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Biomedical subjects

T Dean

Publications and source records attributed to T Dean.

At least 19 recordsLinked to original sources
PubMed2000

Increased optic nerve head blood flow after 1 week of twice daily topical brinzolamide treatment in Dutch-belted rabbits.

OBJECTIVES: Using a three-way crossover study design, we compared the effects of brinzolamide 2%, dorzolamide 2%, and placebo (vehicle) on microvascular optic nerve head (ONH) blood flow, intraocular pressure (IOP), blood pressure, heart rate, and acid-base balance in nine acepromazine-tranquilized Dutch-belted rabbits. METHODS: Baseline measurements were taken before treatment and after drug-free washout periods of 7-14 days. Microvascular ONH blood flow was measured with a fundus camera-based laser Doppler flowmeter (LDF). Intraocular pressure was measured with a Tono-Pen XL. One drop of brinzolamide, dorzolamide, or vehicle was administered twice daily (9 A.M. and 5 P.M.) in right eyes only for 7 days. Experimental measurements were made 90 minutes after the 9 A.M. topical dose was administered on day 8. RESULTS: ONH blood flow was significantly increased (P< or =0.05) in carbonic anhydrase inhibitor (CAI)-treated rabbits, as compared with vehicle-treated controls. The percent increase from baseline was 11.2+/-1.8% in brinzolamide-treated animals and 8.4+/-4.3% in dorzolamide-treated animals. Compared with controls, IOP in the brinzolamide- and dorzolamide-treated groups was significantly decreased (P< or =0.05). The changes in ONH blood flow and IOP were not significantly different between the CAI treatment groups. Small but significant changes in systemic blood gas tensions and pH were present in both CAI treatment groups, as compared with the vehicle group. Systemic blood pressure and heart rate were not significantly changed. CONCLUSIONS: Topical ocular CAI treatment for 1 week with either brinzolamide or dorzolamide significantly reduced IOP and significantly increased ONH blood flow in tranquilized Dutch-belted rabbits, while eliciting minimal systemic acid-base balance disturbances.

Animals↗
PubMed2000

2H-Thieno[3,2-e]- and [2,3-e]-1,2-thiazine-6-sulfonamide 1,1-dioxides as ocular hypotensive agents: synthesis, carbonic anhydrase inhibition and evaluation in the rabbit.

Novel non-chiral 2H-thieno[3,2-e]- and [2,3-e]-1,2-thiazine-6-sulfonamide 1,1-dioxides were synthesized for evaluation as potential candidates for the treatment of glaucoma. All of the compounds prepared were potent high affinity inhibitors of human carbonic anhydrase II, Ki < 0.5 nM. Additionally, inhibition of recombinant human carbonic anhydrase IV was determined for selected compounds; these were shown to be moderate to potent inhibitors of this isozyme with IC50 values ranging from 4.25 to 73.6 nM. Of the compounds evaluated for their ability to lower intraocular pressure in naturally hypertensive Dutch-belted rabbits, 5a, 17a3, 17b1, 17b2, 17h2 and 17i1 showed significant efficacy (> 20% decrease) in this model following topical ocular administration.

Animals↗
PubMed2000

Matrilineal history of the endangered Cape Sable seaside sparrow inferred from mitochondrial DNA polymorphism.

Restriction analyses were conducted on mitochondrial DNA (mtDNA) amplified by long-PCR from an endangered bird, the Cape Sable seaside sparrow. The first of several successful mtDNA amplifications was accomplished using the partially digested tissue remains of a transmitter-monitored bird retrieved from the gut of a snake. As many as 91 mtDNA restriction fragments produced by 18 endonucleases were compared in this and four other Cape Sable specimens against mtDNA similarly amplified by long-PCR from other taxonomic forms in the seaside sparrow complex. Results indicate that the Cape Sable birds belong to an 'Atlantic' matrilineal clade, and are highly divergent from other seaside sparrows along the Gulf of Mexico.

Animals↗
PubMed2000

Trade-offs between location and waiting times in the provision of health care: the case of elective surgery on the Isle of Wight.

BACKGROUND: Recent UK government documents have stated that, within the National Health Service, consumers should be more involved in decision-making. This study considered the technique of discrete choice conjoint analysis (DCCA) for eliciting community views regarding the importance of reducing waiting times. More specifically, the study aimed to establish whether residents living on the Isle of Wight are prepared to travel to the mainland for elective surgery where waiting times are shorter but travel costs may be greater, and, further, if residents are willing to travel, what reduction in waiting time and increase in travel costs would be acceptable. METHODS: A DCCA questionnaire was sent to a random sample of 1,000 individuals living on the Isle of Wight. RESULTS: Seventy-eight per cent of respondents were willing to travel to the mainland for elective surgery. Of these, 48 per cent always chose the mainland and 30 per cent traded between island and mainland, depending on the levels of waiting time and travel costs. Whereas 'traders' preferred the Isle of Wight, they would forgo their preferred location if waiting times were reduced by at least 3.9 months, and they were willing to pay over 12 for a 1 month reduction in waiting time. Different combinations of waiting time reductions and travel cost increases that were acceptable to traders were estimated. CONCLUSIONS: Carrying out elective surgery on the mainland offers the potential to reduce waiting lists for island residents. The majority of respondents would be willing to travel to the mainland. However, one-fifth of respondents were not willing to travel to the mainland for elective surgery. The preferences of this group are important in policy decisions. More generally, the paper demonstrates the potential application of DCCA to public health issues.

Adolescent↗
PubMed1999

Complications associated with pegging hydroxyapatite orbital implants.

OBJECTIVE: Prior studies of hydroxyapatite orbital implant complications have primarily focused on complications of the implant itself with only occasional mention of the complications associated with the peg system. This in part may be because of a low rate of pegging and, thus, a small sample size to evaluate. Therefore, a full range of complications that can occur with pegging has not been presented. The objective of this study was to determine the complications associated with pegging and to discuss ways to manage them. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS/INTERVENTION: The authors analyzed all of the complications associated with pegging 165 of a possible 275 hydroxyapatite implants implanted by 2 surgeons over 7 years. MAIN OUTCOME MEASURES: The following data were recorded: type of surgery performed, size of implant used, type of hydroxyapatite used, peg system used, time of pegging, follow-up duration, problems encountered, and treatment. RESULTS: Sixty-two (37.5%) of the 165 patients who had pegged implants were found to have problems with their pegs. Twenty-one (33.8%) of the 62 patients with peg problems had more than 1 peg-related problem. Complications associated with pegging included discharge (37%; 23 of 62), pyogenic granulomas (30.6%; 19 of 62), peg falling out (29%; 18 of 62), poor transfer of movement (11.2%; 7 of 62), clicking (11.2%; 7 of 62), conjunctiva overgrowing peg (4.8%; 3 of 62), poor-fitting sleeve (4.8%; 3 of 62), part of sleeve shaft visible (4.8%; 3 of 62), peg drilled on an angle (4.8%; 3 of 62), hydroxyapatite visible around peg hole (3.2%; 2 of 62), peg drilled off-center (3.2%; 2 of 62), popping peg (3.2%; 2 of 62), and excess movement of peg (3.2%; 2 of 62). The most serious complication occurring in two individuals (3.2%) was implant infection requiring implant removal. CONCLUSION: There are several potential complications that can occur after pegging the hydroxyapatite implant. These problems are generally of a minor nature but often require additional patient visits that would not ordinarily have been required if the peg was not in place. The most serious peg problem is implant infection, which may necessitate implant removal. These potential peg problems should be reviewed with the patient before the procedure is performed.

Adolescent↗
PubMed1998

Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination.

Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to plasma membrane surfaces by a phosphatidylinositol glycan linkage. We have determined the 2.8-angstroms resolution crystal structure of a truncated, soluble form of recombinant murine CAIV. We have also determined the structure of its complex with a drug used for glaucoma therapy, the sulfonamide inhibitor brinzolamide (Azopt). The overall structure of murine CAIV is generally similar to that of human CAIV; however, some local structural differences are found in the active site resulting from amino acid sequence differences in the "130's segment" and the residue-63 loop (these may affect the nearby catalytic proton shuttle, His-64). Similar to human CAIV, the C-terminus of murine CAIV is surrounded by a substantial electropositive surface potential that may stabilize the interaction with the phospholipid membrane. Binding interactions observed for brinzolamide rationalize the generally weaker affinity of inhibitors used in glaucoma therapy toward CAIV compared with CAII.

Amino Acid Sequence↗
PubMed1998

Structural analysis of inhibitor binding to human carbonic anhydrase II.

X-ray crystal structures of carbonic anhydrase II (CAII) complexed with sulfonamide inhibitors illuminate the structural determinants of high affinity binding in the nanomolar regime. The primary binding interaction is the coordination of a primary sulfonamide group to the active site zinc ion. Secondary interactions fine-tune tight binding in regions of the active site cavity >5 A away from zinc, and this work highlights three such features: (1) advantageous conformational restraints of a bicyclic thienothiazene-6-sulfonamide-1,1-dioxide inhibitor skeleton in comparison with a monocyclic 2,5-thiophenedisulfonamide skeleton; (2) optimal substituents attached to a secondary sulfonamide group targeted to interact with hydrophobic patches defined by Phe131, Leu198, and Pro202; and (3) optimal stereochemistry and configuration at the C-4 position of bicyclic thienothiazene-6-sulfonamides; the C-4 substituent can interact with His64, the catalytic proton shuttle. Structure-activity relationships rationalize affinity trends observed during the development of brinzolamide (Azopt), the newest carbonic anhydrase inhibitor approved for the treatment of glaucoma.

Binding Sites↗
PubMed1997

Managing TMD.

Explore the source record for details and available documents.

American Dental Association↗
PubMed1997

Prevalence of allergic disorders in early childhood.

The purpose of this paper has been to highlight some of the work which has been carried out in "The David Hide Asthma and Allergy Research Centre". Some of results of 1, 2 and 4 years follow-ups of Isle of Wight 1989 cohort have been described. The geographically defined population of Isle of Wight allows epidemiological studies such as this to be carried out with relative ease. The high percentage of those who were followed up although in part is explained by the stable population of the Island, no doubt it also reflects the esteem that David was held in not only in the medical and scientific community but also amongst the local population of Isle of Wight. His legacy will go on and his team will endeavour to carry on with the excellent work that he initiated.

Allergens↗
PubMed1996

Small peptides radiolabeled with 99mTc.

UNLABELLED: The pharmacokinetic characteristics of small peptides radiolabeled with technetium-99m, their physico-chemical properties and radiolabeling techniques are reviewed. METHODS: Physical and chemical characteristics which affect pharmacokinetics are discussed with particular reference to lipophilicity, charge and resistance to peptidases. General biodistribution, pharmacokinetics, metabolism and excretion characteristics, as well as tissue uptake kinetics are described. Methods of radiolabeling small peptides with 99mTc are reviewed, including discussion of chelating groups for technetium. Specific examples drawn either from the literature or from the 99mTc labeled peptides under development by Diatide are presented. RESULT: Although lipophilicity and charge have an impact, the degree of resistance to peptidases is a key determinant of pharmacokinetic behavior. In general, pharmacokinetics and rate of tissue uptake are fast and metabolism occurs mainly via peptidase activity in the liver and kidneys. Although the route depends on a number of factors, excretion also usually is rapid. Chelating groups for 99mTc in the (+5) oxidation state are preferred. Site specific incorporation of the chelating groups during peptide synthesis is also preferred. Examples of renal imaging agents (MAG3), thrombus imaging peptides (P280 and P748), tumor imaging peptides (P587 and P829) and infection/inflammation imaging peptides (fMLF-type and P483H) are presented and discussed. CONCLUSIONS: 99mTc labeled small peptides are characterized by rapid pharmacokinetics and tissue penetration. Furthermore, small peptides are readily synthesized and the desired pharmacokinetic behavior may be engineered into the molecule. They are well suited for development as radiopharmaceuticals.

Animals↗
PubMed1995

A rapid and sensitive method of identification of HTLV-II subtypes.

There are 2 subtypes of human T-cell lymphoma/leukemia virus type II (HTLV-II), A and B. HTLV-II is increasingly associated with rare forms of lymphocytic neoplasia and a neurodegenerative disorder, characterized by hyperspasticity and ataxia. We have used PCR to amplify, clone and sequence 140 bp of the pol gene from many isolates of HTLV-IIA and HTLV-IIB from around the world. Analysis of these and other published sequence established that all HTLV-IIA sequences contained a unique Hinf I site and all HTLV-IIB sequences a unique Mse I site. A rapid and specific oligomer restriction (OR) assay was developed utilizing the primer pair SK110/SK111 and subsequent digestion with these enzymes. Concordance between sequenced and OR-based subtyping of DNA amplified by PCR was absolute among 22 HTLV-II isolates tested. Further OR or sequence analyses on an additional 30 other isolates indicated that the majority of North American non-indian HTLV-II isolates were subtype A, while all Paleo-Amerindian samples, including those from the Seminole of Florida; the Guaymi from Panama; and the Toba, Chorote, Wichi, and Chulupe of Argentina, belonged to subtype B. The SK110/SK111 PCR-OR format should facilitate molecular epidemiology studies of HTLV-II infection and allow for subtype stratification in assessing the sensitivity and specificity of HTLV detection formats and HTLV-II disease association.

Argentina↗
PubMed1995

Risk of dysplasia in anal condyloma.

BACKGROUND: Recent studies suggest an alarming incidence of dysplasia in homosexuals with anal condyloma. The purpose of our study was to determine the incidence of dysplasia in anal condyloma in our male patients and to determine risk factors for premalignant or malignant change. METHODS: Between 1986 and 1994, 103 male patients were referred to our colorectal clinic for evaluation of anal condyloma. Ninety-one patients had biopsy for pathology and form the basis of this report. All charts were reviewed and results analyzed using the chi-squared test with the Yates correction factor. RESULTS: Mean patient age was 31 +/- 11 years (range, 13 to 78 years) and mean duration of disease was 20 +/- 26 months (range, 2 to 120 months). There were 59 heterosexuals and 32 homosexuals/bisexuals. Two heterosexuals (3%) had invasive squamous cell carcinoma and four (6%) had dysplasia. One homosexual/bisexual (3%) had squamous cell carcinoma in situ and nine (28%) had dysplasia (p < 0.05). Statistical analysis revealed that HIV seropositive status and disease location above the dentate line also predicted increased risk of dysplasia, whereas duration of disease, previous topical therapy, substance abuse, and other sexually transmitted diseases were not significant risk factors. CONCLUSIONS: Homosexual orientation, disease above the dentate line and HIV seropositivity increase the risk of dysplasia in perianal condyloma. The incidence of dysplasia in perianal condyloma is significant enough to warrant consideration of biopsy in all patients.

Adolescent↗
PubMed1995

Role of elevated plasma soluble ICAM-1 and bronchial lavage fluid IL-8 levels as markers of chronic lung disease in premature infants.

BACKGROUND: Pulmonary neutrophilia characterises both the relatively transient inflammation associated with infant respiratory distress syndrome (IRDS) and the persistent inflammation of chronic lung disease. The possibility that persistently raised markers of inflammation indicate the development of chronic lung disease in low birth weight (< 1730 g) preterm (< 31 weeks) infants was therefore investigated. METHODS: Soluble ICAM-1 (sICAM-1) levels in plasma, and interleukin (IL)-8 and myeloperoxidase (MPO) levels in bronchial lavage fluid (BLF) obtained from 17 infants on days 1, 5, and 14 following birth were measured and correlations with the number of neutrophils in BLF sought. Peripheral neutrophils were isolated on Polymorphoprep and chemotactic responsiveness to IL-8 was assessed using micro Boyden chambers. RESULTS: Sixteen infants developed IRDS and, of these, 10 infants subsequently developed chronic lung disease. Levels of IL-8 in BLF at 14 days of age correlated with the long term requirement for intermittent positive pressure ventilation (IPPV). Interleukin 8 levels in BLF correlated with neutrophil numbers and MPO concentration, suggesting both recruitment and activation in response to this cytokine. Antibody depletion studies showed that approximately 50% of total neutrophil chemotactic activity in BLF was due to IL-8. No difference in peripheral neutrophil chemotactic responsiveness at any age was observed for infants with IRDS or chronic lung disease. Plasma soluble intercellular adhesion molecule (sICAM-1) was higher at 14 days of age in infants who developed chronic lung disease than in those with resolving IRDS, and correlated with severity of disease, as indicated by duration of IPPV. CONCLUSIONS: The results indicate that high levels of plasma sICAM-1 and IL-8 in BLF at day 14 correlate with the development of chronic lung disease and indicate the severity of disease.

Biomarkers↗
PubMed1995

Cow's milk allergy: therapeutic options and immunological aspects.

Adverse reaction to cow's milk and infant formulas are common during infancy. Cow's milk has more than 20 constituents proteins and in principle many are capable of giving rise to an IgE mediated response. The prevalence of cow's milk allergy is between 0.5-10% of the paediatric population (Frier & Kletter, 1970, Gerrard et al., 1973 Foucard, 1985). The clinical diagnosis of cow's milk allergy is difficult because of the great diversity and varying severity of symptoms and is often based on criteria which is then confirmed by challenge with cow's milk (Bock et al., 1988, Wershil & Walker, 1988). There is no doubt that various immunological mechanisms are involved in cow's milk allergy and in recent years a number of researchers have investigated the role of humoral and cell-mediated immunity in the pathogenesis of cow's milk allergy.

Bottle Feeding↗
PubMed1993

Increased platelet reactivity to prostaglandin E1 in hypertension is linked with altered signal transduction.

Prostaglandin E1 has been shown to induce a greater accumulation of cAMP in platelets from spontaneously hypertensive (SHR) than in platelets from normotensive (Wistar-Kyoto, WKY) rats (Circ. Res. 1978;43:583-591. Thromb. Res. 1988;49:5-21). This study was conducted to determine the mechanisms of increased platelet reactivity to PGE1 in hypertension. The number of PGE1 binding sites/platelet (WKY 280 +/- 8, SHR 287 +/- 5) as well as the Kd for WKY (105 +/- 11 nmol/L) and SHR (120 +/- 14 nmol/L) were found to be similar in WKY and SHR rats. PGE1-induced GTPase activity was determined using WKY and SHR platelet membranes. The basal GTPase activity was similar in WKY and SHR platelets. Incubation of membranes with PGE1 (3 mumol/L) for 1 min increased GTPase activity by 46% in WKY and by 806% in SHR. Incubation of platelets with 1.0 mmol/L IBMX (3-isobutyl-1-methyl-xanthine) for 4 min resulted in a 327 +/- 57% and 320 +/- 11% increase in cAMP in WKY and SHR platelets, respectively. In other experiments, incubation of platelets with 3, 10 and 100 mumol/L forskolin, induced similar increases in cAMP levels in WKY (103 +/- 12%, 530 +/- 42%, 784 +/- 41%) and SHR (111 +/- 13%, 461 +/- 18%, 756 +/- 28%) platelets. These data lead us to suggest that the greater accumulation of cAMP induced by PGE1 in SHR than in WKY platelets is linked with altered PGE1-receptor mediated signal transduction at the G-protein level.

1-Methyl-3-isobutylxanthine↗