Correction to: EUROCAT: an update on its functions and activities.

The published online version contains the following errors: On the cover page "JRC Management Committee" - should be corrected to JRC-EUROCAT Management Committee. In the authors list under the title, same as above, "JRC Management Committee" should be corrected to JRC-EUROCAT Management Committee.

EUROCAT: an update on its functions and activities.

This paper provides an outline of the development and growth of EUROCAT, the European network of congenital anomaly registers. In recent years the network has been through a period of transition and change. The Central Register of data has transferred from the Ulster University to the EU Joint-Research-Centre, Ispra, Italy.The benefits of combining data from across Europe, from different populations and countries are described by the uses to which these data can be put. These uses include:. surveillance of anomalies at a local, regional or pan-European level. pharmacovigilance. registration of rare diseasesNew studies and projects are underway, including EUROlinkCAT (a Horizon 2020 funded data-linkage project), promising a fruitful future in further research of congenital anomalies.

The validity of questionnaire measures for assessing depression after stroke.

OBJECTIVE: Depression has been reported to occur frequently after stroke. The aim of the study was to assess the validity of questionnaire measures for screening for depression after stroke. DESIGN: Cross-sectional correlational study between questionnaire measures of mood and psychiatric interview. SETTING: Hospital and community. PARTICIPANTS: Stroke patients were recruited from hospital wards and from a randomized controlled trial of cognitive behavioural therapy. MAIN MEASURES: Beck Depression Inventory, Wakefield Depression Inventory, General Health Questionnaire 28 and Schedules for Clinical Assessment in Neuropsychiatry. RESULTS: Poor agreement was found between psychiatric diagnosis and questionnaire measures of mood. The sensitivity of the questionnaire measures was high, but specificity was low. No cut-off points with satisfactory sensitivity and specificity could be identified from ROC curves. CONCLUSIONS: Although questionnaire assessments of depression provide a satisfactory screening method, specificity values are too low to provide a basis for the diagnosis of depression. Measures need to be developed with higher specificity to facilitate screening for depression after stroke.

The reliability and validity of the Nottingham Extended Activities of Daily Living Scale in patients with multiple sclerosis.

OBJECTIVE: To investigate whether the Nottingham Extended Activities of Daily Living Scale (EADL) is reliable and valid for the assessment of disability in patients with multiple sclerosis (MS). DESIGN: Questionnaire measures were administered on two occasions four months apart. SUBJECTS: A total of 240 patients recruited through a randomized controlled trial of cognitive assessment and treatment in MS. MEASURES: The Nottingham EADL, Guys Neurological Disability Scale (GNDS) and SF-36 quality of life scale. RESULTS: The EADL items did not form a Guttman Scale (CR 0.8, CS 0.3). The EADL and its four subscales all had high internal consistency (alpha 0.72-0.94). Test-retest reliability was satisfactory (r(s) 0.81-0.90) with a mean difference in scores on the two occasions of 0.29. Factor analysis generally supported the subscale structure. There were significant but weak correlations with quality of life measures. CONCLUSIONS: The EADL shows promise for the assessment of disability in MS, but the range of items needs to be extended. Further evaluation of the scale seems warranted.

Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis.

OBJECTIVES: Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology service, including cognitive assessment and intervention, to patients with multiple sclerosis. METHOD: The study was a single blind randomised controlled trial. A total of 240 patients with clinically definite, laboratory supported, or clinically probable multiple sclerosis were recruited from an multiple sclerosis management clinic and assessed on a brief screening battery. They were randomised into three groups. The control group received no further intervention. The assessment group received a detailed cognitive assessment, the result of which was fed back to staff involved in the patients' care. The treatment group received the same detailed cognitive assessment and a treatment programme designed to help reduce the impact of their cognitive problems. Patients were followed up 4 and 8 months later on the general health questionnaire (GHQ-28), extended activities of daily living scale, SF-36, everyday memory questionnaire, dysexecutive syndrome questionnaire, and memory aids questionnaire. RESULTS: The three groups were compared on the outcome measures at 4 and 8 months after recruitment. There were few significant differences between the groups and those that occurred favoured the control group. Overall, the results showed no effect of the interventions on mood, quality of life, subjective cognitive impairment or independence. CONCLUSIONS: The study failed to detect any significant effects of cognitive assessment or cognitive intervention in this cohort of people with multiple sclerosis.

Assessing quality of life in people with multiple sclerosis.

PURPOSE: The quality of life of multiple sclerosis (MS) patients was assessed using two MS specific quality of life measures (FAMS and SF-54) and a short generic measure (EuroQol) in order to make recommendations for routine assessment. Factors contributing to quality of life within this population were also considered. METHOD: Questionnaires were either sent by post or completed at interview. Ninety-six MS patients known to a consultant in rehabilitation medicine completed the questionnaires. RESULTS: Patients scored very low on subscales related to physical health. Correlations were high between the FAMS and SF-54 but low with the EuroQoL. Stepwise multiple linear regressions showed mood measures to account for the most variance on all quality of life composite scores. The MS patients within the study had much lower SF-36 quality of life scores than the general population and other illness groups. CONCLUSIONS: The EuroQol did not measure the same aspects of quality of life as the FAMS and SF-54 and was not found to be a sensitive measure within this sample. The SF-54 suffered from floor effects on physical health subscales and therefore the FAMS was recommended.

The effect of reminder calls in reducing non-attendance rates at care of the elderly clinics.

BACKGROUND: DNA ("did not attend") at outpatient clinics is an important problem costing the NHS an estimated pound266 million annually. The national DNA rate for 1996-1997 for all clinics was 12%. The DNA rate at Hammersmith Hospital for the same year in the care of the elderly specialty was 21%. The aim of this study was to establish why this was so, and to test the efficacy of a reminder call in increasing attendance rates at care of the elderly clinics. METHODS: 23 DNAs from seven clinics were contacted to ascertain the reasons for non-attendance (group I). For seven further clinics, 84 patients were contacted in advance to reconfirm their appointment (group II). RESULTS: From group II 12 patients were identified who were unaware of their appointment (14%), six of whom agreed to attend; thus six potential DNAs were prevented. Eleven vacant appointments were identified in advance. The unexpected DNA rate was reduced to 5% from a potential 21% as a result of this exercise. The DNA rate for all patients with dementia (both groups) was 44%, whereas the DNA rate for all patients without this diagnosis (both groups) was 16% (p < 0.001). CONCLUSIONS: A preclinic phone call reminder to elderly patients is feasible, increases attendance rates, and identifies vacant appointments. Patients with dementia are more likely to miss clinic appointments; therefore they and their carers need specific reminders about appointment dates.

Assessment of emotional problems in people with multiple sclerosis.

OBJECTIVE: To investigate the occurrence of emotional problems in multiple sclerosis (MS) patients. The utility of rating scales used to measure such problems was studied to make recommendations for clinical practice. DESIGN: Questionnaires were both sent by post and completed with an assistant psychologist at a home visit. SUBJECTS: Ninety-six MS patients in contact with a rehabilitation consultant. MEASURES: Patients were assessed using the Guy's Neurological Disability Scale (GNDS), Extended Activities of Daily Living Scale (EADL), Hospital Anxiety and Depression Scale (HAD), Beck Anxiety and Depression Scales (BAI, BDI), Clinical Outcomes in Routine Evaluation Measure (CORE) and the Brief Symptom Inventory (BSI). RESULTS: Rates of anxiety and depression ranged from 16% to 48% according to the measures used. All mood scales were highly significantly correlated with each other. Disability as measured by the GNDS, but not the EADL, was significantly correlated with all mood measures. Kappa values showed poor correspondence in the classification of cases. Receiver operating characteristic curves indicated an optimum cut-off point of 7/8 on the HAD and 2/3 on the General Health Questionnaire (GHQ-12). CONCLUSIONS: Rates of emotional problems were low given the highly disabled population studied. The HAD was relatively insensitive in comparison with the BAI and BDI. The GHQ-12 was sensitive and therefore recommended as a short screening measure. An alternative short screen, 'Emotional GNDS', was proposed.

CGRP and adrenomedullin binding correlates with transcript levels for calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) in rat tissues.

1. Putative receptors for CGRP and adrenomedullin have been investigated in the rat. Calcitonin Receptor-Like Receptor (CRLR), in combination with Receptor Activity Modifying Proteins (RAMPs) is hypothesized to bind either CGRP or adrenomedullin. The receptors known as RDC1 and L1 have also been shown to bind CGRP and adrenomedullin respectively. 2. In this study it is shown that rat CRLR cDNA specifies a CGRP receptor when co-transfected with RAMP-1 cDNA and an adrenomedullin receptor when co-transfected with either RAMP-2 or RAMP-3 cDNA in human embryonic kidney 293 cells. 3. CRLR, RAMP, RCD1 and L1 mRNA levels and CGRP and adrenomedullin receptor densities have been measured and correlated with each other in eight rat tissues selected for their distinctive patterns of CGRP and adrenomedullin binding. 4. The data are consistent with the predictions of the CRLR/RAMP model. CGRP binding correlates well with RAMP-1 mRNA levels (R=1.0, P=0.007), adrenomedullin binding shows a tendency to vary with RAMP-2 mRNA levels (R=0.85, P=0.14) and total binding is correlated with CRLR mRNA levels (R=0.94, P=0.03). The data do not support the hypothesis that RDC1 and L1 account for the majority of CGRP and adrenomedullin binding respectively.

Measurement of 90Sr in bone ash.

Bone is a critical organ for the accumulation of many radionuclides, including 90Sr. A bone ash has been prepared by NIST to become a standard reference material and the assaying of the 90Sr activity concentration is reported. A radiochemical procedure, based on extraction chromatography using a crown ether, has been developed to separate Sr from the bone ash. The natural Sr content of the bone ash has been determined by isotope dilution inductively coupled plasma mass spectrometry. The 90Sr activity concentration has been measured by low-level liquid scintillation counting.

Lack of correlation of free deoxypyridinoline excretion with Taq1 restriction length polymorphisms in the vitamin D receptor gene in males.

An association between allelic variants in the vitamin D receptor gene and bone mineral density has been previously described. A bimodal variation in the rate of bone resorption (as measured by urinary deoxypyridinoline excretion rate) has also been reported. We have recruited male volunteers, to minimise variation associated with ovarian function, to investigate a possible connection between these observations. Allelic variants in the vitamin D receptor gene were identified as Taq1 restriction fragment length polymorphisms. The ratio of variants TT:Tt:tt occurred with a frequency of 34%:47%:17%. Excretion rates of urinary free deoxypyridinoline, measured by immunoassay, were compared in age-matched males from each genetic group. There were no significant differences based on the paired Student's t-test. Excretion rates declined with age (P = 0.04) and the best fit model fits the same regression line to each group. Genetic variation in the vitamin D receptor is not linked with differences in bone resorption rates.

Radioiodinated N-(alkylaminoalkyl)-substituted 4-methoxy-, 4-hydroxy-, and 4-aminobenzamides: biological investigations for the improvement of melanoma-imaging agents.

The syntheses and radiolabelling of 27 new N-(alkylaminoalkyl)-4-methoxy-, -4-hydroxy-, and -4-aminobenzamides are described and evaluated in C57B1/6 mice with subcutaneously transplanted B16 melanoma in order to screen the optimal chemical structure for melanoma scintigraphy. Using T1(TFA)3 for 131I- labelling, a series of radioiodinated 4-methoxy benzamide derivatives proved to exhibit superior melanoma uptake with outstanding melanoma/non-target-tissue ratios. From the benzamide derivatives tested, N-(2-(1'-piperidinyl)ethyl-3-[131I]iodo-4-methoxybenzamide and N-(2-diethylaminoethyl)-3-[131I]iodo-4-methoxybenzamide demonstrated best results. The introduction of 4-hydroxy and 4-amino groups led to less favourable benzamides. While the former compounds showed little melanoma uptake, the latter revealed unfavourable melanoma/non-target-tissue ratios. Additionally, it could be shown that an amino group was inevitably necessary for melanoma uptake, and that dialkylation of the amide nitrogen and replacing CONH by CH2NH revealed less advantageous results.

The interaction of CGRP and adrenomedullin with a receptor expressed in the rat pulmonary vascular endothelium.

An abundant, seven trans-membrane domain receptor related to the calcitonin receptor has been studied by a number of groups without identification of its ligand. A recent report claimed that the receptor was a type 1 CGRP receptor (Aiyar et al J. Biol. Chem. 271 11325-11329 (1996)). We have studied the equivalent rat sequence in transfected cells. When expressed in 293 cells the receptor interacts with CGRP and adrenomedullin with KD values of 1.2 nM for CGRP and 11 nM for adrenomedullin. Both ligands cause an elevation of intracellular cAMP with EC50 values of 4 nM and 20 nM respectively and these effects are inhibited by the antagonist CGRP8-37. The receptor is expressed at high levels in the pulmonary vascular endothelium. Both the pharmacological data and the localisation are consistent with the conclusion that the orphan receptor is a type J CGRP receptor. However, when expressed in COS-7 cells, no receptor activity could be demonstrated suggesting that 293 cells contain a factor necessary for functional receptor expression.

Pharmacokinetics of iodine-123-IMBA for melanoma imaging.

UNLABELLED: The development of an effective radiopharmaceutical with affinity for malignant melanoma has been a research goal for some time. The early detection of melanoma metastases would greatly improve the therapy outcome for this disease. This article describes the synthesis of radioiodinated IMBA, N-(2-diethylaminoethyl)-3-[123I/131I]iodo-4-methoxybenzamide 8, its organ distribution, its comparison with BZA and other benzamides, and demonstrates the scintigraphic efficacy of the title compound with three melanoma patients. METHODS: The syntheses and radioiodination of eight benzamide derivatives are described. After intravenous injection into C57B16-mice subcutaneously transplanted with B16 melanoma, the organ distribution of the respective benzamides were investigated at 1 and 6 hr. n-octanol/phosphate buffer partition coefficients. The wholebody retention, erythrocyte and serum protein bound fractions of radioiodinated benzamides were measured. RESULTS: While structural changes in the amide substituents of N-(2-dialkylaminoalkyl)-4-iodobenzamides 2-7 resulted in no improvement in organ distribution compared with BZA, the 3-iodo-4-methoxyphenyl form of IMBA showed high melanoma uptake with significantly higher melanoma/nontarget tissue ratios. Compared with BZA the average ratio improved after 1 hr by a factor of eight and was still four times better after 6 hr. BZA and IMBA exhibit almost identical n-octanol/ phosphate buffer partition coefficients, however, IMBA has a faster urinary excretion facilitated by a lower affinity to erythrocytes and serum proteins; this could explain the improved tissue partinioning observed. Scintigraphy of patients with melanoma metastases confirmed the promising characteristics derived from the animal studies. CONCLUSION: Due to rapid background clearance and high melanoma affinity, IMBA showed high tumor contrast already at 4 hr after injection which makes it a promising new radiopharmaceutical for the scintigraphic detection of melanoma metastases.

Nutritional supplementation in elderly medical in-patients: a double-blind placebo-controlled trial.

The aim of this study was to assess the effect of vitamin and/or glucose energy supplementation in elderly medical patients on an intention-to-treat basis. One hundred and six elderly medical in-patients were entered into a double-bind placebo-controlled factorial trial of glucose energy and vitamin supplementation. Supplementation was given for 1 month. This trial was designed to detect a > 2 kg increase in weight and > 3 g/l increase in serum albumin between active and placebo supplementation in 100 patients with 90% power (p < 0.05). Other outcome measures included changes in Barthel activities of daily living, length of stay, and mental test score (MTS). No interaction between vitamin and glucose supplementation was demonstrated. Active energy supplementation with glucose alone was associated with a +0.6 kg change in weight and +0.7 g/l change in albumin [95% confidence interval (CI) -0.8, +2.0 and -1.3, +2.8, respectively]. The respective changes for active vitamin supplementation were -0.6 kg for weight and +0.5 g/l for albumin (95% CI -2.1, +0.8 and -1.5, +2.6, respectively). There were no significant differences in mental test score, Barthel score, or length of stay between the two groups. Compliance with the glucose energy supplementation was poor with only one-third of patients consuming more than 50% of the offered drink. We conclude that the giving of glucose alone and/or vitamin supplementation in elderly patient is of no benefit on an intention-to-treat basis.

Use of surrogate respondents in studies of stroke and dementia.

A study was performed to determine the misclassification of information on exposure when surrogate informants are interviewed. Information from nondementia patients admitted to a geriatric ward was compared with that obtained from the patients' family members or friends (informants). Thirty-seven patients were recruited (17 with current or previous stroke, and 20 no history of stroke). Information on past medical and family history, cigarette smoking and alcohol consumption was collected using a questionnaire that was administered independently to patients and informants. For nonstroke patients, agreement on smoking and alcohol consumption at different ages was generally good. Informants reported slightly lower smoking and alcohol intake than patients: 1.3 fewer total pack-years (95% CI, -3.8, +6.5) and 2.7 fewer units/week (95% CI, -1.5, +6.9), respectively. For stroke patients, informants tended to report a greater smoking consumption at all ages, and a slightly higher alcohol consumption. Informants reported an excess of 7.4 total pack-years (95% CI, -1.2, + 16.0) and 2.19 units/week (95% CI, -1.0, +5.3). Agreement for medical history was good, except for hypertension. There was poor agreement for family medical history. The impact of misclassification is discussed.

The effect of low dose lofepramine in depressed elderly patients in general medical wards.

A double-blind randomised controlled trial of the effect of low dose lofepramine (70 mg once daily) against placebo was carried out on depressed elderly inpatients on general medical wards for the elderly, comparing measures of depression and side-effects between the randomised groups. Patients were identified for the study using the Geriatric Depression Scale (GDS) and the Brief Assessment Schedule Depression Cards (BASDEC). Sixty-three subjects were randomised: 46 patients completed the entire trial of 28 days treatment. BASDEC and GDS were administered on day 8 post-admission, and depressed patients were randomised double-blind to either low dose lofepramine (70 mg daily) (n = 23) or placebo (n = 23). Assessment of changes in depressive states were made using the Montgomery Asberg Depression Rating Scale (MADRS) on days 8, 18 and 36 post-admission. Both groups improved by a similar amount during the trial. Lofepramine tended to be more effective than placebo in those patients who were more depressed (GDS > or = 18). On the other hand, subjects who were less depressed (i.e. GDS < 18) improved more on placebo than lofepramine. Low dose lofepramine may prove useful in moderately or severely depressed patients treated for only 4 weeks. However, low dose lofepramine is not indicated for mild (GDS 15-18) depression.