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PubMed2000

Clinical usefulness of serum and plasma vascular endothelial growth factor in cancer patients: which is the optimal specimen?

Vascular endothelial growth factor (VEGF) is secreted by various human cancer cells and plays a key role in cancer angiogenesis and metastasis. Recently, evidence of VEGF storage in blood cells including platelets has been reported. The serum VEGF levels were reported to increase during clotting as a result of its release from platelets, and plasma sample instead of serum was recommended for measuring the circulating VEGF more accurately. However, platelets have been implicated in tumor metastasis since circulating tumor cells forming aggregates with platelets were observed. The purpose of this study was to clarify which is an optimal specimen to measure VEGF in cancer patients, serum or plasma. We measured serum and plasma VEGF levels and platelet counts in 173 cancer patients and 42 healthy people, and found that serum VEGF levels were significantly higher than matched plasma VEGF and the VEGF difference (serum VEGF - plasma VEGF) correlated with platelet counts (r=0.624, p<0.05) in both cancer patients and healthy controls. We selected cancer patients with normal platelet counts (130-400x103/microl, Plt-normal cancer group). Interestingly, serum VEGF levels were higher in Plt-normal cancer group than in healthy controls. The theoretical platelet-derived VEGF in serum, calculated based on actual blood platelet counts (pg per 106 platelets), was also significantly higher in Plt-normal cancer group than in normal controls. It is, therefore, suggested that, although the serum VEGF levels are affected by blood platelets, platelet-derived VEGF also reflect biology of cancer cells, and that serum would be the more useful specimen for measurement of circulating VEGF in cancer patients for prognosis.

Blood Specimen Collection↗
PubMed2002

Prevention of vascular damage in scleroderma with angiotensin-converting enzyme (ACE) inhibition.

Great strides have been made in identifying and managing the organ-based complications of systemic sclerosis (SSc). There is no room for the nihilism towards treating this disease that used to be so prevalent. However, there is still relatively little hard evidence on which to base treatment decisions. Previous trials have been constrained by the low disease prevalence and the difficulty in recruiting sufficient patients especially with disease of recent onset. The results of past trials have often been confounded by the failure to recognize the marked heterogeneity of SSc and the inclusion of patient subsets with widely varying disease expression, course and outcome. It is recognized that progress will only be made in this area with coordinated multicentre studies. As a result, national and international networks of clinicians with expertise in the management of SSc have been formed. In the UK, the Systemic Sclerosis Study Group has established a national scleroderma register and, together with the Scleroderma Special Interest Group of the British Society for Rheumatology (BSR), a multicentre base for therapeutic studies. As a result of developments in our understanding of the pathogenesis of scleroderma and our ability to subset patients more effectively, a number of rather more rational approaches to treating the disease and its complications are being tested. In parallel with this, considerable progress is being made in developing universally agreed measures of disease activity and severity and in identifying surrogate laboratory markers of disease activity that are relevant to therapeutic studies. These multicentre trials need substantial funding and often do not attract support from the pharmaceutical industry. It was because of the difficulty in financing long-term, multicentre studies in uncommon conditions that the ARC/BSR Clinical Trials Programme was established. The QUINS trial, which is funded by this Programme, is described here as an example of one of several therapeutic protocols being developed by the UK Systemic Sclerosis Study Group that are currently being tested in multicentre trials. Contact details are provided in the appendix for clinicians who are interested in registering patients on the UK Scleroderma Register or participating in this or in the other therapeutic studies.

Adolescent↗
PubMed2006

Mindfulness-based psychotherapies: a review of conceptual foundations, empirical evidence and practical considerations.

OBJECTIVE: This paper, composed by an interest group of clinicians and researchers based in Melbourne, presents some background to the practice of mindfulness-based therapies as relevant to the general professional reader. We address the empirical evidence for these therapies, the principles through which they might operate, some practical questions facing those wishing to commence practice in this area or to refer patients into mindfulness-based therapies, and some considerations relevant to the conduct and interpretation of research into the therapeutic application of mindfulness. METHOD: Databases (e.g. PsycINFO, MEDLINE) were searched for literature on the impact of mindfulness interventions, and the psychological and biological mechanisms that underpin the effects of mindfulness practice. This paper also draws upon the clinical experience of the author group. RESULTS: Mindfulness practice and principles have their origins in many contemplative and philosophical traditions but individuals can effectively adopt the training and practice of mindfulness in the absence of such traditions or vocabulary. A recent surge of interest regarding mindfulness in therapeutic techniques can be attributed to the publication of some well-designed empirical evaluations of mindfulness-based cognitive therapy. Arising from this as well as a broader history of clinical integration of mindfulness and Western psychotherapies, a growing number of clinicians have interest and enthusiasm to learn the techniques of mindfulness and to integrate them into their therapeutic work. This review highlights the importance of accurate professional awareness and understanding of mindfulness and its therapeutic applications. CONCLUSIONS: The theoretical and empirical literatures on therapeutic applications of mindfulness are in states of significant growth and development. This group suggests, based on this review, that the combination of some well-developed conceptual models for the therapeutic action of mindfulness and a developing empirical base, justifies a degree of optimism that mindfulness-based approaches will become helpful strategies to offer in the care of patients with a wide range of mental and physical health problems.

Cognition↗
PubMed1983

Degenerative spondylolisthesis.

This is an interesting group of patients who have in common the roentgenographic finding of degenerative spondylolisthesis. This is a retrospective, uncontrolled review. It would be interesting to have a similar matched group of 132 patients in the same age group without degenerative spondylolisthesis but with marked degenerative changes to compare symptoms, signs, and outcome of treatment. We have not had adequate follow-up on the nonoperative patients and therefore cannot provide data for comparison with the operative group. A total of 51 of our 132 patients had 83 operative procedures. Twenty-five percent, or 13 patients, showed a degenerative spondylolisthesis at L4-5 with a previous history of having undergone a disk excision at the same level. Seven of the 51 patients (14%) developed a progressive slip following surgery. None of these patients had previous fusion. Two patients of the 17 that we operated on primarily (12%) subsequently developed a progressive symptomatic slip. We have concluded from this review that spinal fusion should be performed in conjunction with decompression more frequently in patients with degenerative spondylolisthesis despite the fact that the majority of these patients are over 60 years of age.

Female↗
PubMed2003

Intergroup conflict: individual, group, and collective interests.

Intergroup conflicts generally involve conflicts of interests within the competing groups as well. This article outlines a taxonomy of games, called team games, which incorporates the intragroup and intergroup levels of conflict. Its aims are to provide a coherent framework for analyzing the prototypical problems of cooperation and competition that arise within and between groups, and to review an extensive research program that has used this framework to study individual and group behavior in the laboratory. Depending on the game's payoff structure, contradictions or conflicts are created among the rational choices at the individual, group, and collective levels-a generalization of the contradiction between individual and collective rationality occurring in the traditional mixed-motive games. These contradictions are studied so as to identify the theoretical and behavioral conditions that determine which level of rationality prevails.

Choice Behavior↗
PubMed2000

Sulfhydryls of tubulin. A probe to detect conformational changes of tubulin.

The 20 cysteine residues of tubulin are heterogeneously distributed throughout its three-dimensional structure. In the present work, we have used the reactivity of these cysteine residues with 5, 5'-dithiobis(2-nitrobenzoic acid) (DTNB) as a probe to detect the global conformational changes of tubulin under different experimental conditions. The 20 sulfhydryl groups can be classified into two categories: fast and slow reacting. Colchicine binding causes a dramatic decrease in the reactivity of the cysteine residues and causes complete protection of 1.4 cysteine residues. Similarly, other colchicine analogs that bind reversibly initially decrease the rate of reaction; but unlike colchicine they do not cause complete protection of any sulfhydryl groups. Interestingly, in all cases we find that all the slow reacting sulfhydryl groups are affected to the same extent, that is, have a single rate constant. Glycerol has a major inhibitory effect on all these slow reacting sulfhydryls, suggesting that the reaction of slow reacting cysteines takes place from an open state at equilibrium with the native. Ageing of tubulin at 37 degrees C leads to loss of self-assembly and colchicine binding activity. Using DTNB kinetics, we have shown that ageing leads to complete protection of some of the sulfhydryl groups and increased reaction rate for other slow reacting sulfhydryl groups. Ageing at 37 degrees C also causes aggregation of tubulin as indicated by HPLC analysis. The protection of some sulfhydryl groups may be a consequence of aggregation, whereas the increased rate of reaction of other slow reacting sulfhydryls may be a result of changes in global dynamics. CD spectra and acrylamide quenching support such a notion. Binding of 8-anilino-1-naphthalenesulfonate (ANS) and bis-ANS by tubulin cause complete protection of some cysteine residues as indicated by the DTNB reaction, but has little effect on the other slow reacting cysteines, suggesting local effects.

Anilino Naphthalenesulfonates↗
PubMed1992

Effect of aldose reductase inhibitors on lenticular dulcitol level in galactose fed rats.

We have shown that galactose cataract development is delayed or inhibited with the administration of aldose reductase inhibitors (ARIs). Dulcitol forms and accumulates in the lens of rats fed galactose. We undertook investigations to study the effectiveness of ARIs in preventing the formation and accumulation of dulcitol in the lens. Young Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15 mg sorbinil, 0.15, 0.5, or 1.0 mg E-0722/day/Kg body weight. At desired intervals following the initiation of diets, the lenses were processed for the determination of galactose and dulcitol levels. The lenticular dulcitol increased significantly in all animals fed galactose reaching a maximum level by approximately 15 days with comparatively lower levels in the groups fed ARIs with galactose; this increase was dose dependent in the groups fed E-0722. There was a subsequent, rapid drop in lenticular dulcitol by 18 days in all dietary groups. Interestingly, a second peak of increased lenticular dulcitol was observed in all groups. The correlation between dulcitol accumulation and cataract development is discussed.

Aldehyde Reductase↗
PubMed1993

NGF reduces striatal excitotoxic neuronal loss without affecting concurrent neuronal stress.

Nerve growth factor (NGF) has protective effects against striatal excitotoxic injury in the adult brain. To begin to define the mechanism of NGF-mediated sparing, we sought to determine the effects of biologically delivered NGF on the degree of neuronal stress and the development of excitotoxic lesions in the rat striatum. Immortalized fibroblasts genetically altered to secrete NGF (NGF[+]) or control fibroblasts (NGF[-]) were stereotactically implanted near the striatum 7 d before striatal infusion of an NMDA-receptor agonist. Two days after excitotoxin infusion, the volume of neuronal loss was reduced by 34% (p < 0.001) in the NGF[+] group when compared to the NGF[-] group; however, there was no difference in the volume of 72 kD heat shock protein (HSP72) immunoreactivity expressed in the two groups after 2 d. The final volumes of neuronal loss at 10 d were significantly greater than seen at 2 d, with the volume of neuronal loss in the NGF[+] group reduced by 20% (p < 0.004) when compared to the NGF[-] group. Interestingly, the volume of neuronal loss at 10 d in the NGF[-] group, but not the NGF[+] group, closely approximated the HSP72 immunoreactive volumes seen at 2 d. These results suggest that the cell stress marker, HSP72, is predictive of neuronal loss after striatal excitotoxic insult and while NGF treatment does not alter the overall HSP72 response, it significantly reduces subsequent neuronal loss. We conclude that NGF-mediated neuroprotective mechanisms alter neuronal response to injury without affecting the primary cell stress response to NMDA-receptor activation.

Animals↗
PubMed2004

Implicit strategy affects learning in children with heavy prenatal alcohol exposure.

BACKGROUND: Learning and memory deficits are commonly reported in children with heavy prenatal alcohol exposure. Our recent work suggested that children with heavy prenatal alcohol exposure retained information as well as controls on a verbal learning test but not on a test of nonverbal learning and memory. To better understand the cause of this differential pattern of performance, the current study re-analyzed data from our previous study to determine if the presence of an implicit learning strategy may account, at least in part, for the finding of spared retention. METHODS: The current study examined verbal learning and memory abilities in 35 children with Fetal Alcohol Spectrum Disorders (FASD) and 34 nonexposed controls (CON) matched for age (9-16 years), sex, ethnicity, handedness, and socioeconomic status. Groups were compared on two measures of verbal learning, one with an implicit strategy (California Verbal Learning Test-Children's Version; CVLT-C) and one without (Verbal Learning subtest of the Wide Range Assessment of Memory and Learning; VL-WRAML). RESULTS: Children with FASD learned less information overall than children in the CON group. Both groups learned a greater percentage of information and reached a learning plateau earlier on the CVLT-C compared with the VL-WRAML. Groups also showed comparable rates of retention after a delay on the CVLT-C. In contrast, on the VL-WRAML, children with FASD showed poorer retention rates than children in the CON group. Interestingly, children with FASD did not differ from children in the CON group on CVLT-C semantic clustering scores for learning trials 1 through 3, and greater utilization of semantic clustering was correlated with better learning and memory performance in both groups. This overall pattern of results was not related to overall intellectual level. CONCLUSIONS: The finding of spared retention of verbal information on the CVLT-C in our earlier studies may be related to test characteristics of the CVLT-C rather than a finding of spared verbal retention per se, given that spared retention was not found on a separate test of verbal learning and memory without an implicit learning strategy. These results suggest that the use of an implicit strategy positively affected the ability of alcohol-exposed children to learn and retain new verbal information.

Adolescent↗
PubMed2005

Research strategies for magnetic fields and cancer.

Widespread concerns about whether electric and magnetic fields (EMF) could adversely affect human health have been raised in epidemiologic studies reported since the 1980s. Possible EMF health effects have been widely publicized in the popular press since that time. We consider here three possible mechanisms of action of EMF on childhood leukemia. We identify the first as "magnetic fields": this hypothesis relates the average level of magnetic field to the incidence of childhood leukemia. We identify a second, recently proposed, mechanism as "contact current": this hypothesis relates the low voltage and consequent current that occurs on the domestic water pipe, due to U.S. grounding practices, as a source for exposure of children. The third hypothesis is that the relationship observed is spurious. Using a modified example taken from the work of Von Winterfeldt and Keeney, we use Decision Analysis to estimate the value of information for distinguishing between the three hypotheses. We believe that this improves on the usual process for deciding on research budgets. Depending on which hypothesis we favor a priori, the value of being informed ranges from US 101 dollars to US 233 dollars per "problem household." Since there could be as many as 2 million such households, the value of information for resolving this issue could approach half a billion dollars! We find that there is no value of information for finding the odds ratio given the contact current hypothesis. In writing this article, we have consciously kept the computations as simple as possible so as to engage the reader's attention and interest. In a penultimate section, we suggest numerous possible extensions for a group interested in discussing and deciding on the value of research on the relationship between magnetic fields and cancer.

Child↗
PubMedDate not supplied

Hemangiomas of the head and neck.

Hemangiomas are an interesting group of lesions which affect many anatomical structures of the human body. Interest today is confined to head and neck lesions which can occur in the infant, child or adult. Benign lesions affect the great majority of patients as contrasted to malignant ones. Diagnosis of the superficial lesions is usually made by inspection and palpation while additional diagnostic procedures (radiological studies and surgical exploration) may be indicated in patients with deep lesions.

Head and Neck Neoplasms↗
PubMed2005

What do individuals in different science groups within a life sciences organization think about genetic modification?

An assessment was undertaken of the attitudes of individuals within the science community towards a program to produce genetically modified cattle for altered milk composition, expectantly allowing for research into the treatment of multiple sclerosis in humans. The majority of respondents to an electronic survey expressed favorable attitudes to the program, thought it beneficial, respected individual freedom and was fair and just and disagreed that it was harmful. A passion for science and having a suitable lifestyle were the most important motivating factors for individuals. Finally, there were a wide range of responses to a number of cultural beliefs or myths. Science grouping significantly affected the responses. Compared with Systems and Land groups, Plant and Reproduction groups more strongly agreed with the project, thought it less harmful to interest groups, felt that genetic modification of animals was more morally acceptable, and more strongly agreed with the myth statements. These results indicate a diversity of beliefs and attitudes towards genetic modification amongst those within the science community, and highlight the importance of understanding ethics and myths in dealing with them. It is suggested that the diversity of beliefs could be better used to help shape public policy and understanding of biotechnology.

Agriculture↗
PubMed2005

Structure-activity relationship within the serine protease inhibitors of the pacifastin family.

The members of the Pacifastin family are serine protease inhibitors found in insects and crustacean. They are either small inhibitors (made of one consensus cysteine-rich motif) or proteins (4-9 motifs). Some of these inhibitors are characterized by a species selectivity for the trypsin inhibition. Structural data discriminate the small inhibitors that apparently look very similar into two groups. Interestingly, the inhibitors that display species selectivity fall in the same structural group.

Amino Acid Sequence↗
PubMed1977

National health insurance policy in the United States: a case of non-decision-making.

Despite the vast range of commentaries and research on the current health care crisis, little research attention has been focused specifically on the lack of federal response to this crisis. As a way of focusing analysis on the specifics of Congressional inaction, it is suggested that both the range of health care proposals and the current debates in Congress may be seen as part of an ongoing bargaining process over legitimate alternatives for modication of health care delivery. It is argued that the lack of any new health care legislation may be seen as the result of a series of non-decision by conservative Congressional representatives of the dominant medical interest groups. These non-decisions have successfully excluded any challenges to those interests by reliance upon a predominant "mobilization of bias" to effectively define and/or divert these challenges as illegitimate attempts at change. The changes which eventually evolve from Congressional compromise may represent a modification of the prevailing bias concerning legitimate alternatives, but are unlikely to modify the relation of the controlling interests involved.

American Medical Association↗
PubMed2001

Acid-base balance and nutrition in peritoneal dialysis.

Acidosis has been implicated in increased protein catabolism and malnutrition of dialysis. The present study examines the effect of acid-base balance on the nutrition status of peritoneal dialysis (PD) patients. We followed 43 PD patients for one year. Blood chemistries were measured monthly. Patients were divided on the basis of subjective global assessment (SGA) into well-nourished (A), mildly-to-moderately malnourished (B), and severely malnourished (C) groups. Mean serum bicarbonate and albumin concentrations were, for group A (n = 16), 23.5 mmol/L and 3.96 g/dL respectively; for group B (n = 17), 27.2 mmol/L and 3.50 g/dL respectively; and for group C (n = 10), 25.9 mmol/L and 2.9 g/dL respectively. In group A, mean serum bicarbonate was significantly lower, and albumin concentration significantly higher as compared with the other groups. Interestingly, of 9 patients with serum HCO3 < 22 mmol/L, 6 were in group A and 2 were in group B. Of 6 patients with serum HCO3 > 29 mmol/L, 5 were in group B and 4 were in group C. The data suggest that well-nourished PD patients tend to be more acidotic. Malnutrition in alkalotic PD patients may be due to low protein intake resulting in decreased acid production; however, an effect of alkalosis on protein metabolism cannot be excluded.

Acid-Base Equilibrium↗
PubMed1991

Lethal(1) aberrant immune response mutations leading to melanotic tumor formation in Drosophila melanogaster.

Using P element-mediated mutagenesis we have isolated 20 X-linked lethal mutations, representing at least 14 complementation groups, which exhibit melanotic tumor phenotypes. We present the systematic analysis of this interesting group of lethal mutations that were selected for their visible melanotic or immune response. The lethal and melanotic tumor phenotypes of each lethal(1) aberrant immune response (air) mutation are pleiotropic effects of single genetic lesions. Lethality occurs throughout the larval and early pupal periods of development and larval development is extended in some air mutants. The air mutant lethal syndromes include abnormalities associated with the brain, haematopoietic organs, gut, salivary glands, ring glands, and imaginal discs. Additional characterization of the melanotic tumor mutations Tuml and tu(1)Szts have indicated that the melanotic tumor phenotype is similar to that observed in the air mutants. These studies have led to the proposal that two distinct classes of melanotic tumor mutations exist. Class 1 includes mutants in which melanotic tumors result from "autoimmune responses" or the response of an apparently normal immune system to the presence of abnormal target tissues. The Class 2 mutants display obvious defects in the haematopoietic organs or haemocytes, manifested as overgrowth, and the resulting aberrant immune system behavior may contribute to melanotic tumor formation.

Animals↗
PubMed2006

Comparison of different training models for laparoscopic surgery in neonates and small infants.

BACKGROUND: Minimally invasive surgery in small children and infants requires special skills and training. This experimental study compares the efficiency of an in vitro pelvic trainer (PT) and an a in vivo animal model (AM). METHODS: For this study, 12 residents were prospectively randomized into two groups. Initially, all had to pass a basic skill assessment (3 tasks). Then endoscopic small bowel biopsy was performed (8 times) either with the in vitro PT (group A) or the in vivo AM (group B). Finally, all had to demonstrate this procedure in the in vivo AM and repeat the basic skill assessment. A quality index (complications, suture, biopsy) was evaluated. RESULTS: Initially, there was no difference between the two groups. Interestingly, the mean regression gradient of the index for the in vitro PT (group A) was significantly better than for the in vivo AM (group B). In the final in vivo operation, however, the mean index for the in vitro PT (group A) worsened significantly, whereas it increased for the in vivo AM (group B) (p = 0.037). CONCLUSION: Adequate training for an isolated mechanical task such as gut biopsy can be supplied using a pelvic trainer or animal model with similar effects. However in vivo performance of the same task requires secondary surgical skills, which are conveyed during live training with greater success. Consequently, stepwise teaching with both modules seems reasonable before these procedures are approached in neonates or small children.

Adult↗
PubMed2006

Distribution of L1-retroposons on the giant sex chromosomes of Microtus cabrerae (Arvicolidae, Rodentia): functional and evolutionary implications.

Long interspersed nuclear elements (L1 or LINE-1) are the most abundant and active retroposons in the mammalian genome. Traditionally, the bulk of L1 sequences have been explained by the 'selfish DNA' hypothesis; however, recently it has been also argued that L1s could play an important role in genome and gene organizations. The non-random chromosomal distribution of these retroelements is a striking feature considered to reflect this functionality. In the present study we have cloned and analyzed three different L1 fragments from the genome of the rodent Microtus cabrerae. In addition, we have examined the chromosomal distribution of this L1 in several species of Microtus, a very interesting group owing to the presence in some species of enlarged ('giant') sex chromosomes. Interestingly, in all species analyzed, L1-retroposons have preferentially accumulated on both the giant- and the normal-sized sex chromosomes compared with the autosomes. Also we have demonstrated that L1-retroposons are not similarly distributed among the heterochromatic blocks of the giant sex chromosomes in M. cabrerae and M. agrestis, which suggest that L1 retroposition and amplification over the sex heterochromatin have been different and independent processes in each species. Finally, we proposed that the main factors responsible for the L1 distribution on the mammalian sex chromosomes are the heterochromatic nature of the Y chromosome and the possible role of L1 sequences during the X-inactivation process.

Animals↗