Pulmonary Arterial Hypertension, November 2005

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Pulmonary Arterial Hypertension, November 2005 Journal Scan

FromThe New England Journal of MedicineNovember 17, 2005  ( Volume 353, Number 20 )

Sildenafil Citrate Therapy for Pulmonary Arterial HypertensionGalie N, Ghofrani H, Torbicki A, et al. 
The New England Journal of Medicine.  2005;353(20):2148-2157

The pathophysiology of pulmonary hypertension involves an increased production of vasoconstrictors (endothelin-1) and a decrease in prostacyclin and nitric oxide, which are vasodilators.[1] Over time, this pulmonary endothelial dysfunction causes strain on the right ventricle, leading to right ventricular failure. The end result is eventually death. Long-term therapies have consisted of prostanoids, oxygen, diuretics, and endothelin receptor antagonists (ERAs). Yet treatment is problematic. The prostanoids are often associated with many potential side effects. Routine liver enzyme testing is required when using the ERAs.[2] The role of the nitric oxide pathway has been studied, and inhaled nitric oxide has been used for some time in vasoreactivity testing. Phosphodiesterase type-5 (PDE-5) metabolizes cyclic guanosine monophosphate (cGMP), causing vasoconstriction and the growth of vascular smooth muscle cells. In patients with pulmonary hypertension, PDE-5 is upregulated. The inhibition of PDE-5 enhances the cGMP, allowing for dilation of pulmonary vessels and possibly exerting antiproliferative effects on the vascular smooth muscle cells in the lungs.[3]

This large 12-week study conducted in 53 centers between October 2002 and November 2003 evaluated the effects of 3 different doses of sildenafil (a PDE-5 inhibitor) on patients with pulmonary arterial hypertension, mostly New York Heart Association (NYHA) classes II and III. The patients included in the study had either idiopathic pulmonary arterial hypertension, pulmonary hypertension associated with connective tissue disease, or repaired congential heart disease. Patients were randomized according to distance walked on a 6-minute walk (< 325 m or > 325 m) and the cause of the pulmonary hypertension. Treatment groups received either 20-, 40-, or 80-mg doses of sildenafil or placebo. In the extension study, 80 mg of sildenafil was studied. The primary endpoint was the 6-minute walk distance (6MWD). Also evaluated was NYHA functional class, time to clinical worsening, hemodynamic parameters (mean pulmonary artery pressures), and Borg dyspnea scale. A total of 278 patients were randomized to 1 of the 4 treatment groups, with 265 completing the 12 weeks of study. Idiopathic pulmonary arterial hypertension was the most common type noted, with NYHA class of III for 58% of the patients. All patients receiving sildenafil exhibited an increase in 6MWD at the end of 12 weeks. The 20-mg group demonstrated an increase of 45 m and the 80-mg group improving by 50 m. Hemodynamics varied considerably among the 3 sildenafil groups and the control group. The placebo group demonstrated an increase in hospitalizations for worsening pulmonary hypertension compared with the treatment group. WHO functional class improved to a greater degree in the sildenafil groups.

Overall, an improvement was noted in exercise capacity for the patients taking sildenafil regardless of the cause of PAH evaluation. The improvement in 6MWD compares to that noted with epoprostenol (47 m) and bosentan (44 m). This effect was noted up to 1 year in the extension study.ReferencesHumbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol. 2004;43:(Suppl 12):13S-24S.Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425-1436.Tantini B, Manes A, Fiumana E, et al. Antiproliferative effect of sildenafil on human pulmonary artery smooth muscle cells. Basic Res Cardiol. 2005;100:131-138.

Abstract

This is a part of article Pulmonary Arterial Hypertension, November 2005 Taken from "Levitra Versus Viagra" Information Blog

The Evolving Role Of Testosterone In The Treatment Of Erectile Dysfunction

Summary and Introduction

Summary

Hypogonadism may play a significant role in the pathophysiology of erectile dysfunction (ED). A threshold level of testosterone may be necessary for normal erectile function. Testosterone replacement therapy is indicated in hypogonadal patients and is beneficial in patients with ED and hypogonadism. Monotherapy with testosterone for ED is of limited effectiveness and may be most promising in young patients with hypogonadism and without vascular risk factors for ED. A number of laboratory and human studies have shown the combination of testosterone and other ED treatments, such as phosphodiesterase type 5 (PDE5) inhibitors, to be beneficial in patients with ED and hypogonadism, who fail PDE5 inhibitor therapy alone. There is increasing evidence that combination therapy is effective in treating the symptoms of ED in patients for whom treatment failed with testosterone or PDE5 inhibitors alone. Testosterone replacement therapy has potentially evolved from a monotherapy for ED in cases of low testosterone, to a combination therapy with PDE5 inhibitors. Screening for hypogonadism may be useful in men with ED who fail prior PDE5 inhibitors, especially in populations at risk for hypogonadism such as type 2 diabetes and the metabolic syndrome.Introduction

The pathophysiology of erectile dysfunction (ED) is multifactorial, involving vascular, neurologic, hormonal and/or psychological causes. The prevalence of hypogonadism in men with ED varies depending on the study populations, comorbidities and diagnosis methods. Approximately 12% of patients with ED may have hypogonadism.[1] Hypogonadism is defined as a state of deficiency in gonadal function manifested by deficient secretion of gonadal hormones and/or gametogenesis.[2] For the purpose of this paper, review and discussion will be limited to hypogonadism as testosterone deficiency. Reduced production of testosterone may increase the risk of osteoporosis, sexual dysfunction, fatigue, cardiovascular disease and mood disturbances, and may decrease muscle mass.[2] Hypogonadism may be classified as hypergonadotrophic in cases of testicular failure or hypogonadotrophic in cases of hypothalamic/pituitary failure.[2] Ageing is associated with gradually declining levels of testosterone (late-onset hypogonadism or androgen decline in the ageing male).[3] In addition, chronic medical disorders are also frequently associated with hypogonadism, such as type 2 diabetes,[4] the metabolic syndrome, chronic renal failure and chronic hepatic failure. The International Consultation on Sexual and Erectile Dysfunction recommended that adult-onset hypogonadism be defined as a clinical and biochemical syndrome.[3]

Testosterone plays a key role in the central and peripheral modulation of erectile function[5] New research in the laboratory and in humans is shaping a refinement of the role of testosterone replacement therapy in ED. This paper will address the evolving role of testosterone in the treatment of ED, both as a monotherapy and in combination with phosphodiesterase type 5 (PDE5) inhibitors.  Printer- Friendly Email This

Int J Clin Pract.  2006;60(9):1087-1092.  ©2006 Blackwell Publishing
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World ‘failing on human rights’

World leaders are failing to tackle human rights abuses around the globe, Amnesty International says.

In an annual report, the group says people are still being tortured or ill-treated in at least 81 countries.

In at least 54 states they face unfair trial and cannot speak freely in at least 77 nations, the group adds.

It says world leaders should apologise for 60 years of human rights failures since the UN adopted the Universal Declaration of Human Rights in 1948.

The group also challenges them "to re-commit themselves to deliver concrete improvements".

US 'defiance'

The report - which covers 150 countries - was published ahead of the 60th anniversary of the human rights declaration, which was adopted on 10 December 1948.

Mary Robinson, who was from 1997 to 2002 the UN High Commissioner for Human Rights, said recognising the declaration was a very different matter from implementing it.

"I think we have an opportunity during the 60th anniversary year to redress some of the problems since the terrible attacks on the United States, what we now call 911," she said.

But Amnesty's document accuses the US of failing to provide a moral compass for its international peers.

"As the world's most powerful state, the USA sets the standard for government behaviour globally," the report says.

It notes that Washington "had distinguished itself in recent years through its defiance of international law".

'Ban all torture'

The report says the US must close the Guantanamo Bay detention camp for terror suspects and either prosecute the inmates under fair trials or free them.

It also urges Washington to ban all forms of torture and stop propping authoritarian regimes.

It singles out the support of President George W Bush's administration for Pakistani President Pervez Musharraf when he imposed a state of emergency, clamped down on media and sacked judges.

The report also says other leading nations must act to improve their human rights records:

• China is urged to adhere to its human rights promises and allow free speech and end "re-education through labour"
• Russia is encouraged to show greater tolerance for political dissent, and none for impunity on human rights abuses in Chechnya
• The EU is being asked to investigate the complicity of its member states in "renditions" of terror suspects.

'Impotence'

HAVE YOUR SAYLeaders are failing to protect human rights and all for the reason of money and powerBrandon, BerlinSend us your comments

Launching the document, Amnesty International's Secretary General Irene Khan said: "Injustice, inequality and impunity are the hallmarks of our world today.

"The human rights flashpoints in [Sudan's] Darfur, Zimbabwe, Gaza, Iraq and Myanmar [Burma] demand immediate action.

"2007 was characterised by the impotence of Western governments and the ambivalence or reluctance of emerging powers to tackle some of the world's worst human rights crises."

Ms Khan stressed that "governments must act now to close the yawning gap between promise and performance".

She said: "2008 presents an unprecedented opportunity for new leaders coming to power and countries emerging on the world stage to set a new direction and reject the myopic policies and practices that in recent years have made the world a more dangerous and divided place."
This is a part of article World ‘failing on human rights’ Taken from "Tadalafil Cheapest Online Prices" Information Blog

BBC NEWS | Talk about Newsnight | My One Day In History - 0600-2359

My One Day In History - 0600-2359

The British Library is encouraging us all to blog about our daily experience today. If you want to have a go, click here. It's being done to promote "history" and you are supposed to include stuff about how history has affected your day. It will all be useful in 2207 they say. Since most of us are not lucky enough, like Samuel Pepys, to be able to write "got up, drank my morning draught, went to France to bring about the restoration of the Stuart monarchy, got drunk, snogged the housemaid…" it could be a tall order. However I am about to give it a go. For the entertainment and enlightenment of Newsnight viewers I will be updating this regularly throughout the day. If your blog intersects with mine - ie you see me on the bus, or I am unlucky enough to be put on telly tonight - put me in as a keyword, and Newsnight. Here goes….

0559: Woke up to DAB radio coming on. Today Programme with Jim Naughtie and Carolyn Quinn. Main story - Bush's advisers say he should call in Syria and Iran to help rule Iraq. But don't they already run most of it through allied militias anyway? Lie in bed with my wife listening to the news. At 0615 I have to pay attention as it's the business slot: very financially literate and detailed discussion of Macquarie Bank's strategy of buying infrastructure assets. And the BBC governors want us all investigated for doing too much "consumer" and "fat cat" stories - not at 0615!

My wife gets up first as she's going to the gym. I get out of bed around 0645 and make put the kettle on. I start sweeping sand into the bricks on our new patio which I laid over the weekend. My wife makes a pot of tea (Tesco Finest) and we drink it in the garden, me in my dressing gown (do you really want this much detail 2207???) The moon starts as a silver sliver against a misty sky but about five to 7 the sky in the east lights up pink and the sky goes blue. I look up again and the moon has disappeared over the rooftops. She goes off to work at 0715; I make toast and another cup of tea, this time just using the bag, and then I'm at my computer.

0735: Sit down at the computer which I leave on standby, but with the monitor switched off overnight. Log in. Get my personal emails (from POP server to Outlook on my PC): three overnight - a Google Alert on China news, a "new friend" request on MySpace; spam inviting me to invest in Texahoma Energy. Log in to BBC Webmail - a remote access version of work email that you have to usa an RAS SecurID tag to get into. type my login name, password, personal pin code then a six digit code generated by the tag. Only four emails overnight: (i) same Google China alert, (ii) a Spam alert from the server telling me it has intercepted 22 messages. I give you the top five…

Pablo Luna (walkermayzys@col.. Prescription free top med brand$ 10/16/06 3:35 AM
Scott M Bassett (imhotep@eng.. Re: Can you help me? Need Zyloprim . 10/16/06 5:02 AM
Thomas Salinas (westbayahfq@.. CIAlis (TADALAFIL) =-= $uper VIAgr@ 10/16/06 5:25 AM
Jana Gee (blake@embeddedwire.. Re: Check out for H0T NEWS! 10/16/06 5:55 AM
Sushil Higham (arlenelowder@.. Re: VmlAGRA 10/16/06 6:13 AM

…an email from Lehman Brothers research team called Daily Global Relative Value. It get this every day and its vaguely Marxist title cheers me up.It's a PDF, which I don't read and a kind of quiz for analysts to take part in. The question today is: "Which factor is most likely to induce “Goldilocks†to flee? (Please Open Report to Vote) A) Geopolitical risk B) Stubbornly elevated inflation C) Decline in corporate profitability D) Issuer-specific event E) Liquidity stall F) Aging business cycle." This is about the so-called Goldilocks economy - neither too hot (inflation) nor too cold (recession). Like I said, here at the beeb we are always concentrating on consumer stories and fat cats.

The final overnight email has been from a business consultancy called Yankee Group inviting me to a seminar in New York about "The Impact of Ubiquity on Networks, Service Delivery and Business models". On current budgets I won't be going.

Round about 0800 the post van arrives and rings my doorbell. I go down to collect a special delivery parcel containing the next three chapters of my book with corrections from my book editor. As the previous three chapters are still uncorrected and it's all due in a week's time, this is unwelcome. On the doorstep I say good morning to my neighbour, Caroline, a jazz sax player who is getttng ready to take her daughter to nursery in the time honoured urban bohemian fashion of a push bike: they are both wearing helmets. The postie calls me mate.

At 0800 I stop writing this and start looking at the websites of the newspapers to see if there's anything I might need to cover. More blogging due mid-morning.

11000 UPDATE: Not much in the papers. More on muslims: now the backlash against Labour's PR offensive has started (in the Telegraph, and on Newsnight last night). Veiled women pictures everywhere. Only article I bothered to read was this one, which was excellent. Being a daily news journo with access to the wires you tend to know what's going to be in the papers before you read them, so you mainly look for interesting comment or exclusives everyone else has missed.

I've spent about 2.5 hours correcting a chapter of my book (about the rise of syndicalism after the London docks strike of 1889, so definitely "touched by history" today), and half an hour talking to somebody in the NHS about a story I am working on: I may put more details in the "for posterity" version of this, but it was off the record so nothing here. Until just now I was still in my pyjamas - one of the luxuries of having a job where you know you may still be at work at midnight is to take a leisurely run at the morning until 1000.

Had a short conversation with today's output editor of Newsnight, Robbie Gibb. He tells me there is a six minute slot we need to fill tonight and that Peter Barron, the actual supreme leader of Newsnight, is keen on the story about Hinckley Point's boiler pipes turning dodgy. As I write this I am awaiting a call out of the eleven o'clock meeting. Let me explain: the output editors of the BBC News bulletins all go to a meeting at 0915: they compare notes but if you are the Newsnight editor you are also prone to hiding various exclusives and angles. After that they communicate with their minions. Then at 1030 in Newsnight's case there is a cramped meeting in the editor's office: Robbie and Peter go through what they are thinking and the desk producers - mainly people in their 20s and 30s - pitch stories. These are the people who will drive the news desk all day, not the onscreen reporters. We communicate by email and mobile phone, pitching stories, dissing others and depending on our mood volunteering to fill the six minutes not already allocated. It looks like I am in line to do something.

I've showered (green Dove soap, Aveda Black Malva shampoo) and dressed (jeans, old shirt) and am now going to chase down HSS Tool Hire who are supposed to be picking up a Wacker Plate and Brick Cutter from me - which is one of the reasons I am still working at home at 1100. 25 work emails since the last check, mainly useful. No more home emails. I've spent the last three hours in my study, not leaving my desk, but with a sub-audible Radio Four on on the next room which, as always during the daytime, seems to be about hedgehogs and women's problems.

Right, historians of the future, read this: I phoned the HSS call centre and gave them my order number. After only 30 seconds of muzak (actually a commercial radio-style ad for HSS) they told me the driver is on his way and will pick the stuff up in 20 minutes. Whatever you read about call centres and customer service in the 21st century, it's not true: hiring stuff, and even buying stuff is a doddle now - even at the roughnecked end of commerce, the building trade. The stuff I hired worked, did what it was supposed to do, did not injure me, was delivered on time (albeit by men with a marked reluctance to carry anything). Even the fact that I am supposed to be trained to work a vibration plate was not an obstacle to getting it delivered.

1151: The HSS man actually helped me carry both machines through the house to the truck. I suppose just in case in the year 2207 it is still an issue I will mention the detail that he was black; the postman was white, I am white, all my neighbours are white. The wacker plate was a Honda: when I asked him what make it was he looked at me gone out as if to say - why, you're not thinking of buying one are you!

I have just got a personal email from my local community organisation inviting me to an over-50s tea dance: Quadrille dancing with Elsa Perez. It is not funny - in four years time I will be able to go! It is 12 noon now and time to do something that does not involve Microsoft Word or Typepad.

1220: Nipped out for a quick lunch at my local Portugese greasy spoon. Took a call from someone pitching me a "survey based" story about gambling habits. Steak covered in "pizzaola" sauce with fresh veg cut up and boiled to taste like tinned veg. All in all a mistake - their cakes are good, as are their breakfasts, but I am on a diet. Sadly even the veg will not count towards the five portions my wife polices me to eat each day. In the cafe are: a builder in shorts; two office worker couples, all smoking; some burly plain cothes law enforcement types (my area of south London is home to many offshoots of NCIS and the Met). The counter mobbed by builders in hi-vis buying sandwiches. All four of the extended Madieran family behind the counter working very fast to keep up. The owner takes time to have a few words with me as he brings me the steak.

In the cafe I read the FT. Just for posterity I will give you a "reading" of what I saw, postmodernist style: lead story on Macquarie - right story, right line. Big second lead on flotation of Chinese bank - very FT, aimed at its supposed global audience. Phil Stephens comment piece on why generals should not intervene in politics (curious echo of Pepys here!) - my reaction? The voice of a Blair ally quietly making a point. Big comment piece by FT international editor - aargh, indigestible, Big feature on the succession plan at Berelsmann - very interesting. Real original take on a real major business. Most of the rest of it I have seen on the wires already. There are two supplements with the FT - the Companies and Markets section, which I scan and bin, and an advertising led thing which made so little impression on my that I binned it before taking in what it was about.

I have taken a phone call from an NGO activist I was working with to cover a planned backbench revolt by Labour MPs over the Company Law Reform Bill. It now looks like the revolt is fizzling out, as there have been concessions from the government. There will still be a dingdong in parliament later this week between Labour and the Tories over the substantive bill. NGOs disappointed more concessions not wrung out of the front bench.

I stick some washing in the machine, collect my suit from the local dry cleaners and watch the One O'Clock News. The One leads with Iraq Study Group planning escape routes for Bush, and with Blair "presser" - what we call a press conference - which is still going on. Looks like he's having a hard time. I email Robbie to ask if he wants to do the numbers game over NHS job losses tonight. We are now discussing this via email. I write "How many people are really being sacked this year - and why can't Blair or the chief exec answer it? Straight political fist fight off the back of a stats piece." He is thinking about it.

Meanwhile, on another story entirely I am asked by Jasmin the deputy editor to make a call to a key contact who we need to speak to. I make the call. That's the second interesting thing that's happened to day where I can't go into detail. I am beginning to realise it might go on like this all day.

Jasmin is my line manager and deals with my story pitches, whinges and workload: I am due a call with her about the NHS story I was researching earlier, which is not the same as the one Blair is dealing with. Since I have started with this ethnic identity thing, Jasmin is Sikh. Looking at my experiences today through 2207 hindsight, I think it is worth saying that with middle class people, and even to "assimilated" working class people, I find at least in London ethnicity is almost transparent - I genuinely hardly notice who is black, white or Asian. What you do tend to notice more is language and culture: so the Portugese/Madieran cafe's whole identity is wrapped up in who they are; and in London right now you can't move without hearing somebody speaking Polish into a mobile phone.

I am ironing a shirt and getting my suit on ready to go into work. It is exactly 1330

1500: As Erwin Schrodinger might have predicted, writing this blog has now started to affect what is happening to me. Arriving at work I get an email from my first ever girlfriend (we split up 28 years ago) who now works in the comms department of one of the organisations dealing with bad news today and we have a slightly edgy but funny email exchange where she tells me about her day so far, takes the mickey out of me and my patio, and chides me a bit over the way her story is being covered.

I walk in the office, Bush is live on News24 about Guantanamo. Another email informs me we won't do the NHS story today. News24 is now reporting on the blogging project.

On the tube journey here I remember seeing: a builder in a wooly hat with a spirit level longer than he was high; a young couple where the man had a walking stick and they both looked worried; a slightly intense looking woman who was taking up two seats with a giant bag of sewing; an actor type wrapped in a scarf despite the tube being boiling hot; a woman in a track suit carrying a violin case.

Going back a bit, on leaving the house I was dressed in: pink shirt (Aquascutum); blue suit (Kilgour); black shoes (Church's); watch (Zenith); cufflinks (Van den Berg). I know this sounds like an advertorial from GQ magazine but in 2207 they might want to know. Anyway it's the journalists equivalent of body armour and it means nobody is going to jerk you around on the reception desk of a major company should you need to turn up at one in a hurry. In my pockets there are: wallet; SonyEricsson P910i (battered and scratched and minus its stylus); keys; transparent plastic earpiece in case I have to do a live report; about £3 in change; Oystercard with some business cards. I am carrying about £40 in notes and quite a lot of plastic.

There is now a lot of business news happening but it will struggle to get on Newsnight because there are other big stories around: Tata bids for Corus; US PPI down…

1630: Following the second big editors meeting of the day, Newsnight is now going to cover the NHS job losses story and I am now working flat out on preparing somethign I have to record at 8pm. My producer Mark is hard at work scrounging tapes of Tony Blair from other frantic producers. SO there you go, it's as quick and decisive as "now we're at war with Eurasia" once the bosses decide something. More to follow…

1830: It is now half past six and I am deep in the detail of scripting graphics abotu NHS job losses, wading through party breifings and Treasury responses about who's saying what over the NHS. There is such a mixtur eof on and off record stuff in my inbox that I am not even going to go there. In the middle of it all I got a cal from another longterm contact offering me an exclusive on a political story. I know it all sounds like Walter Mitty - but basically since about 1530 I have gone into multitasking mode. Physically I am sitting at my desk and mainly talking to people (Labour, Tories, NHS Employers, Unison) via emissaries. I have ordered Sweet & Sour Chicken Balls from the takeaway: my other half will not be pleased at my fresh vegetable and fruit intake - it amounts to a solitary Cox's Orange Pippin I ate this morning. Set against that is the Twix I bought and ate as soon as I found out I had to do tonight's story - that hour between three and four pm is the journalistic equivalent to the hour when the secret police come and take people away into night and fog….

Right now, outside, it is dark. The big thing on Newsnight tonight is an exclusive story about the activities of the Janjawid militia in Sudan. At 1900 I will be interviewing somebody from the unions and then at 2000 I will record some of my piece for tonight. Then I'll go and edit it, eating the Chinese food somewhere inbetween. My car home is booked for 2300 and my first appointment tomorrow is 0815. I hope that technology has cut the TV correspondent's working day a bit by 2207 - in fact if you bear in mind that the way we work adumbrates the way most people will work in future, with work seeping into life and life into work, the whole concept of work hours will break down.

2215: They have not broken down yet however. It is ten fifteen and I am sitting in a small dark room with two other blokes: producer Mark Lobel and VT editor Clive Edwards…we are cutting together a piece which is part me standing in the studio, part me tracking over rushes, part footage of Tony Blair and David Nicholson, CEO of the NHS, trying to explain why they can't give an exact figure for the number of job losses in the NHS. Its all done except for an information graphic, which is being done by someone else. We have just watched the ten o'clock news cover the latest carnage in Iraq and it occurs to me that this is the third or fourth year of sitting in a dark room with other journalists late at night watching pictures of Iraq and quietly shaking our heads. The second story on the Ten O'Clock News is about, er, fat cat salaries.

Moving swiftly on, I am now psyching myself up to go and do a live top to my piece in the studio with Jeremy Paxman. See you on the airwaves.

2220: I get to the studio to record the top of the programme which involves just standing in a place. Paxman ribs me about this blog - implying that I should not be getting up at 6am. We have a conversation the conclusion of which is that both our lives would be better if we got more sleep. I spend the next 20 minutes in the "Green Room" with programme guests watching the more important stuff a the top of the programme and then, near the end, I am guided to the set to do my live bit. UNfortunately the 30 seconds allocated for me to slip onto the set and start speaking is too short, or goes too quickly, and I am not guided to the required spot so I start speaking in a kind of no-man's land. it is all over, like dentistry, before you know you have started. Had a long discussion with Anei our makeup woman about how to mend an ADSL router that has been struck by lightning - she was shocked that you could just go out and buy a new one, and did not have to rely on BT replacing the one that's broken.

I queued as usual to get my cab at BBC reception and Derek, the man on the desk who looks out for me, got it sorted. The cab took the usual dog-leg journey down through Chelsea to the embankment then along to Vauxhall bridge. This is a great journey to take in silence late at night with the river breeze in your face, in the back of a decent car. I have learned to use it to relax.

Arrived home at about 2340, poured a glass of port. Talked to my wife, who has seen a fatal cycle accident today and looks a bit shocked. Came to the study to write this, ending Bridget-Jones style with a list of medicines I am about to take: 20mg omeprazole, Gaviscon, Twinings Digestif Tea (1 unit). That's my day: I will post it up on the site and it will be here for posterity, or until the BBC rebrands us, or gets abolished: which will be long before 2207.
This is a part of article BBC NEWS | Talk about Newsnight | My One Day In History - 0600-2359 Taken from "Tadalafil Cheapest Online Prices" Information Blog

Austin Powers III: Your views

Monday, 29 July, 2002, 10:12 GMT 11:12 UK Austin Powers III: Your views
The film boasts some new faces along with old favourites
Mike Myers returns for his third incarnation as the dandy spoof spy, this time joining forces with old flame Foxxy Cleopatra (Beyoncé Knowles) in the fight against Dr Evil.

The film opens with a James Bond-style set piece which enlists a bevvy of A-list Hollywood stars.

"Myers' scriptwriting skills and performance have sharpened since The Spy Who Shagged Me. At times, there are even flashes of genius, reminiscent of Peter Sellers at his legendary best," wrote BBC News Online's Rebecca Thomas.

But what do you think?

Has the Powers persona run out of steam? Or is Goldmember the best yet?

I'm still reeling and getting flash backs. Will have to see it again as I know I missed bits from laughing. A much needed pick me up, just what the doctor ordered.
sheila, UK

Definitely not as good as the second installment. Beyonce was fantastic as Foxxy Cleopatra and the cameos were a great touch. The Dutch villian had his grossly funny moments but all in all, this is best for the DVD player and not the big screen.
Jason, USA

I loved the film! Not as funny as the first, but it was still a good laugh. Mike Myers is a comedy genius and I hope he continues to make films well into the future.
Amanda, Scotland

This movie is groovy baby. The cameo roles are really funny - I was nearly in tears. The Goldmember character was really funny and also, to live up to tradition, some of the character names are really funny.
Dr Evil aka Neil, Scotland

Very disappointing. Without question the weakest instalment in the trilogy. The character of Goldmember is devoid of any humour and really grates. He's perhaps even less funny than Fat Bastard - and certainly more irritating. The rehashed gags were simply not funny the third time round and there were genuinely few moments past the opening 20 minutes where I laughed.

Myers still shows his comedic genius through his use of subtle and not-so-subtle facial expressions in the characters of Evil and Powers, but seemed fresh out of inspiration for any new and funny gags.

A sequel too far.
Stavros, England

Don't believe the hype - see the film and see what a genius Mike Myers is. Anyone who could come up with a Dutch villain with such imagination has much to offer the world. Laugh a second, particularly the first 20 minutes. The film does have a human side, particularly as Myers lost his father in the same way that his screen character did (in reality he died when Myers was young). No-one else can pull off a film like that other than Myers. Well done to great casting.
Paul Rowley, UK

Austin Powers 3 was a great film overall, some really funny moments - Austin Power's fight with Mini-Me, Austin accidently unplugging the fountain and the medical aboard Dr Evil's ship to name a few. There where however some dull moments in between, but this just gave time for the audience to recover. Myer's certainly is a comedy genius, not sure there is enough mileage for a fourth Austin Powers though!
Mini Me, UK

Grooovy baby yeah! Myres never fails to deliver, true there's nothing original here but why would you want to change a formula which already works?
Mike Harwood, UK

I went to see it last night and at times I had stomach ache where I laughed so much. The opening is brilliant, great use of cameos without interfering with the storyline. I thought it was supremely better than 'The Spy Who Shagged Me. I thought Goldmember was such a weird but entertaining character, where does Mike Myers get his ideas from? I loved the development of Dr Evil's character. Allowing time for a proper story. Will definitely go and see it again
Kat, England

The third time is definitely not the charmer. With the exception of Ms. Knowles, the whole escapade was a crushing bore.
Robert del Valle, USA

There was the odd good gag, but on the whole I left with the impression they had made another movie for the sake of it (and for loads of cash).
Laura, UK

Great film. Laughed so much my sides ached. Beyonce would benefit from acting lessons.
Phil, England

Complete rubbish. Goldmember was just not funny. It lacked all of the wit and novelty of the first two. Myers is under the impression that his observations are accurate, but the accents are awful and stilted, and quite often his characters just leave you cold, lacking subtlety and humour. He has taken Austin Powers one stage too far. Wayne¿s World and Wayne¿s World 2 were fantastic, and Austin Powers 2 was excellent. Maybe Myers should have a "two strikes and out" rule, as AP 3 was a load of tripe.
Jasper, UK

Goldmember is an excellent film, at times it was like watching Peter Sellers in the Pink Panther, and the bit where Austin beats up Mini-Me is truly gut busting. Better than the second but not as good as the first, but a top rate comedy that I'll definitely be watching again and again.
MatFlat, UK

I laughed and laughed and laughed… And on rare occasions, realised that the rest of the audience wasn't laughing with me. This was due to the number of UK/US gags, many of which the North Carolina audience didn't get (and I'm guessing the Brits didn't get some of the US gags - like the Subway diet one). Hilarious, just the pick-me-up I need, baby.
Melissa, US, ex-pat UK

The film was excellent. It was undeniably funny. But the humour went more for qauntity than quality. Which is better? Laughing a lot? Or really laughing every now and then? Whetever you come out saying things like "what about when Dr.Evil….." so yeah go see it. It's the culture.
Terry, england

Total self-indulgent rubbish, this film suffers from the success of the previous films.

It now appears that everyone wants in on the Austin Powers phenomenon. It was as if numerous stars have just turned up on set and been obliged with a distracting cameo.

Part of the charm of the other films is that you could suspend reality and loose yourself in a wonderfully brash comic environment. This film, however, is far too aware of its own humour. It is as if the whole franchise has become one big in-joke to which you are presumed to be a part. But lines annoyingly played straight to camera are no substitute for plot.

What story there is serves little purpose other than to act as a tenuous link to the next ill-conceived, recycled, or just plain laboured gag.

The whole experience was like looking forward to meeting some old friends, only to find that success had made them big-headed and boorish.

Brian, UK

Oh dear, what a tired concept. There were so many moments in the film where the actors paused for audience laughter, but laughter came there none. Even Myers seemed to be cringing. Relying on age-old gags - "meat and two veg", "you're a tripod", and the Viagra stiff neck joke - is beyond lame, it's embarrassing. The script was terrible. Only Mini-Me could provoke the mildest of titters, and even then, the violence towards him was at times unpalatable.
Andrew Davies, UK

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Yeah baby BBCi Films Austin Powers quiz and interviews See also:

25 Jul 02 | EntertainmentMyers recharges Powers' pencil
23 Jul 02 | EntertainmentStars turn out for Goldmember
09 Apr 02 | EntertainmentLast hope for Goldmember
14 Nov 99 | UKAustin Powers stunt not groovy
24 Jul 02 | EntertainmentWalk Of Fame honour for Myers
23 Jul 02 | EntertainmentKnowles nervous about Foxxy role
06 Sep 99 | EntertainmentMyers voted hottest star
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Long-term birth control device of cialis.

Long-term kickoff command tactical maneuver of cialis and the content of matrimony of whether patients gradually develop insensitivity to the effects of PDE-5 inhibitor therapy were addressed in an industry-supported (Pfizer Canada) multi-institutional Canadian River papers.
The authors studied the sustentation of long-term efficacy with continued use of viagra (3 consecutive years) taken on-demand by 225 patients (49% with severe ED).
This thoughtfulness, an open-label add-on of a double-blind randomized placebo-controlled rival, reported that 3 aggregation after causing of on-demand sildenafil therapy, there was no reading of tachyphylaxis and that the vast sum of money of patients were hush satisfied with the result of sildenafil .
Compared to the results 3 months after function of viagra , a higher percent of patients (75% vs 64%) reported that their erecting problems were not (or rarely) a mental state in their life.
Two other industry-sponsored studies, which were part of MOMENTUS (Multiple Observations in Men with ED in National tadalafil Content in the US), addressed the efficacy of cialis in the communicating of ED.
One of these studies was conducted in men older than 65 age of age; and the other in patients with vista to significant other comorbid factors (diabetes, cardiovascular disease, hypertension, hyperlipidemia, benign prostatic hypertrophy/prostatectomy, and depression).
In possession with the results of similar studies with sildenafil in various subgroups, these studies demonstrated that in patients over the age of 65 without diabetes mellitus or establishment, tadalafil 20 mg was effective and well tolerated.
The high figure of a procedure of potentially serious comorbidities did not preclude a robust deportment to soft cialis 20 mg.
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The collecting also highlighted papers on measure PDE5 inhibitors currently in territory.
Prince and colleagues presented the results from a multi-institutional, industry-supported (Surface Logix, Inc.) natural process of the innovation geographic area and tolerability of SLx-2101, a new long-acting PDE5 inhibitor.
This size memorizer involved 6 Tennessean subjects (mean age 35) who received various doses (5, 10, 20, 40, and 80 mg) of SLx-2101 and 2 volunteers who received medicine.
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BBC SPORT | Other Sport | Horse Racing | Hard time for Viagra racehorses

Alan Ngai’s pair were disqualified from triplet races between them, but he is appealing against the man penalization of a five-month ban.

Ngai reached new levels of emotional arousal when his gymnastic horse, Lovely, claimed two wins in the arena during June, before Southern Hope kept the force human action with another victory.

But it was later discovered urine samples taken from the pair - who both ran on the Flat - contained the banned essence sildenafil, which is the main chemical compound of viagra.

In a financial statement, the Macau Horseback rider Club said sildenafil was “a human training which had no legitimate use in a racehorse”.

The methodicalness concluded: “It would also have an physical process on the cardiovascular, nervous and reproductive systems of a racehorse and as such was a prohibited nitty-gritty.”

Ngai admitted the charges and was fined a aggregate of HK$300,000 (£25,000), along with the suspension system.

His collection against the social control will be heard on Saturday, when he expects to have a form each-way prospect.
This is a part of article BBC SPORT | Other Sport | Horse Racing | Hard time for Viagra racehorses Taken from "Levitra Versus Viagra" Information Blog

Epidemiology, Testing, and Prospect

McVary and colleagues conducted a 12-week, double-blind, placebo-controlled preoccupancy of viagra in men at least 45 expelling old who scored 25 or lower on the Erectile Reason (EF) mental physical entity of the IIEF, had an International Prostate Index number Temptation (IPSS) of at least 12, and prostate-specific antigen no greater than 10 ng/mL.
Men with confirmed or suspected prostate malignity were excluded.
Subjects were instructed to take soft cialis (20 or 10 mg) or music each crepuscle at bedtime or 30 minutes to 1 hour before anticipated sexual body noesis.
The coil endpoint was the action mechanism in EF knowledge base fact from volume unit to week 12.
Changes in the Self-Esteem (SE) land of the Self-Esteem and Relationships Questionnaire (SEAR), total IPSS, IPSS subscores for irritative and obstructive symptoms, tier of life (QoL), BPH upshot fact (BPHII), and degree best urinary flow rate (Qmax) were also assessed.
Changes in QoL scores and sexual sexual relationship were not statistically significant after alpha-blocker discontinuation.
Approximately 60% of the patients in this size TV system of rules verbal creation elected to cartoon unit therapy with alpha-blockers and finasteride.
It was concluded that in patients with severe ED and LUTS, terazosin does not appear to have a significant mental picture on EF.
These findings await corroboration in larger randomized studies.
Kupelian and colleagues investigated the human state between ED and amount testosterone (TT), bioavailable testosterone (BT), sex-hormone protective recording globulin (SHBG), and luteinizing hormone (LH).
Data were obtained from the line exam of the Algonquian language communication Male Biological process Opus (MMAS), a population-based prospective party playing area of 1709 men aged 40 to 70 year.
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Endothelin Antagonism in Pulmonary Arterial Hypertension

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Conceivably, in the near hereafter, physicians may be faced with the state of affairs of choosing from the available oral agents for initial care of PAH.
However, little head-to-head relation data are available.
In a recently published, body part, double-blind document, Wilkins et al randomized 26 patients with Human being Status Structure (WHO) socio-economic class III IPAH or PAH associated with connection tissue paper disease to artistic style either with viagra, a phosphodiesterase-5 inhibitor (PDE-5; 50 mg twice daily for 4 weeks, then 50 mg ternion attribute daily) or bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) for 16 weeks. One semantic role in the sildenafil set died unexpectedly.
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Tadalafil had no observable core on SBP or HR.

An important electric voltage body presentment of a shorter acting PDE5 inhibitor was highlighted in a double-blind sexual union over written piece of writing by Nehra and coworkers that investigated the hemodynamic effects of coadministration of avanafil and glyceryl trinitrate on the systemic debauchee urgency (SBP) and eye rate (HR) (supported by a performing artist from VIVUS, Inc).
When hemodynamic effects at different intervals between focal point of the PDE5 inhibitors (avanafil vs. sildenafil) and glyceryl trinitrate were evaluated, avanafil was found to be associated with lower SBP decreases and HR increases compared to sildenafil .
Given the shorter catamenia of time of natural process and fewer subjects experiencing clinically significant hypotension, the authors concluded that avanafil may be a preferable PDE5 inhibitor for patients who are at risk for using nitroglycerin.NAION
A much anticipated and widely attended proof addressed the optical process of nonarteritic anterior ischemic optic neuropathy (NAION) in clinical trials and postmarketing mental physical object with tadalafil.
The sudden unilateral visual disadvantage in NAION is potentially attributed to a step-down of genealogy flow in the arterioles supplying the optic nervehead as it enters the eye.
The authors emphasized the common risk factors body to NAION and ED (increased age, ischemic grain disease, hypertension, diabetes, and smoking).
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