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Objective: To determine the earliest symptoms of anosognosia in people with Alzheimer’s disease and to validate a criteria-guided strategy to diagnose anosognosia in dementia. Methods: A consecutive series of 750 patients with very mild or probable Alzheimer’s disease attending a memory clinic, as well as their respective care givers, was assessed using a comprehensive psychiatric evaluation. Results: The factors of anosognosia for (1) basic activities of daily living (bADL), (2) instrumental activities of daily living (iADL), (3) depression and (4) disinhibition were produced by a principal component analysis on the differential scores (ie, caregiver score minus patient score) on the anosognosia questionnaire for dementia. A discrepancy of two or more points in the anosognosia-iADL factor was found to have a high sensitivity and specificity to identify clinically diagnosed anosognosia in people with Alzheimer’s disease. By logistic regression analysis, the severity of dementia and apathy were both shown to be noticeably associated with anosognosia in people with Alzheimer’s disease. Conclusion: Anosognosia in those with Alzheimer’s disease is manifested as poor awareness of deficits in iADL and bADL, depressive changes and behavioural disinhibition. The frequency of anosognosia is found to increase considerably with the severity of dementia. The validity of a specific set of criteria to diagnose anosognosia in people with Alzheimer’s disease was shown, which may contribute to the early identification of this condition.

Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer's disease, and may both have a negative impact on the progression of the illness.To examine the clinical correlates of apathy in Alzheimer's disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline.Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation.Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006).Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.

Background: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. Objective: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. Methods: CSF from patients with was tested for human herpesviruses types 1–6, JC virus, enteroviruses, and Toxoplasma gondii . The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. Results: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3–14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. Conclusions: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

The cases are reported of 13 children seen over a 22 month period who presented with a variety of acute neurological illnesses associated with Mycoplasma pneumoniae infection. Although presentation with a decreased level of consciousness or seizures was common, psychosis, hemiparesis, cranial nerve palsies, and Guillain-Barré syndrome were also seen. In contrast with published reports, only one child had an associated chest infection. Although some children have been left with residual disability, most have made a complete recovery. In this recent experience, M pneumoniae is a not rare cause of neurological illness in childhood and may present in unusual ways.

The presence of depression and cognitive impairments was examined in seventy patients with Parkinson's disease (PD). Forty nine patients of this original cohort were re-examined between three and four years after the first evaluation. While both depressed and non-depressed patients showed a significant decline in cognitive function during the follow up period, intellectual decline was significantly more severe for the depressed group. Depressed patients also showed a faster rate of progression of motor signs (mainly tremor) than the non-depressed group. Patients that died during the follow up period showed significantly more cognitive impairments than patients who were alive at follow up. These findings suggest that either there may be two forms of PD: one with depression and rapid cognitive decline and one without depression and a gradual cognitive decline; or that the mechanisms of cognitive impairment in PD and depression may interact to produce a more rapid evolution in cognitive impairment among PD patients with a previous depression than among patients without a previous depression.

Introduction There are plausible biological mechanisms for how metformin, an oral hypoglycaemic agent, may have protective antitumour activity in adenocarcinoma of the pancreas. Metformin disrupts crosstalk between insulin/insulin-like growth factor-1 (IGF-1) receptor and G-coupled receptor signalling through its agonist effect on 59 AMP-activated protein kinase (AMPK). This inhibits cell proliferation, promotes apoptosis, and reduces tumorigenic factors such as VEGF. The aim of this study was to conduct an epidemiologic aetiological investigation of metformin and pancreatic cancer in two large UK populations. Methods All cases of pancreatic cancer diagnosed in Norfolk (2004–2006) and Leicestershire (2007) were identified, and the diagnosis and staging confirmed by reviewing the clinical notes. The use of metformin was recorded in both cancer patients and a group of dermatology controls of similar ages. The OR of developing pancreatic cancer was estimated using unconditional logistic regression adjusted for gender, age at diagnosis, cigarette smoking, and type II diabetes. Results A total of 206 cases of adenocarcinoma of the pancreas were identified (median age 71 years, range 49–99 years, 52% women) and also 251 controls. The OR for cigarette smokers was 3.71 (95% CI 1.94 to 7.08) and for type II diabetes OR=3.47 (95% CI 1.72 to 7.02). In patients with type 2 diabetes metformin was prescribed less in cancer patients than controls (49% vs 73%, p=0.11). The use of metformin had a borderline statistically significant negative association with the development of pancreatic cancer, OR=0.28 (95% CI 0.06 to 1.22, p=0.09). No effect was found for the sulphonylurea hypoglycaemic drugs (OR= 0.38, 95% CI 0.08 to 1.70, p=0.20). Conclusion These results may support the hypothesis that metformin has anticancer effects for pancreatic cancer, although further identification of cases and controls is continuing to more precisely define the association. Currently, the use of metformin should be measured in future aetiological studies of this aggressive tumour. If the results are consistent, then metformin may be assessed in clinical trials as a chemoprotective agent in those at high risk of the disease.

Introduction The incidence of cholangiocarcinoma has increased worldwide with the mortality still remaining high. The aetiology in Western populations is largely unknown, but diabetes may be involved by influencing the neoplastic process via hyperinsulinaemia and the stimulation of the IGF-1 axis. As there are few population based studies looking at this, the aim of this study was to investigate if there is a positive association between type 2 diabetes and the development of cholangiocarcinoma in two centres in the UK. As oral hypoglycaemics may have anti-cancer properties, these drugs were considered when assessing the effect of diabetes. Methods Cases of cholangiocarcinoma were identified in Norwich (years 2004–2010) and Leicester (year 2007) from multi-disciplinary team meeting clinical databases. Inclusion required diagnostic evidence from CT scans and/or histology. Controls were patients, of similar ages and gender, with basal cell carcinomas treated in the dermatology departments at each hospital. The case notes of all subjects were reviewed to obtain confirmatory clinical information on cholangiocarcinoma and type 2 diabetes. Data were analysed using unconditional logistic regression to calculate ORs with 95% CIs, adjusted for age at diagnosis and gender. Results A total of 80 cases of cholangiocarcinoma (median age at diagnosis = 76 yrs, range 41–96 years, 51% men) and 411 controls were identified. All patients had radiological evidence of cancer, with 86% involving the extrahepatic biliary system. The median survival of cases was 158 days (range 2–1092 days). There was a statistically significant increase in the odds of developing cholangiocarcinoma for those with type 2 diabetes (OR=3.00, 95% CI 1.44 to 6.25), but not for type 1 (OR=1.62, 95% CI 0.165 to 16.08). When the effect of type 2 diabetes was adjusted for use of oral hypoglycaemics, the associations were maintained (metformin OR=3.60, 95% CI 1.26 to 10.25 and sulphonylureas, OR=6.31, 95% CI 2.31 to 17.18). Conclusion This epidemiological data supports the biological evidence for type 2 diabetes promoting the development of cholangiocarcinoma. Type 2 diabetes should be considered as a potential risk factor for cholangiocarcinoma in future aetiological studies. Competing interests None declared.

Introduction There are plausible mechanisms that carcinogenesis may be altered by: aspirin, NSAIDs, calcium-channel blockers and statins, through both inhibition of cyclo-oxygenase enzymes and the production of mediators of the cell cycle. The current epidemiological data in this area is either limited, reports conflicting results or does not consider important confounders. The aim of this study was to investigate whether there is a negative association between these medications and the development of pancreatic cancer in a case-control study in the UK. Methods Clinical management databases were used to identify patients diagnosed with pancreatic cancer managed in Norfolk (years 2004–2006) and Leicestershire (2007). The use of these medications, prior to diagnosis, was recorded from a detailed review of the medical records. The control group were 251 dermatology patients of similar ages treated for basal cell carcinoma. ORs with 95% CI, for the development of pancreatic cancer for each medication, were estimated using unconditional logistic regression and adjusted for gender, age at diagnosis, cigarette smoking and type II diabetes. Results A total of 206 cases of adenocarcinoma of the pancreas (median age=71 years, range 49–99 years, 52% women, a median survival of 3.5 months) and 251 controls were identified. Aspirin use was negatively associated with the development of pancreatic cancer (OR=0.49, 95% CI 0.29 to 0.84, p=0.01). There were no associations with either NSAIDs (OR=0.98, CI 0.50 to 1.91, p=0.95), statins (OR=0.64, CI 0.38 to 1.11, p=0.11) or calcium-channel blockers (OR=0.78, 95% CI 0.43 to 1.39, p=0.40). Conclusion The data support a protective role for aspirin, but not currently for the remaining medications in the aetiology of pancreatic cancer. The work is continuing to identify more cases and controls that may confirm our preliminary results for aspirin9s negative association and also show an effect for statins. Before aspirin can be recommended as a chemo-preventive agent, further population-based studies are required to confirm the association and provide detailed information on the dose of aspirin needed and its duration of use.

Conductive education, which was developed at the Petö Institute in Budapest, has been publicised incorrectly as a method of treatment for children with cerebral palsy. From the results of information given and our own observations during a week's visit to the institute we conclude that a minority of carefully selected children with cerebral palsy and spina bifida, who have a relatively good prognosis, are educated at the institute; the education is carried out with appropriate medical, surgical, and orthotic intervention; and the children probably function better as a result of the intensive programme than do similar children in Britain in areas where therapy is scarce. They seem to achieve, however, what we would expect similar children in Britain to do when facilities are adequate. Though our findings do not therefore justify using public funds to refer children to the institute, some (self selected) families benefit from a visit, particularly from the positive attitudes of the staff. The role of the conductor and the integration of programmes into a classroom setting have much to recommend them, and conductive education, if successfully transferred to Britain, might be beneficial to a wider range of children than in Hungary.

Involvement of the cervical spine by rheumatoid disease is common, but lateral subluxation at the atlanto-axial level has not been recorded previously. The condition is due to asymmetrical erosion of the lateral atlanto-axial facet joint, and may be complicated by collapse of the lateral mass of the axis. The condition should be suspected in patients with rheumatoid arthritis (RA) who present with occipital, auricular, and/or facial pain.

Introduction On the morning of 28 October 1974, Musgrave Park Military Wing had 65 occupied beds against its authorized establishment of. 66. At 1015 hours a bomb exploded without warning in a vehicle parked outside the Sandes Home near Abercorn Barracks, Ballykinler, County Down. News of the bombing and that the first casualties were on their way by air, was received at the Military Wing just before 1130 hours. All departments were informed and: a. The Operating Theatre was opened. b. Both surgical teams were called to readiness. c. The helicopter landing zone was manned. d. All patients fit to leave hospital were discharged. e. Off"duty staff were called in. The first lift of six casualties arrived by helicopter at 1145 hours, and the second of eight less seriously injured patients at 1205 hours. Later in the day five patients were transferred in from the Downpatrick Hospital, and a further five next morning. The admissions are listed in Table I.

Twenty newborn infants with clinically apparent intraventricular haemorrhage were studied in order to determine the factors associated with mortality and morbidity. Ten survived, 4 without handicap and 2 with only moderate handicap. Maturity and not size of haemorrhage appeared to be the main factor affecting mortality and morbidity at 1 year. Coma longer than 24 hours after intraventricular haemorrhage distinguished survivors with handicap from those without and may be a useful prognostic sign.

Results are given of a case-control study on bladder cancer in West Yorkshire. The aim of the study was to assess what risks exist for cigarette smoking in the United Kingdom and also to investigate if a dose response effect was present. The study shows for the first time in the United Kingdom a positive but weak relationship between cigarette smoking and bladder cancer. Close examination of the data with regard to this effect shows that a complex set of relationships result when the quantity smoked and the period of smoking are taken into account. A dose response effect is weakly demonstrated when a medium quantity of cigarettes are smoked but it is not present at all in those who smoked most cigarettes for the longest periods. No risk appears to exist for those who have smoked only filter cigarettes. The results are contrasted with similar studies and the significance of the observations are discussed.

Plasma concentrations of testosterone were estimated in normal men, in patients before treatment for prostatic cancer, and in patients who had had various forms of endocrine treatment for prostatic carcinoma. There was no decline in plasma testosterone levels with age. Patients with non-metastatic disease had levels similar to those of normal controls, but in advanced metastatic disease the levels were low. After orchidectomy the plasma testosterone level fell to that found in normal women. In every patient stilboestrol in doses as small as 1 mg three times a day suppressed plasma testosterone at first to negligible amounts, irrespective of the clinical response. Subsequently a small but significant rise in the concentration was always observed over a period of six months' oestrogen therapy. Pituitary ablation with yttrium-90 lowered the plasma testosterone concentration again to negligible amounts in patients who had been on stilboestrol. In advanced metastatic disease this was often associated with relief of pain. Preliminary studies with aminoglutethimide indicate that it can produce biochemical and clinical effects similar to those of pituitary ablation.

The computed tomogram of a 6 month old girl with familial megalencephaly showed widespread attenuation throughout the white matter. She continued to be developmentally and neurologically normal. Her scan at age 3 years was normal apart from the megalencephaly. A tentative explanation for this unusual series of events is offered.

The practicability of introducing clean intermittent self catheterisation to 24 severely handicapped children with spina bifida was studied. Twenty one children achieved complete or nearly complete continence, which was sustained successfully in 14. The difficulties they overcame and the reasons for failure are analysed.

The New Zealand Medical Association has emerged intact from its recent conflict with the Minister of Health. This outcome prompts memories of 45 years ago when the general practitioners success? fully prevented what would have been the nationalisation of the general practitioner services. The first Labour government in New Zealand swept into power at the 1935 general election with a big majority. At that time there were few welfare benefits despite New Zealand having had a means tested old age pension since 1898. In 1935 the New Zealand Branch of the BMA, as the New Zealand Medical Association was then, was considering the desirability of some sort of national health insurance with benefits related to income and for some reform of the public hospital system. The government's health proposals included a raft of benefits that included a free public hospital system and a series of free benefits for general practice. All this would have given New Zealand a national health service in all but name long before any other English speaking country and on a par with what was being developed in Scandinavia. The free general practitioner consultation and maternity benefits, however, proved to be a battle ground between the BMA and the government. Both sides had difficulty understanding the other's point of view and personality conflicts did not help. The arguments used against the government were that there was no need for sudden change, standards of medicine were best preserved by the private practice system, the patient would be denied a free choice of doctor, a contract system would reduce medicine to a common denomina? tor, medicine would be subordinated to the state, and there should be a payment that was related to the service provided. Nevertheless, despite medical opposition the Social Security Act 1938, a landmark in social legislation, was passed, establishing from April 1939 many welfare benefits as a universal right. At the 1938 general election the Labour party had won another big majority and this was a mandate for the welfare state?since added to by both political parties. The BMA continued its opposition to the general practice proposal of a generous capitation fee (15/-) in full settlement ?for the consultation. Though the doctors refrained from striking they resolutely refused to cooperate with the introduction of the medical benefits and the general practitioners managed to hold fast. The outbreak of war in 1939 made tittle difference to the struggle on the home front and if anything acted as a stiffener. The compromise over general practitioner services did not come until mid-1941, when the impasse was resolved by both sides agreeing to a fee for service that would not be in total settlement of the consultation fee. The patient would pay and a benefit (7/6, later 750) be reimbursed by the state, a generous offer as 10/was the average fee for a surgery visit. Thus the general medical services benefit came in. The government had won on the issue of universality and the BMA had triumphed in resisting a free general practitioner service either by a full capitation fee or a full fee for service. There are several accounts of the conflict13 and how much was a consequence of principle, power, or pence has never been fully resolved. But at least it can be said that money was not really at stake even if there was a final sweetener. As a leading Labour minister said of the doctors, they were "tougher even to deal with than wharfies."4 Ups and downs of health benefits

16 Harrington JM, Shannon HS. Survey of health care in British medical laboratory workers. Br MedJ 1977;i:626-8. 17 Department of Health and Social Security. Health Circular HC(79)3. London: DHSS, 1979. 18 Department of Health and Social Security. Control of laboratory use of pathogens very dangerous to humans. London: DHSS, 1976. 19 Department of Health and Social Security. Interim Advisory Committee on Safety in Clinical Laboratories. Bulletin No 1, January 1980 (G/H118/ 165). 20 Rankine AD. Laboratory safety. Lancet 1979,ii:1244. 21 Howie Sir James. Reducing infection risks in clinical laboratories. Med Tech Sei 1979;12:23-5. 22 Royal Institute of Chemistry. Code of practice for chemical laboratories. London: RIC, 1976. 23 University of Manchester Institute of Science & Technology. Safety Manual. Manchester: UMIST, 1973. 24 Collins CH. Safety in pathology laboratories: bibliographies. London: Institute of Medical Laboratory Sciences, 1976 and 1978. 25 Department of Health and Social Security. Hospital building note. No 15: Pathology laboratories. London: DHSS, 1973 (new edition in prepara tion). 26 Grist NR. Hepatitis in clinical laboratories 1975-6. J Clin Pathol 1978 ;31 : 415-7. 27 Public Health Laboratory Service, unpublished. Comm Dis Rep 79/48; 1979. 28 Collins CH. Safety on the cheap. Med Lab World 1979;3:14-9. 29 United States Department of Health Education and Welfare. Classification of etiologic agents on the basis of hazard. Atlanta: Centre for Disease Control, 1974. 30 Center for Disease Control. Laboratory-associated typhoid fever. Morb Mort Wkly Rep 28/44; Nov, 1979. 81 Pike RM. Laboratory associated infections: summary and analysis of 3921 cases. Health Lab Sei 1976;13:105-14.

Rupture of the thoracic aorta due to the trauma of abrupt deceleration is becoming more common in this age of high-speed travel and collision. The clinical picture of the torn aorta may not be recognized during life as it is not generally realized that it can occur without evidence of external injury to the chest. The injury is closed, rupture usually occurring just distal to the ligamentum arteriosum, this site being the junction of the descending aorta, which is relatively fixed by the paired intercostal vessels, and the arch of the aorta, which is only suspended by the head vessels and which moves forward on impact with a severe shearing strain. One of three things can happen: the aorta may be completely divided and the overlying parietal pleura torn, with immediate exsanguination into the mediastinum and left pleural cavity ; secondly, although rupture of the intima and media is complete, the adventitia may be incompletely disrupted, and this, together with the intact parietal pleura, temporarily contains the expanding aneurysm, which may, within minutes or hours, burst into the pleural cavity ; and, finally, the remaining adventitia and pleura can succeed in containing the aneurysm, so that a localized aneurysmal sac develops which slowly expands until it ruptures. In those patients surviving for a short time it is not possible to know whether rupture is imminent, but evidence of continued internal haemorrhage, an expanding mediastinal shadow on jc-ray examination, and an increasing pleural effusion are signs that early rupture is probable, and surgical treatment should be immediately undertaken.