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Biomedical subjects

B Cook

Publications and source records attributed to B Cook.

At least 19 recordsLinked to original sources
PubMed2006

One year outcome of intensive care patients with decompensated alcoholic liver disease.

BACKGROUND: We aimed to examine the outcome of patients with decompensated alcoholic liver disease (ALD) admitted to a general intensive care unit (ICU). METHODS: Retrospective observational cohort study of intensive care admissions over a 3 yr period was conducted. The study was set in an ICU in a UK university hospital with a tertiary liver referral unit. One hundred and ten admissions, involving 107 patients, with decompensated ALD were included. Intensive care, hospital, and 6 and 12 months mortality were recorded along with the outcome in diagnostic and organ system support subgroups. Intensive care, hospital, 6 month and 12 month mortality rates were 58, 71, 78 and 81%. RESULTS: Hospital mortality in the sepsis/multiorgan failure group was 88%. Sixty-nine per cent of patients who were ventilated but required no other organ support survived to hospital discharge. However, the requirement for any other organ support, or a raised creatinine (>120 micromol litre(-1)) in the first 24 h, reduced the hospital survival to <15%. In those patients requiring acute renal replacement therapy, the hospital mortality was 94%. CONCLUSION: Decompensated ALD requiring intensive care admission is associated with a high hospital mortality and consideration should be given to the futility of escalating organ support measures, particularly when renal replacement therapy is required.

APACHE↗
PubMed2001

Molecular characteristics of non-small cell lung cancer.

We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers. Separation of normal and tumor, as well as histopathological subtypes, was evident by using the 3,921 most abundant transcript tags. This distinction remained when only 115 highly differentially expressed tags were used. Furthermore, these 115 transcript tags clustered into groups suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, whereas squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21(WAF1/CIP1) and 14-3-3final sigma, were consistently underexpressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression patterns observed by SAGE were consistent with results obtained by quantitative real-time PCR or cDNA array analyses by using a total of 43 lung tumor and normal samples. Thus, although derived from only a few tissue libraries, gene expression profiles obtained by using SAGE most likely represent an unbiased yet distinctive molecular signature for the most common forms of human lung cancer.

Base Sequence↗
PubMed2001

Maternal left ventricular transverse and long-axis systolic function during pregnancy.

OBJECTIVES: Circumferential fiber shortening has been the dominant basis for conventional analysis by echocardiography of left ventricular systolic function during pregnancy. Results in the literature have been conflicting due mainly to the fact that geometric assumptions for the calculation of these indices are made that may not be valid due to changes in left ventricular shape during pregnancy. Left ventricular long-axis displacement is expected to be a useful index of systolic function, independent of the changes in left ventricular geometry. The aim of this study was to compare circumferential to long-axis shortening during left ventricular contraction in pregnant women. METHODS: This was a cross-sectional study of 125 pregnant women at 9-42 weeks of gestation and 19 non-pregnant female controls. Two-dimensional and M-mode echocardiography of the left ventricle was performed including measurement of left ventricular long-axis displacement and activation time on the lateral, septal, anterior and inferior sides of the mitral annulus. Activation time was assessed as the time from the start of the Q-wave of the electrocardiogram to the onset of left ventricular long-axis shortening. RESULTS: Mean arterial pressure and activation time decreased during pregnancy, reaching a nadir at about 19 weeks' gestational age of 4% and 13%, respectively, below non-pregnant values; they subsequently increased towards term. Left ventricular long-axis displacement mirrored the changes in mean arterial pressure and activation time and increased with gestational age at all four sites of the atrioventricular plane reaching a peak at about 23 weeks (+ 12% compared to non-pregnant levels). The ejection fraction and fractional shortening remained stable until 30 and 32 weeks, respectively, and then decreased towards term. CONCLUSION: Changes in left ventricular long-axis performance during pregnancy occur earlier than do measures of transverse function.

Adult↗
PubMed2000

Metabolic stress reversibly activates the Drosophila light-sensitive channels TRP and TRPL in vivo.

Drosophila transient receptor potential (TRP) is a prototypical member of a novel family of channel proteins underlying phosphoinositide-mediated Ca(2+) entry. Although the initial stages of this signaling cascade are well known, downstream events leading to the opening of the TRP channels are still obscure. In the present study we applied patch-clamp whole-cell recordings and measurements of Ca(2+) concentration by ion-selective microelectrodes in eyes of normal and mutant Drosophila to isolate the TRP and TRP-like (TRPL)-dependent currents. We report that anoxia rapidly and reversibly depolarizes the photoreceptors and induces Ca(2+) influx into these cells in the dark. We further show that openings of the light-sensitive channels, which mediate these effects, can be obtained by mitochondrial uncouplers or by depletion of ATP in photoreceptor cells, whereas the effects of illumination and all forms of metabolic stress were additive. Effects similar to those found in wild-type flies were also found in mutants with strong defects in rhodopsin, Gq-protein, or phospholipase C, thus indicating that the metabolic stress operates at a late stage of the phototransduction cascade. Genetic elimination of both TRP and TRPL channels prevented the effects of anoxia, mitochondrial uncouplers, and depletion of ATP, thus demonstrating that the TRP and TRPL channels are specific targets of metabolic stress. These results shed new light on the properties of the TRP and TRPL channels by showing that a constitutive ATP-dependent process is required to keep these channels closed in the dark, a requirement that would make them sensitive to metabolic stress.

2,4-Dinitrophenol↗
PubMed2000

Search for neutrino oscillations at the palo verde nuclear reactors

We report on the initial results from a measurement of the antineutrino flux and spectrum at a distance of about 800 m from the three reactors of the Palo Verde Nuclear Generating Station using a segmented gadolinium-loaded scintillation detector. We find that the antineutrino flux agrees with that predicted in the absence of oscillations excluding at 90% C.L. nu;(e)-nu;(x) oscillations with Deltam(2)>1.12x10(-3) eV(2) for maximal mixing and sin (2)2straight theta>0.21 for large Deltam(2). Our results support the conclusion that the atmospheric neutrino oscillations observed by Super-Kamiokande do not involve nu(e).

Journal Article↗
PubMed2000

A role for the bacterial outer membrane in the pathogenesis of Helicobacter pylori infection.

Helicobacter pylori infection in humans is associated with diverse of clinical outcomes which are partly attributed to bacterial strain differences. Secreted bacterial products are thought to be involved in the pathogenesis caused by this non-invasive bacterium. Electron microscopy of gastric biopsies from infected individuals revealed blebbing of the H. pylori outer membrane, similar to the process of outer membrane vesicle shedding which occurs when the bacterium is grown in broth. Porins, a class of proinflammatory proteins, were observed in the outer membrane vesicles. The VacA cytotoxin, which is produced by 50-60% of H. pylori strains and associated with increased pathogenesis of infection, was also found to be vesicle-associated and biologically active. This supports the hypothesis that these vesicles represent a vehicle for the delivery of damaging bacterial products to the gastric mucosa.

Bacterial Outer Membrane Proteins↗
PubMed2000

8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Emission Tomography (PET) and on Post Prandial Serum Triglycerides.

Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.

Journal Article↗
PubMed2000

Phospholipase C and termination of G-protein-mediated signalling in vivo.

In Drosophila photoreceptors, phospholipase C (PLC) and other signalling components form multiprotein structures through the PDZ scaffold protein INAD. Association between PLC and INAD is important for termination of responses to light; the underlying mechanism is, however, unclear. Here we report that the maintenance of large amounts of PLC in the signalling membranes by association with INAD facilitates response termination, and show that PLC functions as a GTPase-activating protein (GAP). The inactivation of the G protein by its target, the PLC, is crucial for reliable production of single-photon responses and for the high temporal and intensity resolution of the response to light.

Animals↗
PubMed2000

Successful correction of depressed scars of the forehead secondary to trauma and morphea en coup de sabre by en bloc autologous dermal fat graft.

BACKGROUND: Atrophic scars of the forehead can result from various pathologic processes including morphea en coup de sabre as well as trauma. A variety of surgical techniques can be used to correct these atrophic scars. OBJECTIVE: Soft tissue augmentation for correction of atrophic scars of the forehead using en bloc autologous dermal fat graft. METHODS: Use of en bloc autologous dermal fat graft harvested from the hip and inserted into a pocket created under the atrophic scar in two patients with depressed scars of the forehead. RESULTS: Overcorrection of the scars with en bloc autologous dermal fat grafts resulted in the treated areas becoming level with the adjacent skin within 3 months. Follow-up for a period of 12 months showed a perfectly level and stable graft with no further resorption. CONCLUSION: En bloc autologous dermal fat grafting appears to be a safe technique that provides excellent cosmetic results for the correction of small to medium depressed scars of the forehead.

Adipose Tissue↗
PubMed2000

Botulinum toxin type A for the treatment of axillary Hailey-Hailey disease.

BACKGROUND: Hailey-Hailey disease is an inherited acantholytic disorder affecting the intertriginous areas of the body which is exacerbated by sweat, moisture, and friction. The disease is frequently resistant to conventional nonsurgical treatment. OBJECTIVE: To evaluate whether chemodenervation of sweat glands would improve the course of the disease in a patient with Hailey-Hailey. METHODS: We used low-dose treatment of the left axilla with botulinum toxin type A, the right axilla being used as a control, followed by treatment of both axillae with the optimal dose routinely used for the treatment of axillary hyperhidrosis. RESULTS: After one treatment with a low dose of botulinum toxin type A, we observed partial improvement of the treated axilla. With subsequent treatment of both axillae with the recommended dose for axillary hyperhidrosis, we observed a sustained complete remission of the disease in the treated axillae. CONCLUSION: Botulinum toxin type A may be an effective and safe nonsurgical alternative for the treatment of benign familial pemphigus in intertriginous areas such as the axillae.

Axilla↗
PubMed2000

Violence and its injury consequences in American movies: a public health perspective.

OBJECTIVES: To evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top-grossing American films of 1994. METHODS: Each scene in each film was examined for the presentation of violent actions on persons and coded by a systematic context-sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined. RESULTS: The median number of violent actions per film was 16 (range, 0-110). Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended. CONCLUSIONS: Violent force in American films of 1994 was overwhelmingly intentional and in 4 of 5 cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.

Humans↗
PubMed2000

Violence and its injury consequences in American movies: a public health perspective.

OBJECTIVES: The purpose of this study was to evaluate the seriousness and frequency of violence and the degree of associated injury depicted in the 100 top grossing American films of 1994. METHODS: Each scene in each film was examined for the presentation of violent actions upon persons and coded by means of a systematic context sensitive analytic scheme. Specific degrees of violence and indices of injury severity were abstracted. Only actually depicted, not implied, actions were coded, although both explicit and implied consequences were examined. RESULTS: The median number of violent actions per film was 16, with a range from 1 to 110. Intentional violence outnumbered unintentional violence by a factor of 10. Almost 90% of violent actions showed no consequences to the recipient's body, although more than 80% of the violent actions were executed with lethal or moderate force. Fewer than 1% of violent actions were accompanied by injuries that were then medically attended. CONCLUSIONS: Violent force in American films of 1994 was overwhelmingly intentional and in four of five cases was executed at levels likely to cause significant bodily injury. Not only action films but movies of all genres contained scenes in which the intensity of the action was not matched by correspondingly severe injury consequences. Many American films, regardless of genre, tend to minimize the consequences of violence to human beings.

Americas↗
PubMed2000

Evaluation of the predictive value of Her-2/neu overexpression and p53 mutations in high-risk primary breast cancer patients treated with high-dose chemotherapy and autologous stem-cell transplantation.

PURPOSE: To ascertain the predictive value of Her-2/neu overexpression and p53 mutations, assessed by immunohistochemistry, in high-risk primary breast cancer (HRPBC) treated with high-dose chemotherapy (HDCT). PATIENTS AND METHODS: We obtained paraffin-embedded tumor blocks from 146 HRPBC patients previously enrolled at our program onto clinical trials of HDCT for four to nine involved axillary lymph nodes, > or = 10 involved axillary nodes, or inflammatory carcinoma. All patients received the same HDCT regimen, with cyclophosphamide, cisplatin, and carmustine (STAMP-I), followed by autologous stem-cell transplantation. Median follow-up was 42 months (range, 5 to 90 months). The same pathologist, blinded to clinical outcome, reviewed all immunostained slides. RESULTS: Positive results for Her-2/neu and p53 were found in 44.5% and 34% of the patients, respectively. Positivity for Her-2/neu was significantly associated with increased risk of relapse and death. No correlation was found between p53 mutations and relapse-free survival (RFS) or overall survival (OS). Multivariate analyses included Her-2/neu overexpression and the following variables previously identified as independent predictors of outcome in this population: tumor size, nodal ratio (number of involved nodes/number of dissected nodes), and hormone receptor status. All four variables had independent value. CONCLUSION: Her-2/neu overexpression is an independent negative predictor of RFS and OS in HRPBC treated with HDCT. Its inclusion in our previously described predictive model increases the predictive capacity of this model for the low-risk subgroup. In contrast, p53 mutations lack predictive value in this setting.

Adult↗
PubMed2000

Feeding behavior of bollworm and tobacco budworm (Lepidoptera: Noctuidae) larvae in mixed stands of nontransgenic and transgenic cotton expressing an insecticidal protein.

Feeding behavior of third-instar bollworm, Helicoverpa zea (Boddie), and tobacco budworm, Heliothis virescens (F.), was observed in pure and mixed stands of nontransgenic and transgenic cotton (BTK), Gossypium hirsutum L., expressing an insecticidal protein CryIA(c) from a bacterium, Bacillus thuringiensis Berliner subsp. kurstaki. Five plant stands composed of BTK and non-BTK plants were evaluated; two pure stands and three mixed stands. Percentage ratios of BTK to non-BTK plants in the stands were 100:0, 75:25, 50:50, 25:75 and 0:100, respectively. In all stands with BTK plants, fewer bollworm and tobacco budworm larvae were found on BTK plants than non-BTK plants 24 h after infestation with third instars. At 48 h, significantly fewer tobacco budworm larvae, but not fewer bollworm larvae, were found on BTK plants. However, the number of larvae of either insect did not increase on non-BTK plants compared with the initial infestation density of three larvae per plant. The number of obacco budworm injured flower buds, and capsules was lower in all plant stands containing BTK plants compared with the pure stand of non-BTK at 48 h after infestation. Higher numbers of larvae on non-BTK plants were possibly the result of larval intoxication, reduced feeding, and increased plant abandonment and death on BTK plants rather than a classical feeding preference. Unexpectedly, the number of flower buds and capsules injured by bollworm and tobacco budworm when averaged per plant for all plants in a stand, differed little among the 75:25, 50:50 and 25:75 plant mixtures. These data suggest that larvae of both species frequently moved among plants, feeding indiscriminately on BTK and non-BTK plants.

Animals↗
PubMed1999

TRP and calcium stores in Drosophila phototransduction.

Phototransduction in Drosophila is mediated by the ubiquitous phosphoinositide cascade, leading to opening of the TRP and TRPL channels, which are prototypical members of a novel class of membrane proteins. Drosophila mutants lacking the TRP protein display a response to light that declines to the dark level during illumination. It has recently been suggested that this response inactivation results from a negative feedback by calcium-calmodulin, leading to closure of the TRPL channels. It is also suggested that in contrast to other phosphoinositide-mediated systems, Ca2+ release from internal stores is neither involved in channel activation nor in phototransduction in general. We now show that inactivation of the light response in trp photoreceptors is enhanced upon reduction of the intracellular Ca2+ concentration. Furthermore, in Ca(2+)-free medium, when there is no Ca2+ influx into the photoreceptors, we demonstrate a significant elevation of intracellular Ca2+ upon illumination. This elevation correlates with ability of the cells to respond to light. Accordingly, malfunctioning of Ca2+ stores, either by Ca2+ deprivation or by application of the Ca2+ pump inhibitor, thapsigargin, confers a trp phenotype on wild type flies. The results indicate that the response inactivation in trp cells results from Ca2+ deficiency rather than from Ca(2+)-dependent negative feedback. The results also indicate that there is light-induced release of Ca2+ from intracellular stores. Furthermore, the response to light is correlated to Ca2+ release, and normal function of the stores is required for prolonged excitation. We suggest that phototransduction in Drosophila depends on Ca(2+)-release mediated signalling and that TRP is essential for the normal function of this process.

Animals↗
PubMed1998

Developmental neuronal death is not a universal phenomenon among cell types in the chick embryo retina.

The goal of this study was to investigate whether all the cell types present in the chick embryo retina undergo developmental neuronal death. Apoptosis was investigated in retinal sections at different developmental stages, processed either with propidium iodide, which stains pyknotic nuclei intensely, or with terminal transferase-mediated deoxyuridine triphosphate (d-UTP)-biotin nick-end labeling (TUNEL). Internucleosomal DNA fragmentation was investigated in tissue extracts by agarose gel electrophoresis. TUNEL-positive (T+) cells and pyknotic nuclei were first detectable in the ganglion cell layer (GCL) around embryonic day (ED) 8 and peaked at ED 10. In the inner nuclear layer (INL), T+ and pyknotic cells first appeared on ED 8, reached maximum frequency on ED 11, and were largely absent after ED 14. DNA ladders were observed at all the stages, when T+ and pyknotic cells were abundant, but not on ED 4, when only scattered dead cells were observed histologically. Dying cells were virtually never detected in the outer nuclear layer (ONL) from ED 4 to postnatal day 2. After unilateral midbrain ablation on ED 5, there was a striking increase in the number of pyknotic and T+ cells in both the GCL and in the INL of the contralateral eye but not in the ONL. The absence of apoptotic cell death in the ONL during normal development and after tectal ablation shows that developmental death is not universal among the various cell populations present in the chick embryo retina and raises questions regarding mechanisms controlling both photoreceptor survival and the matching of pre- and postsynaptic elements in the outer plexiform layer of this species.

Animals↗