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Mark A Turner

Publications and source records attributed to Mark A Turner.

18 recordsLinked to original sources
PubMed2006

The role of angiotensin receptor-1 blockade on electromechanical changes induced by left ventricular hypertrophy and its regression.

OBJECTIVE: The aims of this study were to: i) investigate the role of angiotensin in mediating changes to myocardial electromechanical properties during the development and regression of left ventricular hypertrophy (LVH) generated by constriction of the thoracic aorta; ii) identify any role of angiotensin-1 receptor blockade on ameliorating changes to these electromechanical properties. METHODS: LVH was induced in guinea-pigs by constricting the ascending aorta (AC groups). After 42+/-3 days, the constriction was either removed or left in place. Following the second operation animals were fed losartan (10 mg x kg(-1) x day(-1)) or saline for 42+/-3 days. Sham-operated animals served as controls. In other groups, LVH was generated by subcutaneous angiotensin II (200 ng x kg(-1) x min(-1)) infusion for 42+/-3 days with or without losartan administration (AT groups), and compared to animals undergoing aortic constriction for a similar period. Electromechanical changes were recorded in isolated left ventricular myocardial preparations. RESULTS: Wet and dry heart-to-body weight ratios (HBR) increased significantly in the AC and AT models compared to control. Losartan prevented the increase of HBR in the AT group. Removal of the constriction allowed LVH to regress to control. The force-frequency relationship was reduced in both models and recovered fully on regression. However, the two models generated different electrophysiological changes: in the AC group, longitudinal conduction velocity was reduced and transverse conduction increased, with a consequent reduction of the anisotropic conduction ratio. On regression recovery was only partial; action potential duration was prolonged and did not recover. In the AT group, electrophysiological changes were limited: only an increase of transverse conduction and a reduction of the anisotropic conduction ratio were observed. Losartan had no effect on HBR or electromechanical variables in the aortic constricted animals, nor did it affect the extent of recovery in animals with regression of LVH. CONCLUSIONS: The electromechanical changes to hypertrophied myocardium are different in these two models of LVH. Moreover, losartan was ineffective in modulating the consequences of hypertrophy induced by constriction of the thoracic aorta.

Angiotensin II↗
PubMed2006

TASK channel expression in human placenta and cytotrophoblast cells.

OBJECTIVE: The multinucleate syncytiotrophoblast is the transporting epithelium of the human placental villus, formed throughout pregnancy by fusion and differentiation of underlying mononucleate cytotrophoblast cells. Similar to other epithelia, K+ channels will impact on syncytiotrophoblast transport properties during its development and differentiation. Therefore we investigated expression and activity of the two-pore domain K+ channels TASK1 and 2 in relation to gestation and differentiation, using villous tissue from first and third trimester and cultured cytotrophoblast cells at mononucleate and multinucleate stages of culture. METHODS: Quantitative real-time polymerase chain reaction (PCR), immunofluorescence, and 86Rb+ (K) efflux were used to investigate TASK channel expression and function. RESULTS: TASK2 mRNA expression was higher in first trimester than term (10 to 13 vs 38 to 40 weeks, P < .05). Other K+ alpha-subunit mRNAs, including TASK1, remained unaltered but the regulatory BKCa beta-subunit, like TASK2, was higher in first trimester than term (P < .001). Immunofluorescence showed that TASK2 had an intracellular localization within the trophoblast of first trimester villi but was less abundant and restricted to stem villi at term. TASK2 also showed intracellular localization in mononucleate cytotrophoblast cells in culture and expression was lost with multinucleation. By contrast, TASK1 was localised, independently of cell nucleation, to cytotrophoblast cell plasma membranes. 86Rb+ (K) efflux was measured from multinucleated cytotrophoblast cells. Both basal and pH 8.0-stimulated efflux was inhibited by the TASK1 antagonist anandamide (n = 5 for both conditions; P < .01 and P < .001, respectively). CONCLUSION: TASK1 and 2 are expressed in placental trophoblast cells and TASK1 activity may have a role in regulating syncytiotrophoblast homeostasis and/or solute transport functions.

Arachidonic Acids↗
PubMed2005

Placental phenotypes of intrauterine growth.

The placenta is essential to nutrition before birth. Recent work has shown that a range of clearly defined alterations can be found in the placentas of infants with intrauterine growth restriction (IUGR). In the mouse, a placental specific knockout of a single imprinted gene, encoding IGF-2, results in one pattern of alterations in placenta structure and function which leads to IUGR. We speculate that the alterations in the human placenta can also be grouped into patterns, or phenotypes, that are associated with specific patterns of fetal growth. Identifying the placental phenotypes of different fetal growth patterns will improve the ability of clinicians to recognize high-risk patients, of laboratory scientists to disentangle the complexities of IUGR, and of public health teams to target interventions aimed at ameliorating the long-term adverse effects of inadequate intrauterine growth.

Animals↗
PubMed2005

Acute military psychiatric casualties from the war in Iraq.

BACKGROUND: The view that most military personnel evacuated from war zones are suffering from combat stress reactions, or are otherwise traumatised by the horrors of war, has an impact on all aspects of military psychiatry. AIMS: To delineate the reasons for psychiatric aeromedical evacuation from Iraq from the start of build-up of UK forces in January 2003 until the end of October that year, 6 months after the end of formal hostilities. METHOD: A retrospective study was conducted of field and in-patient psychiatric assessments of 116 military personnel evacuated to the UK military psychiatric in-patient facility in Catterick Garrison. RESULTS: Evacuees were mainly non-combatants (69%). A significant proportion were in reserve service (21%) and had a history of contact with mental health services (37%). Only 3% had a combat stress reaction. In over 85% of cases evacuation was for low mood attributed to separation from friends or family, or difficulties adjusting to the environment. CONCLUSIONS: These findings have implications especially for screening for suitability for deployment, and for understanding any longer-term mental health problems arising in veterans from Iraq.

Acute Disease↗
PubMed2004

GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma.

PURPOSE: Neuroblastoma (NB) is a common childhood malignancy characterized by heterogeneous clinical behavior. The purpose of this study was to identify potential NB biomarkers that may improve outcome prediction. PATIENTS AND METHODS: The suppression subtractive hybridization (SSH) technique was used to identify the genes differentially expressed between NB and control tissue. RNA isolated from 235 primary NB tumor samples obtained from the Children's Cancer Group was evaluated for expression of the candidate markers using quantitative reverse transcriptase polymerase chain reaction (Taqman assays). The association between the mRNA expression levels in the identified candidate genes and clinical outcome was evaluated. RESULTS: SSH analysis identified differential expression of members of the GABAergic gene family in NB. Lower levels of gamma-aminobutyric acid (GABA) receptor-associated protein (GABARAP) gene expression predict decreased survival among all patients. GABA(A) delta receptor subunit gene expression was predictive of a poor outcome among Evans stage IV-S patients. An index of five coexpressed GABA(A) receptor subunits was identified (GABA(A) profile [GAP score]). Patients with a higher GAP score (> -1) had a survival advantage. Multivariate analysis showed that GABARAP and GABA(A) alpha2 receptor subunit gene expression levels and GAP score remained predictors of clinical outcome after accounting for current prognostic indicators. CONCLUSION: Dysregulation of the GABAergic system may constitute a fundamental event in the development of NB, and assessment of GABAergic system gene expression could provide improved patient stratification and potential new therapies.

Adaptor Proteins, Signal Transducing↗
PubMed2004

The regulation of interleukin-6 secretion by prostanoids and members of the tumor necrosis factor superfamily in fresh villous fragments of term human placenta.

OBJECTIVE: To determine whether prostanoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and members of the tumor necrosis factor superfamily can regulate placental secretion of interleukin-6 (IL-6) and whether labor influences any such effects. METHODS: Villous fragments of term, human placenta were kept in culture for up to 4 hours, and IL-6 concentrations were measured in the supernatant. We assessed the effects of the following prostanoids: PGE(2), PGF(2alpha), thromboxane A(2) mimetic (U-46619), and carbacyclin, a stable prostacyclin analogue (all at 1 microM); NSAIDs: indomethacin (150 microM) or nimesulide (100 microM); and Fas ligand (5 ng/mL). RESULTS: Secretion (mean +/- standard error) of IL-6 was, for control conditions, 1.92 +/- 0.28 fmol/mg wet weight per 3 hours; for PGE(2), 3.57 +/- 0.29 fmol/mg wet weight per 3 hours, P <.01; and for carbacyclin, 3.11 +/- 0.44 fmol/mg wet weight per 3 hours, P <.01. Incubation with PGF(2alpha) or the thromboxane A(2) analogue, U46619, had no effect on IL-6 secretion under these conditions. Fas ligand stimulated IL-6 secretion (3.06 +/- 0.38 fmol/mg wet weight per 3 hours, P <.05). Labor did not alter the effects of prostanoids or FasL. The effects of NSAIDs were assessed over 4 hours. Secretion (median, interquartile range) was, under control conditions 3.26, 2.83-6.23 fmol/mg wet weight per 4 hours, with indomethacin 1.4, 1.28-3.21 (P <.05), and with nimesulide 0.75, 0.50-1.56 fmol/mg wet weight per 4 hours. The magnitude of the effect of Fas ligand in the presence of NSAIDs depended on whether the placentas were delivered before or after labor. CONCLUSION: Prostanoids, NSAIDs, and the Fas ligand regulate placental IL-6 secretion. Although the effects of individual agents did not vary with the presence or absence of labor, modulation of IL-6 secretion by labor became apparent when agents were combined.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2004

Post-traumatic stress and disability.

BACKGROUND: Post-traumatic stress is thought to account for significant disability. It is also known to be highly comorbid with other psychiatric conditions such as depression and alcohol dependence. AIMS: To determine the relationship between post-traumatic stress, depression, alcohol dependence and disability. METHOD: Seventy armed services personnel were assessed for DSM-IV diagnoses of post-traumatic stress disorder, major depressive disorder and alcohol dependence, and with continuous measures of symptoms of post-traumatic stress, depression and alcohol dependence following a traumatic event. These variables, as predictors of disability (using the Sheehan Disability Scale), were analysed using multivariate analysis of variance, analysis of covariance and multiple regression backward elimination models. RESULTS: No significant interaction was found for the diagnostic variables even after controlling for the continuous symptom measures. In the regression models, symptoms of depression were a significant predictor of total disability (R(2)=0.39). Symptoms of alcohol dependence and post-traumatic stress did not significantly predict disability. CONCLUSIONS: Since post-traumatic stress was not found to be associated with disability, its clinical importance may be questionable.

Adult↗
PubMed2004

British military forensic psychiatry.

Military psychiatry has recently generated a lot of interest. In contrast there is virtually no literature on military forensic psychiatry. The first section of the paper is a brief review of British military psychiatric services and recent data on the prevalence of mental illness in British armed forces personnel. The second section summarizes the relevant aspects of the British military judicial and penal systems including the practice of summary justice, the court martial system, and sentencing and corrective training. The third section of the paper addresses issues which are particular to forensic psychiatry, including mental defences in relation to the military, the military offences of malingering and impersonation, risk assessment in military contexts and the notion of 'temperamental unsuitability' to military service.

Crime↗
PubMed2003

Electrophysiological effects accompanying regression of left ventricular hypertrophy.

OBJECTIVE: The aim of this study was to investigate changes following regression of left ventricular hypertrophy (LVH). METHODS: Electrophysiolological changes were recorded in isolated guinea-pig myocardial preparations. LVH was induced by constriction of the thoracic aorta and regression was followed after removal of the constriction. Sham-operated animals served as controls. RESULTS: During 42 days constriction, heart/body weight ratio increased (3.19+/-0.49 vs. 3.85+/-0.83 g kg(-1)) and was accompanied by an increase of cell size. Forty-two days after clip removal, values had returned to control values. LVH increased action potential (AP) duration (mean 112% of control) and decreased conduction velocity (60.4+/-3.3 vs. 45.9+/-4.6 cm(-1)). These changes did not return to control after regression of LVH. The changes to condition velocity were attributed solely to increases of intracellular resistivity. The positive staircase response also decreased with LVH, but did recover upon regression. In isolated whole hearts, no changes to subepicardial action potential duration, QRS complex duration or AP refractory period were observed in LVH or its regression. During low-flow ischaemia AP duration shortened reversibly, the rate of shortening was more rapid in hypertrophied hearts but similar to control in regressed hearts. The incidence of ventricular tachyarrhythmias of fibrillation during low-flow ischaemia was similar in control, hypertrophied and regressed hearts. CONCLUSION: Morphological regression of LVH is not accompanied by reversal of electrophysiological changes measured in isolated preparations, whereas some aspects of contractile function to recover.

Action Potentials↗
PubMed2003

Structural remodelling of lungs in chronic heart failure.

In order to determine whether morphological changes could account for a previously reported reduction in pulmonary capillary filtration in heart failure, we studied pulmonary morphology in lungs from a guinea-pig chronic heart failure model. Heart failure was induced by banding the ascending aorta with sham operated animals serving as controls; all animals were studied at 158 +/- 6 days post-operation. Following banding, a reduction in aortic flow, increased peripheral vascular resistance and raised left ventricular end diastolic, left atrial and right ventricular pressures together with increased right ventricle to body weight ratio (all p < 0.05) are indicative of established pulmonary hypertension and heart failure. This was associated with an increase in pulmonary septal volume fraction (38.1 +/- 3.1% vs 24.6 +/- 2.3 %, p < 0.01) and reticulin fibre density. There was also evidence of siderophage infiltration and examination of pulmonary ultra structure revealed a significantly thicker alveolar-capillary barrier in heart failure (1278 +/-76 vs 638 +/- 32 nm, p < 0.001), thickening of both the alveolar (89%, p < 0.01) and capillary (69%, p < 0.05) basal laminae with pericyte and collagen in filtration of the alveolar-capillary barrier. We hypothesise that these pulmonary adaptations provide protection from oedema formation, but whilst initially protective, are also likely to confer major long-term disadvantages in chronic heart failure.

Animals↗
PubMed2003

Physical and psychiatric predictors of late whiplash syndrome.

Approximately 40% of people who sustain whiplash injuries, complain of chronic physical and psychiatric symptoms. Associations have been found between pre-accident physical symptoms and physical outcome and between pre-accident psychiatric variables and both physical and psychiatric outcome. There are no reported investigations of the association between pre-accident physical symptoms and psychiatric outcome. In this study, 33 consecutive cases of whiplash injury met inclusion criteria from a series of psychiatric reports used in civil litigation. Outcome was measured for each patient and correlated with a range of pre-accident physical and psychiatric variables using multivariate regression. There was no association between pre-accident psychiatric factors and overall outcome. Older age and a pre-accident history of musculoskeletal complaints correlated with the physical and psychiatric outcome. In whiplash injury, pre-accident psychiatric factors may have little bearing on long-term prognosis. Physical and psychiatric outcome of late whiplash syndrome is probably worse in older individuals and in patients with a pre-accident history of musculoskeletal complaints.

Adult↗
PubMed2003

Management of mental illness by the British Army.

BACKGROUND: The Ministry of Defence has its own hospital for soldiers requiring admission for mental health problems. AIMS: To assess the efficiency of the army psychiatric hospital at restoring patients to full active duty. To assess whether a new military training and rehabilitation unit (MTRU) that emphasises military-skills training, improves outcome. METHOD: A 2-year, inception-cohort outcome study of hospital in-patients. A 12-month, case-matched, 'before and after' outcome study compared MTRU patients with hospital in-patients. RESULTS: I (hospital in-patients, n=309): at 2-year follow-up 67 (22%) were fully fit for active duty. Military psychiatrists' success rate at predicting recovery to active duty was 27%. 2: the odds of a soldier in the MTRU cohort (n=35) returning to active duty were 14 times greater than for the hospital cohort (n=35). The odds of remaining in the army while unfit for active duty were 20 times less for the MTRU than for the hospital cohort. CONCLUSIONS: The army hospital is inefficient at rehabilitation to active duty. The MTRU significantly increased the odds of returning to active duty and reduced the odds of remaining in the army while still unfit. These findings may be applicable to the emergency services.

Adolescent↗
PubMed2002

A multicenter, randomized, investigator-blinded study of 5- and 10-day gatifloxacin versus 10-day amoxicillin/clavulanate in patients with acute bacterial sinusitis.

BACKGROUND: Treatment guidelines for acute bacterial sinusitis recommend 10 to 14 days of therapy with amoxicillin/clavulanate, high-dose amoxicillin, cefpodoxime, cefuroxime, or a newer fluoroquinolone. OBJECTIVE: This study compared the clinical efficacy of short-course (5-day) gatifloxacin with standard 10-day regimens of amoxicillin/clavulanate or gatifloxacin in patients with a diagnosis of acute, uncomplicated maxillary sinusitis. METHODS: This was a multicenter, investigator-blinded study in adult patients (age >18 years) with physical findings, signs and symptoms (for at least 7 days), and radiographic findings indicating acute, uncomplicated maxillary sinusitis. Patients were randomized to receive gatifloxacin 400 mg once daily for 5 days, gatifloxacin 400 mg once daily for 10 days, or amoxicillin/clavulanate 875 mg twice daily for 10 days. Clinical response was assessed once between days 3 and 5 of treatment, once I to 3 days after the completion of study treatment, once 7 to 14 days posttreatment (test-of-cure visit), and once 21 to 28 days posttreatment. Safety was assessed throughout the study. RESULTS: The study enrolled 445 patients. The treatment groups were similar in terms of history of sinusitis, presenting signs and symptoms, and radiographic findings. The most common presenting symptoms were nasal congestion, sinus tenderness, and purulent nasal discharge (>90% of patients); 99% of patients had abnormal radiographic findings. At the test-of-cure visit, clinical cure rates for clinically evaluable patients in the 3 treatment groups were 74% (102/137) for 5-day gatifloxacin, 80% (101/127) for 10-day gatifloxacin, and 72% (101/ 141) for 10-day amoxicillin/clavulanate (95% CI for the difference in cure rates: 5-day gatifloxacin vs amoxicillin/clavulanate, -7.6 to 13.2; 5- vs 10-day gatifloxacin, -15.2 to 5.1; 10-day gatifloxacin vs amoxicillin/clavulanate, -2.3 to 18.1). The distribution and incidence of drug-related adverse events (AEs) were comparable between treatment groups, and the majority (>95%) were mild or moderate in severity. The most common drug-related AEs included vaginitis, diarrhea, and nausea. CONCLUSION: In this population of patients with acute, uncomplicated sinusitis of presumed bacterial origin, a short course (5 days) of gatifloxacin therapy was associated with comparable clinical cure rates and tolerability to those of standard 10-day therapy with gatifloxacin or amoxicillin/clavulanate.

Adult↗
PubMed2002

Subcortical dementia.

BACKGROUND: Drawing a distinction between cortical and subcortical dementias seems both useful and justified. Recent research has, however, cast doubt on the clinical, neuropsychological, neuroimaging and neuroanatomical basis of the distinction. AIMS: To arrive at a reasoned conclusion about the relationship between the two types of dementia and the validity of distinguishing between them. METHOD: The historical and recent clinical and scientific literature on subcortical dementia was reviewed. RESULTS: The traditional claim that subcortical dementia has distinct clinical manifestations, neuroimaging findings and a neuropathological profile is not altogether borne out by the literature. Some studies show that frontal executive dysfunction and the profile of memory deficits are not significantly different from those seen in Alzheimer's disease. Neuropathological findings also overlap. CONCLUSIONS: The category of subcortical dementia may be clinically useful in highlighting the likelihood that an individual with dementia is more likely to suffer from bradyphrenia and motor difficulties. As neuroscience advances a preoccupation with the distinction may hinder the assessment and treatment of individual cases.

Aged↗
PubMedDate not supplied

Factitious disorders: reformulating the DSM-IV criteria.

The author criticizes and reformulates the DSM-IV criteria in a clinically and nosologically sensitive way. Criterion A, the intentional production of physical or psychological signs or symptoms, emphasizes symptoms and cannot accommodate pseudologia fantastica, voluntary false confessions, and impersonations. Criterion B, the motivation is to assume the "sick role," has no empirical content and fulfills no diagnostic function. The two criteria need reformulating in terms of lies and self-harm, respectively. Criterion C causes misdiagnosis by pushing factitious disorders into the somatoform and malingering categories and should be abandoned. The author discusses the implications for the etiology of conversion disorders and the classification of factitious disorders.

Diagnostic and Statistical Manual of Mental Disord↗