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Biomedical subjects

J Bingham

Publications and source records attributed to J Bingham.

At least 19 recordsLinked to original sources

Transmission of syphilis by solid organ transplantation.

Two organ recipients developed serologic evidence of syphilis infection after renal transplantation from a common deceased donor with a history of treated syphilis. Testing of donor serum for syphilis, which occurred after transplantation, gave results interpreted as consistent with past infection. However, subsequent serologic results in the recipients suggested transmission of infection at transplantation due to active infection of the donor. This may be explained by recent donor re-infection in view of the current syphilis epidemic in the United Kingdom. An initial error in the treatment of recipients further served to highlight unfamiliarity in managing this resurgent infection in the context of organ transplantation.

Adult↗

Cultured skin fibroblast cells derived from bluetongue virus-inoculated sheep and field-infected cattle are not a source of late and protracted recoverable virus.

A recent hypothesis to explain the recurrence of bluetongue disease after winter seasonal absences of the vector has suggested a role for persistent infection of sheep. This report presents combined independent work from two laboratories investigating the possible recovery of Bluetongue virus (BTV) over a protracted period after infection of both sheep and cattle. Prior to infection with either cell-culture-adapted or non-culture-adapted BTV, sheep were subjected to a preliminary exposure to Culicoides sp. insects, which reportedly facilitates recovery of virus from infected sheep several months post-infection (p.i.). A series of skin biopsies at different intervals p.i. was used to establish skin fibroblast (SF) cultures from which attempts were made to detect virus by isolation and by molecular and immunological methods. Also examined was the effect on virus recovery of additional exposure to Culicoides sp. prior to skin biopsy during the post-inoculation period. A herd of cattle sentinels for surveillance of natural BTV infection in northern Australia was monitored prospectively for seroconversion. Evidence of infection initiated attempted virus recovery by establishing SF cultures. It was found that in both cattle and sheep there was not a protracted period over which BTV could be recovered from SF cultures. The data do not support a general hypothesis that BTV persists in either sheep or cattle.

Animals↗

Investigation of prion removal/inactivation from chromatographic gel.

BACKGROUND AND OBJECTIVES: Concerns about the potential for prions to be retained on chromatography gels during the manufacture of plasma products prompted development of an investigational strategy for detecting infectious prions bound to gels. The objective was to firstly examine methods of implanting gels intracerebrally (IC) in mice, then to examine prion cleaning from a scaled-down version of the DEAE Sepharose column used in a production process to fractionate immunoglobulins and albumin from human plasma. MATERIALS AND METHODS: The study consisted of two parts: (i) the pathophysiological impact by IC inoculation of ground gel beads was compared to whole gel beads; (ii) the feedstreams to two DEAE Sepharose columns were spiked with scrapie ME7. One column was subjected to the protein loading and elution portions of the chromatography cycle. The other column was subjected to the full cycle of protein loading and elution, followed by regeneration with 0.5 m NaCl, 1 m NaOH and solvent/detergent washes. The gels were unpacked and bioassayed by IC implantation in mice to quantify infectivity. RESULTS: IC inoculation of ground gel beads resulted in unacceptably high pathological impact in the mice whereas whole gel bead inoculation resulted in a reduced affect. Accordingly, the whole bead model system was used to assess prion removal/inactivation from chromatography gels at the pre- and postcleaning stage of the chromatography cycle. Infectious prions were detected on the DEAE Sepharose prior to the cleaning step; however, the gel cleaning cycle reduced infectivity by a log reduction factor (LRF) of > or = 2.75, thus reducing infectivity by bioassay to below detectable limits. CONCLUSIONS: A model system for assessment of prion inactivation/removal from chromatography gels has been established. Spiked prion infectivity does bind to DEAE Sepharose gel; however, the cleaning cycle removed infectivity to levels below that detectable by bioassay.

Adsorption↗

Mongoose rabies in southern Africa: a re-evaluation based on molecular epidemiology.

Relative to the developed world, rabies has been poorly studied in the vast African continent. The southern African countries of Zimbabwe and South Africa, however, are known to sustain a great diversity of lyssaviruses, with large biological variations amongst genotype 1 (rabies viruses) at present more apparent here than elsewhere on the continent. One recognized biotype of rabies virus in the subcontinent appears to be specifically adapted to a variety of mongooses, belonging to the Viverrinae subfamily (family Herpestidae) and are commonly referred to as viverrid viruses, although the term mongoose rabies would be more correct, considering the taxonomic status of the host species involved. It was our objective to study the genetic relationships of 77 rabies virus isolates of this mongoose biotype, isolated in South Africa and Zimbabwe, towards elucidation of the molecular epidemiology of this interesting group of African viruses. In our study of a 592 nucleotide sequence encompassing the cytoplasmic domain of the glycoprotein and the G-L intergenic region of the viral genomes, we provide the first comprehensive data on the molecular epidemiology of these viruses and indicate a history of extended evolutionary adaptation in this geographical domain. The molecular epidemiological observations reported here are highly unlikely to be limited to the small geographical areas of South Africa and Zimbabwe and illustrate the need for lyssavirus surveillance in the rest of sub-Saharan Africa and throughout the entire continent.

Adaptation, Biological↗

Preventing reservoir calculi after augmentation cystoplasty and continent urinary diversion: the influence of an irrigation protocol.

OBJECTIVE: To evaluate the influence of an irrigation protocol in preventing reservoir calculi forming after augmentation cystoplasty and continent urinary diversion. PATIENTS AND METHODS: Between 1985 and 1995, 91 patients had an augmentation cystoplasty and/or continent urinary diversion (group 1; 54 females and 37 males, mean age 11.1 years, range 1-31); these patients were not routinely instructed to use irrigation after surgery. The segments used included ileum (44), colon (36), stomach (eight) and ureter (three). Between 1995 and 2000, 42 patients (group 2) underwent urinary reconstruction (22 females and 20 males, mean age 14.8 years, range 4-27), the segment used being ileum (30), colon (five), ureter (five) and stomach (two) but in contrast to group 1 they then were placed on a standard prophylactic irrigation protocol. The occurrence of stones in the reservoir was then assessed. RESULTS: Thirty-nine of the 91 patients (42.8%) in group 1 presented with reservoir calculi after reconstruction and 22 had several episodes. The mean time to presentation was 30 months. The incidence of stone formation by underlying diagnosis included: myelomeningocele, 32/48 (66%), exstrophy five/25 (25%), posterior urethral valves two/20 (10%) and rhabdomyosarcoma, none of three. Fifty of the 91 patients had an abdominal stoma, with stone formation in 33 (66%), while 41 used the native urethra, with stone formation in six (15%). Three (7%) of the 42 patients in group 2 developed reservoir calculi after reconstruction, two in patients with myelomeningocele and one in a trauma patient who had residual bone spicules in the bladder; the mean time to presentation was 26.5 months. CONCLUSIONS: These data suggest that the irrigation protocol used in group 2 significantly reduced the number of reservoir calculi after urinary tract reconstruction when bowel was used as part of the reconstruction (43% vs. 7%). The most calculi in both groups were in immobile patients with sensory impairment. Also, patients with an abdominal stoma had a greater risk of reservoir calculi (66%) than those using the native urethra (15%).

Adolescent↗

Molecular epidemiology of canid rabies in Zimbabwe and South Africa.

The epidemiology of rabies in southern Africa is complex, due to a large number of vector species and the presence of at least two distinct biotypes of the virus. Our objective was to contribute to the understanding of the epidemiology of rabies in the southern African subcontinent by studying the genetic relationship of 89 rabies virus isolates from this region. In this study, we have focused on an analysis of viruses that cycle in canid host species (canid biotype) throughout South Africa and Zimbabwe. By phylogenetic analysis of the cytoplasmic domain of the glycoprotein and the non-coding G-L intergenic region, all the southern African canid viruses were found to be closely related and no apparent general distinction could be made between them. Although there was a minor degree of phylogenetic branching, with certain branches associated with cycles defined by species, location and time, the phylogenetic pattern indicated that canid rabies in southern Africa is derived from a single virus lineage, which has spread opportunistically within whatever canid host population is ecologically capable of sustaining prolonged cycles. This molecular epidemiological study presents the first comprehensive comparison of rabies viruses from South Africa and Zimbabwe and has demonstrated the need for multinational approaches towards the control of this important zoonotic disease in Africa.

Animals↗

Can FDG PET be used to successfully direct preoperative biopsy of soft tissue tumours?

Magnetic resonance imaging (MRI) has been the most useful tool in the anatomical definition of soft tissue sarcoma, although there remains the problem of defining the lesions as benign or malignant. The management of such lesions requires biopsy prior to surgical resection. If the most malignant area could be defined more accurately, then this area could be targeted for biopsy. Fluorodeoxyglucose positron emission tomography (FDG PET) has been found to be useful in identifying malignancy and variations in grade in soft tissue masses. The aim of this study was to assess the use of FDG PET scanning with or without co-registered MRI to indicate the most appropriate biopsy site. Twenty consecutive patients presented with soft tissue masses with clinical signs of malignancy. All patients underwent MRI and FDG PET scanning and the two images were co-registered. A biopsy site that was the most likely to be malignant was defined on the PET scan. All patients underwent an initial biopsy and then complete surgical resection of the mass. The histological results from the mass were compared with those from the biopsy specimen obtained from the site suggested by the PET scan. In malignant masses the biopsy site suggested by the FDG PET scan was found to be representative of the most malignant site on the whole mass histology. Benign lesions had low or no FDG uptake. In no case did the co-registered image add significantly to the appropriate biopsy site. FDG PET can be used to appropriately direct biopsy in soft tissue sarcoma and potentially may lead to computed tomography/MRI directed outpatient biopsy prior to definitive treatment.

Adult↗

Clinical and serological response of wild dogs (Lycaon pictus) to vaccination against canine distemper, canine parvovirus infection and rabies.

Wild dogs Lycaon pictuis (n = 8) were vaccinated 4 times against canine distemper (n = 8) (initially with inactivated and subsequently with live attenuated strains of canine distemper) and canine parvovirus infection (n = 8) over a period of 360 days. Four of the wild dogs were also vaccinated 3 times against rabies using a live oral vaccine and 4 with an inactivated parenteral vaccine. Commercially-available canine distemper, canine parvovirus and parenteral rabies vaccines, intended for use in domestic dogs, were used. None of the vaccinated dogs showed any untoward clinical signs. The inactivated canine distemper vaccine did not result in seroconversion whereas the attenuated live vaccine resulted in seroconversion in all wild dogs. Presumably protective concentrations of antibodies to canine distemper virus were present in all wild dogs for at least 451 days. Canine parvovirus haemagglutination inhibition titres were present in all wild dogs prior to the administration of vaccine and protective concentrations persisted for at least 451 days. Vaccination against parvovirus infection resulted in a temporary increase in canine parvovirus haemagglutination inhibition titres in most dogs. Administration of both inactivated parenteral and live oral rabies vaccine initially resulted in seroconversion in 7 of 8 dogs. These titres, however, dropped to very low concentrations within 100 days. Booster administrations resulted in increased antibody concentrations in all dogs. It was concluded that the vaccines were safe to use in healthy subadult wild dogs and that a vaccination protocol in free-ranging wild dogs should at least incorporate booster vaccinations against rabies 3-6 months after the first inoculation.

Animals↗

Development of a bait and baiting system for delivery of oral rabies vaccine to free-ranging African wild dogs (Lycaon pictus).

The objective of the study was to develop a bait and baiting system capable of delivering one effective dose of oral rabies vaccine to each member of a free-ranging African wild dog (Lycaon pictus) pack. Trials were conducted between June and October 2000. The results of cafeteria-style bait preference trials testing seven candidate baits in captive wild dogs revealed a significant preference for chicken heads (June trials: P = 0.023, September trials: P = 0.021). Trials using a topical biomarker (rhodamine B) showed that chicken head baits were sufficiently chewed on most occasions to rupture the vaccine container. Free-ranging wild dogs and young pups ingested chicken head baits. Significant dominance of bait intake by a single individual was seen in four of six study packs and in the three packs in which an alpha pair could be distinguished, the dominant feeder was an alpha animal. Pattern of bait distribution and degree of satiation had no effect on pack coverage (proportion of pack ingesting at least one bait). Pack coverage was significantly related to trial number (r = 0.71, P < 0.001), with pack coverage increasing with increased exposure of the pack to the baits. During 46 hr of diurnal observations of free-ranging wild dogs only two baits were lost to non-target species. A baiting system for the oral vaccination of captive and free-ranging wild dogs is proposed.

Administration, Oral↗

Sexually transmitted infections in Italy: an overview.

In Italy more than 240,000 and 500,000 cases of gonorrhoea and syphilis, respectively, were reported in 1936 but the incidence progressively fell to about 200-300/year by the early 1990s; data available now are probably 100-150% underestimated. An inefficient notification system, diversion of public funding to other fields, and the progressive decline in importance of dermatovenereological centres are responsible for this decline. The advent of the HIV epidemic (with more than 47,000 AIDS reported cases) has drained most public health resources away from the very limited interventions for the control of traditional sexually transmitted infections (STIs). This has led some groups to attempt alternative approaches to the HIV/STI prevention and treatment policies; the potential of these new experiences need to be assessed. A change in culture of the medical body politic is now essential in order to support medical professionals, administrators and programme managers seeking to implement proper STI control programmes.

HIV Infections↗

Report of isolations of unusual lyssaviruses (rabies and Mokola virus) identified retrospectively from Zimbabwe.

Rabies isolates that had been stored between 1983 and 1997 were examined with a panel of anti-lyssavirus nucleocapsid monoclonal antibodies. Out of 56 isolates from cats and various wild carnivore species, 1 isolate of Mokola virus and 5 other non-typical rabies viruses were identified. The Mokola virus isolate was diagnosed as rabies in 1993 from a cat. Genetic analysis of this isolate suggests that it falls in a distinct subgroup of the Mokola virus genotype. The 5 non-typical rabies viruses were isolated from honey badgers (Mellivora capensis), African civets (Civettictis civetta) and an unidentified mongoose (Herpestidae). These isolates are representatives of rarely-reported wildlife-associated strains of rabies, probably maintained by the slender mongoose (Galerella sanguinea). These findings indicate that both Mokola virus and the mongoose-associated variant may be more common in Zimbabwe than is apparent from routine surveillance.

Animals↗

Lymphocytic hypophysitis: spontaneous resolution on MRI with progression of endocrine defect.

Lymphocytic hypophysitis is an uncommon condition that typically occurs during the last trimester of pregnancy or in the postpartum period. Presentation is of an anterior pituitary mass with varying degrees of pituitary dysfunction. We present a case in which there was dramatic resolution of the pituitary lesion on sequential MRI scanning. Despite this apparent resolution, however, the patient continues to have significant pituitary dysfunction.

Adult↗

Informatics issues in large-scale sequence analysis: elucidating the protein kinases of C. elegans.

With the availability of the nearly complete genomic sequence of C. elegans, the first multicellular organism to be sequenced, molecular biology has definitely entered the postgenomic era. Annotation of the genomic sequence, which refers to identifying the genes and other biologically relevant sections of the genome, is an important and nontrivial next step. A first-pass annotation will be necessarily incomplete but will drive further biological experiments, which in turn will help to annotate the genome better. Given the scale of the genome sequence analysis, it is clear that the annotation should be automated as much as possible without sacrificing the quality of analysis. In this work, we outline our approach to identifying the protein kinases of C. elegans from the genomic sequence. We describe new tools we have developed for analysis, management and visualization of genomic data. By developing modular and scalable solutions, this study has provided a framework for future analysis of the Drosophila and human genomes.

Animals↗

Demography and dog-human relationships of the dog population in Zimbabwean communal lands.

Dogs are Zimbabwe's primary vector for rabies, and the majority live in communal lands (traditional agropastoralist rural areas). In 1994, a household questionnaire survey was conducted to provide baseline data on the demography and dog-human relationships of the dogs in the communal lands. The survey showed that all the dogs were owned, and there was no evidence of a feral population. They were unrestricted and semi-dependent on people. The numbers of dogs per capita varied little in each communal land, resulting in higher dog densities in communal lands with higher human densities, and indicating that people were not intolerant of dogs at higher densities. The population turnover was rapid: the life expectancy of the dogs was 1.1 years, the mean age 2.0 years, and 71.8 per cent died in their first year. The population was heavily skewed towards juveniles, with 40.8 per cent aged less than 12 months. Despite the high juvenile mortality, the population was growing by 6.52 per cent per annum. It was estimated that in 1994 there were 1.36 million dogs in communal lands.

Animals↗

New ratiometric fluorescent calcium indicators with moderately attenuated binding affinities.

Mono-halogenated derivatives of the calcium indicators fura-2 and indo-1 were synthesized and their spectroscopic properties evaluated. Halogenation ortho or para to the bridging oxygen in the BAPTA nucleus had a more pronounced weakening effect on binding affinity than in the meta position in the fura derivatives. Two new excitation ratioable fluorescent calcium indicators, benzothiaza-1 and 2, were also synthesized. Kd values of 400 nM to 5.3 microM [Ca2+] were observed in these families of new probes.

Calcium↗

New cases of Mokola virus infection in South Africa: a genotypic comparison of Southern African virus isolates.

Mokola virus, one of the six genotypes within the Lyssavirus genus of the Rhabdoviridae family, is believed to be exclusive to the African continent, where infections in various mammal species have been reported. After an isolation of Mokola virus at Umhlanga on the east coast of South Africa in 1970, the virus was not reported in South Africa until its reappearance in 1995. Since then a total of six new isolates of the virus were made, three from the East London region in 1995 and 1996, two near Pinetown in 1997 and a further isolate in a residential suburb of the city of Pietermaritzburg, in 1998. These isolation sites are respectively about 500 km (East London region) and 23 to 60 km from the site of the 1970 isolation Phylogenetically the three isolates from the East London area were similar and could be distinguished from the four KwaZulu-Natal isolates, which formed a defined group of their own. The viruses comprising these two clusters were also found to be distant from another southern African isolate, made in 1982 in Zimbabwe, Mokola virus isolates thus conforms to a pattern of virus evolution strongly influenced by geographical determinants. In comparison to Rabies virus, of which at least two different biotypes are known and a vast array of different wildlife species contribute to its complex epidemiology on the sub-continent, Mokola viruses have only been isolated form one species, i.e. domestic cats, in South Africa. Nevertheless, the heterogeneity among the Mokola virus isolates is far greater than the degree of variation among the Rabies virus populations of the region.

Animals↗