Establishing priorities for European collaboration in communicable disease surveillance

Background: Several collaborations in communicable disease surveillancehave developed between European Union member states. Involvementin these activities takes time and money. It is vital that collaborationsare established in areas most likely to be beneficial. An exercisewas undertaken to inform national surveillance centres and theEuropean Commission as to priority areas for the developmentof collaborations. Methods: A modified Delphi exercise was undertakenamongst the heads of centres with responsibilities for surveillanceat national level in the member states of the EU. Participantsdeveloped, agreed and ranked criteria for developing collaborations.A list of communicable diseases and syndromes was then rankedusing a Likert-type scale. Three rounds were undertaken. Betweenrounds, scores and a ranking were fed back showing where participantshad ranked items, compared to the overall mean and rank distribution.For the third round participants were asked to use a categoricalscale, nominating six or ten high priority disease areas. Results:Response rates were 87.5% for round 1, 44% round 2 and 87% round3. The low round 2 response rate appeared to be because respondentsdid not wish to alter their rankings. The six high priorityareas were outbreaks of gastroenteritis/food poisoning, CID/otherslow virus infections, serious imported diseases, legionellosis,antimicrobial resistance and tuberculosis. When participantsgave ten high priority areas meningococcal disease, travel advice,vaccination/immunization and influenza were also included. Thefinal lists were accepted at the meeting of participants. Conclusions:The process was successful in developing both a priority listand consensus.     

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study

This study was designed to examine the effects of nisoldipine(relative to placebo), a new dihydropyridine calcium entry blockingagent, in the treatment of silent ischaemia in conventionaldoses. A total of 409 patients with proven coronary artery diseasewere screened and of this 64 had at least six episodes or atotal duration of 30 mm of ST segment depression (1 mm lastingat least 1 min) over 48 h. Fifty-two patients ultimately completeda randomized double-blind cross-over study comparing nisoldipine5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and numberof episodes of ST segment depression when compared to placeboon treatment with nisoldipine 5 mg twice a day and nisoldipine10 mg daily. However, the confidence limits were wide and crossedthe no-treatment effect line. In addition, the nisoldipine dosesneither affected the circadian distribution of ischaemic episodesnor caused an alteration of the workload achieved either atpeak exercise or at 1 mm ST segment depression measured 24 hafter nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients withproven coronary artery disease is relatively uncommon, it accountsfor approximately 16% of patients with positive exercise. Inthese patients nisoldipine, given as 5mg twice a day and 10mg daily, showed no significant therapeutic effects, eitheron the frequency or severity of silent ischaemia. New formulationsof slow release nisoldipine are consequently being developedso that a fuller 24 h therapeutic profile may be obtained.     

Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration.

Thallium (Tl+) toxicity has been related with the generation of reactive oxygen species (ROS) and oxidative stress (OS) in the central nervous system. Since changes in endogenous antioxidant systems might contribute to acute Tl+-induced OS and neurotoxicity, in this study we measured the metal concentration and the levels of lipid peroxidation (LP) in different brain regions (hypothalamus (Ht); cerebellum (Ce); striatum (S); hippocampus (Hc) and frontal cortex (Cx)) in possible correlation with the content of reduced glutathione (GSH), the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the animal performance in behavioral tests, all evaluated after a single administration of thallium acetate (8 or 16 mg/kg, i.p.) to rats. Seven days after Tl+ administration, the metal was homogeneously and dose-dependently accumulated in all regions evaluated. LP was increased in Ht, Ce and S, while GSH was depleted in S. Cu,Zn-SOD activity was also decreased in Ht and S. All these changes occurred with 16 mg/kg dose and at 7 days after treatment, but not at 1 or 3 days. In addition, Tl+-treated animals exhibited general hypokinesis, but no changes were observed in spatial learning. Our findings suggest that a delayed response of the brain to Tl+ may be the result of its residual levels. Also, despite the regional alterations produced by Tl+ in LP and the limited changes in endogenous antioxidants, there is a correlation between the Tl+-induced oxidative damage and the affected behavioral tasks, suggesting that, although still moderate, Tl+ evokes neurotoxic patterns under the experimental conditions tested.     

The effects of nisoldipine on the total ischaemic burden: the results of the ROCKET study

This study was designed to examine the effects of nisoldipine(relative to placebo), a new dihydropyridine calcium entry blockingagent, in the treatment of silent ischaemia in conventionaldoses. A total of 409 patients with proven coronary artery diseasewere screened and of this 64 had at least six episodes or atotal duration of 30 mm of ST segment depression (1 mm lastingat least 1 min) over 48 h. Fifty-two patients ultimately completeda randomized double-blind cross-over study comparing nisoldipine5 mg twice a day, nisoldipine 10 mg daily and placebo. There was a reduction in the ST segment integral and numberof episodes of ST segment depression when compared to placeboon treatment with nisoldipine 5 mg twice a day and nisoldipine10 mg daily. However, the confidence limits were wide and crossedthe no-treatment effect line. In addition, the nisoldipine dosesneither affected the circadian distribution of ischaemic episodesnor caused an alteration of the workload achieved either atpeak exercise or at 1 mm ST segment depression measured 24 hafter nidoldipine 10 mg or 12 h after nisoldipine 5 mg. We conclude that frequent silent ischaemia in patients withproven coronary artery disease is relatively uncommon, it accountsfor approximately 16% of patients with positive exercise. Inthese patients nisoldipine, given as 5mg twice a day and 10mg daily, showed no significant therapeutic effects, eitheron the frequency or severity of silent ischaemia. New formulationsof slow release nisoldipine are consequently being developedso that a fuller 24 h therapeutic profile may be obtained.     

Doppler haemodynamic assessment of clinically and echocardiographically normal mitral and aortic Allcarbon valve prostheses

Doppler echocardiographic characteristics of normally functioningAllcarbon prostheses were studied in 149 consecutive patientswith 157 valves in the mitral (n=73) and aortic (n=84) positionswhose function was considered normal by clinical and echocardiographicevaluation. In the mitral position, the mean gradient and theeffective mitral orifice area were not significantly differentin either the 25-mm or the 31-mm size valves (from 5±1to 4±1 mmHg and from 2.2±0.6 to 2.8±0.9cm², respectively; P=ns for both). Conversely, peak gradientwas significantly and inversely correlated to actual orificearea (r=–0.70; P<0.0006), decreasing from 15±3mmHg in the 25-mm size valve to 9±1 mmHg in the 31-mmsize. In the aortic position, the mean gradient was 29±8 mmHgin the 19-mm size valve; it decreased to 8±2 mmHg inthe 29-mm size. Effective prosthetic aortic valve area, calculatedusing the continuity equation, ranged between 0.9±0.1cm² for the 19-mm size valve to 4.1±0.7 cm² for the 29-mmsize. By analysis of variance, effective prosthetic aortic valvearea differentiated various valve sizes (F=25.3; P<0.0001)better than peak (F=5.34; P=0.012) or mean (F=4.34; P=0.0052)gradients alone, and it correlated better with actual orificearea (r=0.89, r=–0.70 and r=–0.65, respectively).This study provides the normal range for Doppler haemodynamiccharacteristics of the various sizes of the Allcarbon valvein the mitral and aortic positions so that prosthetic malfunctioncan be identified.     

Is on‐demand treatment effective in patients with severe haemophilia?

Summary. On‐demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on‐demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on‐demand and short‐term prophylaxis regimen; the rest was under on‐demand treatment. One hundred and forty‐five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy‐one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty‐three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty‐six patients underwent orthopaedic surgery at least once. These data show that on‐demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.     

Renal tight junction proteins are decreased in cisplatin-induced nephrotoxicity in rats

Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. It is unknown whether renal tight junction (TJ) proteins expression and localization are modified in CP-induced nephrotoxicity.

Objective: To study if the expression of the TJ proteins occludin, claudin-2, claudin-5 and zonula occludens-1 (ZO-1) is modified in rats with CP-induced nephrotoxicity.

Materials and methods: Male Wistar rats (n?=?5/group) were injected with saline solution (V group), and the other group (CP group) was injected with a single dose of saline solution and CP (7.5?mg/kg i.p.). Rats were sacrificed 72?h after CP injection and blood, and 24-h urine samples were collected. Several plasma and urinary injury biomarkers as well as renal histopathology lesions, oxidative and nitrosative stress markers were evaluated, and protein levels of ocludin, claudin-2, claudin-5, ZO-1 were measured by Western blot. Statistically significant changes noted with different p?Results: Nephrotoxicity was evident by histological alterations, glycosuria, decrease in creatinine clearance, increase in fractional excretion of sodium, serum creatinine and kidney injury molecule-1. These changes were associated with oxidative/nitrosative stress (increased renal abundance of 3-nitrotyrosine and protein kinase Cβ2 and decreased renal expression of nuclear factor-erythroid-2-related factor 2) and decreased activity of antioxidant enzymes. Finally, it was found that CP-induced renal damage was associated with decreased renal expression of occludin and claudin-2.

Discussion and conclusion: CP altered the TJ proteins expression and localization in the proximal tubule that was associated with oxidative/nitrosative stress.