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Biomedical subjects

D P O'Brien

Publications and source records attributed to D P O'Brien.

At least 19 recordsLinked to original sources

Detection of spinal ataxia in horses using fuzzy clustering of body position uncertainty.

REASONS FOR PERFORMING STUDY: Subjective neurological evaluation in horses is prone to bias. An objective method of spinal ataxia detection is not subject to these limitations and could be of use in equine practice and research. HYPOTHESIS: Kinematic data in the walking horse can differentiate normal and spinal ataxic horses. METHODS: Twelve normal and 12 spinal ataxic horses were evaluated by kinematic analysis walking on a treadmill. Each body position signal was reduced to a scalar measure of uncertainty then fuzzy clustered into normal or ataxic groups. Correct classification percentage (CCP) was then calculated using membership values of each horse in the 2 groups. Subsequently, a guided search for measure combinations with high CCP was performed. RESULTS: Eight measures of body position resulted in CCP > or = 70%. Several combinations of 4-5 measures resulted in 100% CCP. All combinations with 100% CCP could be obtained with one body marker on the back measuring vertical and horizontal movement and one body marker each on the right fore- and hindlimb measuring vertical movement. CONCLUSIONS AND POTENTIAL RELEVANCE: Kinematic gait analysis using simple body marker combinations can be used objectively to detect spinal ataxia in horses.

Algorithms↗

Temporal and spatial distribution of paramoebae in the water column--a pilot study.

Amoebic gill disease is the main disease affecting the salmonid industry in Tasmania, but no information on the distribution of the causative pathogen, Neoparamoeba pemaquidensis, in the aquatic environment is available. This pilot study aimed to determine temporal and spatial distributions of paramoebae species in the water column, using an immuno-dot blot technique. Water samples were collected from inside fish cages at various depths (0.5, 5.5 and 11.0 m) in both summer and winter, as well as various distances (0, 0.5, 240, 280, 750 and 1100 m) away from the sea cage and farming site. Paramoebae densities were estimated using the most probable number technique (MPN). Temperature, salinity, dissolved oxygen, turbidity, nitrite and nitrates, and bacterial counts were measured for each water sample. Data were analysed using a residual maximum likelihood test and significant associations between paramoebae densities and environmental factors were analysed. Results showed that densities were significantly higher in summer (P = 0.017), at 5.5 m depth (P = 0.029), and reduced to the lowest density at 1100 m away from the cage sites (P = 0.008). Bacterial counts, turbidity and temperature were found to be significantly associated with paramoebae densities.

Amoebida↗

Laminin alpha 2 (merosin)-deficient muscular dystrophy and demyelinating neuropathy in two cats.

We report laminin alpha 2 (merosin) deficiency associated with muscular dystrophy and demyelinating neuropathy in two cats. The cats developed progressive muscle weakness, and atrophy. Either hypotonia or contractures resulted in recumbency, necessitating euthanasia. Muscle biopsies showed dystrophic changes including marked endomysial fibrosis, myofiber necrosis, variability of fiber size, and perimysial lipid accumulation. Immunohistochemistry showed that laminin alpha 2 chain was absent or reduced, while dystrophin and all the components of the dystrophin-associated glycoprotein complex were present and normal. One cat was examined in detail. Motor nerve conduction velocity (MNCV) was decreased, and ultrastructurally the peripheral nerves showed Schwann cell degeneration and demyelination. Brain imaging was not performed, but white matter changes were not apparent in the brain at necropsy. The disease in these cats is similar to primary or secondary merosin (laminin alpha 2)-deficient congenital muscular dystrophy (CMD) in humans and to dystrophia muscularis in mice.

Animals↗

Epithelial permeability is not increased in rats following small bowel resection.

BACKGROUND: Increased intestinal permeability and translocation of bacteria and/or bacterial products may cause infection and liver dysfunction in patients with the short bowel syndrome. In previous studies, serum from mice undergoing small bowel resection (SBR) enhanced growth of cultured rat intestinal epithelial cells (RIEC-6), implicating a role for a serum factor(s) in the enterocyte response to SBR. These experiments tested the hypothesis that epithelial cell permeability is increased following SBR. MATERIALS AND METHODS: Male Sprague-Dawley rats underwent a 75% SBR or sham operation. Intestinal permeability in the remnant ileum was determined by Ussing chambers on Postoperative Day (POD) 3. Additionally, serum was collected on POD 1, 3, and 7 and mesenteric lymph was harvested on POD 3. Once confluent, RIEC-6 cells were incubated for 3 days in media supplemented with 10% fetal bovine serum (FBS; control), 1% FBS, 1% FBS plus 9% Sham serum, or 1% FBS plus 9% SBR serum or exposed to media with varied concentrations of SBR or Sham lymph. Monolayer permeability was determined by measuring the passage of dextran-rhodamine. RESULTS: Intestinal permeability was reduced in rats undergoing SBR. Sham serum-treated monolayers demonstrated the greatest permeability. Incubation with SBR serum reduced permeability to near control media. There were no permeability differences between SBR and Sham lymph-treated monolayers. CONCLUSION: The early adaptive response of the remnant intestine after SBR is associated with reduced permeability. These results suggest an alternative mechanism for the increased bacterial translocation that has been described following SBR.

Adaptation, Biological↗

Risk factors for development of dysautonomia in dogs.

OBJECTIVE: To identify risk factors associated with dysautonomia in dogs. DESIGN: Case-control study. ANIMALS: 42 dogs with dysautonomia examined between October 1988 and January 2000 and 132 control dogs examined during the same period for an unrelated problem. PROCEDURE: Information was gathered from medical records and surveys mailed to owners of case and control dogs. RESULTS: 42 case and 132 control dogs were included; completed surveys were returned by owners of 30 case and 103 control dogs. Dogs with dysautonomia were significantly younger (median, 18 months) than control dogs (median, 60 months) and more likely to come from rural areas and to spend > or =50% of their time outdoors. Compared with rural control dogs that spent at least some time outdoors, affected dogs were more likely to have access to pasture land, farm ponds, and cattle, and to have consumed wildlife, at least occasionally. The largest numbers of dogs with dysautonomia were identified during February and April, with relatively few dogs identified during the summer and early fall. CONCLUSION AND CLINICAL RELEVANCE: Although the cause of dysautonomia is unknown, results suggest that dogs with dysautonomia were significantly more likely to live in rural areas and spend > or =50% of their time outdoors than were control dogs examined for unrelated diseases.

Age Factors↗

Xerostomia, xerophthalmia, and plasmacytic infiltrates of the salivary glands (Sjögren's-like syndrome) in a cat.

A 2.5-year-old domestic shorthair cat was evaluated because of dysphagia and weight loss of 4 weeks' duration. MIld blepharospasm and conjunctival hyperemia were evident in both eyes, oral mucous membranes were tacky on palpation, and salivary glands were enlarged. Results of a Schirmer tear test were 0 mm/min for both eyes. Administration of atropine did not cause salivation or caused secretion fo thick rope-like saliva. Examination of biopsy specimens of salivary glands revealed a plasmacytic infiltrate. Sjögren's syndrome (SS) was diagnosed. Oral administration of prednisone was instituted but was discontinued after a minimal positive response was evident 6 weeks after initiation of treatment. Palliative treatment with a 6% solution of pilocarpine 4 to 5 times/d, cyclosporine, hylan A, and neomycin-polymyxin-bacitracin ophthalmic ointment resulted in clinical improvement in the cat. Although reported rarely in animals, SS may be more common than currently is recognized. Most treatment regimens for SS are aimed at alleviating clinical signs.

Animals↗

Serum from mice after small bowel resection enhances intestinal epithelial cell growth.

BACKGROUND/PURPOSE: The adaptive response of the intestine to massive small bowel resection (SBR) is remarkably complex. An in vitro model of adaptation may facilitate the elucidation of signaling pathways involved in this process. In an effort to establish such a model, the effects of serum from resected mice on cultured intestinal epithelial cells were studied. METHODS: Serum was collected and pooled from male ICR mice 3 days after either 50% SBR or sham operation. Rat intestinal epithelial cells (RIEC-6) were plated at equal density and grown in the presence of 1% fetal bovine serum (FBS), 10% FBS, 1% FBS plus 9% sham serum, or 1% FBS plus 9% SBR serum. Cell number, proliferation, and caspase-3 activity were determined. RESULTS: RIEC-6 cell growth was reduced significantly in 1% FBS or sham serum. SBR serum markedly accelerated cell growth and proliferation when compared with all other groups and significantly suppressed caspase-3 activity. CONCLUSIONS: Massive intestinal resection in mice results in a serum factor that induces intestinal cell growth in vitro. This in vitro model of trophic signaling will permit further detailed investigations into the mechanisms of intestinal adaptation.

Adaptation, Biological↗

Intestinal adaptation: structure, function, and regulation.

After massive small bowel resection (SBR), the remnant intestine undergoes an adaptive process characterized by increases in wet weight, protein and DNA content, villus height and crypt depth, and absorptive surface area. These changes are the result of a proliferative stimulus that increases crypt cell mitosis and augments cellular progression along the villus axis. Functionally, there is upregulation of the Na(+)/glucose cotransporter, Na(+)/H(+) exchanger, and other enzymes involved in intestinal digestion and absorption. These physiologic events are a compensatory response to the sudden loss of digestive and absorptive capacity by the remnant intestine. A major consequence of inadequate intestinal adaptation is lifelong dependence on parenteral nutrition, which results ultimately in cholestatic liver dysfunction. Furthermore, adaptation may be associated with changes in intestinal permeability and an increased risk of bacterial translocation and sepsis. Several mediators thought to be integral to the postresection adaptive response have been proposed, including luminal nutrients, gastrointestinal secretions, and humoral factors. A thorough understanding of intestinal adaptation will be essential in the rational development of new and innovative therapies that amplify this complex but important process.

Animals↗

Malignant eccrine poroma with spinal and cerebrospinal fluid metastases: case report.

OBJECTIVE AND IMPORTANCE: A rare case of metastasizing malignant eccrine poroma (porocarcinoma) is described. This case is unique because metastasis resulted in hydrocephalus in the cerebrospinal fluid and spinal cord compression in the lumbar spine. CLINICAL PRESENTATION: A 57-year-old man presented with acute confusion, lower limb weakness, and urinary concerns. Investigation revealed acute hydrocephalus and extradural cord compression of the lumbar spine. INTERVENTION: The acute hydrocephalous was treated with a ventriculoperitoneal shunt. The spinal cord and conus were decompressed by laminectomy and supplemented with pedicular screw fixation. CONCLUSION: The case reported here is the first with metastases from a malignant eccrine poroma causing spinal cord compression and acute hydrocephalus. Our observation is compared with a review of the literature.

Acrospiroma↗

Nontuberculous mycobacterial disease in northern Australia: a case series and review of the literature.

We performed a retrospective/prospective review of all cases of disease due to nontuberculous mycobacteria (NTM) reported in the Northern Territory, Australia, during the period 1989-1997. Fifty-eight cases were reported, with an average yearly incidence of 3.9 cases per 100,000 persons. The number increased significantly for the second half of the study period (39 vs. 19 cases; P<.02). The yearly incidence of pulmonary Mycobacterium avium/Mycobacterium intracellulare complex (MAC) disease not associated with human immunodeficiency virus (HIV) infection was 2.1 cases per 100,000 population. MAC was the most common isolate (78%) and pulmonary disease the most frequent clinical presentation (62%). Disease due to NTM or MAC was not found more commonly in rural areas. Significant risks for non-HIV-associated pulmonary MAC disease included male sex (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.0-4.5) and age >50 years (OR, 26.5; 95% CI, 10.9-67.3), but aboriginal people appeared underrepresented (OR, 0.77; 95% CI, 0.30-1.87). Mycobacterium tuberculosis was almost 5 times more likely than NTM to be the cause of non-HIV-associated mycobacterial pulmonary disease (153 vs. 32 cases; OR, 4.79; 95% CI, 3.22-7.14). Mycobacterial lymphadenitis in aboriginal children was more likely to be tuberculous than nontuberculous (OR, 6.5; 95% CI, 1.4-41.7), but not in nonaboriginal children (OR, 1.0). With treatment, 66% of the cases of non-HIV-associated pulmonary MAC disease had favorable outcomes, and 7% of patients had progressive fatal disease. Outcomes of therapy for lymphadenitis and skin/soft-tissue disease were excellent, but those of HIV-associated disseminated MAC disease were poor.

AIDS-Related Opportunistic Infections↗

Epidermal growth factor is critical for intestinal adaptation following small bowel resection.

The loss of small intestinal mucosal surface area is a relatively common clinical situation seen in both the pediatric and adult population. The most frequent causes include mesenteric ischemia, trauma, inflammatory bowel disease, necrotizing enterocolitis, and volvulus. Following surgical resection, the remnant intestine compensates or adapts to the loss of native bowel by increasing its absorptive surface area and functional capacity. Unfortunately, many patients fail to adapt adequately, and are relegated to lifelong intravenous nutrition. Research into intestinal adaptation following small bowel resection (SBR) has evolved only recently from the gross and microscopic level to the biochemical and genetic level. As understanding of this process has increased, numerous therapeutic strategies to augment adaptation have been proposed. Epidermal growth factor (EGF) is an endogenous peptide that is secreted into the gastrointestinal tract and able to influence gut ontogeny, as well as mucosal healing. Early studies have demonstrated its ability to augment the adaptive process. Focusing on a murine model of massive intestinal loss, the morphological, structural, biochemical, and genetic changes that occur during the intestinal adaptive process will be reviewed. The role of EGF and its receptor as critical mediators of the adaptive process will be discussed. Additionally, the ability of EGF to augment intestinal proliferation and diminish programmed cell death (apoptosis) following SBR will be examined. Enhancing adaptation in a controlled manner may allow patients to transition off parenteral nutrition to enteral feeding and, thereby, normalize their lifestyle.

Adaptation, Physiological↗

The formation of heterodimers by vancomycin group antibiotics.

The formation of heterodimers in mixtures of glycopeptide antibiotics has been detected by electrospray ionization mass spectrometry (ESI-MS), and dimerization constants have been determined. By using NMR spectroscopy, it has been shown that these heterodimers indeed exist in aqueous solution. The dimerization constants obtained by NMR spectroscopy are in good agreement with those determined by ESI-MS. Structural information on the heterodimer interface of some of the heterodimers is obtained by using two-dimensional NMR techniques and reveals that these heterodimers are similar in structure to the homodimers.

Anti-Bacterial Agents↗

Increasing the frequency of T-cell precursors specific for a cryptic epitope of hen-egg lysozyme converts it to an immunodominant epitope.

Efforts to understand the mechanisms that govern how immunodominant T-cell epitopes are selected from protein antigens have focused mostly on differences in the efficiency of processing and presentation of peptide/major histocompatibility complex (MHC) complexes by antigen-presenting cells, while little attention has been directed at the role of the T-cell repertoire. In this report, the influence of the T-cell repertoire on immunodominance was investigated using transgenic mice that express the beta chain from a T-cell receptor specific for a cryptic Ek restricted epitope of hen-egg lysozyme, HEL85-96. In these mice, the frequency of HEL85-96-specific T-cell precursors is increased 10-20-fold over non-transgenic mice. Transgenic mice respond as well as non-transgenic controls to intact HEL, even though they respond poorly or not at all to a variety of other antigens, including the dominant H-2k restricted epitopes of HEL. Following immunization with native HEL, the only HEL peptide that could recall a response in vitro in the transgenic mice was HEL85-96. Therefore, this normally cryptic epitope is the sole immunodominant epitope in the transgenic mice, and this alteration in immune response is due solely to an increase in the frequency of specific T-cell precursors. An analysis of four additional H-2k restricted cryptic epitopes of HEL suggests that three are similarly limited by T-cell frequency, and that only one is consistent with a defect in efficient antigen presentation. This indicates that there are at least two different types of cryptic epitopes, one in which crypticity is caused by inefficient processing or presentation, and another in which the frequency of specific T-cell progenitors is limiting.

Animals↗

Dynamic helical computed tomography scan accurately detects hemorrhage in patients with pelvic fracture.

BACKGROUND: The purpose of this study was to evaluate the use of dynamic helical computed tomography (CT) scan for screening patients with pelvic fractures and hemorrhage requiring angiographic embolization for control of bleeding. METHODS: Patients admitted to the trauma service with pelvic fractures were identified from the trauma registry. Data retrieval included demographics, hemodynamic instability, Injury Severity Score, blood transfusion requirement, length of stay, and mortality. CT scans obtained during the initial evaluation were reviewed for the presence of contrast extravasation and correlated with angiographic findings. Data are reported as mean +/- SEM, with P<.05 considered significant. RESULTS: Seven thousand seven hundred eighty-one patients were admitted from June 1994 to May 1999. A pelvic fracture was diagnosed in 660 (8.5%). Two hundred ninety (44.0%) dynamic helical CT scans were performed, of which 13 (4.5%) identified contrast extravasation. Nine (69%) were hemodynamically unstable and had pelvic arteriography performed. Arterial bleeding was confirmed in all and controlled by embolization. Patients with contrast extravasation had significantly greater Injury Severity Score, blood transfusion requirement and length of stay. Sensitivity, specificity, and accuracy of CT scan for identifying patients requiring embolization were 90.0%, 98.6%, and 98.3%, respectively. CONCLUSIONS: Early use of dynamic helical CT scanning in the multiply injured patient with a pelvic fracture accurately identifies the need for emergent angiographic embolization.

Abdominal Injuries↗

Psoas abscess secondary to discitis: a case report of conservative management.

We report a case of secondary psoas abscess in a 37-year-old man with a 3-week history of severe low backache managed conservatively without surgical drainage. Apart from bilaterally restricted straight leg raising (<70 degrees), his neurologic examination was within normal limits. Magnetic resonance imaging showed discitis of the L3-L4 space and a left-sided secondary psoas abscess. Aspiration biopsy of the abscess material under radiologic control isolated Staphylococcus aureus, which responded to appropriate antibiotic therapy with complete resolution. A high index of suspicion is necessary for diagnosis of psoas abscess, which should be considered in patients with pyrexia and backache with a neurologic examination that is otherwise normal. We discuss the recommendations for surgical and nonsurgical approaches.

Abscess↗

Ablation of tumor necrosis factor receptor type I (p55) alters oxygen-induced lung injury.

Hyperoxic lung injury, believed to be mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines, complicates the care of many critically ill patients. The cytokine tumor necrosis factor (TNF)-alpha is induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. Both TNF-alpha treatment and blockade with anti-TNF antibodies increased survival in mice exposed to hyperoxia. In the current study, to determine if pulmonary oxygen toxicity is dependent on either of the TNF receptors, type I (TNFR-I) or type II (TNFR-II), TNFR-I or TNFR-II gene-ablated [(-/-)] mice and wild-type control mice (WT; C57BL/6) were studied in >95% oxygen. There was no difference in average length of survival, although early survival was better for TNFR-I(-/-) mice than for either TNFR-II(-/-) or WT mice. At 48 h of hyperoxia, slightly more alveolar septal thickening and peribronchiolar and periarteriolar edema were detected in WT than in TNFR-I(-/-) lungs. By 84 h of oxygen exposure, TNFR-I(-/-) mice demonstrated greater alveolar debris, inflammation, and edema than WT mice. TNFR-I was necessary for induction of cytokine interleukin (IL)-1beta, IL-1 receptor antagonist, chemokine macrophage inflammatory protein (MIP)-1beta, MIP-2, interferon-gamma-induced protein-10 (IP-10), and monocyte chemoattractant protein (MCP)-1 mRNA in response to intratracheal administration of recombinant murine TNF-alpha. However, IL-1beta, IL-6, macrophage migration inhibitory factor, MIP-1alpha, MIP-2, and MCP-1 mRNAs were comparably induced by hyperoxia in TNFR-I(-/-) and WT lungs. In contrast, mRNA for manganese superoxide dismutase and intercellular adhesion molecule-1 were induced by hyperoxia only in WT mice. Differences in early survival and toxicity suggest that pulmonary oxygen toxicity is in part mediated by TNFR-I. However, induction of specific cytokine and chemokine mRNA and lethality in response to severe hyperoxia was independent of TNFR-I expression. The current study supports the prediction that therapeutic efforts to block TNF-alpha receptor function will not protect against pulmonary oxygen toxicity.

Animals↗

Regional anesthesia of the infraorbital and inferior alveolar nerves during noninvasive tooth pulp stimulation in halothane-anesthetized cats.

OBJECTIVE: To determine whether anesthesia of the infraorbital and inferior alveolar nerves abolishes reflex-evoked muscle action potentials (REMP) during tooth-pulp stimulation in halothane-anesthetized cats. ANIMALS: 8 healthy adult cats. PROCEDURE: In halothane-anesthetized cats, an anodal electrode was attached to the tooth to be stimulated and a platinum needle cathodal electrode was inserted in adjacent gingival mucosa. Cathodal and anodal electrodes were moved to the upper and lower canine, upper fourth premolar, and lower first molar teeth for stimulation; baseline REMP was recorded. A 25-gauge 1-cm needle was inserted 0.5 cm into the infraorbital canal. A 25-gauge 1-cm needle was inserted 1 cm rostral to the angular process of the ramus, and advanced 0.5 cm along the medial aspect. Chloroprocaine was injected at each site. Each tooth was stimulated every 10 minutes for 90 minutes. RESULTS: REMP was abolished within 10 minutes for all upper teeth, except for the upper canine tooth in 1 cat, and abolished within 10 minutes for lower teeth in 4 cats. In 1 cat, REMP was not abolished in the lower first molar tooth. In 3 cats, REMP was not abolished in the lower canine and first molar teeth. At 90 minutes, REMP was restored for all teeth except the lower canine tooth in 1 cat, for which REMP was restored at 120 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Regional anesthesia of the infraorbital and inferior alveolar nerves may provide dental analgesia in cats.

Anesthesia, Conduction↗