Diagnosis of somatisation: effect of an educational intervention in a cluster randomised controlled trial.

BACKGROUND: Somatisation is highly prevalent in primary care (present in 25% of visiting patients) but often goes unrecognised. Non-recognition may lead to ineffective treatment, risk of iatrogenic harm, and excessive use of healthcare services. AIM: To examine the effect of training on diagnosis of somatisation in routine clinical practice by general practitioners (GPs). DESIGN OF STUDY: Cluster randomised controlled trial, with practices as the randomisation unit. SETTING: Twenty-seven general practices (with a total of 43 GPs) in Vejle County, Denmark. METHOD: Intervention consisted of a multifaceted training programme (the TERM [The Extended Reattribution and Management] model). Patients were enrolled consecutively over a period of 13 working days. Psychiatric morbidity was assessed by means of a screening questionnaire. GPs categorised their diagnoses in another questionnaire. The primary outcome was GP diagnosis of somatisation and agreement with the screening questionnaire. RESULTS: GPs diagnosed somatisation less frequently than had previously been observed, but there was substantial variation between GPs. The difference between groups in the number of diagnoses of somatisation failed to reach the 5% significance (P = 0.094). However, the rate of diagnoses of medically unexplained physical symptoms was twice as high in the intervention group as in the control group (7.7% and 3.9%, respectively, P = 0.007). Examination of the agreement between GPs' diagnoses and the screening questionnaire revealed no significant difference between groups. CONCLUSION: Brief training increased GPs' awareness of medically unexplained physical symptoms. Diagnostic accuracy according to a screening questionnaire remained unaffected but was difficult to evaluate, as there is no agreement on a gold standard for somatisation in general practice.     

Exteroceptive suppression periods in jaw-closing muscles. Variability and relation to experimental pain and sustained muscle contraction

The duration of the late exteroceptive suppression period (ES₂) of temporal muscle EMG activity has been reported to be reduced in patients suffering from chronic tension-type headache. Methods of recording and analysing ES₂ have varied between centers and reproducibility of results within subjects , although insufficiently studied, has generally been poor. ES₂ was investigated in 30 healthy subjects, using a computerized technique of recording, rectifying and averaging the EMG signals. Hour to hour and week to week variations of ES₂ durations were calculated, and the influence of pain during a cold pressor test and of sustained muscle contraction on ES₂ durations was investigated. The intra-individual variation of ES₂ durations was 16.0% from hour to hour and 20.7% from week to week. The inter-individual variation was 36.7%. The present method for analysis of ES₂ periods proved to be reliable, as the intra-observer variation was 4.2% and the inter-observer variation 4.6%. ES₂ periods were significantly shorter on the first compared to the second day of examination ( p = 0.006) and during experimental pain ( p = 0.0005). We recommend the use of the computerized averaging technique in future studies and caution against the dependence of results upon factors such as conditioning and pain.     

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale.A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery.It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.     

The burden of brain diseases in Europe.

The burden [as defined by the World Health Organisation (WHO)] of brain diseases (neurological, neurosurgical and psychiatric diseases together) is very high and yet resources spent on these diseases are not necessarily commensurate with the extent of this burden. However, hard data on the burden of brain diseases in Europe have not previously been easily accessible. The Global Burden of Disease (GBD) 1990 study conducted jointly by the WHO, Harvard University and the World Bank provided new measures that are now becoming universally accepted and have been used also in a repeat study: The GBD 2000. The key parameter of the study is disability adjusted life years (DALY), which is the sum of years of life lost (YLL) caused by premature death and years of life lived with disability (YLD). In the present report, data from the GBD 2000 study and from the World Health Report 2001 on brain diseases is extracted for the territory of Europe. This territory corresponds roughly to the membership countries of the European Federation of Neurological Societies. The WHO's Report has a category called neuropsychiatric diseases, which comprises the majority but not all the brain diseases. In order to gather all brain diseases, stroke, meningitis, half of the burden of injuries and half of the burden of congenital abnormalities are added. Throughout Europe, 23% of the years of healthy life is lost and 50% of YLD are caused by brain diseases. Regarding the key summary measure of lost health, DALY, 35% are because of brain diseases. The fact that approximately one-third of all burden of disease is caused by brain diseases should have an impact on resource allocation to teaching, reasearch, health care and prevention. Although other factors are also of importance, it seems reasonable that one-third of the curriculum at medical school should deal with the brain and that one-third of life science funding should go to basic and clinical neuroscience. In addition, resource allocation to prevention, diagnosis and treatment of brain diseases should be increased to approach, at least, one-third of health care expenditure. With the present data on hand, neurologists, neurosurgeons, psychiatrists, patient organizations and basic neuroscientists have a better possibility to increase the focus on the brain.     

HLA-A24 and survivin: possibilities in therapeutic vaccination against cancer

Recently, it was described that an HLA-A24 restricted peptide derived from the survivin splice variant survivin-2B can be recognized by CD8(+) cytotoxic T-cells. The identification of an HLA-A24 epitope is critical for survivin-based immunotherapy as HLA-24 is the most frequent HLA allele in Asia. Consequently, this survivin-2B epitope is already a target in a clinical study in patients with advanced or recurrent colorectal cancer expressing survivin. However, the splice variant survivin-2B has been described to be pro-apoptotic, and is only expressed at low levels in most malignant tissues. Furthermore, survivin-2B expression are significantly decreased in later tumor stages and inversely correlated with tumor differentiation and invasion. Consequently, survivin is a more general vaccination candidate than the splice variant survivin-2B. Here, we on the basis of spontaneous immune responses in HLA-A24+ cancer patients describes that a HLA-A24-restricted survivin epitopes does indeed exist. Consequently, this epitope is an attractive target for the ongoing survivin-based peptide immunotherapy against cancer.     

Assessment of MRI criteria for abnormal brain MRI in acute monosymptomatic optic neuritis. Comparison to findings in healthy persons

To evaluate various MRI criteria we studied a representative group of 149 consecutive patients below 50 years with acute monosymptomatic optic neuritis (AMON), a frequent first manifestation of multiple sclerosis (MS). The presence, number, size, and localization of areas of increased signal (AIS) on T₂-weighted brain MRIs obtained at 1.5 T were described and compared with findings in 71 healthy persons aged 21–50 years without diabetes, cerebrovascular or neurologic diseases. MRI was performed within 2–145 days, median 16 days from onset of AMON and showed from 0 to 26 AIS, sized 2–30 mm, in 79 of 149 (53%) patients compared to 0–18 AIS, sized 2–12 mm, in 31 of 71 (44%) healthy persons. In patients, AIS were significantly more frequent in women than in men (χ² = 4.67, p > 0.05). Periventricular AIS were revealed in 70 (47%) patients and in 14 (20%) healthy persons. Subcortical AIS were present in 5 (3%) patients and in 18 (25%) healthy persons. Infratentorial AIS were present in only 3 (2%) patients. The sensitivity and specificity of previously proposed diagnostic MRI criteria for MS were unsatisfactory in our group of patients and have previously only been validated in definite MS. We therefore constructed and tested four new sets of criteria. The set with the best relation between sensitivity (e.g. 41%) and specificity (e.g. 93%) was the following: presence of two or more AIS, of which at least one is periventricular or infratentorial, combined with the absence of subcortical AIS. These criteria are recommended for patients with AMON and might be used in other patients with possible or probable MS.     

The precipitation and cross-linking of lens crystallins by ascorbic acid

Bovine lens beta-crystallin was incubated with increasing concentrations of sugars and sugar derivatives for a period of 2 weeks in the dark at 37 degrees C. Marked protein precipitation and a browning reaction was observed with both ascorbic acid (ASA) and dehydroascorbic acid (DHA), but little or no reaction was seen with several other sugars and sugar analogs. Similar incubations were carried out with 20 mM ASA, 20 mM DHA and 20 mM glucose, but with increasing amounts of the individual crystallins. Glucose was capable of precipitating gamma-crystallin in the presence of air, but this reaction was decreased if dithiothreitol and a chelating agent were added prior to incubation. ASA and DHA produced precipitation and browning with gamma- and beta-crystallin, but not with alpha-crystallin or lens soluble proteins. Similar reactivities were observed both in air and under reducing conditions. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of these reaction mixtures showed little or no cross-linking with any of the lens proteins by glucose. ASA and DHA caused detectable dimer formation with gamma-crystallin, but produced the formation of dimers as well as highly polymerized proteins at the top of the gel with all the other crystallins and with lens soluble proteins. A time-course experiment with alpha-crystallin in the presence of air showed no cross-linking with 100 mM glucose over a 6-week period; however, 10 mM ASA caused definite cross-linking at 2 weeks, and at 6 weeks a dark smear of protein was visible throughout the gel. ASA was still capable of inducing cross-linking under low oxygen conditions but the protein smearing was markedly diminished. Further, the cross-linking pattern was similar to that seen in the water-insoluble fraction from older human lenses and cataracts. This reaction may be significant in vivo because cross-linking was observed under low-oxygen conditions with as little as 2 mM ASA, which is the level of ASA normally present in human lenses.