Antioxidant status in dogs with idiopathic dilated cardiomyopathy.
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Biomedical subjects
Publications and source records attributed to D J Brown.
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OBJECTIVES/HYPOTHESIS: Knowledge and preservation of the neurovascular supply to strap muscles, such as the sternohyoid (SH) muscle, used in laryngotracheal reconstruction are important in preventing loss of tissue and bulk from ischemia and/or denervation. STUDY DESIGN: Arteriovenous and neural supply variations to the strap muscles were examined in cadaver specimens. METHODS: Strap muscle neurovascular supply was studied in 16 cadavers, including one transparent corrosion cast specimen with injected vessels. RESULTS: For the upper SH and upper belly of the omohyoid (OMO), the arterial supply consistently arose from a branch of the superior thyroid artery (STA) most commonly terminating at the cricothyroid membrane. The inferior SH was supplied by the inferior thyroid artery. The ansa cervicalis innervated the SH inferiorly with a branch below the loop. Each arterial branch to the muscles had an accompanying venous tributary. The corrosion cast specimen demonstrated that the arterial lumen diameters were almost threefold larger in branches entering the upper SH, compared with the lower SH or OMO. Small intramuscular arteries without axial supply were found within the middle third of the upper SH, the lower SH, and the upper OMO. CONCLUSIONS: It is possible to preserve neurovascular integrity in an inferiorly based SH flap. The superior and medial borders are released, with dissection of vascular supply laterally and deep to the muscle, and preservation of the inferior terminal ansa branch.
This paper presents an overview of the development of the Learning in Virtual Environments programme (LIVE), carried out in special education over the last four years. It is more precisely a project chronology, so that the reader can sense the historical development of the programme rather than giving emphasis to any one particular feature or breakthrough, which are covered in other papers and available through the authors. The project conception in a special school in Nottingham is followed by a description of the development of experiential and communicational virtual learning environments. These are followed, in turn, by the results of our testing programmes which show that experience gained in a virtual environment can transfer to the real world and that their use can encourage self-directed activity in students with severe learning difficulties. Also included is a discussion of the role of virtual learning environments (VLEs) in special education and of its attributes in the context of contemporary educational theory.
Cardiovascular disease (CVD), particularly in the form of coronary artery disease, is the leading cause of death in the United States. Research in the past 10 years links pathogenic low-density lipoprotein (LDL) modification to oxidation damage by free radicals. This review summarizes the major findings of CVD-related epidemiologic research and clinical trials conducted in the past 5 years on vitamins A, C, and E. Vitamin supplementation behaviors are discussed. In prospective studies, the intake of vitamins A, C, and E has been correlated with lower mortality rates. When recent clinical trials and oxidation studies are analyzed, the weight of evidence suggests that 100-400 IU of daily vitamin E over 2 years or more may be most efficacious in reducing low-density lipoprotein oxidation and positively influencing mortality rates from CVD in primary care. Research also supports vitamin E supplementation in patients with known CAD or a history of transient ischemic attacks. Persons with diabetes or hypertension as well as smokers may benefit from supplemental vitamin C intake. Targeted antioxidant vitamin intake should be included in CVD risk assessment and primary preventive counseling efforts.
When estimated in vitro, the parameters which describe the binding of radiolabelled analogues of cocaine to sites on the dopamine transporter are very much influenced by the methodology used. In the present study, a small animal positron emission tomography (PET) scanner was used to estimate in vivo saturation kinetics for two carbon-11 labelled compounds presently used to monitor dopamine terminal function. The binding of [11C]CFT (WIN 35,428) in rat striatum was adequately described by a single-site model, giving an apparent dissociation constant corresponding to an intravenous dose of 242 nmol/kg. In contrast, the binding of [11C]RTI-121 was better described by a two-site model with the 'high-affinity' site or state (dissociation constant = 1 nmol/kg) being significantly occupied at doses routinely used in PET scanning. Such findings cannot readily be predicted from in vitro work, but could aid in both the choice of ligand and the model used in quantification of scan data. While multi-dose in vivo PET studies are difficult in man, rat PET can easily be employed either pre-clinically for putative radioligands, or experimentally, to study drug interactions and receptor occupancy related to functional efficacy.
"Exotic" European cattle are highly susceptible to T. annulata infection. In immunised animals, several effective anti-parasite responses can be demonstrated, such as anti-macroschizont cytotoxic T cells (CTL), and nitric oxide killing of parasites. The failure of infected animals to mount an effective primary immune response suggests that the presence of the parasite directly interferes with the development of immunity. When the activation pathways of CD4+ T cells in draining lymph nodes were examined during the course of a primary infection it was found that the development of this essential arm of the immune response was altered. Instead of interacting with antigen presenting cells in the paracortex, the majority of CD4+ T cells were rapidly activated by developing infected cells in the medulla of the node. Activation of T cells by infected cells also drastically alters the cytokines produced by the T cells. During effective immune responses, the principal cytokine involved appears to be IL-2, with only small, controlled "bursts" of IFN gamma production. However, IL-2 responsiveness is only transient in animals undergoing primary infection, while IFNg production is greatly elevated. IFN gamma does not appear to control parasitised cells, and may even aid the growth of infected macrophages--large numbers of macrophages enter the cell cycle during the peak period of IFN gamma production. Uncontrolled parasite-induced IFN gamma production is also likely to account for the local failure of antibody responses. Germinal centres in infected lymph nodes lose normal morphology, with IFN gamma sensitive zones failing to develop. A third strategy which the parasite uses to evade immune response destruction is through affecting CTL activity. CTL in infected draining lymph nodes lose expression of the adhesion molecule CD2--a molecule is essential in adherence to target cells for lysis. CD2- CTL are unable to lyse macroschizont infected cells.
In Denmark, 0.4 and 3.4% of the human Salmonella Typhimurium cases registered between 1988 and 1993 were caused by DT2 and DT135, respectively. Separation of these two phage types was, however, problematic as only minor differences in lysis pattern and lysis strength occurred. Molecular characterization of 23 Danish isolates, 10 German isolates and the two type strains have subsequently been performed. With only minor exceptions, strains examined could be separated by combination of 0.5 agglutination, ribotyping, and PFGE typing into two major groups in conformity with their phage types. The differences between the two groups were, however, very small and it has not been completely clarified whether this grouping is the result of two independent types or of two related lines developing in different environments. It is concluded that the classification of related phage types DT2 and DT135 has to be supported by molecular methods.
The case histories of two patients who had had a spinal cord injury (SCI) were selected by the senior author and sent to four experts in the field of SCI. Based on the 1992 American Spinal Injury Association (ASIA) and International Medical Society of Paraplegia (IMSOP) standards, the four participants plus the senior author recorded the motor and sensory scores, the ASIA impairment scale (AIS), the neurological level (NL) and the zone of partial preservation (ZPP). Several minor scoring errors occurred among the participants, especially with motor scores when key muscles could not be tested due to pain, or external immobilization devices. Difficulties with interpretation occurred with the motor levels and the ZPP for the patient with a complete injury. This exercise points to the need for all examiners of SCI patients to thoroughly familiarize themselves with the standards and to use the motor and sensory scores to arrive at a NL and ZPP. They also indicate a need to revise the standards to clarify the determination of sensory levels and how to score muscles whose strength is inhibited by pain.
There has been little research on pain in the acute phase of spinal cord injury (SCI) rehabilitation. This study surveyed the pain experience and management strategies in such patients. The subjects consisted of inpatients who were undergoing rehabilitation following their acute injury, and were assessed regarding the presence and type of any pain upon admission to the rehabilitation ward, and reviewed weekly during their stay. They were reassessed on reporting any new pain. Pain intensity was recorded on a Visual Analogue Scale. The maximum intensity of pain during admission was compared to that at discharge. All interventions directed at pain management were documented. Patients were reviewed one year after discharge regarding current pain experience. Almost all of the patients (n = 23; 96%) experienced pain at some stage during their inpatient rehabilitation. Overall pain intensity for those patients with pain during inpatient admission decreased by the time of discharge. At the one year review however, pain intensity tended towards that seen on admission. The reasons for pain tending to increase after discharge were not apparent. Neuropathic and Myofascial Pain Syndrome (MPS) were the most common types of pain experienced. A combination of pharmacological, interventional, physical and psychological approaches were used in pain management. At one year review, neuropathic pain remained common while MPS and orthopaedic pain had decreased. Pain is a common and significant problem for many SCI patients and is a challenge for the treating team to manage.
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Theileria annulata is a protozoan parasite which infects and transforms bovine macrophages. Infected macrophages possess augmented antigen presentation capabilities, as they are able to activate the majority of T cells from unexposed animals. In vivo, T cells in the draining lymph node (principal site of parasite development) are activated 'non-specifically' by the parasite. This event is followed by failure of the immune response to control the infection. Protective immune responses against intra-macrophage protozoa are usually mediated by T helper 1 (Th1) T cell responses. Here we examine the cytokine responses made by T. annulata-activated T cells. We show that the outcome of in vitro activation of T cells by parasitized macrophages is a skewing of their cytokine responses towards preferential expression of interferon-gamma (IFN-gamma) mRNA. The in vitro response is mirrored during in vivo infection, as greatly elevated amounts of IFN-gamma protein are found in lymph efferent from infected lymph nodes, while expression of IL-4 mRNA within the node stops. IFN-gamma production does not correlate with protection against the parasite, as infected cells flourish during peak IFN-gamma production, and only very small amounts of IFN-gamma are produced during the effective immune response of an immunized animal. Overproduction of IFN-gamma and loss of IL-4 expression are also likely to account for the failure of B cells to reach the light zone of germinal centres, a developmental step which is tightly regulated by cytokines.
Tobacco rattle virus isolate PpK20 is transmitted by the nematode Paratrichodorus pachydermus. RNA 2 of the virus determines vector transmissibility and encodes the viral coat protein and two non-structural proteins with molecular masses of 29.4 kDa and 32.8 kDa. Deletions and a frameshift in the two non-structural genes did not interfere with encapsidation or co-replication of RNA 2 with RNA 1 after mechanical inoculation of plants. Mutations that affected the 29.4K gene or both non-structural genes abolished nematode transmission, whereas a large deletion in the 32.8K gene had no effect on transmission by P. pachydermus. It is concluded that the 29.4K gene but not the 32.8K gene is involved in transmission of isolate PpK20 by this vector.
We describe the use of 11CRTI-55 and the Multiple Objects Coincidences Counter (MOCC) to detect in-vivo binding to peripheral serotonin reuptake sites (left chest comprising platelet and lung serotonin reuptake sites) in man. Displacement and preloading experiments with clomipramine and venlafaxine in two healthy volunteers demonstrated that 11CRTI-55 binding is decreased in a dose-dependent fashion by both these drugs which bind to the serotonin transporter. In addition parallel data from the total head curve (representing 11CRTI-55 binding to central serotonin and dopamine (DA) reuptake sites) suggest that prior blockade of the serotonin transporter may be a useful strategy to maximize radioactive counts in the head when measuring the DA transporter. The MOCC is likely to be useful to determine sequential indices of relative serotonin reuptake blockade in patients on treatment.
Our previous studies have demonstrated a number of effects of cocaine on macrophage (M phi) functions. The present studies were initiated to ascertain the effects of cocaine on virus production in vitro. C57BL/6 mice were injected intraperitoneally with thioglycollate broth, and the peritoneal M phi collected 4 days later were cultured in 96-well microtiter plates as continuous monolayers. Various concentrations of cocaine were incubated with M phi for up to 5 days. Mouse hepatitis virus (MHV) was added to these cultures, which was followed by a methyl cellulose overlay. Cocaine caused a dose-dependent inhibition of viral plaques after 48 hr of incubation. The inhibitory activity was transferable to fresh cultures of M phi, inhibiting both plaque size and number. Specific polyclonal antibodies to alpha + beta-interferon but not tumor necrosis factor or transforming growth factor-beta partially reversed the inhibition of both plaque size and plaque number. It appears that MHV induced interferon in cultured M phi, an effect that was enhanced by cocaine. Since cocaine has been reported to interfere with calcium mobilization, studies were done using ionomycin, a calcium ionophore, in order to reverse possible effects on intracellular calcium that could affect virus production. The presence of ionomycin completely reversed the inhibition of virus production by cocaine. The antiviral effects of cocaine appear to be caused by modulation of intracellular calcium and, to a lesser extent, by the enhancement of interferon production.
Magnesium deficiency has been associated with the development of cardiovascular disease in several species. Cats may be predisposed to alterations in magnesium status because of recent changes in the composition of commercial feline diets. The purposes of this study were 1) to examine the dietary history of cats with hypertrophic cardiomyopathy (HCM), 2) to study magnesium status of cats with HCM compared to normal cats, and 3) to determine the effects of magnesium supplementation in cats with HCM. In part 1 of the study, diets of 65 cats with HCM were examined retrospectively. Forty of the 45 cats for which diets could be determined (89%) ate a diet designed to be magnesium-restricted and/or to produce an acidic urine. In part 2 of the study, 10 cats with HCM were compared to 10 healthy control cats for serum creatinine and magnesium; urine creatinine and magnesium, urine specific gravity and pH, and fractional excretion of magnesium. Urine creatinine and specific gravity were higher in control cats than in cats with HCM. No other differences were found between the 2 groups. In part 3, cats with HCM were supplemented with either 210 mg magnesium chloride (n = 15) or 210 mg lactose (n = 15) for 12 wk. No differences between the 2 groups were found for changes in either magnesium status or echocardiographic parameters. However, the 30 cats with HCM, as a group, did show significant improvements in measures of cardiac hypertrophy over the 12-week period. This was likely the result of treatment with other medications, rather than the magnesium supplementation. The results of this study suggest that cats with HCM are likely to be fed magnesium-restricted diets, but that they do not appear to have altered magnesium status compared to healthy controls.
OBJECTIVE: To describe the historical, clinical, and echocardiographic findings in Dalmatians with dilated cardiomyopathy (DCM). DESIGN: Retrospective case series. SAMPLE POPULATION: 9 Dalmatians with a diagnosis of DCM and congestive heart failure (CHF), 9 Doberman Pinschers with DCM and CHF, and 9 dogs of other breeds with DCM and CHF. PROCEDURE: Disease history; signalment; physical, radiographic, and echocardiographic examination findings; treatment; and outcome from medical records were analyzed. RESULTS: All Dalmatians were male, with a mean age of 6.8 years. Eight dogs had been fed a commercially available low-protein diet formulated for the prevention of urate uroliths. All dogs had clinical signs consistent with left-sided CHF and had marked left ventricular systolic dysfunction and severe left ventricular dilatation, although arrhythmias were not an important finding in this series of dogs. Median duration of survival was 10 months. CLINICAL IMPLICATIONS: The DCM syndrome in Dalmatians has some qualities that are distinct from DCM in other breeds of dogs.
Type VI collagen and gelatinase A are synthesized by human keratocytes in vitro. Keratoconus is a corneal disease that has increased gelatinase A activity. Normal keratocyte culture media analyzed by Western blotting with polyclonal antibody to type VI collagen showed a single 140 kDa band that increased in intensity after phorbol ester treatment. The same 140 kDa band was absent in media collected from keratoconus keratocytes cultured with or without phorbol ester. We speculate that in keratoconus keratocyte cultures, type VI collagen may be degraded or modified by the increased gelatinase A activity so as not to be recognized by the type VI antibody.
Mutations were introduced into four genes encoded by RNA2 of pea early browning virus (PEBV) to determine their possible involvement in the transmission of this virus by nematodes. Deletion of 28 amino acids from the C-terminus of the coat protein abolished the formation of virus particles. Deletion of 15 amino acids at the C-terminus did not affect particle formation but did abolish nematode transmission. In contrast, deletion of 13 amino acids immediately preceding the 16 C-terminal residues did not affect particle formation and decreased rather than abolished nematode transmission. A deletion in the gene encoding a 29-kDa protein and a frameshift mutation in the gene encoding a 23-kDa protein both abolished transmission without affecting virus particle formation. Mutations in an ORF encoding a 9-kDa protein, which is located on the genome between the coat protein gene and 29K gene, gave conflicting results. Removal of the AUG initiation codon from the 9K ORF had no effect on transmission, whereas the introduction of a frameshift mutation, which would prematurely terminate expression of the putative 9-kDa protein, decreased the frequency of transmission. The results show that the coat protein and probably all three of the other RNA2-encoded proteins play a role in the transmission of PEBV by vector nematodes.