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Genes that regulate hormone release are essential for maintaining metabolism and energy balance. Egr1 encodes a transcription factor that regulates hormone production and release, and a decreased in growth hormones has been reported in Egr1 knockout mice. A reduction in growth hormones has also been observed in Nestin-Cre mice, a model frequently used to study the nervous system. Currently, it is unknown how Egr1 loss or the Nestin-Cre driver disrupt pituitary gene expression. Here, we compared the growth curves and pituitary gene expression profiles of Nestin-Cre-mediated Egr1 conditional knockout (Egr1cKO) mice with those of their controls. Reduced body weight was observed in both the Nestin-Cre and Egr1cKO mice, and the loss of Egr1 had a slightly more severe impact on female mice than on male mice. RNA-seq data analyses revealed that the sex-related differences were amplified in the Nestin-Cre-mediated Egr1 conditional knockout mice. Additionally, in the male mice, the influence of Egr1cKO on pituitary gene expression may be overridden by the Nestin-Cre driver. Differentially expressed genes associated with the Nestin-Cre driver were significantly enriched for genes related to growth factor activity and binding. Altogether, our results demonstrate that Nestin-Cre and the loss of Egr1 in the neuronal cell lineage have distinct impacts on pituitary gene expression in a sex-specific manner.

Genes that regulate hormone release are essential for maintaining metabolism and energy balance. Egr1 encodes a transcription factor that regulates hormone production and release, and a decreased in growth hormones has been reported in Egr1 knockout mice. A reduction in growth hormones has also been observed in Nestin-Cre mice, a model frequently used to study the nervous system. Currently, it is unknown how Egr1 loss or the Nestin-Cre driver disrupt pituitary gene expression. Here, we compared the growth curves and pituitary gene expression profiles of Nestin-Cre-mediated Egr1 conditional knockout (Egr1cKO) mice with those of their controls. Reduced body weight was observed in both the Nestin-Cre and Egr1cKO mice, and the loss of Egr1 had a slightly more severe impact on female mice than on male mice. RNA-seq data analyses revealed that the sex-related differences were amplified in the Nestin-Cre-mediated Egr1 conditional knockout mice. Additionally, in the male mice, the influence of Egr1cKO on pituitary gene expression may be overridden by the Nestin-Cre driver. Differentially expressed genes associated with the Nestin-Cre driver were significantly enriched for genes related to growth factor activity and binding. Altogether, our results demonstrate that Nestin-Cre and the loss of Egr1 in the neuronal cell lineage have distinct impacts on pituitary gene expression in a sex-specific manner.

A 9-year-old female spayed Boston Terrier presented for diagnostic investigation of lethargy, poor appetite, weight loss, and a marked leukocytosis. Significant muscle wasting and a palpable abdominal mass were present on physical examination. Abdominal imaging revealed the mass to be of small intestinal origin; consequently, an intestinal resection and anastomosis were performed without complication. The histopathologic diagnosis was a gastrointestinal stromal tumor, verified by immunohistochemical positivity to CD117 (KIT). Two weeks after discharge, the leukocytosis had resolved. Though the exact molecular mediator of the severe leukocytosis was undetermined, resolution following tumor removal suggests a paraneoplastic cause. To the authors' knowledge, this is the first reported case of probable paraneoplastic leukocytosis secondary to a gastrointestinal stromal tumor in the dog. Gastrointestinal tract imaging should be performed when this uncommon hematologic abnormality is present.

A 9-year-old female spayed Boston Terrier presented for diagnostic investigation of lethargy, poor appetite, weight loss, and a marked leukocytosis. Significant muscle wasting and a palpable abdominal mass were present on physical examination. Abdominal imaging revealed the mass to be of small intestinal origin; consequently, an intestinal resection and anastomosis were performed without complication. The histopathologic diagnosis was a gastrointestinal stromal tumor, verified by immunohistochemical positivity to CD117 (KIT). Two weeks after discharge, the leukocytosis had resolved. Though the exact molecular mediator of the severe leukocytosis was undetermined, resolution following tumor removal suggests a paraneoplastic cause. To the authors' knowledge, this is the first reported case of probable paraneoplastic leukocytosis secondary to a gastrointestinal stromal tumor in the dog. Gastrointestinal tract imaging should be performed when this uncommon hematologic abnormality is present.

BackgroundHistiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.ObjectiveTo characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.AnimalsOne hundred two dogs with HS, 62 dogs with meningioma.MethodsRetrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data.ResultsPredisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor.Conclusions and clinical importanceClinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities.

BackgroundHistiocytic sarcoma affecting the central nervous system (CNS HS) in dogs may present as primary or disseminated disease, often characterized by inflammation. Prognosis is poor, and imaging differentiation from other CNS tumors can be problematic.ObjectiveTo characterize the clinicopathological inflammatory features, breed predisposition, and survival in dogs with CNS HS.AnimalsOne hundred two dogs with HS, 62 dogs with meningioma.MethodsRetrospective case series. Records were reviewed for results of cerebrospinal fluid (CSF) analysis, CBC, treatment, and outcome data.ResultsPredisposition for CNS HS was seen in Bernese Mountain Dogs, Golden Retrievers, Rottweilers, Corgis, and Shetland Sheepdogs (P ≤ .001). Corgis and Shetland Sheepdogs had predominantly primary tumors; Rottweilers had exclusively disseminated tumors. Marked CSF inflammation was characteristic of primary rather than disseminated HS, and neoplastic cells were detected in CSF of 52% of affected dogs. Increased neutrophil to lymphocyte ratios were seen in all groups relative to controls (P <.008) but not among tumor subtypes. Definitive versus palliative treatment resulted in improved survival times (P < .001), but overall prognosis was poor.Conclusions and clinical importanceClinicopathological differences between primary and disseminated HS suggest that tumor biological behavior and origin may be different. Corgis and Shetland Sheepdogs are predisposed to primary CNS HS, characterized by inflammatory CSF. High total nucleated cell count and the presence of neoplastic cells support the use of CSF analysis as a valuable diagnostic test. Prognosis for CNS HS is poor, but further evaluation of inflammatory mechanisms may provide novel therapeutic opportunities.

Background Stereotactic brain biopsy (SBB) is a technique that allows for definitive diagnosis of brain lesions. Little information is available regarding the diagnostic utility of SBB in dogs with intracranial diseases. Objective To investigate the diagnostic accuracy (DA) of SBB in dogs with brain tumors. Animals Thirty-one client-owned dogs that underwent SBB followed by surgical resection or necropsy examinations. Methods Retrospective observational study. Two pathologists blinded to SBB and reference standard diagnoses reviewed histologic specimens and typed and graded tumors according to World Health Organization and revised canine glioma classification criteria. Agreement between tumor type and grade from SBB were compared to reference standards and assessed using kappa statistics. Patient and technical factors associated with agreement also were examined. Results Stereotactic brain biopsy specimens were obtained from 24 dogs with gliomas and 7 with meningiomas. Tumor type agreement between SBB and the reference standard was observed in 30/31 cases (kappa = 0.95). Diagnostic concordance was perfect for meningiomas. Grade agreement among gliomas was observed in 18/23 cases (kappa = 0.47). Stereotactic brain biopsy underrepresented the reference standard glioma grade in cases with disagreement. The DA of SBB was 81%, with agreement noted in 56/69 biopsy samples. Smaller tumors and fewer SBB specimens obtained were significantly associated with diagnostic discordance. Conclusions and Clinical Importance The DA of SBB readily allows for the diagnosis of common brain tumors in dogs. Although glioma grade discordance was frequent, diagnoses obtained from SBB are sufficient to currently inform therapeutic decisions. Multiple SBB specimens should be collected to maximize DA.

Background Stereotactic brain biopsy (SBB) is a technique that allows for definitive diagnosis of brain lesions. Little information is available regarding the diagnostic utility of SBB in dogs with intracranial diseases. Objective To investigate the diagnostic accuracy (DA) of SBB in dogs with brain tumors. Animals Thirty-one client-owned dogs that underwent SBB followed by surgical resection or necropsy examinations. Methods Retrospective observational study. Two pathologists blinded to SBB and reference standard diagnoses reviewed histologic specimens and typed and graded tumors according to World Health Organization and revised canine glioma classification criteria. Agreement between tumor type and grade from SBB were compared to reference standards and assessed using kappa statistics. Patient and technical factors associated with agreement also were examined. Results Stereotactic brain biopsy specimens were obtained from 24 dogs with gliomas and 7 with meningiomas. Tumor type agreement between SBB and the reference standard was observed in 30/31 cases (kappa = 0.95). Diagnostic concordance was perfect for meningiomas. Grade agreement among gliomas was observed in 18/23 cases (kappa = 0.47). Stereotactic brain biopsy underrepresented the reference standard glioma grade in cases with disagreement. The DA of SBB was 81%, with agreement noted in 56/69 biopsy samples. Smaller tumors and fewer SBB specimens obtained were significantly associated with diagnostic discordance. Conclusions and Clinical Importance The DA of SBB readily allows for the diagnosis of common brain tumors in dogs. Although glioma grade discordance was frequent, diagnoses obtained from SBB are sufficient to currently inform therapeutic decisions. Multiple SBB specimens should be collected to maximize DA.

Scottish terriers (ST) frequently have increased serum alkaline phosphatase (ALP) of the steroid isoform. Many of these also have high serum concentrations of adrenal sex steroids. The study’s objective was to determine the cause of increased sex steroids in ST with increased ALP. Adrenal gland suppression and stimulation were compared by low dose dexamethasone (LDDS), human chorionic gonadotropin (HCG) and adrenocorticotropic hormone (ACTH) response tests. Resting plasma pituitary hormones were measured. Steroidogenesis-related mRNA expression was evaluated in six ST with increased ALP, eight dogs of other breeds with pituitary-dependent hyperadrenocorticism (HAC), and seven normal dogs. The genome-wide association of single nucleotide polymorphisms (SNP) with ALP activity was evaluated in 168 ST. ALP (reference interval 8–70 U/L) was high in all ST (1,054 U/L) and HAC (985 U/L) dogs. All HAC dogs and 2/8 ST had increased cortisol post-ACTH administration. All ST and 2/7 Normal dogs had increased sex steroids post-ACTH. ST and Normal dogs had similar post-challenge adrenal steroid profiles following LDDS and HCG. Surprisingly, mRNA of hydroxysteroid 17-beta dehydrogenase 2 (HSD17B2) was lower in ST and Normal dogs than HAC. HSD17B2 facilities metabolism of sex steroids. A SNP region was identified on chromosome 5 in proximity to HSD17B2 that correlated with increased serum ALP. ST in this study with increased ALP had a normal pituitary-adrenal axis in relationship to glucocorticoids and luteinizing hormone.We speculate the identified SNP and HSD17B2 gene may have a role in the pathogenesis of elevated sex steroids and ALP in ST.

Intraocular neoplasms in dogs are uncommon in comparison with other anatomic locations [1–4]. Over 75% of these cases are attributed to melanocytic neoplasia [1]. A majority of the remaining cases (~22%) are comprised of lymphoma, metastatic neoplasia, iridociliary epithelial tumors, optic nerve meningiomas, and histiocytic sarcomas in decreasing order of frequency [1, 2]. Rarely, optic nerve astrocytomas have been reported in humans, dogs, and horses [5–7]. In humans, astrocytomas involving the optic nerve are uncommon accounting for only about 1% of neoplasms at this site in comparison with 25% of neoplasms occurring in the brain [5, 8–14]. Most of these neoplasms occur unilaterally, are benign, and arise in children under 10 years of age; those involving the cerebellum have a more favorable prognosis [8, 14]. These younger patients commonly have an underlying familiar disorder such as neurofibromatosis. In older patients in their fourth and fifth decade of life, astrocytomas more commonly involve the cerebrum with a less favorable prognosis and can be associated with familiar disorders such as Li–Fraumeni syndrome [13, 15–17]. Most canine ocular astrocytoma cases are sporadic and not associated with any familial disorder [1, 13, 18–21]. However, Thomas et al. demonstrated a genomic risk factor associated with frequency of chromosome copy number aberrations within canine brain astrocytomas and tumor grade [22]. Similar to humans, canine astrocytomas account for less than 1% of ocular and optic nerve neoplasms and 10–36% of primary intracranial neoplasms [1, 4, 16–18, 20, 21, 23]. There appears to be a breed predisposition for development of intracranial astrocytomas in English Toy Spaniels, Boston Terriers, French Bulldogs, Boxers, and English Bulldog with a peak prevalence at 7– 8 years and 1.5 odds ratio in favor of larger versus smaller breeds [13, 23]. These risk factors have not been shown in association with canine ocular forms of this neoplasm [1, 16, 17].

Intraocular neoplasms in dogs are uncommon in comparison with other anatomic locations [1–4]. Over 75% of these cases are attributed to melanocytic neoplasia [1]. A majority of the remaining cases (~22%) are comprised of lymphoma, metastatic neoplasia, iridociliary epithelial tumors, optic nerve meningiomas, and histiocytic sarcomas in decreasing order of frequency [1, 2]. Rarely, optic nerve astrocytomas have been reported in humans, dogs, and horses [5–7]. In humans, astrocytomas involving the optic nerve are uncommon accounting for only about 1% of neoplasms at this site in comparison with 25% of neoplasms occurring in the brain [5, 8–14]. Most of these neoplasms occur unilaterally, are benign, and arise in children under 10 years of age; those involving the cerebellum have a more favorable prognosis [8, 14]. These younger patients commonly have an underlying familiar disorder such as neurofibromatosis. In older patients in their fourth and fifth decade of life, astrocytomas more commonly involve the cerebrum with a less favorable prognosis and can be associated with familiar disorders such as Li–Fraumeni syndrome [13, 15–17]. Most canine ocular astrocytoma cases are sporadic and not associated with any familial disorder [1, 13, 18–21]. However, Thomas et al. demonstrated a genomic risk factor associated with frequency of chromosome copy number aberrations within canine brain astrocytomas and tumor grade [22]. Similar to humans, canine astrocytomas account for less than 1% of ocular and optic nerve neoplasms and 10–36% of primary intracranial neoplasms [1, 4, 16–18, 20, 21, 23]. There appears to be a breed predisposition for development of intracranial astrocytomas in English Toy Spaniels, Boston Terriers, French Bulldogs, Boxers, and English Bulldog with a peak prevalence at 7– 8 years and 1.5 odds ratio in favor of larger versus smaller breeds [13, 23]. These risk factors have not been shown in association with canine ocular forms of this neoplasm [1, 16, 17].

Background: Biopsy of the liver evaluates a small portion of tissue, with inferences made to the entire organ. The method and number of biopsies obtained are tempered by consideration of the risks and benefits. Recommendations often include biopsy of more than one liver lobe, although the consistency of histopathology among lobes in dogs is unknown. Hypothesis/Objectives: To describe the distribution of histopathologic abnormalities between liver lobes. We hypothesized that discordant results would be evenly distributed among all liver lobes. Animals: Seventy dogs undergoing necropsy. Methods: Prospective study. Liver samples were obtained from all lobes. A primary diagnosis was assigned to each liver sample based on the predominant histopathologic abnormality. Results: In this population of dogs, biopsy of at least 2 liver lobes identified the predominant histologic abnormality in 98.6% of the cases. Ten ( 14%) of the dogs had = 3 lobes in agreement and could not be assigned a predominant diagnosis. The same diagnosis was present in 6/ 6 lobes in 39 ( 56.5%) dogs, 5/ 6 lobes in 10 ( 14.5%) dogs, 4/ 6 lobes in 10 ( 14.5%) dogs, 3/ 6 lobes in 7 ( 10.1%) dogs, and 2/ 6 in 3 ( 4.3%) dogs. The number of discordant results did not differ between the liver lobes. Conclusion and Clinical Importance: The likelihood of obtaining a sample that is reflective of the predominant histologic abnormality in the liver is increased when multiple liver lobes are biopsied.

Background: The liver sampling technique in dogs that consistently provides samples adequate for accurate histopathologic interpretation is not known. Hypothesis/ Objectives: To compare histopathologic results of liver samples obtained by punch, cup, and 14 gauge needle to large wedge samples collected at necropsy. Animals: Seventy dogs undergoing necropsy. Methods: Prospective study. Liver specimens were obtained from the left lateral liver lobe with an 8 mm punch, a 5 mm cup, and a 14 gauge needle. After sample acquisition, two larger tissue samples were collected near the center of the left lateral lobe to be used as a histologic standard for comparison. Histopathologic features and numbers of portal triads in each sample were recorded. Results: The mean number of portal triads obtained by each sampling method were 2.9 in needle samples, 3.4 in cup samples, 12 in punch samples, and 30.7 in the necropsy samples. The diagnoses in 66% of needle samples, 60% of cup samples, and 69% of punch samples were in agreement with the necropsy samples, and these proportions were not significantly different from each other. The corresponding kappa coefficients were 0.59 for needle biopsies, 0.52 for cup biopsies, and 0.62 for punch biopsies. Conclusion and Clinical Importance: The histopathologic interpretation of a liver sample in the dog is unlikely to vary if the liver biopsy specimen contains at least 3- 12 portal triads. However, in comparison large necropsy samples, the accuracy of all tested methods was relatively low.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.

Background: Biopsy of the liver evaluates a small portion of tissue, with inferences made to the entire organ. The method and number of biopsies obtained are tempered by consideration of the risks and benefits. Recommendations often include biopsy of more than one liver lobe, although the consistency of histopathology among lobes in dogs is unknown. Hypothesis/Objectives: To describe the distribution of histopathologic abnormalities between liver lobes. We hypothesized that discordant results would be evenly distributed among all liver lobes. Animals: Seventy dogs undergoing necropsy. Methods: Prospective study. Liver samples were obtained from all lobes. A primary diagnosis was assigned to each liver sample based on the predominant histopathologic abnormality. Results: In this population of dogs, biopsy of at least 2 liver lobes identified the predominant histologic abnormality in 98.6% of the cases. Ten ( 14%) of the dogs had = 3 lobes in agreement and could not be assigned a predominant diagnosis. The same diagnosis was present in 6/ 6 lobes in 39 ( 56.5%) dogs, 5/ 6 lobes in 10 ( 14.5%) dogs, 4/ 6 lobes in 10 ( 14.5%) dogs, 3/ 6 lobes in 7 ( 10.1%) dogs, and 2/ 6 in 3 ( 4.3%) dogs. The number of discordant results did not differ between the liver lobes. Conclusion and Clinical Importance: The likelihood of obtaining a sample that is reflective of the predominant histologic abnormality in the liver is increased when multiple liver lobes are biopsied.

Background: The liver sampling technique in dogs that consistently provides samples adequate for accurate histopathologic interpretation is not known. Hypothesis/ Objectives: To compare histopathologic results of liver samples obtained by punch, cup, and 14 gauge needle to large wedge samples collected at necropsy. Animals: Seventy dogs undergoing necropsy. Methods: Prospective study. Liver specimens were obtained from the left lateral liver lobe with an 8 mm punch, a 5 mm cup, and a 14 gauge needle. After sample acquisition, two larger tissue samples were collected near the center of the left lateral lobe to be used as a histologic standard for comparison. Histopathologic features and numbers of portal triads in each sample were recorded. Results: The mean number of portal triads obtained by each sampling method were 2.9 in needle samples, 3.4 in cup samples, 12 in punch samples, and 30.7 in the necropsy samples. The diagnoses in 66% of needle samples, 60% of cup samples, and 69% of punch samples were in agreement with the necropsy samples, and these proportions were not significantly different from each other. The corresponding kappa coefficients were 0.59 for needle biopsies, 0.52 for cup biopsies, and 0.62 for punch biopsies. Conclusion and Clinical Importance: The histopathologic interpretation of a liver sample in the dog is unlikely to vary if the liver biopsy specimen contains at least 3- 12 portal triads. However, in comparison large necropsy samples, the accuracy of all tested methods was relatively low.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.

This report describes the methodology, diagnostic yield, and adverse events (AE) associated with frame-based stereotactic brain biopsies (FBSB) obtained from 26 dogs with solitary forebrain lesions. Medical records were reviewed from dogs that underwent FBSB using two stereotactic headframes designed for use in small animals and compatible with computed tomographic (CT) and magnetic resonance (MR) imaging. Stereotactic plans were generated from MR and CT images using commercial software, and FBSB performed both with (14/26) and without intraoperative image guidance. Records were reviewed for diagnostic yield, defined as the proportion of biopsies producing a specific neuropathological diagnosis, AE associated with FBSB, and risk factors for the development of AE. Postprocedural AE were evaluated in 19/26 dogs that did not proceed to a therapeutic intervention immediately following biopsy. Biopsy targets included intra-axial telencephalic masses (24/26), one intra-axial diencephalic mass, and one extra-axial parasellar mass. The median target volume was 1.99 cm(3). No differences in patient, lesion, or outcome variables were observed between the two headframe systems used or between FBSB performed with or without intraoperative CT guidance. The diagnostic yield of FBSB was 94.6%. Needle placement error was a significant risk factor associated with procurement of non-diagnostic biopsy specimens. Gliomas were diagnosed in 24/26 dogs, and meningioma and granulomatous meningoencephalitis in 1 dog each. AE directly related to FBSB were observed in a total of 7/26 (27%) of dogs. Biopsy-associated clinical morbidity, manifesting as seizures and transient neurological deterioration, occurred in 3/19 (16%) of dogs. The case fatality rate was 5.2% (1/19 dogs), with death attributable to intracranial hemorrhage. FBSB using the described apparatus was relatively safe and effective at providing neuropathological diagnoses in dogs with focal forebrain lesions.

The field of medical informatics comprises many subdisciplines, united by a common interest in the establishment of standards to facilitate the sharing, reuse, and understanding of information. This work depends in large part on the ability of controlled medical terminologies to represent relevant concepts. This work augments a controlled terminology to provide not only standardized content, but also standardized explanatory knowledge for use in expert systems. This experiment consisted of four phases centered on the use of the controlled terminology-- Systemized Nomenclature of Medicine (SNOMED). The first phase evaluated SNOMED's ability to express explanatory knowledge for clinical pathology. The second developed the Normalized Medical Explanation (NORMEX) syntax for expressing and storing pathways of causal reasoning in the domain of clinical pathology. The third segment examined SNOMED's capacity to represent concepts used in the NORMEX model of clinical pathology. The final phase incorporated NORMEX-based pathways of influence in a Bayesian network to assess ability to predict causal mechanisms as implied by serum analyte results. Findings from this work suggest that SNOMED's capacity to represent explanatory information parallels its coverage of clinical pathology findings. However, SNOMED currently lacks much of the content necessary for both of these purposes. Additional explanatory content was created with an ontology-modeling tool. The NORMEX syntax was defined by SNOMED hierarchy names. Complex sequences of explanations were created using the NORMEX syntax. In addition, medical explanatory knowledge represented in the NORMEX format could be stored in an architectural framework consistent with that used by a controlled terminology such as SNOMED. Once stored, such knowledge could be retrieved from storage without loss of meaning or introduction of errors. Lastly, a Bayesian network constructed from the retrieved NORMEX knowledge produced a network whose p

This report was prepared to describe the wind and wave conditions that can be expected in U.S. Coast Guard geographical operating areas. The intent is to provide operational program managers a tool to use when considering the potential applications of conventional and advanced marine vehicles (AMVs) to Coast Guard missions. It is also intended to supplement research determining the feasibility of alternate energy sources that involve wind or waves. This work was performed by the National Climatic Data Center under the direction of the U.S. Guard Research and Development Center for the Office of Research and Development.