Beta-carotene supplementation in smokers reduces the frequency of micronuclei in sputum.

beta-carotene has been hypothesised to reduce lung cancer risk. We studied the effect of 14 weeks of beta-carotene supplementation (20 mg d-1) on the frequency of micronuclei in sputum in 114 heavy smokers in a double-blind trial. Micronuclei reflect DNA damage in exfoliated cells and may thus provide a marker of early-stage carcinogenesis. Pre-treatment blood levels of cotinine, beta-carotene, retinol and vitamins C and E were similar in the placebo group (n = 61) and the treatment group (n = 53). Plasma beta-carotene levels increased 13-fold in the treatment group during intervention. Initial micronuclei counts (per 3,000 cells) were higher in the treatment group than in the placebo group (5.0 vs 4.0, P < 0.05). During intervention, the treatment group showed a 47% decrease, whereas the placebo group showed a non-significant decrease (16%). After adjustment for the initial levels, the treatment group had 27% lower micronuclei counts than the placebo group at the end of the trial (95% CI: 9-41%). These results indicate that beta-carotene may reduce lung cancer risk in man by preventing DNA damage in early-stage carcinogenesis

Serum cholesterol levels in neutropenic patients with fever

Hypocholesterolemia, which often accompanies infectious diseases has been suggested to serve as a prognostic marker in hospitalized patients. Even though patients with chemotherapyinduced leukopenia are at high risk of infection and mortality, only limited information is available on serum cholesterol levels in these patients. We therefore measured serum cholesterol levels in 17 patients with hematological malignancies during chemotherapyinduced neutropenia and correlated it with clinical outcome. Patients with fever (&gt;38.5 degreesC) showed a significant decrease in serum cholesterol levels within 24 hours. Eight days after onset of the fever nonsurvivors had significantly lower serum cholesterol levels (median 2.09 mmol/l, range 0.492.79, n=6) compared to survivors (median 3.23 mmol/l, range 1.684.86, n=11). Cholesterol levels in survivors returned to baseline levels at the time of discharge from the hospital. At the onset of fever, serum levels of inflammatory cytokines interleukin-6, tumor necrosis factor (TNF) and soluble TNF receptors p55 and p75 were elevated in all patients, but only TNF and TNF receptor p75 levels were significantly different in survivors and nonsurvivors. Our data suggest that a decrease in serum cholesterol levels is a prognostic marker in neutropenic patients with fever. Release of inflammatory cytokines may in part be responsible for hypocholesterolemia in these patients

Garlic and its significance for the prevention of cancer in humans: a critical view.

Recently published results of epidemiologic case-control studies in China and Italy on gastric carcinoma in relation to diet suggest that consuming garlic may reduce the risk of gastric cancer. Chemical constituents of garlic have been tested for their inhibiting effect on carcinogenesis, using in vitro and in vivo models. In most experiments inhibition of tumour growth was established using fresh garlic extract, garlic compounds or synthetically prepared analogs. In this review the strengths and weaknesses of the experiments are discussed and the outcomes are evaluated to assess the possible significance of garlic or garlic compounds for the prevention of cancer in humans. It is concluded that evidence from laboratory experiments and epidemiologic studies is presently not conclusive as to the preventive activity of garlic. However, the available evidence warrants further research into the possible role of garlic in the prevention of cancer in humans

Testicular Adrenal Rest Tumours in Congenital Adrenal Hyperplasia

In adult patients with congenital adrenal hyperplasia (CAH), the presence of testicular adrenal rest tumours (TART) is an important complication leading to gonadal dysfunction and infertility. These tumours can be already found in childhood and puberty. In this paper, we review the embryological, histological, biochemical, and clinical features of TART and discuss treatment options

Charles Dickens and the Role of Legal Institutions in Social and Moral Reform: Oliver Twist, Bleak House, and Our Mutual Friend.

The legal system of Victorian England is integral to Charles Dickens' novels and to their moral intent. Dickens was acutely conscious of the way in which the Victorian novel operated as a form of moral art. As a novelist he is concerned about the victims of his society and the way in which their lots can be improved. He therefore chooses to construct representative victims of legal institutions such as the Poor Law Amendment Act of 1834 and the Court of Chancery in his novels to highlight flaws in his world and the changes that might be made to improve social conditions. This thesis will examine the way in which Dickens' fictional enquiry into the social world his characters stand to inherit is focused on the legal system and its institutions, most particularly, the law of succession. By discussing three novels from different periods of his writing career, Oliver Twist (1837), Bleak House (1853) and Our Mutual Friend (1862-1865), I will suggest how his engineering of moral outcomes shows his development as a writer. The law of succession and related legal institutions such as the Court of Chancery, dealing with wills and inheritance, recurs in Dickens' novels, providing the novelist with social, moral and legal identities for his characters. These identities, as unveiled during the texts, propel the characters and plot development in particular directions in response to the novels' moral intent. The role of inheritance in Victorian society largely provides Dickens with a means to explore the adequacies of existing legal institutions, such as the means by which to prove and execute wills and the operation of the Court of Chancery. The role of inheritance also allows Dickens to examine the social condition of those who are deprived of an inheritance or who are unable to enforce their legal rights. In this respect Dickens concentrates on the appalling conditions of institutions such as workhouses and poorhouses in Victorian society and on resultant criminal activity and prostitution in the community as the disinherited struggle to survive. Dickens' study of crime in particular sheds invaluable light on the prevailing moral standards of, and difficulties with, his society. Dickens acknowledges his pedagogical role as an author, providing synopses of his lessons in the prefaces to his books and forewarning his audience of the literary devices (such as grotesquerie) that are necessary to communicate them effectively. This thesis will examine the way in which Dickens' engineering of moral outcomes through the convenient use of the law of succession becomes increasingly sophisticated as he develops as a writer. The stock plot device of the impoverished orphan child, a representative victim of such a Victorian legal institution as the Poor Laws who is morally saved when elevated into gentility by a secret inheritance, sustains the plot of Oliver Twist. The simplistic and somewhat improbable fortunes of Oliver, however, give way to the more probable moral and legal outcomes of characters such as Jo and Richard Carstone in Bleak House. In Bleak House Carstone, who is certainly a more interesting central protagonist than Esther Summerson in terms of Dickens' examination of legal institutions and their effect on moral and social outcomes in the novel, makes a ruinous attempt to manipulate the legal system and gain control over his fortune by joining the suit of Jarndyce v Jarndyce. In Our Mutual Friend, however, a complex and successful manipulation of the legal system is achieved by Harmon/Handford/Rokesmith, an adult and extremely resourceful character who, in conjunction with other characters such as Bella Wilfer and Mr Boffin, is testament to the inseparability of individual and legal identities as far as moral and social outcomes are concerned. Throughout the novels it can be seen that the abilities of Oliver Twist, Richard Carstone and John Rokesmith to manipulate the law of succession correlate directly to stages of Dickens' maturity as a writer and his increasing confidence about layering texts and developing more complex and sophisticated structures in his novels. Dickens' focus on the role of inheritance, however, entails the development of perspectives on the legal system in entirety. Oliver Twist as a novel drawing upon the traditions of sensation, and turning on events such as 'legacies, birthrights, thefts and deeds of violence', focuses intensely on the criminal justice system and establishes Dickens' famous attraction to repulsion and use of grotesquerie and popular entertainment. Oliver Twist also develops analogies between law and drama, establishing the foundation from which Dickens can employ legal metaphors to great effect in his quest for reforms of the legal system and society at large in Bleak House and Our Mutual Friend. Oliver Twist further establishes the milieu of a stratified society in which finances govern social behaviour and in which the class system is reflected in the legal system through the denial of access to justice to those who are unable to afford it, or suffer gender inequality. Bleak House builds upon the problems outlined in Oliver Twist. It explores the criminal system, particularly the defeminisation of the law and access to justice issues, including the problem of delay in litigation. Specific legal institutions such as the jury system and, most notably, the civil branch of the Victorian legal system with a particular focus on the equitable procedures in the Court of Chancery are examined. Jo is a transmutation of Oliver as representative victim of the Poor Laws, and his fate as such appears more probable. Richard Carstone is, however, the central character in the novel in terms of his construction as the representative victim of the civil system and of the law of succession. In Our Mutual Friend Dickens refines his use of the law of succession and other legal institutions to propel characters into directions suited to his own agendas. The entire plot is constructed from the premise of the execution of a will arising out of the death of John Harmon whose murder is a crime that has never, in fact, been committed. The ramifications of the execution of this will and subsequent codicils are extremely interesting. The novel further examines problems of access to justice and gender inequality under the prevailing legal system, particularly through Bella Wilfer. As part of the development of Dickens' use of the legal system there is a perceptible development of his powers of characterisation. Richard Carstone is a more substantial and believable character than Oliver; John Harmon offers the opportunity for Dickens to experiment with a chameleon identity. This aspect of Dickens' development, however, has received substantial attention already, particularly by Arnold Kettle, Barbara Hardy, Monroe Engel and Grahame Smith. There has been, to the best of my knowledge, little work done on his use of the law of succession, and it is here that I wish to concentrate my argument. Much of Dickens' interest in the law appears to stem from his early career as a legal clerk in Lincoln's Inn and Doctors' Commons. His first job, as a writing clerk in the office of Ellis and Blackmore, a small set of chambers in Holborn Court, involved duties such as copying documents, administering the registration of wills and running errands to other legal offices and law courts. Public offices with which Dickens came into contact in the course of this job were the Alienation Office, the Sixpenny Receivers Office, the Prothonotaries Office, the Clerk of the Escheats, the Dispensation Office, the Affidavit Office, the Filazer's, Exigenter's and Clerk of the Outlawry's Office, the Hanaper Office and the Six-Clerk's office . This employment gave Dickens an exposure to a wide range of jurisdictions and legal precedents. Through this contact with a variety of legal practices, Dickens experienced a broad range of litigation which enabled him to develop opinions on the contemporary operation of the law and its efficacy in the administration of justice. Such experience almost certainly sowed the seeds for much of the critique of the legal system found in his novels. In 1829 when he joined Doctors Commons, Dickens was exposed to ecclesiastical and naval jurisdictions including a Consistory Court, A Court of Arches, the Prerogative Court, the Delegates Court and the Admiralty Court. In this role Dickens was employed by a firm of proctors to take notes on evidence and judgments. This job as a shorthand reporter granted Dickens the opportunity to observe at close range members of the legal profession such as clerks, proctors, secretaries and Doctors. Probably as much through a process of osmosis as anything else, Dickens gained an understanding of the mechanics of basic legal procedures through this type of employment. In order to work as a court reporter, Dickens was required to use shorthand, a method of taking notes that perhaps allowed Dickens to develop the skill to think and write quickly. It was probably at this early stage in his career that the duality of law and literature began to come together for Dickens, developing at a later stage into his volumes of legal fiction. The anonymity of the law writer's existence, as captured later in Dickens' description of Nemo the law-writer in Bleak House, who either lived or did not live by law-writing according to Krook, also may have prompted Dickens to begin writing original works with legal themes

The Acute Inflammatory Response in Trauma / Hemorrhage and Traumatic Brain Injury: Current State and Emerging Prospects

Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future

Diet, faecal pH and colorectal cancer.

We suggest that a lower faecal pH may be correlated with a lower mortality of large-bowel cancer and that faecal pH should always be considered in epidemiological studies on the role of diet in colon carcinogenesis

Volumetric evaluation of CT images of adrenal glands in primary aldosteronism

Objectives: To investigate whether adrenal volumetry provides better agreement with adrenal vein sampling (AVS) than conventional CT for subtyping PA. Furthermore, we evaluated whether the size of this contralateral adrenal was a prognostic factor for clinical outcome after unilateral adrenalectomy.Methods: We retrospectively analyzed volumes of both adrenal glands of the 180 CT-scans (88/180 with unilateral and 92/180 with bilateral disease) of the patients with PA included in the SPARTACUS trial of which 85 also had undergone an AVS. In addition, we examined CT-scans of 20 healthy individuals to compare adrenal volumes with published normal values.Results: Adrenal volume was higher for the left than the right adrenal (mean and SD: 6.49 ± 2.77 ml versus 5.25 ± 1.87 ml for the right adrenal; p &lt; 0.001). Concordance between volumetry and AVS in subtyping was 58.8%, versus 51.8% between conventional CT results and AVS (p = NS). The volumes of the contralateral adrenals in the patients with unilateral disease (right 4.78 ± 1.37 ml; left 6.00 ± 2.73 ml) were higher than those of healthy controls reported in the literature (right 3.62 ± 1.23 ml p &lt; 0.001; left 4.84 ± 1.67 ml p = 0.02). In a multivariable analysis the contralateral volume was not associated with biochemical or clinical success, nor with the defined daily doses of antihypertensive agents at 1 year follow-up.Conclusions: Volumetry of the adrenal glands is not superior to current assessment of adrenal size by CT for subtyping patients with PA. Furthermore, in patients with unilateral disease the size of the contralateral adrenal is enlarged but its size is not associated with outcome.</p