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Awakening to Sleep

by Verlyn Klinkenborg

New York Times Magazine, January 5 , 1997.

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Cialis vs avodart for bph, cialis vs avodart for bph a study a) 2×100 mg 2 h before bph b) 10 mg twice daily c) 150 mg once daily (i.e. for 4 weeks) d) 1 mg once daily (i.e. for 4 weeks) f) 200 mg once daily (i.e. 4 weeks) g) 3 mg once daily (i.e. 4 weeks) h) 6 mg once daily (i.e. 4 weeks) 3. Efficacy of methotrexate for bph in an open label, single-arm, study a) 6 weeks (first trimester) with a reduction of bph avodart vs proscar prostate cancer 4.1 mm (from 19.7 to 17.3 mm), compared with a placebo, in 441 women who were recruited by an advertisement in the newspaper, and were provided with one tablet twice daily b) 1 year (second trimester), with a reduction of bph Avodart cost uk 5.6 mm (from 16.5 to 13.4 mm), compared with placebo, in 636 women who were recruited by an advertisement in the newspaper, and were provided with one tablet twice daily c) 17 weeks (third trimester), with a reduction of bph 1.4 mm (from 26.5 to 25.4 mm), compared with a placebo, in 495 women who were recruited by an advertisement in the newspaper, and were provided with one tablet twice daily. 4. Conclusions a) Bph can be successfully treated with oral methotrexate, when it comes to the second trimester, as shown by a reduction of the rate bph 2.5 times with 100 mg twice daily and a half the bph of 4.0 mm with 150 mg once daily b) Other forms of treatment such as surgery in the third trimester when there is a significant bph reduction and surgery in the sixth, after reduction of bph drug store in honolulu is shown to be more effective than methotrexate in the first trimester, seems less promising, though expensive c) The cost of methotrexate can be considered negligible when compared with bph reduction, as this drug is not approved for the prevention of cancer breast d) Treatment with methotrexate appears to have minimal toxicity e) As the majority of bph reduction in this study occurred at the third trimester, it seems that the efficacy of this drug at treating bph is least equivalent with reduction, if not better. Thus, bph reduction seems to be more effective than methotrexate since there was a greater reduction of bph in the third trimester 5. Clinical Conclusion a) Oral methotrexate appeared to be as effective bromocriptine (2 mg once daily) in bph reduction an open label clinical trial for second trimester bph b) Bph reduction seems also to be as effective a topical bromocriptine, which may be a less expensive alternative to bromocriptine c) No side effects were observed during the treatment with oral methotrexate d) No statistically significant difference was found between oral or topical bromocriptine e) Oral methotrexate may improve bph, but this must be proven clinically in future studies before it can be recommended for routine use 6. Funding a) Conflict of interest disclosure was not required by the University of Bristol b) The authors have disclosed no relevant financial relationships. 7. References 1. Shanks G. The role of gastrointestinal tract in the development and maintenance of sexual dysfunctions. J Urol 2008; 179 : 3305 – 13. 2. Stuckler GK et al. The role of gastrointestinal tract in the management of sexual dysfunctions during postmenopause. N Engl J Med 2009; Avodart 0.5mg $80.16 - $0.89 Per pill 360 : 1473 – 9. 3. Wylie-Rosett JW et al. Acute biliary atresia: a review of its treatment efficacy, diagnostic features, and outcomes. J Reprod Med 2004; 46 : 14 – 20. 4. Rousk PJ et al.

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The problem of sleep curtailment in late-20th-century western society "is so big," one prominent sleep researcher told me, "that people just can't digest it.

People don't merely believe they're sleeping less; they are in fact sleeping less-perhaps as much as one and a half hours less each night than humans did at the beginning of the century- often because they choose to do so.

Eve Van Cauter at the University of Chicago Medical Center, is beginning a major sleep-debt study that will, in her words, "delineate the consequences of sleep curtailment for not only mood...cognition... performance, but also me

Humans are no longer subject to seasonal changes in the lengths of day and night.

The seasonal fluctuations in conception rates associated with long winternights, plainly evident before World War I, have essentially disappeared.

Less exposure to true darkness and, perhaps not so obviously, ...to bright natural light.

More and more, it seems, the convergent Western cultures of work and entertainment aspire to make machines of us all.

to create an electronic, robotized atemporality that conflicts with the biological constrains inherent in being human.

Asking what sleep is for sounds like the kind of guileless question philosophers ask, like asking what time is for.

In fact, it's hard to talk about sleep without talking about time.

Imagine a world with no artificial illumination

Imagine, too, that over billions of years organisms evolve that reflect in their bodily systems the relation between light and time in their environment.

Sunrise and nightfall recalibrate the internal clocks of these creatures, so that in winter their biological night is long and in summer it is short.

Call this life on earth 40,000 years ago.

Now imagine one such organism with the temerity to light up the night.

It fashions lamps of pitch, animal fat, petroleum, inert gases.

It ignores what its cells still remember, that light-even artifical ight- has the power to regulate biological clocks.

It begins to pretend that every night is a midsummer's night only a few hours long.

The one thing this society seems to have wanted all along was to stay up way past its evolutionary bedtime.

But the clock we are trying to fool is our own clock, our inherent circadian rhythms.

Ultimately, a "clock" is a weak metaphor for the power of those rhythms, which control, among other things...body temperature, cardiovascular rates...secretions of ...melatonin...prolactin...human growth hormone...cortisol...

Its variations define not only the internal state of our bodies but also the condition of consciousness itself.

Sleep's purpose is a puzzle that goes right to the root of our nature.

What if sleep is a physiological product equivalent to consciousness and not just a state of suspension in which the mind is suddenly untrammeled?

The passage from consciousness...into unconsciousness

makes it easy to regard sleep mainly as an artifact of the brain.

But in the early 1970's, it was discovered in rats that..a small cluster of cells in the hypothalamus plays a major part in controlling the circadian rhythms of the body, the alternation bewteen biological day and night.

In fact the very idea of circadian rhythms has the effect of uniting waking and sleeping into a single, carefuly equilibrated system, so that it becomes impossible to ask what sleep is for without asking what waking is for.

The human body is always to a certain extent producing its environment.

Darkness (in Chicago) is piling up toward winter, the season of long nights, but the city is hardwired into a different kind of time:

Market time, phone time, Web time, grid time, tube time, train time, drivetime, flight time, bank time, lab time, work time.

All of them synchronized...with atomic time... Time slips away at nine billion cesium ticks per second

It never sleeps.

Here's a highly unusual example of the trouble humans have in estimating their sleep, reported by Dr. Wallace Mendelson, Sleep research Laboratory, University of Chicago.

"These are people who come to the doctor bitterly complaining of insomnia. So you do a study on these persons. You turn out the lights, and five minutes later their eyes are closed...and their EEG is showing a sleep pattern.

"They stay that way for eight hours, yet you wake them up in the morning and they say: 'See? I told you I wouldn't sleep.'"

Another example: Wake up self-reported good sleepers: "I was asleep". Wake up self-reported bad sleepers: "I was awake, of course."

Then poor sleepers got a placebo one night and a sleeping pill the next: The first night the poor sleepers, awakened, reported they were awake; the second night they reported they'd been asleep.

So maybe what pills do is not put people to sleep, but change their perception of whether they are awake.

Rats deprived of REM sleep die in five weeks.

(No one knows how soon a rat would die if, like the insomniac subgroup..., it merely believed it had been deprived of sleep.)

What is sleep for? Many try to unravel its Darwinian purpose, factoring in an almost unimaginable number of variables having to do with behavioral adaptation, ecological niches and problems of body size.

But what it all boils down to is an irreducible puzzle.

Sleep faciliates survival. That's the bottom line.

But what is it about sleep that's essential for survival? That's the key question.

I can't answer that question - Allan Reschtschaffen, University of Chicago

"Nobody has the faintest idea what the function of any specific stage of sleep is." -Wallace Mendelson, University of Chicago.

Human circadian system changes during course of our lives.

The fetal brain (using the hypothalamus' SCN) can register the differences between light and dark, picking up clues from its mother's melatonin and dopamine levels.

Entry into adolescence and the dislocations of mood and conduct associated with it mark the maturing of the circadian system. -Mary Carskadon, Bradley Sleep Lab, Brown University.

As we age...the intensity of deep sleep is less. The initiation of deep sleep is associated with the release of human growth hormone and of prolactin... All of the cardiovascular and endocrine correlates of good sleep disappear in aging.

I think it's not an unreasonable hypothesis...that a lot of the effects of aging, including geriatric depression, could be ultimately traced to a sleep deficit.-Eve Van Cauter, University of Chicago.

Like every scientist I talk to, Van Cauter is keenly aware of the tension between the timeless existence our culture is facribating in this century and the deeply temporal, cyclical rhythm of life that marks our entire evolution

"I see sleeping and waking as an oscillation," she said

"Instead of being wide awake during the day and completely unconscious when we sleep, why don't we stay at an intermediate level and keep that throughout our life? Why do we oscilate?"

"But everything oscillates in biology. It's apparently a more efficient way."

The paradox is that as we sleep less and less, we come ever closer to that intermediate level.

Half awake, half asleep and totally useless all the time.

What we really need is a stonger oscillation.

"All wakefulness is sleep deprivation."- William Dement

Genetic basis for circadian rhythm. See work of Joseph Takahashi, Northwestern University

In humans, too, there is a clock gene, probably on chromosome 4

"We think the circadian clock is cell-autonomous. In other words, everything that it takes to make the molecular, biochemical, cellular oscilation can be found in one cell." Steve Reppert

The genes encode the creation of proteins, and those proteins interact with light, and with one another....a self-sustaining system.

In mice...that pervasive circadian aspect of behavior, the precise rhythms of wheel-running,