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Biomedical subjects

C Turner

Publications and source records attributed to C Turner.

At least 55 records · Page 3Linked to original sources

Antitumor polycyclic acridines. 7. Synthesis and biological properties of DNA affinic tetra- and pentacyclic acridines.

New synthetic routes to a series of tetra- and pentacyclic acridines related in structure to marine natural products are reported. The novel water-soluble agent dihydroindolizino[7,6,5-kl]acridinium chloride 14 has inhibitory activity in a panel of non-small-cell lung and breast tumor cell lines exceeding that of m-AMSA. The salt inhibited the release of minicircle products of kDNA confirming that disorganization of topoisomerase II partly underlies the activity of the compound. COMPARE analysis of the NCI mean graph profile of compound 14 at the GI(50) level corroborates this conclusion with Pearson correlation coefficients (>0.6) to clinical agents of the topoisomerase II class: however, this correlation was not seen at the LC(50) level. The inhibitory action of 14 on Saccharomyces cerevisiae transfected with human topoisomerase II isoforms showed a 3-fold selectivity against the IIalpha isoform over the IIbeta isoform. Unlike m-AMSA, 14 is not susceptible to P-glycoprotein-mediated drug efflux and retains activity in lung cells with derived resistance to the topoisomerase II inhibitor etoposide.

Acridines↗

Determination of vitamins A and E in milk powder using supercritical fluid extraction for sample clean-up.

A method for the analysis of the natural contents of vitamins A and E in milk powder has been developed. The method utilises supercritical fluid extraction, a miniaturised alkaline saponification procedure and reversed-phase HPLC with UV detection. Modifications of the sample matrix, combinations of static and dynamic modes of extraction and effects of changes in extraction parameters such as temperature, flow-rate, time, collection solvent and collection temperature were studied to optimise the extraction efficiency and selectivity. Supercritical CO2 at 80 degrees C and 37 MPa, modified with 5% methanol and pumped at a flow-rate of 1.0 ml/min, gave recoveries of 99 and 96% for vitamins A and E, respectively, using a 15 min static followed by a 15 min dynamic extraction. The measurements gave a within-day RSD of 4% for both vitamin A and E, and between-day RSDs of 4 and 8% for vitamins A and E, respectively.

Animals↗

Jefferson fracture resulting in Collet-Sicard syndrome.

STUDY DESIGN: A case report and review of the literature. OBJECTIVE: To increase awareness of and add to the spectrum of injury that can result from Jefferson fractures, to suggest a possible mechanism of injury, and to give a brief review of pertinent facts regarding C1 burst fractures and the Collet-Sicard Syndrome. SUMMARY OF BACKGROUND DATA: To the author's knowledge, this is the first reported case of a Jefferson fracture resulting in Collet-Sicard Syndrome. It represents only the second reported case of cranial nerve palsy caused by Jefferson fracture. METHODS: A 56-year-old man sustained a C1 burst fracture in a rollover motor vehicle accident. Repeated neurologic examinations over the ensuing days revealed lesions of cranial nerves IX, X, XI, and XII on the left side. RESULTS: Two weeks of traction, 10 weeks in a halo vest, and 2 weeks in a cervical collar resulted in adequate fracture healing and almost complete resolution of the patient's neurologic symptoms. CONCLUSION: Although this is the first reported case of Collet-Sicard Syndrome caused by Jefferson fracture, the authors' review of the literature suggests that cranial nerve injuries may go unrecognized in some patients with C1 burst fractures. The importance of a thorough neurologic examination, including examination of the cranial nerves, in all cases of cervical spine injury cannot be overemphasized.

Accessory Nerve Diseases↗

Seven ring (X) chromosomes lacking the XIST locus, six with an unexpectedly mild phenotype.

Small ring (X) chromosomes lacking the XIST gene at Xq13.2 have been associated with a severe phenotype that includes mental retardation, facial dysmorphism and congenital abnormalities. It has been hypothesised that the loss of XIST results in functional disomy for the sequences contained in the ring. We studied 47 females with a 45,X/46,r(X) karyotype and found seven to have an XIST-negative ring. Only one of the seven patients had the severe phenotype. The remaining six patients had physical phenotypes consistent with Turner syndrome. The rings were characterised cytogenetically and molecularly. The severe phenotype in one patient can be explained by the absence of XIST expression, the relatively large amount of Xp material in the ring and, possibly, the concomitant maternal uniparental isodisomy. We propose three explanations for the unexpectedly mild phenotypes in the remaining six patients; (1) the rings contained limited amounts of X-chromosome material, and sequences that, when functionally disomic, result in a severe phenotype were absent; (2) mosaicism resulting in the absence of the ring from tissues, such as the brain, which are important in the severe phenotype and (3) the presence of an inactive X in some tissues at some time, exemplified by the demonstration of XIST expression in one patient.

Abnormalities, Multiple↗

A clinical, cytogenetic and molecular study of 47 females with r(X) chromosomes.

We studied 47 patients with a 45,X/46,X,r(X) karyotype to identify phenotypic differences between these patients and 45,X patients, and to determine whether these differences could be explained by the status of genes within the ring. Only 2 patients had the 'severe' r(X) phenotype, and both were consistent with this resulting from functional disomy of genes normally subject to X inactivation. A further 7 patients also carried active rings but these patients did not have a more severe phenotype than those whose rings were inactivated, probably because their rings were smaller and did not contain the (as yet unidentified) genes whose functional disomy is particularly damaging. Patients with a r(X) did not show clear physical differences when compared with a 45,X series, except for a possible reduction in the frequency of oedema in those whose r(X) had an Xq breakpoint distal to DXS128E, at Xq13.2. Thus some protection from oedema may be provided by the presence of two copies of Xq13.2.

Adolescent↗

Ring-X chromosomes: their cognitive and behavioural phenotype.

We tested the cognitive abilities and educational attainments of 47 patients with a ring X chromosome, to evaluate the extent to which these variables correlated with failure of r(X) inactivation and with mosaicism. We found possession of a r(X) chromosome was associated with an increased risk of significant learning difficulties, and with associated behavioural maladjustment, compared with 45,X Turner females. Nearly a third had been educated outside mainstream schools. The proportion of cells in peripheral blood containing an inactivated r(X) chromosome was negatively correlated with nonverbal IQ. The parental origin of the normal chromosome did not appear to affect adjustment or abilities. In a minority of r(X) cases associated with mental retardation, there had been a failure to inactivate the ring, due to loss of the XIST locus. However, failure of X-inactivation was not necessarily associated with a severe phenotype. The degree of impairment in IQ depended on the size of the active ring, and hence was proportionate to the number of (as yet unidentified) genes whose functional disomy affected brain development and functioning.

Adolescent↗

The inactivation of foot and mouth disease, Aujeszky's disease and classical swine fever viruses in pig slurry.

The aim of the study was to investigate the decontamination of pig slurry containing exotic viruses of pigs, foot AND mouth disease virus (FMDV), Aujeszky's disease virus (ADV) AND classical swine fever virus (CSFV). Laboratory-scale decontamination experiments showed that FMDV, ADV and CSFV were heat inactivated in slurry within 3 min at 67 degrees C, 3 min at 62 degrees C and 3 min at 60 degrees C and in Glasgow Eagles medium within 5 min at 67 degrees C, 4 min at 65 degrees C and 2 min at 65 degrees C, respectively. At pilot scale, FMDV was heat inactivated at 66 degrees C in water and 61 degrees C in slurry, ADV at 61 degrees C in water or slurry and CSFV at 62 degrees C in water and 50 degrees C in slurry. Treatment of pig slurry for the inactivation of exotic viruses may be achieved through the use of a thermal pilot plant operating in continuous mode. The work demonstrates the suitability of thermal treatment in ensuring the safety of pig slurry following a disease outbreak.

Animals↗

Freezing method affects the concentration and variability of urine proteins and the interpretation of data on microalbuminuria. The Oxford Regional Prospective Study Group.

AIMS: Microalbuminuria and, to a lesser extent, renal tubular proteins are widely used in the early detection of incipient nephropathy in diabetes mellitus. Recent reports have indicated detrimental effects of storage at -20 degrees C on urine proteins. This study investigated the effects of storage on the measurement of urine proteins and discusses implications for the interpretation of data. METHODS: Two-hundred and sixty-eight specimens, collected from children with Type 1 diabetes, split into duplicate aliquots and stored at -20 degrees C and -70 degrees C, respectively, for 6-8 months, were analysed for albumin, retinol binding protein, N-acetyl glucosaminidase and creatinine, in the same assays to eliminate inter-assay variability. Two independent non-diabetic cohorts of children provided urine specimens, which were stored at -20 degrees C for one cohort and -70 degrees C for the other, to determine normal ranges for urine proteins. RESULTS: Storage at -20 degrees C led to a variable underestimation of all three urine proteins in 20% of specimens. Creatinine was unaffected. This underestimation was greater in more concentrated urine (r2 = 0.38, P < 0.001, n = 262). Consequently storage at -20 degrees C increased the variance of the albumin/ creatinine ratio more than the variance of albumin concentration. Temperature of storage affected the normal range, which was 0.1-2.1 mg/mmol at -20 degrees C compared to 0.3-3.1 mg/mmol at -70 degrees C. The prevalence of microalbuminuria (> 2SD above the geometric mean in non-diabetic specimens stored at -20 degrees C) was 27% after storage at -70 degrees C vs. 24% after -20 degrees C. The prevalence of microalbuminuria (>2SD above the geometric mean in nondiabetic specimens stored at -70 degrees C) was 21% after storage at -70 degrees C vs. 17% after -20 degrees C. CONCLUSIONS: Urine proteins are significantly but variably underestimated after storage at -20 degrees C. These effects account for increased variance and differences in the normal range, but have less effect on the detection of microalbuminuria than might be predicted.

Acetylglucosaminidase↗

Is audio computer-assisted self-interviewing a feasible method of surveying in Zimbabwe?

BACKGROUND: Research into reproductive health is dependent on participants accurately reporting sensitive behaviours. We examined whether audio computer-assisted self-interviewing (ACASI), which increased sensitive behaviour reporting in the US, is a feasible method of surveying in developing countries. METHODS: Zimbabwean women in three educational groups were surveyed about demographics and family planning using interviewer and ACASI modes. An exit survey was administered to elicit information about the participants' opinions and experiences using ACASI. RESULTS: The majority of women (86%) preferred ACASI to interviewer mode. The reasons mentioned were always related to increased confidentiality and privacy. Ability to use ACASI and user preferences varied with educational level. More women with primary school or less education (53%) reported problems with computer use than women in the higher educational groups (10-12%). The percentage of women having perfect response concordance between ACASI and interviewer modes increased significantly with education (64%, 81%, and 84% respectively; P(trend) < 0.001). CONCLUSIONS: Use of ACASI may be more feasible in Zimbabwe and other developing countries than was originally thought, but ACASI programs should continue to be improved and tested in various countries and population groups.

Adult↗

Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock.

BACKGROUND: Procalcitonin (PCT), a marker of bacterial sepsis, may also act as a mediator of the inflammatory response to infection, and thus influence outcome. OBJECTIVE: To investigate the relationship between PCT, interleukin (IL)-10, tumor necrosis factor (TNF), organ failure, and mortality in pediatric septic shock. DESIGN: Prospective observational study. SETTING: A 16-bed pediatric intensive care unit of a university hospital. PATIENTS: A total of 75 children with septic shock having a median age of 43.1 months (range, 0.1-192 months). Children who had received antibiotics for >24 hrs were excluded. A total of 37 patients (49%) had meningococcal disease, and 72 patients (96%) required mechanical ventilation. INTERVENTIONS: The pediatric risk of mortality (PRISM) score, multiple organ system failure (MOSF) score, duration of ventilation, length of ICU stay, and outcome were recorded. PCT, IL-10, and TNF were measured at admission to the intensive care unit. Sequential PCT levels were available at 0 hrs and 24 hrs in 39 patients (52%). RESULTS: Observed mortality was 21/75 (28%). Data are median (range). The admission PCT (p = .0002) and TNF levels (p = .0001) were higher in children with higher MOSF scores. In survivors and nonsurvivors, the admission PCT was 82 ng/mL vs. 273 ng/mL (p = .03), IL-10 was 62 pg/mL vs. 534 pg/mL (p = .03), and TNF was 76 pg/mL vs. 480 pg/mL (p = .001), respectively. Area under the mortality receiver operating characteristic curve was 0.73 for PCT, 0.67 for IL-10, and 0.76 for TNF, compared with 0.83 for the PRISM score. Of 39 children, 16 (41%) with sequential PCT measurements showed no fall in PCT after 24 hrs treatment. These children had higher admission levels of IL-10 (p = .03), and TNF (p = .03) compared with children who demonstrated a subsequent fall in PCT. Although the former did not have a higher median PRISM (p = .28) or MOSF score (p = .19), observed mortality was 44% (7 of 16) compared with 9% (2 of 23) (p = .02). CONCLUSION: The admission PCT, like TNF and IL-10, is related to the severity of organ failure and mortality in children with septic shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic significance.

Adolescent↗

Axial distribution and characterization of basolateral P2Y receptors along the rat renal tubule.

BACKGROUND: Several groups have identified P2Y receptors in the basolateral membrane of the rat nephron. These studies have not covered all segments of the nephron and have relied solely on the relative potency of receptor agonists for classification. METHODS: We measured purine and pyrimidine-induced changes in intracellular free calcium concentration ([Ca(2+)](i)) in anatomically defined segments of the rat nephron. To complement these functional studies, we have used reverse transcription-polymerase chain reaction methodology to identify specific P2Y receptor transcripts in these segments. RESULTS: Adenosine 5'-triphosphate (ATP) mobilized [Ca(2+)](i) in all nephron segments, except for the thick ascending limb of Henle, which was poorly responsive. Adenosine (100 micromol/L) was without effect, confirming that the effect of ATP was mediated by P2 receptors. In the proximal convoluted tubule (PCT) and outer medullary collecting duct (OMCD), there was evidence for two receptor subtypes with characteristics of P2Y(1)- and either P2Y(2)- or P2Y(4)-like receptors. A novel finding in the thin limbs was the presence of a receptor with properties of both P2Y(2) and P2Y(4) receptor subtypes. To aid classification, we identified P2Y receptor mRNA in rat nephron segments. In the PCT and OMCD and thin ascending limb of Henle, we found expression of P2Y(1), P2Y(2), and P2Y(4) receptors. In the descending limb of Henle, P2Y(1) and P2Y(2) mRNA was found, but P2Y(4) was not expressed. CONCLUSION: These data suggest that extracellular ATP can influence tubular cell function in all segments of the rat nephron, through P2Y receptors via multiple (and coexpressed) P2Y receptor subtypes.

Adenosine Triphosphate↗

Spiritual issues in family therapy: a graduate-level course.

With the advent of the biopsychosocial approach in family therapy, the domain of spiritual issues is increasingly being recognized as important to families. This article will describe a graduate-level seminar on Spiritual Issues in Family Therapy at the University of San Diego that offers family therapy students the opportunity to examine issues of spirituality, religion, and meaning and their place in therapy. One premise of the course is that research has demonstrated that most clients consider their spiritual life to be relevant to personal problems and would prefer a therapist who is comfortable with such topics. The goals of the course include (1) training in opening a dialogue with individuals and families about spiritual issues and discerning when referral may be appropriate; (2) expanding an awareness of wisdom traditions through use of comparative religions material; and (3) identifying from current practice many of the spiritual issues that may arise in the clinical setting.

Curriculum↗

A study of district nurses' experiences of continuous ambulatory chemotherapy.

As a result of technical developments and policies that promote shorter hospital stays, patients are increasingly receiving high technology treatment in the community. The administration of ambulatory intravenous chemotherapy at home is an example of such treatment. Despite being generalist nurses, district nurses (DNs) are involved in what could be viewed as 'specialist' care - advising and supporting patients while they are receiving treatment. This article reports on a study of 20 DNs from one community trust and examines the sources of the knowledge and skills used in caring for these patients and the communication links with the regional cancer centre.

Antineoplastic Agents↗

Prenatal diagnosis of wormian bones.

The prenatal diagnosis of wormian bones has not been made previously. We report four fetuses with wormian bones but none of the associated anomalies. The diagnosis, differential diagnosis, associated anomalies, and prognosis of this entity are discussed.

Adult↗

Air-contrast sonohysterography as a first step assessment of tubal patency.

We assessed the use of air as a sonographic contrast agent in the investigation of tubal patency by sonohysterography. We examined 115 women assessed for infertility. After saline sonohysterography, small amounts of air were insufflated, and the tubal passage of bubbles was monitored. In five patients (excluded from the results), cervical stenosis prevented the procedure. Ninety-one tubes (right side) and 86 tubes (left side) were definitively patent; 5 and 7, respectively, were probably patent; and 12 and 16, respectively, were nonvisualized. Nine patients had polyps, 3 had synechiae, and 2 had submucosal fibroids. None of the patients had infectious complications. Air-sonohysterography and laparoscopy with chromopertubation showed agreement in 79.4%. In 17.2% of patients, the tubes were considered nonvisualized by air-sonohysterography when they were patent. The sensitivity was 85.7% and specificity 77.2%. In conclusion, air-sonohysterography is a comfortable, simple, and inexpensive first line of tubal patency investigations yielding high accuracy.

Adolescent↗

Antihistamines and aircrew: usefulness of fexofenadine.

INTRODUCTION: The aim of this study was to establish whether fexofenadine hydrochloride, an antihistamine, modulates daytime sleepiness or performance. METHODS: The effects of fexofenadine (120, 180, and 240 mg) on digit symbol substitution, tracking, and vigilance tasks, and on objective (multiple sleep latency test) and subjective sleepiness, were studied in six healthy volunteers (two males, four females, aged 20-34 [mean 26.5] yr) from 1 h pre-ingestion to 8 h post-ingestion. The study was placebo-controlled and double-blind with a six-way cross-over design. The centrally acting antihistamine, promethazine (10 mg), was used as an active control to confirm the sensitivity of the experimental procedures. RESULTS: There were no changes in performance or sleepiness with any dose of fexofenadine at any time, compared with placebo. Promethazine, compared with both placebo and fexofenadine, impaired performance on the digit symbol substitution task (2.5 h post-ingestion), vigilance task (2.5-5h post-ingestion) and tracking task (2.5-3.5 h post-ingestion), increased objective sleepiness (1.5-2.5 h post-ingestion) and subjective sleepiness (1.5-8h post-ingestion). CONCLUSION: Consideration may be given to the clinical use of currently licensed doses of fexofenadine (120-180 mg) by individuals involved in skilled activity. Fexofenadine may be potentially useful for aircrew.

Adult↗

Heterogeneity of coronary heart disease risk factors in Indian, Pakistani, Bangladeshi, and European origin populations: cross sectional study.

OBJECTIVE: To compare coronary risk factors and disease prevalence among Indians, Pakistanis, and Bangladeshis, and in all South Asians (these three groups together) with Europeans. DESIGN: Cross sectional survey. SETTING: Newcastle upon Tyne. PARTICIPANTS: 259 Indian, 305 Pakistani, 120 Bangladeshi, and 825 European men and women aged 25-74 years. MAIN OUTCOME MEASURES: Social and economic circumstances, lifestyle, self reported symptoms and diseases, blood pressure, electrocardiogram, and anthropometric, haematological, and biochemical measurements. RESULTS: There were differences in social and economic circumstances, lifestyles, anthropometric measures and disease both between Indians, Pakistanis, and Bangladeshis and between all South Asians and Europeans. Bangladeshis and Pakistanis were the poorest groups. For most risk factors, the Bangladeshis (particularly men) fared the worst: smoking was most common (57%) in that group, and Bangladeshis had the highest concentrations of triglycerides (2.04 mmol/l) and fasting blood glucose (6.6 mmol/l) and the lowest concentration of high density lipoprotein cholesterol (0.97 mmol/l). Blood pressure, however, was lowest in Bangladeshis. Bangladeshis were the shortest (men 164 cm tall v 170 cm for Indians and 174 cm for Europeans). A higher proportion of Pakistani and Bangladeshi men had diabetes (22.4% and 26.6% respectively) than Indians (15.2%). Comparisons of all South Asians with Europeans hid some important differences, but South Asians were still disadvantaged in a wide range of risk factors. Findings in women were similar. CONCLUSION: Risk of coronary heart disease is not uniform among South Asians, and there are important differences between Indians, Pakistanis, and Bangladeshis for many coronary risk factors. The belief that, except for insulin resistance, South Asians have lower levels of coronary risk factors than Europeans is incorrect, and may have arisen from combining ethnic subgroups and examining a narrow range of factors.

Adult↗