Thursday, November 30, 2006
betablockers en depressie
discriminatie
By Anne Fleckenstein
Usual excuses can't explain the continuing wage gap between women, minorities, and white men.© Getty Images/Shuji Kobayashi
Phoebe Leboy of the Association for Women in Science recalls a conversation she had with a departmental chair, a man not unfamiliar with the issues women in science face.
"It is inevitable that women will earn less than men for comparable jobs," he told her. "Women simply cannot negotiate as aggressively as men for better salaries. And if I met a woman who could, I would not hire her because I would not like her personality."
This anecdote may help explain why a woman will still make less money than a man with the same job, despite the great strides women have made in science over the past 40 years. The same discouraging statistics hold true for minorities in science compared to whites, and the same sorts of subjective factors may be at work.
In the life sciences the average median salary for white men is $80,000, compared to $72,000 for Hispanics, $65,000 for African Americans, and $65,000 for women, according to the most recent figures from the Commission on Professionals in Science and Technology.
Many economists argue that women and minorities tend to be newer in their fields and therefore have less experience, so are naturally paid less than more experienced, senior men. Once women and minorities have been in the workforce as long as men have, these scholars say, there will be no salary gap. They also claim that women and minorities are overwhelmingly drawn to fields that historically pay less than fields to which white men flock, or they may work in less prestigious institutions.
"I think if full transparency of salaries for female and minority scientists existed, we'd all be even more shocked." —Sonya Summerour Clemmons
Let's put aside the question of why certain disciplines and institutions attract more women and minorities than other fields, and study the salaries of people with the same rank, working in the same field, in the same type of institution. A significant salary disparity remains. Female full professors in the life sciences earn, on average, $3,000 less per year than equally ranked men.
A 1993 study of women and men in academic medicine showed that female faculty members, even when performing similar professional tasks, receive fewer rewards for their work, both in professional rank and salary. 1 Nothing much had changed by 2004, when another study of faculty in academic medicine showed that even when controlling for total publications, years of seniority, and hours worked per week, female faculty members were paid on average $12,000 less than their male peers. 2
The gender wage gap is frequently attributed to women taking time off to have children or working fewer hours a week to take care of their families. There may be some truth to this; the family workload continues to fall disproportionately on women, and less time spent on research can hurt productivity. But this doesn't explain why even unmarried women without children advance more slowly in their careers and are paid less than men with equal experience. Women without children may be paid more than those with children, but they still lag behind men.
The common explanations for the wage gap can't completely account for these disparities. Bias and differences in progression provide the missing link. While the salary gap is very narrow for younger scientists, it widens as careers progress because women and minorities are less likely to be promoted than white men, even when their experience and productivity are comparable. Women are often perceived as being less productive than men, even when there is no evidence to support this.
A study in 1997 found that reviewers of the Swedish Medical Research Council consistently gave female applicants lower scores than equally productive men. 3 In fact, the study demonstrated that women had to be even more productive (on the order of three extra papers in Science or Nature or 20 extra papers in other journals) to be ranked the same as male applicants. Often promotion committees tend to judge applicants based simply on the number of papers authored. While it is true women tend to publish less than men, their work tends to get cited more and appears in more high-impact journals, 4 making their scholarly output greater than comparable men's.
What can be done to close this wage gap? One of the main problems is that salaries and benefits are not commonly known. People don't talk about their income, so while minorities may know that they are underpaid, they are often unaware of just how much less they are earning than their white, male peers. How can you know what to negotiate for when you don't know what salaries and benefits your peers are receiving?
According to Sonya Summerour Clemmons, a member of the executive board of the Association for Women in Science, the salary gap for women and minorities persists in science because of fully subjective salary criteria, which need a complete overhaul with regard to how initial salaries and subsequent raises are determined.
"I think if full transparency of salaries for female and minority scientists existed, we'd all be even more shocked," she says. Her advice is to stop blaming women and minorities for the wage gap, and lay the responsibility on the shoulders of the decision-makers holding the purse strings.
Anne Fleckenstein is the postdoctoral research intern at the Association for Women in Science.
References
1. P.L. Carr et al., "Comparing the status of women and men in academic medicine," Ann Intern Med, 119:908-13, 1993.
2. A.S. Ash et al., "Compensation and advancement of women in academic medicine: Is there equity?" Ann Intern Med, 141:205-12, 2004.
3. C. Wenneras, A. Wold, "Nepotism and sexism in peer-review," Nature, 387:341-3, 1997.
4. V.W. Koplin, L.D. Singell Jr., "The gender compositions and scholarly performance of economics departments: a test for employment discrimination," Ind Labor Relat Rev, 49:408-23, 1996.
© 1986-2006 The Scientist
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Tuesday, November 28, 2006
ASCOT
New-Onset Diabetes -- New Analysis of the Blood Pressure-Lowering Arm of ASCOT
DisclosuresLinda Brookes, MSc
Presenter: Ajay K Gupta, MD, MSc (International Centre for Circulatory Health NHLI, Imperial College, London, United Kingdom)
The latest analysis of the results from the blood pressure lowering-arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA) has shown that a regimen based on a calcium channel blocker (CCB) (amlodipine), with or without addition of an angiotensin converting enzyme (ACE) inhibitor (perindopril), reduced the risk of new-onset diabetes by 34% in hypertensive patients, compared with a regimen based on a beta-blocker (atenolol) with or without a thiazide-type diuretic, bendroflumethiazide.[1]
The ASCOT investigators believe that this finding has implications for the future role of beta-blockers and diuretics in the management of patients with hypertension and suggest that physicians adopt what they refer to as "the ASCOT strategy, an evidence-based strategy for combining CCBs and ACE inhibitors," to get their patients to currently recommended target blood pressures. "By so doing, they know that they will reduce the risk of new-onset diabetes by almost one third," the investigators say. On the basis of the results of this most recent analysis, the ASCOT investigators have also developed a new risk score model that can be used to identify those hypertensive patients at highest risk of new-onset diabetes.
ASCOT-BPLA: Main Study
The multicenter, prospective, randomized, controlled ASCOT-BPLA study was designed to compare a newer, CCB-based antihypertensive regimen with the most commonly prescribed combination antihypertensive regimen at the time, a beta-blocker plus a thiazide diuretic, in a population of over 19,000 hypertensive adults at moderate risk of developing cardiovascular disease. ASCOT-BPLA was supported mainly by Pfizer (New York, NY), with additional funding by Servier Research Group (Paris, France).
Patients enrolled in ASCOT were aged 40 to 79 years, had hypertension (screening and baseline blood pressure ≥ 160/100 mm Hg untreated or ≥ 140/90 mm Hg treated with ≥ 1 drugs), no previous myocardial infarction (MI) or current coronary heart disease (CHD), and ≥ 3 other cardiovascular risk factors, such as male gender, age ≥ 55 years, smoking, or diabetes mellitus.[2] Diabetes at baseline was defined as:
Fasting plasma glucose (FPG) ≥ 7 mmol/L (126 mg/dL) and/or random glucose ≥ 11.1 mmol/L (200 mg/dL);
Self-reported diabetes and receiving dietary or drug therapy; or
Presence of both impaired fasting glucose (IFG) (≥ 6 mmol/L) and glucosuria in absence of the above 2 criteria.
Patients were assigned either to amlodipine 5 to 10 mg, adding perindopril 4 to 8 mg as required, or to atenolol 50 to 100 mg, adding bendroflumethiazide 1.25 to 2.5 mg and potassium as required (atenolol-based regimen). Blood pressure targets were < ci =" confidence" hdl =" high-density" hr =" hazard"> 5 mmol/L)†
5.80
5.34-6.43
BMI (per 5-unit increase)
1.49
1.38-1.62
Triglyceride (per mmol/L)
1.12
1.07-1.17
SBP (per 10 mm Hg)
1.07
1.04-1.10
Use of non-CAD medication (Y/N)
1.25
1.11-1.40
*For all comparisons, P < .001†Baseline risk = FPG ≤ 5 mmol/L. BMI >35 kg/m2 given similar risk; hazard ratio per 5-unit increase from baseline.BMI = body mass index; CI = confidence interval; FPG = fasting plasma glucose; HR = hazard ratio.
Dividing the patient population into quartiles based on these factors showed that risk of new-onset diabetes increased with risk score, the patients with the highest score (4th quartile) having an almost 20-fold higher risk than the patients in the lowest (1st) quartile (Table 3). Within each quartile, the patients taking the atenolol-based regimen were at higher risk than those on the amlodipine-based regimen. Comparison of the observed numbers of events with the expected probabilities of the development of diabetes predicted using the risk score showed no difference.
Table 3. New-Onset Diabetes According to Risk Quartiles
1st Quartile
2nd Quartile
3rd Quartile
4th Quartile
Hazard ratio
1
2.5
5.0
19.0
(95% CI)
(1.8-3.5)
(3.7-6.8)
(14.3-25.4)
CI = confidence interval; HR = hazard ratio
Dr. Gupta believes that this risk model "is robust, has an excellent discriminative ability, and could potentially play an important role in clinical practice." The designated discussant at the World Cardiology Congress, José L. Zamorano Gomez, MD, PhD (University Clinic San Carlo, Madrid, Spain), agreed that the risk score obtained by combining the most important risk factors for new-onset diabetes "makes it possible to calculate in advance a risk score which was extremely good at discriminating between risk groups presented in quartiles."
Implications for Treatment of Hypertension
Dr. Gomez also pointed out that, although the ASCOT analysis and other trials seem to indicate that amlodipine has a neutral effect with respect to development of new-onset diabetes, it is unlikely that the 34% difference in the 2 ASCOT treatment groups was entirely due to the ACE inhibitor in the "amlodipine plus or minus perindopril group," because not all patients in this group received perindopril. "Consequently, a certain proportion of the final effect must be due to the atenolol plus or minus diuretic group, particularly atenolol," he stated. Dr. Gomez believes that now that the risk of new-onset diabetes with these drugs has been demonstrated, preventing new-onset diabetes should be regarded in the same light as a "compelling indication" in hypertension management guidelines.
Commenting separately on the latest data, Neil Poulter, MD, MSc (Imperial College, London, UK), Secretary of the ASCOT Executive Committee, said: "These findings have critically important implications for many thousands of people. Hypertension already increases the risk of diabetes 2-3 times. Now we know that the commonly used combination of a beta-blocker plus or minus diuretic significantly increases the risk compared with a new combination, amlodipine plus or minus perindopril. Physicians should think carefully before using the beta-blocker-based strategy to treat hypertension."
The main results of ASCOT reported in 2005[3] prompted a review of guidelines for the management of hypertension in the United Kingdom by the National Institute for Health and Clinical Excellence (NICE), working with the British Hypertension Society. The resulting joint guideline, published in June 2006,[5] included the recommendation that beta-blockers should no longer be preferred initial therapy for hypertension, relegating them to fourth line. Although the greater risk of new-onset diabetes with beta-blockers was acknowledged, the guideline also pointed out that most clinical trials upon which the recommendation was based used atenolol, and other beta-blockers might not carry the same risk. The guideline retained diuretics as a first-line option in patients aged ≥ 55 years, although reports of ongoing discussions had indicated that diuretics would also be removed as recommended first-line drugs.
Commenting in Barcelona on the UK guideline, Peter S. Sever, MD, PhD (Imperial College, London), Co-chairman of the ASCOT Executive Committee, said, "We know from other trials, including Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT),[6] that diuretics are metabolically unfriendly, that they increase fasting plasma glucose, and they are not lipid friendly and there is no doubt that they do contribute to the diabetes." He stressed that "the evidence for not including a diuretic at least in your first and second choice and replacing it with a CCB and an ACE inhibitor is very strong. Why would you want to increase the risk, even if it is not as great as for a beta-blocker, if you have alternative therapies that are now available in generic formulations, so that there is no cost issue as there was before?"
Prof. Sever stressed the increased risk hypertensive patients face if they have diabetes. Regardless of the presence of other risk factors such as hypertension, dyslipidemia, or smoking, or how many risk factors are present, "in a patient with diabetes the overall risk is enhanced dramatically," he said. "A patient with hypertension and diabetes is at equivalent risk to a hypertensive patient who has already had an MI and is nondiabetic. We regard it as the equivalent to secondary prevention in patients with diabetes -- we have to assume they have got established cardiovascular disease," he added.
The ASCOT Strategy
Prof. Sever and his colleagues urge physicians to adopt "the ASCOT strategy," ie, combining CCBs and ACE inhibitors for treatment of hypertension, with the addition of a statin, based on evidence from the lipid-lowering arm of the ASCOT study (ASCOT-LLA), for which over 10,000 patients in the blood pressure lowering study also received atorvastatin 10 mg or placebo daily.[7] "We know from ASCOT-BPLA that this combination will reduce cardiovascular mortality and all-cause mortality, reduce the incidence of MI, and reduce stroke incidence compared with the more conventional and widely used beta-blocker/thiazide combination therapy," said Prof. Sever. "We also know from ASCOT-LLA that most hypertensives will benefit from addition of a statin. The risk reductions were greater than one third for MI and about one quarter for stroke."
Another crucial management strategy to get blood pressure to target is to get a fast, early reduction, according to Prof. Sever.
"We know, from unpublished data from ASCOT, that the early and rapid reductions in blood pressure were associated with dramatic reductions in event rates, MI, and stroke. So with good blood pressure control, the addition of lipid lowering with statins and the preference for the so-called 'newer strategy' of CCB and ACE inhibitors, with all that package -- the ASCOT strategy -- we can confidently say that in hypertensive patients we can reduce the incidence of MI and stroke by nearly two thirds. Out in the real world the majority of hypertensives are poorly controlled, often on inappropriate treatment, and the vast majority are not receiving statins. This is the sort of package that will deliver cardiovascular protection if it was adopted more widely in coronary care."
Although the overall ASCOT population was mainly (95%) white, Prof. Sever believes the strategy based on the ASCOT findings can be applied to other ethnic groups, including black and Asian patients. "These populations are at very real risk of developing new-onset diabetes and we see no reason why our results should not be applied to other ethnic groups," he said.
References
Gupta A. Determinants of new-onset diabetes among hypertensive patients randomised in the ASCOT-BPLA Trial. Presented at the World Congress of Cardiology 2006, September 2-6, 2006, Barcelona, Spain: Clinical trial update I, September 6, 2006.
Sever PS, Dahlöf B, Poulter NR, et al; ASCOT investigators. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. J Hypertens. 2001;19:1139-1147. Abstract
Dahlöf B, Sever PS, Poulter NR, for the ASCOT investigators. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomized controlled trial. Lancet. 2005;366:895-906. Abstract
WHO. Department of Non-Communicable Disease Surveillance. WHO 1999 criteria for diagnosis of diabetes mellitus. Geneva: World Health Organization; 1999: 1-59.
NICE clinical guideline 34. Hypertension: management of hypertension in adults in primary care (partial update of NICE clinical guideline 18). London: National Institute for Health and Clinical Excellence; 2006. Available at www.nice.org.uk/CG018.
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:1981-1997.
Sever PS, Dahlöf B, Poulter NR, et al; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial -- Lipid Lowering Arm (ASCOT-LLA): a multicentre randomized controlled trial. Lancet. 2003;361:1149-1158. Abstract
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Monday, November 27, 2006
hersentumor
Druckversion
QUIVIVE vom 15.11.2006
Hauptthema: Diagnose Hirntumor
Die Diagnose Hirntumor erschüttert das Leben der Betroffenen. Gibt es überhaupt Heilungschancen? Lässt sich der Tumor operieren? Ist die mir angebotene Behandlung die richtige oder soll ich mir eine weitere Meinung einholen? Die Diagnose Hirntumor ist ein Schock. Die Wesensveränderung, die ein Mensch durch den im Kopf wachsenden Tumor zeigt, entfremden ihn zum Teil so sehr von seinen Angehörigen, dass es besonders schwierig ist, den Patienten zu begleiten bei der meist langen und mühevollen Therapie. Und nicht immer ist eine Heilung garantiert. Was sind Hirntumoren? Ein Hirntumor ist eine Gewebswucherung des Gehirns. Meistens entstehen sie aus dem Nervenstützgewebe (Gliome/Astrozytome), der Hypophyse oder es handelt sich um Tochtergeschwulste (Metastasen) aus anderen Organen. Tumoren der Hirnhaut (Meningeom) gehören zwar zu den im Schädel wachsenden Tumoren, zählen aber nicht zu den "eigentlichen" Hirntumoren. Da sie jedoch ab einer gewissen Größe immer auch Hirnstrukturen verdrängen, werden sie genauso behandelt wie Hirntumoren. Es wird zwischen gutartigen und bösartigen Tumoren unterschieden: So genannte gutartige Tumore verdrängen das umgebende Gewebe, wachsen jedoch nicht in dieses hinein. Innerhalb des Schädels können sie jedoch auch zu einem lebensbedrohlich erhöhten Hirndruck führen. Da sie auch lebenswichtige Strukturen verdrängen können, ist der Begriff "gutartig" irreführend und bezieht sich nur auf die Tatsache, dass diese Tumoren nicht in das umliegende Gewebe infiltrieren. Bei vollständiger Entfernung ist auch eine Heilung möglich. Abgesehen von einigen sehr speziellen Ausnahmen metastasieren Hirntumoren nicht. Bösartige Hirntumoren wachsen infiltrierend, das heißt, sie sind nicht scharf vom umliegenden Gewebe getrennt. Nach einer Operation verbleiben einzelne Zellen im Randbereich, die dann wieder zu einem Tumor wachsen. Abhängig von dem Grad der Bösartigkeit - die WHO unterscheidet Grad I bis Grad IV - kann dies schneller oder langsamer geschehen. Ein Beispiel für einen gutartigen Hirntumor ist das Akustikusneurinom, ein bösartiger Tumor ist das Glioblastom. Besonders wichtige Arten von Gehirntumoren sind Gliome. Sie entstehen aus dem Stützgewebe des Gehirns und machen etwa 50 Prozent der primären Hirntumoren aus. Darunter befindet sich mit dem WHO-Grad IV auch das Glioblastom, das mit 50 Prozent auch das häufigste Gliom ist. Die mittlere Überlebensdauer nach der Diagnose ist nur ein Jahr. Meningeome entwickeln sich aus den Zellen der Gehirnhäute. Sie sind meist gutartig und gut behandelbar. Sie machen etwa 20 Prozent aller Geschwülste im Schädelinnern aus, und betreffen überwiegend Erwachsene im mittleren und höheren Lebensalter. Metastasen sind Tochtergeschwülste von Tumoren anderer Organe im Gehirn. Sie machen im höheren Lebensalter 30-40 Prozent aller Gehirntumoren aus. In den meisten Fällen handelt es sich dabei um eine Streuung von Lungenkrebs oder Brustkrebs. Ursachen Die Auslöser für das Entstehen von Hirntumoren sind bislang unbekannt. Weder Schädel-Hirnverletzungen, noch Handy-Nutzung oder riskante Lebensgewohnheiten (wie Rauchen und Alkohol) konnten mit der Entstehung von Hirntumoren in Verbindung gebracht werden. Genetische Faktoren mögen eine Rolle spielen, konnten aber auch noch nicht näher bestimmt werden. Häufigkeit Hirntumoren können in jedem Lebensalter auftreten. Sie sind aber besonders häufig im Kindesalter und im Alter zwischen 50 und 70 Jahren. Symptome Die Symptome können ganz unterschiedlich sein und hängen entscheidend von der Lage des Tumors im Gehirn ab. Je nachdem, wo der Tumor wächst, treten Symptome recht schnell oder mitunter auch erst nach Jahren auf. Symptome können sein: Kopfschmerzen, Übelkeit, Erbrechen, Krampfanfälle (epileptische Anfälle), Sprach- und Sehstörungen, Koordinationsstörungen, Lähmungen, hormonale Störungen, Gefühlsstörungen und auch Wesensveränderungen. Gerade die Wesensveränderungen werden von den Patienten und ihren Angehörigen oft missgedeutet. Diagnostik Mit bildgebenden Verfahren wie CT, MRT und manchmal auch einer PET = Positronen-Emissions-Tomographie lassen sich Hirntumoren gut diagnostizieren. Mithilfe einer Gewebeentnahme, Biopsie, lässt sich Art und Charakter (Bösartigkeit) eines Tumors genauer bestimmen. Behandlung Die Behandlung ruht in der Regel auf drei Säulen: Operation, Bestrahlung und Chemotherapie. Und es wäre noch eine vierte, aber sehr entscheidende wichtige Säule: die psychologische und soziale Betreuung der Patienten und ihrer Angehörigen. Gerade bei den unheilbaren Glioblastomen geht es darum, eine Perspektive für die letzte – befristete – Lebensphase zu finden. Die Patienten brauchen Hilfe. Auch um mit unter Umständen auftretenden Behinderungen zu leben, wie zum Beispiel Lähmungen, Sprach- oder Sehstörungen. Und auch die Angehörigen brauchen in dieser Zeit seelische Unterstützung, denn auch sie müssen sich auf einen Abschied vorbereiten und nicht immer ist der Patient so wie vor der Erkrankung. Der Patient verändert sich mit dieser Krankheit, weil der Tumor im Gehirn wächst. Aber auch weil er damit umgehen muss, dass der Tod naht. Betreuende Ärzte bemerken immer wieder, dass es einen Unterschied macht, wie die Patienten die Diagnose psychisch verarbeiten. Doch trotz dieser Erkenntnis fehlt es oft an Zeit und Ausbildung, um den Patienten angemessen zu begleiten. Dabei wäre das so entscheidend, denn der Lebensmut stärkt das Immunsystem. Patienten, die sich aufgeben, sterben früher. Jeder Patient braucht Unterstützung. Psychologen beobachten verschiedene Phasen während einer Erkrankung, die alle besondere Rücksicht und Begleitung erfordern. Schon oft vor der Diagnosestellung verändern sich die Patienten. Sie merken, dass an ihnen etwas nicht stimmt, wissen aber nicht was. Sie werden launisch, lethargisch oder leiden auch an Ausfällen wie Sprachstörungen oder vorübergehenden Lähmungen. Dann folgt eine Zeit der Arztbesuche, wo nach der Ursache geforscht sind. Zwar gibt es auch einen kurzen Augenblick der Erleichterung, wenn eine Diagnose gefunden ist. Denn vorher leiden Patienten darunter, dass sie nicht wissen, was mit ihnen los ist. Aber dann folgt die Erkenntnis, dass nun ein schwerer Weg vor ihnen liegt mit Operation und Therapien. Manchmal auch Todesangst. Wie die Diagnose aufgenommen wird und wie der Patient und seine Angehörigen damit umgehen, hängt stark davon ab, wie der Patient informiert wird und wie viel Einfühlungsvermögen der übermittelnde Arzt hat. Dieser Bereich der medizinisch-psychologischen Betreuung ist in der Hirntumorbehandlung bislang unterentwickelt. Operation Die Radikalität der Operation ist begrenzt durch das zu erwartende Ergebnis nach der OP. Das heißt, man operiert so viel wie nötig und so wenig wie möglich. Die Entwicklung moderner Operationstechniken hat dazu geführt, dass heutzutage weitaus risikoärmer am Gehirn operiert werden kann als noch vor 15 oder 20 Jahren. Heute wird fast immer mit einem Operationsmikroskop ein solcher Eingriff durchgeführt. Es besteht die Möglichkeit, auch während der Operation bildgebende Verfahren einzusetzen. Nicht selten werden Patienten in einem wachen Zustand operiert. Das ermöglicht dem Neurochirurgen zu überprüfen, welche Funktionen im Gehirn mit betroffen sind. So können Patient und Chirurg miteinander sprechen und gleichzeitig kann zum Beispiel die Sprachfähigkeit überprüft werden. Ziel ist es, den Tumor möglichst komplett herauszuoperieren, bei gleichzeitiger Schonung des normalen Gewebes und dem maximalen Erhalt von Gehirnfunktionen. Gerade bei Gliomen ist dies aber oft nicht möglich, weil diese Tumoren keine klaren Abgrenzungen zum gesunden Gewebe haben. Eine zumindest relative Verbesserung verspricht hier das neu entwickelte „5-ALA Verfahren“, das nach einer Pilotstudie kurz vor der Zulassung steht. Dabei trinken die Patienten vor der Operation eine Lösung, die 5-Aminolaevulinsäure (5-ALA) enthält. Die Säure färbt das Tumorgewebe rot ein. Unter UV-Licht lässt sich dann im Operationssaal die genauere Ausdehnung des Tumors besser erkennen. Trotz dieser Methode bleibt das Problem, dass die Grenzen zwischen Gliom und gesundem Gewebe weiterhin nicht eindeutig auszumachen sind. Bestrahlung: Die Wirkung der Bestrahlung beruht auf einer Schädigung der schnell wachsenden Tumorzellen durch ionisierende Strahlen bei weitestgehender Schonung des umgebenden gesunden Gewebes. Das wird möglich durch neuartige Hochpräzisionsgeräte, die eine millimetergenaue Bestrahlung des Tumorgewebes ermöglichen. In der Charité Campus Virchow steht eines der modernsten Bestrahlungsgeräte der Welt. Entscheidend ist die exakte Lagerung des Patienten. So ist es zum Beispiel möglich, gutartige Meningeome mithilfe der Strahlentherapie über 10 bis 15 Jahre unter Kontrolle zu halten bei einer Nebenwirkungsrate von unter zwei Prozent. Chemotherapie: Bislang werden vor allem Zytostatika zur Zerstörung der Tumorzellen eingesetzt, aber es gibt auch Versuche, die Angiogenese, die Neubildung der Blutgefäße zur Versorgung des Tumors zu unterbinden. Neue Behandlungsmöglichkeiten: An vielen Fronten wird derzeit weiter nach neuen Behandlungsmöglichkeiten gesucht. Dabei spielt die Gentherapie, wie bei vielen anderen Erkrankungen, auch hier eine Rolle. Die Immuntherapie macht Fortschritte mit der Idee, das eigene Immunsystem so zu manipulieren, dass es die bösartigen Tumorzellen als Feind erkennt und bekämpft. Und auch die Hyperthermie (Überhitzung des Tumorgewebes) wird vereinzelt angewandt, aber ein wirklicher Durchbruch ist bislang bei diesen Therapien noch nicht gelungen. Stand der Information: 15.11.2006
Saturday, November 25, 2006
folium zuur
Folic acid should be used to reduce heart disease and stroke
24 November 2006
There is enough evidence to support using folic acid for heart disease and stroke prevention, experts argue in this week's issue of the British Medical Journal.
They say that, overall, data support a causal link between homocysteine and cardiovascular disease (CVD), and they therefore propose that increased folic acid consumption would reduce the risk of CVD events according to the degree of homocysteine reduction that is achieved.
"Debate remains over whether raised serum homocysteine concentrations cause ischemic heart disease and stroke, and whether folic acid, which lowers homocysteine, will help reduce the risk of these disorders," David Wald (Queen Mary's School of Medicine and Dentistry, London, UK) and colleagues note.
In an attempt to clarify the issue, Wald and team conducted separate meta-analyses of cohort studies, genetic studies, and randomized controlled trials in this field.
The large cohort studies looked at homocysteine levels and the occurrence of ischemic heart disease events (fatal and nonfatal myocardial infarction and sudden cardiac death) and stroke, while genetic studies focused on the link between polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) that cause increases in homocysteine and ischemic heart disease, and randomized controlled trials tested the effects on CVD events of lowering homocysteine.
The cohort and genetic studies yielded similar results, indicating a protective effect from lower homocysteine levels, despite not sharing the same sources of possible error.
Meanwhile, although the trials were too small to be conclusive, data were consistent with the expected protective effects of folic acid.
The researchers say that a causal link between homocysteine increases and CVD explains the observations, even if results from any one type of study alone are insufficient to reach that conclusion.
"No single alternative explanation can account for all the observations," they write.
"We therefore take the view that the evidence is now sufficient to justify action on lowering homocysteine concentrations, although the position should be reviewed as evidence from ongoing clinical trials emerges," the authors conclude.
Br Med J 2006; 333: 1114-1117
aspirin (groot artikel)
- Aspirin shown to block arterial inflammation
- Other anti-inflammatory and anticoagulation agents may not yield similar preventive benefit in reducing the risk of heart attack and stroke compared with aspirin
- Aspirin use lessens stroke severity
- Therapeutic benefit shown when combining aspirin with additional agents, such as anticoagulants and statins
- Nighttime use of aspirin yields greater reductions in blood pressure
- Aspirin still underused and potentially underprescribed
- Guidelines stipulate patients at risk of coronary artery disease without history of heart disease should be administered aspirin therapy
Described below, recent studies further confirm the therapeutic benefits of aspirin by highlighting its anti-inflammatory properties and by demonstrating its efficacy over other pharmacologic regimens.
Aspirin's Anti-inflammatory Role
For years, clinicians have attributed aspirin's circulatory benefits to its anticlotting properties. However, the latest data suggest that the drug's anti-inflammatory actions may also play a role. According to a study published in the June 4th issue of Circulation,[2] aspirin may be able to protect blood vessels from the deleterious effects of inflammation and infection, 2 factors thought to initiate and promote atherosclerosis. Researchers from University College (London, England) tested the effects of aspirin on 17 healthy volunteers who were given a typhoid vaccine to initiate a blood vessel inflammatory response. Twelve of the participants were randomized to receive either 1.2 g of oral aspirin or placebo 2 hours prior to the vaccination. The remaining 5 received a local infusion of aspirin after the vaccination.Before and after vaccination, researchers measured levels of interleukin-1 (IL-1), which, when elevated in the blood, indicates inflammation. In the placebo group, IL-1 peaked at 3 hours and remained elevated until 8 hours following vaccination. By contrast, the group that received aspirin prior to the vaccination showed no change in IL-1 response. Venous occlusion plethysmography was performed 16 hours prior to and 8 hours following the vaccination to assess endothelial function in the forearm vessels. Researchers found that the placebo group had a significant decrease in forearm blood flow 8 hours after the vaccination, which was indicative of an inflammatory response that temporarily stiffened the blood vessels. By contrast, those who received pretreatment aspirin maintained blood flow at prevaccination levels. In addition, aspirin seemed to exert anti-inflammatory effects only when administered prior to vaccination, as patients treated with an aspirin infusion following vaccination showed no improvement in endothelial function. The results confirm previous studies showing that mild systemic inflammation impairs endothelium-dependent blood vessel dilation. This study provides evidence that pretreatment with aspirin can provide an anti-inflammatory protective effect to the vasculature.
Are All Anti-inflammatory and Anticoagulation Agents Created Equal?
The correlation between inflammation and atherosclerosis may lead one to believe that other anti-inflammatory agents such as ibuprofen and acetaminophen may also have similar cardiovascular benefits. As the population ages and as the incidence and prevalence of arthritis and other painful conditions increases, a growing number of patients will be taking other pain-reliever medicines, including nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors. The cardiovascular effects of such drugs, however, remain uncertain.Researchers at Harvard Medical School (Boston, Massachusetts) concluded that, with the exception of naproxen, NSAIDs did not reduce heart attack risk (Table 1). Their study findings, published in the Archives of Internal Medicine,[3] were based on an analysis of 22,125 patients (4425 hospitalized for a heart attack and a control group of 17,700 without heart attack). Patients who had been prescribed an NSAID were no more or less likely to have a heart attack than those without a prescription. Upon examining individual NSAIDs, the researchers found that patients receiving naproxen were 16% to 20% less likely to suffer a heart attack, but that the cardiovascular benefits of naproxen did not exceed those of aspirin therapy.
COX-2 inhibitors may complicate those at high risk for heart disease. Preclinical research[4] from the University of Pennsylvania (Philadelphia) indicated that COX-2 inhibitors were more likely to promote blood clotting and blood vessel constriction compared with NSAIDs. Whereas traditional NSAIDs block both COX-1 and -2 enzymes, COX-2 inhibitors inhibit the production of prostacyclin, a component known to prevent thrombus formation and promote vasodilation. Researchers postulate that, without the presence of prostacyclin, the vasoconstrictive effects associated with thromboxane A2 (a product of the COX-1 enzyme) will increase cardiovascular risk. When comparing the injury response in mice genetically engineered to lack both prostacyclin and thromboxane A2 vs those engineered to lack prostacyclin alone, platelet response was substantially more overactive in the latter group. This finding led investigators to conclude that an increased response to injury may also translate into higher cardiovascular risk, particularly in patients who are already at high risk of cardiac events. As a result of an earlier this study, which found that Vioxx (Merck, rofecoxib), a COX-2 inhibitor used for the treatment of arthritis, was associated with higher rates of heart attack and other cardiac events compared with patients on naproxen, Merck announced a label change for its arthritis drug, Vioxx to account for the drugs potential cardiovascular risks.
While they will not cause an initial occurrence of heart failure (HF), NSAIDs may increase the risk of recurrence in patients with 1 previous episode of HF, according to a Dutch study published in the Archives of Internal Medicine.[5] Researchers found that among 345 patients with previous HF, those who filled at least 1 NSAID prescription were nearly 10 times more likely than those who did not use NSAIDs to have a recurrence of HF.
According to researchers at the University of Pennsylvania (Philadelphia), combining ibuprofen with aspirin may interfere with the latter's antiplatelet properties. The study, published in The New England Journal of Medicine (NEJM),[6] examined the potential effects of combining aspirin with 4 other common pain medications: acetaminophen and 3 NSAIDs -- ibuprofen, rofecoxib (Vioxx), and diclofenac. While none of the other pain relievers showed a deleterious effect, when used in combination with aspirin therapy, ibuprofen was found to undermine the cardioprotective effects of aspirin.
Other recent findings suggest that patients with heart disease who are less sensitive to the effects of aspirin are at significantly higher risk of heart attack and death. A study published in the April 9th issue of Circulation[7] found that people with higher blood levels of thromboxane, a substance usually blocked by aspirin, were significantly more likely to have a heart attack or stroke. The data suggest that these patients are resistant to the effects of aspirin and should be treated with higher aspirin doses or another antiplatelet agent, such as clopidogrel, in combination with aspirin.
In general, these studies have demonstrated that NSAIDs and COX-2 inhibitors are relatively safe for the general population, but caution should be exercised when prescribing them for patients with existing heart disease or those at high cardiac risk. The substantial increase in availability of over-the-counter (OTC) pain-reliever drugs places a great burden on the healthcare industry to properly educate patients on potential adverse effects (both immediate and long-term) associated with combining any drugs, whether they be prescribed or otherwise. There is often a misconception on the part of the patient that OTC drugs are harmless, in part because of their easy accessibility. Acknowledging the potential interactions and limitations of such agents is pivotal to ensuring proper heart disease prevention and risk reduction.
Reducing Stroke Severity
Aspirin may also have a preventive benefit among patients at high risk of ischemic stroke, and recent research suggests that aspirin may help limit stroke severity. Trial of Org 10172 in Acute Stroke Treatment (TOAST), a 1200-patient study published in Stroke,[8] found that people who took aspirin within a week prior to suffering an ischemic stroke were more likely to have a milder stroke than those who had not taken aspirin within the same timeframe. Overall, about 50% of patients who used aspirin had mild strokes and about 10% had severe strokes. By contrast, 43% of nonaspirin users had mild strokes and about 15% had a severe stroke. Rates of death, however, did not differ between the 2 groups. Researchers believe that these results could be due in part to the antioxidant properties of aspirin, which may help prevent tissue damage during stroke.Further support for these findings is presented in a recent joint scientific statement from the American Stroke Association and the American Academy of Neurology, which reports that the administration of 160-325 mg of aspirin within as little as a 48-hour window before stroke onset significantly reduces the death rates and disability from stroke.[9] Derived from a systematic review of the literature that examined large, prospective studies, the statement aimed to define the roles of antiplatelet agents vs anticoagulants. Unlike aspirin, anticoagulants such as heparin were not shown to reduce risk of death when used within the same time period. Recommendations could not be made regarding the therapeutic benefits of other antiplatelet agents, such as clopidogrel and ticlopidine, due to insufficient data. The statement recommends that the use of subcutaneous heparin may be considered to prevent deep-vein thrombosis in some at-risk patients, but the dose of the drug should be minimized in order to prevent hemorrhage.
Aspirin appears to be an effective preventive agent in nearly all patients at risk for ischemic stroke, with the notable exception of patients with atrial fibrillation (AF), which is known to greatly increase the risk of embolic stroke. In AF patients, the anticoagulant warfarin has been demonstrated to be significantly more effective at preventing stroke than aspirin, although warfarin carries a higher risk for bleeding. In the November 15th issue of NEJM,[10] researchers presented data comparing the preventive benefits of aspirin and warfarin in patients with AF who had already experienced a stroke. More than 2200 stroke patients were randomized to receive either aspirin or warfarin and were then followed for 2 years. Mortality rates were similar in the 2 groups, as were bleeding and other side effects, indicating that aspirin therapy may be an effective (and less costly) preventive option in this patient group.
A report published in the July issue of NEJM[11] confirmed the cost-effective benefits of using aspirin therapy over clopidogrel (Plavix). In a cost comparison that evaluated the drug cost and the patient-years of life saved for patients receiving either drug alone or in combination with one another, one 75-mg tablet of clopidogrel was found to cost $3.22, 80 times the cost of one 325-mg tablet of aspirin. Researchers believe the most cost-effective way to use the 2 drugs is to prescribe aspirin to the 94.3% of coronary heart disease patients who can tolerate it and offer clopidogrel to the remaining 5.7% who cannot take aspirin because of allergy or other causes. An editorial published in the same issue of NEJM[12] criticized the study, suggesting that it was unfair to assume that the costs of a new treatment with equivalent or superior therapeutic benefits would have to parallel the costs of an existing and established therapy.
Benefits of Aspirin Combination Therapy
Some have proposed that when aspirin is used in combination with other anticoagulant agents, its benefits may be magnified, particularly in the setting of acute coronary syndrome (ACS). The Antithrombotics in the Secondary Prevention of Events in Coronary Thrombosis-2 (ASPECT-2), published in the July 13th issue of The Lancet,[13] randomized 999 ACS patients with acute myocardial infarction (MI) or unstable angina to 1 of 3 arms: low-dose aspirin, high-dose oral anticoagulation (phenprocoumon or acenocoumarol), or a low-dose aspirin plus mild-intensity anticoagulation. With respect to the trial's composite clinical end point (MI, stroke, or death), patients treated with high-intensity anticoagulation or mild-intensity anticoagulation and low-dose aspirin therapy had a significantly reduced risk when compared with low-dose aspirin therapy (5% vs 5% vs 9%, respectively). However, secondary end points of major and minor bleeding were as high or higher in patients on high-intensity or on combination therapy compared with aspirin therapy alone. Researchers attribute the findings to the clinical efficacy of controlling the activation of the coagulation cascade that occurs in ACS.Closely following the publication of the ASPECT-2 trial, investigators from the Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis (APRICOT)-2 study[14] confirmed the angiographic and clinical benefits of combined anticoagulant therapy (aspirin + moderate dose of coumarin [n = 123]) vs aspirin alone (n = 128) in patients who had suffered an MI. Patients on combination therapy also received heparin until moderate anticoagulation was achieved, translating into an additional 66 additional hours of heparin therapy. Aspirin-only patients did not receive any additional heparin. Three-month follow-up revealed that fewer reocclusions had occurred in the combination group (15% vs 28%), and problem-free survival was significantly higher than in the group receiving aspirin therapy alone (86% vs 66%, respectively).
Although a US Food and Drug Administration advisory panel initially rejected Bristol-Myers Squibb's (BMS) proposed copackaging of its statin, pravastatin (Pravachol), with aspirin, the panel reversed its original decision in late July, voting in conditional support of the combination, which will be copackaged to contain 1 of 3 different doses of the statin with either 81 mg or 325 mg of aspirin. This recommendation comes a few weeks following the publication of the favorable Heart Protection Study (HPS),[15] which documented the therapeutic and preventive properties of statin therapy, even in nontraditional patients (see "HeartBytes: Does a Statin a Day Keep the Doctor Away?"). The combination may prove fruitful, particularly in light of recent findings confirming the benefit of aspirin therapy. BMS hopes to file for approval of a single combination tablet at a later date. The FDA is expected to make a final decision shortly.
Bedtime Use Best?
Research suggests that bedtime may be the best time for prophylactic aspirin use, especially for patients with high blood pressure. A study presented at the 17th Annual Scientific Meeting of the American Society of Hypertension, held in New York, NY, found that patients who took low-dose aspirin before going to bed had a significantly greater reduction in blood pressure than those who took aspirin at other times of the day. Other studies using aspirin to treat hypertension have shown inconsistent results, which may be due to the timing of aspirin administration, according to researchers. Patients in the study who took aspirin at night had an average 7-mm Hg decrease in their systolic blood pressure and 4.8-mm Hg decrease in their diastolic blood pressure. By contrast, those who took aspirin upon awakening showed no change in their blood pressure. The researchers speculate that when aspirin is taken at night, it reaches peak plasma levels at just about the same time that the activities of platelets and angiotensin, which have an impact on blood pressure, are at their highest levels.
Aspirin Underused and Underprescribed
Despite the well-published benefits of aspirin use for patients at high risk for cardiovascular disease, there are still many eligible patients who are not using aspirin therapy. According to the results of a Duke University Medical Center patient survey, published in the March 15th issue of the American Journal of Cardiology,[16] aspirin use increased substantially in the mid to late 1990s. Even though the percentage of patients reporting aspirin use rose from 59% in 1995 to 81% in 1999, these levels still fall short of what they should be. Perhaps most alarming, the survey found that people at high risk of coronary or neurovascular events, including those with HF, diabetes, or high blood pressure, were less likely to be taking aspirin than people without these risk factors. Patients in the survey who said they never took aspirin were 85% more likely to die during the 5-year study period than patients taking aspirin.
New Aspirin Guidelines
Recognizing the underutilization of aspirin therapy and the array of information regarding the candidates most likely to benefit, the US Preventive Services Task Force (USPSTF), a panel convened by the Agency for Healthcare Research and Quality, released new guidelines for the proper use of aspirin for preventive care in patients without a history of cardiovascular disease who are at increased risk of developing coronary heart disease (CHD). According to the guidelines, published in the January 15th issue of the Annals of Internal Medicine,[17] aspirin prevention therapy is best suited for people at high risk of developing CHD (those with a 5-year risk of >/= 3%), since the benefits of aspirin use in this patient population significantly outweigh the risks. The USPSTF studied 5 trials of aspirin in healthy people who had 1 or more risk factors for heart disease. Overall, regular aspirin use reduced the incidence of heart attack by 28% and reduced the risk of death from heart disease by 13%, but it also increased the risk of hemorrhagic stroke and major gastrointestinal (GI) bleeding (Table 2). When patients were stratified by risk category, the researchers calculated that aspirin use in patients with a moderately high risk of CHD events (5-year risk of 5%) would prevent 14 heart attacks and cause 1 hemorrhagic stroke and 3 major GI bleeds. In patients with a 1% risk, the number of bleeding events would equal or outweigh the benefits of the drug (Table 3). The task force recommends that patients at increased CHD risk discuss the potential benefits and risks of aspirin prevention protocols with their physician.
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Mary Thompson is Editor-in-Chief, Medtech Insight, Tustin, California.
Medscape Cardiology 6(2), 2002. © 2002 Medscape
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ASPIRIN
aspirin
- Comment in:
- Stroke. 2003 Apr;34(4):847-8.
Comparison of triflusal and aspirin for prevention of vascular events in patients after cerebral infarction: the TACIP Study: a randomized, double-blind, multicenter trial.
Service of Neurology, Hospital General Universitario de Alicante, Spain. matias_jor@gva.es
BACKGROUND AND PURPOSE: The efficacy of the antiplatelet agent triflusal for prevention of vascular events after stroke has been reported in a pilot study. However, there is a need to confirm those results in a larger study. METHODS: We performed a randomized, double-blind, multicenter study to test the efficacy of triflusal (600 mg/d) versus aspirin (325 mg/d) for prevention of vascular events in patients with stroke or transient ischemic attack (Triflusal versus Aspirin in Cerebral Infarction Prevention [TACIP]). We assessed a combined end point (incidence of nonfatal ischemic stroke, nonfatal acute myocardial infarction, or vascular death) as well as the incidence of these events separately and the incidence of major hemorrhage. RESULTS: Of 2113 patients, 1058 received triflusal and 1055 aspirin. The mean follow-up period was 30.1 months. The incidence of combined end point (13.1% for triflusal, 12.4% for aspirin) as well the survival analysis (hazard ratio [HR] for triflusal versus aspirin, 1.09; 95% CI, 0.85 to 1.38) showed no differences between groups. The incidence of nonfatal stroke (HR, 1.09; 95% CI, 0.82 to 1.44), nonfatal acute myocardial infarction (HR, 0.95; 95% CI, 0.46 to 1.98,) and vascular death (HR, 1.22; 95% CI, 0.75 to 1.96) was also similar. A significantly higher incidence of major hemorrhages in the aspirin group was recorded (HR, 0.48; 95% CI, 0.28 to 0.82). The overall incidence of hemorrhage was significantly lower in the triflusal group (16.7% versus 25.2%) (odds ratio, 0.76; 95% CI, 0.67 to 0.86; P<0.001).>
PMID: 12649515 [PubMed - indexed for MEDLINE]
Friday, November 24, 2006
neanderthal
Mens en Neandertaler al zeker 120.000 jaar gescheiden
Uitgegeven: 15 november 2006 22:20
Laatst gewijzigd: 15 november 2006 22:55
Dit blijkt uit diverse studies van Duitse, Amerikaanse en Kroatische wetenschappers waarover de tijdschriften Science en Nature woensdag berichtten. Onduidelijk is vooralsnog of later nog een menging van de soorten heeft plaatsgevonden. 
Homo sapiens en Neandertaler leefden honderdduizenden jaren samen op het Europese continent totdat de neandertaler 30.000 jaar geleden uitstierf. In 1856 werden voor het eerst resten ontdekt in het Duitse Neandertal.
De wetenschappers die erfelijk materiaal uit neanderthalerbotjes analyseerden, hopen over twee jaar het hele genoom van de verre bloedverwant in kaart te hebben gebracht. Zij hopen dan ook meer te kunnen zeggen over de vraag of neanderthalers konden praten op een manier die lijkt op de taal van de moderne mens.
jongens versus meisjes
Uitgegeven: 20 november 2006 13:08
AMSTERDAM - Jongeren die extravert en impulsief zijn, hebben een grotere kans om agressief of crimineel gedrag te ontwikkelen dan introverte jongeren. Die ontwikkelen juist eerder depressieve of angstige gevoelens. Dat concludeert psychologe Joyce Akse in haar promotieonderzoek aan de Universiteit Utrecht. Doordat extraverte jongeren hun impulsen de vrije loop laten, hebben zij een grotere kans om agressief of crimineel gedrag te vertonen. De introverte jongeren hebben hun impulsen juist 'te goed' in bedwang. Daardoor hebben zij meer kans op het ontwikkelen van depressieve of angstige gevoelens, stelt de onderzoekster. 
Uit het onderzoek blijkt dat van de jongeren meisjes eerder depressief of angstig gedrag ontwikkelen. Jongens hebben juist eerder kans op het ontwikkelen van meer agressief of crimineel gedrag.
Akse heeft in de periode van 2001 tot 2004 in de provincie Utrecht duizend schoolgaande jongeren in de leeftijd van 12 tot 19 jaar ondervraagd. De psychologe promoveert vrijdag.
scizophrenia
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