European Forensic Veterinary Pathology Comes of Age.

During the mid-1700s, development of the veterinary profession was largely focussed on equine medicine and surgery. Subsequently, rather erratic development encompassed other species and eventually led to specialization in different disciplines. Teaching of veterinary pathology was well established in Europe and North America by the late 19th century. Specialization in this discipline was boosted in the 1940s by the formation, in the USA, of the Register of Veterinary Pathology and American College of Veterinary Pathologists. National societies followed soon afterwards in Europe. The European Society of Veterinary Pathology evolved during this period and the European College of Veterinary Pathologists (ECVP) was created in 1995 to promote high standards in the discipline. As an accrediting body, its emphasis is on training and harmonization across Europe. There is an increasing demand for high-grade forensic veterinary pathology reports which address the requirements of the legal system, but so far only a few countries have defined protocols for these reports. In recognition of the need for a specific qualification that benchmarks the competences and experience expected of forensic veterinary pathologists, the ECVP recently launched the Certificate in Forensic Veterinary Pathology.

The Veterinary Forensic Necropsy: A Review of Procedures and Protocols.

Investigation of animal-related crime, and therefore submission of forensic cases to veterinary pathology facilities, is increasing, yet many veterinary pathologists are unfamiliar and often uncomfortable with involvement in the forensic necropsy. This article discusses various aspects of the forensic necropsy without specific attention to any particular species group or crime. General advice is given on procedures, documentation, and recording of the examination, and the article indicates how these features may differ from those used in investigation of natural disease. It also discusses evidence management, including recordkeeping, identification of evidence, labeling of photographs, and use of standard operating procedures and protocols. Various written and visual methods for documentation of the forensic necropsy are covered, and adjunctive topics such as sample collection, assessment, and description of wounds and taphonomy are included. Cause, mechanism, and manner of death are defined, and guidance to the use of these terms is given. The aim of this article is to offer guidance on procedural aspects of the forensic necropsy that will help those developing their forensic services, contribute to standardization of the provision of forensic veterinary pathology, and build the confidence of the "uncomfortable" forensic veterinary pathologist.

Some challenges in forensic veterinary pathology: a review.

Forensic veterinary pathology is a diverse discipline that is in an early phase of its development. Common challenges include estimation of the age of skin wounds and bruises, the diagnosis of drowning and estimation of the time since death. However, many details of the pathological findings related to these various aspects await validation. The 'multispecies' nature of veterinary pathology, combined with the preponderance of published observations originating from animal experimentation, rather than casework, poses two challenges. Firstly, extrapolation of results between species may jeopardize the reliability (and credibility) of the forensic opinion. Secondly, experimental studies may not truly reflect the spectrum of changes seen in actual cases (e.g. extent of injuries, infection, age and health of victim). With regard to drowning, diagnosis based on post-mortem findings remains problematical. Methods for estimation of the time since death (also known as the post-mortem interval) continue to be a major focus of study, with fresh avenues such as post-mortem diagnostic imaging offering interesting possibilities.

Robust, routine haematology reference ranges for healthy adults.

Accurate, reliable laboratory reference ranges are essential for effective clinical evaluation and monitoring. We present robust reference ranges established for haematology, coagulation and haematinic parameters using the Sysmex XE 2100, CA 1500 and Beckman-Coulter Access analysers. Blood samples were taken from 250 healthy laboratory personnel and routine haematology, coagulation and haematinic parameter analysis performed. Our data represent findings from an extensive study to establish reference ranges in healthy adults.

Differential effects of acute and chronic social defeat stress on hypothalamic-pituitary-adrenal axis function and hippocampal serotonin release in mice.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) stress axis and disturbances in serotonin (5-HT) neurotransmission have been implicated in the pathogenesis of depressive disorder. Repeated social defeat of male NMRI mice has been shown to induce increases in core body temperature and corticosterone, indicative of a state of chronic stress in subordinate animals. The present study further characterised the HPA axis response to social defeat stress, and also examined hippocampal extracellular 5-HT release during the stress. Exposure to an acute social defeat elicits increases in plasma adrenocorticotrophic hormone and corticosterone levels, peaking at 15 and 30 min, respectively, and enhances corticotrophin-releasing factor (CRF) mRNA, but not arginine vasopressin (AVP) mRNA within the medial parvocellular division of the hypothalamic paraventricular nucleus. A concomitant increase in hippocampal corticosterone and 5-HT levels is observed. By contrast, although chronic social defeat is associated with greatly elevated corticosterone levels, the predominant drive appears to be via parvocellular AVP rather than CRF. Furthermore, subordinate animals allowed to recover for 9 days after chronic social defeat display an increase in immobility in the forced swimming model of depression, indicating that animals previously exposed to the homotypic defeat stress are sensitised to the behavioural effects of a novel stressor. These results demonstrate that social defeat induces prolonged activation of the HPA axis and alterations in 5-HT neurotransmission that could be of relevance to some of the pathological abnormalities observed in clinical depression.

Retigabine: chemical synthesis to clinical application.

Retigabine [D23129; N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamic acid ethyl ester] is an antiepileptic drug with a recently described novel mechanism of action that involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels. These channels (primarily K(V)7.2/7.3) enable generation of the M-current, a subthreshold K(+) current that serves to stabilize the membrane potential and control neuronal excitability. In this regard, retigabine has been shown to have a broad-spectrum of activity in animal models of electrically-induced (amygdala-kindling, maximal electroshock) and chemically-induced (pentylenetetrazole, picrotoxin, NMDA) epileptic seizures. These encouraging results suggest that retigabine may also prove useful in the treatment of other diseases associated with neuronal hyperexcitability. Neuropathic pain conditions are characterized by pathological changes in sensory pathways, which favor action potential generation and enhanced pain transmission. Although sometimes difficult to treat with conventional analgesics, antiepileptics can relieve some symptoms of neuropathic pain. A number of recent studies have reported that retigabine can relieve pain-like behaviors (hyperalgesia and allodynia) in animal models of neuropathic pain. Neuronal activation within several key structures within the CNS can also be observed in various animal models of anxiety. Moreover, amygdala-kindled rats, which have a lowered threshold for neuronal activation, also display enhanced anxiety-like responses. Retigabine dose-dependently reduces unconditioned anxiety-like behaviors when assessed in the mouse marble burying test and zero maze. Early clinical studies have indicated that retigabine is rapidly absorbed and distributed, and is resistant to first pass metabolism. Tolerability is good in humans when titrated up to its therapeutic dose range (600-1200 mg/day). No tolerance, dependence or withdrawal potential has been reported, although adverse effects can include mild dizziness, headache, nausea and somnolence. Thus, retigabine may prove to be useful in the treatment of a diverse range of disease states in which neuronal hyperexcitability is a common underlying factor.

Relationship between diet and liver carcinomas in roe deer in Kielder Forest and Galloway Forest.

The winter diets of roe deer culled from Kielder Forest, in north-east England, where the incidence of liver carcinomas in roe deer is high, and Galloway Forest, in south-west Scotland, where the incidence of liver carcinomas is low, were compared by microhistological analysis of faeces. Both areas are planted with spruce forests but the diets of the deer from Kielder Forest were less varied and contained more spruce and heather than the diets of the deer from Galloway Forest.

Analytical Representations of Elastic Moduli Data With Simultaneous Dependence on Temperature and Porosity.

An analytical model providing simultaneous, self-consistent representations of the temperature and porosity dependence of the elastic and bulk moduli of polycrystalline ceramics is applied to data compiled from the literature for 24 oxide ceramics.

Endoanal sonography in assessment of fecal incontinence following obstetric trauma.

OBJECTIVES: Fecal incontinence is a common, incapacitating and largely unrecognized medical problem and can be caused by various factors. Obstetric trauma is the most common cause of fecal incontinence secondary to trauma. We aimed to analyze the role of endoanal ultrasound in assessment of this type of fecal incontinence, and report the functional results of surgical treatment. METHODS: We reviewed the records of all 22 patients with fecal incontinence secondary to obstetric trauma who were evaluated by endoanal ultrasound and underwent surgical management in our department from April to 1997 to April 2002. Pre- and postoperative evaluation of the degree of incontinence was done using the incontinence score of Jorge and Wexner. RESULTS: The patients had a median age of 43 (range, 29-68) years. All had vaginal deliveries, five of which (22.7%) were instrumental. Most of the patients had total fecal incontinence (solids) with preoperative incontinence score values of 15-20 (median, 18). Endoanal ultrasound confirmed structural defects in the anterior external anal sphincter alone in 16 (72.7%) patients, and both anterior external and internal sphincter defects in six (27.3%) patients. A thinned perineal body was present in all patients. All patients received surgical treatment with overlapping sphincteroplasty and there was improvement of continence in 19 (86.4%) patients with postoperative incontinence score values between 4 and 0 (median, 2). CONCLUSIONS: Endoanal sonography is an accurate method for assessing sphincter anatomy, delineating both internal and external anal sphincters. Surgical treatment of sphincter defects is associated with good outcome.

Defining the spatial impacts of poultry farm ammonia emissions on species composition of adjacent woodland groundflora using Ellenberg Nitrogen Index, nitrous oxide and nitric oxide emissions and foliar nitrogen as marker variables.

The marker variables, Ellenberg Nitrogen Index, nitrous oxide and nitric oxide fluxes and foliar nitrogen, were used to define the impacts of NH3 deposition from nearby livestock buildings on species composition of woodland ground flora, using a woodland site close to a major poultry complex in the UK. The study centred on 2 units in close proximity to each other, containing 350,000 birds, and estimated to emit around 140,000 kg N year(-1) as NH3. Annual mean concentrations of NH3 close to the buildings were very large (60 microg m(-3)) and declined to 3 microg m(-3) at a distance of 650 m from the buildings. Estimated total N deposition ranged from 80 kg N ha(-1) year(-1) at a distance of 30 m to 14 kg N ha(-1) year(-1) at 650 m downwind. Emissions of N2O and NO were 56 and 131 microg N m(-2) h(-1), respectively at 30 m and 13 and 80 microg N m(-2) h(-1), respectively at 250 m downwind of the livestock buildings. Species number in woodland ground flora downwind of the buildings remained fairly constant for a distance of 200 m from the units then increased considerably, doubling at a distance of 650 m. Within the first 200 m downwind, trends in plant species composition were hard to discern because of variations in tree canopy composition and cover. The mean Ellenberg N Index ranged from 6.0 immediately downwind of the livestock buildings to 4.8 at 650 m downwind. The mean abundance weighted Ellenberg N Index also declined with distance from the buildings. Tissue N concentrations in trees, herbs and mosses were all large, reflecting the substantial ammonia emissions at this site. Tissue N content of ectohydric mosses ranged from approximately 4% at 30 m downwind to 1.6% at 650 m downwind. An assessment of the relative merits of the three marker variables concludes, that while Ellenberg Index and trace gas fluxes of N2O and NO give broad indications of impacts of ammonia emissions on woodland vegetation, the application of a critical foliar N content for ectohydric mosses is the most useful method for providing spatial information which could be of value to policy developers and planners.

Chronic pain, chronic stress and depression: coincidence or consequence?

Chronic pain and depressive illness are debilitating disease states that are variably resistant to currently available therapeutic agents. Animal models of chronic pain are associated with activation of the hypothalamo-pituitary-adrenal (HPA) axis, upon which chronic pain acts as an inescapable stressor. Inescapable stress is also associated with 'depressive-like' symptoms in experimental animals. Based on reports of the comorbidity between chronic pain and depressive illness in human patients, it is possible that these disease states are linked, via chronic stress-induced HPA dysfunction. Here, we discuss the possible involvement of the HPA axis in the aetiology of both chronic pain and clinical depression, and suggest a strategy for the development of novel pharmacotherapies.

Responses of magnocellular neurons to osmotic stimulation involves coactivation of excitatory and inhibitory input: an experimental and theoretical analysis.

How does a neuron, challenged by an increase in synaptic input, display a response that is independent of the initial level of activity? Here we show that both oxytocin and vasopressin cells in the supraoptic nucleus of normal rats respond to intravenous infusions of hypertonic saline with gradual, linear increases in discharge rate. In hyponatremic rats, oxytocin and vasopressin cells also responded linearly to intravenous infusions of hypertonic saline but with much lower slopes. The linearity of response was surprising, given both the expected nonlinearity of neuronal behavior and the nonlinearity of the oxytocin secretory response to such infusions. We show that a simple computational model can reproduce these responses well, but only if it is assumed that hypertonic infusions coactivate excitatory and inhibitory synaptic inputs. This hypothesis was tested first by applying the GABA(A) antagonist bicuculline to the dendritic zone of the supraoptic nucleus by microdialysis. During local blockade of GABA inputs, the response of oxytocin cells to hypertonic infusion was greatly enhanced. We then went on to directly measure GABA release in the supraoptic nucleus during hypertonic infusion, confirming the predicted rise. Together, the results suggest that hypertonic infusions lead to coactivation of excitatory and inhibitory inputs and that this coactivation may confer appropriate characteristics on the output behavior of oxytocin cells. The nonlinearity of oxytocin secretion that accompanies the linear increase in oxytocin cell firing rate reflects frequency-facilitation of stimulus-secretion coupling at the neurohypophysis.

Surveillance of antibiotic resistance in invasive isolates of Neisseria meningitidis in Australia 1994-1999.

A total of 1434 strains of Neisseria meningitidis isolated from cases of invasive meningococcal disease (IMD) in Australia between 1994 and 1999 were examined by standard methods for susceptibility to antibiotics used for treatment and prophylaxis. The proportion of isolates fully susceptible to penicillin decreased from 45% in 1994 to 26% in 1999 (P<0.001). All the other isolates were less sensitive to penicillin except for two meningococci with a penicillin MIC of 1 mg/l. The geometric mean penicillin MIC increased from 0.045 to 0.065 mg/l from 1994 to 1999. There was no significant difference in the geometric mean penicillin MICs of serogroup B and serogroup C meningococci. Penicillin susceptibility was significantly associated with a poorer outcome. Isolates from survivors of IMD had a higher geometric mean penicillin MIC (0.06 mg/l) than those from fatal cases (0.048 mg/l) (P< 0.001). This suggests that factors other than the decrease in susceptibility to penicillin observed were more relevant to outcome in IMD. All isolates were fully susceptible to ceftriaxone. Rifampicin resistance was infrequent (eight isolates in 6 years) and sporadic. A single isolate had decreased quinolone susceptibility. Despite the significant shift in susceptibility to penicillin recorded, this group of antibiotics remains a suitable treatment for IMD in Australia.

Non-multiresistant and multiresistant methicillin-resistant Staphylococcus aureus in community-acquired infections.

OBJECTIVE: To survey Staphylococcus aureus strains isolated from patients presenting from the community, comparing clinical features and antibiotic sensitivity profiles between multiresistant and non-multiresistant methicillin-resistant and methicillin-sensitive isolates. DESIGN: Retrospective case series. PARTICIPANTS AND SETTING: Patients who presented to emergency or dermatology departments in hospitals served by the South Western Sydney Area Health Service between 1 May 1998 and 30 April 1999. All patients with methicillin-resistant S. aureus (MRSA) and the first 100 with methicillin-sensitive S. aureus were eligible. MAIN OUTCOME MEASURES: Patient demographic characteristics; risk factors; clinical presentation; treatment; outcome; and isolate antibiotic susceptibility. RESULTS: 139 patients were eligible, and 122 had clinical records available. Ten of these 122 (8%) had multiresistant MRSA, 26 (21%) non-multiresistant MRSA and 86 (70%) methicillin-sensitive S. aureus. Among patients with non-multiresistant MRSA, 29% (7/24) were born in New Zealand, Samoa or Tonga, a higher proportion than among those with multiresistant MRSA or methicillin-sensitive S. aureus (P= 0.03). Nearly half (44%) of non-multiresistant MRSA strains were community-acquired in patients with no risk factors. Two-thirds of patients with non-multiresistant MRSA (17/26) presented with cellulitis or abscess, and 58% (11/19 evaluable patients) required surgical treatment. CONCLUSIONS: Non-multiresistant MRSA strains are common, especially among people born in New Zealand, Samoa or Tonga, and are usually community acquired. Medical practitioners should routinely swab all staphylococcal lesions for culture and sensitivity.

Prothrombin time inhibition detected with recombinant but not with conventional thromboplastins in two patients with high-titre IgM and moderate-titre IgA anticardiolipin antibodies.

We report two cases of high-titre IgM and moderate-titre IgA anticardiolipin antibodies (ACA) in whom prothrombin times (PT) derived using recombinant thromboplastins (rTP) were prolonged but were normal when measured with conventional thromboplastins. The anticoagulant nature of these antibodies cannot be categorized as the classical lupus type. We suggest that routine screening for the presence of antiphospholipid antibodies (APA) should be performed in patients who fall into this category.

Community-acquired, non-multiresistant oxacillin-resistant Staphylococcus aureus (NORSA) in South Western Sydney.

Community-acquired oxacillin-resistant Staphylococcus aureus (ORSA) infections are an emerging problem in the 1990s in Sydney, Australia. Laboratory data pertaining to all specimens that grew S. aureus between 1/1/1990 and 31/12/1999 were analysed. A total of 12,909 isolates of S. aureus were obtained. The proportions that were nonmultiresistant oxacillin-resistant S. aureus (NORSA) increased from 0.09% in 1990 to 5.5% in 1999. Resistance of NORSA strains to erythromycin was 8.5%, ciprofloxacin 8.4%, tetracycline 13%, rifampicin 0.7%, and fusidic acid 5.3%. A chart review was performed for cases of NORSA infection which occurred 1/1/1998-3/5/1998. Isolates from these cases underwent E-test oxacillin MIC testing, mecA determinant PCR, phage typing and pulsed-field gel electrophoresis. All nine of the patients with NORSA were Polynesians, and all had serious soft tissue infections. Bacteraemia was not seen. Only one patient received vancomycin yet all recovered. Isolates from all nine patients contained the mecA determinant. Oxacillin MICs were 1-8 mg/l. Strain differentiation with phage typing and pulsed-field gel electrophoresis showed isolates from eight patients were closely related and were similar to New Zealand WSPP1 and WSPP2 strains. Medical practitioners should take specimens for culture and sensitivity from lesions where infection with S. aureus is likely. Empirical treatment of staphylococcal infections in Polynesians needs to cover NORSA. Methods to detect oxacillin resistance need to be robust.

Mineralocorticoid treatment attenuates activation of oxytocinergic and vasopressinergic neurons by icv ANG II.

Central oxytocin (OT) neurons limit intracerebroventricular (icv) ANG II-induced NaCl intake. Because mineralocorticoids synergistically increase ANG II-induced NaCl intake, we hypothesized that mineralocorticoids may attenuate ANG II-induced activation of inhibitory OT neurons. To test this hypothesis, we determined the effect of deoxycorticosterone (DOCA; 2 mg/day) on icv ANG II-induced c-Fos immunoreactivity in OT and vasopressin (VP) neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus and also on pituitary OT and VP secretion in male rats. DOCA significantly decreased the percentage of c-Fos-positive (%c-Fos+) OT neurons in the SON and PVN, both in the magnocellular and parvocellular subdivisions, and the %c-Fos+ VP neurons in the SON after a 5-ng icv injection of ANG II. DOCA also significantly reduced the %c-Fos+ OT neurons in the SON after 10 ng ANG II and tended to attenuate 10 ng ANG II-induced OT secretion. However, the %c-Fos+ OT neurons in DOCA-treated rats was greater after 10 ng ANG II, and DOCA did not affect the %c-Fos+ OT neurons in the PVN nor VP secretion or c-Fos immunoreactivity in either the SON or PVN after 10 ng ANG II. DOCA also did not significantly alter the effect of intraperitoneal (ip) cholecystokinin (62 microg) on %c-Fos+ OT neurons or of ip NaCl (2 ml of 2 M NaCl) on the %c-Fos+ OT and VP neurons. These findings indicate that DOCA attenuates the responsiveness of OT and VP neurons to ANG II without completely suppressing the activity of these neurons and, therefore, support the hypothesis that attenuation of OT neuronal activity is one mechanism by which mineralocorticoids enhance NaCl intake.