1A receptor agonist actions, but dose-dependently blocked the effects of agonists at both the postsynaptic 5-HT1A receptor in the CA1 region of the hippocampus, and the somatodendritic 5-HT1A receptor located on dorsal raphe 5-HT neurones. In vivo, WAY-100635 also dose-dependently blocked the ability of 8-OH-DPAT to inhibit the firing of dorsal raphe 5-HT neurones, and to induce the '5-HT syndrome', hypothermia, hyperphagia and to elevate plasma ACTH levels. In the mouse light/dark box anxiety model, WAY-100635 induced anxiolytic-like effects. WAY-100635 had no intrinsic effect on cognition in the delayed-matching-to-position model of short-term memory in the rat, but reversed the disruptive effects of 8-OH-DPAT on motor motivational performance. These data clearly demonstrate that WAY-100635 is the first potent, selective and silent 5-HT1A receptor antagonist. Furthermore, [3H]WAY-100635 is the first antagonist radioligand to become available for 5-HT1A receptor binding studies both in vitro and in vivo. The positive effects of WAY-100635 in an anxiety model also indicate that a postsynaptic 5-HT1A receptor antagonist action may contribute to the anxiolytic properties of 5-HT1A receptor partial agonists.

Adrenocorticotropic Hormone↗

The effects of WAY-100135 and 8-hydroxy-2-(di-n-propylamino)tetralin on feeding in the rat.

We have examined the effects of the selective 5-HT1A receptor antagonist, WAY-100135, on feeding and on 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced hyperphagia in rats. Given alone, WAY-100135 (1-10 mg/kg s.c.) did not affect the food intake of fasted or satiated rats; however, in free feeding rats, WAY-100135 (3 mg/kg s.c.) significantly attenuated 8-OH-DPAT-induced hyperphagia (0.1 mg/kg s.c.). Using a satiety sequence analysis of feeding behaviour, WAY-100135 (1 mg/kg s.c.) did not affect behaviour per se, but significantly antagonised the increased incidence of feeding, but not the decrease in observations of grooming following 8-OH-DPAT (0.1 mg/kg s.c.). These data provide the first demonstration of the antagonism, by a selective 5-HT1A receptor antagonist, of 8-OH-DPAT-induced feeding; an effect mediated via the somatodendritic 5-HT1A autoreceptor. These results also suggest that 5-HT1A receptor antagonists may have no intrinsic effect on food intake or feeding behaviour.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Laparoscopic surgery in patients with human immunodeficiency virus.

Fifteen patients with acquired immune deficiency syndrome (AIDS), and one who tested positive for human immunodeficiency virus but had no AIDS-defining diagnosis, underwent a range of laparoscopic procedures between March 1991 and March 1993. Seven cholecystectomies and one cholecystojejunostomy were performed. Three patients underwent diagnostic laparoscopy after presenting with abdominal emergencies. Two further patients had laparoscopic adhesiolysis and one appendicectomy. A further patient underwent laparoscopically assisted end colostomy and another an inguinal hernia repair, both performed electively. Two patients died in the postoperative period. There was little postoperative morbidity. Six patients died 3-18 months after surgery from progressive AIDS. This early experience suggests that laparoscopic surgery is well tolerated in these patients.

Acquired Immunodeficiency Syndrome↗

Antitrust pitfalls in outpatient services.

Increasingly, services traditionally provided to inpatients are moving to the outpatient setting, resulting in greater antitrust risk. Antitrust issues are most likely to arise when a hospital with a large share of the inpatient market attempts to increase outpatient volume by restricting their patients' choices of outpatient providers, or when providers who control scarce outpatient resources attempt to restrict competition by denying other providers access to a facility. This trend has affected physicians both as competitors of hospitals in the outpatient services market and as participants with hospitals in ventures for the provision of outpatient care.

Ambulatory Care↗

The antinociceptive activity of meptazinol depends on both opiate and cholinergic mechanisms.

1 Antinociceptive responses to meptazinol, morphine and oxotremorine and the effects of pretreatment with naloxone or scopolamine on these responses in mice and rats, were examined. 2 Meptazinol evoked larger increases in nociceptive thresholds in the mouse than in the rat, whereas morphine induced large increases in both species. Oxotremorine was both a more potent and a more effective antinociceptive agent in the mouse than in the rat. 3 Antinociceptive responses to meptazinol were consistently inhibited in animals pretreated with naloxone, whereas scopolamine attenuated the effects of meptazinol in some, particularly the mouse tail immersion test, but not in all of the procedures used. 4 Naloxone inhibited all antinociceptive responses to morphine, and scopolamine inhibited all responses to oxotremorine. However, there was no significant interaction between naloxone and oxotremorine or between scopolamine and various opioid analgesic agents. 5 These results indicate that meptazinol, unlike established opioid drugs, may induce antinociception by a dual action on opiate and cholinergic mechanisms.

Analgesics↗

Radiological recanalization of an occluded anterior resection anastomosis.

We present a case of occluded colorectal anastomosis following surgery for rectal tumor. Contrast enema and antegrade ileography confirmed occlusion by a thin membrane. This was thought amenable to needle puncture and placement of a temporary stent under fluoroscopy guidance, avoiding surgery and its associated morbidity. This provides a minimally invasive alternative to surgery and has only been reported once before.

Aged↗