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Biomedical subjects

D Tyrrell

Publications and source records attributed to D Tyrrell.

At least 19 recordsLinked to original sources
PubMed2006

Transient renal tubulopathy in a racing Greyhound.

A 2-year-old female Greyhound was presented for inappetence and lethargy. On referral, results of diagnostic tests indicated renal glucosuria, increased excretion of selected amino acids and abnormal fractional excretion of electrolytes consistent with renal tubular dysfunction. Systemic blood pressure was elevated. Renal biopsy revealed mild proximal renal tubular damage consistent with a subacute toxic or hypoxic insult. Systemic hypertension, renal glucosuria and altered fractional excretion of electrolytes resolved during the 7 day period of hospital treatment. The Greyhound resumed training without recurrence of renal dysfunction.

Amino Acids↗
PubMed2005

Balloon dilation of a urethral stricture in a dog.

A 2-year-old male neutered Scottish Terrier presented with dysuria caused by complete urethral obstruction due to a stricture secondary to catheter-induced trauma. The urethral obstruction was resolved by balloon dilation of the stricture under fluoroscopic guidance.

Animals↗
PubMed2004

Interferon treatment of multiple pulmonary malignancies associated with papilloma virus.

Over a period of four years, beginning in spring 1988, a previously healthy man developed a primary squamous cell carcinoma of the tonsil, treated with radiotherapy, followed by 10 distinct, primary bronchial squamous cell carcinomas. Four of the cancers were surgically resected, all of which were positive by hybridization for human papilloma virus (type 16). Following the institution of alpha interferon, three smaller lesions disappeared and a larger one shrank in size, facilitating surgical resection. Over the following seven years no new ones have appeared. The finding of papilloma virus in malignancies should prompt consideration of antiviral therapy.

Adult↗
PubMed2001

Antivirals for the common cold.

BACKGROUND: The common cold is a ubiquitous short and usually mild illness for which preventive and treatment interventions have been under development since the mid-40s. As our understanding of the disease has increased, more experimental antivirals have been developed. This review attempts to draw together experimental evidence of the effects of these compounds. OBJECTIVES: To identify, assemble, evaluate and (if possible) synthesise the results of published and unpublished randomised controlled trials of the effects of antivirals to prevent or minimise the impact of the common cold. SEARCH STRATEGY: We searched electronic databases, corresponded with researchers and handsearched the archives of the MRC's Common Cold Unit (CCU). SELECTION CRITERIA: We included original reports of randomised and quasi-randomised trials assessing the effects of antivirals on volunteers artificially infected and in individuals exposed to colds in the community. DATA COLLECTION AND ANALYSIS: We included 241 studies assessing the effects of Interferons, interferon-inducers and other antivirals on experimental and naturally occurring common colds, contained in 230 reports. We structured our comparisons by experimental or community setting. MAIN RESULTS: Although intranasal interferons have high preventive efficacy against experimental colds (protective efficacy 46%, 37% to 54%) and to a lesser extent against natural colds (protective efficacy 24%, 21% to 27%) and are also significantly more effective than placebo in attenuating the course of experimental colds (WMD 15.90, 13.42 to 18.38), their safety profile makes compliance with their use difficult. For example, prolonged prevention of community colds with interferons causes blood-tinged nasal discharge (OR 4.52, 3.78 to 5.41). Dipyridamole (protective efficacy against natural colds 49%, 30% to 62%), ICI 130, 685 (protective efficacy against experimental colds 58%, 35% to 74% ), Impulsin (palmitate) (protective efficacy against natural colds 44%, CI 35% to 52% ) and Pleconaril (protective efficacy against experimental colds 71%, 15% to 90% ) appear to have important antiviral properties and are well-tolerated. The evidence of effectiveness of other compounds in the treatment of experimental or natural colds is sparse. REVIEWER'S CONCLUSIONS: There are no licensed effective antivirals for the common cold. Because prolonged intranasal administration causes a clinical picture which is not distinguishable from the common cold, interferons have no place in everyday use. Further assessment of the effects of dipyridamole, palmitate, ICI 130, 685, Impulsin and Pleconaril in preventing the common cold should be carried out. Given the multi-agent nature of the causes of the common cold, future research efforts should focus on non virus-specific compounds.

Administration, Intranasal↗
PubMed2001

Progressive neurological signs associated with systemic mastocytosis in a dog.

A 9-year-old dog was presented with nonregenerative anaemia and severe thrombocytopenia, diarrhoea, spinal hyperalgesia and progressive hindlimb paresis. A moderately well differentiated cutaneous mast cell tumour (MCT) was removed from the skin of the right elbow along with the enlarged right prescapular lymph node. Due to deterioration of the dog's neurological condition, euthanasia was performed. On necropsy examination, haemorrhage and accumulations of poorly differentiated mast cells were found in the lumbosacral region and cauda equina. This article describes an unusual presentation of systemic mastocytosis and the previously unreported finding of metastasis of mast cells to the spinal cord.

Animals↗
PubMed2000

Specificities of heparin-binding sites from the amino-terminus and type 1 repeats of thrombospondin-1.

Interactions of heparin with intact human thrombospondin-1 (TSP1) and with two heparin-binding fragments of TSP1 were characterized using chemically modified heparins, a vascular heparan sulfate proteoglycan, and a series of heparin oligosaccharides prepared by partial deaminative cleavage. The avidity of TSP1 binding increased with oligosaccharide size, with plateaus at 4 to 6 and at 8 to 10 monosaccharide units. The dependence on oligosaccharide size for binding to the recombinant amino-terminal heparin-binding domain of TSP1 was the same as that of the intact TSP1 molecule but differed from that of a synthetic heparin-binding peptide from the type 1 repeats, suggesting that the interaction between intact TSP1 and heparin is primarily mediated by the amino-terminal domain. Based on activities of chemically modified heparins, binding to TSP1 depended primarily on 2-N- and 6-O-sulfation of glucosamine and to a lesser degree on 2,3-O-sulfation and the carboxyl residues of the uronic acids. In contrast, all of these modifications were required for binding of heparin to the type 1 repeat peptides. Affinity purification of heparin octasaccharides on immobilized TSP1 type 1 repeat peptides revealed a preference for oligosaccharides containing the disaccharide sequence IdoA(2-OSO(3))alpha1-4-GlcNS(6-OSO(3)). Binding of these oligosaccharides to the peptide required the Trp residues. These data demonstrate that the heparin-binding specificities of intact TSP1 and peptides from the type 1 repeats overlap with that of basic fibroblast growth factor (FGF2) and are consistent with the ability of these TSP1-derived molecules to inhibit FGF2-stimulated angiogenesis.

Amino Acid Sequence↗
PubMed2000

A phase I trial in HIV negative healthy volunteers evaluating the effect of potent adjuvants on immunogenicity of a recombinant gp120W61D derived from dual tropic R5X4 HIV-1ACH320.

Thirty healthy HIV negative volunteers were randomised to receive 200 micrograms of rgp120W61D in either: 3D-MPL and QS21, with an oil and water emulsion (SBAS-2) (13); or 3D-MPL and QS21 (SBAS-1) (11); or alum (six). Immunizations were given at 0, 4 and 28 weeks and 23 (77%) participants completed the schedule. Adverse events were more frequent (P < 0.001) and more severe (P < 0.001) in the SBAS-2 group. Binding antibodies to the homologous rgp120W61D were detected after the first immunisation only in those receiving SBAS-1 and SBAS-2, were maximal after the third immunization in all three groups, and persisted to week 84 only in the novel adjuvant groups. These differences were significant (p = 0.02). Neutralising antibodies to TCLA-strains of HIV-1 were observed after the second immunization in all three groups, were maximal after the third immunization, but did not neutralise homologous or heterologous PBMC derived primary HIV-1 isolates. Proliferative T-cell responses to rgp120W61D were maximal after the second immunization and reached very high values in the SBAS-2 group. HIV-1 specific CD8+ MHC Class I restricted cytotoxic T-lymphocytes were not seen in a subset of participants tested at a single timepoint. SBAS-2 with rgp120W61D induced antibody titres as high as those seen in HIV infection, but the quality of the antibodies remained different in that there was no evidence of primary isolate neutralisation. Although cell-mediated immunity was enhanced by SBAS-2 in terms of lymphoproliferative responses, HIV-1 specific CD8+ cytotoxicity was not demonstrated.

AIDS Vaccines↗
PubMed1998

Matrix metalloproteinase inhibitors: a structure-activity study.

Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

Chromatography, High Pressure Liquid↗
PubMed1998

An analysis of operations for gastroesophageal reflux disease: identifying the important technical elements.

BACKGROUND: Better understanding of the pathogenesis of gastroesophageal reflux disease in recent years has not been accompanied by appreciable advances in the design of antireflux operations. In many cases, operations are still being performed just as they were described 30 years ago. It is important now to go beyond the eponymous procedures traditionally associated with antireflux operations and to identify the technical elements that contribute to effective and durable fundoplications. OBJECTIVES: To compare antireflux operations and identify the important technical elements. DESIGN AND SETTING: Retrospective study in a university-based tertiary care center. PATIENTS: Two hundred one patients had laparoscopic fundoplications for gastroesophageal reflux disease. The first 22 patients underwent Nissen-Rossetti procedures (360 degree wrap; no division of short gastric vessels). Subsequently, 82 patients had a total (360 degree Nissen wrap) fundoplication and 97 patients had a partial (240 degree Guarner wrap) fundoplication (both with the short gastric vessels divided), with the choice between them based on the quality of esophageal peristalsis. The 3 groups of patients were similar in age, duration of symptoms, incidence of hiatal hernia, and incidence of esophagitis. MAIN OUTCOME MEASURES: Resolution of heartburn, incidence of postoperative dysphagia, and stability of the reconstruction. RESULTS: The resolution of heartburn was achieved for 15 patients (68%) who had the Nissen-Rossetti procedure, 73 patients (89%) who had a 360 degrees Nissen wrap, and 88 patients (91%) who had a 240 degree Guarner wrap. Postoperative dysphagia occurred in 3 patients (14%) having the Nissen-Rossetti procedure, 5 patients (6%) having a 360 degree wrap, and 2 patients (2%) having a 240 degree wrap. Herniation or disruption of the wrap occurred postoperatively in 9 patients (4.5%). Review of the videotapes of these 9 operations showed that important technical elements had been omitted in 8. Seven patients required a second operation. CONCLUSION: Laparoscopic antireflux operations control symptoms without producing adverse effects if the following technical elements are included: the hernia is repaired and the hiatus reduced to a normal size, the short gastric vessels are divided, a total or partial wrap is used based on the quality of esophageal peristalsis, and the wrap is anchored in the abdomen.

Digestive System Surgical Procedures↗
PubMed1998

Results of laparoscopic antireflux surgery for dysphagia and gastroesophageal reflux disease.

BACKGROUND: Little attention has been paid to nonobstructive dysphagia (dysphagia in the absence of an esophageal stricture) in patients with gastroesophageal reflux disease (GERD). The objectives of this study were to assess (a) the incidence of nonobstructive dysphagia in patients with GERD; and (b) the effects of laparoscopic fundoplication on nonobstructive dysphagia. METHODS: Esophageal manometry and pH monitoring identified 666 patients with GERD. Two hundred and eight patients (31 %) without esophageal strictures complained of dysphagia in addition to heartburn and regurgitation. Forty-nine (24%) of these patients underwent laparoscopic fundoplication. Esophageal function tests were repeated postoperatively in 12 patients (25%). Main outcome measures were effects of laparoscopic fundoplication on symptoms and esophageal motor function. RESULTS: Dysphagia resolved postoperatively in 44 patients (90%), and improved in 2 patients (4%). Postoperative esophageal manometry showed a significant increase in the length and pressure of the lower esophageal sphincter, without changes in its ability to relax in response to swallowing. CONCLUSIONS: About one third of GERD patients without strictures experienced dysphagia; and dysphagia resolved in about 90% of such patients following a laparoscopic fundoplication.

Deglutition↗
PubMed1998

Laparoscopic repair of paraesophageal hiatal hernias.

BACKGROUND: Regardless of symptoms, paraesophageal hiatal hernias should be repaired in order to prevent complications. This study reports the University of California San Francisco experience with laparoscopic repair of paraesophageal hiatal hernias, emphasizing the technical steps essential for good results. PATIENTS AND METHODS: From May 1993 to September 1997, 55 patients, 27 women and 28 men, with a mean age of 67 years (range, 35-102 years) underwent laparoscopic repair of paraesophageal hernias at the University of California San Francisco. Symptoms, which had been present an average of 85 months before surgery, consisted mainly of pain (55%), heartburn (52%), dysphagia (45%), and regurgitation (41%). Of the four patients who presented with acute illness, two had gastric obstruction, one had severe dyspnea, and one had gastric bleeding. Endoscopy demonstrated esophagitis in 25 (69%) of 36 patients, and 24-hour pH-monitoring demonstrated acid reflux in 22 (67%) of 33 patients. Manometry detected severely impaired distal esophageal peristalsis in 17 (52%) of 33 patients. The preferred operation consisted of reduction of the hernia, excision of the sack and the gastric fat pad, closure of the enlarged hiatus without mesh, and construction of a fundoplication anchored by sutures within the abdomen. RESULTS: Of the 55 patients, the operations of 49 were completed laparoscopically using the following reconstructions: Guarner (270-degree) fundoplication (30 patients); Nissen fundoplication (10 patients); and gastropexy (9 patients). Five (9%) operations were converted to laparotomies. The average operating time was 219 minutes; the average blood loss was less than 25 mL; resumption of an unrestricted diet, 27 hours; and mean hospital stay, 58 hours. Intraoperative technical complications occurred in five (9%) patients. One patient died during surgery from a sudden pulmonary embolus. Two (4%) patients required a second operation for recurrent paraesophageal hernias. CONCLUSIONS: Laparoscopic repair of paraesophageal hiatal hernias is safe and effective, but the operation is difficult and good results hinge on details of the operative technique and the surgeon's experience. In this series, the crus could always be closed securely without using mesh. We realized early that a fundoplication should be a routine step, because it corrects reflux and is the best method to secure the gastroesophageal junction in the abdomen.

Adult↗
PubMed1995

Role of the conserved histidine and aspartic acid residues in activity and stabilization of human gelatinase B: an example of matrix metalloproteinases.

Gelatinase B (MMP-9), a member of the matrix metalloproteinase family, is a zinc- and calcium-dependent endopeptidase that is known to play a role in tumor cell invasion and in destruction of cartilage in arthritis. It contains a conserved sequence. 400His-(X)3-His-(X)28-Asp-Asp-(X)2-436Gly, the function of which is under investigation. The conserved Asp-432 and Asp-433 residues were individually replaced with Gly; these substitutions reduced the gelatinolytic activity of the enzyme to 23% and 0%, respectively. Replacing Asp-433 with Glu, however, decreased the gelatinolytic activity of the enzyme by 93% and proteolytic activity of the enzyme for the Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by 79%. The wild-type and D432G and D433E, mutant enzymes had similar Km values for the synthetic substrate and similar Ki values for the competitive inhibitor, GM6001. The kcat/Km values for D432G and D433E mutant enzymes, however, were reduced by a factor of approximately 4 and their KaCa values were increased by four- and sixfold, respectively. The significance of His-400 in the activity of the enzyme was assessed by replacing this residue with Ala and Phe. Both H400A and H400F mutants were inactive toward gelatin substrate. These data demonstrate that Asp-432, Asp-433, and His-400 residues are important for the activity of gelatinase B. His-400 may act as a zinc-binding ligand similar to the His-197 in interstitial collagenase (MMP-7) and Asp-432 and Asp-433 residues are probably involved in stabilization of the active site of the enzyme. The His-400 and Asp-433 residues are conserved in all members of the MMP family. Therefore, our results are relevant to this group as a whole.

Amino Acid Sequence↗
PubMed1994

Flaccid trunk paralysis in free-ranging elephants (Loxodonta africana) in Zimbabwe.

An epizootic of flaccid trunk paralysis began in free-ranging Zimbabwean elephants (Loxodonta africana) on the southern shore of Lake Kariba in 1989. It involved a selective neuropathy of peripheral nerves supplying the trunk, with axon and myelin degeneration, muscle atrophy, compensatory hypertrophy, and fine endomyseal fibrosis, without inflammatory changes.

Animals↗
PubMed1991

Structural requirements for the carbohydrate ligand of E-selectin.

The acute inflammatory response requires that circulating leukocytes adhere to, and then migrate through, the vascular wall at the site of injury or infection. Several receptors have been implicated in this adhesion and migration process, including the selectins, a family of carbohydrate-binding proteins. The ligand for one of these proteins, E-selectin (LECAM-2, ELAM-1) has been described by several groups to contain a polylactosamine structure bearing a terminal sialic acid residue and at least one fucose residue. We report here a more detailed investigation into the minimum structural requirements for carbohydrate recognition by E-selectin. Using both direct binding and inhibition studies we demonstrate that the sialyl Lewisx tetrasaccharides Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc, and Sia(alpha 2-3)Gal(beta 1-4)[Fuc(alpha 1-3)]Glc are the smallest oligosaccharides recognized by the lectin. In addition, an oligosaccharide containing the sialyl Lewisa epitope is also recognized, but less avidly. We propose a structural model of functional groups necessary for recognition by E-selectin, based on these data and additional experiments on modifications of sialic acid and the reducing terminal saccharide.

Animals↗