PubMed Health⌕ Search

Biomedical subjects

T Dean

Publications and source records attributed to T Dean.

33 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Comparative efficacy of religious and nonreligious cognitive-behavioral therapy for the treatment of clinical depression in religious individuals.

Two versions of cognitive-behavioral therapy (CBT), one with religious content (RCT) and one with standard protocol (NRCT), were used to treat 19-20 religious patients each. Fifty-nine religious patients who met the Research Diagnostic Criteria for nonpsychotic, nonbipolar depression were treated in 18-20 1-hr sessions over 3 months. Religious and nonreligious therapists were used in each CBT group. Pastoral counseling (PCT) treatment-as-usual and waiting-list control (WLC) conditions each contained 10-11 patients. RCT and PCT patients reported significantly lower posttreatment depression and adjustment scores than did either the NRCT or the WLC condition. The CBT difference was due largely to superior performance of the nonreligious therapists (with dissimilar values to the patients) in the RCT over the NRCT condition. Improvement in the three treatment conditions was equal at 3-month and 2-year follow-ups and greater than posttreatment WLC improvement levels.

Adaptation, Psychological↗

Patients leaving hospital without the knowledge or permission of staff--absconding.

A series of 100 consecutive psychiatric in-patients who absconded from a psychiatric hospital a total of 231 times over ten months was studied. The reasons given for absconding, duration of absence, and mode of return are described. The legal status and ethnic origins of absconders differed significantly from those of the base hospital population.

Attitude to Health↗

Vial breakage by frozen mannitol solutions: correlation with thermal characteristics and effect of stereoisomerism, additives, and vial configuration.

The thermal characteristics as a function of cooling rate of mannitol solutions were studied by Differential Scanning Calorimetry (DSC). The exotherm appearing during warming at -25 +/- 1 degree C could be correlated with the temperature at which frozen mannitol solutions broke vials during warming. This temperature was also consistent with the temperature at which a sharp increase in resistance was reported in a preceding paper. The DSC exotherm did not appear to be due to crystallization of amorphous mannitol but rather to some other type of solid state transition. The peak was initially broadened and then obliterated by increasing amounts of additives such as lactose, glycine, potassium chloride, and sodium chloride. The presence of these ingredients in small amounts (less than 1% of the mannitol concentration) significantly reduced or prevented breakage. Other stereoisomers of mannitol, e.g., sorbitol and dulcitol, did not show any exotherm or break vials on freezing and thawing. It was also found that different types of vials exhibited different susceptibilities to breakage.

Calorimetry, Differential Scanning↗