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Biomedical subjects

D R Jones

Publications and source records attributed to D R Jones.

At least 73 records · Page 4Linked to original sources

Empirical assessment of effect of publication bias on meta-analyses.

OBJECTIVE: To assess the effect of publication bias on the results and conclusions of systematic reviews and meta-analyses. DESIGN: Analysis of published meta-analyses by trim and fill method. STUDIES: 48 reviews in Cochrane Database of Systematic Reviews that considered a binary endpoint and contained 10 or more individual studies. MAIN OUTCOME MEASURES: Number of reviews with missing studies and effect on conclusions of meta-analyses. RESULTS: The trim and fill fixed effects analysis method estimated that 26 (54%) of reviews had missing studies and in 10 the number missing was significant. The corresponding figures with a random effects model were 23 (48%) and eight. In four cases, statistical inferences regarding the effect of the intervention were changed after the overall estimate for publication bias was adjusted for. CONCLUSIONS: Publication or related biases were common within the sample of meta-analyses assessed. In most cases these biases did not affect the conclusions. Nevertheless, researchers should check routinely whether conclusions of systematic reviews are robust to possible non-random selection mechanisms.

Clinical Trials as Topic↗

Characterisation of mucosal and systemic immune responses in rainbow trout (Oncorhynchus mykiss) using surface plasmon resonance.

Mucosal and systemic antibody production in rainbow trout, Oncorhynchus mykiss (Walbaum), was evaluated following different antigen delivery routes. A BIAcore instrument (Pharmacia) allowed direct detection of antibody-antigen interactions by surface plasmon resonance changes. These interactions were measured in real-time without secondary reagents or extraneous labels. Groups of rainbow trout were immunised with a hapten-carrier antigen consisting of fluorescein isothiocyanate (FITC) conjugated to keyhole limpet haemocyanin (KLH) or phosphate buffered saline (PBS) pH 7.2. Antigens were administered intraperitoneally (i.p.) with or without Freund's complete adjuvant (FCA) or peranally (p.a.) directly to the gastrointestinal (GI) tract. Serum and mucosal anti-FITC responses were significantly (P<0.05) higher in FITC-KLH/FCA groups, clearly showing that adjuvant incorporation enhances mucosal as well as sytemic immunity. Antigen uptake and processing in fish immunised p.a. and i.p. without adjuvant was much less efficient and resulted in relatively low levels of serum and mucosal antibody production. Interestingly, mucosal responses in these groups peaked prior to serum responses suggesting possible early stimulation of mucosal defences. Mucosal antibody production in fish receiving FITC-KLH/FCA correlated more closely with serum responses, indicating possible transfer of serum derived antibody to mucosal sites. Mucosal and serum responses were confirmed as immunoglobulin (Ig) by subsequent reactivity with an anti-trout serum IgM monoclonal antibody (1.14) passed over flow cells containing anti-FITC antibodies. Further analysis showed significantly lower (P<0.05) reactivity of early mucus anti-FITC components (4 weeks post-immunisation) to 1.14. Purified serum and mucus Ig from non-immunised fish showed different protein banding patterns by SDS-PAGE under reducing conditions. Immunoblotting with 1.14 also showed weak reactivity to mucus Ig in control fish while reacting strongly to mucus Ig from immunised fish. These data suggest that early mucosal responses in trout may consist of heterogeneous forms of Ig differing in characteristics to serum Ig. BIAcore analysis in this context and as a means of measuring antibody response proved useful, and has the potential to become a valuable new tool in the study of fish immunology.

Adjuvants, Immunologic↗

Inhibition of NF-kappaB sensitizes non-small cell lung cancer cells to chemotherapy-induced apoptosis.

BACKGROUND: Most non-small cell lung cancers (NSCLC) are chemoresistant. Identification and modulation of chemoresistance cell-signaling pathways may sensitize NSCLC to chemotherapy and improve patient outcome. The purpose of this study was to determine if chemotherapy induces nuclear factor-kappa B (NF-kappaB) activation in NSCLC in vitro and whether inhibition of NF-kappaB would sensitize tumor cells to undergo chemotherapy-induced apoptosis. METHODS: Non-small cell lung cancer cells were treated with gemcitabine, harvested, and nuclear extracts analyzed for NF-kappaB DNA binding by electrophoretic mobility shift assays. Additionally, NSCLC cells that stably expressed a plasmid encoding the superrepressor IkappaBalpha protein (H157I) or a vector control (H157V) were generated. These cells were then treated with gemcitabine and apoptosis determined by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: Chemotherapy induced NF-kappaB nuclear translocation and DNA binding in all NSCLC cell lines. H157I cells had enhanced cell death compared with H157V cells, suggesting that NF-kappaB is required for cell survival after chemotherapy. The observed cell death following the loss of NF-kappaB occurred by apoptosis. CONCLUSIONS: Inhibition of chemotherapy-induced NF-kappaB activation sensitizes NSCLC to chemotherapy-induced apoptosis in vitro. Novel treatment strategies for patients with advanced NSCLC may involve chemotherapy combined with inhibition of NF-kappaB-dependent cell-survival pathways.

Antimetabolites, Antineoplastic↗

Breathing frequencies of northern elephant seals at sea and on land revealed by heart rate spectral analysis.

Elephant seals breathe episodically at sea and on land and surprisingly long apnoeas occur in both situations. An important difference is that recovery from apnoeic periods is much quicker at sea, which might be due, in part, to differences in the ventilatory response. Respiratory frequencies of juvenile northern elephant seals diving at sea and resting on land were estimated from time-frequency maps of the Wigner distribution of heart rate variability. Simultaneous direct measurement of respiration and estimation of respiratory frequency (fR) in the laboratory demonstrated that the error of estimation was small (mean +/- S.D.= 1.05+/-1.23%) and was independent of the magnitude of fR. Eupnoeic fR at sea was 2.4 times higher than on land (22.0+/-2.0 vs. 9.2+/-1.3 breaths min(-1), respectively), facilitating quick recovery from the preceding dive and allowing a 34% increase in time spent apnoeic at sea versus on land. The overall fR (no. of breaths in a eupnoea divided by the total time of the apnoea+eupnoea cycle) of 2.3+/-0.6 breaths min(-1) at sea was no different from the rate on land and was inversely related to the preceding dive duration, suggesting that metabolism on longer dives may be reduced.

Animals↗

Pragmatic randomized trial of antenatal intervention to prevent post-natal depression by reducing psychosocial risk factors.

BACKGROUND: Social support theory and observational risk factor studies suggest that increased antenatal psychosocial support could prevent post-natal depression. We used empirical knowledge of risk and protective factors for post-natal depression not employed previously in order to develop and evaluate an antenatal preventive intervention. METHODS: We conducted a pragmatic randomized controlled trial in antenatal clinics. We screened 1300 primiparous women and 400 screened positive, 69 screen-positive women were untraceable or not eligible. Of 292 women who completed baseline assessment, 209 consented to randomization, of these 190 provided outcome data 3 months post-natally. 'Preparing for Parenthood', a structured antenatal risk factor reducing intervention designed to increase social support and problem-solving skills, was compared with routine antenatal care only. We compared the percentage depressed at 3 months after childbirth using the self-completion General Health Questionnaire Depression scale and Edinburgh Post-natal Depression Scale (EPDS), and the Schedules for Clinical Assessment in Neuropsychiatry a systematic clinical interview. RESULTS: Assignment to the intervention group did not significantly impact on post-natal depression (odds ratio for GHQ-Depression 1.22 (95% CI 0.63-2.39), P = 0.55) or on risk factors for depression. Forty-five per cent of the intervention group women attended sufficient sessions to be likely to benefit from intervention if effective. Attenders benefited no more than non-attenders. CONCLUSIONS: Prevention services targeting post-natal depression should not implement antenatal support programmes on these lines until further research has demonstrated the feasibility and effectiveness of such methods. The development of novel, low cost interventions effective in reducing risk factors should be completed before further trial evaluation.

Adolescent↗

Intravenous diltiazem and CYP3A-mediated metabolism.

AIMS: To study whether intravenous diltiazem, a calcium channel blocker commonly prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a substrate. METHODS: Ten healthy volunteers were studied in a randomized two-way crossover design. The two arms were 1) administration of a 20 mg dosage of lovastatin orally and 2) administration of a 20 mg dosage of lovastatin orally 1 h after an intravenous loading dosage and constant infusion of diltiazem. Blood samples were collected up to 25 h in order to quantify lovastatin and diltiazem concentrations in the separated serum. Lovastatin and diltiazem concentrations were quantified by GC-MS and h.p.l.c., respectively. RESULTS: Intravenous diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of lovastatin. CONCLUSIONS: These data suggest that the interaction of lovastatin with diltiazem does not occur systemically and is primarily a first-pass effect. Thus, drug interactions with diltiazem may become evident when a patient is moved from intravenous to oral dosing.

Adult↗

Birth weight and 24-hour ambulatory blood pressure in nonproteinuric hypertensive pregnancy.

OBJECTIVE: The aim of this study was to examine the relationship between maternal ambulatory blood pressure monitor measurements during pregnancy and birth weight in a population of women considered to have hypertension according to conventional antenatal clinic measurement. STUDY DESIGN: A prospective observational study was carried out within the obstetric departments of Leicester Royal Infirmary and Queen Charlotte's Hospital. A total of 237 women were found to have hypertension (blood pressure >/=140/90 mm Hg) without significant proteinuria during examination in the antenatal assessment area. Sequential-day unit blood pressure recordings and a 24-hour automated ambulatory blood pressure recording were performed, and the results were compared with the principal outcome measure of birth weight. RESULTS: A significant inverse association (gradient, -13.5; 95% confidence interval -23.4 to -3.6) was found between daytime ambulatory diastolic blood pressure measurement and birth weight. An increase of 5 mm Hg in daytime mean diastolic blood pressure was associated with a fall in birth weight of 68.5 g. This association remained after adjustment for potential confounders that included maternal age, maternal weight, smoking status, ethnicity, and gestational age at delivery. No such association was found between obstetric day unit assessment of blood pressure and birth weight. CONCLUSION: There is a significant association between blood pressure and birth weight in nonproteinuric hypertensive pregnancies. The best predictor of this association is the daytime mean ambulatory diastolic blood pressure measurement. This is further evidence that maternal blood pressure may be an important confounding and potentially genetic variable in the association between birth weight and subsequent adult hypertension.

Adult↗

Changes in the balance between mitogenic and antimitogenic lipid second messengers during proliferation, cell arrest, and apoptosis in T-lymphocytes.

Control of lymphocyte cell survival and proliferation is critical for both the immune response and for the prevention of autoimmune and infectious diseases. The actions of interleukin-2, the major T-cell regulatory cytokine, are mediated by the complex network of divergent signalling pathways controlled by its high-affinity receptor. Various studies have indicated that the generation of certain lipid second messengers is an important mechanism in the control of proliferation and cell death. We have examined the relationship between diacylglycerol and ceramide and the levels of the lipids phosphatidylcholine and sphingomyelin, their potential precursors, in the human T-cell line Kit 225 cultured in three distinct conditions to favor apoptosis, cell arrest, and proliferation. Our data show that, in proliferating cells, the ratios of diacylglycerol/ceramide and phosphatidylcholine/sphingomyelin are higher than those found in arrested cells and increase with time in culture. These ratios are rapidly reversed in apoptotic cells. Further experiments reveal that de novo synthesis of both diacylglycerol and phosphatidylcholine is greatest in proliferating cells, whereas sphingomyelin synthase activity is increased in cells undergoing apoptosis. In summary, our results demonstrate for the first time that the ratio of mitogenic/antimitogenic lipids changes dramatically during T-cell proliferation and cell death. These results indicate that lipid second messengers and the enzymes that are responsible for their generation may provide targets for novel therapeutic interventions in the clinical management of immunosuppression and autoimmune disease.

Apoptosis↗

Gastrointestinal autonomic nerve sarcoma presenting as a giant intra-abdominal cyst.

Gastrointestinal autonomic nerve sarcomas are rare tumours. A 36-year-old man presented with abdominal pain, distension and constipation. Abdominal ultrasound and CT scanning demonstrated a giant cystic intra-abdominal mass. Laparotomy confirmed a large cystic mass arising from the ileum with multiple metastases. Immunohistochemical staining was positive for vimentin, neuronal-specific enolase and PGP9.5. This is the first reported case to present as a giant intra-abdominal cyst. Specialist histopathological and immunohistochemical analysis is essential to establish the diagnosis of this rare tumour.

Abdomen↗

Fear of flying--no longer a symptom without a disease.

This commentary accompanies the article "Fear of flying treatment programs for passengers: an international review," by Van Gerwen and Diekstra, a report on the international aviation community's approach to fearful air travelers. Most of the aeromedical literature has dealt with fear of flying in aircrew; little has been written about such fears among passengers. The aviation community has dealt with fearful passengers through variations in cognitive-behavioral methods, but without any underlying medical model. As a result, these programs go mainly unsupervised and unregulated, and do not address such matters as differential diagnosis, informed consent for treatment, clear therapeutic goals, organized follow-up, or outcome criteria and statistics. Treating agencies also tend to apply the same treatment methods to all applicants, in spite of emerging data that show that, in fact, different causes call for different treatments. This commentary reviews these findings in the larger context of the medical model and calls for further research along the lines developed by Van Gerwen and Diekstra (11).

Aerospace Medicine↗

An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation.

An in vitro model is proposed to account for the clinically observed inhibition of cytochrome P450 (CYP) 3A that results from administration of clarithromycin, fluoxetine, or diltiazem. Rates for loss of CYP3A4 enzymatic activity resulting from metabolic intermediate complex formation and the concentration dependencies thereof were determined in vitro for clarithromycin, fluoxetine, and N-desmethyl diltiazem, which is the primary metabolite of diltiazem. Using the in vitro concentration-dependent rates for loss of activity, in vivo rates of CYP3A4 inactivation were predicted for these compounds at a clinically relevant unbound plasma concentration of 0.1 microM. Based on the predicted rates combined with published rates for in vivo CYP3A degradation, our model predicts that fluoxetine, clarithromycin, and the primary metabolite of diltiazem reduce the steady-state concentration of liver CYP3A4 to approximately 72, 39, or 21% of initial levels, respectively. These reductions correspond to 1.4-, 2.6-, or 4.7-fold increases, respectively, in the area under the plasma concentration-time curve of a coadministered drug that is eliminated exclusively by hepatic CYP3A4 metabolism. These predicted results are in good agreement with reported clinical data. The major implication of this work is that fluoxetine, clarithromycin, and the primary metabolite of diltiazem, at clinically relevant concentrations, inactivate CYP3A4 enzymatic activity at rates sufficient to affect in vivo concentrations of CYP3A4 and thereby affect the clearance of compounds eliminated by this pathway. We speculate that mechanisms involving substrate-mediated mechanistic inactivation of CYPs play a major role in many clinically observed drug-drug interactions.

Anti-Bacterial Agents↗

Bayesian methods in health technology assessment: a review.

BACKGROUND: Bayesian methods may be defined as the explicit quantitative use of external evidence in the design, monitoring, analysis, interpretation and reporting of a health technology assessment. In outline, the methods involve formal combination through the use of Bayes's theorem of: 1. a prior distribution or belief about the value of a quantity of interest (for example, a treatment effect) based on evidence not derived from the study under analysis, with 2. a summary of the information concerning the same quantity available from the data collected in the study (known as the likelihood), to yield 3. an updated or posterior distribution of the quantity of interest. These methods thus directly address the question of how new evidence should change what we currently believe. They extend naturally into making predictions, synthesising evidence from multiple sources, and designing studies: in addition, if we are willing to quantify the value of different consequences as a 'loss function', Bayesian methods extend into a full decision-theoretic approach to study design, monitoring and eventual policy decision-making. Nonetheless, Bayesian methods are a controversial topic in that they may involve the explicit use of subjective judgements in what is conventionally supposed to be a rigorous scientific exercise. OBJECTIVES: This report is intended to provide: 1. a brief review of the essential ideas of Bayesian analysis 2. a full structured review of applications of Bayesian methods to randomised controlled trials, observational studies, and the synthesis of evidence, in a form which should be reasonably straightforward to update 3. a critical commentary on similarities and differences between Bayesian and conventional approaches 4. criteria for assessing the reporting of a Bayesian analysis 5. a comprehensive list of published 'three-star' examples, in which a proper prior distribution has been used for the quantity of primary interest 6. tutorial case studies of a variety of types 7. recommendations on how Bayesian methods and approaches may be assimilated into health technology assessments in a variety of contexts and by a variety of participants in the research process. METHODS: The BIDS ISI database was searched using the terms 'Bayes' or 'Bayesian'. This yielded almost 4000 papers published in the period 1990-98. All resultant abstracts were reviewed for relevance to health technology assessment; about 250 were so identified, and used as the basis for forward and backward searches. In addition EMBASE and MEDLINE databases were searched, along with websites of prominent authors, and available personal collections of references, finally yielding nearly 500 relevant references. A comprehensive review of all references describing use of 'proper' Bayesian methods in health technology assessment (those which update an informative prior distribution through the use of Bayes's theorem) has been attempted, and around 30 such papers are reported in structured form. There has been very limited use of proper Bayesian methods in practice, and relevant studies appear to be relatively easily identified. RESULTS: Bayesian methods in the health technology assessment context 1. Different contexts may demand different statistical approaches. Prior opinions are most valuable when the assessment forms part of a series of similar studies. A decision-theoretic approach may be appropriate where the consequences of a study are reasonably predictable. 2. The prior distribution is important and not unique, and so a range of options should be examined in a sensitivity analysis. Bayesian methods are best seen as a transformation from initial to final opinion, rather than providing a single 'correct' inference. 3. The use of a prior is based on judgement, and hence a degree of subjectivity cannot be avoided. However, subjective priors tend to show predictable biases, and archetypal priors may be useful for identifying a reasonable range of prior opinion.

Bayes Theorem↗

Involvement of phosphatidylinositol 3-kinase in stromal cell-derived factor-1 alpha-induced lymphocyte polarization and chemotaxis.

The role of phosphatidylinositol 3-kinase (PI3-kinase), an important enzyme involved in signal transduction events, has been studied in the polarization and chemotaxis of lymphocytes induced by the chemokine stromal cell-derived factor-1 alpha (SDF-1 alpha). This chemokine was able to directly activate p85/p110 PI3-kinase in whole human PBL and to induce the association of PI3-kinase to the SDF-1 alpha receptor, CXCR4, in a pertussis toxin-sensitive manner. Two unrelated chemical inhibitors of PI3-kinase, wortmannin and Ly294002, prevented ICAM-3 and ERM protein moesin polarization as well as the chemotaxis of PBL in response to SDF-1 alpha. However, they did not interfere with the reorganization of either tubulin or the actin cytoskeleton. Moreover, the transient expression of a dominant negative form of the PI3-kinase 85-kDa regulatory subunit in the constitutively polarized Peer T cell line inhibited ICAM-3 polarization and markedly reduced SDF-1 alpha-induced chemotaxis. Conversely, overexpression of a constitutively activated mutant of the PI3-kinase 110-kDa catalytic subunit in the round-shaped PM-1 T cell line induced ICAM-3 polarization. These results underline the role of PI3-kinase in the regulation of lymphocyte polarization and motility and indicate that PI3-kinase plays a selective role in the regulation of adhesion and ERM proteins redistribution in the plasma membrane of lymphocytes.

Antigens, CD↗

Diacylglycerol kinase inhibition prevents IL-2-induced G1 to S transition through a phosphatidylinositol-3 kinase-independent mechanism.

Stimulation via IL-2R ligation causes T lymphocytes to transit through the cell cycle. Previous experiments by our group have demonstrated that, in human T cells, IL-2 binding induces phosphatidic acid production through activation of the alpha isoform of diacylglycerol kinase. In this study, using the IL-2-dependent mouse T cell line CTLL-2, we demonstrate that pharmacological inhibition of IL-2-induced diacylglycerol kinase activation is found to block IL-2-induced late G1 to S transition without affecting cell viability. Herein, we demonstrate that diacylglycerol kinase inhibition has a profound effect on the induction of the protooncogenes c-myc, c-fos, and c-raf by IL-2, whereas expression of bcl-2 and bcl-xL are not affected. When the IL-2-regulated cell cycle control checkpoints are examined in detail, we demonstrate that inhibition of diacylglycerol kinase activation prevents IL-2 induction of cyclin D3 without affecting p27 down-regulation. The strict control of cell proliferation exerted by phosphatidic acid through activation of diacylglycerol kinase is independent of other well-characterized IL-2R-derived signals, such as the phosphatidylinositol-3 kinase/Akt pathway, indicating the existence of a different and important mechanism to control cell division.

Animals↗

The identification of phosphatidylinositol 3,5-bisphosphate in T-lymphocytes and its regulation by interleukin-2.

In recent times 3-phosphoinositides have emerged as important regulators of cell metabolism, survival, and proliferation. During the last year, the phospholipid phosphatidylinositol 3, 5-bisphosphate (PtdIns3,5P2) was identified in yeast, fibroblasts, SV40-transformed kidney (COS-7) cells, and platelets. The discovery of this novel phospholipid has increased the complexity of the metabolism relating to the generation of biologically active inositol-containing lipids. We describe here the identification of PtdIns3,5P2 in the CTLL-2 mouse T-lymphocyte cell line using two in vivo radiolabeling protocols. Treatment of the cells with UV radiation led to an increase in the cellular content of PtdIns3,5P2. In contrast, preincubation of the cells with wortmannin or treatment with hypertonic medium (high concentration sorbitol) led to the opposite effect. Herein we demonstrate that interleukin-2 (IL-2), the growth factor required for CTLL-2 cell proliferation, was able to increase the level of PtdIns3,5P2 with similar kinetics to that of the formation of phosphatidylinositol 3,4-bisphosphate (PtdIns3, 4P2). An increase in this novel 3-phosphorylated lipid in response to IL-2 seems to be a general property of this cytokine because a similar result was obtained when the pre-B cell line BaF/3 expressing the high affinity IL-2 receptor was used. Using a constitutively active regulatory subunit of type I phosphatidylinositol 3-kinase and cells expressing a deletion of the serine-rich domain of the IL-2 receptor beta chain, which is required for IL-2-stimulated type I phosphatidylinositol 3-kinase activation, we demonstrate that IL-2-induced generation of PtdIns3, 5P2 is related to the activation of this enzyme. The results show for the first time the identification of PtdIns3,5P2 in both T- and B-lymphocytes and indicate its positive regulation by the mitogen IL-2.

Animals↗

Interleukin-2 causes an increase in saturated/monounsaturated phosphatidic acid derived from 1,2-diacylglycerol and 1-O-alkyl-2-acylglycerol.

Phosphatidic acid generation through activation of diacylglycerol kinase alpha has been implicated in interleukin-2-dependent T-lymphocyte proliferation. To investigate this lipid signaling in more detail, we characterized the molecular structures of the diradylglycerols and phosphatidic acids in the murine CTLL-2 T-cell line under both basal and stimulated conditions. In resting cells, 1,2-diacylglycerol and 1-O-alkyl-2-acylglycerol subtypes represented 44 and 55% of total diradylglycerol, respectively, and both showed a highly saturated profile containing primarily 16:0 and 18:1 fatty acids. 1-O-Alk-1'-enyl-2-acylglycerol represented 1-2% of total diradylglycerol. Interleukin-2 stimulation did not alter the molecular species profiles, however, it did selectively reduce total 1-O-alkyl-2-acylglycerol by over 50% at 15 min while only causing a 10% drop in 1,2-diacylglycerol. When radiolabeled CTLL-2 cells were challenged with interleukin-2, no change in the cellular content of phosphatidylcholine nor phosphatidylethanolamine was observed thereby ruling out phospholipase C activity as the source of diradylglycerol. In addition, interleukin-2 failed to stimulate de novo synthesis of diradylglycerol. Structural analysis revealed approximately equal amounts of 1,2-diacyl phosphatidic acid and 1-O-alkyl-2-acyl phosphatidic acid under resting conditions, both containing only saturated and monounsaturated fatty acids. After acute (2 and 15 min) interleukin-2 stimulation the total phosphatidic acid mass increased, almost entirely through the formation of 1-O-alkyl-2-acyl species. In vitro assays revealed that both 1,2-diacylglycerol and 1-O-alkyl-2-acylglycerol were substrates for 1,2-diacylglycerol kinase alpha, the major isoform in CTLL-2 cells, and that the lipid kinase activity was almost totally inhibited by R59949. In conclusion, this investigation shows that, in CTLL-2 cells, 1,2-diacylglycerol kinase alpha specifically phosphorylates a pre-existing pool of 1-O-alkyl-2-acylglycerol to form the intracellular messenger 1-O-alkyl-2-acyl phosphatidic acid.

Animals↗

Inadequacy of computed tomography in assessing patients with esophageal carcinoma after induction chemoradiotherapy.

BACKGROUND: Induction chemoradiotherapy followed by surgery may improve survival of patients with esophageal carcinoma. Computed tomography (CT) has been used to evaluate the tumor response after completing induction chemoradiotherapy. The authors examined the ability of CT to evaluate the pathologic tumor response to induction therapy and to stage the tumor correctly. METHODS: Preinduction and postinduction chemoradiotherapy CT scans were reviewed retrospectively for 50 patients enrolled in a protocol of induction chemoradiotherapy followed by surgery. All studies were performed on third-generation or fourth-generation scanners. Radiographic response was determined using Eastern Cooperative Oncology Group solid tumor response criteria for bidimensional measurable disease. This was compared with the pathologic tumor response. CT-tumor (T) classification using the modified Tio scale was compared with the pathologic T classification. RESULTS: CT-T classification did not correlate with the pathologic stage (P = 0.09) or the pathologic tumor response (P = 0.22). The postinduction chemoradiotherapy CT accurately staged the T classification in 42% of patients but overstaged 36% of patients and understaged 20% of patients. CT had a sensitivity of 65%, a specificity of 33%, a positive predictive value of 58%, and a negative predictive value of 41% in evaluating the pathologic tumor response. CONCLUSIONS: CT is a poor diagnostic study tool for determining the pathologic tumor response or the pathologic disease stage after induction chemoradiotherapy in patients with esophageal carcinoma.

Adult↗