Hantavirus outbreak in Western Europe: reservoir host infection dynamics related to human disease patterns.

Within Europe, Puumala virus (PUUV) is the causal agent of nephropathia epidemica (NE) in humans, a zoonotic disease with increasing significance in recent years. In a region of Belgium with a historically high incidence of NE, bank voles (the PUUV reservoir hosts), were monitored for PUUV IgG antibody prevalence in nine study sites before, during, and after the highest NE outbreak recorded in Belgium in 2005. We found that the highest numbers of PUUV IgG-positive voles coincided with the peak of NE cases at the regional level, indicating that a PUUV epizootic in bank voles directly led to the NE outbreak in humans. On a local scale, PUUV infection in voles was patchy and not correlated to NE incidence before the epizootic. However, during the epizootic period PUUV infection spread in the vole populations and was significantly correlated to local NE incidence. Initially, local bank-vole numbers were positively associated with local PUUV infection risk in voles, but this was no longer the case after the homogeneous spreading of PUUV during the PUUV outbreak.

Inducible expression of human C9ORF72 36x G4C2 hexanucleotide repeats is sufficient to cause RAN translation and rapid muscular atrophy in mice.

The hexanucleotide G4C2 repeat expansion in the first intron of the C9ORF72 gene explains the majority of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) cases. Numerous studies have indicated the toxicity of dipeptide repeats (DPRs) which are produced via repeat-associated non-AUG (RAN) translation from the repeat expansion and accumulate in the brain of C9FTD/ALS patients. Mouse models expressing the human C9ORF72 repeat and/or DPRs show variable pathological, functional, and behavioral characteristics of FTD and ALS. Here, we report a new Tet-on inducible mouse model that expresses 36x pure G4C2 repeats with 100bp upstream and downstream human flanking regions. Brain specific expression causes the formation of sporadic sense DPRs aggregates upon 6 months dox induction but no apparent neurodegeneration. Expression in the rest of the body evokes abundant sense DPRs in multiple organs, leading to weight loss, neuromuscular junction disruption, myopathy, and a locomotor phenotype within the time frame of four weeks. We did not observe any RNA foci or pTDP-43 pathology. Accumulation of DPRs and the myopathy phenotype could be prevented when 36x G4C2 repeat expression was stopped after 1 week. After 2 weeks of expression, the phenotype could not be reversed, even though DPR levels were reduced. In conclusion, expression of 36x pure G4C2 repeats including 100bp human flanking regions is sufficient for RAN translation of sense DPRs and evokes a functional locomotor phenotype. Our inducible mouse model suggests early diagnosis and treatment are important for C9FTD/ALS patients.

African pouched rats for the detection of pulmonary tuberculosis in sputum samples.

SETTING: Resource-limited settings in sub-Saharan African countries. OBJECTIVE: To utilise African giant pouched rats (Cricetomys gambianus) for the diagnosis of tuberculosis (TB) in human sputum. DESIGN: A specially designed cage with 10 sniffing holes and cassette-carrier was used. The sputum samples were put in the sample cassette, containing 10 samples in line, placed under matching sniffing holes. Rats were trained to sniff each consecutive sample, and indicate TB positives by fixing their nose for 5 seconds at the sniffing hole. This behaviour was maintained by food reinforcement upon correct indications. A total of 3416 samples were used. RESULTS: Of the 20 trained rats, 18 were able to discriminate positive from negative sputum samples, with average daily sensitivities ranging from 72% to 100%, and average daily false-positives ranging from 0.7% to 8.1%. The use of multiple rats significantly increased sensitivity and negative predictive value. CONCLUSION: Utilising trained sniffer rats for TB detection is a potentially faster screening method and is at least as sensitive as smear microscopy. This method could therefore be suitable for active case finding, especially where large numbers of samples are to be analysed in resource-limited settings, to complement existing diagnostic techniques.

Population, environmental, and community effects on local bank vole (Myodes glareolus) Puumala virus infection in an area with low human incidence.

In this study, the distribution of Puumala hantavirus (PUUV) infection in local bank vole Myodes glareolus populations in an area with low human PUUV infection (nephropathia epidemica [NE]) incidence in northern Belgium was monitored for 2 consecutive years. Bank voles were trapped in preferred habitat and tested for anti-PUUV IgG. Infection data were related to individual bank vole features, population demography, and environmental variables. Rare occurrence of PUUV infection was found and PUUV prevalence was low compared with data from the high NE incidence area in southern Belgium. Small-scale climatic differences seemed to play a role in PUUV occurrence, vegetation index and deciduous forest patch size both influenced PUUV prevalence and number of infected voles in a positive way. The data suggested a density threshold in vole populations below which PUUV infection does not occur. This threshold may vary between years, but the abundance of bank voles does not seem to affect the degree of PUUV seroprevalence further. We found indications for a dilution effect on PUUV prevalence, dependent on the relative proportion of nonhost wood mice Apodemus sylvaticus in a study site. In conclusion, we regard the combination of a dilution effect, a possible threshold density that depends on local conditions, and a higher fragmentation of suitable bank vole habitat in our study area as plausible explanations for the sparse occurrence of PUUV infection and low prevalence detected. Thus, beside human activity patterns, local environmental conditions and rodent community structure are also likely to play a role in determining PUUV infection risk for humans.

[The effect of different chemoembolization materials on CT-based attenuation correction in PET/CT]. / Effekt verschiedener Chemoembolisationsmaterialien auf die CT-basierte Schwächungskorrektur der PET/CT.

PURPOSE: Primary and secondary hypervascularized liver tumors may be treated with transarterial chemoembolization (TACE). The purpose of this study was to experimentally quantify the effect of different chemoembolization materials on the PET activity concentration in PET/CT. MATERIALS AND METHODS: Different concentrations of lipiodol, tungsten, tantalum, and a different number of platinum coils embedded in a carrier substance were placed in a liver phantom. An insert filled with only the carrier substance served as the negative control. The liver phantom was placed in a body phantom. The liver phantom was filled with 63.3 KBq [18-F]-Fluor-2-deoxy-D-glucose (FDG)/ml water, the body phantom was filled with 19.7 KBq FDG/ml water. PET/CT was performed and PET attenuation correction was performed based on the CT data. We defined: Activity concentration over embolization material (kBq/ml) approximately measured activity concentration; activity concentration over negative control (kBq/ml) approximately real activity concentration. An overestimation of the activity concentration was quantified by the following ratio: Activity concentration overestimation = activity concentration over embolization material (kBq/ml)/activity concentration over negative control (kBq/ml). RESULTS: All chemoembolization materials led to an overestimation of the PET activity concentration when using CT information for PET attenuation correction. The extent of overestimation is dependent on the concentration and the density of the chemoembolizing agent. PET activity overestimation was 11-151% with lipiodol, 34-1827% with tungsten, 16-1205% with tantalum, and 4-29% with platinum coils. CONCLUSION: Conventional chemoembolization materials cause an overestimation of the PET activity concentration in CT-based attenuation-corrected PET/CT images. This is of importance for the clinical routine since activity concentration quantification may not be used in the presence of chemoembolizing agents for imaging follow-up. If an increased FDG uptake is detected after transarterial chemoembolization, non-attenuation-corrected PET images must be assessed in addition to the attenuation-corrected images in order to differentiate artificially increased tracer uptake from a true increase in activity concentration of the tracer. The use of non-attenuating chemoembolizing materials (e.g. drug-eluting beads) for TACE may serve as an alternative to avoid embolization-associated PET artifacts.

Spectral EMG Changes in Cervical Dystonia Patients and the Influence of Botulinum Toxin Treatment.

Botulinum toxin (BoNT) injections in the dystonic muscles is the preferred treatment for Cervical Dystonia (CD), but the proper identification of the dystonic muscles remains a challenge. Previous studies showed decreased 8-14 Hz autospectral power in the electromyography (EMG) of splenius muscles in CD patients. Cumulative distribution functions (CDF's) of dystonic muscles showed increased CDF10 values, representing increased autospectral powers between 3 and 10 Hz, relative to power between 3 and 32 Hz. In this study, we evaluated both methods and investigated the effects of botulinum toxin. Intramuscular EMG recordings were obtained from the splenius, semispinalis, and sternocleidomastoid muscles during standardized isometric tasks in 4 BoNT-naïve CD patients, 12 BoNT-treated patients, and 8 healthy controls. BoNT-treated patients were measured 4-7 weeks after their last BoNT injections and again after 11-15 weeks. We found significantly decreased 8-14 Hz autospectral power in splenius muscles, but not in the semispinalis and sternocleidomastoid muscles of CD patients when compared to healthy controls. CDF10 analysis was superior in demonstrating subtle autospectral changes, and showed increased CDF10 values in all studied muscles of CD patients. These results did not change significantly after BoNT injections. Further studies are needed to investigate the origin of these autospectral changes in dystonia patients, and to assess their potential in muscle selection for BoNT treatment.

Prospective study on diagnostic strategies in osteochondral lesions of the talus. Is MRI superior to helical CT?

Our aim in this prospective study was to determine the best diagnostic method for discriminating between patients with and without osteochondral lesions of the talus, with special relevance to the value of MRI compared with the new technique of multidetector helical CT. We compared the diagnostic value of history, physical examination and standard radiography, a 4 cm heel-rise view, helical CT, MRI, and diagnostic arthroscopy for simultaneous detection or exclusion of osteochondral lesions of the talus. A consecutive series of 103 patients (104 ankles) with chronic ankle pain was included in this study. Of these, 29 with 35 osteochondral lesions were identified. Twenty-seven lesions were located in the talus. Our findings showed that helical CT, MRI and diagnostic arthroscopy were significantly better than history, physical examination and standard radiography for detecting or excluding an osteochondral lesion. Also, MRI and diagnostic arthroscopy performed better than a mortise view with a 4 cm heel-rise. We did not find a statistically significant difference between helical CT and MRI. Diagnostic arthroscopy did not perform better than helical CT and MRI for detecting or excluding an osteochondral lesion.

Disease course after liver transplantation for hepatocellular carcinoma in patients with complete tumor necrosis in liver explants after performance of bridging treatments.

AIM: To study the disease course of patients with hepatocellular carcinoma (HCC) showing complete tumor necrosis in their liver explants after undergoing bridging treatments followed by liver transplantation (LTx). PATIENTS AND METHODS: We evaluated data corresponding to 10 patients with liver cirrhosis undergoing bridging treatments for HCC prior to LTx. In all cases there was complete tumor necrosis in the explanted livers. RESULTS: There were 8 men and 2 women. Percutaneous radiofrequency ablation (RFA) was performed under computed tomographic guidance in 4 patients. The remaining 6 patients underwent transarterial chemoembolization (TACE). Five of them received one session of TACE, while the remaining one received a series of 4 sessions prior to LTx. Six patients had solitary nodules with a median diameter of 3.5 cm (range 2.5-4.2 cm). Four of them underwent RFA. Segmental tumor chemoembolization was performed in 2 patients. The remaining 4 patients had 2 tumors each with a median total diameter of 4.4cm (range 4.2-6.0 cm) prior to TACE. They underwent bilobar hepatic chemoembolization, which under staged the tumors prior to live donor liver transplantation (LDLTx). Six patients underwent deceased donor orthotopic liver transplantation. LDLTx was performed in 4 patients. Median waiting time to LTx was 53 days. All patients are alive without recurrence after a median follow-up of 19 months. CONCLUSION: Achievement of 100% tumor necrosis by means of bridging treatments followed by LTx for HCC is characterized by a very low recurrence rate and should receive further consideration and study.

Directional Recording of Subthalamic Spectral Power Densities in Parkinson's Disease and the Effect of Steering Deep Brain Stimulation.

BACKGROUND: A new 32-contacts deep brain stimulation (DBS) lead, capable of directionally steering stimulation, was tested intraoperatively. OBJECTIVE: The aim of this pilot study was to perform recordings from the multidirectional contacts and to investigate the effect of directional current steering on the local field potentials (LFPs). METHODS: In eight patients with Parkinson's disease, after standard microelectrode recording and clinical testing, the new lead was temporarily implanted. The 32-channel LFP recordings were measured simultaneously at different depths and directions before and after directional stimulation. RESULTS: The spatial distribution of LFPs power spectral densities across the contact array at baseline marked the borders of the subthalamic nucleus (STN) with a significant increase in beta power and with a mean accuracy of approximately 0.6 mm in four patients.The power in the 18.5-30 Hz frequency band varied across different directions in all patients. In the three cases that showed improvement of rigidity, this was higher when current was steered toward the direction with the highest LFP power in the beta band. Subthalamic LFPs in six patients showed a differential frequency-dependent suppression/enhancement of the oscillatory activity in the 10-45 Hz frequency band after four different 'steering' modes as compared to ring mode, suggesting a higher specificity. CONCLUSIONS: Through a new 32-contact DBS lead it is possible to record simultaneous subthalamic LFPs at different depths and directions, providing confirmation of adequate lead placement and multidirectional spatial-temporal information potentially related to pathological subthalamic electrical activity and to the effect of stimulation. Although further research is needed, this may improve the efficiency of steering stimulation.

A rare case of adductor longus muscle rupture.

An adductor longus muscle rupture is a rare injury. This case report describes a 32-year-old patient with an adductor longus rupture. The trauma mechanism was a hyperabduction movement during a soccer game. Nonoperative treatment was initiated. After a follow-up of 4 years, the patient was without pain but a small swelling was still visible. This report describes the anatomy, pathophysiology, and evidence-based treatment of adductor longus rupture.

Optimization of adult performance determines host choice in a grass miner.

Models and empirical studies on host selection in plant-insect, algae-amphipod, host-parasite and prey-predator systems assume that oviposition preference is determined by the quality of the oviposition site for offspring development. According to the oviposition-preference-offspring-performance hypothesis, oviposition-preference hierarchy should correspond to host suitability for offspring development because females maximize their fitness by optimizing offspring performance. We show, we believe for the first time, that adult feeding site and related adult performance may explain most of the variation in adult feeding and oviposition site selection of an oligophagous grass miner, Chromatomyia nigra (Diptera). This study advances our understanding of the complex interactions between plants and herbivores because it shows that host-preference patterns are not only shaped by the optimization of offspring performance, as previously assumed, but also by the optimization of adult performance.

Incidence of hantavirus infections in Belgium.

Over the last two decades, and from the moment that serological detection was possible, human hantavirus infections have been documented in most European countries. This paper summarises the available data on hantavirus cases in Belgium. These data enable the demonstration of the existence of a 3-year epidemic cycle in Belgium, which is apparently linked to rodent population dynamics.

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.

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.

Population and coherence transfer induced by double frequency sweeps in half-integer quadrupolar spin systems.

We have recently shown that the sensitivity of single- and multiple-quantum NMR experiments of half-integer (N/2) quadrupolar nuclei can be increased significantly by introducing so-called double frequency sweeps (DFS) in various pulse schemes. These sweeps consist of two sidebands generated by an amplitude modulation of the RF carrier. Using a time-dependent amplitude modulation the sidebands can be swept through a certain frequency range. Inspired by the work of Vega and Naor (J. Chem. Phys. 75, 75 (1981)), this is used to manipulate +/-(m - 1) <--> +/-m (3/2 < or = m < or = N/2) satellite transitions in half-integer spin systems simultaneously. For (23)Na (I = 3/2) and (27)Al (I = 5/2) spins in single crystals it proved possible to transfer the populations of the outer +/-m spin levels to the inner +/-1/2 spin levels. A detailed analysis shows that the efficiency of this process is a function of the adiabaticity with which the various spin transitions are passed during the sweep. In powders these sweep parameters have to be optimized to satisfy the appropriate conditions for a maximum of spins in the powder distribution. The effects of sweep rate, sweep range, and RF field strength are investigated both numerically and experimentally. Using a DFS as a preparation period leads to significantly enhanced central transition powder spectra under both static and MAS conditions, compared to single pulse excitation. DFSs prove to be very efficient tools not only for population transfer, but also for coherence transfer. This can be exploited for the multiple- to single-quantum transfer in MQMAS experiments. It is demonstrated, theoretically and experimentally, that DFSs are capable of transferring both quintuple-quantum and triple-quantum coherence into single-quantum coherence in I = 5/2 spin systems. This leads to a significant enhancement in signal-to-noise ratio and strongly reduces the RF power requirement compared to pulsed MQMAS experiments, thus extending their applicability. This is demonstrated by (27)Al 3QMAS experiments on 9Al(2)O(3). 2B(2)O(3) and the mineral andalusite. In the latter compound, Al experiences a quadrupolar-coupling constant of 15.3 MHz in one of the sites. Finally a 5QMAS spectrum on 9Al(2)O(3). 2B(2)O(3) demonstrates the sensitivity enhancement of this experiment using a double frequency sweep.

Serological and molecular characterization of leptospira serovar Kenya from captive African giant pouched rats (Cricetomys gambianus) from Morogoro Tanzania.

Two identical leptospiral isolates coded Sh9 and Sh25 obtained from the urine of captive African giant pouched rats (Cricetomys gambianus), destined for use as biodetector of antipersonnel landmines were typed as serovar Kenya using cross-agglutination absorption test and DNA fingerprinting with the insertion element sequences IS1533 and IS1500 derived primers. The two isolates were previously characterized using cultural and serological-microagglutination test as pathogenic leptospires of the serogroup Ballum, closely related to serovars Kenya and Peru. To our knowledge, this is the first reported in-depth characterization of leptospira isolates from Tanzania.

Proximal tibial varus osteotomy. Indications, technique, and five to twenty-one-year results.

BACKGROUND: Although high tibial osteotomy has been proved effective for the treatment of painful osteoarthritis of the medial compartment of the knee, the role of proximal tibial varus osteotomy for the treatment of painful osteoarthritis of the lateral compartment still remains controversial. METHODS: From 1974 to 1993, we performed proximal tibial varus osteotomy for the treatment of osteoarthritis of the lateral compartment of the knee in thirty-six consecutive patients. The procedure consisted of a proximal lateral opening-wedge varus osteotomy of the tibia with use of corticocancellous bone grafts from the iliac crest. The valgus deformity was posttraumatic in twenty-three patients, followed a lateral meniscectomy in five, was due to overcorrection of a varus deformity in four, and was idiopathic in four. The preoperative valgus deformity averaged 11.6 degrees (range, 4 degrees to 22 degrees ). RESULTS: At a mean of eleven years (range, five to twenty-one years) after the operation, the clinical results for thirty-four of the thirty-six patients were analyzed. None of the patients had severe progression of the osteoarthritis after the osteotomy, and none had a meaningful loss in the range of motion of the knee joint. A superficial wound infection developed in one patient, and another patient had thrombophlebitis. Three patients (9%) had a transient palsy of the peroneal nerve. According to the system of Insall et al., the mean knee score was 84 points (range, 54 to 99 points). According to the knee score described by Lysholm and Gillquist, the subjective result was excellent in nine patients (26%), good in twenty-one (62%), fair in three (9%), and poor in one (3%). CONCLUSIONS: We concluded that when the indications outlined in this study are followed and our opening-wedge technique is used, a proximal lateral opening-wedge varus osteotomy of the tibia is a good alternative for the treatment of isolated osteoarthritis of the lateral compartment of the knee. High accuracy in preoperative planning, based on a slight overcorrection, is important to prevent failure.

Eradication of hantavirus infection among laboratory rats by application of caesarian section and a foster mother technique.

Hantavirus antibodies were demonstrated by the indirect immunofluorescent antibody assay, in the serum of inbred strains of laboratory rats, during the period 1973-1982, at the Unit of Experimental Immunology in the Catholic University of Louvain, Brussels, Belgium. LOU rats, as well as immunocytomas, which were requested by laboratories in the U.K. and The Netherlands, were supplied at a time when the infection was unknown and unsuspected in Europe. Hantavirus-infected laboratory rats were rendered free of virus through re-derivation by caesarian section and suckling by virus-free foster mothers. Immunocytomas were tested for the presence of hantaviruses by implantation into seronegative laboratory rats. The strain of hantavirus causing the laboratory infection was clearly different from the one circulating in free-living bankvoles in Belgium. The exchange of laboratory rats and rat tumours in relation to the potential risk of laboratory-acquired hantavirus infection, is discussed.

Arthroscopy for problems after ankle fracture.

From 1990 to 1994 we undertook arthroscopy of the ankle on 34 consecutive patients with residual complaints following fracture. Two groups were compared prospectively. Group I comprised 18 patients with complaints which could be attributed clinically to anterior bony or soft-tissue impingement. In group II the complaints of the 16 patients were more diffuse and despite extensive investigation the definitive diagnosis was not clear before arthroscopy. At the time of the fracture, some osteophytes were already present in 41% of the patients. These were related to previous supination trauma and participation in soccer. Arthroscopic treatment consisted of removal of the anteriorly located osteophytes and/or scar tissue. After two years, group I showed a significantly better score for patient satisfaction (p = 0.02). There were good or excellent results in group I in 76% and group II in 43%. Patients with residual complaints after an ankle fracture and clinical signs of anterior impingement may benefit from arthroscopic surgery. The place for diagnostic ankle arthroscopy is limited.

Echinococcus multilocularis (Cestoda, Taeniidae) in Red foxes (Vulpes vulpes) in northern Belgium.

The first record of the tapeworm Echinococcus multilocularis (Cestoda, Taeniidae) in Red foxes (Vulpes vulpes) in northern Belgium is described. Between 1996 and 1999, 237 dead foxes were examined for the presence of this tapeworm using the intestinal scraping technique. Four foxes (1.7%) were found to be infected with E. multilocularis and showed medium to very high parasitic burdens. Three infected foxes originated from the south of the study area and the fourth animal came from the north of the study area near the border with The Netherlands. These findings are discussed in relation to the high endemicity of E. multilocularis in southern Belgium and to the increased distribution of the Red fox (V. vulpes) in northern Belgium during the last two decades.