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.

The natural history of canine occult Grade II medial patellar luxation: an observational study.

OBJECTIVES: To determine the risk of lameness and the rate of subsequent medial patellar luxation surgery in dogs that present with occult Grade II medial patellar luxation. MATERIALS AND METHODS: Retrospective owner survey and review of clinical records of adult dogs diagnosed with Grade II medial patellar luxation that were initially asymptomatic and managed non-surgically that had a minimum of 4-year follow-up. Clinical notes and owner questionnaires identified dogs that subsequently developed lameness and required surgery on the previously asymptomatic stifle. RESULTS: Thirty-eight dogs were included with an average follow-up of 51 months. Seventeen dogs re-presented for unscheduled contralateral medial patellar luxation surgery at an average of 15 months after initial presentation. A further two dogs had chronic contralateral limb lameness after an average of 33 months after initial surgery and may have been potential surgical candidates. CLINICAL SIGNIFICANCE: Fifty percent of adult dogs presenting with occult Grade II medial patellar luxation subsequently developed chronic lameness or required surgery.

Impact of intra-operative hypotension on mortality rates and post-operative complications in dogs undergoing cholecystectomy.

OBJECTIVES: To report the mortality rate within a cohort of dogs undergoing cholecystectomy and investigate the impact of intra-operative hypotension on mortality. MATERIALS AND METHODS: Clinical records at five UK referral centres were reviewed for dogs undergoing cholecystectomy. Data collected included presenting signs, pre-operative blood test results, intra-operative data including frequency and duration of hypotension and the incidence and type of post-operative complications. RESULTS: Data from 119 dogs were included. Sixteen dogs (13%) died before discharge and by 28 days after surgery the total mortality was 19 dogs (17%). Hypotension lasting over 10 minutes during general anaesthesia occurred in 65 dogs (54.6%), with a mean ± sd duration of 36.1 ± 30.0 minutes. Intra-operative hypotension or the number of hypotensive episodes did not appear to be associated with in-hospital or 28-day mortality. American Society of Anaesthesiologists grade (of fitness for surgery) was significantly associated with both in-hospital and 28-day mortality on univariable analysis, as were post-operative hypoproteinaemia, ileus and pancreatitis. However on multivariable analysis, only ileus and pancreatitis were found to significantly impact mortality. CLINICAL SIGNIFICANCE: Dogs presenting with a higher American Society of Anaesthesiologists grade appear to have a higher risk of mortality, although intra-operative hypotension did not appear to be part of this risk.

Development of a large-animal human brain tumor xenograft model in immunosuppressed cats.

A large-animal model was developed to facilitate the noninvasive investigation of the effect on the human glioma-derived D-54 MG (glioblastoma multiforme) continuous cell line of a variety of therapeutic regimens. Twenty random-bred male cats were inoculated intracerebrally with 1 x 10(7) D-54 MG tumor cells after being initiated on one of three preparatory regimens of cyclosporin A p.o. Reproducible success of D-54 MG xenotransplantation (100%, 6 of 6 cats) was achieved only after pretreatment with 120 mg cyclosporin A p.o. (24-30 mg/kg) daily for greater than or equal to 10 days prior to tumor implantation. High-performance liquid chromatography-derived whole blood cyclosporin A 12-h trough levels of greater than or equal to 640 ng/ml were seen in successful implants. Lesions ranging from 2 to 20 mm in diameter were seen in cats sacrificed 27-44 days after implantation with no growth seen in control animals. Histopathological examination revealed the tumors to be well-circumscribed anaplastic intracerebral tumors with some invasion into surrounding host parenchyma. Perivascular lymphocytic cuffing was observed, but intratumoral lymphocytic infiltration was minimal. Gadolinium-EDTA-enhanced nuclear magnetic resonance imaging provided accurate tumor localization in T1-weighted images (TE 26 ms; TR 600 ms). Biochemical tests of kidney, liver, and hematological function were within normal limits, although 10% (2 of 20) of the animals developed gingival hyperplasia, and 5% (1 of 20) developed intussusception. The reproducible growth of the D-54 MG human glioblastoma cell line in a large-animal model eliminates many of the limitations associated with the standard nude mouse/rat model, thereby providing a novel test bed for a variety of imaging modalities as well as for drug immunoconjugate localization and toxicity studies.

In vivo functional analysis of the daughter of sevenless protein in receptor tyrosine kinase signaling.

One mechanism used by receptor tyrosine kinases to relay a signal to different downstream effector molecules is to use adaptor proteins that provide docking sites for a variety of proteins. The daughter of sevenless (dos) gene was isolated in a genetic screen for components acting downstream of the Sevenless (Sev) receptor tyrosine kinase. Dos contains a N-terminally located PH domain and several tyrosine residues within consensus binding sites for a number of SH2 domain containing proteins. The structural features of Dos and experiments demonstrating tyrosine phosphorylation of Dos upon Sev activation suggested that Dos belongs to the family of multisite adaptor proteins that include the Insulin Receptor Substrate (IRS) proteins, Gab1, and Gab2. Here, we studied the structural requirements for Dos function in receptor tyrosine kinase mediated signaling processes by expressing mutated dos transgenes in the fly. We show that mutant Dos proteins lacking the putative binding sites for the SH2 domains of Shc, PhospholipaseC-gamma (PLC-gamma) and the regulatory subunit of Phosphoinositide 3-kinase (PI3-K) can substitute the loss of endogenous Dos function during development. In contrast, tyrosine 801, corresponding to a predicted Corkscrew (Csw) tyrosine phosphatase SH2 domain binding site, is essential for Dos function. Furthermore, we assayed whether the Pleckstrin homology (PH) domain is required for Dos function and localization. Evidence is provided that deletion or mutation of the PH domain interferes with the function but not with localization of the Dos protein. The Dos PH domain can be replaced by the Gab1 PH domain but not by a heterologous membrane anchor, suggesting a specific function of the PH domain in regulating signal transduction.

Bcl-2 gene rearrangements in primary B-cell lymphoma of the gastrointestinal tract reveal follicular lymphoma as a subtype.

The principal objective of this study was to investigate whether follicular center cell lymphomas occur among B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). We used a molecular genetic/immunohistochemical approach and analysed 21 cases with the primary site in the gastrointestinal tract. Only two bcl-2 gene rearrangements were detected in our series and were found in two out of seven lymphomas with a nodular growth pattern. A chromosomal translocation t(14;18) was demonstrated by comigration of rearranged bcl-2 and JH sequences in one of these two cases. Additionally, both lymphomas showed bcl-2 protein positive neoplastic follicles, CD10 expression, and lack of vimentin. Therefore, these two cases were defined as follicular lymphomas. In contrast to the two follicular lymphomas of MALT, three other, nodular growing, bcl-2 protein positive lymphomas were found to have no bcl-2 gene rearrangements, to be CD10 negative and to express vimentin. These three lymphomas might be composed of neoplastic extrafollicular cells which secondarily invaded reactive follicles. We conclude that the presence of bcl-2 protein positive follicles is consistent with both a follicular and extrafollicular origin of a B lymphoma of MALT. However, the detection of a bcl-2 gene rearrangement is the most valuable criterion in such a situation, and additional immunophenotypic criteria, such as CD10 expression and lack of vimentin within the neoplastic population, further substantiate the diagnosis of a follicular lymphoma in MALT.

Misonidazole combined with hyperfractionation in the management of malignant glioma.

Multiple daily fractionated radiation therapy (MDF) may be more effective than conventionally fractionated radiation therapy (CF) in the treatment of malignant glioma. The hypoxic cell sensitizer misonidazole (MISO) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug. To evaluate MDF and MDF in combination with MISO, a randomized prospective trial was initiated. Between January 1981, and December 1982, patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were randomized to CF (5800 cGy, 30 fractions, 6 weeks), MDF (6141 cGy, 69 fractions, 4 1/2 weeks, at 89 cGy every 4 hours 3 times daily) and MDF in combination with MISO (1.25 gm/M2 three times weekly for the first 3 weeks). In January 1983, the CF arm was dropped and a high dose MDF arm added (7120 cGy, 80 fractions, 5 1/2 weeks, at 89 cGy per fraction every 4 hours 3 times daily). CCNU chemotherapy was given at the time of tumor progression. One hundred and twenty-eight patients were evaluated (38 CF, 42 MDF, 37 MDF plus MISO, and 11 high dose MDF). Median survival was 29 weeks for CF, 45 weeks for MDF and 50 weeks for MDF plus MISO. Survival was significantly improved for patients treated with MDF compared to patients treated with CF (p less than .002). The addition of MISO to MDF did not result in further improvement in survival. Acute toxicity was acceptable. No clinically apparent delayed toxicity was observed.

Percutaneous trephine lung biopsy: evolving role.

The Steele trephine was employed to perform 134 transthoracic biopsies in 120 patients. Resultant cores of tissue and "lung juice" provided a diagnosis in 89 percent (107) of the patients. Complications occurred in 41 percent (49) of the patients, the incidence being greatest in those with diffuse parenchymal disease. Most complications were of a minor nature. Although the precise role of trephine lung biopsy in the physician's diagnostic armamentarium remains to be defined, there is no doubt that it is a useful and safe technique in the elucidation of intrathoracic disease.

"Mesothelioma of the atrioventricular node" with long-standing complete heart block. Report of a case.

A case of mesothelioma of the atrioventricular node is presented. The patient had complete heart block for many years before death. The origin of the tissue in this apparently congenital tumor is discussed with reference to the literature.

Histopathology and molecular basis of iridogoniodysgenesis syndrome.

Iridogoniodysgenesis is an autosomal dominant disorder in which there are abnormalities in the development of the iris stroma and trabecular meshwork tissues commonly resulting in glaucoma. The unoperated eye from an affected member of a family with iridogoniodysgenesis syndrome (IGDS) was removed shortly after death. Histopathological studies showed an incomplete, normally positioned line of Schwalbe and iris stromal hypoplasia. The molecular basis underlying the disorder is a missense mutation in the RIEG gene at 4q25, mutations of which have been previously shown to cause Axenfeld-Rieger syndrome (ARS). Coupled with another report of a missense mutation of the RIEG gene in a family with IGDS, we suggest that these mutations may interfere less with gene function and thereby may be responsible for a milder phenotype than occurs in the more characteristic ARS.

Intracranial vascular complications of choriocarcinoma.

Choriocarcinoma is the most malignant of the tumors of chorionic tissue that (most commonly) arise from fetal tissues and invade the maternal vasculature. Two cases of choriocarcinoma are presented. One patient had a suprasellar mass in conjunction with a neoplastic carotid-cavernous fistula. The mass and the fistula disappeared after apparently successful radiation therapy and chemotherapy. The second patient had a ruptured arterial aneurysm associated with an intracerebral hematoma treated by evacuation of the hematoma and resection of the aneurysm. The vascular complications of this tumor are reviewed, and a management plan is suggested.

Effects of photoradiation therapy on normal rat brain.

Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. We conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

Anatomic details of intradural channels in the parasagittal dura: a possible pathway for flow of cerebrospinal fluid.

OBJECTIVE: The absorption of cerebrospinal fluid occurs primarily by means of arachnoid granulations (AG) in the superior sagittal sinus (SSS) and the lacunae laterales (LL) in the parasagittal dura. Previous descriptions of this region suggest a network of intradural channels, but finer details of extent and relationship between channels and AG were not addressed. Therefore, we undertook an anatomic study of cadaveric parasagittal dura. METHODS: The SSS and parasagittal dura of 20 formalin-fixed adult cadavers and 15 autopsy specimens from patients ranging in age from 18 weeks of gestation to 80 years were studied by use of a light microscope, a scanning electron microscope, and corrosion casting. Intradural injections into the parasagittal region were performed in two formalin-fixed and four autopsy specimens from adults by use of normal saline and corrosion casting. RESULTS: Extensive networks of intradural channels from 0.02 to 2.0 mm in diameter were noted in all of the specimens. Channels either were connected to the SSS at intervals along the side wall or drained directly into the LL, which extended up to 3 cm from midline. Channels lined with endothelium stained positive for Factor VIII, as did the endothelium of the LL and SSS. In some places, the network of channels seemed to coalesce to form LL. The underside of the dura was coarse and trabeculated where the channels were abundant, and AG were interdigitated between these trabeculae. In regions of the dura where channels were sparse or absent, the dural underside was smooth and lacked AG. Underlying cortical veins opened directly into the SSS and were unrelated to intradural channels. Intradural parasagittal injections from the epidural side accessed the SSS by way of channels using pressures between 0 and 20 cm H2O at 1.5 ml/min. CONCLUSION: These channels may represent a pathway for the flow of cerebrospinal fluid from AG to the SSS.

Comparison of intrathecal administration of urokinase and tissue plasminogen activator on subarachnoid clot and chronic vasospasm in a primate model.

Safety and efficacy of the thrombolytic agent urokinase (URO) in the elimination of subarachnoid clot and prevention of chronic vasospasm was compared with tissue-type plasminogen activator (rt-PA) in a blind, randomized placebo-controlled trial. Twenty monkeys were randomly assigned to one of five groups of four. Each group underwent baseline cerebral angiography followed by bilateral craniectomy and experimental subarachnoid hemorrhage. An Ommaya reservoir was inserted on the right side with its catheter placed into the ipsilateral subarachnoid space. Twenty-four hours later, depending upon group assignment, the animals received 100,000 IU URO, 200,000 IU URO, 1 mg rt-PA, 2 mg rt-PA, or the equivalent volume of normal saline (control group). On Day 7, angiography was repeated and the animals were killed. One animal died as a result of complications during the baseline angiography, presumably due to blood loss and prolonged anesthesia, and a replacement animal was obtained. No animals demonstrated any delayed neurological deficits. The study demonstrated that a single intracisternal bolus injection of rt-PA, 2.0 mg in 2 ml sterile water, or URO, 200,000 IU in 2 ml sterile water, 24 hours after induction of experimental subarachnoid hemorrhage in primates, was equally effective in thrombolysing ipsilateral clot, but neither dosage prevented angiographic vasospasm. Vasospasm occurred bilaterally in all groups. Whereas gross subarachnoid clot was found bilaterally in all animals in the placebo group and both smaller-dose URO and rt-PA groups, right-sided subarachnoid clot was virtually absent and left-sided clot reduced in both higher-dose URO and rt-PA groups.(ABSTRACT TRUNCATED AT 250 WORDS)

New long-wavelength Nd:YAG laser at 1.44 micron: effect on brain.

A wavelength-shifted Nd:YAG laser, tuned to coincide with the infrared absorption peak of water at 1.44 microns, was used to make lesions in normal rabbit brain. A total of 48 lesions were made with power up to 20 W, with energy up to 40 joules, and with two different spot sizes. These lesions were compared to lesions made with 1.06 microns radiation from an Nd:YAG laser under identical operating conditions. Measurements of blood-brain barrier damage and width, depth, and volume of tissue affected were obtained 30 minutes after placement of the lesions. It was found that 1.44-microns lesions produced photoevaporative tissue loss at the highest intensities used. The layer of coagulated tissue remaining after photovaporization had a mean thickness of 0.6 mm irrespective of the volume of tissue removed. There was no photovaporization in the 1.06-microns lesions. In addition, the amount of peripheral edema per unit volume of tissue coagulated was approximately half at the 1.44-microns wavelength. These findings suggest that the 1.44-microns Nd:YAG laser may be a useful surgical instrument since it combines the photoevaporative effect of the CO2 laser while maintaining the advantages of the conventional Nd:YAG laser (quartz fiber delivery and effective hemostasis).

Radiotherapy and CCNU in the treatment of high-grade supratentorial astrocytomas.

Forty-one consecutive patients with supratentorial primary brain tumors (38 Grade III and IV astrocytomas, one giant-cell astrocytoma, and two cases with insufficient tissue for diagnosis) were randomly allocated within 2 weeks of surgery to one of three therapeutic groups. Group 1 (15 patients) received radiation therapy totaling 4000 to 4500 rads in 4 to 5 weeks. Group 2 (13 patients) received 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea CCNU) 130 mg/sq m orally every 6 weeks. Group 3 (13 patients) received radiation therapy plus CCNU as for Groups 1 and 2. When the disease progressed, patients in Groups 1 and 2 were crossed over to receive CCNU and irradiation respectively. The median survival time in these groups was 188, 259, and 252 days, and the mean survival 263, 262, and 329 days. The median time from diagnosis to crossover (Groups 1 and 2) or to progression (Group 3) was 163, 99, and 220 days, and the mean time was 172, 108, and 231 days. There was no statistically significant difference between the means or medians in any of these situations.

Effect of clot removal at 24 hours on chronic vasospasm after SAH in the primate model.

The efficacy of complete clot removal 24 hours after subarachnoid hemorrhage (SAH) in the prevention of chronic cerebral vasospasm was evaluated in monkeys in a blind randomized controlled trial. Twenty-four monkeys were randomized to one of three groups to undergo sham-operation (sham-operated group), clot placement only (clot group), or clot placement and removal (clot-removal group). By means of standard microsurgical techniques, the major cerebral vessels bilaterally were dissected free of arachnoid. An autologous hematoma averaging 5 gm was placed around the vessels in the subarachnoid spaces in the clot and clot-removal groups. Saline solution was instilled in the subarachnoid spaces of the sham-operated group. All animals underwent reoperation 24 hours after the first procedure. In the clot-removal group, the hematoma was evacuated. In the sham-operated and clot groups, the incision was simply closed again after 3 hours of anesthesia. Indices monitored before and 7 days after SAH induction included neurological status, angiographic cerebral vessel caliber, and arterial blood pressure. All animals were evaluated with magnetic resonance imaging (MRI); representative animals were evaluated with computerized tomography (CT) brain scans. There were no neurological deficits in either the sham-operated or the clot-removal groups. One animal in the clot group developed a progressive delayed ischemic deficit on Day 5 after SAH. A second animal in this group died suddenly on Day 4 post-SAH. An autopsy revealed a recent infarct in the territory of the superior cerebellar artery. Clinical findings correlated with MRI and CT images. Significant vasospasm (25% to 100% reduction in vessel caliber) was present on Day 7 in 100% of the clot animals (p less than 0.01). There was no significant vasospasm (p greater than 0.05) on Day 7 in either the sham-operated or the clot-removal groups. A large volume of clot placed bilaterally resulted in a 25% incidence of delayed ischemic deficit. Evacuation of subarachnoid hematoma within 24 hours of SAH prevented the development of chronic vasospasm and delayed ischemic deficit in the primate model.

Etiology of cerebral vasospasm in primates.

A primate model was used to determine whether oxyhemoglobin (OxyHb), methemoglobin (MetHb), or bilirubin is likely to be responsible for cerebral vasospasm following subarachnoid hemorrhage (SAH). Forty cynomolgus monkeys were randomly assigned to one of five groups. On Day 0, each animal underwent angiography followed by right craniectomy and placement of an Ommaya reservoir with its catheter adjacent to the right middle cerebral artery (MCA). The animals received intrathecal injections twice a day for 6 days of one of the following solutions: mock cerebrospinal fluid (CSF); OxyHb; MetHb; bilirubin; or supernatant fluid from an incubated mixture of autologous blood and mock CSF. On Day 7, angiography was repeated and the animals were killed. Comparison of angiograms obtained on Day 0 and Day 7 of the experiment showed significant vasospasm of the right MCA and the right anterior cerebral and internal carotid arteries in the animal groups that had received OxyHb or supernatant fluid. There was a smaller reduction in diameter of the same vessels in the bilirubin group (not statistically significant), while no effects were observed in the groups receiving MetHb or mock CSF. Electron microscopy of the right MCA's gave results consistent with the angiographic findings. One monkey in the OxyHb group developed a delayed-onset right MCA infarction. These data suggest that OxyHb is the cause of cerebral vasospasm following SAH.

Fatal rebleeding from a dural arteriovenous malformation of the posterior fossa: case report with pathological examination.

A seventy-year-old woman suffered a fatal cerebellar rehemorrhage from a large venous aneurysm associated with a dural arteriovenous malformation (AVM) of the posterior fossa. The malformation, fed by branches of the right vertebral, occipital and middle meningeal arteries, had a nidus in the transverse sinus wall with a pedunculated extension reaching the pial surface of the adjacent cerebellum, from where the malformation drained exclusively into an aneurysmal cerebellar vein. There was no associated venous sinus obstruction. Histopathological examination of the venous sinuses, arteriovenous malformation and venous drainage is described and these findings as they relate to the pathogenesis of dural AVMs are discussed. Vascular malformations of the dura mater do not appear to be a single clinical or pathological entity. The serious risk of hemorrhage from a parenchymal venous aneurysm is emphasized.

Attempted experimental modification of the postlaminectomy membrane by local instillation of recombinant tissue-plasminogen activator gel.

A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel (rt-PA) could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots. It was concluded that the local instillation of gel rt-PA after laminectomy did not inhibit scar formation or scar adherence to the dura mater.