The value of virtual biobanks for transparency purposes with respect to reagents and samples used during test development and validation.

Biobanks represent a valuable resource in many areas of biomedical research and development. They function as repositories for well-documented and well-characterised biological material that can be used as the basis for this work. Virtual biobanks amplify the availability of this resource by linking multiple biobanks via a single interface. Test development and validation is an essential process that helps to provide confidence in diagnostic test results and, by extension, the disease and health status of animal populations demonstrated by such results. The quality of the development and validation pathway can be enhanced by the use of well-characterised material for standards and validation panels. Virtual biobanks represent a powerful mechanism for enhancing access to such material, and allow other parties to both have greater confidence in the work done, and to be able to repeat it themselves, as required.

Les biobanques constituent une ressource précieuse dans un grand nombre de domaines de la recherche et du développement biomédicaux. Elles servent d'archives destinées au stockage de matériels biologiques suffisamment documentés et caractérisés pour être utilisés comme éléments de base dans ces domaines. Les biobanques virtuelles opèrent comme multiplicateurs des ressources disponibles en reliant plusieurs biobanques sur une même interface. La mise au point et la validation des tests constituent un processus essentiel qui contribue à asseoir la confiance dans les résultats d'un test et, par voie de conséquence, dans le statut sanitaire d'une population animale tel qu'il ressort de ces résultats. La qualité du processus de développement et de validation peut être améliorée en faisant appel à des matériels bien caractérisés en tant que panels de référence et de validation. Les biobanques virtuelles sont un mécanisme puissant pour améliorer l'accès à ce type de matériels et permettent à d'autres intervenants d'avoir une plus grande confiance dans les travaux réalisés, et de pouvoir eux-mêmes les répéter, si besoin.

Los biobancos constituyen un recurso muy útil en numerosas vertientes de la labor de investigación y desarrollo (I+D) en biomedicina. Estos bancos funcionan como repositorios de material biológico bien descrito y caracterizado que cabe utilizar como base de dicha labor. Los biobancos virtuales, al vincular entre sí múltiples biobancos por medio de una única interfaz, ponen este recurso al alcance de muchos más usuarios. La creación y validación de pruebas analíticas es un proceso esencial, que ayuda a ofrecer confianza en los resultados de una prueba de diagnóstico y, por extensión, en la condición sanitaria de las poblaciones animales que dichos resultados indican. Es posible conferir mayor calidad al procedimiento de creación y validación utilizando muestras biológicas bien caracterizadas como material de referencia y para establecer paneles de validación. Los biobancos virtuales, amén de constituir un potente mecanismo para mejorar el acceso a material biológico, infunden a terceras partes mayor confianza en la labor realizada y permiten a estas partes replicar por sí mismas el proceso de ser necesario.

Atypical scrapie in Australia.

BACKGROUND: Since its initial detection in Norway in 1998, atypical scrapie ('atypical/Nor98 scrapie') has been reported in sheep in the majority of European countries (including in regions free of classical scrapie) and in the Falkland Islands, the USA, Canada, New Zealand and Australia. CASE SERIES: The diagnosis in Australia of atypical scrapie in four Merino and one Merino-cross sheep showing clinical signs of neurological disease was based on the detection of grey matter neuropil vacuolation (spongiform change) in the brain (particularly in the molecular layer of the cerebellar cortex) and associated abnormal prion protein (PrPSc ) deposition in both grey and white matter. Changes were minimal in the caudal brainstem, the predilection site for lesions of classical scrapie. CONCLUSION: The distinctive lesion profile of atypical scrapie in these five sheep highlights the diagnostic importance of routine histological evaluation of the cerebellum for evidence of neuropil vacuolation and associated PrPSc deposition in adult sheep with suspected neurological disease.

Inpatient treatment for functional neurologic disorders.

Patients with functional neurologic disorders present to clinicians with a variety of symptomatic manifestations, with various levels of severity, chronicity, and comorbidity, as well as with various degrees of past adversity, intrinsic resilience, and available external support. Clearly, treatment must be individualized. For those patients who have been severely or chronically impaired, especially if adequate prior outpatient treatments have failed, inpatient treatment that integrates the various modalities outlined here provides a rational route of rescue from a course otherwise potentially characterized by protracted dependence and disability. Based on the data currently available, we believe this treatment approach is worthy of further study to refine the component treatment strategies and enhance the potentially most effective ingredients. For patients with severe levels of disability, who could be managed in a multimodal day-treatment program, that approach also warrants further consideration.

Complete regression of renal tumour following ligation of an accessory renal artery during repair of an abdominal aortic aneurysm.

The existence of concomitant intra-abdominal pathology with abdominal aortic aneurysms is not uncommon. The optimal management is often controversial. We describe the successful treatment of a case of an abdominal aortic aneurysm (AAA) associated with a renal tumour without performing a nephrectomy. An accessory lower pole renal artery supplying the tumour was ligated at the time of open AAA repair. The lower pole renal tumour (suspected renal cell carcinoma) reduced in size dramatically and progressively on follow-up computed tomography and the patient remains well at over two years after surgery. The successful treatment of the two conditions in such a manner represents an alternative management strategy and adds to the options available in selected patients who present with challenging and unusual pathology.

Simple posterior elbow dislocation and brachial artery transection.

We report the uncommon occurrence of a complete brachial artery transection following simple posterior dislocation of the elbow, successfully managed by cephalic vein interposition grafting. This case together with a review of the literature was conducted with the aim of highlighting important issues regarding the diagnosis, management and prognosis of this rare complication.

The zoonotic flaviviruses of southern, south-eastern and eastern Asia, and Australasia: the potential for emergent viruses.

The genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south-eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick-borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito-borne, six are tick-borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya-Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread.

Dieback and recovery in poplar and attack by the hornet clearwing moth, Sesia apiformis (Clerck) (Lepidoptera: Sesiidae).

A survey of 801 poplar trees in central east England in 1999 demonstrated a correlation between crown dieback and infestation by hornet clearwing moth (Sesia apiformis), induced by a period of drought in 1995-1996. To determine whether trees colonised by S. apiformis would subsequently deteriorate and die or whether they could recover despite infestation and damage to the stem, all trees in the original survey were re-assessed in 2001, 2003 and 2005. The repeat surveys showed that trees with 70% or less crown dieback in 1999 replaced their canopy and generally improved by 2005, irrespective of the numbers of S. apiformis in the stem, whereas trees that had 75% or more crown dieback in 1999 either died or declined further. The presence of S. apiformis did not prevent tree recovery, and there was little evidence that infestation slowed the rate of recovery. Populations of S. apiformis, measured in terms of the numbers of adult emergence holes visible in the base of the trees, decreased between 2001 and 2005 at the same time as the amount of dieback visible in the canopy of the poplars markedly decreased. However, the fall in numbers of emergence holes at this time reflected a decline in larval establishment 2-3 years earlier, and indicated that the moth population had responded to a more rapid restoration in the internal state of the trees, which was not reflected immediately by the gradual replacement of dead branches and reduction in dieback symptoms.

The influence of exercise on foot perfusion in diabetes.

AIMS: Diabetic foot disease is associated with both macro- and microvascular disease. Exercise has both positive and negative effects on the perfusion of lower limbs with peripheral arterial occlusive disease (PAOD). We aimed to measure changes in foot perfusion following a brief period of lower-limb exercise in individuals with and without Type 2 diabetes and non-critical PAOD. METHODS: Subjects were allocated to groups according to the presence or absence of diabetes, PAOD on colour duplex imaging and clinically detectable peripheral neuropaIthy. Transcutaneous oxygen tension (TcPO(2)), transcutaneous carbon dioxide tension (TcPCO(2)), ankle-brachial pressure indices, toe pressures and toe-brachial pressure indices (TBI) were measured. RESULTS: One hundred and sixteen limbs were studied in 61 subjects. Post-exercise, toe pressure and TBI increased in the non-diabetic group with arterial disease, but not in the groups with diabetes. Foot TcPO(2) values increased in groups with diabetes and TcPCO(2) decreased in all groups with arterial disease. Increased chest TcPO(2) and decreased TcPCO(2) were demonstrated in the groups with diabetes. CONCLUSIONS: Elevations in foot TcPO(2) and reductions in TcPCO(2) indicate improved cutaneous perfusion response to local heating post-exercise. Elevated toe pressures in the non-diabetes group suggest that improved perfusion may be associated with enhanced lower limb macrovascular haemodynamics. However, improvements in TcPO(2) and TcPCO(2) at foot and chest sites in diabetes imply a global change in cutaneous perfusion. The results suggest that brief exercise results in an improvement in cutaneous perfusion in non-critical PAOD, particularly in individuals with diabetes.

Japanese encephalitis in a racing thoroughbred gelding in Hong Kong.

A horse in Hong Kong that had been vaccinated against Japanese encephalitis suffered a pyrexic episode that culminated in a hyperexcitable state and self-inflicted trauma. Japanese encephalitis was diagnosed on the basis of clinical, pathological and serological observations, and confirmed by the detection of genomic sequences of the virus in spinal cord tissue. Phylogenetic analyses of E gene and NS5-3'UTR sequences revealed divergent clustering of these segments with previously described genotypes, suggesting the possibility that the horse might have been infected with a recombinant between genotype I and genotype II viruses. Horses are considered to be dead-end hosts for the disease, but the occurrence of an infected horse in a population may have implications for the health status of the national herd. The effect that this case had on the horse industry in Hong Kong is discussed with specific reference to the movement of horses and the vaccination programme for Japanese encephalitis.

Diagnosing foot infection in diabetes.

Infection represents the presence of an inflammatory response and tissue injury due to the interaction of the host with multiplying bacteria. The disease spectrum is a consequence of the variability in these interactions. Diabetes, because of its effects on the vascular, neurological, and immune systems, can compromise the local and systemic response to infection, potentially masking the typical clinical features and hindering diagnosis. The early recognition of infection, particularly osteomyelitis, is paramount in the management of diabetic foot disease. Careful clinical appraisal remains the cornerstone of the assessment. Hematologic, biochemical, and radiological investigations are important aids in assessing the severity of infection. Microbiological assessment, particularly in more severe infection, requires good-quality samples, combined with rapid transport in an appropriate medium and effective communication with the laboratory. A focused, systematic approach to the accurate diagnosis and treatment of infection, combined with careful monitoring, ensures the maintenance of optimal management.

Wound dressings in diabetic foot disease.

Wound dressings represent a part of the management of diabetic foot ulceration. Ideally, dressings should alleviate symptoms, provide wound protection, and encourage healing. No single dressing fulfills all the requirements of a diabetic patient with an infected foot ulcer. Dressings research in this area is generally poor. However, each category of dressings has particular characteristics that aid selection. Nonadhesive dressings are simple, inexpensive, and well tolerated. Foam and alginate dressings are highly absorbent and effective for heavily exuding wounds. Hydrogels facilitate autolysis and may be beneficial in managing ulcers containing necrotic tissue. Dressings containing inidine and silver may aid in managing wound infection. Occlusive dressings should be avoided for infected wounds. All dressings require frequent change for wound inspection. Heavily exudating ulcers require frequent change to reduce maceration of surrounding skin. Dressing choice should be guided by the characteristics of the ulcer, the requirements of the patient, and costs.

Phaeochromocytoma--views on current management.

AIMS: To evaluate the current investigation and management of phaeochromocytoma. METHODS: Retrospective analysis of patients who underwent surgical excision of phaeochromocytoma in the Department of Endocrine Surgery at the University Hospital of Wales, Cardiff. Forty-seven patients (24 female and 23 males) were studied. Preoperative diagnosis was established by measurement of urinary catecholamines (HMMA, metadrenalines, and fractionated catecholamines). Tumour localisation was achieved by using ultrasound, CT, MRI and MIBG scintigraphy. Preoperative medical preparation and control of hypertension was achieved in the majority of cases by alpha adrenergic blockade with phenoxybenzamine and the beta blocker propranol. Surgery was performed by a variety of approaches which included laparotomy, posterior extraperitoneal and laparoscopic methods. All patients were followed up post-operatively in a surgical endocrine clinic. RESULTS: Seventy percent of patients presented with hypertension but only 21.3% gave a history of paroxsmal hypertension. CT scanning and MRI proved to be the most sensitive localisation investigations. Excellent preoperative control of hypertension was achieved with alpha adrenergic blockade but induction of anaesthesia, rather than tumour handling was noted to be associated with most hypertensive surges of blood pressure. There was a zero 30 day post-operative mortality but 10 complications of surgery occurred in 8 patients (21.3%). Cure of hypertension was achieved in 80% of patients. Attempts to perform cortex sparing procedures in patients with familial disease and multiple tumours was not successful in the long term. CONCLUSIONS: Surgical excision of phaeochromocytoma is a procedure, which can be performed with zero mortality and a low morbidity resulting in a high cure rate for hypertension. Adequate preoperative pharmacological control of hypertension is mandatory. Localisation techniques permit a focussed approach with increasing use of laparoscopy. Those patients with familial disease and those with multiple tumours pose particular management challenges. For an optimum and satisfactory outcome a planned multidisciplinary approach is required.

Experimental infections of pigs with Japanese encephalitis virus and closely related Australian flaviviruses.

The flavivirus Japanese encephalitis (JE) virus has recently emerged in the Australasian region. To investigate the involvement of infections with related enzootic flaviviruses, namely Murray Valley encephalitis (MVE) virus and Kunjin (KUN) virus, on immunity of pigs to JE virus and to provide a basis for interpretation of serologic data, experimental infections were conducted with combinations of these viruses. Antibody responses to primary and secondary infections were evaluated using panels of monoclonal antibody-based blocking enzyme-linked immunosorbent assays and microtiter serum neutralization tests (mSNTs). Identification of the primary infecting virus was possible only using the mSNTs. Following challenge, unequivocal diagnosis was impossible due to variation in immune responses between animals and broadened and/or anamnestic responses. Viremia for JE virus was readily detected in pigs following primary infection, but was not detected following prior exposure to MVE or KUN viruses. Boosted levels of existing cross-neutralizing antibodies to JE virus suggested a role for this response in suppressing JE viremia.

Emerging viral diseases of Southeast Asia and the Western Pacific.

Over the past 6 years, a number of zoonotic and vectorborne viral diseases have emerged in Southeast Asia and the Western Pacific. Vectorborne disease agents discussed in this article include Japanese encephalitis, Barmah Forest, Ross River, and Chikungunya viruses. However, most emerging viruses have been zoonotic, with fruit bats, including flying fox species as the probable wildlife hosts, and these will be discussed as well. The first of these disease agents to emerge was Hendra virus, formerly called equine morbillivirus. This was followed by outbreaks caused by a rabies-related virus, Australian bat lyssavirus, and a virus associated with porcine stillbirths and malformations, Menangle virus. Nipah virus caused an outbreak of fatal pneumonia in pigs and encephalitis in humans in the Malay Peninsula. Most recently, Tioman virus has been isolated from flying foxes, but it has not yet been associated with animal or human disease. Of nonzoonotic viruses, the most important regionally have been enterovirus 71 and HIV.

The appearance of a second genotype of Japanese encephalitis virus in the Australasian region.

In mid-January 2000, the reappearance of Japanese encephalitis (JE) virus activity in the Australasian region was first demonstrated by the isolation of JE virus from 3 sentinel pigs on Badu Island in the Torres Strait. Further evidence of JE virus activity was revealed through the isolation of JE virus from Culex gelidus mosquitoes collected on Badu Island and the detection of specific JE virus neutralizing antibodies in 3 pigs from Saint Pauls community on Moa Island. Nucleotide sequencing and phylogenetic analyses of the premembrane and envelope genes were performed which showed that both the pig and mosquito JE virus isolates (TS00 and TS4152, respectively) clustered in genotype I, along with northern Thai, Cambodian, and Korean isolates. All previous Australasian JE virus isolates belong to genotype II, along with Malaysian and Indonesian isolates. Therefore, for the first time, the appearance and transmission of a second genotype of JE virus in the Australasian region has been demonstrated.

Propranolol treatment of chronically hospitalized aggressive patients.

Violent behavior in psychiatric patients may result in long-term hospitalization. There is no FDA-approved psychopharmacologic treatment for aggression. In this study, 20 chronically aggressive hospitalized patients were administered 1 week of placebo followed by an open trial of increasing doses of propranolol. Patients who had an equivocal or definite clinical response were entered into an open add-on double-blind discontinuation study phase. Aggressive behavior was objectively documented throughout the study. After the open phase of the study, 7 patients had a greater than 50% decrease in aggressive behavior. Four patients entered the double-blind discontinuation phase. The clinical course of 3 of those patients was consistent with the positive response to propranolol. The results of this study are consistent with a therapeutic effect of propranolol in some patients with aggressive behavior. Further studies are indicated.

A study on organotin levels in Canadian drinking water distributed through PVC pipes.

A study on organotin compounds in Canadian drinking water was carried out in winter-spring 1996 (28 sites) and autumn 1996 (21 sites). Approximately 29% and 40% of distribution waters supplied through PVC pipes installed recently (typically less than 6 months) contained organotin compounds in the winter-spring and autumn surveys respectively. Monomethyl-, dimethyl-, monobutyl- and dibutyltin levels ranged up to 291 ng Sn/L, 49.1 ng Sn/L, 28.5 ng Sn/L and 52.3 ng Sn/L, respectively. An additional study in summer 1996, of locations where the highest organotin levels were detected in the winter-spring survey, indicated that organotin levels had decreased in most distribution water samples. Samples of PVC pipe/tubing contained organotin compounds consistent with the organotin patterns found in the distribution water samples.

A decay-accelerating factor-binding strain of coxsackievirus B3 requires the coxsackievirus-adenovirus receptor protein to mediate lytic infection of rhabdomyosarcoma cells.

The composition of the cellular receptor complex for coxsackievirus B3 (CVB3) has been an area of much contention for the last 30 years. Recently, two individual components of a putative CVB3 cellular receptor complex have been identified as (i) decay-accelerating factor (DAF) and (ii) the coxsackievirus-adenovirus receptor protein (CAR). The present study elucidates the individual roles of DAF and CAR in cell entry of CVB3 Nancy. First, we confirm that the DAF-binding phenotype of CVB3 correlates to the presence of key amino acids located in the viral capsid protein, VP2. Second, using antibody blockade, we show that complete protection of permissive cells from infection by high input multiplicities of CVB3 requires a combination of both anti-DAF and anti-CAR antibodies. Finally, it is shown that expression of the CAR protein on the surface of nonpermissive DAF-expressing RD cells renders them highly susceptible to CVB3-mediated lytic infection. Therefore, although the majority of CVB3 Nancy attaches to the cell via DAF, only virus directly interacting with the CAR protein mediates lytic infection. The role of DAF in CVB3 cell infection may be analogous to that recently described for coxsackievirus A21 (D. R. Shafren, D. J. Dorahy, R. A. Ingham, G. F. Burns, and R. D. Barry, J. Virol. 71:4736-4743, 1997), in that DAF may act as a CVB3 sequestration site, enhancing viral presentation to the functional CAR protein.