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Biomedical subjects

M A Turner

Publications and source records attributed to M A Turner.

At least 19 recordsLinked to original sources
PubMed2006

Isolated parenchymal lesions on cranial ultrasound in very preterm infants in the context of maternal infection.

AIM: To explore the associations between a clinical diagnosis of maternal infection (CDMI) and findings on the initial cranial ultrasound scan in very preterm infants. METHODS: Among infants born at less than 32 weeks gestation, cases of CDMI and controls were identified on the basis of routinely available obstetric data. Neonatal cranial ultrasound scans carried out soon after birth were retrospectively reviewed for evidence of parenchymal echodensity (PED), intraventricular haemorrhage (IVH) or PED contiguous with IVH. RESULTS: Any PED was identified in 20/40 (50%) cases of CDMI and 9/30 (30%) of controls. Logistic regression was used to adjust for differences between the two study groups. When compared with normal scans, isolated PED was more likely with CDMI odds ratio, OR (95% confidence interval, CI), 41.8 (2.64, 662) and lower Apgar score at 5 min 2.89 (1.05, 7.98). IVH was more likely with lower gestational age, OR for each completed week of gestation 0.64 (0.46, 0.88) and a protective effect of female sex, OR 0.25 (0.063, 0.98), PED contiguous with IVH was more likely with lower gestational age OR 0.59 (0.336, 1.04). CONCLUSIONS: CDMI may be associated with isolated PED in very preterm infants. We speculate that isolated PED (including "flares") identify infants who have sustained early brain injury because of intrauterine infection. Isolated PED may be a useful intermediate outcome in perinatal cohort studies.

Apgar Score↗
PubMed2006

The extent and variability of effects of culture conditions on the secretion of human chorionic gonadotrophin and interleukin-6 by human, term placental explants in culture.

Culture of explants derived from third trimester human placenta is used in a range of contexts as an experimental model that retains tissue architecture. This study aimed to explore the variability between, and within, individuals of secretion by explants of human chorionic gonadotrophin (hCG) and interleukin-6 (IL-6). Standard culture medium contained hydrocortisone, insulin, retinoic acid and serum. Under these conditions explants displayed significant differences in the time-course and extent of hCG secretion. Peak hCG secretion varied between 1.19 and 242 mIU/mg protein/h (coefficient of variation (CV) = 111%) and could occur between days 4 and 7 of culture. hCG secretion was more variable if explant protein was < 400 microg. Unadjusted day 7 hCG secretion showed marked variation: intra-placental CV = 15%, inter-placental CV = 86%. When day 7 hCG secretion was standardised by day 6 secretion, intra-placental CV was 6.9%, inter-placental CV was 4.0%. When this standardisation was applied, hCG secretion during day 7 of culture was not affected by removal of hydrocortisone, insulin or serum from the medium or by the addition of tumour necrosis factor-alpha (TNF-alpha). The secretion of IL-6 during day 7 of culture (standardised by taking natural logarithms) was increased markedly by the addition of TNF-alpha but unaltered by removing hydrocortisone, insulin or serum. Thus, we have shown that although variable, secretion by placental explants can be used to investigate how placental tissue adapts to different culture conditions. However, explants of the same protein content may have markedly different secretory properties.

Chorionic Gonadotropin↗
PubMed2006

Do people with autistic spectrum disorder show normal selection for attention? Evidence from change blindness.

People in the general population are typically very poor at detecting changes in pictures of complex scenes. The degree of this 'change blindness', however, varies with the content of the scene: when an object is semantically important or contextually inappropriate, people may be more effective at detecting changes. Two experiments investigated change blindness in people with autism, who are known from previous research to be efficient in detecting features yet poor at processing stimuli for meaning and context. The first experiment measured the effect of semantic information while the second investigated the role of context in directing attention. In each task, participants detected the dissimilarity between pairs of images. Both groups showed a main effect of image type in both experimental tasks, showing that their attention was directed to semantically meaningful and contextually inappropriate items. However, the autistic group also showed a greater difficulty detecting changes to semantically marginal items in the first experiment. Conclusions point to a normal selection of items for attention in people with autism spectrum disorders, although this may be combined with difficulty switching or disengaging attention.

Adolescent↗
PubMed2005

Human placental explants in culture: approaches and assessments.

Placental explant cultures in vitro are useful for studying tissue functions including cellular uptake, production and release of secretory components, cell interactions, proliferation, growth and differentiation, gene delivery, pharmacology, toxicology, and disease processes. A variety of culture conditions are required to mimic in utero environments at different times of gestation including differing oxygen partial pressures, extracellular matrices and culture medium. Optimization of explant methods is examined for first and third trimester human placental tissue and the biological processes under investigation.

Biocompatible Materials↗
PubMed2005

Effect of Mycobacterium vaccae on cytokine responses in children with atopic dermatitis.

The increasing prevalence of atopic diseases over the last few decades is thought to be due to reduced exposure to environmental microbes that normally down-regulate allergic responses (hygiene hypothesis). We have shown previously that administration of the environmental microbe Mycobacterium vaccae ameliorates atopic dermatitis in school-age children at 3 months post-treatment. The present study tested the hypothesis that M. vaccae suppresses Th2-type cytokine activity and increases transforming growth factor (TGF)-beta(1) immunomodulatory activity in these children. Interleukin (IL)-4, IL-5, TGF-beta(1) and interferon (IFN)-gamma activity were assessed in resting and stimulated peripheral blood mononuclear cells (PBMC) isolated from 12 of the children who received M. vaccae in our original clinical trial. A cDNA expression array was used to examine a broader range of cytokine pathway transcripts. There were no significant changes in either Th2-type or TGF-beta(1) activity. A 5- to 10-fold increase in Th1-type activity was found at 1 month post-M. vaccae administration (P < 0.05), but it had returned to baseline by 3 months. The results do not support the hypothesis that M. vaccae reduces Th2-type or increases TGF-beta(1) activity of PBMC isolated from children with atopic dermatitis. The transient surge in IFN-gamma at 1 month is unlikely to explain any improvement in eczema score at 3 months.

Adolescent↗
PubMed2004

Gestational age and the C reactive protein response.

C reactive protein (CRP) concentrations are used routinely in the investigation and monitoring of neonatal sepsis. In this study, CRP responses were examined in the first week after birth. Among infants showing a clinically relevant CRP response, CRP concentrations > 60 mg/l were more likely with increasing gestational age.

Bacterial Infections↗
PubMed2002

Secretion of interleukin-1beta and interleukin-6 by fragments of term human placental villi: signalling pathways and effects of tumour necrosis factor alpha and mode of delivery.

The regulation of cytokine secretion has not been extensively investigated in placental tissue. Fragments of term human placenta were incubated in Tyrode's medium for 3h and cytokine concentrations were measured in the supernatant. IL-1beta secretion after vaginal delivery (VD) was (mean +/- SEM fmol/mg wet weight/3h) 0.193 +/- 0.005 (basal) and 0.549 +/- 0.18 (+1n M TNFalpha) and was more sensitive to TNFalpha dose after elective Caesarean section in the absence of clinical labour (CS) than VD. Secretion of IL-6 after VD was 2.3 +/- 0.47 (basal) and 3.01 +/- 0.34 (+1n M TNFalpha), was correlated with the secretion of IL-1beta and was more sensitive to TNFalpha dose after VD than CS. The inhibitors SB203580, PD98059, SN50, cycloheximide and D-ribofuranosylbenzimidazole each reduced the basal and TNFalpha-stimulated secretion of IL-1beta and also reduced IL-6 secretion with the exception of SN50. There were no interactions between effects of inhibitors and mode of delivery or TNFalpha. In summary we found that term placenta spontaneously secretes IL-1beta and IL-6 in vitro. Delivery after labour alters placental sensitivity to TNFalpha. Exposure to agents known to inhibit MAPK pathways, NF-kappaB, or synthesis of protein and mRNA reduces placental cytokine secretion.

Adult↗
PubMed2001

Capillary filtration is reduced in lungs adapted to chronic heart failure: morphological and haemodynamic correlates.

OBJECTIVE: To determine pulmonary capillary filtration in experimental chronic heart failure and to investigate some morphological and haemodynamic mechanisms that could account for reduced filtration in lungs adapted to chronic heart failure. METHODS: We studied pulmonary capillary filtration, vascular resistances and morphology in lungs from guinea-pigs adapted to chronic heart failure. Heart failure was induced by banding of the ascending aorta (n=66) or sham control operation (n=78) in guinea-pigs which were studied at 150+/-8 days post-operation. RESULTS: Reduced cardiac output, increased systemic vascular resistance and LV end diastolic pressure and increased LV and RV weight:body weight ratio (all P<0.05) indicated chronic heart failure at 5 months following aortic banding in guinea-pigs. Lung weight was increased (61%, P<0.05) in heart failure compared with controls, but lung water content was reduced (5.5%, P<0.05), a reversal of the pattern seen acutely. Studies in isolated perfused lungs demonstrated a reduced capillary filtration coefficient (0. 018+/-0.003 vs. 0.003+/-0.002 ml min(-1)mmHg(-1)g(-1), P<0.001), increased arterial (61%) and venous resistance (50%) in heart failure lungs, P<0.05. Wall thickness:lumen ratio was increased in small (<250 microm) pulmonary arterioles (0.15+/-0.02 vs. 0.08+/-0. 01) and venules (0.06+/-0.005 vs. 0.04+/-0.002) in heart failure, P<0.01. Alveolar septal volume fractions (35.2+/-5.1 vs. 23.1+/-2.7) and septal:air-space volume ratios (60.5+/-13.6 vs. 31.9+/-5.3) were also increased in heart failure, P<0.05. CONCLUSIONS: Pulmonary adaptation to chronic heart failure is associated with vascular and alveolar remodelling that contributes to increased vascular resistance and reduced capillary filtration. These changes are likely to be important in mediating resistance to pulmonary oedema in chronic heart failure.

Adaptation, Physiological↗
PubMed2001

High failure rate after laparoscopic adjustable silicone gastric banding for treatment of morbid obesity.

OBJECTIVE: To report the results from one of the eight original U.S. centers performing laparoscopic adjustable silicone gastric banding (LASGB), a new minimally invasive surgical technique for treatment of morbid obesity. SUMMARY BACKGROUND DATA: Laparoscopic adjustable silicone gastric banding is under evaluation by the Food & Drug Administration in the United States in an initial cohort of 300 patients. METHODS: Of 37 patients undergoing laparoscopic placement of the LASGB device, successful placement occurred in 36 from March 1996 to May 1998. Patients have been followed up for up to 4 years. RESULTS: Five patients (14%) have been lost to follow-up for more than 2 years but at last available follow-up (3-18 months after surgery) had achieved only 18% (range 5-38%) excess weight loss. African American patients had poor weight loss after LASGB compared with whites. The LASGB devices were removed in 15 (41%) patients 10 days to 42 months after surgery. Four patients underwent simple removal; 11 were converted to gastric bypass. The most common reason for removal was inadequate weight loss in the presence of a functioning band. The primary reasons for removal in others were infection, leakage from the inflatable silicone ring causing inadequate weight loss, or band slippage. The patients with band slippage had concomitant poor weight loss. Bands were removed in two others as a result of symptoms related to esophageal dilatation. In 18 of 25 patients (71%) who underwent preoperative and long-term postoperative contrast evaluation, a significantly increased esophageal diameter developed; of these, 13 (72%) had prominent dysphagia, vomiting, or reflux symptoms. Of the remaining 21 patients with bands, 8 currently desire removal and conversion to gastric bypass for inadequate weight loss. Six of the remaining patients have persistent morbid obesity at least 2 years after surgery but refuse to undergo further surgery or claim to be satisfied with the results. Overall, only four patients achieved a body-mass index of less than 35 and/or at least a 50% reduction in excess weight. Thus, the overall need for band removal and conversion to GBP in this series will ultimately exceed 50%. CONCLUSIONS: The authors did not find LASGB to be an effective procedure for the surgical treatment of morbid obesity. Complications after LASGB include esophageal dilatation, band leakage, infection, erosion, and slippage. Inadequate weight loss is common, particularly in African American patients. More study is required to determine the long-term efficacy of the LASGB

Adult↗
PubMed2001

The functional regeneration of syncytiotrophoblast in cultured explants of term placenta.

We have investigated the functional characteristics of term human placental villous explants kept in long-term (7-11 days) culture. Fragments of placental villous tissue (approximately 5-10 mg wet wt) were cultured in supplemented CMRL-1066 culture medium for up to 11 days. After the first day of culture, the syncytiotrophoblast appeared vacuolated and eventually degenerated. However, a new syncytiotrophoblast developed by day 4, being indistinguishable from that of a fresh placenta by 11 days. Release of human chorionic gonadotrophin increased and activity of lactate dehydrogenase in culture medium decreased with culture time. Transport variables were measured over the first 7 days of culture. Basal (86)Rb efflux was reduced with time in culture and was inhibited by Ba2+, suggesting the efflux was mediated by K+ channels. At all stages of culture, (86)Rb efflux was stimulated by ATP, hyposmotic medium, and ANG II. A complex pattern of efflux changes with culture time and type of stimulator was observed, suggesting that several compartments of the tissue contributed to stimulated efflux. This culture system provides opportunities for studies of chronic regulation of placental function.

Cell Survival↗
PubMed2000

Endogenous and exogenous coronary vasodilatation are attenuated in cardiac hypertrophy: a morphological defect?

Reactive hyperaemia (RH) following brief ischaemia is reduced in hypertrophied hearts, and this may contribute to reduced coronary flow reserve. We studied vasodilatation during RH and in response to exogenous stimuli in control and hypertrophied hearts and explored the mechanisms underlying RH. Vascular reactivity was assessed in isolated hypertrophied hearts (55+/-3 days after aortic banding or sham operation) by constructing dose-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and adenosine. Reactive hyperaemic vasodilatation was assessed after global ischaemia (5-120 s) in the presence/absence of L -NAME, 8-phenyltheophylline (8-PT) and glibenclamide. Purine release and NO overflow in the coronary perfusate were analysed. Aortic constriction increased heart/body weight ratio (47%), myocyte size (19%) and arteriolar wall thickness (51%), all P<0.01. Coronary reserve was reduced in hypertrophy (105+/-8%v 182+/-12%, P<0.01). Dose response curves for ACh, SNP and adenosine were reduced in hypertrophy (69%, 86% and 68%, all P<0.01) v shams; however ED(50)values were unchanged. The peak flow and duration of RH were also attenuated (50%, P<0.001) in hypertrophy. While purine washout during RH was related to the duration of preceding ischaemia, nitrate washout was not. RH experiments in the presence of L -NAME, 8-PT and glibenclamide indicated that RH is mediated by combined actions of K(ATP)channels>adenosine>NO in both groups. RH is mediated by similar mechanisms in control and hypertrophied hearts. All vasodilatation was similarly attenuated in hypertrophy, independent of endothelial activation. We hypothesize that increased arteriolar wall thickness may limit vasodilator responses to all stimuli in hypertrophy.

Animals↗
PubMed2000

Type I collagen degradation by invasive oral squamous cell carcinoma.

Expression of extracellular matrix-degrading proteases is required for tumor cell invasion. In the present study we examined the production of type I collagen-degrading matrix metalloproteinases (MMPs) in the invasive oral squamous cell carcinoma-derived cell line HSC-3. In the absence of serum or exogenous growth factors, HSC-3 cells displayed no collagen degradation activity. Addition of serum slightly increased collagen proteolysis. However, addition of epidermal growth factor (EGF) resulted in nearly complete degradation of the collagen matrix. Zymography showed that MMP-2 and -9 are secreted by HSC-3 cells. EGF stimulated secretion of an additional gelatinase with a molecular weight similar to that of MMP-1. Immunoblotting of conditioned medium confirmed that EGF and, to a lesser degree type I collagen, increased production of MMP-1. Finally, in situ hybridization revealed intense expression of MMP-1 in oral squamous cell carcinoma specimens. Together, these results indicate that MMP-1 is expressed, induced by EGF, and required for type I collagen degradation in oral squamous cell carcinoma.

Biopsy↗
PubMed2000

Magnetic resonance cholangiopancreatography (MRCP) in the assessment of pancreatic duct trauma and its sequelae: preliminary findings.

BACKGROUND: The purpose of this study was to determine the utility of magnetic resonance cholangiopancreatography (MRCP) in the evaluation of pancreatic duct trauma and pancreas-specific complications. METHODS: Ten hemodynamically stable patients with clinically suspected pancreatic injury related to blunt abdominal trauma (n = 8), penetrating trauma (n = 1), or iatrogenic trauma (n = 1) underwent MRCP. Two abdominal radiologists conducted a review of the MRCPs to assess for the presence or absence of pancreatic duct trauma and pancreas-specific complications such as pseudocysts. The MRCP findings were correlated with endoscopic retrograde cholangiopancreatograms (n = 2), surgical findings (n = 1), computed tomographic scans (n = 10), and with clinical, biochemical or imaging follow-up (n = 10). RESULTS: Diagnostic quality MRCPs were obtained in each of the 10 patients. A mean imaging time of 5 minutes was required to perform the MRCPs. Pancreatic duct injuries were detected in four patients; pseudocysts were detected in three of these four patients. The pancreatic duct injuries in three patients were acute or subacute. In one of the three patients, disruption of a side branch of the pancreatic duct diagnosed with MRCP was not detected with endoscopic retrograde cholangiopancreatography but was confirmed surgically. In the fourth patient, the pancreatic duct injury was chronic; MRCP revealed a posttraumatic stricture in this patient who had sustained blunt abdominal trauma 17 years previously. In the remaining six patients, pancreatic duct trauma was excluded with MRCP. The information derived from the MRCPs was used to guide clinical decision-making in all 10 patients. CONCLUSIONS: MRCP enables noninvasive detection and exclusion of pancreatic duct trauma and pancreas-specific complications and provides information that may be used to guide management decisions.

Adolescent↗
PubMed2000

Oxalate and calcium excretion in cystic fibrosis.

BACKGROUND: A patient with cystic fibrosis (CF) and repeated calcium oxalate renal stones prompted us to investigate other children for risk factors for this recognised complication of CF. METHODS: Twenty four hour urinary excretion of calcium, oxalate, and glycolate was measured in children with CF and no symptoms of renal tract stones. Normal diet and treatments were continued. RESULTS: In 26 children (aged 5-15.9 years) oxalate excretion was correlated with age; 14 of 26 children had oxalate excretion above an age appropriate normal range. There was a positive correlation between oxalate excretion and glycolate excretion. Mean calcium excretion was 0.06 mmol/kg/24 h with 21 of 24 children having calcium excretion below the normal range. CONCLUSIONS: Hyperoxaluria may reflect malabsorption although correlation between excretion of oxalate and glycolate suggests a portion of the excess oxalate is derived from metabolic processes. The hypocalciuria observed here may protect children with CF from renal stones.

Adolescent↗