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Biomedical subjects

D Bailey

Publications and source records attributed to D Bailey.

At least 19 recordsLinked to original sources

Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance.

The effect of drinking grapefruit juice on the acute pharmacokinetic and haemodynamic actions of the dihydropyridine calcium antagonist felodipine given as a 5 mg plain tablet has been studied in nine, healthy, middle-aged males. Compared to water, grapefruit juice caused an increase in Cmax from mean 6 to 16 nmol.l-1, and in the AUC from 23 to 65 nmol.h.l-1. The change in AUC corresponded to an increase in the systemic availability of felodipine from 15 to 45%, assuming no change in its clearance. This change was probably caused by inhibition of the oxidation of felodipine to the inactive dehydrofelodipine by flavonoids in grapefruit juice. The interaction with grapefruit juice is believed to be a class effect for the dihydropyridines, as oxidation of the dihydropyridine ring to the corresponding pyridine derivative is a major metabolic route for all these drugs. The higher plasma concentrations of felodipine taken with grapefruit juice resulted in a greater change in blood pressure measured in the morning 3 h after dosing (-9%) than did water (0%).

Adult

Facilitator not teacher: a role change for tutors in open learning nursing education.

Open learning is now an established, if rapidly changing, part of post-compulsory education and training in the United Kingdom. It has also developed in significant ways within nurse education. A key role in successful open learning is that of the tutor. Differences between the activities of teaching and facilitation are defined and ways of mapping the tutor's role within these are suggested. Differences in approach can be clustered around the topics of: the locus of control; learning methodology; the learning context and media; and the curriculum. These are discussed in turn to elicit what are the key issues for tutoring in relation to each one.

Curriculum

Decreased leukocyte adhesion with anti-CD18 monoclonal antibodies is mediated by receptor internalization.

BACKGROUND: Adhesion of polymorphonuclear leukocytes (PMNs) to endothelial cells is mediated partially by CD11/CD18 integrins. The purpose of this study was to define (1) the response of PMNs to anti-CD18 monoclonal antibody binding, and (2) the mechanism responsible for anti-CD18 monoclonal antibody-mediated decreases in PMN adhesion to endothelial cells. METHODS: Canine PMN O2- production, myeloperoxidase, and lysozyme release in response to the anti-CD18 monoclonal antibody IB4 were measured by standard assays. To examine endocytosis of CD18 receptors, PMNs incubated with IB4 and a fluorescein isothiocyanate secondary antibody were analyzed by flow cytometry. RESULTS: Treatment of PMNs with IB4 did not stimulate O2- production or degranulation but decreased adhesion of 51Cr-labeled PMNs to ex vivo canine aorta. Incubation of PMNs at 25 degrees C resulted in a decrease in fluorescence intensity that was not affected by NaN3 or vanadate but was blocked by NaF, 4 degrees C, and bafilomycin, which prevents endosomal acidification. Treatment with an antifluorescein antibody decreased the fluorescence intensity in NaF and 4 degrees C, but not in bafilomycin-treated neutrophils. CONCLUSIONS: IB4 decreases PMN-endothelial cell adhesion but does not stimulate neutrophil oxidative metabolism or degranulation. These data suggest that reduced adhesion may be the result of internalization of the CD18/IB4 complex. Anti-CD18 monoclonal antibodies may be useful in preventing PMN adhesion without the potentially deleterious effects of cell activation.

Animals

Identification of a cell-surface antigen associated with activated T lymphoblasts and activated platelets.

We have identified and biochemically characterized an antigen, 8A3, which is expressed on activated T lymphoblasts and activated platelets. Monoclonal antibodies to 8A3 were raised against the primitive lymphoid/myeloid cell line KG1a and additionally bound to the erythroleukemia-derived cell line HEL, whilst exhibiting little or no reactivity with a panel of other hematopoietic cell lines. The 8A3 antigen was expressed on poorly differentiated T-cell leukemias and on phytohemagglutinin-activated T-cells maintained in interleukin-2 (7,000 sites/cell). This antigen, though not detected on resting platelets, was expressed on thrombin-activated platelets (2,000 sites/platelet). Antibodies to 8A3 identified polypeptides of Mr 170,000 and 150,000 in lysates of surface-iodinated KG1a cells, T lymphoblasts, and activated platelets under both reducing and nonreducing conditions. However, peptide mapping and susceptibily to glycosidases indicated that the 8A3 antigen was a monomeric glycoprotein of Mr 170,000 which contained two N-linked endoglycosidase H-sensitive glycans, and that the Mr 150,000 structure was derived from it by proteolytic degradation. The 8A3 antigen was not detectably phosphorylated in KG1a cells in vivo, nor did immune complexes containing it exhibit kinase activity in vitro. Structural and serologic characteristics of the 8A3 antigen indicate that it is different from other previously described leukocyte activation antigens including transferrin receptors, interleukin-2 receptors, members of the integrin family of adhesion molecules, or "restricted" members of the leukocyte-common antigen/CD45 cluster. Furthermore, the 8A3 antigen does not appear to be related to the other previously described activation-specific platelet molecule, GMP140/PADGEM. This antibody may be useful in monitoring T-cell activation status in some clinical situations and in characterizing clinically relevant activation-associated platelet membrane alterations.

Animals

Translocation (14;19) in acute biphenotypic leukemia.

Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation.

Adult

A normalization technique for 3D PET data.

Prior to reconstruction, emission data from a multi-ring PET camera must be corrected (normalized) for variations in detector sensitivity. The appropriate correction coefficients are obtained by measuring the response of all coincidence lines to a calibrated source of activity (a blank scan). State-of-the-art cameras may contain up to a million such lines of response (LORs), and therefore around 400 million counts will be required to calibrate each LOR to a statistical accuracy of 5%. Alternatively, by modelling the LOR sensitivity as the product of the individual detector efficiencies and a geometrical factor, a calibration procedure has been proposed which requires the determination of only 6000 parameters from this same data set. A significant improvement in the statistical accuracy of the coefficients can therefore be expected. Recently, multi-ring scanners have been operated with the septa retracted, increasing the number of measured LORs by a factor of eight. The acquisition of the calibration data necessary to achieve adequate statistical accuracy then becomes prohibitive. We show that, by modelling the LOR sensitivity, it is possible, with certain approximations, to normalize a septa-retracted emission data set with good accuracy. The input to the model is a high statistics blank scan acquired with the septa extended, which offers a number of practical advantages.

Calibration

A method of studying pharmacokinetics in man at picomolar drug concentrations.

1. We describe a new method that enables the tissue kinetics of picomolar concentrations of drugs to be measured in man. The method is based on the administration of a drug, labelled with a short-lived positron-emitting radioisotope, such as carbon-11 (t1/2 = 20.4 min, beta + = 99.8%) or fluorine-18 (t1/2 = 109.8 min, beta + = 96.9%), which is then detected in vivo by an array of 10 large uncollimated sodium iodide scintillation detectors, arranged as five opposing pairs, with each pair collecting data over one major organ or region of the body. 2. To illustrate the scope of the new method we report the results of administering [O-methyl-11C]-diprenorphine, an established radioligand for central opiate (mu, kappa, and delta) receptors and L-6-[18F]-fluoro-DOPA, a marker for dopaminergic neurons. 3. Only 2-10 muCi (74-370 kBq) of radioactivity are used and, as a consequence of the high specific activities with which carbon-11 and fluorine-18 labelled compounds can be prepared, the method requires less than a nanomole of drug to be administered. In many cases, this amount of drug might be considered low enough to avoid any adverse biological effect. Furthermore repeat studies are possible in many without delivering unacceptable radiation burdens. 4. The high sensitivity realised for both radioactivity and mass suggests a mean for determining the human biodistribution of a new drug at a very early stage in its development. This has potential benefit to drug discovery programmes and to ensuing drug therapies.

Blood-Brain Barrier

Increased flow-induced ATP release from isolated vascular endothelial cells but not smooth muscle cells.

1. Freshly harvested smooth muscle cells and endothelial cells isolated from the rabbit aorta were perfused (0.5 ml min-1) and stimulated twice by an increase of flow rate (3.0 ml min-1) in order to compare their ability to release adenosine 5'-triphosphate (ATP). 2. In smooth muscle cells, the basal release of ATP (0.0265 +/- 0.0033 pmol ml-1 per 10(6) cells) was not increased during periods of increased flow (P = 0.2). 3. In endothelial cells, the concentration of ATP in the perfusate during periods of low flow (0.0335 +/- 0.0038 pmol ml-1 per 10(6) cells) was significantly increased by 14 times and 5 times during the first and second periods of increased flow, respectively. 4. The release of ATP by endothelial cells did not appear to be caused by the lysis of cells during the period of increased flow because it can be reproduced several times and because there was no difference between lactate dehydrogenase activity in perfused cells and that in non-perfused cells. 5. These results show that, of the two major cell types of the vascular wall, only endothelial cells react to shear stress by releasing ATP.

Adenosine Triphosphate

A personal experience.

David Bailey, who is 14 years old, has a left transverse total forearm deficiency and bilateral longitudinal femur partial deficiencies. The latter fall into Torode and Gillespie's Group I, with marked femoral shortening. A wedge osteotomy was performed for his gross right coxa vara, which was successful, but an intractable fixed flexion deformity of the right knee led eventually to a knee disarticulation being performed.

Abnormalities, Multiple

Immunohistochemical staining of germ cell tumors and intratubular malignant germ cells of the testis using antibody to placental alkaline phosphatase and a monoclonal anti-seminoma antibody.

Antibody to placental alkaline phosphatase (PLAP) has been previously used in immunoperoxidase (IMP) staining studies of germ cell tumors and intratubular malignant germ cells (ITMGC) of the testis, the latter believed to be the precursor of these tumors. In this study, we compared staining by IMP using monoclonal antibody (mAb) and polyclonal antibody to PLAP with that seen using a mAb, M2A, which was previously shown to react with testicular seminomas and ITMGC. Antibody to PLAP and M2A reacted with different cellular components, as assessed by IMP staining of placenta and prepubertal testis and by Western blotting of seminoma lysates. Antibody to PLAP stained pure seminomas (seven of seven), pure embryonal carcinomas (four of four), and the seminoma (three of three) and embryonal carcinoma (six of six) components of mixed testicular germ cell tumors. M2A stained pure seminomas (26 of 26) and the seminoma component (three of three) of the mixed tumors, but failed to stain pure embryonal carcinomas (zero of four) or the embryonal carcinoma component (zero of five) of the mixed tumors. Both antibody to PLAP and M2A stained ITMGC of the testis. Since M2A stained seminomas and ITMGC but not embryonal carcinomas, seminomas would appear to be more closely related to ITMGC than embryonal carcinomas. This result has led us to speculate on the histogenesis of testicular germ cell tumors.

Alkaline Phosphatase

Hepatocellular carcinoma: a review of 30 years experience.

The clinical characteristics of 51 patients with hepatocellular carcinoma over a 30-year period were reviewed. Presenting symptoms commonly included abdominal pain (47 percent), anorexia (41 percent), and ascites (22 percent); however, the ability to make an early diagnosis was complicated by a variety of unusual symptoms accounting for 23 percent of presentations. While cirrhosis (41 percent) was a common associated finding, most patients (92 percent) had no prior diagnosis of liver disease. Histologic diagnosis was made by blind percutaneous biopsy (three performed, 100 percent positive), needle aspiration biopsy (four performed, 100 percent positive), laparotomy (26 percent, 85 percent positive), or autopsy (20). Only six of 51 patients underwent surgical resection. The overall median survival of 4.1 months and seven percent two-year survival in our series illustrates that thus far medical treatment is not helpful in prolonging life. Attempts to elucidate more effective systemic and regional therapy for established cases of hepatocellular carcinoma and attempts to reduce the incidence of the disease in high-risk populations through the use of hepatitis B vaccine are therefore advised.

Academic Medical Centers

Life events: children's reports.

Children 7 to 12 years of age were asked to indicate events they had experienced in the previous three months in a questionnaire devised for the study. Most children were able to complete the questionnaire and reported positive and negative events, the most common themes being personal achievement, illness-related events and problems in relationships. The agreement between parents and child reporting of individual events was uneven and children reported more events than parents. Psychiatrically disturbed children noted an excess of negative and loss events and children attending paediatric clinics reported fewer events, particularly fewer positive happenings, than non-attending primary school children. A child Life Events questionnaire may be of use to explore disturbed and ill children's perception of their lives.

Child

Paediatrician identification of psychological factors associated with general paediatric consultations.

In a study of children 7-12 yr of age referred to general paediatric clinics, paediatricians reported psychological factors associated to somatic presentations in 47% of the children. These cases presented with a variety of somatic symptoms, but abdominal/chest/joint pains and soiling were particularly common. From research interviews with the parents we found increased rates of psychiatric disorder (abnormalities of emotions, behaviour or relationships) amongst them. The most common psychiatric symptoms were depressive mood changes and relationship problems. We also identified an excess of certain personality features in the children and of family health problems in this group. Paediatricians commonly identify psychosomatic issues in children attending general paediatric clinics and independent evidence supports the validity of their assessments.

Affective Symptoms

Pediatric bone marrow transplants: psychological aspects.

On a pediatric bone marrow transplant unit, hematologist-oncologists, nurses, social workers, psychiatrists, psychologists, and others on the team deal with children and adolescents whose cancers are either treatable by marrow transplantation or are ultimately fatal. Contrary to original assumptions, many children and families cope well, especially in relatively uncomplicated cases with good outcome. Treatment may include direct psychotherapeutic intervention with the child and family, as well as use of psychopharmacologic agents such as antidepressants or anxiolytics for frank psychiatric disorders. Psychotherapists often have to function adjunctively with other staff members in their interactions with the patient and the family. A stress disorder model appears to best explain child, parent and family reactions to bone marrow transplantation. Given the medical severity and complexity of the conditions treated, and the approximately equal rates of overall success and failure, a supportive consultative approach is usually most helpful for child patients, parents and staff throughout the procedure. A retrospective study of the children treated over seven years in a tertiary pediatric hospital bone marrow transplant unit is presented. The level of child, parent, and family psychopathology was usually mild to moderate, but there were clear differences between patients. Mothers were more supportive than fathers under this extreme type of stress. Prospective longitudinal studies of children and families are needed to establish causal chains and optimal therapeutic interventions.

Adaptation, Psychological

Thyroiditis as the presenting manifestation of disseminated extrapulmonary Pneumocystis carinii infection.

A 38-yr-old male with acquired immunodeficiency syndrome developed neck pain in association with mild hyperthyroidism and a diffusely enlarged thyroid gland. Radioactive iodine scanning was consistent with thyroiditis, and biopsy of the thyroid demonstrated the presence of pneumocystis carinii in thyroid tissue. Treatment with pentamidine followed by trimethoprim sulfamethoxazole led to rapid normalization of thyroid size in association with the development of hypothyroidism. This case illustrates the natural history of pneumocystis carinii thyroiditis and suggests that thyroid disease be added to the spectrum of human immunodeficiency virus-associated endocrine dysfunction.

Acquired Immunodeficiency Syndrome

Chronic myeloid leukemia arising in a progenitor common to T cells and myeloid cells.

Until recently, T cells were believed not to be involved in chronic myeloid leukemia. We describe an example of CML in T lymphoblastic crisis with massive generalized lymphadenopathy in which the blasts were CD2(+), CD5(+), and CD7(+), variably CD1(+) and CD3(+), and both responded to and could be induced to produce the T cell growth factor, interleukin-2. Additionally, the blasts were shown to contain the CML-related tyrosine kinase P210bcr-abl rather than the smaller kinase associated with Ph1(+) ALL. Finally, the participation of the T lymphoid lineage in the CML clone was proven by the presence of the same BCR rearrangement in blasts as in granulocytes, suggesting the existence of a bone marrow progenitor common to the T cell and myeloid lineages.

Adult