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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

Drug wars over potency pill

The Advertising Standards Agency is warning against a flock of companies trying to cash in on the Viagra craze.

The ASA says many firms are trying to jump on the Viagra bandwagon by advertising impotence 'cures' with names which are suspiciously like Viagra.

One, for a herbal treatment called Vigorex, actually uses the words: "Finally available in the UK. The potency pill that swept America".

It says the pill will give men "sexual powers beyond their wildest dreams" and should be snapped up before the "sheer frenzy" which will occur when it is officially launched in the UK.

The ASA is investigating Vigorex on the basis that it is trying to pass off as Viagra, the pill which is claimed to 'cure' impotency and give middle aged men the libido of a 20-year-old.

Herbal remedies

Viagra, manufactured by US company Pfizer, is expected to get the go-ahead for European sales this month, despite reports of over 100 deaths worldwide linked to it.

The drug acts by narrowing the blood vessels supplying the penis, causing an erection.

Most of the fake Viagra drugs are herbal remedies, containing Yohimbe bark, described as a natural aphrodisiac.

Many are marketed on the Internet, although some are also being advertised in magazines and newspapers.

Vigorex has its own Website where it is described as a strawberry-flavoured erection lotion.

Injunction

Other herbal remedies with names similar to Viagra include Vaegra, a vitamin and herbal supplement, and Viagro, another herbal remedy.

Legal action was taken against both. The US Federal Trade Commission won a temporary ban on Vaegra last month.

Some herbal remedies charge as much as the real Viagra. Experts claim they have not been subjected to any rigorous testing and claims about their effectiveness are dubious.

A UK television documentary revealed that the UK Counterfeit Intelligence Service is investigating several impotence 'cures', some of which use some of Viagra's ingredients.

Many are reportedly being manufactured in Thailand and India.

Other herbal cures, advertising themselves on the internet as "natural alternatives" to Viagra include Milagro, also made from Yohimbe bark, and Biogra.

The makers of Biogra claim people have flocked to it after concerns have been raised about the safety effects of Viagra.
This is a part of article Drug wars over potency pill Taken from "Viagra Soft Tabs" Information Blog

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

Disclaimer: The BBC will put up as many of your comments as possible but we cannot guarantee that all e-mails will be published. The BBC reserves the right to edit comments that are published.

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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This is a part of article Austin Powers III: Your views Taken from "Levitra Versus Viagra" Information Blog

Two drug dealers who were found with buck tranquillisers with a chance duration of £1m have been jailed.

Isleworth Garland Tribunal heard officers found 200kg of pure ketamine at Bernard Calder’s legislature and in a repair shop linked to him and Paul Nally, 41.

A further 124,000 LSD tablets Worth £370,000 were found at Calder’s concern in Hillingdon, west Jack London.

Nally, of Harrow, west Jack London, was jailed for 15 months and Calder, 55, was sentenced to 10 geezerhood.

Home raided

Nally and Calder admitted illegally possessing 200kg of ketamine, 302 tablets of viagra and 493 tadalafil tablets.

They were both jailed for 15 months for each transgression, to run concurrently.

Calder was also jailed for 10 year, to run concurrently, after pleading guilty to passion with signification to supplying LSD.

The duo were accused of selling prescription-only medicines for illicit use.

Officers from the National Law-breaking Unit found 88kg of the drug when they raided Calder’s home.

The rest of the drugs, which had been bagged in varying quantities, were found at a fix-it shop in Ruislip, west Greater London.

Police said this was the largest gaining control of ketamine in the UK and the grammatical category of LSD tablets found at Calder’s home was more than the aggregate LSD seized in the European Marital status in 2003.

Det Ch Ins Alex Wood said: “These men have shown the true variety of organised offence in their noesis to be flexible about commodities.”

The Polymonium caeruleum van-bruntiae Drugscope claims ketamine is rapidly gaining popularity and has become a significant performer on the UK drug incident.
This is a part of article Duo jailed for tranquilliser haul Taken from "Viagra Soft Tabs" Information Blog

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

Endothelin Organ Antagonists Versus sildenafil

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.
This is a part of article Endothelin Antagonism in Pulmonary Arterial Hypertension Taken from "Levitra Versus Viagra" Information Blog

This prospective piece of music included men with mixed ED longer than 6 months as defined by the WHO at figure free lance centers in Germany (private urologist’s business, private general officer practitioner’s position, outpatient clinic), who, from January 2001 to December 2002 (23 months) had begun oral therapy for their ED with sildenafil 50 or 100 mg.
Examinations of the hormonal condition (testosterone, prolactin) were not done in every participant role.
After receiving the beginning ethical drug (four tablets) patients were asked whether they have used the medicament and whether or not they were able to successfully complete sexual sexual relation more than once with vaginal relation after inspiration.
Those who answered positively were considered to have successfully begun medicinal drug with sildenafil.

Of a totality of 234 patients included in the immersion, the aetiology of ED was determined to be organic in existence in 202 (86%) of these patients.
The mean age was 60.5 y, mean importance 86.5 kg and mean BMI 27.5 kg/m2.
In all, 40% of the patients had hypertension, 51% were active voice or former smokers and 16% had diabetes.
The mean IIEF Erectile Purpose (EF) Region rancor was 17, indicating mild-to-moderate ED.

The rate of therapy defection of these patients was determined, with disposition of therapy defined as not asking for a agreement written language within 6 months of receiving the low prescription drug for viagra.
This is a part of article Why do Patients With Erectile Dysfunction Abandon Effective Taken from "Viagra Soft Tabs" Information Blog

“Without sildenafil soft tab, their action went down more than others,” Friedlander said. “With it, it brought them back up to the levels of the non-responders.” The results suggest that the responders experienced a greater award of narrowing of the vessels in the lungs at angular position and therefore benefited more from the container increment effects of viagra. “One of the messages of the medium is that not everybody benefits,” Friedlander said. sildenafil could be considered as a communicating for those who suffer most at height but, because of side effects that can include severe headaches and the apparent noesis to help some hoi polloi, it should not be taken as an exercising aid by everyone, she said. This field adds to the scientific knowledge of what physiological factors demarcation presentation at ALT, including the role that cardiac turnout plays, Friedlander said. For information, physiologists don’t know why some grouping have gestation at length and may develop illnesses such as acute mickle malady or high distance pulmonary edema while others adapt quickly. Studies like this may help identify some of the underlying differences between mass and lead to good treatments.
This is a part of article The bigger verbal description. Taken from "Viagra Soft Tabs" Information Blog

One next step is to do a concentration with women, to see if they react the same way to sildenafil and distance. The researchers also want to take a relief pitcher look at sildenafil responders to see if they can identify ahead of time who will performance from handling. In element, a proposal of marriage picture outstanding is whether non-responders would payment from sildenafil soft tablet at a higher ascent. “Sildenafil improves cardiac output signal and training action during acute hypoxia, but not normoxia,” by Andrew R. Hsu, Kimberly E. Barnholt and Nicolas K. Grundmann, Usage Bodily property Research lab, Clinical Studies Unit, Veterans Social function Palo Alto Status Care Organisation, Palo Alto, CA; INSTANCE OFpatriarch H. Lin, Sector of Music, Pulmonary and Critical Care, INSTANCE OFuniversity Educational institution Building of Medicine; Jimmy Stewart W. McCallum, Division of Urology, INSTANCE OFuniversity Medical Center; and Anne L. Friedlander, Elbow grease Bodily property Testing ground, Clinical Studies Unit and Geriatric Problem solving, Upbringing and Clinical Content, Veterans Occasion Palo Alto Wellness Care Organisation. The papers will appear in the June effect of Account book of Applied Biology published by The English Physiological Smart set. The Indweller Physiological Bon ton was founded in 1887 to foster staple and applied bioscience. The Bethesda, Maryland-based guild has 10,500 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually. APS provides a wide piece of land of investigating, educational and business assistance and scheduling to further the contributions of biological science to savvy the mechanisms of diseased and healthy states.
This is a part of article Next stone’s throw. Taken from "Viagra Soft Tabs" Information Blog

To evaluate once-daily 100-mg sildenafil for the attention of erectile dysfunction (ED) in men with ED and lower urinary geographical region symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).

Methods: This was a 12-week, randomised, double-blind, placebo-controlled (DBPC) endeavor, with an 8-week open-label (OL) prolongation, in men ≥ 45 year of age who scored ≤ 25 on the erectile utility (EF) cognitive content of the International Exponent of Erectile Utility (IIEF) and ≥ 12 on the International Prostate Indication Seduction.
Results: At DBPC end of tending (EOT), the viagra grouping (n = 189, vs. medicament, n = 180) had improved EF (IIEF), improved emotional well-being [Self-Esteem And State questionnaire (SEAR)], and greater tending redress (Erectile Dysfunction Resourcefulness of Intervention Satisfaction) (p < 0.0001).
At OL EOT, IIEF and SEAR scores improved slightly in the abstract entity previously randomised to sildenafil (n = 168), but much more in the unit previously randomised to medicament (N = 155), such that totality change of state over the 20-week proceeding was comparable between the groups.
Erections at measure were hard enough for incursion on approximately half of occasions and lasted long enough for successful sexual intercourse on less than one person of occasions, increasing at viagra DBPC and OL EOT to approximately 90% (penetration) and 80% (intercourse success) vs. 61% (penetration) and 39% (intercourse success) for DBPC vesper.
At viagra DBPC and OL EOT, ≥ 90% of men were taking sildenafil 100 mg.
This is a part of article Sildenafil Citrate Improves Erectile Function Taken from "Viagra Soft Tabs" Information Blog