Management of potential human cases of influenza A/H5N1: lessons from Belgium.
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Belgium↗
Biomedical subjects
I Thomas
Publications and source records attributed to I Thomas.
Spinal anaesthesia in a patient with hereditary spastic paraplegia: case report and literature review.
We report the use of spinal anaesthesia in a patient with hereditary spastic paraplegia who presented for manual removal of placenta following a normal vaginal delivery. This 18-year-old primigravida had been diagnosed with hereditary spastic paraplegia at 8 years of age when neurological examination revealed mild bilateral lower limb spasticity. A 25-gauge Whitacre spinal anaesthetic needle was inserted at the L3-4 intervertebral space and 0.5% plain bupivacaine 2 mL plus fentanyl 25 microg administered. The procedure was uneventful. At 24 hours postoperatively, there was full neurological recovery to pre-anaesthetic levels. The hereditary spastic paraplegias are a group of neurological disorders characterised by a slowly progressing spastic paraparesis. The neurological disorder and its anaesthetic implications are reviewed.
Adolescent↗
Randomised controlled trial of mammographic screening in women from age 40: results of screening in the first 10 years.
Debate continues over the effectiveness of screening by mammography in women below age 50. We report here on results of screening in the first 10 years of a randomised trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41 compared to first invitation to the 3-yearly UK national programme at age 50-52. The trial is taking place in 23 NHS breast screening centres. Between 1991 and 1997, 160 921 women were randomised in the ratio 1 : 2 to intervention and control arms. Screening is by two views at first screen and single view subsequently; data on screening up to and including round five are now complete. Uptake of invitation to screening is between 68 and 70% at all but the latest screening rounds. Rates of referral for assessment are 4.6% at first screen and 3.4% at subsequent screens. Invasive cancer detection rates are 0.09% at first screen, and similar at rescreens until the sixth and later screens. There is little evidence of regular mammography in the trial control arm. The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme.
Adult↗
Prevalence of human erythrovirus B19 DNA in healthy Belgian blood donors and correlation with specific antibodies against structural and non-structural viral proteins.
BACKGROUND AND OBJECTIVES: Human parvovirus (erythrovirus) B19 is recognized as a major contaminant of blood and blood products. To reduce the risk of contamination, plasma-pool screening and exclusion of highly viraemic donations are recommended. The objectives of this study were to estimate the prevalence of B19 DNA in our blood-donor population, to determine the appropriate pool size to be tested (taking into account parameters such as prevalence, viral load, test sensitivity, and the efficacy of inactivation procedures), and to correlate viral loads with the serological status of donors as regards antibodies against different viral proteins. MATERIALS AND METHODS: Pools of different sizes were tested for B19, using a sensitive nested polymerase chain reaction (PCR) as well as an simple, un-nested, less sensitive PCR. Positive pools were resolved to the level of individual donations, and the viral load and serological markers were determined. RESULTS: Of 16,859 donations, 27 (one of 625) were found to be B19 DNA positive, with viral loads ranging from 10(2) to > 10(7) IU/ml. Twenty-five of the positive donations were tested for VP-specific anti-B19 antibodies, and eight (32%) were negative for both immunoglobulin (Ig)M and IgG. They were probably collected in the preseroconversion window period or from chronic carriers without detectable antibodies. We regarded the seven (28%) IgM-positive donors as being in the early phase of infection. The remaining 10 (40%) IgM-negative, IgG-positive donors were probably carriers of persistent infection (i.e. PCR positive despite the presence of IgG antibodies), as suggested by their low viral loads (< 10(4) IU/ml). Fifteen out of 36 major pools contained one or more contaminated donations. Among these, 12 tested positive by nested PCR and only three by un-nested PCR, this reflecting a viral load of > 10(4) IU/ml. CONCLUSIONS: By testing all donations as pools of 480 by un-nested PCR, and resolving positive pools to identify the responsible donations, it is possible to ensure that the viral load in fractionation pools (5000 donations) remains < 10(3) IU/ml, compatible with the efficacy of inactivation procedures and complying with Food and Drug Administration (FDA) recommendations.
Algorithms↗
Assessment of the reproducibility of intradermal administration of capsaicin as a model for inducing human pain.
The reproducibility and tolerability of intradermal (i.d.) administration of capsaicin as a method for eliciting human pain was assessed in healthy male volunteers (n = 12). The primary endpoints for assessing pain were spontaneous pain response and areas of allodynia, pinprick hyperalgesia and neurogenic inflammation. These were recorded before, immediately after, and at regular intervals following each of four doses (250 microg) of capsaicin (two per trial day). Within- and between-subject variability to the technique was assessed by measuring the maximum recorded values (max), time to maximum value (t(max)) and area under the curve (AUC(0-1 h)) of each of the endpoints. Tolerability to the technique was addressed by recording adverse events. Reproducibility of the i.d. capsaicin model was demonstrated for each type of capsaicin-induced pain. Following each dose, the magnitude and profile of response and overall AUC values were similar for each parameter although some decrease in pinprick hyperalgesia was observed over time. For spontaneous pain, evidence of a period effect was observed in mean AUC data, with values increasing following the second dose of each trial day. This effect was confounded by the possibility of an arm effect, with the non-dominant arm appearing to be more sensitive to pain than the dominant arm. The data were not sufficient to confirm the existence of these effects. Between-subject variability and within-day, within-subject variability accounted for most of the variability observed in the trial. By optimising study design to eliminate these sources of variability, it was estimated that spontaneous pain and the area of allodynia would be the least variable endpoints. A positive correlation was found between the area of allodynia and area of pinprick hyperalgesia (r(2) = 0.835). Overall, the model was well tolerated with no reports of adverse events. We conclude that the tolerability profile, and variability of i.d. capsaicin-induced pain is acceptable for pharmacological profiling of novel anti-nociceptive agents, with limited number of subjects.
Analysis of Variance↗
Nucleic acid testing for emerging viral infections.
The development of new technologies leads to the discovery of new viruses. For each of these new infectious agents, relevance to transfusion, including transmissibility by transfusion, pathogenicity, prevalence in blood donors, persistence and the availability of screening assays needs to be assessed. Since 1995, one virus and a new family of viruses have been identified. GB virus-C/hepatitis G virus (GBV-C/HGV), a flavi virus with some homology with and epidemiological features of HCV, is not related to post-transfusion hepatitis but seems to positively interfere with human immunodeficiency virus replication. Human circoviruses include TT virus (TTV) and SEN-V. Both are highly variable, constituting a large family of distantly related viruses. They appear ubiquitous, infecting humans very early in life and are largely persistent. No clinical symptoms or pathogenicity is associated with TTV, but SEN-V might be associated with some non-A-E post-transfusion hepatitis. Parvovirus B19 has been known for many years, but its transmission to recipients of plasma derivatives despite viral inactivation raised the issue of screening plasma pools by nucleic acid testing. Most fractionators quantify B19 DNA in plasma pools to ensure a viral load of <10(4) IU mL-1.
Blood Donors↗
Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure.
BACKGROUND: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. METHODS AND RESULTS: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6+/-0.7, -5.4+/-0.7, and -4.6+/-0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0+/-0.4, -3.7+/-0.4, and -3.5+/-0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11+/-17, 68+/-17, 152+/-19, and 176+/-18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. CONCLUSIONS: In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.
Antidiuretic Hormone Receptor Antagonists↗
Effects of omapatrilat on hemodynamics and safety in patients with heart failure.
Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction < or = 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by approximately 6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an approximately 2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.
Administration, Oral↗
Genetic characterization of Puumala hantavirus strains from Belgium: evidence for a distinct phylogenetic lineage.
Puumala hantavirus (PUUV) sequences were recovered from red bank voles (Clethrionomys glareolus) trapped between 1996 and 1998 in four localities of southern Belgium: Thuin, Montbliart, Momignies and Couvin. In addition, three PUUV isolates originating from bank voles trapped in the 1980s in southern (Montbliart) and northern (Turnhout) Belgium were genetically characterized. Analysis of the complete S and partial M segment sequences showed that the Belgian PUUV strains constitute a genetic lineage, distinct from other known PUUV lineages from Europe and Japan. This lineage also includes a wild strain (Cg-Erft) originating from a neighbouring area of Germany. Within the Belgian lineage, geographical clustering of genetic variants was observed. In the Montbliart site, the range of diversity between the most temporally distant strains (from 1986 and 1996-1998) was higher than between those from 1996 and 1998, suggesting slight genetic drift via accumulation of neutral or quasi-neutral substitutions with time.
Animals↗
Deprivation and mortality: the implications of spatial autocorrelation for health resources allocation.
This paper aims at investigating whether the relationship between mortality and socio-economic deprivation is affected by the spatial autocorrelation of ecological data. A simple model is used in which mortality (all-ages and premature) is the dependent variable, and deprivation, morbidity and other socio-economic indicators are the explanatory variables. Deprivation is measured by the Townsend index; the other socio-economic variables are the median income, unequal income distribution (Gini coefficient) and population density. Morbidity is estimated on the basis of hospital admission rates and overweight prevalence. Spatial autocorrelation is measured by the Moran's I coefficient. All mortality and morbidity variables have significant, positive, and moderate-to-high spatial autocorrelation. Two multivariate models are explored: a weighted least-squares model ignoring spatial autocorrelation and a simultaneous autoregressive model. The paper concludes that spatial autocorrelation has a significant impact on the relationship between mortality and socio-economic variables. Future ecological models intended to inform health resources allocation need to pay greater attention to the spatial dimension of the data used.
Belgium↗
Ochrobactrum anthropi Pseudobacteraemia.
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Bacteremia↗
Ends versus means: the role of markets in expanding access to contraceptives.
Achieving and sustaining universal access to contraceptives are key policy goals of interventions supplying contraceptive commodities. Donor support for contraceptive supplies is substantial and many public and national programmes rely on donated and subsidized supplies of contraceptives. Sustainability of programme benefits is a concern to both national governments and donor agencies. At the same time, market-based provision of contraceptives has become a major source of contraceptives for individuals in a number of countries. While the goals or 'ends' of policy are to increase and sustain universal access to contraceptives, there is debate about the role of markets and their negative impacts on equity and universality. There is also concern that while public programmes supplying free contraceptives may, in the medium-term, achieve high coverage, they may hamper the achievement of long-term sustainability and the development of commercial markets. This paper focuses on the tension between the public health and market paradigms, and uses economic analysis as a framework in order to examine the relative roles or 'means' for subsidized public and commercial private sector supply of contraceptives. The review of the theory and evidence focuses on the trade-offs between public sector and market provision of contraceptives, examining the role for the public sector given the potential for market failures, the impact of public provision on the development of markets, and the role of price in demand. However, because of the potential conflict between these policy objectives, we argue that strategies to deliver contraceptives should be based on the specific characteristics of the context. In particular four variables (contraceptive prevalence rates, HIV prevalence, income level of country, size and geographic spread of private sector development) are important in characterizing this context, and these are highlighted in a matrix of programme priorities. Public choices need to take into account the ways in which they will affect the potential for development of sustainable private sources of supply. Undertaking a 'market assessment' should be a key stage in the analysis of policy options. Such an assessment should address demand factors, health priorities, actual and potential sources of supply and the relationships between public and private supply. Clearly the development of markets for contraceptives is not an end in itself, but may prove an important means of improving the health of women and men.
Contraceptive Agents↗
Linear IgA bullous dermatosis associated with vancomycin and disseminated varicella-zoster infection.
Linear IgA bullous dermatosis (LABD) is characterized by linear deposits of IgA at the basement membrane zone. Most cases are idiopathic, but medications, infections, autoimmune disorders, and malignancies have been documented as potential inducers. We report a case where both vancomycin and varicella-zoster infection were present as triggers.
Aged↗
Cutaneous manifestations of systemic cryptococcosis in immunosupressed patients.
Since its discovery 100 years ago, the encapsulated yeast Cryptococcus neoformans has been implicated in systemic infections of many immunocompromised patients and has been a leading cause of morbidity and mortality in AIDS patients. Clinical symptoms are often initially subtle or lacking. Cutaneous involvement often carries a dismal prognosis as it is usually a sign of dissemination. However, lesions may develop before any systemic or constitutional symptomatology, and despite their non specific appearance, are easily accessible for scrapings, biopsies and cultures. A high index of suspicion is of utmost importance in high risk individuals to avoid delaying the diagnosis and treatment.
Cryptococcosis↗
Ectopic adrenal tissue in the cow.
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Adrenal Glands↗
Triclabendazole-resistant Fasciola hepatica in southwest Wales.
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Animals↗
Spatial and temporal dynamics of Puumala hantavirus infection in red bank vole (Clethrionomys glareolus) populations in Belgium.
Dynamics of hantavirus infection and population densities in rodents were investigated from 1996 to 1999 in southern Belgium. Evidence of Puumala infection was restricted to Clethrionomys glareolus. Although the serotype was not determined, antibodies against hantavirus were also found in eight Apodemus sylvaticus. In fall 1996, the seroprevalence in C. glareolus was high (20.1%, 37 of 184) and the infection was widely distributed in the area studied whereas a focal occurrence of positive rodents and lower seroprevalence rates were recorded in spring 1997 (14.3%, six of 42), fall 1997 (6. 6%, 11 of 166), spring 1998 (6.4%, three of 47) and fall 1998 (6.7%, 11 of 165). A pullulation of rodents was observed in spring 1999 and was associated with a markedly higher seroprevalence in C. glareolus (47.7%, 189 of 396). In all seasons, infection rates in adults were higher than in juveniles and subadults. No significant difference of prevalence was recorded between males and females. In two trapping sites, the temporary disappearance of positive animals after a crash in rodent populations suggests that a threshold in density is necessary for the maintenance of the enzootic cycle.
Animals↗
Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: results of the ELITE ventricular function substudy.
BACKGROUND: The mechanism by which angiotensin-converting enzyme inhibitors reduce mortality rates and disease progression in patients with heart failure is likely mediated in part through prevention of adverse ventricular remodeling. This study examined the effects of the angiotensin-converting enzyme inhibitor captopril and the angiotensin II type 1 receptor antagonist losartan on ventricular volumes and function in elderly patients with heart failure and reduced left ventricular ejection fraction (< or =40%). METHODS: Patients underwent radionuclide ventriculograms (RVG) at baseline and were randomized to either captopril (n = 16) or losartan (n = 13). After 48 weeks, another RVG was obtained. Therapy was then withdrawn for at least 5 days, and the RVG was repeated while the patient was not receiving the drug. RESULTS: At 48 weeks both captopril and losartan significantly reduced left ventricular (LV) end-diastolic volume index (135 +/- 26 to 128 +/- 23 mL/m(2) for losartan, P <.05 vs baseline; 142 +/- 25 to 131 +/- 20 mL/m(2) for captopril, P <.01; mean (SD). Captopril also reduced LV end-systolic volume index (98 +/- 24 to 89 +/- 21 mL/m(2), P <.01 vs. baseline), whereas a nonsignificant trend was observed for the losartan group (97 +/- 23 to 90 +/- 16 mL/m(2), P = not significant). The between-group differences in the changes in LV volumes were not statistically significant. After drug withdrawal, LV end-diastolic volume index remained significantly lower than baseline in the captopril group (P <.01). CONCLUSIONS: Both captopril and losartan prevent LV dilation, representing adverse ventricular remodeling, previously seen with placebo treatment. Reverse remodeling was observed in the captopril group. On the basis of these results, the relative effects on LV remodeling do not provide a rationale for a survival benefit of losartan over captopril.
Aged↗