Long-term adverse effects of paracetamol - a review.

Paracetamol (acetaminophen) is the most commonly used drug in the world, with a long record of use in acute and chronic pain. In recent years, the benefits of paracetamol use in chronic conditions has been questioned, notably in the areas of osteoarthritis and lower back pain. Over the same period, concerns over the long-term adverse effects of paracetamol use have increased, initially in the field of hypertension, but more recently in other areas as well. The evidence base for the adverse effects of chronic paracetamol use consists of many cohort and observational studies, with few randomized controlled trials, many of which contradict each other, so these studies must be interpreted with caution. Nevertheless, there are some areas where the evidence for harm is more robust, and if a clinician is starting paracetamol with the expectation of chronic use it might be advisable to discuss these side effects with patients beforehand. In particular, an increased risk of gastrointestinal bleeding and a small (~4 mmHg) increase in systolic blood pressure are adverse effects for which the evidence is particularly strong, and which show a degree of dose dependence. As our estimation of the benefits decreases, an accurate assessment of the harms is ever more important. The present review summarizes the current evidence on the harms associated with chronic paracetamol use, focusing on cardiovascular disease, asthma and renal injury, and the effects of in utero exposure.

The ancestors of Norman Bethune (1890-1939) traced back to the Bethunes of Skye, leading members of the MacBeth/Beaton medical dynasty.

Norman Bethune became famous through his work in the Spanish Civil War, his advocacy of socialised medicine in North America and his association with Mao Zedong's revolutionary movement in China. It has been suggested that he may have been descended from the Bethune or Beaton medical dynasty, who for generations served as physicians to kings of Scotland, the Lords of the Isles and to some of the larger Scottish clans. This paper traces his lineage back to the Isle of Skye. In the absence of old parish records as aids to tracing genealogy, other available evidence has confirmed that Bethune was indeed in the direct line of descent from the Bethunes or Beatons of Husabost, in Skye, one of the largest branches of this medical kindred, who were physicians to the MacLeods of Dunvegan.

A sceptic and an empiric in medicine: George Young (1692-1757) and the beginnings of the Scottish medical Enlightenment.

The Edinburgh surgeon-apothecary and physician George Young was an empiric who emphasised observation, practical experience and a sceptical approach to evidence in medicine. He was an early member of the Rankenian Club, a group of young intellectuals whose ideas were to be at the heart of Scottish Enlightenment thinking. Young certainly influenced his pupil Robert Whytt, who went on to make important contributions to the understanding of nerve and muscle function. James Hill, Young's apprentice, to whom he emphasised the importance of experience and observation, would later advance thinking and practice in the management of head injury. Young was an important, but to date relatively neglected, figure in the early years of the Edinburgh Medical School and the Scottish Enlightenment. This paper describes what is known of his life and work, aims to assess his legacy and suggests that he deserves greater recognition and appreciation.

Scientific surgeon of the Enlightenment or 'plagiarist in everything': a reappraisal of Benjamin Bell (1749-1806).

The Edinburgh surgeon Benjamin Bell has been regarded as a scientific thinker in the Enlightenment tradition, despite being accused during his lifetime of both plagiarism and a failure to be innovative. Yet subsequent historical accounts regard him much more favourably. A review of his life and work discusses possible explanations for this apparent lack of concordance.

Chronic pain after laparoscopic and open mesh repair of groin hernia.

BACKGROUND: The aim of this study was to compare the incidence of chronic pain or discomfort after laparoscopic totally extraperitoneal (TEP) repair and open mesh repair of groin hernia, and to assess the impact of such pain on patients' physical activity. METHODS: A postal questionnaire was sent to patients who had TEP or open mesh repair of groin hernia between January 1998 and December 1999. The patients were asked about any persistent pain or discomfort in relation to the groin hernia repair and whether this pain or discomfort restricted their ability to undertake physical or sporting activity. RESULTS: Of the 560 available patients 454 (81.1 per cent) replied. Laparoscopic TEP repair was performed in 240 patients (52.9 per cent) and open mesh repair in 214 (47.1 per cent). Of the 454 patients, 136 (30.0 per cent) reported chronic groin pain or discomfort, which was significantly more common after open repair than after laparoscopic repair (38.3 versus 22.5 per cent; P < 0.01). Chronic groin pain or discomfort restricted daily physical or sporting activity in 18.1 per cent of the patients. The patients who had open repair complained of significantly more restriction of daily physical activity than patients who underwent laparoscopic repair (walking, P < 0.05; lifting a bag of groceries, P < 0.01). CONCLUSION: Chronic pain or discomfort was reported by 30.0 per cent of patients after groin hernia repair and was significantly more common after open mesh repair than after laparoscopic TEP repair. It restricted physical or sporting activities in 18.1 per cent of the patients and significantly more so after open mesh repair.

Groin hernia repair in Scotland.

BACKGROUND: The use of mesh for groin hernia repair has dramatically changed the way this common operation is performed. The aim of this study was to survey the methods of groin hernia repair in Scotland and to assess patient satisfaction with the operation. METHODS: Between 1 April 1998 and 31 March 1999 all patients who underwent groin hernia repair in the National Health Service in Scotland were identified. As well as looking at the type of hernia repair performed and postoperative morbidity, patients were sent a Short Form-36 about 3 months after the operation to assess satisfaction and return to normal activity. RESULTS: Information was obtained on 5506 (97 per cent) of patients who underwent groin hernia repair during the study period. Eighty-five per cent of patients had an open mesh repair and 4 per cent had a laparoscopic repair. Most operations (85 per cent) were performed using general anaesthesia on an inpatient basis (78 per cent), and 8 per cent were for repair of a recurrent hernia. Potentially serious intraoperative complications were rare (seven patients), although they were significantly (P < 0. 001) more likely to be associated with a laparoscopic approach or repair of a femoral hernia: relative risk compared with open inguinal hernia repair 33 (95 per cent confidence interval (c.i.) 6-197) and 22 (95 per cent c.i. 3-152) respectively. Wound complications were common and 10 per cent of patients required a district nurse to attend the wound. Patients expressed a high degree of satisfaction; 94 per cent would recommend the same operation to someone else if required. CONCLUSION: An open mesh repair using general anaesthesia has become the repair of choice for a groin hernia in Scotland. Despite a high incidence of wound complications, patients are satisfied with this operation.

Laparoscopic or Lichtenstein repair for recurrent inguinal hernia: one unit's experience.

Surgical treatment of recurrent inguinal hernia is controversial. This is a prospective study of 50 patients who had laparoscopic total extraperitoneal repair (n = 25) or Lichtenstein repair (n = 25) for recurrent inguinal hernia. The two groups of patients were comparable in age, sex and type of hernia. Post-operatively, a seroma or a wound haematoma developed in 12 patients after Lichtenstein repair and in 4 patients after laparoscopic repair (p < 0.05). On average, analgesia was taken for 6.4 days after Lichtenstein repair compared with 3.4 days after laparoscopic repair (p < 0.05). In our unit, laparoscopic repair was associated with fewer complications and a significantly shorter duration of post-operative analgesia than Lichtenstein repair for recurrent inguinal hernia.

Does the mesh require fixation?

As the technique of laparoscopic mesh repair of groin hernia has evolved, the need for mesh fixation has been questioned. Staple fixation has resulted in nerve injury, and some recurrences have been attributed to the use of a mesh that is too small. Drawing on a successful experience from open preperitoneal techniques, laparoscopic surgeons are now reporting results using large mesh without fixation. Early reports show varying success with the technique. Although the problem of nerve damage has been solved, high recurrence rates are reported in which the technique has been used to repair recurrent hernias. Although further studies are required to establish the causes and natural history of mesh migration, initial experience with the technique appears promising.

Retroperitoneal perforation of duodenal ulcer presenting as scrotal sepsis.

Retroperitoneal extravasation is an extremely uncommon complication of duodenal ulcer perforation. The preoperative diagnosis is difficult and may even by missed at operation. There were 25 cases reported in the literature. Only one patient was correctly diagnosed preoperatively and only seven patients survived. We describe the first case of retroperitoneal extravasation from perforated duodenal ulcer presenting as scrotal sepsis.

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.

Gastric cancer distal to the cardia--prevention or cure?

Adenocarcinoma of the stomach distal to the cardia remains one of the most common cancers in the world. The interest in the aetiology of this disease has been rekindled because of recent epidemiological and molecular studies linking this cancer to H. pylori and certain dietary factors. The authors provide an updated review of the aetiology of gastric cancer. This review seeks to summarize the disease, to propose pathways of carcinogenesis and to suggest ways in which the "traditional" risk factors may be interpreted on the basis of evolving knowledge.

Diagnostic use of endoscopic mucosal resection.

We report two cases of gastric carcinoma where repeated, multiple conventional endoscopic biopsies were falsely negative. Endoscopic mucosal resection gave a positive diagnosis in both these patients. New equipment for aspiration mucosectomy makes the technique easier to perform, and a larger, deeper biopsy is obtained.

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.

We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.