Clinical findings, surgical treatment and outcome in dogs with parotid duct ectasia: 14 cases (2010-2023).

OBJECTIVES: To describe the clinical presentation, diagnostic findings, surgical treatment and outcome of dogs diagnosed with parotid duct ectasia. MATERIALS AND METHODS: Medical records of dogs diagnosed with parotid duct ectasia between 2010 and 2023 at six small animal referral hospitals were retrospectively reviewed. Outcome was assessed by contacting the owners or referring veterinarians. RESULTS: Fourteen dogs were included. Lateral facial swelling was the most common clinical presentation. CT revealed a tortuous cavitary tubular fluid-filled structure consistent with a dilated parotid duct in all dogs. Surgical treatment included marsupialisation of the parotid duct papilla, surgical exploration of the duct alone, parotid duct marsupialisation with surgical exploration of the duct, parotidectomy or en-bloc parotid duct resection. The aetiology of parotid duct ectasia was not established in 13 of 14 dogs. In one case, a foreign body was retrieved from the duct. No recurrence of clinical signs was noted during the follow-up period (range 21 to 2900 days). CLINICAL SIGNIFICANCE: Parotid duct ectasia should be considered for dogs with a lateralised fluctuant non-painful tubular facial swelling. Surgical management was associated with a favourable prognosis without evidence of recurrence in all cases reported in the case series.

Diagnostic findings in sinonasal aspergillosis in dogs in the United Kingdom: 475 cases (2011-2021).

OBJECTIVES: To describe the diagnostic tests used and their comparative performance in dogs diagnosed with sinonasal aspergillosis in the United Kingdom. A secondary objective was to describe the signalment, clinical findings and common clinicopathologic abnormalities in sinonasal aspergillosis. MATERIALS AND METHODS: A multi-centre retrospective survey was performed involving 23 referral centres in the United Kingdom to identify dogs diagnosed with sinonasal aspergillosis from January 2011 to December 2021. Dogs were included if fungal plaques were seen during rhinoscopy or if ancillary testing (via histopathology, culture, cytology, serology or PCR) was positive and other differential diagnoses were excluded. RESULTS: A total of 662 cases were entered into the database across the 23 referral centres. Four hundred and seventy-five cases met the study inclusion criteria. Of these, 419 dogs had fungal plaques and compatible clinical signs. Fungal plaques were not seen in 56 dogs with turbinate destruction that had compatible clinical signs and a positive ancillary test result. Ancillary diagnostics were performed in 312 of 419 (74%) dogs with observed fungal plaques permitting calculation of sensitivity of cytology as 67%, fungal culture 59%, histopathology 47% and PCR 71%. CLINICAL SIGNIFICANCE: The sensitivities of ancillary diagnostics in this study were lower than previously reported challenging the clinical utility of such tests in sinonasal aspergillosis. Treatment and management decisions should be based on a combination of diagnostics including imaging findings, visual inspection, and ancillary testing, rather than ancillary tests alone.

Women's satisfaction with early home medical abortion with telephone follow-up: a questionnaire-based study in the U.K.

A questionnaire-based study was undertaken to assess women's satisfaction with the home medical abortion service. Over a 15-month period, questionnaires were conducted at 24 h and 2 weeks following the procedure. A total of 127 women took part in the study and filled in a questionnaire at 24 h, with 77 completing the questionnaire at 2 weeks. At 24 h, over 95% of women who responded, agreed or strongly agreed that they felt prepared for the pain and bleeding that they experienced at home. At 2 weeks, 97.3% of respondents felt that they had had enough information and knew what to expect, and were therefore satisfied with the procedure. Only 15% of women were lost to clinical follow-up at 2 weeks. The majority of women are satisfied with the home medical abortion service. These high satisfaction rates are maintained at 2 weeks. Telephone follow-up 2 weeks after the abortion was safe and effective.

Outcome of caudal superficial epigastric axial pattern flaps in dogs and cats: 70 cases (2007-2020).

OBJECTIVES: To describe the outcome and complications associated with the use of caudal superficial epigastric axial pattern flaps in dogs and cats. MATERIAL AND METHODS: Multicentre retrospective review and descriptive study of clinical records of dogs and cats having undergone caudal superficial epigastric axial pattern flaps between 2007 and 2020. Data retrieved included signalment, aetiology of surgical defect, tumour type, presence/absence of clean surgical margins, presence/absence of post-operative wound infection, use of peri- and post-operative antibiotics, duration of anaesthesia, duration of surgery, presence and duration of hypothermia, presence and duration of hypotension, presence/absence of post-operative surgical drain and length of caudal superficial epigastric axial pattern flap. The incidence of complications and outcomes were documented. RESULTS: Seventy cases met the inclusion criteria; 51 dogs and 19 cats. In dogs, 67% of cases developed complications (59% minor, 8% major) and 33% had uneventful wound healing. In cats, 53% of cases developed complications, (47% minor, 5% major) and 47% had uneventful wound healing. In dogs, the percentage of cases experiencing dehiscence, necrosis, seroma, oedema and post-operative infection was 31%, 29%, 26%, 26% and 16% respectively. In cats, this was 26%, 16%, 11%, 0% and 5% respectively. A good overall outcome was seen in 77% of dogs and 79% of cats. A poor overall outcome was seen in 4% of dogs and 0% of cats. CLINICAL SIGNIFICANCE: Caudal superficial epigastric axial pattern flaps are traditionally thought more robust than other flaps, yet complication rates remain high, despite a high overall success rate.

Surgical valvulotomy for tricuspid valve stenosis in a dog.

A 2-year, 4-month-old neutered female Labrador retriever was brought for evaluation of right-sided congestive heart failure. Echocardiographic examination revealed tricuspid valve dysplasia with only two small orifices in the valve resulting in severe tricuspid stenosis. The dog underwent a right fifth lateral intercostal thoracotomy and surgical tricuspid valvulotomy, under cardiopulmonary bypass. The stenosis was relieved by dividing the valve leaflets between the two orifices with continuation to the commissures, creating a 'bileaflet' valve. The dog made a good recovery initially, with echocardiography at 48 h after surgery showing a reduction in tricuspid valve E and A wave velocities and pressure half-time (from 230 ms to 65 ms). She was discharged five days after surgery, and spironolactone, benazepril, pimobendan, and clopidogrel were prescribed. The dog was re-presented two days later having collapsed, with pyrexia, facial swelling, and pitting edema on the ventral neck and intermandibular region. Investigations did not reveal an underlying cause, and the clinical signs resolved with supportive therapy. Two years after surgery, the dog was free of clinical signs with normal exercise tolerance and only mild tricuspid regurgitation on echocardiography, with discontinuation of all medications.

BDNF has opposite effects on the quantal amplitude of pyramidal neuron and interneuron excitatory synapses.

Recently, we have identified a novel form of synaptic plasticity that acts to stabilize neocortical firing rates by scaling the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of neuronal activity. Here, we show that the effects of activity blockade on quantal amplitude are mediated through the neurotrophin brain-derived neurotrophic factor (BDNF). Exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the effects of activity blockade on pyramidal quantal amplitude. BDNF had opposite effects on pyramidal neuron and interneuron quantal amplitudes and modified the ratio of pyramidal neuron to interneuron firing rates. These data demonstrate a novel role for BDNF in the homeostatic regulation of excitatory synaptic strengths and in the maintenance of the balance of cortical excitation and inhibition.

Plasticity in the intrinsic excitability of cortical pyramidal neurons.

During learning and development, the level of synaptic input received by cortical neurons may change dramatically. Given a limited range of possible firing rates, how do neurons maintain responsiveness to both small and large synaptic inputs? We demonstrate that in response to changes in activity, cultured cortical pyramidal neurons regulate intrinsic excitability to promote stability in firing. Depriving pyramidal neurons of activity for two days increased sensitivity to current injection by selectively regulating voltage-dependent conductances. This suggests that one mechanism by which neurons maintain sensitivity to different levels of synaptic input is by altering the function relating current to firing rate.

Relationship between brachycephalic airway syndrome and gastrointestinal signs in three breeds of dog.

OBJECTIVES: To assess the breed-specific prevalence of, and effects of corrective airway surgery on, gastrointestinal signs in French bulldogs, English bulldogs and pugs presenting with brachycephalic airway syndrome to a referral teaching hospital. MATERIALS AND METHODS: In this retrospective study, ptyalism, regurgitation and vomiting were graded at presentation using a previously established scoring system. Staphylectomy and nares resection were performed on all dogs. Gastrointestinal signs were re-assessed via telephone follow-up at least 6 weeks after surgery. RESULTS: Ninety-eight dogs were included: French bulldogs (n=43), English bulldogs (n=12) and pugs (n=43). Overall population prevalence of all gastrointestinal signs was 56%. Breed-specific prevalence for French bulldogs was 93%, English bulldogs 58% and pugs 16%. There was post-surgical clinical improvement in gastrointestinal signs for the whole study population, especially in French bulldogs. CLINICAL SIGNIFICANCE: The prevalence of gastrointestinal signs in dogs presenting with brachycephalic airway syndrome and improvement in these clinical signs following corrective surgery may vary between breeds.

The incidence of surgical site dehiscence following full-thickness gastrointestinal biopsy in dogs and cats and associated risk factors.

OBJECTIVES: The objectives of this study were to: (1) document the incidence of surgical site dehiscence after full-thickness gastrointestinal biopsy in dogs and cats and (2) identify potential risk factors. METHODS: Data relating to dogs and cats undergoing full-thickness gastrointestinal biopsy were reviewed retrospectively following submission of a completed questionnaire by 12 referral institutions. Outcome measures were definite dehiscence, possible dehiscence (clinical records suggestive of dehiscence but not confirmed), suspected dehiscence (definite and possible combined) and death within 14 days. Logistic regression was planned for analysis of association of dehiscence with low preoperative serum albumin, biopsy through neoplastic tissue, biopsy alongside another major abdominal surgical procedure and biopsy of the colon. RESULTS: Of 172 cats, two (1·2%) had definite dehiscence, and four (2·3%) had possible dehiscence. Low preoperative serum albumin was significantly associated with definite dehiscence in univariable analysis and with suspected dehiscence and death within 14 days in univariable analysis, but all odds ratios had wide 95% confidence intervals. A histopathological diagnosis of neoplasia was significantly associated with death within 14 days in univariable analysis. Of 195 dogs, two (1·0%) had definite dehiscence, and three (1·5%) had possible dehiscence. In dogs, there was no association between any outcome measure and the putative risk factors. CLINICAL SIGNIFICANCE: Incidence of dehiscence following full-thickness gastrointestinal biopsy was low in this study. When determining the appropriateness of biopsy in individual cases, this information should be balanced against the potentially life-threatening consequences of dehiscence.

High molecular weight kininogen deficiency: a patient who underwent cardiac surgery.

A 66 year old male, referred for cardiac surgery, was found to have high molecular weight kininogen deficiency (activity <1%). Apart from activated partial thromboplastin time (APTT) >300 s, tests of haemostasis were otherwise normal (factors VIII, IX, XI, XII and prekallikrein). No inhibitor of coagulation was found. The activated coagulation time (ACT) was 800 s pre-operatively and >1000 s after heparin. Heparin levels were measured directly by an anti-Xa chromogenic assay, with values of between 2.9 and 3.2 u/ml during cardiopulmonary bypass. Thrombin-antithrombin levels rose from 2.3*g/l before surgery to a peak of 83.5*g/l at the end of cardiopulmonary bypass. Cross linked fibrin d-dimers (XDP) levels rose from 100 ng/ml before operation to 600 ng/ml after protamine administration. The patient had no excess bleeding and no thrombotic complications from surgery. This patient shows that high molecular weight kininogen is not required for thrombin formation or fibrinolysis during cardiac surgery and illustrates the need to measure heparin directly in patients with such contact factor deficiencies.

A comparison of cortical bone atrophy secondary to fixation with plates with large differences in bending stiffness.

Two internal-fixation plates with large differences in bending stiffness were applied to pairs of intact femora of six adult mongrel dogs to study the osteoporosis induced by rigid fixation. After nine and twelve months of plate application a significant, increased amount of bone atrophy was seen on the rigidly plated side. Biomechanical measurements of specimens from various segments of both femoral diaphyses showed the bones to have similar mechanical properties (as tissue), but different structural properties (as organ). These findings suggest that the osteoporosis due to rigid plate fixation occurs by thinning of the cortex rather than by reduction of the mechanical properties of the osseous tissue.

Expression of genes for interleukins, neuropeptides, growth hormone receptor, and leptin receptor in adipose tissue from growing broiler chickens.

In this study, total RNA was collected from abdominal adipose tissue samples obtained from 10 broiler chickens at 3, 4, 5, and 6 wk of age and prepared for quantitative real-time PCR analysis. Quantitative real-time PCR analysis was used to examine the influence of age on the expression of the adipose tissue genes for IL-1ß, -6, -10, -15, -18; brain-derived neurotropic factor; ciliary neurotropic factor; interferon γ, neuropeptide Y receptor Y1; neuropeptide Y; nucleobindin 2; growth hormone receptor; leptin receptor; and visfatin. Between 3 and 6 wk of age, leptin receptor expression decreased (P=0.013) with age, whereas expression of IL-15 (P=0.015) and growth hormone receptor (P=0.002) increased. Furthermore, IL-18 (P<0.001) and visfatin (P=0.007) expression increased between 4 and 6 wk of age. This is a unique exhibition of age-related changes in cytokine gene expression in chicken adipose tissue. Future studies are needed to elucidate the role of adipose tissue cytokines in growth and, possibly, disease resistance.

Evidence for indigenous Streptomyces populations in a marine environment determined with a 16S rRNA probe.

A 16S rRNA genus-specific probe was used to determine whether Streptomyces populations are an indigenous component of marine sediment bacterial communities. Previous debates have suggested that marine Streptomyces isolates are derived not from resident populations but from spores of terrestrial species which have been physically transported to marine ecosystems but remain dormant until isolation. Rigorously controlled hybridization of rRNA extracted from coastal marsh sediments with the genus-specific probe indicated that Streptomyces rRNA accounted for 2 to 5% of the sediment community rRNA and that spores are not the source of the hybridization signal. Streptomyces populations must therefore be at least the 26th most abundant genus-level source of bacterial rRNA. the relative amounts of rRNAs from Streptomyces spp. and members of the Bacteria (69 to 79%) and Archaea (4 to 7%) domains were highly consistent in these marine sediments throughout an annual cycle, indicating that the species composition of sediment bacterial communities may be more stable than recent studies suggest for marine planktonic bacterial communities. Laboratory studies designed to investigate the possible functional roles of Streptomyces populations in coastal sediments demonstrated that population levels of this genus changed relatively rapidly (within a time frame of 6 weeks) in response to manipulation of substrate availability. Amendments of intact sediment cores with two compounds (vanillic acid and succinic acid) consistently resulted in Streptomyces populations contributing an increased percentage of rRNA (6 to 15%) to the total bacterial rRNA pool.

Stimulus response coupling in the human neutrophil. I. Kinetic analysis of changes in calcium permeability.

The relationship between receptor-ligand interaction in human neutrophils and initiation of enhanced Ca permeability ("45Ca uptake") has been correlated with cell function. Different ligands varied in their efficacy in provoking 45Ca permeability changes: chemotactic peptide f-Met-Leu-Phe greater than concanavalin A greater than immune complexes greater than phorbol myristate acetate. Mixtures of stimuli at optimal concentrations elicited no summation of responses, indicating that interaction of f-Met-Leu-Phe, concanavalin A, and phorbol myristate acetate with their respective "receptors" regulates a common site of 45Ca uptake. The onset of Ca uptake was an early event, preceding onset of aggregation, O-2 generation, and degranulation. Enhanced 45Ca permeability during neutrophil activation is dependent on mobilization of intracellular Ca, since 8-(N,N-diethylamino)-octyl:3,4,5-trimethoxybenzoate hydrochloride was a potent inhibitor of the Ca permeability response. In contrast, calmodulin antagonists did not inhibit Ca permeability changes; the requirement for calmodulin in the physiological responses of aggregation, O-2 generation, and degranulation must therefore be subsequent to activation of the "Ca translocator." We propose a role for a "Ca-translocating mechanism" as an amplifying factor in neutrophil activation.

BDNF regulates the intrinsic excitability of cortical neurons.

Neocortical pyramidal neurons respond to prolonged activity blockade by modulating their balance of inward and outward currents to become more sensitive to synaptic input, possibly as a means of homeostatically regulating firing rates during periods of intense change in synapse number or strength. Here we show that this activity-dependent regulation of intrinsic excitability depends on the neurotrophin brain-derived neurotrophic factor (BDNF). In experiments on rat visual cortical cultures, we found that exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the change in pyramidal neuron excitability produced by activity blockade. Most of these effects were also observed in bipolar interneurons, indicating a very general role for BDNF in regulating neuronal excitability. Moreover, earlier work has demonstrated that BDNF mediates a different kind of homeostatic plasticity present in these same cultures: scaling of the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of activity. Taken together, these results suggest that BDNF may be the signal controlling a coordinated regulation of synaptic and intrinsic properties aimed at allowing cortical networks to adapt to long-lasting changes in activity.

Where the sun never shines: anorectal melanoma.

BACKGROUND: Melanoma occurring in the anorectal region is recognized to be an uncommon tumour with a poor prognosis. Queensland has the highest incidence rate of cutaneous melanoma in the world. The purpose of the present study was to determine if the very high incidence of cutaneous melanoma in Queensland has any bearing on the incidence of anorectal melanoma, and to compare this with published studies from other parts of the world. An assessment of the authors' results in the treatment of anorectal melanoma was made by a review of patients presenting during the last decade throughout Queensland. METHODS: All cases of melanoma occurring in Queensland are accumulated in the Melanoma Register, administered by the Queensland Melanoma Project, and data from this were used to derive the results in the present study. Queensland population data were provided by the Australian Bureau of Statistics. RESULTS: During the study period 1985-95 in Queensland there were 21,391 cases of cutaneous melanoma which occurred in an average population, during that time, of 2.89 million. During the same time there were nine cases of anorectal melanoma, giving a relative incidence therefore of 0.04%. This contrasts with published relative incidences of 0.2% for white people in North America, 11% for Southwestern Native Americans, and 14.2% for Northern Pakistan (P < 0.0001). However, the population-based incidence rates of anorectal melanoma for Queensland, United States white people, Southwestern Native Americans and Northern Pakistan are not significantly different from each other. All patients in the present series presented with large tumours, and none survived beyond 25 months despite standard surgical and adjuvant therapy. CONCLUSIONS: The protection against cutaneous melanoma afforded by skin pigmentation is not apparent in the anal area. Anorectal melanoma is no more or less frequent in Queensland, even with the very high incidence rate of cutaneous melanoma. Sun exposure appears to be neither protective nor a risk factor. The outcome of therapy for this condition remains disappointing in the authors' experience.

Brain-derived neurotrophic factor mediates the activity-dependent regulation of inhibition in neocortical cultures.

The excitability of cortical circuits is modulated by interneurons that release the inhibitory neurotransmitter GABA. In primate and rodent visual cortex, activity deprivation leads to a decrease in the expression of GABA. This suggests that activity is able to adjust the strength of cortical inhibition, but this has not been demonstrated directly. In addition, the nature of the signal linking activity to GABA expression has not been determined. Activity is known to regulate the expression of the neurotrophin brain-derived neurotrophic factor (BDNF), and BDNF has been shown to influence the phenotype of GABAergic interneurons. We use a culture system from postnatal rat visual cortex to test the hypothesis that activity is regulating the strength of cortical inhibition through the regulation of BDNF. Cultures were double-labeled against GABA and the neuronal marker MAP2, and the percentage of neurons that were GABA-positive was determined. Blocking spontaneous activity in these cultures reversibly decreased the number of GABA-positive neurons without affecting neuronal survival. Voltage-clamp analysis of inhibitory currents demonstrated that activity blockade also decreased GABA-mediated inhibition onto pyramidal neurons and raised pyramidal neuron firing rates. All of these effects were prevented by incubation with BDNF during activity blockade, but not by neurotrophin 3 or nerve growth factor. Additionally, blockade of neurotrophin signaling mimicked the effects of activity blockade on GABA expression. These data suggest that activity regulates cortical inhibition through a BDNF-dependent mechanism and that this neurotrophin plays an important role in the control of cortical excitability.

Female hormones reduce neutrophil responsiveness in vitro.

Neutrophils were preincubated with 17 beta-estradiol and progesterone to determine the effects of these hormones on chemotactic peptide-stimulated superoxide anion (O2-) generation and degranulation. At pharmacologic levels 17 beta-estradiol was more active than progesterone with respect to inhibition of O2- generation as well as degranulation. An increase of preincubation time from 5 minutes to 25 minutes increased the percent inhibition. When 17 beta-estradiol and progesterone were combined at levels which approximate those measured during gestation, there was small but significant inhibition of O2- generation. Dexamethasone at equal molar concentration inhibited O2- generation only after 25 minutes of preincubation and at no time reached the level of inhibition attained by either of the sex hormones alone. Both estradiol and progesterone at pharmacologic levels significantly inhibited beta-glucuronidase and lysozyme release, whereas dexamethasone did not inhibit degranulation despite prolonged preincubation. Neutrophils isolated from women during various phases of the menstrual cycle and during the third trimester of pregnancy did not differ with respect to chemotactic peptide-stimulated O2- generation. These data suggest that inhibition of neutrophil responses requires the continuous presence of pharmacologic levels of estradiol and progesterone.

Neutrophil stimulation: receptor, membrane, and metabolic events.

In the neutrophil, binding of ligands to their appropriate receptors initiates a sequence of events culminating in the physiological responses of aggregation, degranulation, and superoxide anion generation. Calcium has been proposed as a second messenger in the activation sequence of the neutrophil. Increments in cytosolic free calcium are one of the first measurable events subsequent to receptor occupancy, followed by enhanced plasmalemmal permeability to calcium, a process that may serve to enhance the physiological responses. In contrast to calcium, cyclic AMP (cAMP) does not act as a signal in the activation sequence of the neutrophil. Increments in cAMP that are triggered by complete secretagogues may act as an inhibitory feedback mechanism. Protein kinases, both cAMP- and calcium/phospholipid-sensitive enzymes, may play a role in the activation sequence. Phosphorylation of proteins occurs during neutrophil activation. A role for phosphatidylinositol/phosphatidic acid turnover in calcium gating has been proposed. In addition, modulation of phospholipids could serve to activate a protein kinase C. Finally, phospholipids can serve as a source for arachidonic acid, which is metabolized by a 5-lipoxygenase pathway in the neutrophil. Products of this pathway, such as leukotriene B4, may serve to mediate or modulate the activation sequence.