Elimination of rabies from red foxes in eastern Ontario.

The province of Ontario (Canada) reported more laboratory confirmed rabid animals than any other state or province in Canada or the USA from 1958-91, with the exception of 1960-62. More than 95% of those cases occurred in the southern 10% of Ontario (approximately 100,000 km2), the region with the highest human population density and greatest agricultural activity. Rabies posed an expensive threat to human health and significant costs to the agricultural economy. The rabies variant originated in arctic foxes: the main vector in southern Ontario was the red fox (Vulpes vulpes), with lesser involvement of the striped skunk (Mephitis mephitis). The Ontario Ministry of Natural Resources began a 5 yr experiment in 1989 to eliminate terrestrial rabies from a approximately 30,000 km2 study area in the eastern end of southern Ontario. Baits containing oral rabies vaccine were dropped annually in the study area at a density of 20 baits/km2 from 1989-95. That continued 2 yr beyond the original 5 yr plan. The experiment was successful in eliminating the arctic fox variant of rabies from the whole area. In the 1980's, an average of 235 rabid foxes per year were reported in the study area. None have been reported since 1993. Cases of fox rabies in other species also disappeared. In 1995, the last bovine and companion animal cases were reported and in 1996 the last rabid skunk occurred. Only bat variants of rabies were present until 1999, when the raccoon variant entered from New York (USA). The success of this experiment led to an expansion of the program to all of southern Ontario in 1994. Persistence of terrestrial rabies, and ease of elimination, appeared to vary geographically, and probably over time. Ecological factors which enhance or reduce the long term survival of rabies in wild foxes are poorly understood.

Clinical management of avulsed permanent incisors using Emdogain: initial report of an investigation.

The enamel matrix derivative Emdogain was recently approved for clinical use in a number of countries, including Canada. It has been shown to stimulate regeneration of periodontal ligament following periodontal surgery in adults. This paper reviews pertinent clinical and laboratory studies of Emdogain and describes the protocol and methods used for a longitudinal outcome study of replantation of avulsed permanent incisors in children and adolescents. Application of these methods is described in an illustrative case report of Emdogain use. This paper is meant to inform clinicians and guide those who are instituting similar investigations.

Synthesis and characterization of the dimethyl-substituted bisbenzimidazole ligand and its manganese complex.

Macrocycles with unique properties provide new avenues for the design of novel catalysts and materials. Here, we report, for the first time, the synthesis and characterization of the dimethyl-substituted bisbenzimidazole ligand (Me2BBZ) and its manganese complex (Mn-Me2BBZ). The Me2BBZ ligand is similar to porphyrin and phthalocyanine macrocycles in terms of its cavity size and metal-binding mode, but owing to electronic and charge differences, it exhibits properties that make it distinct from its structural counterparts. For instance, the optical spectra of bisbenzimidazoles lack transitions in the 500-900 nm region. Perhaps the most significant feature of the Me2BBZ ligand, however, is its inherent nonplanarity. Geometric restraints within this nonplanar ligand give rise to two atropisomers, which, when separated, could have potential in chiral catalysis and recognition. In addition, here we show that this nonplanarity can help to promote unusual crystal-packing interactions. Within the structure of the Mn-Me2BBZ complex, intermolecular pi-stacking interactions of the phenyl and benzimidazole groups lead to the formation of a distinct two-dimensional "staircase" lattice comprised of alternating Mn-Me2BBZ atropisomers. The potential significance of this structural arrangement is revealed by temperature-dependent magnetic studies that indicate weak antiferromagnetic coupling between the metal ions in the crystal. Fine-tuning of these long-range electronic and magnetic interactions could be useful for the design of novel molecular materials.

The development of ISO 9002 quality management standards for Canadian dental practices.

The department of dentistry of the Hospital for Sick Children has actively maintained a quality assurance system since the early 1980s. In addition, members of the department have taught courses and published articles on risk management and quality assurance for over a decade. The decision to achieve ISO 9002 registration led to an intensive 10-month process to adapt ISO systems and standards to Canadian institutional dental practice. This article describes the ISO registration system and the changes required for an existing quality assurance program to conform to ISO standards.

Evaluation of a laser Doppler flowmeter to assess blood flow in human primary incisor teeth.

PURPOSE: This study determined whether the portable Advance Laser Flowmeter Model 21, a clinical instrument, would indicate significant values when pulpal blood flow was present or absent; whether the analog output of the flowmeter was time-linked to the heart rate; and whether labial and lingual crown surfaces produced different flow values. METHODS: Teeth were tested under two conditions: with the teeth in situ and extracted, or with the pulp present and removed. RESULTS: Values before and after the teeth were extracted, and those before and after pulpectomy with the tooth in situ were significantly different. These findings verified that the flowmeter measured the presence of bloodflow. Peaks of the electrocardiogram waves and the regular signal fluctuations of the flowmeter were time-linked and verified the measurement of the heart rate from the dental pulp. Differences in the values for the lingual and labial surfaces of individual teeth were not significant. CONCLUSIONS: This instrument proved a valid means of determining the presence of pulpal blood flow in primary incisors.

Results of an oral rabies vaccination program for coyotes.

OBJECTIVE: To determine effectiveness of large-scale distribution of an oral rabies vaccine contained in a palatable bait for halting expansion of a canine rabies epizootic in coyotes (Canis latrans). DESIGN: Prospective study. ANIMALS: 98 coyotes during prevaccination surveillance and 449 coyotes and 60 other wild animals during postvaccination surveillance. PROCEDURE: A vaccinia recombinant oral rabies vaccine was inserted into an edible bait for coyotes that also contained tetracycline as a biomarker. Vaccine units were then distributed via aircraft, using automated distribution equipment and flight plans developed by incorporating global positioning system equipment. The target area was along the northern edge of an area that had an epizootic of canine rabies. This area was identified through previously conducted epidemiologic surveillance of rabies cases. During postvaccination surveillance, dental specimens were examined for biomarker evidence of bait acceptance, and serum samples were analyzed for rabies neutralizing antibodies. RESULTS: Samples from 449 coyotes were obtained during postvaccination surveillance. Seroconversion was detected in 39 of 96 (40.6%) coyotes that had evidence of tetracycline biomarker. Additionally, the number of rabies cases in the target area decreased, and expansion of the epizootic area ceased. CLINICAL IMPLICATIONS: Mass distribution of an oral rabies vaccine in a palatable bait is an effective means to halt expansion of a rabies epizootic involving coyotes.

Colorectal cell line suppression of lymphokine activated killer cell generation is reversed by suramin.

Progressive tumor growth is associated with a state of immunosuppression. One mode of immunosuppression is thought to be mediated by immunosuppressive factors of tumour origin. We have investigated in vitro the possibility that suramin could be used to blockade tumor derived suppressor factors and enhance the effectiveness of rhIL-2 therapy. These data show that factors derived from cultures of the colorectal carcinoma cell line LoVo suppressed the percentage of cells expressing the natural killer cell antigen CD56 in 92% of individuals and the cytotoxic T cell antigen CD8 in 77% of individuals tested from a panel of 13 normal healthy volunteers. Suramin at 200 micrograms/ml restored the percentage of cells expressing CD56 to levels higher than the control cultures and reduced the suppression in those expressing CD8 to non-significant levels. LoVo produced factors also suppressed the expression of the activation associated antigens CD25, CD71 and HLA-Dr with suramin restoring CD25 expression but not CD71 or HLA-Dr. Functional studies using 51Cr-release assays showed that LoVo produced factors could suppress cytotoxicity in 46% of individuals tested, and of these a reduction in suppression by suramin was demonstrated in 50% of individuals against Daudi target cells and 33% against K562 target cells.

Disseminated neuroblastoma with initial presentation as an intraoral mass: case report.

Neuroblastoma is an uncommon malignant neoplasm that derives from neural crest progenitor cells that normally give rise to the sympathetic nervous system. It represents 8 to 10% of all extracranial tumors in childhood. The purpose of this paper is to report a case in which a mandibular soft tissue mass was the initial presenting sign of disseminated neuroblastoma in a 2-year-old child, and to discuss the clinicopathologic features and biologic behavior of neuroblastoma.

Background prevalence of tetracycline-like fluorescence in teeth of free ranging red foxes (Vulpes vulpes), striped skunks (Mephitis mephitis) and raccoons (Procyon lotor) in Ontario, Canada.

We collected and examined teeth from 3406 red foxes (Vulpes vulpes) collected in Ontario, Canada, from 1978 to 1986, prior to large scale rabies vaccine baiting. We found tetracycline-like fluorescence in five (0.2%) of the samples. Also, we observed similar fluorescences in five (0.4%) of 1103 striped skunks (Mephitis mephitis) and in six (0.8%) of 744 raccoons (Procyon lotor). The low prevalence of such marks would not appear to invalidate the use of tetracycline as a marking agent in vaccine baiting trials.

Programmed cell death (apoptosis) in immunity and haematological neoplasia.

Programmed cell death, also commonly referred to as apoptosis, is a genetically controlled sequence of events, often requiring protein synthesis, which results in cell death. Although initially described 20 years ago, it is only recently that its role as a mechanism in controlling cell population size and content has been fully realised. In this review the biochemical events of apoptosis are discussed briefly, followed by a more detailed look at the role of programmed cell death in the control of haemopoiesis and the maintenance of a balanced functional immune system. The role of proto-oncogenes and suppressor genes known to regulate programmed cell death is covered, and also their influence on the induction and maintenance of neoplastic disease. Finally, the potential role of apoptosis in the resistance of haematological malignancies to chemotherapy is commented on.

Tactics for the control of wildlife rabies in Ontario (Canada).

Two different tactics are currently being utilized to control rabies in foxes, skunks and raccoons in Ontario, Canada. The first tactic, which involves live-capturing with cage-traps and vaccinating by intramuscular injection, was successful in immunizing 54%-72% of the skunk and raccoon populations in a 60 km2 area of Toronto, Ontario. This area has been free of rabies for two-and-a-half years. The second tactic, involving the distribution of baits containing modified live-virus (ERA) rabies vaccine, was implemented to control rabies in foxes in both urban and rural areas of Ontario. In Toronto, 50% and 63% of the foxes were vaccinated during 1989 and 1990, respectively. Over the same period, 45% and 61% of the foxes in a 30,000 km2 area of south-eastern Ontario were immunized. Rabies is declining in both of these areas. A contingency plan has been devised to control an epizootic of raccoon rabies which is threatening to invade Ontario from the United States of America.

Modulation of CD4 by suramin.

Suramin is a polysulphonated compound which can selectively bind to, and inhibit the activity of, a wide range of growth factors. There has been renewed interest recently in suramin as an anti-cancer agent and therefore we have studied its effects on lymphocyte subset populations and recombinant human IL-2 (rhIL-2) activation on lymphocytes in vitro. In the presence of rhIL-2 (1000 U/ml), suramin (200 micrograms/ml) caused a decrease in percentage of cells expressing the predominantly T cell antigen CD3; no change in percentage of cells expressing the T suppressor/cytotoxic subset antigen, CD8; a small rise in those expressing the natural killer cell antigen, CD56; and a large significant fall in those expressing the T helper subset antigen CD4 (48.51% versus 27.97%; P < 0.001). CD4 modulation by suramin was also found on the CD4+ cell lines CEM and MOLT-4. The effect of suramin on rhIL-2-induced activation antigen expression remains equivocal, since a small rise in CD25 expression and small falls in CD71 and HLA-Dr expression were recorded. The modulatory effect of suramin on CD4 expression was not reversible over a 96-h culture period in its continued presence. However, on removal of suramin by extensive washing, recovery of CD4 expression was detected within 24 h. Suramin-induced modulation, but not PMA-induced modulation, could be partially inhibited by preincubation with tyrphostin (12 microM), a tyrosine kinase inhibitor.

Suture technique affects perianastomotic colonic crypt cell production and tumour formation.

Suture line recurrence is an important cause of failure after potentially curative resection for colonic carcinoma. Our aim was to determine whether suture technique affected the incidence of perianastomotic tumours in experimentally induced colonic cancer. Sprague-Dawley rats were randomized into three groups. A 1 cm longitudinal colotomy was repaired with four interrupted 6/0 polypropylene monofilament sutures, using either a transmural technique (n = 18) or a seromuscular technique (n = 18). Control animals (n = 18) had a sham laparotomy. All animals received nine, weekly, subcutaneous injections of azoxymethane (total dose 90 mg/kg) starting 6 weeks after laparotomy. Surviving animals were killed 32 weeks after laparotomy. Five animals from each group were given intraperitoneal bromodeoxyuridine (100 mg/kg) 1 h before being killed. At death, perianastomotic tumours occurred more frequently in animals with transmural sutures than in either controls or those with seromuscular sutures. This difference was associated with a greater mucosal bromodeoxyuridine crypt cell labelling index in the transmural suture group. We conclude that a transmural anastomotic suture technique promotes the development of experimental perianastomotic colonic tumours.

Wild carnivore acceptance of baits for delivery of liquid rabies vaccine.

A series of experiments are described on the acceptance, by red foxes (Vulpes vulpes) and other species, of two types of vaccine-baits intended to deliver liquid rabies vaccine. The baits consisted of a cube of sponge coated in a mixture of tallow and wax, or a plastic blister-pack embedded in tallow. All baits contained tetracycline as a biological marking agent: examination of thin sections of carnivore canines under an ultraviolet microscope revealed a fluorescent line of tetracycline if an individual had eaten baits. Baits were dropped from fixed-wing aircraft flying about 100 m above ground at approximately 130 km/h. Flight lines followed the edges of woodlots midway between parallel roads. Baits were dropped at one/sec, resulting in one bait/36 m on the ground, or 17 to 25 baits per km2. Crows (Corvus brachyrhynchos) removed many baits, but did not appear to lower the percent of the fox population which took bait. Dropping baits only into corn and woodland to conceal baits, to reduce depredation by crows, reduced acceptance by foxes. Acceptance by foxes ranged between 37 and 68%. Meat added as an attractant did not raise acceptance. Presence, absence, color and perforations of plastic bags did not alter bait acceptance. Dispersal by juvenile foxes probably lowered the estimates of bait acceptance. It took 7 to 17 days for 80% (n = 330) of foxes to eat their first bait. The rapidity with which foxes picked up their first bait appeared more affected by unknown characteristics of years or study areas than by experimental variables. Skunks (Mephitis mephitis) and raccoons (Procyon lotor) also ate these baits, but acceptance was lower. Small mammals contacted baits, but rarely contacted the vaccine, which had the potential for vaccine-induced rabies in some species. Aerial distribution of baits was more cost-effective than ground distribution as practiced in Europe. This system has potential for field control of rabies, although higher acceptance will be desirable.