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Biomedical subjects

J Bingham

Publications and source records attributed to J Bingham.

At least 19 recordsLinked to original sources

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↗

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↗

Biliary complications associated with laparoscopic cholecystectomy: analysis of common misconceptions

AIMS: General surgeons often express the view that the majority of biliary complications following laparoscopic cholecystectomy are caused by trainee surgeons; complications occur most often in the presence of difficult anatomy or pathology; biliary injuries occur more proximally in the biliary tree than at open cholecystectomy; most injuries are recognized at the time of surgery; and most complications can be managed non-operatively. The aim of this study was to determine if these views are substantiated in clinical practice. METHODS: Thirty consecutive patients were referred to a specialist hepatobiliary unit over a 7-year period with biliary complications following laparoscopic cholecystectomy. The mode of presentation, management and outcome of these patients were analysed. RESULTS: In 21 cases the initial operator was a consultant. Four of the 30 complications occurred in the presence of an anatomical variation or unusually difficult pathology. Only patients in whom a previous attempt at repair had been made had injuries at or proximal to the bile duct confluence; the only two deaths occurred in this group. Only 41 per cent of injuries were detected at the time of surgery and 89 per cent required further surgical intervention, hepaticojejunostomy being the most common procedure performed (75 per cent). CONCLUSIONS: The majority of bile duct injuries are not caused by trainees, do not occur because of unusual anatomy or pathology, do not occur in the proximal biliary tree, are not recognized at the time of the initial operation and often require major reconstructive procedures for their management.

Journal Article↗

Visualizing large hierarchical clusters in hyperbolic space.

SUMMARY: HyperTree is an application to visualize and navigate large trees in hyperbolic space. It includes color-coding, search mechanisms and navigational aids, as well as focus+context viewing, allowing enormous trees to fit within the fixed space of a computer screen or printed page.

Animals↗

Evaluation of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) in the detection of malignant peripheral nerve sheath tumours arising from within plexiform neurofibromas in neurofibromatosis 1.

OBJECTIVES: The ability of (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) to detect malignant change in plexiform neurofibromas from patients with neurofibromatosis 1 (NF1) was evaluated. METHODS: Eighteen NF1 patients who presented with pain, increase in size, or neurological deficit associated with a plexiform neurofibroma were assessed. Magnetic resonance imaging determined the site and extent of the lesion. Qualitative(18)FDG PET was performed and the standard uptake value (SUV) measured the regional glucose metabolism. Histological confirmation of the diagnosis was obtained in 10 patients. RESULTS: Twenty three plexiform neurofibromas were detected in 18 patients. Seven malignant peripheral nerve sheath tumours, four high grade and three low grade tumours, occurred in five patients. In one patient the clinical and radiological characteristics of the tumour suggested malignancy, but histology was inconclusive. Fifteen benign plexiform neurofibromas were identified in 12 patients and these findings were confirmed histologically in five lesions from four patients. Ten plexiform neurofibromas occurring in eight patients were considered benign on(18)FDG PET and the patients did not undergo surgery. They remained stable or their symptoms improved on clinical follow up (median 9 months). The results of qualitative (18)FDG PET were interpreted as indicating that 13 plexiform neurofibromas were benign and 10 were malignant. No malignant tumours were classified as benign, but two benign tumours were reported as malignant. The SUV was calculated for 20 tumours and was significantly higher in five malignant tumours 5.4 (SD 2.4), than in 15 benign tumours 1.54 (SD 0.7), p=0.002. There was an overlap between benign and malignant tumours in the SUV range 2.7-3.3. CONCLUSIONS: (18)FDG PET is helpful in determining malignant change in plexiform neurofibromas in NF1. Increased separation between benign and malignant lesions could be obtained by calculating the SUV at about 200 minutes after injection of (18)FDG, when the peak activity concentration is obtained in malignant tumours.

Adolescent↗

Biliary complications associated with laparoscopic cholecystectomy--an analysis of common misconceptions.

BACKGROUND: Several views are expressed by surgeons on biliary complications following laparoscopic cholecystectomy as follow: most are caused by trainees; complications occur in the presence of difficult anatomy/pathology; injuries occur more proximally than at open cholecystectomy; most injuries are recognised immediately and most can be managed non-operatively. The aim of our study was to determine if these views are substantiated in clinical practice. METHODS: The mode of presentation, management and outcome of thirty-two patients referred to a hepatobiliary unit over a seven year period were analysed. RESULTS: In 72% of cases the initial operator was a consultant. Five of the 32 complications (16%) occurred in the presence of difficult anatomy/pathology. Two patients had proximal biliary tree injuries, the only mortalities (two) occurring in this group. Only 41% of injuries were detected immediately; 87% required surgical intervention, hepaticojejunostomy being the most common procedure performed (75%). CONCLUSION: Our study shows that the majority of bile duct injuries are not caused by trainees, do not occur because of unusual anatomy/pathology, do not occur in the proximal biliary tree and are not recognised at the time of operation. Most injuries ultimately require major reconstructive surgery for definitive management.

Biliary Tract Diseases↗

The protein kinases of Caenorhabditis elegans: a model for signal transduction in multicellular organisms.

Caenorhabditis elegans should soon be the first multicellular organism whose complete genomic sequence has been determined. This achievement provides a unique opportunity for a comprehensive assessment of the signal transduction molecules required for the existence of a multicellular animal. Although the worm C. elegans may not much resemble humans, the molecules that regulate signal transduction in these two organisms prove to be quite similar. We focus here on the content and diversity of protein kinases present in worms, together with an assessment of other classes of proteins that regulate protein phosphorylation. By systematic analysis of the 19,099 predicted C. elegans proteins, and thorough analysis of the finished and unfinished genomic sequences, we have identified 411 full length protein kinases and 21 partial kinase fragments. We also describe 82 additional proteins that are predicted to be structurally similar to conventional protein kinases even though they share minimal primary sequence identity. Finally, the richness of phosphorylation-dependent signaling pathways in worms is further supported with the identification of 185 protein phosphatases and 128 phosphoprotein-binding domains (SH2, PTB, STYX, SBF, 14-3-3, FHA, and WW) in the worm genome.

Animals↗

Efficacy of SAG-2 oral rabies vaccine in two species of jackal (Canis adustus and Canis mesomelas).

Trials were carried out to test the efficacy of SAG-2 oral rabies vaccine in two species of jackals, namely the side-striped jackal (C. adustus) and the black-backed jackal (C. mesomelas). The first trial tested the efficacy of SAG-2 when given by direct oral administration at doses of 6.5 and 7.5 log10 median tissue culture infectious doses (TCID50). One side-striped jackal which had received the higher dose did not seroconvert and succumbed to challenge, while all other jackals seroconverted and resisted a lethal challenge. The second trial tested the efficacy in side-striped jackals only of the SAG-2 vaccine when given within chicken head baits. A volume of 1.8 ml of vaccine fluid with titers of 7.0 or 8.0 log10 TCID50/ml were placed into blisters which were stapled under the skin of the chicken heads. All jackals (5/5) which received 8.0 log10 TCID50/ml and 3 of 5 which received 7.0 log10 TCID50/ml seroconverted and resisted lethal challenge. A third trial tested the rate of vaccine virus titer loss in chicken head baits placed under field conditions. Titer loss was marked in baits which were not protected from direct sunshine, whereas under vegetation cover approximately log10 TCID50/ml was lost every 3 days. Hence, it was concluded that a bait vaccine virus titer of 8.0 log10 TCID50/ml will be sufficient to immunize wild jackal populations if enough baits can be consumed by jackals within 3 days. This conclusion needs to be tested through the use of oral vaccine in field trials.

Administration, Oral↗