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Biomedical subjects

J Turner

Publications and source records attributed to J Turner.

At least 19 recordsLinked to original sources

Cavernous haemangioma of the temporal bone.

Cavernous haemangioma of the temporal bone is a rare lesion and nearly always of limited extent. A case of a large and rapidly progressive temporal bone haemangioma in a child is presented. Negative angiography led to biopsy at which profuse and troublesome haemorrhage was encountered. Subsequent Red Blood Cell labelled scan demonstrated blood pooling in the lesion. The combination of positive RBC labelled scan and negative angiography can only occur in lesions in which blood pooling takes place, enabling biopsy with its hazards to be avoided. The tumour was resected using a skull base, infratemporal approach. Morbidity was minimal. There was no evidence of recurrence at a 15 month follow-up.

Child, Preschool

Sleep disordered breathing and cognitive function in a retirement village population.

Sleep disordered breathing (SDB) may be associated with cognitive dysfunction in non-demented elderly people. A random sample of 96 retirement village residents were given both neuropsychological assessment and overnight sleep monitoring with a portable microprocessor based system (Vitalog PMS-8). Respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. RDI was not associated with 'memory', 'verbal', and 'motor' factors identified from the analysis of cognitive tests, but was associated with the 'cerebral efficiency' factor (R2 = 0.21, p less than 0.0001). Seventy-three subjects had repeat neuropsychological tests, median time to follow-up being 17 months. Baseline RDI did not predict changes in scores on the two factors identified from the second analysis. We conclude that mild to moderate disturbance of breathing during sleep is not associated with cognitive dysfunction in non-demented subjects.

Activities of Daily Living

Location of monoclonal antibody binding sites in the capsid protein of feline calicivirus.

We report the localization of three monoclonal antibody (MAb) binding sites in the capsid protein of feline calicivirus. Gene fragments were generated by restriction enzyme digestion or the polymerase chain reaction, and expressed as beta-galactosidase fusion proteins in Escherichia coli. These chimeric molecules were screened using three MAbs. A non-neutralizing MAb recognized a region within 36 amino acids of the C terminus. Two neutralizing MAbs bound to a different region of 37 amino acids in the centre of the protein. Comparative sequence analysis shows this area to be the major variable region of the capsid protein.

Amino Acid Sequence

Myocardial dysfunction in ankylosing spondylitis.

Echocardiographic evidence has suggested abnormalities of the myocardial function in patients with ankylosing spondylitis. In this work the cardiac function in patients with ankylosing spondylitis and in normal volunteers was evaluated. Twenty four normal volunteers and 21 patients with ankylosing spondylitis aged 18-45 were studied. None had overt cardiac disease. Cardiac function was assessed at rest with echocardiography, at rest and during supine bicycle exercise using radionuclide angiography in the left anterior oblique position following equilibration with 740 MBq of technetium-99. The subjects undertook supine bicycle exercise with 30 W increments every three minutes to the point of fatigue. Comparison of data from normal volunteers and patients with ankylosing spondylitis were made using Student's t test for independent samples or the Mann-Whitney non-parametric technique, as appropriate. Subjects were matched for age, sex, height, and weight. There were no echocardiographic differences; however, global nuclide left ventricular function showed several differences between normal volunteers and patients with ankylosing spondylitis. The peak filling rate during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 6.5 (SD 1.2); patients with ankylosing spondylitis 5.7 (1.2). The time to reach peak filling during exercise was significantly lower in patients with ankylosing spondylitis: normal volunteers 102 (22); patients with ankylosing spondylitis 120 (23). Regional analysis also showed differences between patients with ankylosing spondylitis and normal volunteers both at rest and during exercise. In the anteroseptal region the filling fraction and peak filling rate were significantly lower in patients with ankylosing spondylitis. Most of the differences (although not all) were in the variables of diastolic function. This study shows that there are subtle abnormalities in cardiac function in patients with ankylosing spondylitis. The major abnormalities are in the diastolic function, suggesting a decrease in left ventricular compliance.

Adult

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity. To explore this hypothesis, we prospectively studied 166 research volunteers (19 patients with research diagnostic criteria (RDC) major depression, 9 patients with RDC bipolar depression, 45 patients with RDC schizophrenia, and 94 RDC normal controls), examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio (VBR) and indices of LHPA axis function (cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), CSF adrenocorticotropic hormone (ACTH), and 24-hour urinary-free cortisol secretion). We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers. Of the indices of LHPA activity, only CSF CRF concentrations distinguished the four subject groups, with CSF CRF being significantly elevated in the more severely depressed major depression patients. Indices of LHPA activity were not significantly correlated with VBR in any of the three patient groups or in the normal volunteers. These preliminary results suggest that VBR is not highly associated with alterations in LHPA activity, at least as determined cross-sectionally. Further longitudinal studies with reference to diagnostic subtypes, severity, symptom profiles, and more specific neuroanatomic regions may allow the elucidation of possible relationships between LHPA pathology and structural brain alterations.

Adrenocorticotropic Hormone

Treatment of cryptosporidiosis with paromomycin. A report of five cases.

Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted.

AIDS-Related Opportunistic Infections

Analysis of antibody responses directed against two Onchocerca volvulus antigens defined by monoclonal antibodies.

Monoclonal antibodies, reactive with antigens solubilised from the body wall of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol, have been characterised. Two IgG1 antibodies, Cam1 and Cam28, recognised antigens of apparent molecular weights of 18,000 and 28,000; and 120,000, respectively. The target antigens of Cam1 and Cam28 could be localised in the cuticle. Inhibition ELISAs showed that target epitopes of both monoclonal antibodies induce an antibody response in onchocerciasis patients. 153 sera from Sierra Leonean patients were tested for their individual antibody levels against antigen epitopes recognised by Cam1 and Cam28. Patients within the age of 5-8 years had the highest levels of antibodies against the Cam28-epitope, whereas patients above 60 years had almost none. Amicrofilaremic patients had higher anti-Cam28 antibody levels than microfilaremic patients and there was a significant difference between groups with no chronic skin disease and those with mild or severe signs. A high percentage of patients (80.4%) recognised the Cam1-epitope, highest antibody levels being found in patients within the age group of 15 to 45 years and in microfilaremic patients. However, levels of antibodies inhibiting monoclonal antibody Cam1 could not be correlated with presence or absence of skin disease.

Adolescent

Regions of the T cell receptor alpha and beta chains that are responsible for interactions with CD3.

The T cell antigen receptor consists of the Ti alpha/beta heterodimer which recognizes antigen, and the associated CD3 chains, thought to be involved in signal transduction. To understand the nature of the interaction between Ti and CD3, chimeric molecules which included the COOH-terminal segments of Ti alpha or beta linked to the extracellular segment of CD8, were transfected into a mutant T cell deficient in Ti beta chain expression and cell surface CD3. Both chimeric chains were required to express the chimeric Ti and to restore CD3 surface expression. CD8/Ti and CD3 cointernalized and coimmunoprecipitated. Stimulation of the chimeric receptor induced transmembrane signaling events and cell activation. These results demonstrate that the Ti alpha and beta COOH termini containing the transmembrane domains are sufficient for structural and functional coupling of Ti to CD3.

Antigens, Differentiation, T-Lymphocyte

A Southwest Oncology Group study on the use of a human tumor cloning assay for predicting response in patients with ovarian cancer.

A total of 211 patients with epithelial ovarian cancer (168 with tumors refractory to prior chemotherapy and 43 with no prior chemotherapy) from 33 different Southwest Oncology Group institutions had their tumors sampled and specimens shipped to two central laboratories for drug-sensitivity testing in a human tumor cloning assay. The 168 patients with a prior history of chemotherapy failure (median of four prior chemotherapeutic agents) were treated with the most effective agent(s) found in the cloning assay (23 patients), and those patients whose tumors did not form colonies in vitro or did not manifest any sensitivity to agent(s) were treated with a clinician's choice of agent(s) (101 patients). The remaining 44 of the 168 patients were not treated with chemotherapy because of deteriorating performance status or early death. The complete and partial response rate in patients treated according to assay results was 28% versus 11% for the patients treated according to clinician's choice (P = 0.03). There was no statistically significant difference in survival between the two options (6.25 versus 7 months, respectively). The 43 patients with no history of prior chemotherapy were all treated with standard combination chemotherapy, and their clinical response was compared with their in vitro sensitivity to the same agents. Overall there was a 100% true-positive rate and 100% true-negative rate for the seven evaluable patients. From these data the authors conclude that use of the human tumor cloning assay may increase the response rate but not the survival for selected patients with advanced chemotherapy-refractory ovarian cancer. The study is weakened, however, by the many steps of patient selection necessitated by inadequate tumor colony formation in vitro and the inability to treat all patients (because of early death or a rapid decline in performance status). The assay does appear to be worthy of additional study for predicting response to combination chemotherapy in patients without a prior history of chemotherapy. Finally the use of central chemosensitivity testing laboratories is feasible for testing in vitro predictive assays in a cooperative group setting.

Antineoplastic Combined Chemotherapy Protocols

Phenotypic changes in T-cyt-transformed potato plants are consistent with enhanced sensitivity of specific cell types to normal regulation by root-derived cytokinin.

From over forty independently isolated potato lines transformed with wild-type and promoter-mutated T-cyt genes, a number of lines were selected for examination of phenotypic changes in growth and development for plants grown in soil in a controlled environment. The three lines chosen for most detailed examination showed a wide spectrum of phenotypic changes. In comparisons with control potato cv. Désirée, the plants of one line had a two- to three-fold increase in biomass production during early vegetative growth, advanced senescence and a shortened plant life-span. Another line showed abnormal cellulytic senescence. In two lines there were increases in tuber numbers and more skewed tuber size distributions which correlated with reduced shoot apical dominance and shortened dormancy of the stored tubers. None of the lines showed altered timing of onset of tuberization or flowering, although tuberization was consistently delayed when expressed as a function of increasing total plant weight. A hypothesis is proposed to explain the diverse phenotypes which postulates that (1) T-cyt transformation causes enhanced sensitivity to cytokinins in specific types of shoot cells which are already targets for regulation by normal root-derived cytokinins; (2) two distinct types of shoot target cells are present, one in shoot meristems and one in leaves; (3) the two types can acquire enhanced sensitivity, either separately or in combination depending on the particular T-cyt transformation event. The scope for using the transformed plants in subsequent physiological, biochemical and molecular studies, aimed at examining the molecular basis of the model or selected consequences of T-cyt transformation in altering regulation of potato plant growth and development, is discussed. The attention is drawn to the possible involvement at the subcellular level of sucrose phosphate synthase in mediating the phenotypic effects caused by T-cyt transformation.

Adaptation, Physiological

Response rates, duration of response, and dose response effects in phase I studies of antineoplastics.

Over a period of 14 years, 7,960 patients were treated in 228 phase I trials. In these patients, there were 75 complete and 432 partial responses for an overall objective response rate of 6%. Complete responses lasted a median of six months (range 1-18), while partial responses lasted a median of three months (range 1-17). Of note is that no drug has made it to the market which has not had a response in phase I trials. Responses were noted in very diverse histologic types of tumors. Although there were responses at doses which were as low as 3-5% of the recommended dose for phase II trials, the majority of responses did occur at 80-120% of the dose recommended for phase II trials. Although the response rate in phase I trials is indeed low, responses do occur. This response rate information should help the clinician provide facts for the patient considering a phase I trial with new anticancer agents. These findings also emphasize that although phase I trials are characteristically dose-finding studies, if no responses are noted in phase I studies, it is unlikely the drug will be used routinely in the clinic.

Antineoplastic Agents

Cohort reconstruction: which infants can be restudied at school age?

Longer-term follow-up of infants with specific health concerns, such as low birthweight, is critical to assessing the effect of medical interventions. This report examines the approach of reconstructing previously studied cohorts in terms of the factors discriminating between respondents and non-respondents. Follow-up was attempted during 1987-1988 for 1875 children born during a 6-month period in 1978 in three geographically defined regions in the United States, for whom 1-year assessments of health and developmental status were obtained at 1 year of age as part of a previous study. For a 25% sample, participation involved a clinic visit for developmental assessments; for the remainder an interview by telephone or home visit. Follow-up was obtained for 72.5% of the cohort. Refusal rates were low (7%); most non-response was due to an inability to locate the families. Predictors of non-response reflected primarily low socio-economic status; completion rates were not influenced by mode of assessment. The role of a tracing agency is discussed. We conclude that cohort reconstruction is feasible with response rates comparable to some prospective studies with ongoing cohort maintenance.

Child Development

Tyranny and freedom: looking at ideas in the practice of family therapy.

This article comments upon recent "second-order" family therapy concerns about the nature of the therapeutic relationship, and explores how ideas held by therapists may rule and restrict therapeutic conversations. Ideas are examined in the light of how adherence to them might open space (free) or close space (tyrannize) with respect to the therapeutic relationship. The authors propose a philosophical viewpoint, a methodology, and practical suggestions for therapists wishing to maintain a stance of relative freedom with respect to ideas in their work with clients.

Attitude of Health Personnel