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Biomedical subjects

D Bailey

Publications and source records attributed to D Bailey.

At least 109 records · Page 6Linked to original sources

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↗

Nebulized albuterol in acute childhood asthma: comparison of two doses.

Thirty-three children and adolescents from 5 to 17 years of age with moderate to severe acute asthma were given nebulized albuterol therapy in either a high (0.30 mg/kg body weight) or standard (0.15 mg/kg) dose administered at three hourly intervals in a randomized double-blind study. The high-dose hourly regimen resulted in significantly greater improvement in the forced expiratory volume in 1 second (FEV1). Furthermore, patients receiving the high dose showed a steady improvement in the FEV1 from the start to the end of the study, whereas FEV1 plateaued after the second dose in the standard-dose group. Although a rise in heart rate and a fall in serum potassium level occurred, neither of these changes nor other side effects were different in the two groups. The high-dose therapy resulted in much higher serum albuterol levels than the standard dose. There was no correlation between the drug levels and side effects or initial and subsequent FEV1. It is concluded that occasional hourly high-dose albuterol therapy should be considered for some pediatric patients with acute asthma of moderate severity, especially those who relapse between doses.

Adolescent↗

Isochromosome 7q as the sole abnormality in an unusual case of T-cell lineage malignancy.

We present a case of large cell lymphoma in a 20-year-old Oriental male who presented with massive splenomegaly and mild anemia. Surface marker and molecular genetic analyses of lymphomatous cells obtained from the spleen indicated a T-cell origin. Chromosomal analysis identified an isochromosome 7q as the sole abnormality. This is the first report of isochromosome 7q as the sole cytogenetic abnormality in a T-lineage malignant clonal expansion.

Adult↗

The spinal antinociceptive actions of morphine metabolites morphine-6-glucuronide and normorphine in the rat.

The profound and prolonged effects of morphine in patients with renal dysfunction have been associated with high plasma levels of the opiate metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) rather than an increased concentration of morphine. We present here electrophysiological evidence to suggest that potent spinal antinociception can be produced by both M6G and normorphine, another metabolite of morphine. Extracellular recordings of A beta- and C-fibre-evoked responses of convergent dorsal horn neurones were made in the halothane anaesthetised rat. M6G elicited dose-dependent, naloxone-reversible inhibitions of C-fibre-evoked responses which were completely suppressed (8% of control) by 2 micrograms M6G whereas A beta-fibre-evoked responses were only reduced to 57% of controls. The ED50 for the effects of M6G on C-fibre-evoked activity was calculated to be 0.53 micrograms. Systemic administration of M6G (2 mg/kg) also profoundly reduced noxious evoked neuronal activity. Intrathecal normorphine was less potent than M6G but complete selective inhibitions of C-fibre-evoked response could be elicited by 25 micrograms and the ED50 was calculated to be 2.68 micrograms. No such inhibitions were observed following administration of M3G. A comparison with intrathecal morphine in the same preparation reveals that normorphine is equipotent with morphine whereas M6G is 13-fold more potent. These results therefore confirm that M6G and normorphine might be significant contributers to opiate analgesia after administration of morphine.

Action Potentials↗

High affinity dopamine binding to mouse thymocytes and Mytilus edulis (Bivalvia) hemocytes.

The present report demonstrates that both mouse thymocytes and Mytilus edulis hemocytes contain a novel type of dopamine receptor. Scatchard analysis of these data revealed a single class of high-affinity binding sites with an affinity constant (Kd) of 6.6 nM, and a binding site density (Bmax) of 141 pmol/g protein in mice and a Kd of 7.6 nM and a Bmax of 66 pmol/g protein for the hemocytes. In older Mytilus the Kd was the same; however, there was a significant decrease in the Bmax (48 pmol/g protein; P greater than 0.05). Age changes were not evident for the mouse cells. The ability of a variety of other related drugs to displace specifically bound dopamine was investigated. The catecholamines (norepinephrine greater than epinephrine) and the dopamine agonist epinine were the most potent of the ligands tested and apomorphine and butaclamol were of moderate potency. This may serve to indicate that this dopamine binding site may be very different from the known D1 and D2 sites. This particular site may represent a third type of dopaminergic receptor. Furthermore, the hemocytes of Mytilus appear to be of two major types, namely, cells with a granular cytoplasm and those whose cytoplasm is agranular. Histofluorescence studies on the hemocytes reveal that a subpopulation of the granule-containing cells appears to contain serotonin.

Animals↗

Research comparing the dyadic adjustment and sexual functioning concerns of diabetic and nondiabetic women.

The dyadic relationship and sexual functioning concerns of a group of diabetic women and a matched control group of nondiabetic women were compared. There was no statistically significant difference in overall dyadic adjustment between the two groups. Both diabetic and nondiabetic women were moderately well adjusted. However, diabetic women were significantly more concerned than nondiabetic women in the following six specific sexual functioning areas: (a) frequency of feeling sexual repulsion, (b) frequency of difficulty with vaginal lubrication, (c) frequency of difficulty reaching orgasm, (d) impact of genital discomfort, (e) frequency of performance anxiety, and (f) impact of performance anxiety. Therefore, health care professionals need to use the suggested holistic approaches in helping diabetic women overcome these sexual functioning concerns. Finally, the relationship between level of sexual functioning concerns and overall dyadic adjustment was not statistically significant for either group. This finding supports the belief that sexual and marital factors may operate independently.

Adolescent↗

Immunophenotypic and gene probe analysis of a case of Richter's syndrome.

A rare case of diffuse large cell lymphoma (DLL) arising in the stomach of a patient with long-standing chronic lymphocytic leukemia (CLL) has been examined by a combination of immunophenotypic and gene probe methods. Both the resected lymphoma and the CLL (obtained from an infiltrate in perigastric lymph nodes) expressed surface membrane markers consistent with a B-cell origin (HLA-DR+; B1+; B4+), but surface membrane immunoglobulin (SmIg) could be detected only on the CLL cells (SmIgM lambda+). Neither neoplasm expressed cytoplasmic immunoglobulin. DNA probe analysis using the Southern blot method and probes to the joining (J-H) region of the immunoglobulin heavy chain gene and to the constant (C) regions of the immunoglobulin kappa and lambda light chain genes revealed different light and heavy chain gene rearrangements in the two neoplasms. These findings suggest that the large cell lymphoma arose from a different clone than the CLL and the development of large cell lymphoma may have represented a de novo neoplastic event in a predisposed person.

Antigens, Neoplasm↗