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While systemic intravenous thrombolysis decreases mortality in patients with high-risk pulmonary embolism (PE), it clearly increases haemorrhagic risk. There are many contraindications to thrombolysis, and efforts should aim at selecting those patients who will benefit most, without suffering complications. The current review summarises the evidence for the use of thrombolytic therapy in PE. It clarifies the pathophysiological mechanisms in PE and acute cor pulmonale that increase the risk of bleeding following thrombolysis. It discusses future management challenges, namely tailored drug administration, new treatment monitoring techniques and catheter-directed thrombolysis.

Meeting abstracts MGN1703 is a synthetic DNA-based immunomodulator acting as TLR-9 agonist which has shown preclinical activity in metastatic colorectal carcinoma (mCRC) as well as a good safety profile in patients with metastatic solid tumours in a Phase 1 trial. The IMPACT trial was conducted to

Two papers that reported that the blood pressure drug ramipril was beneficial in patients with intermittent claudication due to peripheral artery disease have been retracted after an investigation found that data were fabricated by the studies’ lead author, Anna A Ahimastos, a researcher at the prestigious Baker IDI Heart and Diabetes Institute in Melbourne, Australia. The first paper,1 published in JAMA in …

When employees at the German drug firm Boehringer Ingelheim learnt that the conclusions of a company study clashed with a marketing claim that its new anticoagulant did not need monitoring, they sought to have the paper revised and even questioned whether it should be published at all, internal company documents released by a US court indicate. In an email one employee, whose name was redacted, complained that the paper would harm the company’s marketing efforts and make discussions with regulatory agencies more difficult. “Can’t this be avoided?” the employee asked. Another employee, Andreas Clemens, a medical team leader for the drug, wrote that he believed that the findings were important and should be published but with revision. “The world is crying for this information—but the tricky part is that we have to tailor the messages smart.” In another email Clemens expressed concern that the paper “could be a liability issue” for the company. The study involved dabigatran etexilate (marketed as Pradaxa), a thrombin inhibitor that is approved in the United States and Europe for the prevention of stroke and embolic events in patients with atrial fibrillation. One of the …

Research studies on the side effects of commonly prescribed drugs constituted the three most read papers published by the BMJ in 2005, according to an internal audit that assessed their use by readers. Studies that showed increased risk of myocardial infarction in patients taking cyclo-oxygenase-2 (COX 2) inhibitors and that explored the link between selective serotonin reuptake inhibitors and suicide came top. For the audit Sara Schroter, the BMJ 's senior researcher, analysed research papers using three measures: the number of citations a paper received, the number of times it was accessed on the web, and the number of rapid responses it generated. The top scoring paper was a case-control study that showed greater risk of myocardial infarction in patients taking the COX 2 inhibitor rofecoxib (Vioxx) and in patients taking diclofenac …

A paper chromatographic analysis in 60 patients with muscular dystrophy from 49 families and in 351 of their relatives showed a high incidence of generalized hyperaminoaciduria in both patients and relatives. There was a higher incidence of threoninuria in patients and their relatives than in controls. One family was found to have excess histidinuria and another excess lysinuria.

Objectives: Although epileptic seizures are an infrequent feature of acute attacks of the neuropsychiatric porphyrias, there are no significant reports of porphyria in chronic epilepsy. This paper attempts to redress the balance. Methods: Three case reports, including detailed laboratory and molecular diagnostics. Results: Two patients with variegate porphyria and one with acute intermittent porphyria, referred within 1 year to a specialist porphyria service, with a long history of chronic refractory epileptic seizures, are described. Conclusions: Porphyria may be an aetiological factor in some cases of chronic refractory partial or generalised epilepsy. Porphyria should also be considered if addition of a new anti-epileptic medication causes a major deterioration in the epilepsy.

Objective: To calculate the best possible estimates for age specific life expectancy (LE) and anticipated age at the time of death (AAD) in patients with Parkinson’s disease (PD) compared with the general population in the UK. These may be of greater value to patients than standardised mortality ratios (SMRs), which are usually reported in studies on mortality in PD. Methods: A literature review identified articles with data on age stratified life expectancy or SMRs to calculate estimations of LE using the Gompertz function and data on mortality and LE in the UK from the Office of National Statistics and Actuarial Department for the year 2003. Results: Two UK studies and four from Western Europe were used to estimate LE and AAD for patients with PD from SMRs. The mean LEs of patients with PD compared with the general population were: 38 (SD 5) years for onset between 25 and 39 years compared with 49 (SD 5) years; 21 (SD 5) years for onset between 40 and 64 years compared with 31 (SD 7) years; and 5 (SD 4) years for onset age ⩾65 years compared with 9 (SD 5) years. The average AAD of patients with PD with onset between 25 and 39 years was 71 (SD 3) years and considerably lower than that of the general population (82 (SD 2) years). The difference between average AAD for older individuals with PD (onset ⩾65 years) and the general population was smaller, with an AAD of approximately 88 (SD 7) years compared with 91 (SD 5) years. Conclusions: The calculations showed that LE and AAD in PD are reduced for all onset ages but this reduction is greatest in individuals with a young onset. While the results are average estimates, these can provide useful indications of LE and AAD.

Background: A wide variety of movement disorders may occur as a consequence of the administration of antiepileptic drugs (AEDs). Although it has been suggested that the risk of parkinsonism is 10-fold higher in those taking valproate as compared with other AEDs, there have been no large, systematic trials assessing this. Aim: To establish more precisely the prevalence of and risk factors for developing parkinsonism associated with valproate use,and to assess the occurrence of movement disorders with the newer AEDs. Methods: Patients with epilepsy were recruited from the Toronto Western Hospital Epilepsy Clinic (University of Toronto, Toronto, Ontario, Canada). Each patient was examined by a movement disorder specialist who was blinded to the treatment status of the patient. Results: 201 patients were included. Postural tremor was the most common movement disorder (45%), followed by parkinsonism (4.5%). The odds of having parkinsonism were 5 times higher with valproate than with other AEDs. No single factor predicted the presence of parkinsonism; however, many (5/9) of the patients concurrently used other drugs or had comorbidities that could have caused or exacerbated parkinsonism. None of the newer AEDs were clearly associated with the presence of movement disorders; however, the numbers were too small to make a formal analysis. Conclusion: Although the risk of parkinsonism with valproate is higher than with other AEDs, it is lower than originally reported. The cases available were not enough to accurately comment on the prevalence of movement disorders with the newer AEDs.

Background: Depersonalisation is a subjective experience of unreality and detachment from the self often accompanied by derealisation; the experience of the external world appearing to be strange or unreal. Feelings of unreality can be evoked by disorienting vestibular stimulation. Objective: To identify the prevalence of depersonalisation/derealisation symptoms in patients with peripheral vestibular disease and experimentally to induce these symptoms by vestibular stimulation. Methods: 121 healthy subjects and 50 patients with peripheral vestibular disease participated in the study. For comparison with the patients a subgroup of 50 age matched healthy subjects was delineated. All completed (1) an in-house health screening questionnaire; (2) the General Health Questionnaire (GHQ- 12); (3) the 28-item depersonalisation/derealisation inventory of Cox and Swinson (2002). Experimental verification of ''vestibular induced'' depersonalisation/derealisation was assessed in 20 patients and 20 controls during caloric irrigation of the labyrinths. Results: The frequency and severity of symptoms in vestibular patients was significantly higher than in controls. In controls the most common experiences were of ''dejavu'' and ''difficulty in concentrating/ attending''. In contrast, apart from dizziness, patients most frequently reported derealisation symptoms of ''feel as if walking on shifting ground'', ''body feels strange/not being in control of self'', and ''feel 'spacey' or 'spaced out'''. Items permitted discrimination between healthy subjects and vestibular patients in 92% of the cases. Apart from dizziness, caloric stimulation induced depersonalisation/derealisation symptoms which healthy subjects denied ever experiencing before, while patients reported that the symptoms were similar to those encountered during their disease. Conclusions: Depersonalisation/derealisation symptoms are both different in quality and more frequent under conditions of non-physiological vestibular stimulation. In vestibular disease, frequent experiences of derealisation may occur because distorted vestibular signals mismatch with the other sensory input to create an incoherent frame of spatial reference which makes the patient feel he or she is detached or separated from the world.

Background: To determine whether withdrawal of anticonvulsant drugs (AED) can be carried out safely in patients with non-epileptic seizures (NES). Methods: Prospective evaluation of safety and outcome in 78 patients with NES who satisfied a standardised set of criteria for excluding the diagnosis of coexisting or underlying epilepsy. Findings: The patients were taking from one to three AED. Sixty four patients were withdrawn as outpatients, 14 as inpatients. Five patients stopped their drugs abruptly, and two had AED restarted and had to be withdrawn again. Otherwise all patients adhered to withdrawal schedules. A new type of attack in addition to NES was seen in three patients (complex partial seizures in all three cases). NES frequency declined in the group as a whole over the period of the study (follow up 6–12 months) in all individuals except for eight patients in whom there was a transient increase. Fourteen patients reported new physical symptoms after withdrawal; however, no serious adverse events were reported. Conclusions: With appropriate diagnostic investigation and surveillance during follow up withdrawal of AED can be achieved safely in patients with NES.

Objective: To report our experience with repeat microvascular decompression (MVD) for hemifacial spasm (HFS) in patients who have failed their first operation. Methods: The authors describe 41 redo MVDs for HFS in 36 patients performed over a 3 year period. Seven patients underwent early re-operation after an aborted seventh nerve decompression. Eight patients underwent early re-operation for clinical failure. Eighteen patients underwent late re-operation for spasm recurrence long after their original MVD. Eight MVDs were performed on patients who had already undergone at least two prior operations. Results: Twenty four patients experienced complete spasm resolution (70.6%), eight patients had near total resolution (23.5%), and two patients failed re-operation (5.9%). Two patients were lost to follow up (5.6%). A favourable outcome was reported by 82.4% of patients at a mean follow up interval of 18 months. A total of 91.7% of patients 50 years of age or younger were cured at follow up versus 59.1% of patients older than 50 (p = 0.04). Patients undergoing early re-operation were significantly more likely to be cured or improved than patients undergoing late re-operation (p = 0.03). Conclusions: Repeat MVD for HFS is effective in experienced hands. Younger patients respond better to repeat MVD. Late repeat MVD for HFS is a reasonable treatment option, although results are less favourable than for early re-operation.

Objective: To learn if the left compared with the right hemisphere of right handed subjects exerts bilateral compared with contralateral motor control when performing precise and coordinated finger movements. Methods: The study investigated intertask differences of manual motor asymmetries such as speed, precision, and independent finger movements, in patients with unilateral lesions of the left (LHD) or right hemisphere (RHD) and normal controls (C). Results: Normal subjects showed the greatest right hand preference on a task that required rapid coordinated and precise independent finger movements (coin rotation). Both hemisphere damaged groups revealed contralateral motor deficits, but the magnitudes of asymmetries were found to be significantly different (RHD>C>LHD) with contralateral and ipsilateral deficits for LHD subjects. The greatest ipsilateral deficits for the LHD subjects were on those tasks that require precision (grooved pegboard and coin rotation). Conclusions: The degree of hemispheric specialisation is, in part, dependent upon the nature of the motor task, with left hemisphere motor control necessary for tasks that require precision and coordinated independent finger movements.

Objectives: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. Methods: 330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables. Results: The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings. Conclusions: Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors.

Aims —An increased concentration of insulin-like growth factor 1 (IGF-1) is an independent risk factor for premenopausal breast cancer. Tamoxifen is thought initially to reduce concentrations of IGF-1 and increase concentrations of the IGF binding proteins. The aim of this study was to compare concentrations of IGF-1, IGF binding protein 1 (IGF-BP1), and IGF-BP3 in patients with breast cancer (n = 14) with those seen in control subjects (n = 23) and to assess the effect of tamoxifen on IGF status in these patients. Methods —Non-fasting blood samples were collected from patients with breast cancer before surgery and after nine, 18, and 27 months of tamoxifen treatment. The baseline concentrations were compared with those of age and sex matched healthy control subjects. Results —IGF-1, IGF-BP3, and IGF-BP1 concentrations were not significantly different in cases and controls. Tamoxifen treatment significantly increased IGF-BP1 after 18 and 27 months (baseline: mean, 21.6 ng/ml; SD, 16.6; 18 months: mean, 52.0 ng/ml; SD, 41.8; p = 0.019; 27 months: mean, 40.7 ng/ml; SD, 24.9; p = 0.043) and IGF-BP3 after nine, 18, and 27 months (baseline: mean, 3119 ng/ml; SD, 507; nine months: mean, 3673 ng/ml; SD, 476; p = 0.004; 18 months: mean, 3445 ng/ml; SD, 634; p = 0.034; 27 months: 3409 ng/ml; SD, 501; p = 0.043) when compared with baseline values. IGF-1 was not altered significantly from baseline at any time point. However, the IGF-1 to IGF-BP3 ratio was significantly decreased at both nine and 18 months (baseline: mean, 0.058; SD, 0.014; nine months: mean, 0.039; SD, 0.008; p = 0.033; 18 months: mean, 0.044; SD, 0.012; p = 0.01). This ratio was not significantly different from baseline at 27 months (mean, 0.054; SD, 0.01; p = 0.08). Conclusions —Tamoxifen increases IGF-BP3 and IGF-BP1 concentrations. It also decreases the IGF-1 to IGF-BP3 ratio but this effect may be limited after long term use. Longer follow up, with larger numbers of patients, should determine when, and for how long, tamoxifen can reduce circulating IGF-1.

Objectives—To determine whether inter- ference between postural control and mental task performance in patients with balance system impairment and healthy subjects is due to general capacity limita- tions, motor control interference, compe- tition for spatial processing resources, or a combination of these. Method—Postural stability was assessed in 48 patients with vestibular disorder and 24 healthy controls while they were stand- ing with eyes closed on (a) a stable and (b) a moving platform. Mental task perform- ance was measured by accuracy and reac- tion time on mental tasks, comprising high and low load, spatial and non-spatial tasks. Interference between balancing and performing mental tasks was assessed by comparing baseline (single task) levels of sway and mental task performance with levels while concurrently balancing and carrying out mental tasks. Results—As the balancing task increased in diYculty, reaction times on both low load mental tasks grew progressively longer and accuracy on both high load tasks declined in patients and controls. Postural sway was essentially unaVected by mental activity in patients and con- trols. Conclusions—It is unlikely that dual task interference between balancing and men- tal activity is due to competition for spatial processing resources, as levels of interference were similar in patients with vestibular disorder and healthy controls, and were also similar for spatial and non- spatial tasks. Moreover, the finding that accuracy declined on the high load tasks when balancing cannot be attributed to motor control interference, as no motor control processing is involved in main- taining accuracy of responses. Therefore, interference between mental activity and postural control can be attributed princi- pally to general capacity limitations, and is hence proportional to the attentional demands of both tasks. (J Neurol Neurosurg Psychiatry 2001;71:48-52)

Aims—To see whether a correlation exists between clinicopathological parameters, argyrophilic nucleolar organiser regions (AgNORs), and nucleolar counts in the nuclei of tumour cells in patients with transitional cell bladder carcinoma. Methods—Paraffin wax embedded sections from a total of 62 cases of primary transitional cell bladder carcinoma were stained with the silver colloid method. The numbers of individual silver grains (AgNORs) in nucleoli and the numbers of nucleoli were counted in 100 nuclei. The correlation between AgNORs and nucleolar counts and patients' sex, tumour grade, disease stage, recurrence pattern, and tumour related survival was analysed. Results—The numbers of nucleoli in tumour cells were higher in male patients (p < 0.032). AgNOR numbers correlated with tumour grade (p = 0.017) and recurrence (p = 0.046). In multivariate analysis, the variation coefficient of AgNOR scores was found to be the only independent predictor of the duration of tumour free period in patients with recurrent disease (p < 0.002). AgNOR scores and nucleolar counts were of no value in distinguishing superficial and invasive tumours or in predicting tumour related survival. Conclusions—AgNOR scores in transitional cell bladder carcinoma reflect variations in tumour biological behaviour; however, the clinical value of this technique in patients with urinary bladder carcinoma is limited.

Objective —To develop a questionnaire to assess audit activity and to use it to evaluate systematically the quality of audit in obstetrics and gynaecology within NHS hospitals in the UK. Design —Retrospective review of 212 consecutive questionnaires completed at hospital recognition committee visits for training accreditation, between 1 January 1993 and 31 August 1998, validated against hospital trust annual audit reports. Main measures —Use of seven quality criteria developed within the Royal College of Obstetricians and Gynaecologists clinical audit unit and also assessment of support for audit and participation in regional and national audit. Results were compared between 1993/4 (n=72), 1995/6 (n=72), and 1997/8 (n=68) for evidence of improvement. Results —After modifications to the questionnaire the version used from 1993 proved to be a satisfactory tool with minimal need for subsequent change. The results showed that there has been a significant improvement in the quality of obstetric and gynaecology audit with time (p

Objectives - The principal aim was to determine whether the emergency readmission rate varies between medical specialties, and to identify whether differences in emergency readmission rates between hospital trusts can be reduced by standardising for specialty. Possible factors influencing emergency readmission were also investigated, including frequency of previous admission and cause of readmission. Design - Emergency readmission rates were obtained from the Scottish Morbidity Record scheme (SMR1) using record linkage, standardised for age and sex. Rates throughout Scotland were analysed by specialty, and rates for general medicine compared among teaching hospital trusts. Cause of emergency readmission was determined from hospital records in a random sample (177 patients). Setting - Medical specialties throughout Scotland. Subjects - All patients readmitted as an emergency within 28 days of discharge (October 1990 to September 1994). Results - Emergency readmissions varied markedly between medical specialties, with highest rates in nephrology (24.2%, 95% CI 23.5 to 24.8) and haematology (20.4%, 95% CI 19.9 to 20.9), and the lowest in homeopathy (2.2%, 95% CI 1.6 to 2.7) and metabolic diseases (3.5%, 95% CI 2.4 to 4.5). The largest number of emergency readmissions was in general medicine, accounting for 63% of the total. Restricting emergency readmission rates to general medicine significantly altered previous rates. In the year preceding the emergency readmission, 59% of all patients had been admitted to hospital at least once, and most emergency readmissions (73.3%) resulted from a chronic underlying condition. Conclusions - Significant variations in emergency readmission rates occurred between medical specialties, suggesting that differences between hospital trusts are influenced by differences in specialties and thus case mix. The majority of emergency readmissions occurred in patients with an underlying chronic condition, and many had a history of multiple previous hospital admissions. The emergency readmission rate is therefore unlikely to be a valid outcome indicator reflecting quality of care until routine data are available for standardisation by case mix.

Objectives: To investigate patterns of self monitoring of blood glucose concentration in diabetic patients who use insulin and to determine whether frequency of self monitoring is related to glycaemic control. Setting: Diabetes database, Tayside, Scotland. Subjects: Patients resident in Tayside in 1993-5 who were using insulin and were registered on the database and diagnosed with insulin dependent (type 1) or non-insulin dependent (type 2) diabetes before 1993. Main outcome measures: Number of glucose monitoring reagent strips dispensed (reagent strip uptake) derived from records of prescriptions. First recorded haemoglobin A1c concentration in the study period, and reagent strips dispensed in the previous 6 months. Results: Among 807 patients with type 1 diabetes, 128 (16%) did not redeem any prescriptions for glucose monitoring reagent strips in the 3 year study period. Only 161 (20%) redeemed prescriptions for enough reagent strips to test glucose daily. The corresponding figures for the 790 patients with type 2 diabetes who used insulin were 162 (21%; no strips) and 131 (17%; daily tests). Reagent strip uptake was influenced both by age and by deprivation category. There was a direct relation between uptake and glycaemic control for 258 patients (with recorded haemoglobin A1c concentrations) with type 1 diabetes. In a linear regression model the decrease in haemoglobin A1c concentration for every extra 180 reagent strips dispensed was 0.7%. For the 290 patients with type 2 diabetes who used insulin there was no such relation. Conclusions: Self monitoring of blood glucose concentration is associated with improved glycaemic control in patients with type 1 diabetes. Regular self monitoring in patients with type 1 and type 2 diabetes is uncommon. Key messages Several studies have indicated the importance of self monitoring of blood glucose concentration for prevention of complications in patients with diabetes Uptake of reagent strips for self monitoring of blood glucose among diabetic patients who used insulin was low, with only 20% of patients with type 1 diabetes and 17% of those with type 2 diabetes obtaining enough strips to test blood glucose concentration once daily Reagent strip uptake depends on characteristics such as age and social deprivation category, and patient groups with low uptake should be identified and targeted There was a direct association between strip uptake in the previous 6 months and glycaemic control in patients with type 1 diabetes but not in those with type 2 diabetes

OBJECTIVE—To assess the impact of spinal cord stimulation (SCS) on the need for acute admissions for chest pain in patients with refractory angina pectoris. DESIGN—Retrospective analysis of case records. PATIENTS—19 consecutive patients implanted for SCS between 1987 and 1997. All had three vessel coronary disease, and all were in New York Heart Association functional group III/IV. METHODS—Admission rates were calculated for three separate periods: (1) from initial presentation up until last revascularisation; (2) from last revascularisation until SCS implantation; (3) from SCS implantation until the study date. Post-revascularisation rates were then compared with post-SCS rates, without including admissions before revascularisation, as this would bias against revascularisation procedures. RESULTS—Annual admission rate after revascularisation was 0.97/patient/year, compared with 0.27 after SCS (p = 0.02). Mean time in hospital/patient/year after revascularisation was 8.3 days v 2.5 days after SCS (p = 0.04). No unexplained new ECG changes were observed during follow up and patients presented with unstable angina and acute myocardial infarction in the usual way. CONCLUSIONS—SCS is effective in preventing hospital admissions in patients with refractory angina, without masking serious ischaemic symptoms or leading to silent infarction. Keywords: spinal cord stimulation; refractory angina pectoris; admission rate; cost effectiveness

OBJECTIVE—To investigate the use of intravascular ultrasound (IVUS) in detecting the presence of arterial remodelling in patients with unstable angina. DESIGN—Prospective case study. PATIENTS—60 of 95 consecutively admitted patients with unstable angina (41 male, 19 female), mean (SD) age 61.2 (8.1) years. INTERVENTIONS—Qualitative and quantitative coronary angiography and IVUS. MAIN OUTCOME MEASURES—Adaptive or constrictive remodelling (AR, CR) was considered present when the cross sectional area of the external elastic membrane at the lesion site was larger than the proximal cross sectional area or smaller than the distal cross sectional area, respectively. RESULTS—22 of the 60 patients (37%) showed AR and 14 (23%) showed CR. No remodelling was seen in 24 patients (group NR). The plaque contained more thrombus and plaque rupture in group AR than in groups CR and NR (thrombus: 91% v 50% and 67%, respectively, p = 0.023; rupture: 73% v 29% and 42%, p = 0.020). AR was associated with a larger plaque cross sectional area (12.6 (SD 4.6) mm2 v 10.8 (6.3) and 9.2 (3.7) mm2, p = 0.001) and larger external elastic membrane cross sectional area (16.5 (5.8) mm2 v 13.2 (5.2) and 14.4 (3.6) mm2, p = 0.01 in group AR v groups CR and NR, respectively), while the plaque burden was larger in groups AR (74.9 (9.1)%) and CR (72.4 (16.6)%) than in group NR (66.2 (18.1)%, p = 0.005). CONCLUSIONS—IVUS is capable of detecting adaptive and constrictive remodelling of target lesions and its relation to plaque morphology in unstable angina. Keywords: unstable angina; intravascular ultrasound; arterial remodelling; angiography

Objectives—To assess willed actions in patients with schizophrenia using reaction time (RT) tasks that diVer in the degree to which they involve volitionally controlled versus stimulus driven responses. Methods—Ten patients diagnosed with schizophrenia and 13 normal controls of comparable age were tested. Subjects performed a visual simple RT (SRT), an uncued four choice reaction time (CRT), and a fully cued four choice RT task. A stimulus 1(S1)˛stimulus 2(S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 (no warning signal or precue) 200, 800, 1600, or 3200 ms. Results—The patients with schizophrenia had significantly slower RTs and movement times than normal subjects across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, fully cued CRTs were significantly faster than the uncued CRTs. However, the S1˛S2 interval had a diVerential eVect on CRTs in the two groups. For the normal subjects fully cued CRTs and SRTs were equivalent when S1-S2 intervals were 800 ms or longer. A similar pattern of e Vects was not seen in the patients with schizophrenia, for whom the fully cued CRT were unexpectedly equivalent to SRT for the 200 ms interval and expectedly for the 1600 ms S1-S2 interval, but not the 3200 or 800 ms intervals. Conclusions—Patients with schizophrenia were able to use advance information inherent in SRT or provided by the precue in fully cued CRT to speed up RT relative to uncued CRT. However, in the latter task, in which the volitional demands of preprogramming are higher since a different response has to be prepared on each trial, patients showed some unusual and inconsistent interval eVects suggesting instability of attentional set. It is possible that future studies using RT tasks with higher volitional demands in patients with predominance of negative signs may disclose greater deficits in willed action in schizophrenia. (J Neurol Neurosurg Psychiatry 1999;66:502‐509)

Objective—To compare transthoracic and transoesophageal echocardiography (TTE, TOE) in patients with permanent pacemaker lead infection and to evaluate the safety of medical extraction in cases of large vegetations. Methods—TTE and TOE were performed in 23 patients with definite pacemaker lead infection. Seventeen patients without previous infection served as a TOE reference for non-infected leads. Results—TTE was positive in seven cases (30%) whereas with TOE three different types of vegetations attached to the leads were visualised in 21 of the 23 cases (91%). Of the 20 patients with vegetations and lead culture, 17 (85%) had bacteriologically active infection. Left sided valvar endocarditis was diagnosed in two patients. In the control group, strands were visualised by TOE in five patients, and vegetations in none. Medical extraction of vegetations ⩾ 10 mm was performed in 12 patients and was successful in nine (75%) without clinical pulmonary embolism. After 31.2 (19.1) months of follow up (mean (SD)), all patients except one were cured of infection; three died from other causes. Conclusions—Combined with bacteriological data, vegetations seen on TOE strongly suggest pacemaker lead infection. Normal TTE examinations do not exclude this diagnosis because of its poor sensitivity. Medical extraction of even large vegetations appeared to be safe. Keywords: pacemaker lead infection; transoesophageal echocardiography

OBJECTIVE To investigate the role of the cerebellum in postural adaptation for changes to the stimulus type of support surface displacements (backward translations v “toes up” rotations). METHODS A group of 13 patients with chronic, isolated lesions of the cerebellum and 15 control subjects were tested. Automatic postural responses of the medial gastrocnemius and anterior tibial muscles were recorded. The first paradigm consisted of 10 rotational perturbations followed by 10 backward translations of the platform, and 10 backward translations followed by 10 rotations. The second paradigm consisted of 18 rotations and two randomly interposed translational perturbations, and 18 translations with two rotations randomly interposed. RESULTS When the type of perturbation changed from an expected translation to an unexpected rotation and vice versa both control subjects and cerebellar patients showed an immediate and significant change in the response amplitude of the medial gastrocnemius and at the same time an immediate and significant change in the response amplitude of the anterior tibial muscles. Neither controls nor cerebellar patients showed effects of prediction in surface displacements of unexpected types of perturbation. Both controls and cerebellar patients showed no gradual increase in the gastrocnemius response in subsequent trials of surface translations following a block of 10 surface rotations and no gradual increase in the response amplitude of the anterior tibial muscle in subsequent trials of surface rotations following a block of 10 surface translations. CONCLUSIONS Despite postural hypermetria, the integrity of the cerebellum does not seem critical for adaptation of postural synergies to changing stimulus types of surface displacements. The present results support previous findings suggesting that the main role of the cerebellum in automatic postural responses may be gain control.

Objectives—To compare the value of a series of cardiovascular measurements in patients with symptomatic disease receiving an effective treatment (rate responsive pacing). Patients—12 pacemaker dependent patients with VVIR units. Interventions—Single blind crossover between VVI and VVIR. Outcome measures—Exercise capacity was assessed by treadmill tests (modified Bruce protocol and a fixed workload protocol) with respiratory gas analysis. Self paced corridor walk tests were also undertaken. Quality of life (QOL) was assessed by questionnaire. Daily activity was measured in the patients' homes using shoe and belt pedometers. Results—Treadmill tests and QOL questionnaires correctly identified the clinical benefit associated with VVIR. The modified Bruce protocol was superior to the fixed workload protocol as it was better tailored to the fairly well preserved exercise capacity of the patients. Symptom scores, but not walking times, were improved with VVIR during corridor walk tests. VVIR did not improve daily activity measured using either the belt or shoe pedometers. Conclusions—VVIR pacing improved some but not all measures of exercise capacity. This finding illustrates the difficulty of selecting an instrument to measure symptomatic improvement in clinical research; and raises the question, what is the best way of measuring exercise capacity? Keywords: rate responsive pacing; exercise capacity; quality of life

OBJECTIVES— To investigate capabilities of arm trajectory modification in patients with Parkinson's disease and elderly subjects using a double step target displacement paradigm. METHODS—Nine patients with Parkinson's disease and seven age matched control subjects were instructed to move a stylus towards visual targets presented on a digitising table. Within each session, in some trials the target location was changed before initiation of movement and the subjects were to modify their movements towards the new target (switching trials). In other trials the target location was not changed (control trials). This procedure was repeated for four different target configurations, using interstimulus time intervals of six different durations. The subjects' hand trajectories were recorded and their kinematic characteristics were analysed. RESULTS—In switching trials, about 40% of the movements were aimed directly toward the final target location in both groups. When the trajectories were initially directed toward the first target and then modified toward the second, the reaction time (RT) to the second stimulus (RT2) was longer than to the first stimulus (RT1). The RT2/RT1 ratio was significantly larger in patients with Parkinson's disease than in healthy elderly subjects. CONCLUSIONS—Patients with Parkinson's disease and elderly subjects are substantially slower in responding to a required modification of their movement than in responding to the required movement initiation. Patients with Parkinson's disease have impaired capabilities in processing simultaneously the motor responses to two visual stimuli presented in rapid succession.

OBJECTIVES Among the classification criteria for the diagnosis of Creutzfeldt-Jakob disease, akinetic mutism is described as a symptom which helps to establish the diagnosis as possible or probable. Akinetic mutism has been anatomically divided into two forms—the mesencephalic form and the frontal form. The aim of this study was to delimit the symptom of akinetic mutism in patients with Creutzfeldt-Jakob disease from the complex of symptoms of an apallic syndrome and to assign it to the individual forms. METHODS Between April and December 1996, 25 akinetic and mute patients with Creutzfeldt-Jakob disease were consecutively examined. The patients were classified according to the definition of akinetic mutism by Cairns and secondly in accordance with the features constituting the complete picture of an appalic syndrome (defined by Gerstenbrand). RESULTS From 25 patients with definite Creutzfeldt-Jakob disease, 24 patients showed impoverishment of speech and, after a mean duration of four (range 1.1–11.2) months, almost complete absence of voluntary movements and speech. Seven patients were classified as being mute and akinetic and assigned to the mesencephalic form whereas 13 patients were classified as apallic. One patient was mute without being akinetic and four patients were comatose. CONCLUSION Diffuse brain damage underlies akinetic mutism in patients with Creutzfeldt-Jakob disease. The term can be used as a classification criterion for the diagnosis of Creutzfeldt-Jakob disease; however, it should be applied very carefully and delimited clearly from the apallic syndrome.

OBJECTIVES Sudden falls have been described in patients with partial epilepsy. However, no study has detailed the clinical, EEG, and evolutive features of partial epilepsies with drop attacks. METHODS In a consecutive series of 222 patients with partial epilepsy admitted for uncontrolled seizures over a 10 year period, 31 patients presented with epileptic drop attacks during evolution of their illness. Twenty two patients had frontal, five temporal, and four multifocal or undefinable lobe epilepsy; 74% of the cases showed an EEG pattern of secondary bilateral synchrony during evolution. A statistical comparison of some clinical and EEG features between the patients with epileptic drop attacks and patients with partial epilepsy without drop attacks (control group of 191 patients) was carried out. RESULTS Seventy four per cent of patients had a poor prognosis and 45% were mentally retarded; 52% of patients with epileptic drop attacks continued to have epileptic falls associated with partial seizures and mental deterioration at the end of the follow up. These characteristics of patients with epileptic drop attacks were significantly different from the control group. CONCLUSION Almost all literature reports concur that the physiopathogenetic substrate of epileptic drop attacks is a mechanism of secondary bilateral synchrony. A localised epileptic focus may lead to a process of secondary epileptogenesis involving the whole brain, causing a progressive cerebral disturbance with worsening of the epileptic seizures and higher cerebral functions.

Introduction and Methods: We report 20 patients aged 18–24 years from Latvia with diphtheritic polyneuropathy. All lived in a closed community and 80% were known to have been fully vaccinated against diphtheria until at least 14 years old. Diphtheria antitoxin had been administered within 3 days of the onset of upper respiratory tract infection in 16 patients and 15 received antibiotics. Results: Neurological symptoms developed after a median of 43 days (range 35–58) compared to only 10 days in previous studies of unvaccinated patients. All showed evidence of mild limb polyneuropathy with electrophysiological evidence of polyneuropathy. Only 30% showed early bulbar abnormalities compared to the usual rate of over 95% in diphtheritic polyneuropathy. However, 45% had later bulbar deterioration coinciding with the limb polyneuropathy. Conclusions: These patients show that an attenuated form of polyneuropathy of later onset, with less prominent early bulbar features, can occur in patients vaccinated against diphtheria according to schedule but living in a closed community in a country where diphtheria remains endemic.

Objectives: To assess the reliability of the Epworth Sleepiness Scale (ESS), Daytime Sleepiness Scale (DSS), Chalder Fatigue Scale (CFS), and Krupp’s Fatigue Severity Scale (KFSS) in patients with myotonic dystrophy type 1 (DM1). Methods: In total, 27 patients with DM1 were administered the questionnaires on two occasions, with a 2 week interval. Internal consistency and test retest reliability were measured using intraclass correlation coefficients (ICCs), and Cronbach’s α, Cohen’s κ, and Goodman-Kruskal’s γ coefficients. Results: Internal consistency of the CFS and KFSS were adequate (α>0.70) but that of the ESS was weak (α = 0.24). Both daytime sleepiness and fatigue rating scales showed significant test retest reliability. Test retest reliability for individual items revealed inconsistencies for some ESS and CFS items. Conclusions: Reliability of the CFS, DSS, and KFSS was high, allowing their use for individual patients with DM1, but that of the ESS was lower, rendering its current usage in DM1 questionable. Fatigue rating scales such as the KFSS, which are based on the behavioural consequences of fatigue, may constitute a more accurate and comprehensive measure of fatigue severity in the DM1 population.

Peak flow monitoring is widely recommended in international asthma guidelines. However, suspicions about the accuracy of conventional pen and paper records were confirmed when studies with electronic spirometers showed poor adherence and falsification of data.1 There seems to be a prevailing nihilistic attitude to peak flow monitoring, largely based on the perception that satisfactory adherence cannot be achieved. We aimed to measure long term adherence to electronic peak flow monitoring when participants were aware that data were being stored and used to guide treatment. We obtained data from a 72 week randomised study comparing two starting doses of budesonide in patients aged 18-75 with poorly controlled asthma. The design and outcomes of the study are reported elsewhere.2 The study incorporated two novel features: twice daily monitoring with electronic diary spirometers (MicroMedical DiaryCard; MicroMedical, Rochester, UK) and titration of dose of budesonide (weeks 17-72) by using a clinical algorithm based on peak flow and diary data. …

Inspiratory muscle strength in patients with neuromuscular disorders can be assessed using sniff inspiratory nasal pressure (Pn(sn)) and maximum inspiratory mouth pressure (PI(max)). However, the relative merits of Pn(sn) against PI(max) are not known in patients with severe neuromuscular disease.To investigate whether severity of disease modifies the relation between Pn(sn) and PI(max).Vital capacity (VC), Pn(sn), and PI(max) were measured in 258 patients with neuromuscular disorders.Data were analysed from 241 patients, 17 being unable to perform PI(max) or Pn(sn) manoeuvres. The correlation between Pn(sn) and PI(max) was +0.94 (p0.0001), with a mean (SD) difference between Pn(sn) and PI(max) of -4.8 (21.2) cm H(2)O (the limits of agreement were 37.6 and -47.2 cm H(2)O). VC (% predicted) was positively correlated with Pn(sn)/PI(max) (r = +0.86; p0.0001), with a lower Pn(sn)/PI(max) value in patients with a VC40% of predicted than in those with a VC40% (0.80 (0.35) v 1.04 (0.41); p0.0001).PI(max) is greater than Pn(sn) in patients with a severe restrictive ventilatory defect caused by neuromuscular disease. Pn(sn) may not accurately reflect inspiratory muscle strength in such patients and it is thus advisable to use both tests.

Aims—To determine serum salicylic acid concentrations in non-vegetarians and vegetarians not taking salicylate drugs, and to compare these concentrations with those found in patients taking aspirin, 75 mg daily. Methods—Serum samples were obtained from vegetarians (n = 37) and non-vegetarians (n = 39) not taking salicylate drugs. Non-vegetarians and vegetarians were recruited from the community and from a Buddhist monastery, respectively, in Dumfries and Galloway, Scotland. Patients (n = 14) taking aspirin (75 mg daily) were recruited from the Dumfries diabetic clinic. Serum salicylic acid concentrations were determined using a high performance liquid chromatography method with electrochemical detection. Results—Salicylic acid was detected in every serum sample analysed. Higher serum concentrations of salicylic acid were found in vegetarians than non-vegetarians: median concentrations of 0.11 (range, 0.04–2.47) µmol/litre and 0.07 (range, 0.02–0.20) µmol/litre, respectively; the median of the difference was 0.05 µmol/litre (95% confidence interval for difference, 0.03 to 0.08; p < 0.0001). The median serum concentration of salicylic acid in patients taking aspirin (75 mg daily) was 10.03 (range, 0.23–25.40) µmol/litre, which was significantly higher than that found in non-vegetarians and vegetarians. There was overlap in serum salicylic acid concentrations between the vegetarians and patients taking aspirin. Conclusions—Salicylic acid, a non-steroidal anti-inflammatory drug, is present in fruits and vegetables and is found in higher concentrations in vegetarians than non-vegetarians. This suggests that a diet rich in fruits and vegetables contributes to the presence of salicylic acid in vivo. There is overlap between the serum concentrations of salicylic acid in vegetarians and patients taking aspirin, 75 mg daily. These findings may explain, in part, the health promoting effects of dietary fruits and vegetables. Key Words: salicylic acid • salicylates • diet • low dose aspirin

OBJECTIVE—To assess the diagnostic value and safety of sublingual glyceryl trinitrate tilt testing compared with isoprenaline infusion in patients with unexplained syncope. DESIGN—Glyceryl trinitrate and isoprenaline tilt tests were performed in two successive days on a random basis in cases and controls. SETTING—Outpatient cases with syncope referred to Shahid Rajaii Heart Hospital. SUBJECTS—65 consecutive patients with unexplained syncope after thorough work up; 20 healthy volunteers. RESULTS—Positive responses were observed in 20 patients during the passive phase. Of the other 45 patients, positive responses occurred in 25 cases during the glyceryl trinitrate phase and in 26 cases during the isoprenaline phase. In the control group, positive responses during the passive, glyceryl trinitrate, and isoprenaline phases occurred in one, one, and two cases, respectively. The sensitivity and specificity of the protocols were 55% and 94.7%, respectively, for glyceryl trinitrate v 58% and 89.4% for isoprenaline. Owing to discordant responses in 75% of the cases, the sequential use of the tests (if one was negative) would increase the sensitivity to 84% while decreasing the specificity slightly (to 84%). Side effects were less frequent with glyceryl trinitrate. CONCLUSIONS—Sublingual glyceryl trinitrate tilt testing is an effective and safe alternative to the isoprenaline infusion test and can be used as a complementary test. Keywords: syncope; tilt table test; isoprenaline; glyceryl trinitrate

The benefits of thrombolysis in patients with acute myocardial infarction are time dependent, with a potential 48% reduction in mortality if treatment is received within an hour of onset of symptoms.1 The benefits diminish thereafter. However the “call to needle” standard set by the national service framework2 has been achieved for only a third of patients nationally because of lengthy ambulance journeys and delays in hospital. Prehospital thrombolysis may be the most feasible means of achieving timely reperfusion, and all published studies have shown the accuracy of diagnosis, patient selection, and administration of thrombolysis.3 The Joint Royal Colleges Ambulance Liaison Committee favours autonomous prehospital thrombolysis by paramedics as a long term objective.4 We tested the feasibility of physician assisted and autonomous models of paramedic prehospital thrombolysis.M View this table: Summary statistics for time from event to response (minutes) All 64 paramedics serving the study hospital took part in the study. Of these, 48 (75%) received formal training in recording 12 lead electrocardiograms, diagnosing ST …

Hedonistic homeostatic dysregulation is a neuropsychological behavioural disorder associated with substance misuse and addiction. The disorder has been recognised as a consequence of dopamine replacement therapy (DRT) in 15 patients with Parkinson's disease. The syndrome typically develops in male patients with early onset Parkinson's disease, and can occur with orally and subcutaneously administered DRT. These patients take increasing quantities of their DRT, despite increasingly severe drug induced dyskinesias, and may develop a cyclical mood disorder with hypomania or manic psychosis. There is impairment of social and occupational functioning. Tolerance develops to mood elevating effects of DRT and a negative affective withdrawal state occurs if the drugs are withdrawn or doses decreased. The clinical features and guidelines for managing this syndrome are discussed. A set of diagnostic criteria for further investigating this condition is proposed.

EDITOR—The green paper Who Decides? highlights two central issues: whether advance directives should have a statutory basis, and how capacity should be assessed in patients who may be unable to make decisions for themselves.1 A potentially important problem brings these two issues together: how should doctors assess the capacity of a patient to complete an advance directive? Healthy people may not be well placed to make decisions concerning their future incompetent selves1 because …

To derive a risk score for the combination of death from all causes, myocardial infarction, and disabling stroke in patients with stable symptomatic angina who require treatment for angina and have preserved left ventricular function.Multivariate Cox regression analysis of data from a large multicentre trial.Outpatient cardiology clinics in western Europe, Israel, Canada, Australia, and New Zealand.7311 patients with all required data available.Death from any cause or myocardial infarction or disabling stroke during a mean follow-up of 4.9 years.1063 patients either died from any cause or sustained myocardial infarction or disabling stroke. The five year risk of this composite ranged from 4% for patients in the lowest tenth of risk to 35% for patients in the highest tenth. The risk score combines 16 routinely available clinical variables (in order of decreasing contribution): age, left ventricular ejection fraction, smoking, white blood cell count, diabetes, casual blood glucose concentration, creatinine concentration, previous stroke, at least one angina attack a week, coronary angiographic findings (if available), lipid lowering treatment, QT interval, systolic blood pressureor = 155 mm Hg, number of drugs used for angina, previous myocardial infarction, and sex. Fitting the same model separately to all cause death, myocardial infarction, and stroke gave similar results. The risk score did not seem to predict the nature of the event (death in 39%, myocardial infarction in 46%, and disabling stroke in 15%) or the incidence of angiography or revascularisation, which occurred in 29% of patients.This risk score is an objective aid in deciding on further management of patients with stable angina with the aim of reducing serious outcome events. The score can also be used in planning future trials.

Kessing LV, Andersen PK. Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? J Neurol Neurosurg Psychiatry 2004;75:1662–6. [OpenUrl][1][Abstract/FREE Full Text][2] Q Does an increasing number of prior affective episodes increase the risk of developing dementia in people with depressive and bipolar disorders? ### ![Graphic][3] Design: Cohort study. ### ![Graphic][4] Follow up period: 14 years. ### ![Graphic][5] Setting: Denmark from 1970 to 1999. ### ![Graphic][6] People: 18 726 people with depressive disorder (ICD-8) and 4248 people with bipolar disorder (ICD-10). Inclusions: people who at their first discharge from a psychiatric hospital after 1 January 1970 had a diagnosis of primary affective disorder. Main exclusions: diagnosis of organic psychosis or schizophrenia at discharge before 1 January 1986. ### ![Graphic][7] Risk factors: The Denmark nationwide register was used to identify participants’ psychiatric ward admissions and discharge diagnoses. The relation between number of prior hospital admissions and subsequent dementia diagnosis was estimated using a … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BNeurology%252C%2BNeurosurgery%2B%2526%2BPsychiatry%26rft.stitle%253DJ.%2BNeurol.%2BNeurosurg.%2BPsychiatry%26rft.issn%253D0022-3050%26rft.aulast%253DKessing%26rft.auinit1%253DL%2BV%26rft.volume%253D75%26rft.issue%253D12%26rft.spage%253D1662%26rft.epage%253D1666%26rft.atitle%253DDoes%2Bthe%2Brisk%2Bof%2Bdeveloping%2Bdementia%2Bincrease%2Bwith%2Bthe%2Bnumber%2Bof%2Bepisodes%2Bin%2Bpatients%2Bwith%2Bdepressive%2Bdisorder%2Band%2Bin%2Bpatients%2Bwith%2Bbipolar%2Bdisorder%253F%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fjnnp.2003.031773%26rft_id%253Dinfo%253Apmid%252F15548477%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jnnp&resid=75/12/1662&atom=%2Febmental%2F8%2F2%2F46.atom [3]: /embed/inline-graphic-1.gif [4]: /embed/inline-graphic-2.gif [5]: /embed/inline-graphic-3.gif [6]: /embed/inline-graphic-4.gif [7]: /embed/inline-graphic-5.gif

Insulin glargine is a new insulin analogue with delayed absorption and a prolonged duration of action.1 A 34 year old woman who had had type 1 diabetes for six years had previously been treated with premixed biphasic isophane insulin (Humulin M3), twice a day. This regimen had been changed to a basal bolus regimen of Actrapid and Insulatard during pregnancy, but she subsequently resumed twice daily injections (but …

Ram FS, Wedzicha JA, Wright J, et al. Hospital at home for patients with acute exacerbations of chronic obstructive pulmonary disease: systematic review of evidence. BMJ 2004;329:315. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chronic liver disease and hepatocellular carcinoma are major worldwide public health problems in countries with endemically high levels of viral hepatitis (B and C).1 However, even in western countries chronic liver disease is an emerging problem, due not only to viral hepatitis but also to the effects of lifestyle factors such as heavy alcohol consumption and obesity.2 3 Liver function tests are widely performed blood tests used in patients with suspected liver disease or unexplained illness and in some specific situations such as screening of blood donors. The most widely used tests are those used to detect the aminotransferases—alanine and aspartate—which are associated with hepatocellular injury. Raised concentrations may …

(2002) J Neurol Neurosurg Psychiatry 72, 193; Powell J, Heslin J, Greenwood R. . Community based rehabilitation after severe traumatic brain injury: a randomised controlled trial. . Feb; . : . –202 . [OpenUrl][1][Abstract/FREE Full Text][2] QUESTION: In patients with severe traumatic brain injury (TBI), does a multidisciplinary community based outreach rehabilitation programme improve activities of daily living, social participation, and psychological wellbeing? Randomised (allocation concealed*), blinded (outcome assessors)*, controlled trial with a mean follow up of 24.8 months. An urban setting of east London, UK. 110 patients, 16–65 years of age, who sustained severe TBI 3 months to 20 years previously with no other neurological conditions. 94 patients (85%, mean age 34 y, 76% men) participated in the end of study assessment. 54 patients were allocated to a multidisciplinary community based outreach rehabilitation programme and 56 were allocated to an information only group. Rehabilitation was highly individualised in intensity, duration, and form of treatment with patients seen in their homes or other community settings for 2–6 hours per week for … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BNeurology%252C%2BNeurosurgery%2B%2526%2BPsychiatry%26rft.stitle%253DJ.%2BNeurol.%2BNeurosurg.%2BPsychiatry%26rft.issn%253D0022-3050%26rft.aulast%253DPowell%26rft.auinit1%253DJ%26rft.volume%253D72%26rft.issue%253D2%26rft.spage%253D193%26rft.epage%253D202%26rft.atitle%253DCommunity%2Bbased%2Brehabilitation%2Bafter%2Bsevere%2Btraumatic%2Bbrain%2Binjury%253A%2Ba%2Brandomised%2Bcontrolled%2Btrial%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fjnnp.72.2.193%26rft_id%253Dinfo%253Apmid%252F11796769%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jnnp&resid=72/2/193&atom=%2Febmental%2F5%2F3%2F84.atom

Objective—To investigate the specificity and sensitivity of the combination of redistribution in exercise thallium-201 single photon emission computed tomography (SPECT) and exercise induced ST elevation for detecting the viable myocardium in patients with acute myocardial infarction. Design—37 patients were studied within seven weeks of onset of Q wave myocardial infarction (anterior in 22, inferior in 15). All patients underwent exercise four hour redistribution thallium-201 SPECT and positron emission tomography using fluorine-18-fluorodeoxyglucose (FDG) and nitrogen-13 ammonia under fasting conditions. Results—Sixteen patients showed exercise induced ST elevation ⩾ 1.5 mm, and 15 of these had increased FDG uptake in the infarct region. Eleven of 16 patients (10 of 11 patients with anterior infarctions) with irreversible thallium-201 defects and increased FDG uptake showed exercise induced ST elevation. The sensitivity, specificity, and predictive accuracy of redistribution, exercise induced ST segment elevation, or both for detecting increased FDG uptake were 82%, 75%, and 67% (94%, 75%, and 91% for anterior infarctions), respectively. Conclusions—In patients with acute Q wave myocardial infarction, the combination of redistribution in exercise thallium-201 SPECT and exercise induced ST elevation can detect the viable myocardium in the infarct region with high sensitivity and specificity, especially in patients with anterior infarctions. Keywords: acute myocardial infarction; viability; exercise induced ST elevation; exercise thallium-201 SPECT

BACKGROUND: To assist clinicians and researchers in choosing outcome measures for patients with chronic obstructive pulmonary disease attending routine outpatient clinics, a comparative assessment was undertaken of four questionnaires designed to reflect the patients' perception of their physical and emotional health in terms of their feasibility, validity, reliability, and responsiveness to health change. METHODS: Two condition specific questionnaires, the St George's Respiratory Questionnaire (SGRQ) and Guyatt's Chronic Respiratory Questionnaire (CRQ), and two generic questionnaires, the Short Form-36 Health Survey (SF-36) and Euroqol (EQ), were compared for their discriminative and evaluative properties. Spirometric tests and a walking test were also performed. One hundred and fifty six adults who were clinically judged to have COPD and who attended an outpatient chest clinic were assessed at recruitment and six and 12 months later. Patients were also asked whether their health had changed since their last assessment. RESULTS: Completion rates and consistency between items for dimensions of the SGRQ were lower than for dimensions of the other questionnaires. The distributions of responses were skewed for certain dimensions in all questionnaires except the CRQ. Validity was supported for all instruments insofar as patients' scores were associated with differences in disease severity. The generic questionnaires better reflected other health problems. All instruments were reliable over time. The condition specific questionnaires were more responsive between baseline and first follow up visit but this difference did not persist. While certain dimensions of the SF-36 were responsive to patient perceived changes, this did not apply to the derived single index of the EQ. The rating scale of the EQ, however, provided a quick and easy indicator of change. CONCLUSIONS: Evidence from this study supports the CRQ and the SF-36 as comprehensive outcome measures for patients with longstanding COPD.

This paper reports a double-blind trial of a new antianginal drug, perhexiline. Fifty-five patients suffering from angina pectoris were studied for periods of 12 or 24 weeks in a cross-over comparison against a placebo in four centres in the United Kingdom and Ireland. Perhexiline was effective in most patients as judged by reducing the number of anginal attacks in 84% and the consumption of glyceryl trinitrate tablets in 64%. The major side effect, dizziness, noted in one-third of the patients, may be dose/body-weight related. Perhexiline is a valuable new agent for the treatment of patients with angina, especially those who do not respond to other antianginal agents.

Three cases are reported of tumour-like lesions of the liver in women who had been on oral contraceptives for long periods. These malformations have a prominent vascular component and may present with haemoperitoneum and shock. The possibility of an association between liver hamartomas and oral contraceptive therapy has to be considered.

Continuous intravenous infusion of small amounts of insulin has been used in the management of a series of patients with diabetic ketoacidosis. In 13 patients with a plasma glucose level on admission of 725 mg/100 ml (+/- 80 S.E. of mean) and an arterial pH of 7.07 +/- 0.05 a mean loading dose of 6.5 +/- 0.82 units of soluble insulin was administered intravenously, and thereafter a sustaining infusion of 6.5 +/- 0.82 U/hr was continued until ketosis was corrected and the plasma glucose fell below 300 mg/100 ml. The total insulin dose needed to achieve this was 39.2 +/- 6.6 units given over a 3 to 10-hour period. Plasma insulin was measured in patients who had not previously received insulin and the mean level at an infusion rate of 4 U/hr was 75.6 +/- 8.0 muU/ml. Plasma glucose fell at a regular rate of 101 +/- 11 mg/100 ml/hr, and ketosis improved in parallel. Plasma potassium was well maintained throughout treatment. This regimen of treatment was clinically effective and simple to follow.

Protein was found significantly more frequently in single urine samples from 504 patients with malignancy (290; 58%) than in 529 controls (119; 22%) (p less than 0.01). Median protein concentration was greater (p less than 0.001) in patients with neoplasia (0.14 g/l) than in controls (0.07 g/l). Actuarial analysis showed a median survival of 4.5 months in patients with proteinuria compared with 10 months in those without (p less than 0.001). The association between proteinuria and shorter survival was statistically significant for patients with gut tumours, lung tumours, and tumours at other sites analysed as a group. Patients with myeloma or urinary tract tumours were not studied. In many patients with malignancy the presence of proteinuria may be associated with a substantially reduced survival time.