If you would like to receive a complete copy of these studies, please contact us and we will send you a copy via email.
Lung Cancer Survival With Herbal Medicine & Vitamins In A Whole-Systems Approach: 10-Year Follow-Up Data Analyzed With Marginal Structural Models and Propensity Score Methods
McCulloch MF, Broffman M, van der Laan M, Hubbard A, Kushi L, Kramer A, Gao J, Colford JM: Lung Cancer Survival With Herbal Medicine & Vitamins In A Whole-Systems Approach: 10-Year Follow-Up Data Analyzed With Marginal Structural Models and Propensity Score Methods. 2011. [Epub ahead of print, PMID 21964510] Integrative Cancer Therapies.
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21824893
Abstract: Complementary and alternative medicines are used by up to 48% of lung cancer patients but have seen little formal assessment of survival efficacy. In this 10-year retrospective survival study, the authors investigated Pan-Asian medicine + vitamins (PAM+V) therapy in a consecutive case series of all non-small-cell lung cancer patients (n = 239) presenting at a San Francisco Bay Area Chinese medicine center (Pine Street Clinic). They compared short-term treatment lasting the duration of chemotherapy/radiotherapy with long-term therapy continuing beyond conventional therapy. They also compared PAM+V plus conventional therapy with conventional therapy alone, using concurrent controls from the Kaiser Permanente Northern California and California Cancer Registries. They adjusted for confounding with Kaplan-Meier, Cox regression, and newer methods – propensity score and marginal structural models (MSMs), which when analyzing data from observational studies or clinical practice records can provide results comparable with randomized trials. Long-term use of PAM+V beyond completion of chemotherapy reduced stage IIIB deaths by 83% and stage IV by 72% compared with short-term use only for the duration of chemotherapy. Long-term PAM+V combined with conventional therapy reduced stage IIIA deaths by 46%, stage IIIB by 62%, and stage IV by 69% compared with conventional therapy alone. Survival rates for stage IV patients treated with PAM+V were 82% at 1 year, 68% at 2 years, and 14% at 5 years. PAM+V combined with conventional therapy improved survival in stages IIIA, IIIB, and IV, compared with conventional therapy alone. Prospective trials using PAM+V with conventional therapy for lung cancer patients are justified.
Colon Cancer Survival With Herbal Medicine & Vitamins In A Whole-Systems Approach: 10-Year Follow-Up Data Analyzed With Marginal Structural Models And Propensity Score Methods
McCulloch MF, Broffman M, van der Laan M, Hubbard A, Kushi L, Abrams DI, Gao J, Colford JM: Colon Cancer Survival With Herbal Medicine & Vitamins In A Whole-Systems Approach: 10-Year Follow-Up Data Analyzed With Marginal Structural Models And Propensity Score Methods. 2011. Sep 30. [Epub ahead of print, PMID 21964510] Integrative Cancer Therapies.
PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21964510
Abstract: Although localized colon cancer is often successfully treated with surgery, advanced disease requires aggressive systemic therapy that has lower effectiveness. Approximately 30% to 75% of patients with colon cancer use complementary and alternative medicine (CAM), but there is limited formal evidence of survival efficacy. In a consecutive case series with 10-year follow-up of all colon cancer patients (n = 193) presenting at a San Francisco Bay-Area center for Chinese medicine (Pine Street Clinic, San Anselmo, CA), the authors compared survival in patients choosing short-term treatment lasting the duration of chemotherapy/radiotherapy with those continuing long-term. To put these data into the context of treatment responses seen in conventional medical practice, they also compared survival with Pan-Asian medicine + vitamins (PAM+V) with that of concurrent external controls from Kaiser Permanente Northern California and California Cancer Registries. Kaplan-Meier, traditional Cox regression, and more modern methods were used for causal inference-namely, propensity score and marginal structural models (MSMs), which have not been used before in studies of cancer survival and Chinese herbal medicine. PAM+V combined with conventional therapy, compared with conventional therapy alone, reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%. There was no significant difference between short-term and long-term PAM+V. Combining PAM+V with conventional therapy improved survival, compared with conventional therapy alone, suggesting that prospective trials combining PAM+V with conventional therapy are justified.
It’s been another fantastic year at the Pine Street Foundation…we’ve published peer-reviewed research, presented papers at conferences, received lots of media coverage in the national press, hosted community health screenings, and made huge strides with all our other ongoing research projects.
Published Research: Complementary & Alternative Medicine For Lung & Colon Cancer
For patients with lung and colon cancer, does adding complementary and alternative medical (CAM) therapy to standard treatment extend survival? We analyzed more than 10 years of follow-up data from the Pine Street Clinic for patients who used CAM therapy and compared their outcomes to a control group. In two papers published this autumn in Integrative Cancer Therapies, one of the most important peer-reviewed journals in this field, we found that patients who took an integrative approach had significantly better longevity than those patients who only had standard treatment. Click here for more.
Continuing Research: Can Dogs Detect Ovarian Cancer?
Is there meaningful information contained within the breath that could lead to the early detection of ovarian cancer? In collaboration with Baylor University and the University of California at San Francisco, we are using dogs to find biomarkers in the exhaled breath of women with ovarian cancer that could lead to earlier detection – and better treatment outcomes – for women diagnosed with this disease.
We’ve made great progress on this study this past year and, in preliminary analysis of our data, have seen that training dogs to detect ovarian cancer is highly feasible and efficient, similar to what was seen in our 2006 paper on patients with lung and breast cancers.
To complete this study, we just need to recruit eight more women who are either newly diagnosed with ovarian cancer but have not yet begun treatment, or have been previously treated and now have a rising CA-125 but have not yet resumed treatment. Click here to see if you or someone you know is eligible to participate.
As The Year Draws To A Close…
Whether you’ve known us since 1989 or have only recently discovered our work, it is important to note that the Pine Street Foundation is one of the most efficient and cost-ef- fective research organizations of its kind in the country. And since the vast majority of all our funding comes from individual donors like you, your financial support truly helps us advance the field of integrative medicine and benefits those in need of better treatments. Click here to make a secure donation now.
As you consider your year-end charitable giving, please keep the Pine Street Foundation in mind. We really appreciate it!
Pine Street Foundation
2011 PUBLICATIONS (PEER REVIEWED)
1. McCulloch MF, Broffman M, van der Laan M, Hubbard A, Kushi L, Kramer A, Gao J, Colford JM: Lung Cancer Survival With Herbal Medicine & Vitamins In A Whole-Systems Approach: 10-Year Follow-Up Data Analyzed With Marginal Structural Models and Propensity Score Methods. 2011. [Epub ahead of print, PMID 21964510] Integrative Cancer Therapies.
2. McCulloch MF, Broffman M, van der Laan M, Hubbard A, Kushi L, Abrams DI, Gao J, Colford JM: Colon Cancer Survival With Herbal Medicine & Vitamins In A Whole-Systems Approach: 10-Year Follow-Up Data Analyzed With Marginal Structural Models And Propensity Score Methods. 2011. Sep 30. [Epub ahead of print, PMID 21964510] Integrative Cancer Therapies.
3. See, CJ, McCulloch MF, Smikle C, & Gao J. (2011). “Chinese herbal medicine and clomiphene citrate for anovulation: a meta-analysis of randomized controlled trials.” Journal of Alternative and Complementary Medicine 17(5): 397-405.
2011 Novel Statistical Approaches to Evaluating Whole Systems Therapies: The Case of Lung and Colon Cancer Survival
2011 Project-Based Learning: Research in Chinese Medicine, A Course for 3rd year students on how to read, and conduct research. American College of Traditional Chinese Medicine. San Francisco, CA. (Presented in two consecutive semesters)
REVIEWER FOR THE FOLLOWING JOURNALS & COMPETITIONS
European Respiratory Journal: 2011
Integrative Cancer Therapies: 2011
We held two free health screenings for members of our community in Marin County, California. Click here to learn more about these events.
In the autumn of 2011, we published the Pine Street Survival Study, our landmark lung and colon cancer survival study research papers. Both papers were published in one of the leading journals focusing on Complementary and Alternative Medicine (CAM) specific to the needs of people with cancer: Integrative Cancer Therapies.
In our study, we looked at whether complementary and alternative medical therapy in combination with standard treatments helped extend survival in people with lung and colon cancers. The treatments being examined combined Chinese herbal medicine, vitamins, acupuncture, exercise, dietary guidance, and meditation into a comprehensive approach that in research is called a “Whole Systems” protocol.
In conducting this study, the Pine Street Foundation collaborated with scientists at the University of California Berkeley, University of Cali- fornia San Francisco, Kaiser Permanente, and the California Cancer Registry. Pine Street’s Clinical Director, Michael Broffman, led data collection efforts and Research Director, Michael McCulloch, designed the data analysis, which involved a novel approach that had not yet been done before with CAM studies of cancer treatment.
The primary data source being used for the Pine Street Foundation’s Survival Study is a large database developed from ten years of follow- up records on patients treated between 1989 and 1993 at the Pine Street Clinic in San Anselmo, California. This database contains follow- up results on 235 patients with lung cancer and 193 patients with colon cancer. Because these data were recorded in a consecutive case series, they contain the records of all patients with these conditions treated by the Pine Street Clinic. This is important because the survival data from this set of patients are a complete representation of the treatment experience at the Pine Street Clinic with these patients, and not sim- ply the hand-picked “best case” records often seen in studies of CAM therapies.
The common variables examined for each patient included how long patients received a specific therapy as well as specific dosage schedules of herbal-vitamin products. Data have also been collected on the most important characteristics of patients treated, including age, gender, biopsy results (cell type), stage of disease, type of conventional treatment received, and ethnicity. This allowed for the analysis of the impact of treatment protocol on overall survival.
Using these data, survival among the Pine Street Clinic patients – those using CAM – was compared to survival of patients who did not use CAM. Those comparison patients were obtained from data from local Kaiser Permanente hospitals as well as from the National Cancer In- stitute’s Surveillance, Epidemiology, and End Results (SEER) database.
RESULTS OF THIS STUDY
Patients with both lung and colon cancers who used herbal and vitamin therapy had significantly longer survival than carefully matched controls whose records were obtained from local cancer registries:
» In patients with lung cancer, combination therapy reduced the risk of death in stage IIIA patients by 46%, stage IIIB by 62%, and stage IV by 69%, compared with conventional therapy alone.
» In patients with colon cancer, combination therapy reduced the risk of death in stage I by 95%, stage II by 64%, stage III by 29%, and stage IV by 75%, compared with conventional therapy alone.
Patients with advanced (stage IIIB and IV) lung cancer who continued with long-term use of herbal and vitamin therapy after treatment survived significantly longer than those who used it only short-term during their chemotherapy programs:
» Long-term use of herbal/vitamin therapy beyond completion of chemotherapy reduced stage IIIB deaths by 83% and stage IV by 72%, compared with short-term use only for the duration of chemotherapy.
For colon cancer patients, however, there was no significant difference in survival between people using CAM short-term versus long-term.
WHY THIS STUDY IS IMPORTANT
Large numbers of people throughout the United States – as many as 36% of adults – are using complementary and alternative medicine. However, there are very few published papers that specifically examine one of the most important questions patients diagnosed with cancer ask: Will combin- ing complementary and alternative medicine together with my conventional therapies help me live longer? Our papers provide preliminary data suggesting that the approach used in our Pine Street Survival Study (a comprehensive combination of herbal medicine, antioxidants, vitamins, exer- cise, healthful eating, and stress reduction) can significantly improve longevity when used in concert with conventional treatments.
If you would like to receive a complete copy of these studies, please contact us and we will send you a copy via email when we have permission from the publisher to do so.
The Pine Street Foundation is sponsoring a live public debate, held in San Francisco on June 11, which all are welcome to attend. This event will be a fun, entertaining, and informative way for the public to hear a spirited discussion about issues concerning us all in Chinese medicine. The debate brings together in a public forum many well-known names from the field, debating important questions facing the profession today.
2010 has been a productive year for the Pine Street Foundation. We’ve published peer-reviewed research, presented papers at conferences, received lots of media coverage in the national press, and reached thousands of patients and doctors through our newsletter, Avenues.
Scent Identification in Criminal Investigations and Prosecutions. In this comprehensive summary of the use of canine scent lineups in the investigation of crimes, we review the proper procedures helping establish scent lineups can be valuable evidence for a jury to consider. Click here to read the full paper.
We’ve submitted for publication a landmark cancer survival study in collaboration with Kaiser Permanente, the Northern California Cancer Center, and the University of California at Berkeley. This research project encompasses a 10-year follow-up of patients with lung cancer and colon cancer, addressing the question of whether complementary and alternative medical therapy in combination with standard treatments can help extend survival. By using data about these patients gathered over a ten-year period, this study will explore the potential survival benefits associated with long-term use of an herbal-vitamin combination protocol. These two papers are now in the peer-review process.
We’re presented our research results at two conferences:
- The Annie Appleseed Foundation, in Florida
- A conference for researchers in canine scent detection, in the Netherlands
Avenues Newsletter Distributed
In 2010, we physically distributed nearly 15,000 copies of our newsletter, Avenues, bringing our audience important information such as our comprehensive reviews on the benefits of vitamin D3 and uncovering some of the many issues surrounding the massive efforts directed against the swine flu outbreak. Additionally, thousands copies have been electronically downloaded from our website.
New Research Initiative Launched
We’ve launched a new research initiative, a systematic review and meta-analysis of all published randomized trials in which patients treated with Chinese herbal medicine combined with chemotherapy were compared to those treated with chemotherapy alone. Pine Street researchers will be looking for the impact of Chinese herbal medicine on both immediate results (do people using herbal medicine experience less damage to white blood cells or less drug toxicity?) and long-term results (do people using herbal medicine live longer after treatment and is their quality of life better?), as compared to treatment with chemotherapy alone. We will also be looking carefully at the quality of the published studies. Most of the studies we have located in our systematic search of the medical literature were published in China and one of our goals with this meta-analysis is to better understand the level of scientific quality of these studies; many researchers in the Western scientific community have criticized Chinese studies for their low quality of design and reporting. By analyzing these studies, we’ll determine what study quality problems are most significant and where improvement is needed. Pine Street has three primary aims in conducting this meta-analysis. First, we are using the results of this study as a basis for designing a double-blinded, randomized trial for patients with colon cancer. Second, by pointing out where improvements in study methodology are needed, we hope to contribute to the improvement in quality of clinical studies in China. Third, we want to educate readers outside of China on the vast quantity of research being conducted there, research that highlights the potential clinical benefits of integrative medical care.
A Selection of Media Clippings from 2010
Parade Magazine: Our work was prominently featured in the article “Cancer In America: Sniffing Out Disease.”
Huffington Post: In an op-ed in the Huffington Post, John Robbins wrote: “If you want to support an organization fighting breast cancer, you might want to know about the little known but extraordinary Pine Street Foundation.”
We were included in Cesar Milan’s new book, Cesar’s Rules: Your Way to Train a Well-Behaved Dog. Click here to read the chapter.
Everyone knows that sleep is important. Yet, as a nation, we’re sleeping a full hour less per night on average than we were just ten years ago.(Jean-Louis, Kripke et al. 2000) This trend is certainly not new; for more than 25 years, Americans have been sleeping less and less each night and, in a recent study, up to half of all American adults report having sleep problems in any one year. (Becker 2006) Of all the sleep disorders, insomnia is, by far, the most common, affecting nearly 70 million of us; in a recent sur- vey, 35% of respondents had insomnia every night and nearly 60% reported insomnia at least a few nights per week. Sleep problems have been dubbed “a hallmark of modern living.”(Bollinger, Bollinger et al. 2010)
Why this is happening is not clear. Is it because we often favor work, play, socializing, or learning over sleep? Are we sleeping less because of problems with our local living environ- ment? Are sleep disturbances really a sign of some underlying disease? Is the problem, as many want to suggest, simply stress? While most people do experience some level of stress in their lives, one theory is that it’s a deficiency in positive coping skills, rather than the stress itself, that lets the body veer out of balance and causes sleep problems. Also interesting to note, recent re- search suggests that high positive emotions (not just high nega- tive emotions) can also cause a poor night’s sleep, too.(Baglioni, Spiegelhalder et al. 2010)
Given that so many of us aren’t getting enough high-quality sleep, it is worthwhile to educate ourselves on how sleep or sleep deprivation affects our health. What do scientists know about sleep? Why do we even need to sleep? How many hours of sleep do we really need each night and what happens if we sleep for less than this optimal number? Equipped with answers to these questions, we will be more apt to make healthy choices regarding sleep.
WHAT IS KNOWN ABOUT SLEEP?
What Happens During Sleep & Why Do We Need It?
Sleep may have given humans an evolutionary advantage, pro- ducing immobility at times when activity would be unproductive (preventing wasteful energy expenditure) or dangerous (prevent- ing unnecessary exposure to predators).
Sleep was first described physiologically in the 1930s(Loomis, Harvey et al. 1935) and our understanding was greatly enhanced by the discovery of rapid eye movement (REM) in the 1950s.(Aserinksy and Kleitman 1953) Our sleep is usually divided into various phases, based on the differences in brain activity throughout the night. During these various phases, our bodies repair and our memories are organized.
Current research suggests that the interplay between ho- meostasis and circadian rhythm determines our sleep pattern. Homeostasis, which is the ability of the body to adjust its physi- ology in response to fluctuations in the outside environment and the weather, would have us sleeping in small increments through- out the day to balance our wakeful hours.
Circadian rhythm, on the other hand, is the 24-hour cycle in physiological functioning found in most living organisms. Until recently, it was assumed that the human circadian rhythm was also 24 hours in length. However, there are several curious anomalies to human circadian rhythm for which a clear answer is not yet available. Two unique features of the human circadian system are (1) an internal tendency toward “desynchronization,” in which core body temperature has a cycle of about 25 hours, and (2) a sleep-waking cycle of about 30 hours.(Yamanaka, Honma et al. 2009) While it is now known that exposure to bright light appears to re-synchronize the body to the planetary 24-hour cycle,(Yamanaka, Honma et al. 2009) it is not yet clear why the body’s day/night clock is longer than the duration of one day.
A comparison to simpler organisms is also curious: hu- man beings experience drastic disturbances to our biological clocks with sudden shifts in our daily schedules, leading to sleep disorders, mood disorders, and impaired performance. Honey- bees, on the other hand, do not have this liability and are able to very quickly adjust their own physiological rhythms when they are subjected to drastic changes in their work schedules. It is the complex and highly interactive social environment of the honeybees that help them in making these nimble adjustments. (Shemesh, Eban-Rothschild et al. 2010) Perhaps this tendency for the human nervous system to drift toward desynchronization is the result of having a very well-developed brain; it is analogous to high-performance sports cars, where greater sophistication requires more frequent maintenance and tune-ups.
The Problem Doesn’t Start at Bedtime
One reason a person’s night can become disturbed is because their day is out of balance. If you can’t get to sleep, the problem didn’t begin just at that moment, but can have its roots much further back in time. In the physiology of the body, timing is a critical issue and a person’s misuse of time can lead to loss of coordina- tion between important body functions, a term called chrono- disruption. Whether this chrono-disruption, or “physiological bad timing,” is the result of poor sleep, or can itself cause sleep disorders, is not clear. However, both common sense and the following research data would suggest that conducting oneself contrary to one of nature’s most fundamental cycles of time, the diurnal rhythm (or daytime-nighttime cycles), is probably not a good idea.
The Role of Light
Light plays a key role in our sleep cycle, centered on critical light-receptive cells on the retina of the eye that help regulate not only circadian timing and neuroendocrine function, but also a person’s behavioral responses. When exposed to bright light, those photoreceptive cells stimulate parts of the brain that are not image-forming centers, but serve primarily as the body’s master biological clock. Furthermore, when the retinas are exposed to light much more dim than sunlight (as is most indoor lighting),
this light deficiency causes an information deficiency in the brain that sets in motion a chain-reaction of harmful side-effects in- cluding insomnia, depression, and impaired cognition.(Turner, van Someren et al. 2010) In other words, if you spend most of your daytime hours indoors, you may well be “light deficient.” This daytime light deficiency may be a common cause of night- time sleep disorders.
Recent research from the Institute of Medical Microbiology and Hygiene in Germany provides detailed insights that were first explained by 3rd Century BC medical texts from China: That circadian rhythm is controlled by both central control systems in the brain as well as local/regional cellular centers in other body tissues. For the immune system specifically, the effect of sleep deprivation can be to inhibit immune function by disrupting the circadian rhythms within immune system cells themselves, which in turn may be a long-term consequence of disturbances in hormonal cycles and circadian rhythms. These researchers also suggest that sleep, through the lowering of body temperature, “primes” the cells of the immune system and by doing so provides a timing signal for circadian clocks in the blood cell-producing bone marrow. It is chronic sleep disruption that desynchronizes these different time clocks, which in turn leads to dysregulation of the body’s immune responses.(Bollinger, Bollinger et al. 2010)
Sleep & Learning
One important function of sleep that is of interest to students is that it consolidates or reorganizes memory.(Kopasz, Loessl et al. 2010) Based on the results of three separate meta-analyses of 17 studies conducted by a team in the netherlands, successful learning and school performance are linked to sleep quality, sleep duration, and the absence of daytime sleepiness.(Dewald, Meijer et al. 2010) This means that in order to remember what you stud- ied during the day, you need to get a good night’s sleep at night. Renowned sleep researcher Matthew P. Walker at the University of California at Berkeley has also added important understand- ing to the relationship between sleep and learning; not only does sleep help the brain integrate individual bits of information into broader themes and patterns, it may fundamentally enhance the brain’s capacity for creativity. (Walker, 2009)
NON-REM & REM: THE TWO STATES OF SLEEP
This is the “deep” phase of sleep, which conserves energy, restores the central nervous system (CnS) or components of the CnS (such as the frontal cortex and glycogen stores), cools the body and the brain, and promotes immune function.(Dement and vaughan 2000)
This is the more active “rapid-eye-movement” (REM) phase of sleep that helps the mind with psychological and/or emotional adaptation. By virtue of its stimulating effect, REM sleep also promotes development of the central nervous system and compensates for the deep brain stillness and brain cooling that happens during non-REM sleep. Furthermore, REM sleep facilitates periodic awakening to help a person survey their environment.(Dement and vaughan 2000)
SLEEP AND THE IMMUNE SYSTEM
When we get sick, we tend to feel tired and sleep more. But is this coincidental or is sleep a recuperative immune function? One study showed that infected rabbits that slept more had a better prognosis, suggesting that sleep might enhance recovery. But it’s unclear whether other factors, such as stress, might have been the cause of disrupted sleep in the rabbits that didn’t fare so well. (Dement and vaughan 2000)
In humans, there’s an increasing amount of research evi- dence that suggest that the right amount of sleep might prolong life; one study of 185 people aged 60 to 80 found that the quality of their sleep predicted the length of their remaining lifespan. (Dew, Hoch et al. 2003)
As more research is conducted on this subject, it is hoped that the exact nature of the relationship between sleep and the immune system’s role in controlling tumor growth can be ascertained.
GETTING A “GOOD” NIGHT’S SLEEP
What is the Definition of Good Sleep?
What constitutes “good” sleep is highly subjective, but most people would agree that an evening of high quality sleep is one in which you’re able to fall asleep quickly, stay asleep throughout the night, and wake up feeling refreshed. To achieve this sort of sleep, there are several approaches, from behavioral to pharmacological.
Good sleep can be defined in terms of sleep architecture – it is characterized by an optimal length of each sleep stage (which is age and gender specific), an appropriate distribution of sleep stages throughout the night, and a low frequency of arousal from sleep. Good sleep can also be defined in terms of general physi- ological activity; non-REM sleep, which constitutes approxi- mately 80% of sleep in a night (when optimal), is characterized by reduced physiological activity, such as reduced metabolism.
A person’s subjective assessment of their sleep quality and daytime functionality also define their “sleep health.” These tend to correlate well with objective performance estimates of daytime functioning.(Dement and vaughan 2000)
WHAT ARE THE DIFFERENT TYPES OF SLEEP DISORDERS?
Homeostasis in the human body dictates that for every two hours of wakefulness, we require one hour of sleep. If sleep cycles become disturbed, we end up “owing” hours of sleep and these hours are our “sleep debt.” Sleep debt is cumulative and carries over from one day to the next. The number of hours of sleep required per day varies with age and with individuals. On average, adults need to sleep eight hours per day, but this decreases with age.(neikrug and Ancoli- Israel 2009) Children and teens require ten hours per day on average.
Chronic Versus Acute Sleep Loss
While chronic sleep loss has been shown to be harmful to well-being, there is growing evidence that the occasional acute sleep disturbance might actually boost the immune system. (Rechtschaffen, Gilliland et al. 1983; Everson 1993; Landis and Whitney 1997)
In a study involving sleep-deprived rats, the animals’ ability to defend against infection was dependent on the length of their sleep deprivation. Evolutionarily, it may be that the immune sys- tem needs to be enhanced by brief total sleep loss, such as when being hunted by a predator. But without sleep, the immune sys- tem does eventually fail.(Dement and vaughan 2000)
WHAT CAUSES OR EXACERBATES POOR SLEEP?
In addition to the obvious causes of poor sleep that are a function of lifestyle and choice, there are many medical problems that can lead to poor sleep, some of which we review here.
A core part of brain function involves the compound serotonin, which is a neurotransmitter that is biochemically derived from the amino acid tryptophan and is critical to the transmission of nerve signals between neurons. The cells which produce this neurotransmitter, although few in number, are essential to the regulation of important brain functions including those that fol- low circadian rhythms: Sleep and waking, thinking, mood, appe- tite, sexual interest, body temperature, and behavioral regulation of aggression and impulse.(Jacob and Fornal 1995) Insufficient production of serotonin has widespread effects on the brain, play- ing a role in insomnia and mood disorders including depression, anxiety, and obsessive compulsive and bipolar disorders.(Davis, Charney et al. 2002)
Chronic Pain & Sleep
While people generally recognize that chronic pain can interfere with sleep,(Wells, Li et al. 2009) new research has shown that the effect goes in both directions, and that sleep disturbance con- tributes to increased pain levels.(Moldofsky 2010)
In people with cancer, there frequently occurs a combination of pain, fatigue, and sleep disturbance. A recent meta-analysis has provided evidence that these symptoms can all be improved by guided imagery/hypnosis and cognitive-behavioral therapy and coping-skills training, relaxation training, meditation training, and music.(Kwekkeboom, Cherwin et al. 2010)
Obstructive Sleep Apnea
In the Wisconsin Sleep Cohort study, which began over 20 years ago and monitors the sleep health of over 3000 people, re- searchers discovered that for every 10 persons, 1 to 2 suffer from untreated sleep apnea.(Young, Palta et al. 2009) Sleep apnea is a breathing problem in which a sleeping person frequently snores, often becoming louder until interrupted by a period of silence in which breathing stops and is then restarted after a loud gasping. This snoring returns often very frequently during the night. The problem stems from anatomical abnormalities in the back of the throat; usually, the body can compensate by the brain’s input to the muscles which dilate the upper airway, but those signals are suppressed during sleep, leading to the collapse of the airway in the throat.(Dempsey, veasey et al. 2010)
It has long been known that the frequent nighttime episodes of lower oxygen levels that result from this airway collapse are linked to sexual problems (erectile dysfunction), cardiovascular problems (heart disease, high cholesterol, stroke, and swelling in the legs), performance deficits (daytime drowsiness, waking up groggy, depression, hyperactivity, insomnia, memory problems, headaches, personality changes, cognitive impairment, and poor concentration), liver disease (liver inflammation and fibrosis), and to an increasingly more common health problem: diabetes. (Zias, Bezwada et al. 2009; Brondel, Romer et al. 2010; Drager, Jun et al. 2010; Eastwood, Malhotra et al. 2010; Tian, Zhang et al. 2010; Tsai 2010)
The relationship of sleep problems to diabetes has been much better understood with recent research. Compared with men, the odds that a woman with sleep apnea developing diabetes are 11 to 1, based on the results of a 16-year follow-up study. (Celen, Hedner et al. 2010) Furthermore, the type of sleep prob- lems a person has can predict their subsequent risk of developing diabetes: sleep of short duration (less than 5 to 6 hours per night), sleep of very long duration (over 8 to 9 hours per night), or dif- ficulty in getting to sleep or maintaining sleep all increase the risk of developing diabetes between 28% and 84% (nearly double). (Cappuccio, D’Elia et al. 2010)
While sleep apnea can sometimes be successfully treated by surgery,(Ye, Liu et al. 2009) there are no clearly established evidence-based guidelines for assessing suitability for surgery as based on a patient’s degree of airway obstruction and the likeli- hood of receiving surgery depends on the level of clinician expe- rience and resources available at individual hospitals.(Georgalas, Garas et al. 2010)
Although not widely used by sleep medicine centers, it has been known for the past 15 years by Japanese researchers that abnormal positioning of the jaw during sleep (too far to the back) can cause sleep apnea.(Masumi, nishigawa et al. 1996; Smith 1996) Continued research on this discovery in Japan, China, Italy, and the US has led to the development of small splints that can be inserted into the jaw, helping move the jaw forward and opening up the airway at the back of the throat to allow for better air passage during sleep. Besides improving sleep, this also helps correct the heart rate abnormalities caused by sleep apnea.(Smith 1996; villa, Bernkopf et al. 2002; Coru- zzi, Gualerzi et al. 2006; Arai, nakayama et al. 2007; Tsuda, Tsuda et al. 2007; Zeng and Gao 2009) Dentists who have special training can use an x-ray examination of the skull and jaw to identify whether or not a patient is likely to benefit from a splint(Monteith 2004) and can also provide special exercises that a patient can perform to improve jaw positioning.(Ueda, Almeida et al. 2009)
In people not helped by the splint or exercises, sleep apnea can still be successfully treated by a device called C-PAP, which blows air at a prescribed pressure through a mask worn during sleep, helping keep the airway open. Although awkward and unsexy, the devices can still be effective. A new oral device based on the splint, called OPAP, was tested at Stanford University for use in combination with C-PAP and recently received FDA approval (more information available at opaphealthcare.com).
Although overnight evaluation and treatment at clinical sleep centers can be helpful in treating obstructive sleep apnea, it is nevertheless a daunting (and expensive) process. Encour- agingly, researchers at the University of Saskatchewan this year published an excellent clinical study demonstrating that at-home diagnosis and treatment using a take-home device was just as good as that same procedure being done at a sleep center. This equivalence was demonstrated in terms of outcomes in sleepiness scores, sleep quality, quality of life, blood pressure, and compliance in the use of the CPAP device.(Skomro, Gjevre et al. 2010)
A wide range of other physical ailments can also cause sleep prob- lems. In hepatitis C, up to 60% of patients will experience newly diagnosed sleep problems, which is encouragingly reduced to 30% of patients who undergo treatment with interferon.(Socka- lingam, Abbey et al. 2010)
It is known that anxiety and sleep problems can follow a cancer diagnosis.(Price, Zachariae et al. 2009; Savard, villa et al. 2009) It can also work in the other direction: sleep problems (and the resulting disturbances in day/night variations of melatonin levels in the blood) can predate diagnoses of breast and prostate cancer by many years. new research from Case Western Reserve University has found that sleeping less than 6 hours per night increases the risk of colon cancer by nearly 50%.(Thompson, Larkin et al. 2010) Additionally, in a large- scale survey of 363 people newly diagnosed with breast cancer, researchers found that compared to age-matched controls, those diagnosed were 40% more likely to have reported keep- ing lights on while sleeping, 40% more likely to sleep during the daytime, and 20% more likely to regularly close the win- dow shades while sleeping at night. These results, while not statistically significant, nevertheless suggest a plausible theory. (Li, Zheng et al. 2010)
As the intention in going to a hospital is usually to get better, it is ironic that the noise levels in most hospitals can interfere with pa- tients’ sleep, particularly in intensive care units.(xie, Kang et al. 2009) This is especially problematic in that poor sleep is associ- ated with poor intensive care unit medical outcomes.(Weinhouse, Schwab et al. 2009; Weinhouse and Watson 2009)
WHAT ARE THE CONSEQUENCES OF NOT SLEEPING WELL?
Your Own Safety and the Safety of Others
A curious anomaly in human performance is that people often overestimate their own abilities to perform critical tasks, such as driving. Most people also misjudge their level of sleepiness and amount of sleep debt and are usually wrong about how likely they will fall asleep in the near future, which leads people to think they’re alert enough to drive when they really aren’t. Unfortunately, sleepiness behind the wheel is a major cause of fatal crashes(Abe, Komada et al. 2010; Sagaspe, Taillard et al. 2010; valent, Di Bartolomeo et al. 2010; vennelle, Engleman et al. 2010) and people with sleep apnea are six times more likely to have traffic accidents than those people without this problem. (volna and Sonka 2006) And when you add alcohol to the mix, combining even a small amount of alcohol while you’re already tired is the functional equivalent of having a lot of alcohol when you’re well-rested.(Rodenstein 2009)
Researchers at the Institute of Medicine, an independent federal research agency, recently published a comprehensive report in which they found that the frequency of serious medical errors goes up when medical residents are deprived of sleep. Medical residents are physicians who have graduated from medical schools, but are practicing medicine in a hospital or clinic under the supervision of fully licensed physicians. Almost all hospital stays involve being cared for by a medical resident at some point.
The problem involving medical errors centers around the difference between being awake and being competently alert. It is possible to use stress (adrenaline), exercise, and caffeine or other stimulant drugs to stay awake. It is not possible, however, to use these stimulants to overcome the damaging impact of sleep depri- vation on job performance and judgment.(Czeisler 2009) In this way, medical personnel being underslept leads directly to medical errors because of impaired skill and judgement.
This poses numerous ethical dilemmas for hospitals. Should hospitals limit physicians’ work hours to protect patient safety? Because sleep disorders increase substantially with age, should medical personnel be tested for suitability for long work shifts over the course of their careers?(Czeisler 2009)
Resident physicians at US hospitals are allowed to work for up to 30 hours in one shift. (Olson, Drage et al. 2009) Two-thirds of medical residents report that “sleep loss and fatigue have a major impact on my personal life” and nearly half report that “sleep loss and fatigue have a major impact on my work.”(Rosen, Gimotty et al. 2006) The number of medi- cal errors that can result from these working conditions are, not surprisingly, quite high. For example, in a survey of 254 internal medicine resident physicians, 41% reported that their own fatigue directly caused the most serious medical error they had made, and that a third of these errors led to the death of a patient.(Wu, Folkman et al. 1991)
Lurking beneath these issues of human performance are the financial incentives for hospitals, which depend on the profit mar- gin between payments they receive from Medicare or third party insurers and the low wages they pay to their resident physicians- in-training.
Emotional & Psychiatric Health
Mood disorders, anxiety, dementia, emotional instability, and the use of antidepressant medications, are all associated with sleep disorders. In many of these disorders, it is not yet known which came first: the sleep problem or the psychiatric problem.(Diekel- mann, Wilhelm et al. 2009; Sateia 2009; Teman, Tippmann- Peikert et al. 2009)
Lack of Sleep May Lead to Overeating
In a study published March 2010 in the American Journal of Clinical nutrition, researchers reported, “sleep restriction could be one of the environmental factors that contribute to the obe- sity epidemic.” They closely followed the eating, sleeping, exer- cise, and eating activities of 12 healthy young men during two 48-hour periods. The researchers first observed those men for a two-day “baseline” or control period. They then followed them closely for an active two-day study period. On the first day, the men in the study were asked to go to bed at 12 am and wake up at 8 am; on the second day, they went to bed at 2 am and woke up at 6 am. What the researchers found was that after sleeping only four hours, the men in the study ate an average of 22% (or over 500) more calories per day than they did after eight hours of sleep.
HOW TO SLEEP BETTER: UNDERSTANDING OUR NEEDS AND PATTERNS
The first step to better sleep is to determine your sleep needs and circadian pattern. This can be accomplished by keeping notes on the times when you are at peak alertness during the day. These peaks in alertness are ideal times for tackling your most challeng- ing tasks. During troughs in alertness are appropriate times for napping, resting, not driving, and other inconsequential tasks. Having then determined those optimal cycles, you can then make choices that help you lead a lifestyle that respects your body’s natural sleep patterns.
Treat sleep like exercise and diet. It is essential to pay atten- tion to it and manage it for the sake of health and longevity.
A website sponsored by the American Academy of Sleep Medi- cine provides a list of sleep clinics. This site can be searched geo- graphically and is available at www.sleepcenters.org.
A recent study from researchers in Taiwan found that people who listened to soft, slow music at bed time “experienced physical changes that aided restful sleep, such as lower heart and respira- tory rates.” Participants listened to 45-minute relaxing music tapes at bedtime for three weeks. The study found that this resulted in “significantly better sleep quality” and that “sleep improved weekly, indicating a cumulative dose effect.” (Lai and Good 2005)
A recent study showed that participants who attended regular yoga sessions reported “significantly lower sleep disturbance” as com- pared to a control group. In this study, the benefits of yoga included better quality of sleep, the ability to fall asleep quicker, longer sleep duration, and less use of sleep medications. (Cohen 2004)
SLEEP HYGIENE TIPS
SLEEP ONLY WHEN SLEEPYThis reduces the time you’re awake in bed. If you can’t fall asleep within 20 minutes, get up and do something boring until you feel sleepy. Avoid bright light during this time.
DON’T TAKE NAPSThis will help make you tired at bedtime. If you must nap, sleep for less than an hour before 3pm.
GO TO BED ON TIMEGet up and go to bed the same time every day, even on weekends. It’s easier to sleep when you have a regular sleep cycle.
TIME YOUR EXERCISERegular exercise can help improve your sleep, but don’t do so too close to bedtime (at least 4 hours).
DEVELOP SLEEP RITUALSIt is important to give your body cues that it is time to sleep, such as listening to relaxing music, drinking herbal tea, or meditating.
ONLY USE YOUR BED FOR SLEEPINGRefrain from using your bed to watch TV, pay bills, do work, or read.
AVOID CAFFEINE, NICOTINE, AND ALCOHOLCaffeine and nicotine are stimulants and alcohol can cause poor, fragmented sleep. Avoid them all for at least 4 hoursbefore bedtime.
HAVE A LIGHT SNACK BEFORE BEDSleeping on too empty or too full a stomach can interfere with sleep, but eat your last heavy meal at least 3 hours before bedtime.
TAKE A HOT BATHWhile a hot bath 90 minutes before bedtime will initially raise your body temperature, the subsequent drop in temperature afterwards may make you feel sleepy.
COOL YOUR ROOMSleeping in too hot an environment can be difficult. A cooler room, at a sleep-promoting 65 degrees with enough blankets to stay warm, is recommended.
KEEP THINGS DARK AND QUIETBlackout shades or an eye mask can help block out light and earplugs or a white noise machine can help reduce noise.
RESET YOUR BIOLOGICAL CLOCKAs soon as you get up in the morning, go outside and turn your face to the sun for 15 minutes.
WHAT ABOUT WORKING NIGHT SHIFTS?
European researchers have done extensive research on the effect of shift-work (defined as work at times other than the normal 9 to 5 work schedule) and found that the people whose sleep is impacted most by their work hours are those who work nights and early-mornings as well as those who work slowly backward- rotating shifts (as compared to rapidly forward-rotating shifts). (Sallinen and Kecklund 2010)
Melatonin was first isolated roughly 50 years ago(Lerner, Case et al. 1960) and is a chemical that has been functionally linked to the body’s regulation of circadian(Malpaux, Migaud et al. 2001; Malpaux, Tricoire et al. 2002) and seasonal rhythms,(Reiter 1993) immune function,(Guerrero and Reiter 2002) and tumor inhibition.(Blask, Dauchy et al. 2002; Blask, Sauer et al. 2002) Melatonin is not a hypnotic or soporific but rather seems to func- tion as a chemical that “opens the gate” to sleep, not something that induces sleep itself.(Kennaway and Wright 2002)
Melatonin production takes place in the brain and is mostly regulated by ambient light; only during darkness does the major- ity of melatonin production take place. The amount of melatonin an individual produces is also genetically determined, but age can also be a factor as people tend to produce less melatonin as they grow older.
Melatonin: Timing Is Everything
Researchers have revealed a substantial body of evidence on how melatonin influences sleep. That some of this information is conflicting suggests that the full story is not yet fully understood. Medicine is a work in progress and new research in the next few years should help fill in some of the gaps in knowledge on this important topic.
Melatonin has been shown to “open the gates” to sleep, so timing is very important depending on the desired effect.
Bright light exposure after darkness should be avoided since it disrupts the melatonin rhythm and alters the circadian clock. When used for night-time sleep pro- motion, melatonin is best taken 30 minutes before desired sleep onset.
WHEN TAKEN AT DUSK
Melatonin advances the internal clock, making you feel like it’s later than it really is.
WHEN TAKEN EARLY AT DAWN
Melatonin delays the internal clock, making you feel like it’s earlier than it really is.
TAKIN MELATONIN WHEN TRAVELING EAST
If you were traveling from san Francisco to Paris, take melatonin at dusk san Francisco time (which may be on the plane). Then take melatonin at dusk Paris time when you’ve arrived. a day or so before head- ing home, take melatonin at dusk Paris time and then, once home, at dusk san Francisco time.
TAKING MELATONIN WHEN TRAVELING WEST
If you were traveling from san Francisco to Beijing, take melatonin once you arrive at dusk Beijing time. Before you leave, take melatonin at dusk Beijing time and then, once home, at dusk san Francisco time. note: it has been suggested that westbound travel causes less jetlag. also, it has been suggested that melatonin is not very effective for westbound travel of less than four time zones.
Source: Reiter 2003
Dietary tryptophan, which can cross the blood-brain barrier,(Young and Gauthier 1981) is a precursor to serotonin production in the brain. The levels of serotonin in the brain can be increased by up to two-fold with a dose of tryptophan of 3,000 mg,(Young and Gauthier 1981), which is an amount capable of improving mood and cognitive function, reducing anxiety, and helping to achieve better sleep. Tryptophan achieves this by increasing the release of melatonin. Melatonin helps facilitate restful sleep, shortening the time it takes to get to sleep, increas- ing average duration of sleep, and improving sleep quality.(Shell, Bullias et al. 2010; Silber and Schmitt 2010)
Although its reputation was marred by a single manufacturing malfunction that caused serious medical problems in a small group of people back in the mid-1990s, tryptophan is now back on the market and is backed by numerous studies supporting its benefits. Because it is a mild sedative, tryptophan, like other sleep medications, can reduce reaction time.(Silber and Schmitt 2010)
Post-thanksgiving Drowsiness: It’s how much you eat, not the turkey
While many people think it’s the tryptophan in turkey that makes people sleepy at Thanksgiving, the real culprit that leads to drowsiness may really just be the overeating that comes with this high- calorie meal. it’s been known for over 60 years that the tryptophan content of turkey is similar to both other meats in general and other poultry in particular.(greenhut, Potter et al. 1947)
Tryptophan is found in nearly all protein-based foods as well as many vegetables. it is abundant in dairy products (milk, yogurt, cottage cheese), sweets (chocolate, dried dates), grains (oats) and meats (red meat, eggs, fish, poultry), nuts and seeds (sesame, sunflower seeds, pumpkin seeds, and peanuts), and legumes (chickpeas, soybeans). among the foods with the highest amounts are eggwhites, atlantic cod, and spirulina.
One of the fastest growing segments of the prescription drug market are sleep aids. These drugs are generally effective in making it easier to fall asleep, stay asleep, and increase total time asleep. There are, however, adverse affects, such as dependency, withdrawal, and tolerance. The World Health Organization broadly defines dependence as “the state of needing or depending on something or someone for support or to function or survive,” and as applied specifically to alcohol and other drugs, “a need for repeated doses of the drug to feel good or to avoid feeling bad.” Withdrawal symptoms are generally defined as those that start after a drug is discontinued or reduced (i.e. symptoms not present before treatment). Tolerance is defined as a decrease in a drug’s effect with continued administration, which results in the need to increase the dose of the drug.(World Health Organization 2010)
not all users of hypnotics become dependent, tolerant, or expe- rience withdrawal. There are various strategies, such as intermittent use, that can minimize adverse effects. It’s important to evaluate the potential benefits and risks with your doctor before beginning any prescription sleep drug program. However, because many sleep-aid drugs can cause side-effects, it’s worthwhile to improve sleep hygiene and work with other exercise, relaxation, or natural medicine ap- proaches before going the sleep medication route.
PUTTING IT ALL TOGETHER
Several key points emerge from our systematic review of the re- search on human sleep patterns:
» Sleep is essential to health. Optimal functioning of almost every body system requires sleep.
» The body needs to be re-synchronized on a daily basis through food, exercise, and face-to-face interaction with other peo- ple. Benjamin Franklin’s saying, “early to bed, early to rise…”, and what your grandmother told you about frequent exercise and regu- lar mealtimes are all true and supported by very recent research.
» Prescription medications, while helpful on an occasional or short-term basis, can have unwanted consequences that include the “rebound effect,” where sleep becomes worse after stopping the use of medication.
» Avoiding information overload is helpful, particularly in the evening.
» Helping the body get in the right mood for sleep is essen- tial, like an airplane taking the proper approach to landing.
» Sleep is a body function most people can’t consciously con- trol, but the way you treat yourself during the day can have a direct impact on whether your body can achieve good sleep at night.
Abe, T., Y. Komada, et al. (2010). “Short sleep duration and long spells of driving are associated with the occurrence of Japanese drivers’ rear-end collisions and single-car accidents.” J Sleep Res 19(2): 310-316.
Arai, Y. C., M. Nakayama, et al. (2007). “The effects of jaw thrust and the lateral position on heart rate variability in anesthetized children with obstructive sleep apnea syndrome.” Anesth Analg 104(6): 1352-1355, table of contents.
Aserinksy, E. and N. Kleitman (1953). “Regularly occurring periods of eye motility and concomitant phenomena, during sleep.” Science 118: 273-274.
Baglioni, C., K. Spiegelhalder, et al. (2010). “Sleep and emotions: A focus on insomnia.” Sleep Med Rev.
Becker, P. M. (2006). “Insomnia: prevalence, impact, pathogenesis, differential diagnosis, and evaluation.” Psychiatr Clin North Am 29(4): 855-870; abstract vii.
Blask, D. E., R. T. Dauchy, et al. (2002). “Light during darkness, melatonin suppression and cancer progression.” Neuro Endocrinol Lett 23 Suppl 2: 52-56.
Blask, D. E., L. A. Sauer, et al. (2002). “Melatonin as a chronobiotic/anticancer agent: cellular, biochemical, and molecular mechanisms of action and their implications for circadian-based cancer therapy.” Curr Top Med Chem 2(2): 113-132.
Bollinger, T., A. Bollinger, et al. (2010). “Sleep, Immunity, and Circadian Clocks: A Mechanistic Model.” Gerontology.
Brondel, L., M. A. Romer, et al. (2010). “Acute partial sleep deprivation increases food intake in healthy men.” Am J Clin Nutr 91(6): 1550-1559.
Cappuccio, F. P., L. D’Elia, et al. (2010). “Quantity and quality of sleep and incidence of type 2 diabetes: a systematic review and meta-analysis.” Diabetes Care 33(2): 414-420.
Celen, Y. T., J. Hedner, et al. (2010). “Impact of gender on incident diabetes mellitus in obstructive sleep apnea: a 16-year follow-up.” J Clin Sleep Med 6(3): 244-250.
Cohen, L., C. Warneke, et al. (2004). “Psychological adjustment and sleep quality in a randomized trial of the effects of a Tibetan yoga intervention in patients with lymphoma.” Cancer 100(10): 2253-60.
Coruzzi, P., M. Gualerzi, et al. (2006). “Autonomic cardiac modulation in obstructive sleep apnea: effect of an oral jaw-positioning appliance.” Chest 130(5): 1362-1368.
Czeisler, C. A. (2009). “Medical and genetic differences in the adverse impact of sleep loss on performance: ethical considerations for the medical profession.” Trans Am Clin Climatol Assoc 120: 249-285.
Davis, K. L., D. Charney, et al., Eds. (2002). Neuropsychopharmacology: The Fifth Generation of Progress., American College of Neuropsychopharmacology.
Dement, W. C. and C. Vaughan (2000). The Promise of Sleep: A Pioneer in Sleep Medicine Explores the Vital Connection Between Health, Happiness, and a Good Night’s Sleep, Dell.
Dempsey, J. A., S. C. Veasey, et al. (2010). “Pathophysiology of sleep apnea.” Physiol Rev 90(1): 47-112.
Dew, M. A., C. C. Hoch, et al. (2003). “Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up.” Psychosom Med 65(1): 63-73.
Dewald, J. F., A. M. Meijer, et al. (2010). “The influence of sleep quality, sleep duration and sleepiness on school performance in children and adolescents: A meta-analytic review.” Sleep Med Rev.
Diekelmann, S., I. Wilhelm, et al. (2009). “The whats and whens of sleep-dependent memory consolidation.” Sleep Med Rev 13(5): 309-321.
Drager, L. F., J. Jun, et al. (2010). “Obstructive sleep apnea and dyslipidemia: implications for atherosclerosis.” Curr Opin Endocrinol Diabetes Obes.
Eastwood, P. R., A. Malhotra, et al. (2010). “Obstructive Sleep Apnoea: From pathogenesis to treatment: Current controversies and future directions.” Respirology.
Everson, C. A. (1993). “Sustained sleep deprivation impairs host defense.” Am J Physiol 265(5 Pt 2): R1148-1154.
Georgalas, C., G. Garas, et al. (2010). “Assessment of obstruction level and selection of patients for obstructive sleep apnoea surgery: an evidence-based approach.” J Laryngol Otol 124(1): 1-9.
Greenhut, I. T., R. L. Potter, et al. (1947). “The phenylalanine and tryptophan content of meats.” Arch Biochem 15(3): 459-464.
Guerrero, J. M. and R. J. Reiter (2002). “Melatonin-immune system relationships.” Curr Top Med Chem 2(2): 167-179.
Jacob, B. L. and C. A. Fornal (1995). Serotonin and behaviour. A general hypothesis. In:. Psychopharmacology: The Fourth Generation of Progress. F. E. Bloom and D. J. Kupfer. New York, Raven Press Ltd.: 461–469.
Jean-Louis, G., D. F. Kripke, et al. (2000). “Sleep duration, illumination, and activity patterns in a population sample: effects of gender and ethnicity.” Biol Psychiatry 47(10): 921-927.
Kennaway, D. J. and H. Wright (2002). “Melatonin and circadian rhythms.” Curr Top Med Chem 2(2): 199-209.
Kopasz, M., B. Loessl, et al. (2010). “Sleep and memory in healthy children and adolescents – A critical review.” Sleep Med Rev.
Kwekkeboom, K. L., C. H. Cherwin, et al. (2010). “Mind-body treatments for the pain-fatigue-sleep disturbance symptom cluster in persons with cancer.” J Pain Symptom Manage 39(1): 126-138.
Lai, H. L. and M. Good (2005). “Music improves sleep quality in older adults.” J Adv Nurs 49(3): 234-44.
Landis, C. A. and J. D. Whitney (1997). “Effects of 72 hours sleep deprivation on wound healing in the rat.” Res Nurs Health 20(3): 259-267.
Lerner, A. B., J. D. Case, et al. (1960). “Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands.” J Biol Chem 235: 1992-1997.
Li, Q., T. Zheng, et al. (2010). “Light at night and breast cancer risk: results from a population-based case-control study in Connecticut, USA.” Cancer Causes Control.
Loomis, A. L., E. N. Harvey, et al. (1935). “Potential Rhythms of the Cerebral Cortex during Sleep.” Science 81(2111): 597-598.
Malpaux, B., M. Migaud, et al. (2001). “Biology of mammalian photoperiodism and the critical role of the pineal gland and melatonin.” J Biol Rhythms 16(4): 336-347.
Malpaux, B., H. Tricoire, et al. (2002). “Melatonin and seasonal reproduction: understanding the neuroendocrine mechanisms using the sheep as a model.” Reprod Suppl 59: 167-179.
Masumi, S., K. Nishigawa, et al. (1996). “Effect of jaw position and posture on forced inspiratory airflow in normal subjects and patients with obstructive sleep apnea.” Chest 109(6): 1484-1489.
Moldofsky, H. (2010). “Rheumatic manifestations of sleep disorders.” Curr Opin Rheumatol 22(1): 59-63.
Monteith, B. D. (2004). “Altered jaw posture and occlusal disruption patterns following mandibular advancement therapy for sleep apnea: a preliminary study of cephalometric predictors.” Int J Prosthodont 17(3): 274-280.
Neikrug, A. B. and S. Ancoli-Israel (2009). “Sleep Disorders in the Older Adult: A Mini-Review.” Gerontology.
Olson, E. J., L. A. Drage, et al. (2009). “Sleep deprivation, physician performance, and patient safety.” Chest 136(5): 1389-1396.
Price, M. A., R. Zachariae, et al. (2009). “Prevalence and predictors of insomnia in women with invasive ovarian cancer: anxiety a major factor.” Eur J Cancer 45(18): 3262-3270.
Rechtschaffen, A., M. A. Gilliland, et al. (1983). “Physiological correlates of prolonged sleep deprivation in rats.” Science 221(4606): 182-184.
Reiter, R. J. (1993). “The melatonin rhythm: both a clock and a calendar.” Experientia 49(8): 654-664.
Reiter, R. J. (2003). “Melatonin: clinical relevance.” Best Pract Res Clin Endocrinol Metab 17(2): 273-285.
Rodenstein, D. (2009). “Sleep apnea: traffic and occupational accidents–individual risks, socioeconomic and legal implications.” Respiration 78(3): 241-248.
Rosen, I. M., P. A. Gimotty, et al. (2006). “Evolution of sleep quality, sleep deprivation, mood disturbances, empathy, and
burnout among interns.” Acad Med 81(82–5).
Sagaspe, P., J. Taillard, et al. (2010). “Sleepiness, near-misses and driving accidents among a representative population of French drivers.” J Sleep Res.
Sallinen, M. and G. Kecklund (2010). “Shift work, sleep and sleepiness – differences between shift schedules and systems.” Scand J Work Environ Health.
Sateia, M. J. (2009). “Update on sleep and psychiatric disorders.” Chest 135(5): 1370-1379.
Savard, J., J. Villa, et al. (2009). “Prevalence, natural course, and risk factors of insomnia comorbid with cancer over a 2-month period.” J Clin Oncol 27(31): 5233-5239.
Shell, W., D. Bullias, et al. (2010). “A randomized, placebo-controlled trial of an amino acid preparation on timing and quality of sleep.” Am J Ther 17(2): 133-139.
Shemesh, Y., A. Eban-Rothschild, et al. (2010). “Molecular dynamics and social regulation of context-dependent plasticity in the circadian clockwork of the honey bee.” J Neurosci 30(37): 12517-12525.
Silber, B. Y. and J. A. Schmitt (2010). “Effects of tryptophan loading on human cognition, mood, and sleep.” Neurosci Biobehav Rev 34(3): 387-407.
Skomro, R. P., J. Gjevre, et al. (2010). “Outcomes of home-based diagnosis and treatment of obstructive sleep apnea.” Chest 138(2): 257-263.
Smith, S. D. (1996). “A three-dimensional airway assessment for the treatment of snoring and/or sleep apnea with jaw repositioning intraoral appliances: a case study.” Cranio 14(4): 332-343.
Sockalingam, S., S. E. Abbey, et al. (2010). “A review of sleep disturbance in hepatitis C.” J Clin Gastroenterol 44(1): 38-45.
Teman, P. T., M. Tippmann-Peikert, et al. (2009). “Idiopathic rapid-eye-movement sleep disorder: associations with antidepressants, psychiatric diagnoses, and other factors, in relation to age of onset.” Sleep Med 10(1): 60-65.
Thompson, C. L., E. K. Larkin, et al. (2010). “Short duration of sleep increases risk of colorectal adenoma.” Cancer.
Tian, J. L., Y. Zhang, et al. (2010). “Sleep apnea hypopnea syndrome and liver injury.” Chin Med J (Engl) 123(1): 89-94.
Tsai, J. C. (2010). “Neurological and neurobehavioral sequelae of obstructive sleep apnea.” NeuroRehabilitation 26(1): 85-94.
Tsuda, H., T. Tsuda, et al. (2007). “Effect of jaw position on forced maximum inspiratory airflow in normal Japanese subjects and in Japanese patients with sleep apnea syndrome.” Int J Prosthodont 20(1): 25-30.
Turner, P. L., E. J. Van Someren, et al. (2010). “The role of environmental light in sleep and health: Effects of ocular aging and cataract surgery.” Sleep Med Rev.
Ueda, H., F. R. Almeida, et al. (2009). “Effect of 2 jaw exercises on occlusal function in patients with obstructive sleep apnea during oral appliance therapy: a randomized controlled trial.” Am J Orthod Dentofacial Orthop 135(4): 430 e431-437; discussion 430-431.
Valent, F., S. Di Bartolomeo, et al. (2010). “A case-crossover study of sleep and work hours and the risk of road traffic accidents.” Sleep 33(3): 349-354.
Vennelle, M., H. M. Engleman, et al. (2010). “Sleepiness and sleep-related accidents in commercial bus drivers.” Sleep Breath 14(1): 39-42.
Villa, M. P., E. Bernkopf, et al. (2002). “Randomized controlled study of an oral jaw-positioning appliance for the treatment of obstructive sleep apnea in children with malocclusion.” Am J Respir Crit Care Med 165(1): 123-127.
Volna, J. and K. Sonka (2006). “Medical factors of falling asleep behind the wheel.” Prague Med Rep 107(3): 290-296.
Weinhouse, G. L., R. J. Schwab, et al. (2009). “Bench-to-bedside review: Delirium in ICU patients – importance of sleep deprivation.” Crit Care 13(6): 234.
Weinhouse, G. L. and P. L. Watson (2009). “Sedation and sleep disturbances in the ICU.” Crit Care Clin 25(3): 539-549, ix.
Wells, G. A., T. Li, et al. (2009). “Assessing quality of sleep in patients with rheumatoid arthritis.” J Rheumatol 36(9): 2077-2086.
Wu, A. W., S. Folkman, et al. (1991). “Do house officers learn from their mistakes?” JAMA(265): 2089–2094.
Xie, H., J. Kang, et al. (2009). “Clinical review: The impact of noise on patients’ sleep and the effectiveness of noise reduction strategies in intensive care units.” Crit Care 13(2): 208.
Yamanaka, Y., S. Honma, et al. (2009). “[Daily phase adjustment of human sleep-wake cycle].” Nippon Rinsho 67(8): 1475-1482.
Ye, J., H. Liu, et al. (2009). “Postoperative respiratory complications of adenotonsillectomy for obstructive sleep apnea syndrome in older children: prevalence, risk factors, and impact on clinical outcome.” J Otolaryngol Head Neck Surg 38(1): 49-58.
Young, S. N. and S. Gauthier (1981). “Effect of tryptophan administration on tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human lumbar and cisternal cerebrospinal fluid.” J Neurol Neurosurg Psychiatry 44(4): 323-328.
Young, S. N. and S. Gauthier (1981). “Tryptophan availability and the control of 5-hydroxytryptamine and tryptamine synthesis in human CNS.” Adv Exp Med Biol 133: 221-230.
Young, T., M. Palta, et al. (2009). “Burden of sleep apnea: rationale, design, and major findings of the Wisconsin Sleep Cohort study.” WMJ 108(5): 246-249.
Yun, C. H. and K. H. Ji (2010). “Zolpidem-induced sleep-related eating disorder.” J Neurol Sci 288(1-2): 200-201.
Zeng, X. L. and X. M. Gao (2009). “[Current research of dentistry on obstructive sleep apnea hypopnea syndrome].” Beijing Da Xue Xue Bao 41(1): 10-15.
Zias, N., V. Bezwada, et al. (2009). “Obstructive sleep apnea and erectile dysfunction: still a neglected risk factor?” Sleep Breath 13(1): 3-10.
Welcome to the last Avenues of 2010!
OUR 2010 ACCOMPLISHMENTS
This past year has been a productive one for the Pine Street Foundation. We’ve published peer-reviewed research, presented papers at conferences, received lots of media coverage in the national press, and reached thousands of patients and doctors through our newsletter, Avenues. Click here for some of the highlights from our successful year.
CAN DOGS DETECT OVARIAN CANCER?
Is there meaningful information contained within the breath that could lead to the early detection of ovarian cancer? In a collaboration with the University of Maine and the University of California at San Francisco, we are using dogs to find biomarkers in the breaths of women with ovarian cancer that could lead to earlier detection – and better treatment outcomes – for this disease.
So far, we’ve received breath samples from more than 100 wom- en and now just need:
» 12 More Women with Ovarian Cancer » 13 More Women with Endometriosis or PCOS
Visit pinestreetfoundation.org/ovarian to learn more about this project.
Recruiting patients for any research project is costly. But your donation – of any size – will directly help us locate enough eligible women and obtain samples of their breath to complete this important research.
Visit pinestreetfoundation.org/donate to show your support.
AS THE YEAR DRAWS TO A CLOSE…
Whether you’ve known us since 1989 or have only recently dis- covered our work, it is important to note that the Pine Street Foundation is one of the most efficient and cost-effective research organizations of its kind in the country. And since the vast major- ity of all our funding comes from individual donors like you, your financial support truly helps us advance the field of integrative medicine and benefits those in need of better treatments.
As you consider your year-end charitable giving, please keep the Pine Street Foundation in mind. We really appreciate it!