Role of protein kinase C isoforms in phorbol ester-induced vascular endothelial growth factor expression in human glioblastoma cells
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Journal Article↗
Biomedical subjects
K Abrams
Publications and source records attributed to K Abrams.
The application of color power angiography to the longitudinal quantification of blood flow volume in the fetal middle cerebral arteries, ascending aorta, descending aorta, and renal arteries during gestation.
OBJECTIVE: This study was undertaken to determine by means of color power angiography the longitudinal changes in the diameters and the flow volumes of 4 major fetal arteries during gestation. STUDY DESIGN: The middle cerebral artery, the ascending aorta, the descending aorta, and the renal arteries in 81 appropriate-for-gestational-age fetuses were examined longitudinally between 24 and 38 weeks' gestation by means of color power angiography. In addition to measurement of the diameters of these arteries, Doppler velocimetry was performed. Flow volume was calculated from the cross-sectional areas of the arteries and the velocity integral of the Doppler waveforms. RESULTS: The mean (+/-SD) gestational age at delivery and birth weight were 39.8 +/- 1. 6 weeks and 3326 +/- 345 g, respectively. The diameters and flow volumes of all the arteries increased significantly as gestational age advanced. Flow volume increased from 39 +/- 19.0 mL/min to 140 +/- 63.9 mL/min in the middle cerebral artery, from 216.2 +/- 77.6 to 937.4 mL/min in the ascending aorta, from 124.4 +/- 76.6 to 390.0 mL/min in the descending aorta, and from 27.5 +/- 16.8 to 80.3 +/- 57.3 mL/min in the renal arteries. When blood flow volume was adjusted to milliliters per kilogram body weight, an initial significant fall in blood flow was seen in all the vessels to a minimal level at 30 weeks' gestation; blood flow rose thereafter, although not significantly, until term. The ratios of flow volume in the ascending aorta to those in the other vessels increased with gestation, with the highest ratio being that between the ascending aorta and the renal arteries. CONCLUSION: Identification of fetal arteries with color power angiography is easy and highly sensitive. The distributions of blood flow in various fetal arteries exhibited regional differences, with significantly more blood flow to the brain. These normative baseline values may be useful in the diagnosis of congenital cardiac anomalies and also in the diagnosis and monitoring of fetuses with intrauterine growth restriction.
Angiography↗
The relationship between anxiety disorders and alcohol use disorders: a review of major perspectives and findings.
It is generally agreed that problems related to alcohol use and anxiety tend to occur within the same individual ("comorbidity"); however, the cause of this association remains controversial. Three prominent perspectives are that anxiety disorder promotes pathological alcohol use, that pathological alcohol use promotes anxiety disorder and that a third factor promotes both conditions. We review laboratory, clinical, family, and prospective studies bearing on the validity of these explanatory models. Findings converge on the conclusion that anxiety disorder and alcohol disorder can both serve to initiate the other, especially in cases of alcohol dependence versus alcohol abuse alone. Further, evidence from clinical studies suggests that anxiety disorder can contribute to the maintenance of and relapse to pathological alcohol use. Relying heavily on pharmacological and behavioral laboratory findings, we tentatively propose that short-term anxiety reduction from alcohol use, in concert with longer-term anxiety induction from chronic drinking and withdrawal, can initiate a vicious feed-forward cycle of increasing anxiety symptoms and alcohol use that results in comorbidity.
Adult↗
Colorectal cancer prevention in ulcerative colitis: a case-control study.
BACKGROUND: The risk of colorectal cancer (CRC) in ulcerative colitis (UC) increases with extent and duration of disease. Identifying other risk factors would allow targeting of sub-groups at greatest risk, enabling more cost-effective surveillance. METHODS: We conducted a case-control study comparing 102 cases of CRC in UC with matched controls. Odds ratios (OR) for cancer risk were estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables. RESULTS: Regular 5-aminosalicylic acid (5-ASA) therapy reduces cancer risk by 75% (OR 0.25, 95% CI: 0.13-0.48, P < 0.00001). Adjusting for other variables, taking mesalazine regularly reduces risk by 81% (OR 0.19, 95% CI: 0.06-0.61, P=0.006) and visiting a hospital doctor more than twice a year also reduces risk (OR 0.16, 95% CI: 0.04-0.60, P=0.007). Considering variables independently, having a family history of sporadic CRC in any relative increases risk fivefold (OR 5.0, 95% CI: 1.10-22.82, P < 0.04). CONCLUSIONS: CRC risk among UC patients can be reduced by regular therapy with 5-ASA medication. Colonoscopic surveillance may be best targeted on those unable to take 5-ASAs (e.g. due to allergy) and those with a positive family history of CRC.
Adolescent↗
Individual differences predictive of drinking to manage anxiety among non-problem drinkers with panic disorder.
BACKGROUND: Alcohol problems co-occur with anxiety disorders at a rate that far exceeds chance ("comorbidity"). One view suggests that risk for developing a comorbid alcohol use disorder is increased when alcohol is used routinely to cope with anxiety symptoms ("self-medication"). Indicating that this view is overly broad, however, the literature suggests that only a subgroup of anxiety-disordered individuals tend to drink to manage their symptoms. Therefore, we set out to identify psychological characteristics that might mark those for whom drinking to cope with anxiety is most likely. Our survey of the literature identified several possibilities, including anxiety-related personality traits (anxiety sensitivity, self-consciousness and Trait Anxiety); higher-order personality dimensions (Harm Avoidance, Reward Dependence, and Novelty Seeking); and, finally, alcohol outcome expectancies (specifically, those related to tension-reducing effects from alcohol). METHODS: In a sample of nonproblem drinkers with panic disorder, we regressed predictor variables on several alcohol use measures, including drinking aimed at the control of anxiety symptoms ("self-medication"). RESULTS: Although each variable related positively to a self-medicating style of drinking, expectancies for tension reduction from alcohol use accounted for about twice as much variance as did the other predictors. With simultaneous entry in a step-wise regression analysis, only tension-reduction alcohol outcome expectancies and the Harm Avoidance personality dimension were retained as significant predictors. CONCLUSIONS: Findings suggest that development of a self-medicating style of drinking among individuals with panic disorder is predicated, in part, on specific psychological characteristics of the individual. Alcohol outcome expectancies emerged as the single most important predictor of drinking behavior in this anxiety-disordered sample.
Adult↗
Role of protein kinase C isoforms in phorbol ester-induced vascular endothelial growth factor expression in human glioblastoma cells.
Aberrant expression of the potent angiogenic cytokine, vascular endothelial growth factor (VEGF), has been demonstrated to be associated with most human solid tumors. Both transcriptional and post-transcriptional mechanisms have been shown to modulate VEGF expression in a multitude of cell types. Here we report that when protein kinase C (PKC) pathways were activated in human glioblastoma U373 cells by phorbol 12-myristate 13-acetate (PMA), VEGF mRNA expression was up-regulated via a post-transcriptional mRNA stabilization mechanism. PMA treatment exhibited no increase in VEGF-specific transcriptional activation as determined by run-off transcription assays and VEGF promoter-luciferase reporter assays. However, PMA increased VEGF mRNA half-life from 0.8 to 3.6 h which was blocked by PKC inhibitors but not by protein kinase A or cyclic nucleotide-dependent protein kinase inhibitors. When U373 cells were transfected with antisense oligonucleotide sequences to the translation start sites of PKC-alpha, -beta, -gamma, -delta, -epsilon, or -zeta isoforms, both PKC-alpha and -zeta antisense oligonucleotides showed substantial inhibition of PMA-induced VEGF mRNA. In addition, overexpression of PKC-zeta resulted in a strong constitutive up-regulation of VEGF mRNA expression. This study demonstrates for the first time that specific PKC isoforms regulate VEGF mRNA expression through post-transcriptional mechanisms.
Endothelial Growth Factors↗
Psychological impact of predicting individuals' risks of illness: a systematic review.
The aim of this review is to determine the frequency and circumstances under which predicting individuals' risk of illness has adverse psychological effects. Using systematic review methodology, the literature was searched for studies that had assessed the adverse psychological outcomes of risk assessment programmes. The outcomes investigated are emotional (anxiety, depression, distress) cognitive (intrusive thoughts, perceptions of health) and behaviour (work absenteeism). The impact of both positive and negative test results are summarised in terms of the number of studies showing significant effects between and within groups in the short (one month or less) and longer term (more than one month). Where sufficient data were available, a meta-analysis was conducted to assess effect size. Fifty-four studies met the criteria for inclusion. The studies assessed the impact of informing individuals about cardiovascular risk (21), risk of AIDS (eight), risk of cancer (10), risk of Huntington's disease (10), risk of diabetes (two), risk of spinocerebellar ataxia (one) and risk of osteoporosis (two). Overall, the quality of studies assessed was limited, with only two using a randomised design to determine the psychological impact of risk assessment. Receiving a positive test result was associated in the short term in the great majority of studies with depression, anxiety, poorer perceptions of health and psychological distress. Data were available for a quantitative synthesis of results on three outcomes, anxiety, depression and distress. Anxiety and depression were significantly higher in those tested positive compared with those tested negative in the short term but not the longer term. Distress could only be assessed in the longer term: there was no evidence of an increase for those receiving positive test results. The five experimental studies that reported interventions aimed at preventing some of these adverse effects all reported favourable results. There was little evidence of any adverse psychological effects of receiving an unfavourable test result. Adverse psychological effects are a common immediate consequence of positive test results following risk assessment. Results from the few experimental studies reviewed suggest that these adverse outcomes should not be seen as inevitable.
Acquired Immunodeficiency Syndrome↗
The Crohn's and Colitis Knowledge Score: a test for measuring patient knowledge in inflammatory bowel disease.
OBJECTIVE: The aim of this study was to develop a valid and reliable questionnaire assessing patient knowledge of inflammatory bowel disease (IBD) and its treatment--the Crohn's and Colitis Knowledge (CCKNOW) Score. METHODS: A total of 30 multiple choice questions were constructed into a draft questionnaire. This was piloted on a random selection of participants with differing IBD knowledge levels; junior doctors, nurses, and ward clerks. Factor analysis eliminated questions with poor discriminant ability. The resulting 24-item questionnaire (CCKNOW score) was retested on the three groups, and a Kruskal-Wallis test determined the questionnaire's ability to discriminate between the groups. Reliability and readability were tested using Cronbach's a and the Flesch Kincaid reading score. The validated CCKNOW was then tested on patients from the Leicestershire IBD database. RESULTS: CCKNOW scores differed significantly across the groups of doctors, nurses, and ward clerks (median 22, 16, and five, respectively) T = 40.35, p < 0.0001. The reliability was very good with a Cronbach's alpha of 0.95 and the readability was also high. The median score on the CCKNOW for IBD patients was 10, with no significant difference between ulcerative colitis and Crohn's disease. Patients who are members of NACC (National Association of Crohn's and Colitis) achieve statistically significantly higher scores than do nonmembers (difference in medians 4, 95% confidence interval 4-6, p < 0.0001). CONCLUSIONS: The CCKNOW score provides a valuable index of overall knowledge. It is self-administered and psychometric tests show it to be valid, reliable, and readable. It may be used in the future as a tool to evaluate patient education programs.
Adult↗
Patterns and correlates of tobacco use among suburban Philadelphia 6th- through 12th-grade students.
BACKGROUND AND OBJECTIVES: Tobacco use among teenagers is increasing, even in the face of an understanding of its harmful effects. Data suggest that tobacco use often begins before entrance to eighth grade. This study examined the prevalence of tobacco use among students in 6th grade and compared it to the prevalence of tobacco use among 8th, 10th, and 12th graders in a northeastern suburban community and to national data. METHODS: We used a survey that measured selected tobacco and smokeless tobacco use, demographic variables, school-related factors, and social influences on the use of tobacco products. RESULTS: Sixth-grade tobacco use existed but was minimal compared to the rates seen in 8th, 10th, and 12th graders. Only 1% of 6th graders reported they were current smokers, compared with 41% of 12th graders. Risk factors for becoming a smoker were smoking habits of parents, siblings, and friends. CONCLUSIONS: Cigarette experimentation and use begins as early as sixth grade and increases substantially by eighth grade. Our data suggest that efforts toward primary prevention of smoking should be pursued between sixth and eighth grade.
Adolescent↗
Lessons of a hip failure. Register exists in Trent region.
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Arthroplasty, Replacement, Hip↗
Safety and fetal outcome of early and midtrimester amniocentesis.
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Abortion, Spontaneous↗
Approximate Bayesian inference for random effects meta-analysis.
Whilst meta-analysis is becoming a more commonplace statistical technique, Bayesian inference in meta-analysis requires complex computational techniques to be routinely applied. We consider simple approximations for the first and second moments of the parameters of a Bayesian random effects model for meta-analysis. These computationally inexpensive methods are based on simple analytical formulae that provide an efficient tool for a qualitative analysis and a quick numerical estimation of posterior quantities. They are shown to lead to sensible approximations in two examples of meta-analyses and to be in broad agreement with the more computationally intensive Gibbs sampling.
Antibiotic Prophylaxis↗
Effect of a low-impact exercise program on bone mineral density in Crohn's disease: a randomized controlled trial.
BACKGROUND & AIMS: Physical exercise increases bone mineral density (BMD) in healthy young adults and slows the rate of bone loss in later life. The aim of this randomized controlled trial was to investigate the effect of exercise on BMD in patients with Crohn's disease. METHODS: A total of 117 patients with Crohn's disease were randomized to a control group or a low-impact exercise program of increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS: Nonsignificant gains in BMD occurred at the hip and spine in the exercise group compared with controls (P > 0.05). In fully compliant patients, BMD increased by 3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at Ward's triangle, and 7.77% (8.2%) at the greater trochanter. Compared with controls, gain in BMD at the greater trochanter was statistically significant (difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02). Increases in BMD were significantly related to the number of exercise sessions completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04). CONCLUSIONS: Progressive low-impact exercise is a potentially effective method of increasing BMD in Crohn's disease. If sustained, the increases in BMD may reduce the risk of osteoporotic fracture.
Adult↗
Newborn acid-base status and umbilical cord morphology.
OBJECTIVE: To assess the relation between umbilical cord morphology and intrapartum fetal status and umbilical cord blood gases at birth. METHODS: In a prospective study of 134 consecutive newborns and their umbilical cords, relations were investigated between umbilical cord morphologic characteristics (umbilical cord length, number of vascular coils, coiling index, and vessel length index) and intrapartum fetal heart rate (FHR) decelerations, color of amniotic fluid, operative delivery for suspected fetal acidosis, umbilical vessel blood gases, and acid-base status. RESULTS: Statistically significant linear correlations were found between umbilical venous pH and the umbilical cord length (r = 0.30; 95% confidence interval [CI] 0.13, 0.46; P < .001), number of vascular coils (r = 0.27; 95% CI 0.10, 0.43; P = .001), coiling index (r = 0.15; 95% CI 0, 0.33; P = .05), and vessel length index (r = 0.30; 95% CI 0.13, 0.46; P < .001). Statistically significant negative linear correlations were found between the umbilical venous partial pressure of carbon dioxide (PCO2) and cord length (r = -0.34, 95% CI -0.49, -0.17; P < .001), number of vascular coils (r = -0.30, 95% CI -0.46, -0.13; P < .001), coiling index (r = -0.17, 95% CI -0.34, 0; P = .03), and vessel length index (r = -0.34, 95% CI -0.49, -0.17; P < .001). The umbilical artery pH was related to vessel length index and to the number of umbilical vascular coils (r = 0.17, 95% CI 0.03, 0.36; P = .04 and r = 0.17, 95% CI 0.02, 0.35; P = .047, respectively). No relation was found between umbilical cord indices and intrapartum FHR decelerations, meconium staining of the amniotic fluid, or mode of delivery. Placental weight also correlated with umbilical cord length and vessel length index (95% CI 0.15, 0.46; P < .001 and 95% CI 0.05, 0.38; P = .01, respectively), but not with the number of umbilical cord coils or the coiling index. CONCLUSION: Umbilical venous pH and PCO2 and umbilical artery pH are related to umbilical cord morphology. Associated variations in placental morphology or placental blood flow affecting maternal-fetal gas exchange may explain these findings.
Acid-Base Equilibrium↗
Osteoporosis and determinants of bone density in patients with Crohn's disease.
Low bone mineral density (BMD) is common in patients with Crohn's disease; however, the pathogenesis of bone loss and risk factors for osteoporosis are not established. Our aim was to evaluate the clinical, dietary, and nutritional determinants of BMD in Crohn's disease. A cross-sectional analysis of 117 patients with Crohn's disease was undertaken. All patients underwent a clinical and dietary evaluation including assessment of nutritional state and life-style. BMD was measured at the hip and lumbar spine by dual-energy x-ray absorptiometry; and z scores obtained by comparison with age- and sex-matched normal values for the healthy UK population. Multiple regression analysis was used to assess associations between BMD and potential risk factors, allowing for possible confounding variables. Thirteen (11%) patients had osteoporosis (z score < -2), with osteopenia (z score < -1, > -2) in a further 34 (29%). Patients with jejunal disease had significantly lower BMD at the spine (P = 0.03) and femoral neck (P = 0.02) than those with disease at other sites. Mean BMD was significantly lower at the hip of patients with previous bowel resection (diff in means = 0.53, 95% CI -0.97, -0.08, P = 0.02), but type of surgery was not significant. Active disease, menstrual history, diet, level of physical activity, and smoking were not associated with low bone mass. At the lumbar spine, body weight (P < 0.0001), male sex (P < 0.0001), and current prednisolone use (P < 0.02) were independently predictive of low bone mass. Body weight (P < 0.0001), male sex (P < 0.0001), and cumulative steroid dose (P = 0.02) were predictive at the femoral neck. The major determinants of BMD in Crohn's disease are body weight, current steroid use, and cumulative steroid dose. Men with Crohn's disease are at greatest risk of osteoporosis, with jejunal involvement and previous bowel resection also contributing to the low bone mineral density.
Absorptiometry, Photon↗
Sex hormone status and bone metabolism in men with Crohn's disease.
BACKGROUND: Men with Crohn's disease (CD) are at risk of osteoporosis, but the factors contributing to low bone mineral density and its optimum treatment have not been established. AIM: To investigate the sex hormone status of men with CD, and to establish the influence of sex hormones on their bone metabolism. METHODS: Bone density was measured by dual energy X-ray absorptiometry at the hip and lumbar spine in 48 men with CD. Total serum testosterone and gonadotrophins were measured in all subjects and the free androgen index calculated in men with low or borderline total testosterone. Serum osteocalcin, pro-collagen carboxy-terminal peptide, bone specific alkaline phosphatase and urinary deoxypyridinoline were measured as markers of bone turnover. RESULTS: Eight (17%) men had osteoporosis, and a further 14 (29%) had osteopenia. Three (6%) men had a low free androgen index and normal gonadotrophins consistent with secondary hypogonadism, two of whom had osteopenia of the hip and spine. Age (P = 0.002) and small bowel Crohn's disease (P = 0.02) were the only independent predictors of serum testosterone. There was a significant association between total testosterone and osteocalcin (r = 0.53, 95%, CI: 0.29-0.71, P = 0.0001) which was independent of age and current steroid use (P = 0.0001). CONCLUSIONS: Previously undiagnosed hypogonadism is an uncommon cause of low bone density in men with CD. The independent association between testosterone and the bone formation marker osteocalcin suggests sex hormone status influences bone metabolism in men with CD. The results suggest testosterone replacement might be effective treatment for some men with osteoporosis and Crohn's disease.
Absorptiometry, Photon↗
The effect of rectally administered steroids on bone turnover: a comparative study.
BACKGROUND: Oral glucocorticoids contribute significantly to the risk of osteoporosis in patients with inflammatory bowel disease. Less well established are the effects of rectally administered steroids on bone metabolism. AIM: To investigate the effects of two widely used rectal foam preparations (prednisolone metasulphobenzoate and hydrocortisone acetate) on biochemical markers of bone turnover. METHODS: Twenty-four patients with active inflammatory bowel disease randomly received a standard course of either prednisolone metasulphobenzoate or hydrocortisone acetate for 2 weeks. Biochemical markers of bone turnover were measured before, during and after treatment. Bone formation markers measured were serum osteocalcin (BGP) and bone-specific alkaline phosphatase (BALP). Urinary deoxypyridinoline (DPD) was measured to assess bone resorption. RESULTS: Disease activity scores improved during treatment (difference in mean Powell-Tuck score = 3.4, 95% CI: 2.0-4.8, P < 0.0001) and were similar in both hydrocortisone and prednisolone-treated groups. There was no significant reduction in BALP or BGP during treatment with either steroid preparation, and urinary DPD did not change significantly during treatment. CONCLUSIONS: During a 2-week course of rectal hydrocortisone acetate or prednisolone metasulphobenzoate, there was no significant change in biochemical markers of bone formation or resorption. These results suggest that pharmacological doses of rectal steroid foam preparations do not significantly impair bone turnover in patients with inflammatory bowel disease.
Administration, Rectal↗
Increased bone resorption in patients with Crohn's disease.
BACKGROUND: Patients with Crohn's disease are at risk of osteoporosis and premature fracture. However, the pathophysiology underlying bone loss remains poorly understood and the optimum treatment has not been established. AIM: To investigate mechanisms of bone loss in Crohn's disease using biochemical markers of bone turnover. METHODS: Bone mineral density was measured at the hip and spine using dual-energy X-ray absorptiometry in 117 patients (48 male) with Crohn's disease. Bone turnover was assessed by measuring serum osteocalcin (BGP), pro-collagen carboxy-terminal propeptide (PICP), bone specific alkaline phosphatase (BALP) and urinary deoxypyridinoline (DPD); and compared to age-matched healthy controls (n = 28). RESULTS: Bone mineral density was reduced (z-score < -1) in 48 (41%) patients with Crohn's disease. Mean values for bone formation markers in patients with Crohn's disease were all within the normal reference range (BGP 8.92 (+/- 3.23) ng/mL (normal range 3.4-10.0), BALP 17.6 (+/- 12.6) U/L (normal range 11.6-43.3), PICP 95.1 (+/- 46.5) ng/mL (normal range 69-163)) and were not significantly different to the control population. However, mean urinary DPD was significantly higher in patients with Crohn's disease compared to healthy controls (10.97 (+/- 9.22) nM DPD/mM creatinine vs. 5.02 (+/- 1.03) nM DPD/mM creatinine, difference in means = 5.95, 95% CI: -9.6 to -2.3, P = 0.00001) and compared to the UK reference range DPD levels were increased in 74 (63%) patients. CONCLUSIONS: Bone resorption as evidenced by urinary DPD was frequently increased in patients with Crohn's disease and was significantly higher than in an age-matched control population. The high levels of urinary DPD suggest increased bone collagen degradation may contribute to osteoporosis in patients with Crohn's disease. These results suggest anti-resorptive agents such as the bisphosphonates may be effective treatment for osteoporosis in Crohn's disease.
Adult↗