Deaths from nvCJD rise sharply
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Journal Article↗
Biomedical subjects
J Jones
Publications and source records attributed to J Jones.
Correlation of beta-actin messenger RNA localization with metastatic potential in rat adenocarcinoma cell lines.
The actin cytoskeleton is involved in the motility of tumor cells. It has been shown in several cell types that beta-actin mRNA is localized in the protrusions of cells in which actin is actively polymerized, and the ability to localize mRNA is correlated with the efficiency of motility. In this context, we studied the distribution of beta-actin mRNA in two different tumor cell lines and correlated it with their metastatic potential. The two cell lines used were the highly metastatic MTLn3 cells and nonmetastatic MTC cells. Nonmetastatic MTC cells have two different pools of beta-actin mRNA (perinuclear and at the leading edge), whereas highly metastatic MTLn3 cells have only a perinuclear distribution of beta-actin mRNA. These differences in mRNA localization are correlated with profound differences in the polarity and plasticity of cell motility of these cells in culture and the histopathology of primary breast tumors derived from these cells. In particular, MTLn3 cells are unpolarized by all cell shape and motility criteria in culture and in their histopathological organization in primary tumors. By comparison, MTC cells are polarized in all identical measurements. These results suggest that the increased plasticity of cell locomotion and the invasiveness of MTLn3 cells result from the failure of metastatic cells to localize beta-actin mRNA properly, causing them to be less polarized and therefore more flexible in their direction of motility. Thus, differences in the polarized organization of cells in the primary tumor that are correlated with beta-actin mRNA localization may have prognostic value in predicting metastatic potential.
Actins↗
Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells.
Little is known about the expression of the receptor for complement anaphylatoxin C3a (C3aR) in the central nervous system (CNS). In this study, we provide the first evidence that neurons are the predominant cell type expressing C3aR in the normal CNS. By using in situ hybridization (ISH) and immunohistochemistry, we found that C3aR is constitutively expressed at high levels in cortical and hippocampal neurons as well as in Purkinje cells. Moreover, we showed that primary culture of human astrocytes and microglia express the C3aR mRNA as assessed by RT-PCR. In situ hybridization performed on rat primary astrocytes confirmed the RT-PCR result demonstrating C3aR expression by astrocytes. In experimental allergic encephalitis (EAE), C3aR expression was elevated on microglia, infiltrating monocyte-macrophage cells and a few astrocytes, whereas neuronal expression remained unchanged during the course of the disease. These data demonstrate that the C3aR is expressed primarily by neurons in the normal CNS and that its neuronal expression is not dramatically upregulated under inflammation. This is in contrast to the increased neuronal expression of the C5aR in several inflammatory CNS conditions. The high constitutive expression of the C3aR by neurons suggests this receptor may play an important role in normal physiological conditions in the CNS.
Anaphylatoxins↗
Prediction of early-onset asthma in genetically at-risk children.
The W.T. Grant Foundation Asthma Risk Study was designed to prospectively examine children who were considered at a genetically increased risk for the development of asthma. The respective contributions of 11 potential risk factors, both environmental and biological, were assessed in order to determine their relative roles in affecting the early onset of asthma. This is a report of an inception cohort of children born to asthmatic mothers and followed for a 3-year period. All 150 families were recruited from the general community and living within 2 h of the National Jewish Center for Immunology and Respiratory Medicine (Denver, CO). Mothers in the index risk sample had been previously diagnosed with asthma and were recruited during their pregnancy through physician referrals and media solicitation. The index sample of 150 families was 92% Caucasian and predominantly middle class. The mean age of mothers was 29.3 years, and of fathers, 31.1 years. The main outcome was the determination of the early onset of asthma and its association with quantified risk factors. By age 3 years, 14 of the 150 children had developed asthma. Frequent illness, IgE levels at age 6 months, parenting difficulties, and early eczema were significantly associated with the onset of asthma (P = 0.003, P = 0.006, P = 0.01, and P = 0.03, respectively). Only frequent illness, elevated serum IgE levels, and parenting difficulties entered a predictive model where they were independently related to the development of asthma.
Age of Onset↗
Increased maternal bone formation in type I diabetic pregnancies.
There is evidence that infants of insulin-dependent diabetics have increased intrauterine bone resorption and reduced bone mineral content at birth. The aim of this study was to determine if type I diabetes is associated with abnormal maternal bone metabolism. We measured the circulating levels of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in the third trimester of pregnancy in samples obtained from 19 pregnant women with type I diabetes and 19 pregnant controls, to monitor the rate of bone formation and degradation, respectively. Diabetic control was considered to be good as the mean hemoglobin A(1) level was less than 8.5%. The circulating levels of PICP were significantly higher in pregnant women with insulin-dependent diabetes than in controls with uncomplicated pregnancy (median IDDM 147 microgram/liter, control 115 microgram/liter, P = 0.0014), but there was no significant difference in the circulating levels of ICTP between the two groups (median IDDM 4.6 microgram/liter, control 4.6 microgram/liter, P = 0.907). Therefore, our findings suggest that there is an increase in bone formation in pregnant women with type I diabetes which may be related to the increased amount of insulin administered and the improvement in diabetic control associated with pregnancy.
Adolescent↗
Toxicity and phototoxicity of mixtures of highly lipophilic PAH compounds in marine sediment: can the SigmaPAH model Be extrapolated?
The additivity of toxic units was tested using sediments contaminated with mixtures of highly lipophilic (log Kow > 4.5) parent and alkylated PAHs. The direct toxicity and photoinduced toxicity of these mixtures were examined in standard 10-day sediment toxicity tests using the infaunal amphipod Rhepoxinius abronius, with mortality and the survivors' ability to rebury as endpoints. Survivors of the initial 10-day tests were then exposed for 1 h to ultraviolet (UV) radiation and the results compared to initial (10-day) endpoints. Tissue residues and lipids were measured and biota-sediment accumulation factor (BSAF) values determined. The results indicated that the bioaccumulated contaminants were not initially toxic, however, they were highly phototoxic. Although the summed toxic units of these contaminants appeared to be nonadditive, additivity was not disproved as inaccuracies in extrapolating the Kow-LC50 QSAR or insufficient exposure duration might also have accounted for the observed results. Critical body residue (CBR) estimates for R. abronius were similar while BSAF values were much larger (10x) in comparison to other studies, which used amphipods and PAHs. The phototoxicity of mixtures of contaminants were similar to the phototoxicity of single contaminants when expressed on a molar basis, which suggests that phototoxicities may be roughly additive.
Journal Article↗
Incidence of and survival from upper aerodigestive tract cancers in the U.K.: the influence of deprivation.
The aim of the study was to investigate the effect of social deprivation on the incidence of and survival from upper aerodigestive tract (UAT) cancers in the U.K. Incidence was calculated on 25,903 cases of malignant upper aerodigestive tract cancers collected from four cancer registries in the U.K. for the period 1984-1993. A Cox proportional hazard model was used to determine the influence of deprivation, measured in Carstairs quintiles for crude and cause-specific survival on 17,393 of these cases. Patients with UAT cancers who were younger, males or of South Asian origin were more likely to live in a deprived area than in an affluent area. The incidence of UAT cancers in a district was correlated with deprivation score for the district for both men (r = 0.78) and for women (r = 0.60). People who lived in deprived areas had a relative risk of 1.25 (95% confidence interval (CI): 1.15-1.35) of dying from their cancer and of 1.24 (95% CI: 1.13-1.35) of dying from all causes compared with people who lived in affluent areas. People living in deprived areas were more likely to get UAT cancer and were more likely to die from their cancer than people living in affluent areas.
Aged↗
Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.
To evaluate the utility of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a cancer therapeutic, we created leucine zipper (LZ) forms of human (hu) and murine (mu) TRAIL to promote and stabilize the formation of trimers. Both were biologically active, inducing apoptosis of both human and murine target cells in vitro with similar specific activities. In contrast to the fulminant hepatotoxicity of LZ-huCD95L in vivo, administration of either LZ-huTRAIL or LZ-muTRAIL did not seem toxic to normal tissues of mice. Finally, repeated treatments with LZ-huTRAIL actively suppressed growth of the TRAIL-sensitive human mammary adenocarcinoma cell line MDA-231 in CB.17 (SCID) mice, and histologic examination of tumors from SCID mice treated with LZ-huTRAIL demonstrated clear areas of apoptotic necrosis within 9-12 hours of injection.
Animals↗
QTc dispersion and complex ventricular arrhythmias in untreated newly presenting hypertensive patients.
Increased dispersion of ventricular repolarisation (increased QT dispersion) is believed to predispose to arrhythmias associated with sudden death in certain cardiac diseases. Hypertension is also associated with increased risk of sudden death, particularly in those with left ventricular hypertrophy (LVH). Therefore, the first aim of this study is to look into the possible pathogenic role of QT dispersion on the ventricular arrhythmias occurring in a group of never-treated hypertensive patients. The second aim is to look at other possible determinants of QT dispersion (ie, level of blood pressure, hypokalaemia, electrocardiographic LVH and presence or absence of strain pattern) in hypertensive patients, and their relevance to complex ventricular arrhythmias. QTc (corrected QT) was measured in 70 newly presenting (never-treated) hypertensive patients (47 male, 23 female, mean age 51.9 +/- 12.5 years) from a standard 12-lead surface electrocardiogram (ECG). Blood pressure measurements and 24-h ECG holter recordings were performed in all patients. Serum potassium level was measured in 51 of the patients. Ventricular arrhythmias were classified using a modified Lown's scoring system. Maximum QTc, minimum QTc and QTc dispersion for all patients were 442 +/- 30.3 ms, 380 +/- 26.7 ms and 61.5 +/- 21.6 ms respectively. High grade ventricular arrhythmias (Lown's score >/=3) were found in 43% of the patients. The QTc dispersion was strongly correlated with the Lown's classification of arrhythmia and the age of the patients. Patients with more severe ectopy (Lown's score >/=3) were significantly older (57.4 +/- 10.3 years) compared to those with score </=2 (48.3 +/- 12.6 years) (P = 0.0067) and had a significantly greater QTc dispersion (69.9 +/- 22.5 ms vs55.2 +/- 18. 8 ms; P = 0.002). Presence of electrocardiographic strain did not affect the severity of arrhythmia, as 29% of the patients with LVH and strain had grade >/=3 Lown's score compared to 39% in the group with LVH but without strain. In the presence of relative hypokalaemia, hypertensive patients with LVH showed more QTc dispersion (85.7 +/- 15.5 ms) and a greater tendency for complex ventricular arrhythmias (100% grade >/=3 Lown's score) compared to those with LVH and normal serum potassium levels (64.1 +/- 22.6 ms and 35%, QTc dispersion and Lown's score >/=3, respectively P = 0. 05). The level of blood pressure had no effect on either the QTc dispersion or the prevalence of complex ventricular arrhythmias. Prevalence of complex ventricular arrhythmias in hypertensive patients is strongly correlated with QTc dispersion and age. When hypertensive patients with LVH have low potassium levels the risk of developing complex ventricular arrhythmias is significantly increased.
Aging↗
The British Association of Dermatologists audit of atopic eczema management in secondary care. Phase 1: audit of service structure.
This first comprehensive study of atopic eczema management describes an audit of service structure (phase 1), process (phase 2) and outcome (phase 3) in the U.K. This paper describes the phase 1 results. Service structure was audited by a single-page questionnaire containing 10 questions on outpatient facilities. This was sent to the lead dermatologist at 187 dermatology centres throughout the U.K., and a final response rate of 98% was achieved. Although the percentage of centres reporting the presence of recommended facilities did not reach the 100% working standard for any one specific criterion, about half of the recommended items, such as provision of height and weight measuring facilities, access to a dietician, patch testing and photochemotherapy, was reported in over 90% of centres. Areas of service structure which were infrequently reported to be in place were issuing of new appointment letters asking patients to bring their treatment details to clinic (52% of centres) and access to nurses with dermatology experience on paediatric wards (57% of centres). Some audit measures, e.g. access to counselling services, showed wide regional variation (range 33-94% of centres), and these variations could not be explained simply in terms of provision of specialists. Some of the elements of service structure, such as access to nurses with dermatology experience on paediatric wards, may be difficult to change in the short term because of funding and staffing constraints, but others, such as provision of growth charts, are easy to change at little cost. This preliminary audit serves as a framework for future audits of atopic eczema management.
Dermatitis, Atopic↗
Relationship between serum and urinary insulin-like growth factor-I through childhood and adolescence: their use in the assessment of disordered growth.
OBJECTIVE: Serum insulin-like growth factor-I (sIGF-I) measurement as an index of growth hormone status has become a common test in the investigation of disordered growth. IGF-I may also be measured in the urine. The aims of this study were to investigate the correlation between serum and urinary IGF-I in normal children and compare their use in the evaluation of growth disorders. DESIGN: Normal ranges for serum and urinary IGF-I were devised from a cross-sectional study of normal schoolchildren. These were then used to assess the sensitivity and specificity of serum and urinary IGF-I in the diagnosis of childhood GH deficiency. PATIENTS: A cohort of 333 (M = 156, F = 177) healthy schoolchildren aged 5-19 years were recruited and data previously collected from 22 growth hormone deficient (GHD) and 47 short normal (SN) children were compared with those of the normal children. MEASUREMENTS: Height, weight and pubertal status were assessed in all children. Serum IGF-I (sIGF-I) (n = 305) and total amount of urinary IGF-I excreted overnight (TuIGF-I) (n = 205) were measured by RIA using excess IGF-II to block the interference of IGFBPs. RESULTS: Serum IGF-I was loge transformed and overall levels (geometric mean +/- 1 tolerance factor) were higher in females than males (F: 569 (329, 985) micrograms/l; M: 398 (227, 696) micrograms/l). LogeIGF-I correlated with age (F: r = +0.76, P < 0.001, M: r = +0.71, P < 0.001) and was significantly affected by both sex and Tanner stage of puberty (TS) (both P < 0.001). The distribution of TuIGF-I was normalized by performing a square root transformation (square root of TuIGF-I). square root of TuIGF-I was correlated with age (F: r = +0.36, P < 0.001; M: r = +0.5, P < 0.001) and was significantly affected by TS (P < 0.001). In both sexes there was a highly significant correlation between logeIGF-I and square root of TuIGF-I (F: r = +0.39, P < 0.001; M: r = +0.41, P < 0.001). Using the third centile of our normal ranges as a cut off to identify GHD, sIGF-I had a sensitivity of 82% and specificity of 62%, whereas TuIGF-I had a sensitivity of 18% and specificity of 79%. CONCLUSIONS: This study demonstrates that although urinary IGF-I has no place in the diagnosis of growth disorders, in normal children there is a highly significant relationship between serum and urinary IGF-I with levels of each changing in a similar manner through childhood and adolescence. Thus, TuIGF-I could be used as a valid surrogate for sIGF-I in the physiological assessment of the relationship between IGF-I status and the normal growth process.
Adolescent↗
An integrated treatment algorithm for pharmacotherapy and psychotherapy.
OBJECTIVE: As in Australia, demand for psychotherapy is rising in Britain, and the wide variety of psychological treatments available within the National Health Service (NHS), the independent sector, and voluntary agencies leads to uncertainty about which patients are most suitable for which type of psychotherapy, as well as the appropriate balance between psychological and pharmacological interventions. This paper describes how Birmingham Health Authority (HA), the largest HA in England and Wales with a population of just under one million, developed and implemented an evidence-based strategy for the use of psychotherapy services. METHOD: A literature search and health needs assessment for psychotherapy in Birmingham was performed. RESULTS: It was possible to estimate the need for evidence-based psychotherapy services using routinely available epidemiological data. By matching specific techniques to individual diagnosis and estimating the size of the population for whom this was appropriate, demand for psychotherapy exceeded service provision by a factor of four. CONCLUSIONS: The following steps were undertaken: (i) setting priorities for the commissioning of psychotherapy on the basis of the scientific literature including greater use of brief and focused forms of integrative therapy from a variety of psychotherapeutic schools; (ii) targeting interventions on the basis of objective criteria to ensure that patients were referred for the appropriate level and intensity of psychological intervention using the full range of available services within the NHS, the independent sector, and voluntary agencies; (iii) agreeing on an integrated treatment algorithm (ITA) for the use of the most cost-effective treatments while ensuring that a range of alternative interventions was available for patients for whom a first line therapy was not suitable. Such an ITA could be adapted to assist general practitioners in their management and referral decisions; (iv) sharing skills between specialist psychotherapy services and members of primary and mental health teams through training, supervision and consultation-liaison.
Algorithms↗
A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoracotomy pain, pulmonary function and stress responses.
Both epidural and paravertebral blocks are effective in controlling post-thoracotomy pain, but comparison of preoperative and balanced techniques, measuring pulmonary function and stress responses, has not been undertaken previously. We studied 100 adult patients, premedicated with morphine and diclofenac, allocated randomly to receive thoracic epidural bupivacaine or thoracic paravertebral bupivacaine as preoperative bolus doses followed by continuous infusions. All patients also received diclofenac and patient-controlled morphine. Significantly lower visual analogue pain scores at rest and on coughing were found in the paravertebral group and patient-controlled morphine requirements were less. Pulmonary function was significantly better preserved in the paravertebral group who had higher oxygen saturations and less postoperative respiratory morbidity. There was a significant increase in plasma concentrations of cortisol from baseline in both the epidural and paravertebral groups and in plasma glucose concentrations in the epidural group, but no significant change from baseline in plasma glucose in the paravertebral group. Areas under the plasma concentration vs time curves for cortisol and glucose were significantly lower in the paravertebral groups. Side effects, especially nausea, vomiting and hypotension, were troublesome only in the epidural group. We conclude that with these regimens, paravertebral block was superior to epidural bupivacaine.
Adolescent↗
The role of insulin-like growth factor binding protein-1 phosphoisoforms in pregnancies with impaired placental function identified by doppler ultrasound.
This study was performed to investigate the hypothesis that insulin-like growth factor binding protein-1 (IGFBP-1) is involved in the pathogenesis of trophoblast invasion and impaired placentation in human pregnancy. The role of total and non-phosphorylated IGFBP-1 in women with fetal growth restriction and in high risk pregnancies identified by uterine artery Doppler ultrasound screening was examined. This was a prospective study of women booked for antenatal care having second trimester anomaly scans and Doppler screening between 22-26 weeks gestation. Women were divided into three groups and compared: normal uterine artery Doppler and normal fetal growth (control group, n = 10); abnormal Doppler and normal fetal growth [bilateral uterine artery notches (BN; n = 16); abnormal Doppler and intrauterine growth restriction (IUGR; n = 8)]. Maternal serum was collected, stored and assayed simultaneously for total and non-phosphorylated IGFBP-1. There was elevated total and non-phosphorylated IGFBP-1 (mean 44.99 +/- 12.19 and 29.61 +/- 10.38 microg/l respectively) in the IUGR group compared with controls (mean 17.96 +/- 3.24 and 12.18 +/- 1.55 microg/l, P < 0.05). This finding suggests that the various IGFBP-1 isoforms, the degree of phosphorylation and the ratios of these different forms locally may be important during trophoblast invasion and may be implicated in clinical manifestations of impaired placentation later in the second trimester.
Female↗
Effect of antenatal dexamethasone therapy on maternal plasma human chorionic gonadotrophin, oestradiol and progesterone.
The aim of this study was to determine whether the current regimen of dexamethasone administration to induce fetal lung maturation affected the circulating concentrations of placental hormone. A standard regimen of dexamethasone that comprised two doses of 12-mg intramuscular injections, 12 h apart was administered to 12 pregnant women to promote fetal lung maturation in anticipation of premature delivery before 34 completed weeks of gestation. Blood samples were collected before starting the dexamethasone therapy, 24 h, and 48 h after completing therapy for the measurement of the plasma concentrations of human chorionic gonadotrophin (HCG), oestradiol and progesterone. There was a progressive fall in the plasma concentrations of HCG following dexamethasone therapy (P = 0.049 and P = 0.034, 24-h and 48-h post therapy respectively). There was an initial fall in the plasma concentrations of oestradiol after dexamethasone therapy (z = 3.059; P = 0.002, 24-h post therapy), which recovered by 48 h (P = 0.239). There was no difference between the plasma concentrations of progesterone at the three time points. The effect of dexamethasone on HCG concentrations suggests that it has a direct inhibitory effect on placental hormone synthesis or secretion. Further studies are needed to define the mechanism of action of dexamethasone on placental HCG production.
Adult↗
Umbilical artery waveforms in triplet and quadruplet pregnancies.
The incidence of abnormal umbilical waveforms in triplet and quadruplet pregnancies and its correlation with adverse pregnancy outcome was studied by a retrospective review of all our triplet and quadruplet pregnancies (1986-1993) with documented Doppler flow assessment. Obstetrical outcomes were analyzed in relation to abnormal umbilical artery waveforms. Nineteen triplet and 4 quadruplet pregnancies were studied. Of 73 fetuses, 6 had abnormal umbilical artery waveforms (8.2%). All abnormal waveforms were characterized by persistent absence of the end-diastolic velocities (AEDV). In comparing the abnormal and normal groups, significant differences were found in birth weights (910+/-433 vs. 1,724+/-434 g; p = 0.0004), small for gestational age rate [5/6 (83%) vs. 5/67 (7.5%); p = 0.0003], and perinatal mortality rate [3/6 (50%) vs. 2/67(3%); p = 0.001]. There were no differences in congenital anomalies, gestational age at birth, and neonatal intensive care admission. In conclusion, it seems that Doppler umbilical artery waveforms in multiple pregnancies were either normal or extremely abnormal (e.g. AEDV). AEDV was associated with adverse perinatal outcomes such as low birth weight, growth restriction and perinatal mortality.
Birth Weight↗
An unusual case of ureteral ectopia in the seminal vesicle: diagnosis and surgical management.
We report the case of a young man who presented with numerous episodes of ipsilateral epididymitis. Selected imaging studies with consideration of urogenital embryology lead to the rare diagnosis of a dysplastic kidney with ureteral ectopia in the seminal vesicle. After nephroureterectomy and vesiculectomy, convalescence was uneventful. No specific symptoms, equivocal diagnostic findings and the small number of patients limit the surgical experience in diseases of the seminal vesicle. Suprainguinal extravesical extirpation, however, appears to be an excellent operative approach in cases of unilateral seminal vesicle cysts.
Adult↗
Selective embolization of bleeding renal angiomyolipoma in pregnancy.
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Adult↗