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Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis | |
Classification and external resources | |
This MRI (parasagittal FLAIR) demonstrates increased T2 signal within the posterior part of the internal capsule and can be tracked to the subcortical white matter of the motor cortex, outlining the corticospinal tract, consistent with the clinical diagnosis of ALS. However, typically MRI imaging is unremarkable in a patient with ALS. |
DiseasesDB | 29148 |
MedlinePlus | 000688 |
eMedicine | neuro/14 emerg/24 pmr/10 |
MeSH | D000690 |
Amyotrophic lateral sclerosis (ALS) – also referred to as motor neurone disease in some Commonwealth of Nations countries and as Lou Gehrig's disease in the United States – is a debilitating disease with varied etiology characterized by rapidly progressive weakness, muscle atrophy and fasciculations, muscle spasticity, difficulty speaking (dysarthria), difficulty swallowing (dysphagia), and difficulty breathing (dyspnea). ALS is the most common of the five motor neuron diseases.
Contents |
Signs and symptoms[edit]
The disorder causes muscle weakness and atrophy throughout the body caused by the degeneration of the upper and lower motor neurons. Unable to function, the muscles weaken and atrophy. Individuals affected by the disorder may ultimately lose the ability to initiate and control all voluntary movement, although bladder and bowel sphincters and the muscles responsible for eye movement are usually, but not always, spared until the terminal stages of the disease.[1]
Cognitive function is generally spared for most patients, although some (about 5%) also have frontotemporal dementia.[2] A higher proportion of patients (30–50%) also have more subtle cognitive changes which may go unnoticed, but are revealed by detailed neuropsychological testing. Sensory nerves and the autonomic nervous system are generally unaffected, meaning the majority of people with ALS will maintain hearing, sight, touch, smell, and taste.
Initial symptoms[edit]
The earliest symptoms of ALS are typically obvious weakness and/or muscle atrophy. Other presenting symptoms include muscle fasciculation (twitching), cramping, or stiffness of affected muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. The parts of the body affected by early symptoms of ALS depend on which motor neurons in the body are damaged first. About 75% of people contracting the disease experience "limb onset" ALS, i.e., first symptoms in the arms or legs. Patients with the leg onset form may experience awkwardness when walking or running or notice that they are tripping or stumbling, often with a "dropped foot" which drags gently along the ground. Arm-onset patients may experience difficulty with tasks requiring manual dexterity such as buttoning a shirt, writing, or turning a key in a lock. Occasionally, the symptoms remain confined to one limb for a long period of time or for the whole length of the illness; this is known as monomelic amyotrophy.
About 25% of cases are "bulbar onset" ALS. These patients first notice difficulty speaking clearly or swallowing. Speech may become slurred, nasal in character, or quieter. Other symptoms include difficulty swallowing and loss of tongue mobility. A smaller proportion of patients experience "respiratory onset" ALS, where the intercostal muscles that support breathing are affected first. A small proportion of patients may also present with what appears to be frontotemporal dementia, but later progresses to include more typical ALS symptoms.
Over time, patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Symptoms of upper motor neuron involvement include tight and stiff muscles (spasticity) and exaggerated reflexes (hyperreflexia) including an overactive gag reflex. An abnormal reflex commonly called Babinski's sign also indicates upper motor neuron damage. Symptoms of lower motor neuron degeneration include muscle weakness and atrophy, muscle cramps, and fleeting twitches of muscles that can be seen under the skin (fasciculations). Around 15–45% of patients experience pseudobulbar affect, also known as "emotional lability", which consists of uncontrollable laughter, crying or smiling, attributable to degeneration of bulbar upper motor neurons resulting in exaggeration of motor expressions of emotion[citation needed]. To be diagnosed with ALS, patients must have signs and symptoms of both upper and lower motor neuron damage that cannot be attributed to other causes.
Disease progression and spread[edit]
Although the order and rate of symptoms varies from person to person, eventually most patients are not able to walk, get out of bed on their own, or use their hands and arms. The rate of progression can be measured using an outcome measure called the "ALS Functional Rating Scale (Revised)", a 12-item instrument administered as a clinical interview or patient-reported questionnaire that produces a score between 48 (normal function) and 0 (severe disability). Though there is a high degree of variability and a small percentage of patients have much slower disease, on average, patients lose about 1 FRS point per month. Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. In limb-onset ALS, symptoms usually spread from the affected limb to the opposite limb before affecting a new body region, whereas in bulbar-onset ALS symptoms typically spread to the arms before the legs.
Disease progression tends to be slower in patients who are younger than 40 at onset,[3] have disease restricted primarily to one limb, and those with primarily upper motor neuron symptoms.[4] Conversely, progression is faster and prognosis poorer in patients with bulbar-onset disease, respiratory-onset disease, and frontotemporal dementia.[4]
Late stage disease symptoms[edit]
Difficulty swallowing and chewing make eating normally very difficult and increase the risk of choking or aspirating food into the lungs. In later stages of the disease, aspiration pneumonia and maintaining a healthy weight can become a significant problem and may require insertion of a feeding tube. As the diaphragm and intercostal muscles (rib cage) that support breathing weaken, measures of lung function such as forced vital capacity and inspiratory pressure diminish. In respiratory onset ALS, this may occur before significant limb weakness is apparent. External machines such as bilevel positive pressure ventilation (frequently referred to by the tradename BiPAP) are frequently used to support breathing, first at night, and later during the daytime as well. BiPAP is only a temporary remedy, however, and it is recommended that long before BiPAP stops being effective, patients should decide whether to have a tracheotomy and long term mechanical ventilation. At this point, some patients choose palliative hospice care. Most people with ALS die of respiratory failure or pneumonia.
Although respiratory support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Most people with ALS die from respiratory failure, usually within three to five years from the onset of symptoms. The median survival time from onset to death is around 39 months, and only 4% survive longer than 10 years.[5] The best-known person with ALS, Stephen Hawking, has lived with the disease for more than 50 years, though his is an unusual case.[6]
Genetic factors[edit]
There is a known hereditary factor in familial ALS (FALS), where the condition is known to run in families. A defect on chromosome 21, which codes for superoxide dismutase, is associated with approximately 20% of familial cases of ALS, or about 2% of ALS cases overall.[7][8][9] This mutation is believed to be transmitted in an autosomal dominant manner, and has over a hundred different forms of mutation. The most common ALS-causing SOD1 mutation in North American patients is A4V, characterized by an exceptionally rapid progression from onset to death. The most common mutation found in Scandinavian countries, D90A, is more slowly progressive than typical ALS and patients with this form of the disease survive for an average of 11 years.[10]
In 2011, a genetic abnormality known as a hexanucleotide repeat was found in a region called C9orf72, which is associated with ALS combined with frontotemporal dementia ALS-FTD,[11] and accounts for some 6% of cases of ALS among white Europeans.[12] The high degree of mutations found in patients that appeared to have "sporadic" disease, (i.e., without a family history) suggests that genetics may play a more significant role than previously thought and that environmental exposures may be less relevant.
To date, a number of genetic mutations have been associated with various types of ALS. The currently known associations are as follows:
Type | OMIM | Gene | Locus | Remarks |
ALS1 | 105400 | SOD1 | 21q22.1 | The most common form of familial ALS |
ALS2 | 205100 | ALS2 | 2q33.1 | |
ALS3 | 606640 | ? | 18q21 | |
ALS4 | 602433 | SETX | 9q34.13 | |
ALS5 | 602099 | ? | 15q15.1–q21.1 | Juvenile onset |
ALS6 | 608030 | FUS | 16p11.2 | |
ALS7 | 608031 | ? | 20p13 | |
ALS8 | 608627 | VAPB | 20q13.3 | |
ALS9 | 611895 | ANG | 14q11.2 | |
ALS10 | 612069 | TARDBP | 1p36.2 | |
ALS11 | 612577 | FIG4 | 6q21 | |
ALS12 | 613435 | OPTN | 10p13 | |
ALS13 | 183090 | ATXN2 | 12q24.12 | |
ALS14 | 613954 | VCP | 9p13.3 | Very rare, described only in one family[13] |
ALS15 | 300857 | UBQLN2 | Xp11.23–p11.1 | Described in one family[14] |
ALS16 | 614373 | SIGMAR1 | 9p13.3 | Juvenile onset, very rare, described only in one family[15] |
ALS17 | 614696 | CHMP2B | 3p11 | Very rare, reported only in a handful of patients |
ALS18 | 614808 | PFN1 | 17p13.3 | Very rare, described only in a handful of Chinese families[16] |
ALS-FTD | 105550 | C9orf72 | 9p21.2 | Accounts for around 6% of ALS cases among white Europeans |
The precise cause of ALS is not known, though an important step toward determining the cause came in 1993 when scientists discovered that mutations in the gene that produces the Cu/Zn superoxide dismutase (SOD1) enzyme were associated with some cases (approximately 20%) of familial ALS. This enzyme is a powerful antioxidant that protects the body from damage caused by superoxide, a toxic free radical generated in the mitochondria. Free radicals are highly reactive molecules produced by cells during normal metabolism. Free radicals can accumulate and cause damage to both mitochondrial and nuclear DNA and proteins within cells. To date, over 110 different mutations in SOD1 have been linked with the disease, some of which have a very long clinical course (e.g. H46R), while others, such as A4V, being exceptionally aggressive. Evidence suggests that failure of defenses against oxidative stress up-regulates programmed cell death (apoptosis), among many other possible consequences. Although it is not yet clear how the SOD1 gene mutation leads to motor neuron degeneration, researchers have theorized that an accumulation of free radicals may result from the faulty functioning of this gene. Current research, however, indicates that motor neuron death is not likely a result of lost or compromised dismutase activity, suggesting mutant SOD1 induces toxicity in some other way (a gain of function).[17][18]
Studies involving transgenic mice have yielded several theories about the role of SOD1 in mutant SOD1 familial amyotrophic lateral sclerosis. Mice lacking the SOD1 gene entirely do not customarily develop ALS, although they do exhibit an acceleration of age-related muscle atrophy (sarcopenia) and a shortened lifespan (see article on superoxide dismutase). This indicates that the toxic properties of the mutant SOD1 are a result of a gain in function rather than a loss of normal function. In addition, aggregation of proteins has been found to be a common pathological feature of both familial and sporadic ALS (see article on proteopathy). Interestingly, in mutant SOD1 mice (most commonly, the G93A mutant), aggregates (misfolded protein accumulations) of mutant SOD1 were found only in diseased tissues, and greater amounts were detected during motor neuron degeneration.[19] It is speculated that aggregate accumulation of mutant SOD1 plays a role in disrupting cellular functions by damaging mitochondria, proteasomes, protein folding chaperones, or other proteins.[20] Any such disruption, if proven, would lend significant credibility to the theory that aggregates are involved in mutant SOD1 toxicity. Critics have noted that in humans, SOD1 mutations cause only 2% or so of overall cases and the etiological mechanisms may be distinct from those responsible for the sporadic form of the disease. To date, the ALS-SOD1 mice remain the best model of the disease for preclinical studies but it is hoped that more useful models will be developed.
Other factors[edit]
Where no family history of the disease is present – i.e., in around 95% of cases – there is no known cause for ALS. Potential causes for which there is inconclusive evidence includes head trauma, military service, and participation in contact sports.
Studies also have focused on the role of glutamate in motor neuron degeneration. Glutamate is one of the chemical messengers or neurotransmitters in the brain. Scientists have found that, compared to healthy people, ALS patients have higher levels of glutamate in the serum and spinal fluid.[8] Riluzole is currently the only FDA approved drug for ALS and targets glutamate transporters. It only has a modest effect on survival, however, suggesting that excess glutamate is not the sole cause of the disease.
Certain studies suggested a link between sporadic ALS, specifically in athletes, and a diet enriched with branched-chain amino acids. BCAAs, a common dietary supplement among athletes, cause cell hyper-excitability resembling that usually observed in ALS patients. The proposed underlying mechanism is that cell hyper-excitability results in increased calcium absorption by the cell and thus brings about cell death, specifically of neuronal cells which have particularly low calcium buffering capabilities.[21][22]
According to Medical News Today, "A group of investigators from the University of British Columbia and the Vancouver Coastal Health Research Institute have discovered a crucial link between prions and the neurodegenerative disease ALS" [23]
Many other potential causes, including chemical exposure, electromagnetic field exposure, occupation, physical trauma, and electric shock, have been investigated but without consistent findings.[24]
The defining feature of ALS is the death of both upper and lower motor neurons in the motor cortex of the brain, the brain stem, and the spinal cord. Prior to their destruction, motor neurons develop proteinaceous inclusions in their cell bodies and axons. This may be partly due to defects in protein degradation.[25] These inclusions often contain ubiquitin, and generally incorporate one of the ALS-associated proteins: SOD1, TAR DNA binding protein (TDP-43, or TARDBP), or FUS.
No test can provide a definite diagnosis of ALS, although the presence of upper and lower motor neuron signs in a single limb is strongly suggestive. Instead, the diagnosis of ALS is primarily based on the symptoms and signs the physician observes in the patient and a series of tests to rule out other diseases. Physicians obtain the patient's full medical history and usually conduct a neurologic examination at regular intervals to assess whether symptoms such as muscle weakness, atrophy of muscles, hyperreflexia, and spasticity are getting progressively worse.
Because symptoms of ALS can be similar to those of a wide variety of other, more treatable diseases or disorders, appropriate tests must be conducted to exclude the possibility of other conditions. One of these tests is electromyography (EMG), a special recording technique that detects electrical activity in muscles. Certain EMG findings can support the diagnosis of ALS. Another common test measures nerve conduction velocity (NCV). Specific abnormalities in the NCV results may suggest, for example, that the patient has a form of peripheral neuropathy (damage to peripheral nerves) or myopathy (muscle disease) rather than ALS. The physician may order magnetic resonance imaging (MRI), a noninvasive procedure that uses a magnetic field and radio waves to take detailed images of the brain and spinal cord. Although these MRI scans are often normal in patients with ALS, they can reveal evidence of other problems that may be causing the symptoms, such as a spinal cord tumor, multiple sclerosis, a herniated disk in the neck, syringomyelia, or cervical spondylosis.
Based on the patient's symptoms and findings from the examination and from these tests, the physician may order tests on blood and urine samples to eliminate the possibility of other diseases as well as routine laboratory tests. In some cases, for example, if a physician suspects that the patient may have a myopathy rather than ALS, a muscle biopsy may be performed.
Infectious diseases such as human immunodeficiency virus (HIV), human T-cell leukaemia virus (HTLV), Lyme disease,[26] syphilis[27] and tick-borne encephalitis[28] viruses can in some cases cause ALS-like symptoms. Neurological disorders such as multiple sclerosis, post-polio syndrome, multifocal motor neuropathy, CIDP, and spinal muscular atrophy can also mimic certain facets of the disease and should be considered by physicians attempting to make a diagnosis.
ALS must be differentiated from the "ALS mimic syndromes" which are unrelated disorders that may have a similar presentation and clinical features to ALS or its variants.[29] Because of the prognosis carried by this diagnosis and the variety of diseases or disorders that can resemble ALS in the early stages of the disease, patients should always obtain a specialist neurological opinion, so that alternative diagnoses are clinically ruled out.
However, most cases of ALS are readily diagnosed and the error rate of diagnosis in large ALS clinics is less than 10%.[30][31] In one study, 190 patients who met the MND / ALS diagnostic criteria, complemented with laboratory research in compliance with both research protocols and regular monitoring. Thirty of these patients (15.78%) had their diagnosis completely changed, during the clinical observation development period.[32] In the same study, three patients had a false negative diagnoses, myasthenia gravis (MG), an auto-immune disease. MG can mimic ALS and other neurological disorders leading to a delay in diagnosis and treatment. MG is eminently treatable; ALS is not.[33] Myasthenic syndrome, also known as Lambert-Eaton syndrome (LES), can mimic ALS and its initial presentation can be similar to that of MG.[34][35]
Current research focuses on abnormalities of neuronal cell metabolism involving glutamate and the role of potential neurotoxins and neurotrophic factors. [36]
Slowing progression[edit]
Riluzole (Rilutek) is the only treatment that has been found to improve survival but only to a modest extent.[37] It lengthens survival by several months, and may have a greater survival benefit for those with a bulbar onset. It also extends the time before a person needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and people taking it must be monitored for liver damage (occurring in ~10% of people taking the drug).[38] It is approved by Food and Drug Administration (FDA) and recommended by the National Institute for Clinical Excellence (NICE).
Disease management[edit]
Other treatments for ALS are designed to relieve symptoms and improve the quality of life for patients. This supportive care is best provided by multidisciplinary teams of health care professionals working with patients and caregivers to keep patients as mobile and comfortable as possible.
Pharmaceutical treatments[edit]
Medical professionals can prescribe medications to help reduce fatigue, ease muscle cramps, control spasticity, and reduce excess saliva and phlegm. Drugs also are available to help patients with pain, depression, sleep disturbances, dysphagia, and constipation. Baclofen and diazepam are often prescribed to control the spasticity caused by ALS, and trihexyphenidyl or amitriptyline may be prescribed when ALS patients begin having trouble swallowing their saliva.[1]
Physical, occupational and speech therapy[edit]
Physical therapists and occupational therapists play a large role in rehabilitation for individuals with ALS. Specifically, physical and occupational therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, preventing complications, and promoting functional independence.[39]
Occupational therapy and special equipment such as assistive technology can also enhance patients' independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living (ADL's), walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help patients fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc.) and wheelchairs that help patients remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable people to retain as much safety and independence in activities of daily living as possible.
ALS patients who have difficulty speaking may benefit from working with a speech-language pathologist. These health professionals can teach patients adaptive strategies such as techniques to help them speak louder and more clearly. As ALS progresses, speech-language pathologists can recommend the use of augmentative and alternative communication such as voice amplifiers, speech-generating devices (or voice output communication devices) and/or low tech communication techniques such as alphabet boards or yes/no signals.
Feeding and nutrition[edit]
Patients and caregivers can learn from speech-language pathologists and nutritionists how to plan and prepare numerous small meals throughout the day that provide enough calories, fiber, and fluid and how to avoid foods that are difficult to swallow. Patients may begin using suction devices to remove excess fluids or saliva and prevent choking. Occupational therapists can assist with recommendations for adaptive equipment to ease the physical task of self-feeding and/or make food choice recommendations that are more conducive to their unique deficits and abilities. When patients can no longer get enough nourishment from eating, doctors may advise inserting a feeding tube into the stomach. The use of a feeding tube also reduces the risk of choking and pneumonia that can result from inhaling liquids into the lungs. The tube is not painful and does not prevent patients from eating food orally if they wish.
Researchers have stated that "ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake."[40] Both animal[41] and human research[40][42] suggest that ALS patients should be encouraged to consume as many calories as possible and not to restrict their calorie intake.
Breathing support[edit]
When the muscles that assist in breathing weaken, use of ventilatory assistance (intermittent positive pressure ventilation (IPPV), bilevel positive airway pressure (BIPAP), or biphasic cuirass ventilation (BCV)) may be used to aid breathing. Such devices artificially inflate the patient's lungs from various external sources that are applied directly to the face or body. When muscles are no longer able to maintain oxygen and carbon dioxide levels, these devices may be used full-time. BCV has the added advantage of being able to assist in clearing secretions by using high-frequency oscillations followed by several positive expiratory breaths.[43] Patients may eventually consider forms of mechanical ventilation (respirators) in which a machine inflates and deflates the lungs. To be effective, this may require a tube that passes from the nose or mouth to the windpipe (trachea) and for long-term use, an operation such as a tracheostomy, in which a plastic breathing tube is inserted directly in the patient's windpipe through an opening in the neck.
Patients and their families should consider several factors when deciding whether and when to use one of these options. Ventilation devices differ in their effect on the patient's quality of life and in cost. Although ventilation support can ease problems with breathing and prolong survival, it does not affect the progression of ALS. Patients need to be fully informed about these considerations and the long-term effects of life without movement before they make decisions about ventilation support. Some patients under long-term tracheostomy intermittent positive pressure ventilation with deflated cuffs or cuffless tracheostomy tubes (leak ventilation) are able to speak, provided their bulbar muscles are strong enough. This technique preserves speech in some patients with long-term mechanical ventilation. Other patients may be able to utilize a speaking valve such as a Passey-Muir Speaking Valve with the assistance and guidance of a speech-language pathologist.
Palliative care[edit]
Social workers and home care and hospice nurses help patients, families, and caregivers with the medical, emotional, and financial challenges of coping with ALS, particularly during the final stages of the disease. Social workers provide support such as assistance in obtaining financial aid, arranging durable power of attorney, preparing a living will, and finding support groups for patients and caregivers. Home nurses are available not only to provide medical care but also to teach caregivers about tasks such as maintaining respirators, giving feedings, and moving patients to avoid painful skin problems and contractures. Home hospice nurses work in consultation with physicians to ensure proper medication, pain control, and other care affecting the quality of life of patients who wish to remain at home. The home hospice team can also counsel patients and caregivers about end-of-life issues.
ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. One or two out of 100,000 people develop ALS each year.[44] ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women.
Although the incidence of ALS is thought to be regionally uniform, there are three regions in the West Pacific where there has in the past been an elevated occurrence of ALS. This seems to be declining in recent decades. The largest is the area of Guam inhabited by the Chamorro people, who have historically had a high incidence (as much as 143 cases per 100,000 people per year) of a condition called Lytico-Bodig disease which is a combination of symptoms similar to ALS, parkinsonism, and dementia. Lytico-Bodig disease has been linked to the consumption of cycad seeds and in particular, the chemical found in cycad seeds, β-methylamino-L-alanine (BMAA).[45] Two more areas of increased incidence are West Papua and the Kii Peninsula of Japan.[46][47]
Although there have been reports of several "clusters" including three American football players from the San Francisco 49ers, more than fifty football players in Italy,[48] three football-playing friends in the south of England,[49] and reports of conjugal (husband and wife) cases in the south of France,[50][51][52][53][54] these are statistically plausible chance events[citation needed]. Although many authors consider ALS to be caused by a combination of genetic and environmental risk factors, so far the latter have not been firmly identified, other than a higher risk with increasing age.
Amyotrophic comes from the Greek language: A- means "no", myo refers to "muscle", and trophic means "nourishment"; amyotrophic therefore means "no muscle nourishment," which describes the characteristic atrophication of the sufferer's disused muscle tissue. Lateral identifies the areas in a person's spinal cord where portions of the nerve cells that are affected are located. As this area degenerates it leads to scarring or hardening ("sclerosis") in the region.
Year | Event |
1824 | Charles Bell writes a report about ALS.[55] |
1850 | English scientist Augustus Waller describes the appearance of shriveled nerve fibers |
1869 | French doctor Jean-Martin Charcot first describes ALS in scientific literature[56] |
1881 | "Amyotrophic Lateral Sclerosis" is translated into English and published in a three-volume edition of Lectures on the Diseases of the Nervous System |
1939 | ALS becomes a cause célèbre in the United States when baseball legend Lou Gehrig's career—and, two years later, his life—is ended by the disease. He gives his farewell speech on 4 July 1939.[57] |
1950s | ALS epidemic occurs among the Chamorro people on Guam |
1991 | Researchers link chromosome 21 to FALS (Familial ALS) |
1993 | SOD1 gene on chromosome 21 found to play a role in some cases of FALS |
1996 | Rilutek becomes the first FDA-approved drug for ALS |
1998 | The El Escorial criteria is developed as the standard for classifying ALS patient in clinical research |
1999 | The revised ALS Functional Rating Scale (ALSFRS-R) is published and soon becomes a gold standard measure for rating decline in ALS patient in clinical research |
2011 | Noncoding repeat expansions in C9ORF72 are found to be a major cause of ALS and frontotemporal dementia |
Clinical research[edit]
A number of clinical trials are underway globally for ALS; a comprehensive listing of trials in the US can be found at ClinicalTrials.gov.
Thalidomide and lenalidomide have shown efficacy in protecting motor neurons in transgenic (G93A) mice.[58]
Dexpramipexole (KNS-760704) is under clinical investigation in ALS patients. It is hoped that the drug will have a neuroprotective effect. It is one enantiomer of pramipexole, which is approved for the treatment of Parkinson's disease and restless legs syndrome.[59] The single-enantiomer preparation is essentially inactive at dopamine receptors, is not dose limited by the potent dopaminergic properties of pramipexole.[60] Results of a phase II clinical trial conducted by Knopp Neurosciences and involving 102 patients were reported in 2010; the trial found a dose-dependent slowing in loss of function.[61] A larger phase II trial conducted by Biogen Idec found the drug to be safe, well tolerated, and associated with a dose-dependent slowing in the decline of ALS.[62] In January 2013, Biogen Idec announced that it was discontinuing its development of dexpramipexole in ALS due to lack of efficacy in a phase III study.
A phase II trial on talampanel was completed by Teva Pharmaceutical Industries in April 2010, however it was found to be negative for treatment viability.[63]
A phase I trial using human fetal neural stem cells conducted by Neuralstem, Inc. in 2010–2012 showed "no significant disease progression" in a number of participants. A phase II trial of the technology has received FDA approval and is scheduled to commence in 2013.[64]
See also[edit]
- ALS Association
- ALS Society of Canada
- ALS Therapy Development Institute
- Motor Neurone Disease Association
- Muscular Dystrophy Association
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- ^ Wu, C. H.; Fallini, C.; Ticozzi, N.; Keagle, P. J.; Sapp, P. C.; Piotrowska, K.; Lowe, P.; Koppers, M. et al. (2012). "Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis". Nature 488 (7412): 499–503. doi:10.1038/nature11280. PMID 22801503.
- ^ Reaume A, Elliott J, Hoffman E, Kowall N, Ferrante R, Siwek D, Wilcox H, Flood D, Beal M, Brown R, Scott R, Snider W (1996). "Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury". Nat Genet 13 (1): 43–7. doi:10.1038/ng0596-43. PMID 8673102.
- ^ Bruijn L, Houseweart M, Kato S, Anderson K, Anderson S, Ohama E, Reaume A, Scott R, Cleveland D (1998). "Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1". Science 281 (5384): 1851–4. doi:10.1126/science.281.5384.1851. PMID 9743498.
- ^ Furukawa Y, Fu R, Deng H, Siddique T, O'Halloran T (2006). "Disulfide cross-linked protein represents a significant fraction of ALS-associated Cu, Zn-superoxide dismutase aggregates in spinal cords of model mice". Proc Natl Acad Sci USA 103 (18): 7148–53. doi:10.1073/pnas.0602048103. PMC 1447524. PMID 16636274.
- ^ Boillée S, Vande Velde C, Cleveland D (2006). "ALS: a disease of motor neurons and their nonneuronal neighbors". Neuron 52 (1): 39–59. doi:10.1016/j.neuron.2006.09.018. PMID 17015226.
- ^ Manuel, M.; Heckman, C. J. (2011). "Stronger is not always better: Could a bodybuilding dietary supplement lead to ALS?". Experimental Neurology 228 (1): 5–8. doi:10.1016/j.expneurol.2010.12.007. PMC 3049458. PMID 21167830.
- ^ Carunchio, I.; Curcio, L.; Pieri, M.; Pica, F.; Caioli, S.; Viscomi, M. T.; Molinari, M.; Canu, N. et al. (2010). "Increased levels of p70S6 phosphorylation in the G93A mouse model of Amyotrophic Lateral Sclerosis and in valine-exposed cortical neurons in culture". Experimental Neurology 226 (1): 218–230. doi:10.1016/j.expneurol.2010.08.033. PMID 20832409.
- ^ "Crucial Link Between Prions And ALS Discovered - May Transform Treatment". Medical News Today. 22 Sep 2011. Retrieved 21 December 2012.
- ^ Sutedja NA, Fischer K, Veldink JH, van der Heijden GJ, Kromhout H, Heederik D, et al. (2009). "What we truly know about occupation as a risk factor for ALS: a critical and systematic review". Amyotrophic Lateral Sclerosis 10 (5–6): 295–301. doi:10.3109/17482960802430799. PMID 19922116.
- ^ Deng, HX; Chen, W, Hong, ST, Boycott, KM, Gorrie, GH, Siddique, N, Yang, Y, Fecto, F, Shi, Y, Zhai, H, Jiang, H, Hirano, M, Rampersaud, E, Jansen, GH, Donkervoort, S, Bigio, EH, Brooks, BR, Ajroud, K, Sufit, RL, Haines, JL, Mugnaini, E, Pericak-Vance, MA, Siddique, T (2011-08-21). "Mutations in UBQLN2 cause dominant X-linked juvenile and adult onset ALS and ALS/dementia". Nature 477 (7363): 211–5. doi:10.1038/nature10353. PMC 3169705. PMID 21857683.
- ^ Hansel Y, Ackerl M, Stanek G. (1995). "ALS-like sequelae in chronic neuroborreliosis". Wien Med Wochenschr. 145 (7–8): 186–8. PMID 7610670.
- ^ el Alaoui-Faris M, Medejel A, al Zemmouri K, Yahyaoui M, Chkili T (1990). "Amyotrophic lateral sclerosis syndrome of syphilitic origin. 5 cases". Rev Neurol (Paris) 146 (1): 41–4. PMID 2408129.
- ^ Umanekii KG, Dekonenko EP (1983). "Structure of progressive forms of tick-borne encephalitis". Zh Nevropatol Psikhiatr Im S S Korsakova. 83 (8): 1173–9. PMID 6414202.
- ^ Silani, V.; Messina, S.; Poletti, B.; Morelli, C.; Doretti, A.; Ticozzi, N.; Maderna, L. (2011). "The diagnosis of Amyotrophic lateral sclerosis in 2010". Archives italiennes de biologie 149 (1): 5–27. doi:10.4449/aib.v149i1.1260. PMID 21412713.
- ^ Eisen, A. (2002). "Amyotrophic lateral sclerosis: A review". BCMJ 44 (7): 362–366.
- ^ Davenport, R. J.; Swingler, R. J.; Chancellor, A. M.; Warlow, C. P. (1996). "Avoiding false positive diagnoses of motor neuron disease: Lessons from the Scottish Motor Neuron Disease Register". Journal of Neurology, Neurosurgery & Psychiatry 60 (2): 147. doi:10.1136/jnnp.60.2.147.
- ^ Chieia, M. A.; Oliveira, A. S. B.; Silva, H. C. A.; Gabbai, A. A. (2010). "Amyotrophic lateral sclerosis: Considerations on diagnostic criteria". Arquivos de Neuro-Psiquiatria 68 (6): 837–842. doi:10.1590/S0004-282X2010000600002. PMID 21243238.
- ^ Al-Asmi, A.; Nandhagopal, R.; Jacob, P. C.; Gujjar, A. (2012). "Misdiagnosis of Myasthenia Gravis and Subsequent Clinical Implication: A case report and review of literature". Sultan Qaboos University medical journal 12 (1): 103–108. PMC 3286704. PMID 22375266.
- ^ "Lambert-Eaton Myasthenic Syndrome (LEMS)". Misc.medscape.com. Retrieved 18 April 2013.
- ^ "LEMS.com, Lambert-Eaton Myasthenic Syndrome: About". Lems.com. Retrieved 18 April 2013.
- ^ Walling, A. (1999). "Amyotrophic lateral sclerosis: Lou Gehrig's disease". American Family Physician 59 (6): 1489–1496.
- ^ Carlesi, C; Pasquali, L, Piazza, S, Lo Gerfo, A, Caldarazzo Ienco, E, Alessi, R, Fornai, F, Siciliano, G (March 2011). "Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis". Archives italiennes de biologie 149 (1): 151–67. doi:10.4449/aib.v149i1.1267. PMID 21412722.
- ^ Miller, RG; Mitchell JD, Lyon M, Moore DH, G (2007). "Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND)". In Miller, Robert G. Cochrane Database of Systematic Reviews (1): CD001447. doi:10.1002/14651858.CD001447.pub2. PMID 17253460.
- ^ Lewis, M. & Rushanan, S. (2007). "The role of physical therapy and occupational therapy in the treatment of Amyotrophic Lateral Sclerosis". NeuroRehabilitation 22 (6): 451–461. PMID 18198431.
- ^ a b Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ (Jan 1996). "Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death". Am J Clin Nutr. 63 (1): 130–7. PMID 8604660.
- ^ Hamadeh MJ, Rodriguez MC, Kaczor JJ, Tarnopolsky MA (Feb 2005). "Caloric restriction transiently improves motor performance but hastens clinical onset of disease in the Cu/Zn-superoxide dismutase mutant G93A mouse". Muscle Nerve 31 (2): 214–20. doi:10.1002/mus.20255. PMID 15625688.
- ^ Slowie LA, Paige MS, Antel JP (Jul 1983). "Nutritional considerations in the management of patients with amyotrophic lateral sclerosis (ALS)". J Am Diet Assoc 83 (1): 44–7. PMID 6863783.
- ^ Sviri S, Linton DM, Van Heerden PV (Jun 2005). "Non-invasive Mechanical Ventilation Enhances Patient Autonomy in Decision-Making Regarding Chronic Ventilation". Critical Care and Resuscitation 7 (2): 116–118. PMID 16548804.
- ^ "ALS Topic Overview". Archived from the original on 1 May 2008. Retrieved 2008-05-01.
- ^ Reed D, Labarthe D, Chen KM, Stallones R (Jan 1987). "A cohort study of amyotrophic lateral sclerosis and parkinsonism-dementia on Guam and Rota". Am J Epidemiol. 125 (1): 92–100. PMID 3788958.
- ^ S. Kuzuhara, Y. Kokubo P3-146Marked increase of parkinsonism-dementia (P-D) phenotypes in the high incidence amyotrophic lateral sclerosis (ALS) focus in the Kii peninsula of Japan. Alzheimer's and Dementia, Volume 2, Issue 3, Pages S417-S417
- ^ Spencer PS, Palmer VS, Ludolph AC (Aug 2005). "On the decline and etiology of high-incidence motor system disease in West Papua (southwest New Guinea)". Mov. Disord. 20 (Suppl 12): S119–26. doi:10.1002/mds.20552. PMID 16092101.
- ^ "Sla, indagini nei club. Pesticidi nel mirino". Archived from the original on 3 October 2008. Retrieved 2008-10-02.
- ^ Wicks P, Abrahams S, Masi D, Hejda-Forde S, Leigh PN & Goldstein LH (2005) The Prevalence of Depression and Anxiety in MND, Amyotrophic Lateral Sclerosis and other Motor Neuron Disorders, Volume 6, Supplement 1, p. 147
- ^ Rachele MG, Mascia V, Tacconi P, Dessi N, Marrosu F (April 1998). "Conjugal amyotrophic lateral sclerosis: a report on a couple from Sardinia, Italy". Ital J Neurol Sci. 19 (2): 97–100. doi:10.1007/BF02427565. PMID 10935845.
- ^ Poloni M, Micheli A, Facchetti D, Mai R, Ceriani F (April 1997). "Conjugal amyotrophic lateral sclerosis: toxic clustering or change?". Ital J Neurol Sci. 18 (2): 109–12. doi:10.1007/BF01999572. PMID 9239532.
- ^ Camu W, Cadilhac J, Billiard M. (March 1994). "Conjugal amyotrophic lateral sclerosis: a report on two couples from southern France". Neurology 44 (3 Pt 1): 547–8. doi:10.1212/WNL.44.3_Part_1.547. PMID 8145930.
- ^ Cornblath DR, Kurland LT, Boylan KB, Morrison L, Radhakrishnan K, Montgomery M. (November 1993). "Conjugal amyotrophic lateral sclerosis: report of a young married couple". Neurology 43 (11): 2378–80. doi:10.1212/WNL.43.11.2378. PMID 8232960.
- ^ Corcia P, Jafari-Schluep HF, Lardillier D, Mazyad H, Giraud P, Clavelou P, Pouget J, Camu W (November 2003). "A clustering of conjugal amyotrophic lateral sclerosis in southeastern France". Neurol. 60 (4): 553–7. doi:10.1001/archneur.60.4.553. PMID 12707069.
- ^ Tyler HR, Shefner J. Amyotrophic lateral sclerosis. Handb Clin Neurol. 1991;15:169–215. Serial publication.
- ^ Rowland LP (March 2001). "How amyotrophic lateral sclerosis got its name: the clinical-pathologic genius of Jean-Martin Charcot". Arch. Neurol. 58 (3): 512–5. doi:10.1001/archneur.58.3.512. PMID 11255459.
- ^ "Farewell Speech". lougehrig.com. 4 July 1939. Archived from the original on 12 April 2008. Retrieved 16 April 2008.
- ^ Kiaei, M; Petri, S; Kipiani, K; Gardian, G; Choi, DK; Chen, J; Calingasan, NY; Schafer, P et al. (1 March 2006). "Thalidomide and lenalidomide extend survival in a transgenic mouse model of amyotrophic lateral sclerosis". The Journal of Neuroscience (Original article) 26 (9): 2467–2473. doi:10.1523/JNEUROSCI.5253-05.2006. PMID 16510725.
- ^ Abramova NA et al. (2002 Feb 15). "Inhibition by R(+) or S(-) pramipexole of caspase activation and cell death induced by methylpyridinium ion or beta amyloid peptide in SH-SY5Y neuroblastoma". J Neurosci Res 67 (4): 494–500. doi:10.1002/jnr.10127. PMID 11835316.
- ^ Gribkoff, V. K.; Bozik, M. E. (2008). "KNS-760704 [(6R)-4,5,6,7-tetrahydro-N6-propyl-2, 6-benzothiazole-diamine dihydrochloride monohydrate] for the Treatment of Amyotrophic Lateral Sclerosis". CNS Neuroscience & Therapeutics 14 (3): 215. doi:10.1111/j.1755-5949.2008.00048.x.
- ^ Robinson, R. (2010). "New Als Drug Shows Dose-Dependent Efficacy in Phase 2 Trial". Neurology Today 10 (13): 1–3. doi:10.1097/01.NT.0000384108.10957.21.
- ^ Cudkowicz, M.; Bozik, M. E.; Ingersoll, E. W.; Miller, R.; Mitsumoto, H.; Shefner, J.; Moore, D. H.; Schoenfeld, D. et al. (2011). "The effects of dexpramipexole (KNS-760704) in individuals with amyotrophic lateral sclerosis". Nature Medicine 17 (12): 1652–1656. doi:10.1038/nm.2579. PMID 22101764.
- ^ "Talampanel Trial Concluded with Negative Results". ALS Association. 17 May 2010. Retrieved 2013-06-13.
- ^ "Stem Cell Trial Dramatically Slows ALS". Retrieved 13 June 2013.
Further reading[edit]
- "ALS Hope Foundation". Archived from the original on 12 May 2008. Retrieved 2008-06-21. "Dedicated to the care and cure of people with Lou Gehrig's Disease. (from site page us.php)"
- "Lou Gehrig: The Official Web Site". CMG Worldwide. Archived from the original on 9 May 2008. Retrieved 2008-06-21. "The Official Web site of Lou Gehrig is an informational Web site intended to honor the life, the legend and the career of Lou Gehrig. (from site page siteinfo/index.htm)"
- Patrick Aebischer; Ann C. Kato (November 2007). "Playing defense against Lou Gehrig's Disease" (Paper). Scientific American (Verlagsgruppe Georg von Holtzbrinck). pp. 86–93. Retrieved 2008-06-21. "Researchers have proposed potential therapies for a paralyzing disorder once thought to be untreatable (sub-title)"
External links[edit]


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Greenpeace activists plant young beech trees in a Natura2000 sanctuary in Spessart Mountains. They replace approximately 2000 non-native, fast-growing Douglas pine seedlings with young beech seedlings.04/10/2012
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When it comes to shooting rifles, folks can be as passionate about the action type as they are about the calibers they prefer. It seems that each design has a niche, and yet all of them have been used for military, hunting, and target shooting applications. Is there one action type that can rule them all?
When it comes to speed of operation and ammunition capacity, the semi-automatic is king. The flexibility of this action makes it a popular choice in every shooting arena. However, this action type is more complex. As a result, it's more likely to jam, malfunction, or to be less accurate than other designs. And yet, quality manufacturing combined with a good ammunition match seems to overcome these problems.
Bolt actions provide some of the best shooting there is. This action offers dependable accuracy and the chamber strength needed to handle large, powerful cartridges. The bolt design is relatively simple, which increases its reliability. The sacrifice that comes with this design is slower operational speeds and lower ammunition capacities. This action tends to be popular with hunters and folks who are looking for long range accuracy.
The venerable old lever action, often seen in cowboy movies, is still alive and kicking. Thanks to period reenactment organizations and committed shooters, manufacturers are still turning out these actions. Usually levers are found attached to handy, carbine sized rifles. Though commonly found chambered in .30-30 and pistol calibers, modern examples of this breed chambered in serious hunting calibers can be found in the marketplace.
Pump actions, also known as slide actions, are commonly associated with shotguns. But don't let the sliding forearm fool you because pump action rifles are still on the shelf. The break actions also evoke visions of single-shot shotguns, but plenty of rifle variants are hanging around. The break action is possibly the most simple and sturdy of the common designs, but it limits the shooter to one shot per loading.
What qualities do you want in your rifle? Does it need to be sturdy, fast, powerful, accurate, or handy? Tell us which actions you are passionate about.
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text: I've realized that I'm acting like a jerk, correcting grammar mistakes and such, and decided to stop, it's annoying others. I've also been acting like an idiot with the whole 'Unofficial Moderator' thing, so I'll erase any traces of that, too. I've been trying to act funny by posting non-funny comments or pictures, and that also makes me look like a moron. I apologize to anyone who has been annoyed by me. I will stop correcting, acting like a mod, and trying to be funny or cool. Again, I'm sorry if I've ever annoyed you.


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We have stayed here at least twice a year for the past 6 years to attend races at the Texas Motor Speedway in Fort Worth. Six months ago we decided to stay at a Marriott closer to the track. We will never do that a again! There was just no comparison to the Residence Inn in Lewisville. We came back... More
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A model for the inhibition of CRISPR immunity by CRISPR decoys. Decoys consist of a silent CRISPR array cloned into a high copy number plasmid that presumably binds the targeting crRNA ribonucleoprotein complex, effectively reducing their availability to attack the target.
RNA Biology serves as a forum for current thinking on RNA, from coding and noncoding to therapeutic strategies based on that still very magic molecule. Our journal emphasizes RNA regulatory mechanisms (both natural and potentially therapeutic) and genomics as well as include post-transcriptional regulation at the mRNA level, even if a non-coding RNA is not involved. The scope covers non-coding RNAs, non-coding regions in mRNAs, and RNA-binding proteins.
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Medline/PubMed, PubMed Central, Science Citation Index Expanded (available as the ISI Web of Science, ISI Alerting Services, Biosis Previews and Biological Abstracts).


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Formation of hexagonal phase of TbMnO3 thin film and its multiferroic properties. J. Mater. Res. 2007;22:2156.
Epitaxial Stabilization of a New Multiferroic Hexagonal Phase of TbMnO3 Thin Films. Adv. Mater. 2006;18:3125.


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Banane Joe's Westminster Fame Tour
Last week, an adorable Affenpinscher named Banana Joe took home the top prize in American dog showing: the Best in Show title at the Westminster Kennel Club Dog Show. So how did the 2013 Best in Show winner spend his first 24 hours as America's most famed dog? Like most celebrities, Banana Joe spent his day making TV appearances, meeting other celebrities, dining at famous restaurants and enjoying photo opportunities at popular places, including making an appearance in a Broadway play, "The Mystery of Edwin Druid", at Studio 54.
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We continue to accept transfer student applications for the Fall 2013 semester on a space-available basis. International applicants, please review our new SAT/ACT policy.
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A variety of topics are covered in our Ask Admissions pages, including academics, housing and residence life, and more. Use the navigation links to the right to access questions and answers for the topics indicated.
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Seattle First Baptist offers many other events not listed in this special "music events" listing section. On our events calendar you will find listings for all of the events offered at Seattle First Baptist throughout each month.
Seattle Jazz Vespers is a monthly professional concert featuring the best jazz and blues performers in Seattle in one of the most acoustically resonant venues in the metro area. The performers play and sing their best music, their favorite numbers. They have the treat of performing to an appreciative, diverse audience where they are not competing with food and conversation. In this great concert setting, audiences truly get to know the performers and enjoy their artistry "up close." After the concert, join us for light refreshments and a chance to meet the performers. Seattle Jazz Vespers is sponsored by the historic Seattle First Baptist Church. An free-will offering will be taken to support the musicians. There are no tickets, no entry costs, no reservations necessary. It's just 100 minutes of Seattle's best jazz and blues with an inspirational interlude. Now, in its eleventh season, SJV is held the first Sunday of the month October through June. There is lighted adjacent parking at the church. The Seattle Jazz Vespers is designed for the general public, family friendly and persons of all faiths.


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Scent is better on a handkerchief than on the body. To see what I mean, try this simple test. Spray eau de cologne into the air, walk into the cloud and wait ten minutes. Much of the time, there'll be no discernable scent remaining, which does no good.
On the other hand, a scent remains fresh all day after it's sprayed into a handkerchief. Carried in a side pocket it doesn't offend people who dislike perfume. And it doesn't interact with your body chemistry, so it smells as it was intended to be smelled. Just open the handkerchief for a pleasant interaction.
During the day, a light fragrance like Acqua di Parma Colonia seems like a good choice. The lemony scent with a floral undertone hasn't changed since its origination in 1916, and, unlike many other good things, it's widely available. About $65 per 1.7 oz.
For evening, consider Creed's Vintage Tabarome, a leather and tobacco power scent that was originally commissioned for England's King George IV. Part of Creed's Private Collection, it's difficult to find in quantities smaller than 8.4 ounces (that's about a five year supply unless it's used for bathing), but the eBay wholesaler Perfume Wizdome sells it decanted into 2.5 ounce bottles priced at $130. Be aware that most of what's out there is a newer version called Tabarome Millesime which is not the same scent.
When it comes to handkerchiefs, I like them in colored cotton like the ones in the photo at the top from Schweitzer Linens (on sale for $30 each). With a spray of scent.
Friday, November 2, 2007
The Scent Of Your Handkerchief
5 comments:
- John said...
Will, I have spent a lot of money on pocket squares trying to convince myself that I should be wearing them. But in the end, I always go back to my folded white linen pocket square. The others seem to be too dressy for me. And I buy conservative ones from Paul Stuart and Ralph Lauren and Turnbull & Asser. But the one you showed seems like it may be good for me. I think I'll try it out along with the cologne. Thanks and great post as always.
- November 2, 2007 at 9:33:00 AM PDT
- Jocke said...
Aqua di Parma is hardly a light fragrance in my opinion..
Also, I'm not sure I get the point of spraying your handkerchief. To smell yourself or for others to smell? - November 2, 2007 at 9:48:00 AM PDT
- Will said...
Compare Acqua di Parma to Vintage Tabarome and you'll think it's light. :-)
I spray my handkerchief for me. - November 2, 2007 at 6:25:00 PM PDT
- Matthew said...
If I remember correctly creeds use of milleseme simply denotes that the scent is a eau de parfum and not just a eau de toilette.
- November 3, 2007 at 5:50:00 PM PDT
- Will said...
That's right but they are two different scents. I have them both.
- November 3, 2007 at 6:30:00 PM PDT


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LFX27L3-BS12 comes with a limited two-year warranty and replaces the following popular batteries: 53030L, YB30CL-B, YB30L-B, YIX30L, YIX30L-BS. So whether you have a motorcycle, ATV, jetski or a snowmobile, choose Shorai LFX27L3-BS12 as the battery of your choice!
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Market chairman lands national role (From The Oxford Times)
When It Happens Panel Get involved: send your photos, videos, news & views by texting 'OXFORD NEWS' to 80360 or email
Market chairman lands national role
5:20pm Wednesday 11th April 2012 in Bicester
DEDDINGTON Farmers' Market chairman Geoff Todd has been elected to the Council of the National Farmers' Retail and Markets Association (Farma) for the next three years.
Mr Todd helped set up the market in 2001 as part of Deddington Market Management Group.
He has seen the market grow from 12 to 60 stalls over the past decade.
Over the years he has been the group's treasurer, headed up marketing and public relations and now is its chairman.
Mr Todd said: "Naturally I am honoured to have been elected.
"I'm looking forward to sharing the experience gained at Deddington Farmers' Market."


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The Paige is a new addition to the Justin® Ladies Jeweled Flip-Flops by M&F®! The unique styling of these sandals makes them a must have for anyone's wardrobe. The Paige sandal, in black, has a clear stone bling strap that provides amazing sparkle. The front center of the Paige features a clear stone cross accented by smaller stones along the edge of the cross. This sandal has a 1 3/4" wedge heel and a 1 1/4" strap over the foot. For comfort and style, step out in a pair of Justin® Jeweled Flip-Flops by M&F®.


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I am in a state of exhausted delirium right now, or maybe it's delirious exhaustion. As a result, I decided to make myself a Terminal greeter that tells me a true statement every time I log in to BASH. I coded it in about half an hour just a few minutes ago, with great results. Some I've gotten so far are "robots are sick", "cyborgs are most bitchin'", "dolphins are the bomb", "SNES games are nifty", and "pizzas are radical". It just picks a random noun and a random adjective, with the occasional modifier and the ultra-rare super secret sentence extension (it's "to the MAXX"). Also, for some reason, I was in the mood to come up with rhyming couplets based on the ends of my sentences; I'll tweet them @EmmettButler when I come up with them. My favorite is
I'm a jerkface in the workplace
I keep all my shirts in a shirt case
A good evening.
If I were choosing a movie to watch as the world was ending, I'd have to go with "2001: A Space Odyssey".
Glamour shot, activate!


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- Home Photo Galleries Photo
- PHOTO GALLERY: Looking back at Return Day
- Posted Nov. 7, 2012 midnight
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When truth stumbles in the street
The sovereignty of God and the free will of man are parallel truths that we experience as we move toward the coming of the Son of Man.
God makes it clear in His word that what He decides is greatly dependent on the behavior of man- eternal life or judgment.
As we look at our national situation through the study of Scripture. May God awaken us to His righteousness.
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Looks like this event has already ended.
Check out upcoming events by this organizer, or organize your very own event.
Reproductive Science Center Family Day 2012RSC of the Bay AreaSunday, August 19, 2012 from 11:00 AM to 4:00 PM (PDT)San Ramon, CA |
Who's Going
Event Details
The doctors and Staff at RSC are proud to announce Family Day 2012.
Every few years we try to organize a reunion of former patients for a day of fun and games.
Food will be provided (from 12:30 - 2:00pm) and a number of fun activities will be organized at Little Hills Ranch (http://theranchatlittlehills.com/index.php) in San Ramon.
For Everyone | Just for Kids |
*Basketball | *The Grand Sand Box |
*Ping Pong |
*Playground |
*Horseshoes | *Air-brush body art |
*Volleyball | *Bounce House |
*Self-guided hiking | |
*Kayak Races | Picnic Favorites |
*TV for sports viewing | *Rock Climbing Wall |
*Tetherball | *Softball |
*Trout Pond | *Swimming Pool |
*Badminton |
When & Where
The Ranch at Little Hills, San Ramon
18013 Bollinger Canyon Rd
San Ramon,
Sunday, August 19, 2012 from 11:00 AM to 4:00 PM (PDT)
Add to my calendar
RSC of the Bay Area
Reproductive Science Center –San Francisco Bay Area's Fertility Clinic for more than 25 Years
RSC is a leading San Francisco infertility network that has proudly served the Bay Area since 1983. With several San Francisco fertility treatment options available, it's important to find trusted specialists with experience. Our doctors, some of the nation's most distinguished infertility pioneers, have offered more than a quarter-century of fertility care to thousands of families from across the globe. When it comes to treating infertility, RSC is the Bay Area fertility clinic known for its outstanding success rates and egg donor program. We will work with you to help achieve your dreams of a family.


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6. | frequent flier | ||
(FREE-kwent FLY-er) noun. someone who wants a discount or freebie because they purchase controlled substances from the same supplier on a regular basis Sue: Hey, I want to buy another teener today. Could I have a discount as I am a frequent flier?
Sue: Since I am a frequent flier can I get this at half price? |
1. | frequent flier | ||
1) Commonly, someone who is a repeat user of a product or service, regardless of the nature of the business.
2) In healthcare, someone who is frequently showing up for similar injuries or disorders. Often, this is applied specifically in the world of drug and alcohol rehabilitation (rehab) to somebody who has tried to get sober (clean up or dry out) but has had frequent relapses. According to current statistics, the majority of addicts (80%) are likely to relapse after the first try. 1)"You watch the register, I'll take care of Mr. Jones. Don't worry, I've already got his order. It's the same thing every day. He's one of our frequent fliers."
2)"Looks like we've got Sandy back again. Room 5. Yup, heroin again. We've got her on some Seroquel and an Ativan drip, so at least she's calm this time. She's another one of our frequent fliers." |
2. | frequent flier | ||
Someone who is constantly high on cheap or unreliable drugs, such as Pot or Crack Hey look at that high guy!
Yeah, he's a frequent flier DAUMMN! |
3. | frequent flier | ||
Somebody who uses class A drugs often.
i.e is frequently flying Is John ok, he looks like he needs an ambulance ?
No, he's used to this kind of thing, he's a frequent flyer. |
4. | frequent flier | ||
Someone who has a lot of patience to go through airport security numerous amounts of times. Damn, I don't know how a frequent flier can handle the tight security here.
5. | frequent flier | ||
One who travels often by air, especially on one airline. My stepdad is a frequent flier, he is a super gold level on his frequent flier account. At this rate he will never have to but another airline ticket again because he has so many frequent flier miles.
7. | frequent flier | ||
1) One who travels by airplane often.
2) A person most likely to prematurely leave a gathering. 1) I fly lots, so it's cheaper.
2) Mitch sure fucked off quick, didn't he? |


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Economic Stimulus Bill Mandates $954 Million For Vaccinations |
Feb 13 2009, 11:52 AM
Group: Valued Member Posts: 2,327 Joined: 23-October 06 Member No.: 145 |
They are giving away our jobs overseas, stealing from us, planning another war and they are concerned we don't get enough vaccinations??
http://www.prisonplanet.com/economic-stimu...s-programs.html Economic Stimulus Bill Mandates $954 Million for Vaccinations, $545 Million for Genomics Programs Mike Adams Natural News Friday, Feb 13, 2009 While the Obama administration is attempting to pass the American Recovery and Reinvestment Act of 2009 in a hurry, NaturalNews readers have begun actually reading the bill, and theyre finding some worrying language that should raise concern among people interested in preserving health freedom and protecting the health of all Americans. Specifically, one section of the economic stimulus bill designates nearly a billion dollars for new vaccinations of children. This was discovered by Elisha Celeste, a NaturalNews reader. As stated in the bill: $954,000,000 shall be used as an additional amount to carry out the immunization program authorized by section 317(a), (j), and (k)(1) of the Public Health Service Act (section 317 immunization program) The issue of whether vaccinations are actually helpful or harmful is hotly debated, of course. The pro-vaccine camp believes that the human immune system is a technological failure and that chemical intervention is the only way to protect children. The anti-vaccine camp believes that exposure to non-fatal infections actually strengthens the immune system, creating stronger protections against future infections. Thus, vaccines actually interfere with normal, healthy immune function while injecting children with dangerous chemicals and substances derived from sick, diseased animals. NaturalNews is against childhood vaccines as explained in this article that completely debunks conventional beliefs about vaccinations: http://www.naturalnews.com/025596.html Genomics programs? The economic stimulus bill also requests more than half a billion dollars for genomics programs, saying: $545,000,000 shall be used as an additional amount to carry out chronic disease, health promotion, and genomics programs Whats interesting about this last quote is that it essentially says this half a billion dollars should be used to carry out three things: 1) Chronic disease programs 2) Health promotion 3) Genomics programs I dont have a problem with the second point. Health promotion sounds good (unless its nothing more than mammograms and mental health screening programs designed to sell more chemotherapy and psych drugs). But what, exactly, is meant by the phrase to carry out chronic disease? And what is meant by genomics programs? Are we talking about government-funded genetic experimentation on human babies, perhaps? It wouldnt be the first time. See: http://www.naturalnews.com/019189.html |
Feb 22 2009, 10:26 AM
Group: Global Mod Posts: 5,019 Joined: 2-October 07 From: USA, a Federal corporation Member No.: 2,294 |
You can get PDF copies of thousands? of pages of the "Stimulus Pacackage" here:
http://appropriations.house.gov/ |
Feb 22 2009, 10:28 AM
Group: Global Mod Posts: 5,019 Joined: 2-October 07 From: USA, a Federal corporation Member No.: 2,294 |
Official: Obama plans to slash deficit in half By LIZ SIDOTI, Associated Press Writer 55 mins ago WASHINGTON President Barack Obama has committed hundreds of billions of dollars to help revive the economy and is working on a plan to cut the federal deficit in half by the end of his first term. Obama will touch on his efforts to restore fiscal discipline at a White House fiscal policy summit on Monday and in an address to Congress on Tuesday. On Thursday he plans to send at least a summary of his first budget request to Capitol Hill. The bottom line, said an administration official Saturday, is to halve the federal deficit to $533 billion by the time his first term ends in 2013. He inherited a deficit of about $1.3 trillion from former President George W. Bush. The official, speaking on condition of anonymity because the president has not yet released his budget for the fiscal year 2010, which begins Oct. 1, said the deficit will be shrunk by scaling back Iraq war spending, ending the temporary tax breaks enacted by the Bush administration for those making $250,000 or more a year, and streamlining government. "We can't generate sustained growth without getting our deficits under control," Obama said in his weekly radio and Internet address that seemed to preview his intentions. He said his budget will be "sober in its assessments, honest in its accounting, and lays out in detail my strategy for investing in what we need, cutting what we don't, and restoring fiscal discipline." Obama's budget also is expected to take steps toward his campaign promises of establishing universal health care and lessening the country's reliance on foreign oil. Obama has pledged to make deficit reduction a priority both as a candidate and a president. But he also has said economic recovery must come first. Last week, he signed into law the $787 billion stimulus measure that is meant to create jobs but certainly will add to the nation's skyrocketing national debt. He also is implementing the $700 billion financial sector rescue passed on Bush's watch; about $75 billion of which is being used toward Obama's plan to help homeowners facing foreclosure. |
Feb 22 2009, 10:37 AM
Group: Administrator Posts: 7,987 Joined: 13-September 06 Member No.: 49 |
Let me guess how Obama is going to cut the deficit in half - expand government programs, keep our troops overseas, and spend a ton of money bailing out banks and car manufacturers? I guess the only thing we can infer is he intends to print a lot of money and seriously raise taxes.
What a joke. What a disaster. |
Feb 24 2009, 10:21 PM
Group: Active Forum Pilot Posts: 832 Joined: 23-December 06 Member No.: 360 |
The medical-Trust me the Satanism is in the details.
HIPPA, that promise of "private" medical records well the real purpose of HIPPA was to indoctrinate the medical community into a Nazi like "service your client in complete secrecy" zombinalic trance. Once "your" medical records are digitized the entire world can access them without your knowledge, consent or route to challenge/appeal/look at. The complete chart is here. http://www.patientprivacyrights.org/site/P...Medical_Records Second point Big pharma is ramping up prices on drugs sometimes in the Thousand percent range. Why? Because they know mandatory insurance (yes, like mAssashuetts you MUST buy) is coming. You "vill" support big pharma, like it or not, afford it or not. Another clue from the past -Bill Frist Dennis Hastert Immunity for Big Pharma http://www.citizen.org/documents/050406PandemicFinal_1.pdf Then Codex alimentarius or the global depletion of natural foods and suppliments. Don't worry big pharma will sell you "the cure". Plus genetic information allows them to really create The ultimate bioweapons. So go ahead, try to find a non-electronic doctor. How bout I just stick that needle in your eye. My most recent experience was dealing with both my aging parents so in November of this year I got an education by the parasitic, Satan inspired medical and legal establishment. Please do the Ghandi thing and stop ingesting their crap unless you absolutely need it. If you absolutely need it, find out why and if there are natural alternatives. |
Jun 21 2009, 01:39 AM
Group: Global Mod Posts: 5,019 Joined: 2-October 07 From: USA, a Federal corporation Member No.: 2,294 |
Lo-Fi Version | Time is now: 20th June 2013 - 12:31 AM |


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Post by Hal Lindsey
Last January, then Secretary of State Hillary Clinton appeared before the Senate Foreign Relations Committee. The committee was probing the attack on our diplomatic compound in Benghazi, Libya, that resulted in the deaths of U.S. Ambassador Chris Stevens and three others from the mission.
In a moment of frustration that has already returned to haunt Mrs. Clinton, the Secretary blurted out: "What difference, at this point in time, does it make?"
She was responding to combative questions about "who" the killers were – terrorists or a runaway mob protesting an obscure movie promo on the internet. Obviously straining hard to avoid truthfully answering the question and thus indicting herself and her boss, Mrs. Clinton almost screamed, "What difference… does it make?"
Two things disturb me about that question. First, if our Secretary of State honestly didn't realize what difference it makes, then she should not have been Secretary of State (or even a Senator as she was previously), much less President (as she wants to be).
Second, if she did realize the difference it makes, then she was scrambling hard to cover up her and her boss's culpability (and dishonesty) and she thought she could bully the Senators into submission.
Either conclusion is disturbing.
Fast forward to April 17. Present Secretary of State John Kerry appeared before a House committee hearing. During the questioning, the subject of Benghazi came up. When pressed about what he planned to do about rectifying the situation and finding the culprits responsible for the breakdown of security that caused the death of our Ambassador, Kerry also became a bit annoyed and dismissed the questioning with this statement: "We got a lot more important things to move on to and get done."
Again, two things disturb me about that response. First, for a Secretary of State, who is personally responsible for the safety of the Ambassadors and personnel under his leadership, what could possibly be more important than discovering what went wrong in Benghazi, who was responsible, where the killers are now, and how we can prevent it from happening again?
Second, doesn't anyone in the Democrat party remember the motto of one of their most respected past Presidents? Harry Truman famously displayed a slogan on his desk that was unequivocal. It read: "The buck stops here."
Apparently this Administration thinks that slogan means "the male deer stops by here occasionally to graze the south lawn!" (Speaking of ducking responsibility, I see today that Nancy Pelosi is publicly blaming George W. Bush for the IRS scandal. See what I mean?)
I don't know how anyone could have watched last week's House hearings and not been incredulous at the way the Administration handled that crisis. How could you not be outraged that those same officials who stood by as our Ambassador and three others were brutally killed, then chose to cover up their incompetence (or worse, it could be their fear of offending Muslims or their fear of offending the American electorate) by lying to the American people for weeks after the tragedy.
On this week's program, I'll give you several reasons why I think Benghazi matters to America.
Wired magazine recently revealed that the new immigration bill currently wending its way through Congress may contain a little surprise. Within the 800-page bipartisan bill "is language mandating the creation of… 'photo tool', a massive federal database administered by the Department of Homeland Security and containing the names, ages, Social Security numbers and photographs of everyone in the country with a driver's license or other state-issued photo ID."
Requiring employers to search this database before hiring anyone, the idea is to stop employers from hiring illegal aliens. But this measure swats that fly with a sledgehammer!
Even the ACLU is uncomfortable with the idea of the government "keeping a record of all things."
Hey, I know one guy who will be very appreciative if this system is in place when he finally rises to power. I don't know his name yet, he's not been revealed, but I'll bet he's watching to see what happens to this legislation.
Syria continues to spiral into chaos. I don't recall there being a regional or national crisis as geopolitically confusing or sensitive as this one. There really aren't any "good guys" in this civil war. Of course, Bashar al Assad is a brutal dictator (though not as decisively brutal as his father), but the rebels are led by none other than al Qaeda. And though the West doesn't want Assad to remain in power, neither do we want the rebels to gain control of his chemical WMD arsenal. And, surprisingly, Israel would prefer to deal with the devil it knows (the self-preserving Assad), than the devil it doesn't (the terrorist rebels with chemical weapons).
As a result, the New York Times is calling southern Syria "an ungoverned area." Sounds like the Sinai peninsula, doesn't it? Israel continues to be surrounded by a ring of enemies that are growing increasingly hostile: Lebanon (Hezbollah), Syria, the "rebels" in lawless southern Syria, Jordan (under increasing threat by the Palestinian majority), the jihadists in the lawless Sinai peninsula, Egypt, and Gaza (Hamas). Of course, beyond them are Iraq, Iran, and the other Arab/Muslim states that despise Israel; and within Israel are the Palestinians.
And the Syrian crisis is making for some strange bedfellows. Turkey's fear of Syria is encouraging a rapprochement with Israel. Even Russia, which stands to lose its Mediterranean naval base at Tartus, is making unusual and disquieting diplomatic overtures to Israel.
Prophetically, we know that Syria will sooner or later fall into tremendous armed conflict. The prophet Isaiah predicts in the 17th chapter of his book that, overnight, Damascus will be utterly destroyed and rendered forever uninhabitable. We know that prophecy has yet to be fulfilled because Damascus is still standing today and is the world's oldest inhabited city that has never been destroyed and rebuilt.
If nothing else, that unfulfilled prophecy alone should encourage all of us to be ready for Christ's imminent return to rapture His Church before the awful events of the Great Tribulation begin.
And speaking of Christ's church, it grieves me to say that I believe the "church" in America in these last days more closely resembles the church at Laodicea described by the Apostle John in Revelation 3. Jesus said that it was blind to its own failures and shortcomings and mistakenly thought it was successful because it was rich and needed nothing. Instead, Jesus said, it disgusted Him because it was "neither cold nor hot," but "lukewarm." And because it was lukewarm, He wanted to "spit you out of My mouth."
Friends, as we rush headlong into the final days of the Church Age, let's follow Christ's own advice in the third chapter of Revelation. Humbly ask Him to make us "gold refined by fire" and provide us "white garments (His righteousness) so that you may clothe yourself" and "eye salve to anoint your eyes so that you may see." As never before, we believers need to be righteous and pure before God and clear-eyed to see the danger around us in these final days.
Do that today. Ask His forgiveness of your "lukewarmness." Confess the sins you know about in your life and trust Him to forgive you (1 John 1:9). Then He'll do more than that, He'll cleanse you of "all unrighteousness," which means the sins of which you are unaware, but guilty.
And if you've never accepted the free pardon that Jesus Christ purchased with His death on Calvary, you can do that right now, too. In fact, in Revelation 3:20, Jesus says that He stands outside the door of your heart and patiently knocks. He promises, "…if anyone hears My voice and opens the door, I will come in to him and will dine with him, and he with Me."
As you read this, many of you "hear" Him knocking at the door of your heart. Don't leave Him standing there. Open your heart to Jesus and, just as He promises, He will come in and fellowship with you.
Simply invite Him in. Ask Him to forgive you of your sins. Ask Him to become Lord of your life. Believe that He has done so and accept His free gift of pardon. Just like that, if you are sincere, you have become a part of God's "forever family." Now, you need not fear what waits for you after this life, you've just changed your destination reservation! You are bound for heaven!
Finally, now that you've joined God's family, ask Him to guide you to a solid, Bible-believing church. As we near the end of this Age, the Apostle Paul warned that these would be "perilous times." You will need the strength and encouragement that comes from fellowship with other sincere believers. And you need to continue to grow in the Word of God. So find a church or fellowship that believes, preaches, and trusts the whole Word of God, not just the "feel good" variety.
Don't miss this week's Report on TBN, Daystar, CPM Network, The Word Network, various local stations, http://www.hallindsey.com or http://www.hischannel.com. Check your local listings.
God Bless,
Hal Lindsey
mail: HLMM, P.O. Box 470470, Tulsa, OK 74147
email: email@example.com
web: http://www.hallindsey.com


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Eagles may not want Gus Bradley to leave Philly
Is the bus slowing down?
While the Eagles are set to meet with Gus Bradley sometime this afternoon and could conceivably come to an agreement to name him their next head coach today, a source close to the situation said that a deal was not imminent.
The Eagles met with Bradley in Atlanta on Saturday for a first interview, but the meeting lasted only approximately two hours because he was still preparing to face the Falcons the following day in a divisional playoff game. The Seahawks lost, however, and the Eagles are now considering the second interview an extension of the first, the source said.
Bradley is scheduled to land in Philadelphia around 2:30 p.m. this afternoon. He will sit down with owner Jeffrey Lurie, general manager Howie Roseman and team president Don Smolenski. Bradley also interviewed with the Chargers on Thursday, but San Diego came to terms with Broncos offensive coordinator Mike McCoy today.
While the team has one less suitor to compete with if they indeed have set their sights solely on Bradley -- and the scuttlebutt around the NFL is that they have -- he does have another interview scheduled with the Jaguars on Wednesday.
It may be within Lurie's best interest to not allow Bradley to leave Philadelphia without signing a contract. That being said, the process could take longer than expected if there is a snag in negotiations. The Eagles have turned over a number of stones in their two-week long search for Andy Reid's replacement.
So what's another few days?
They have already interviewed Falcons defensive coordinator Mike Nolan and Falcons special teams coordinator Keith Armstrong on Jan. 2, Penn State coach Bill O'Brien on Jan. 3, Oregon coach Chip Kelly on Jan. 5, McCoy on Jan. 6, former Ravens coach Brian Billick on Jan. 7, Notre Dame coach Brian Kelly on Jan. 8, former Bears coach Lovie Smith on Jan. 10, Bradley on Jan. 12, former Cardinals coach Ken Whisenhunt and Bengals offensive coordinator Jay Gruden on Jan. 14.
Those are just the confirmed interviews. Bradley is the only one that has had a second meeting. The Eagles were granted permission to meet with Colts offensive coordinator Bruce Arians, but that interview has yet to be scheduled, according to a NFL source.
The Eagles opened their search intent on snaring an innovation college coach like Chip Kelly or O'Brien. When both elected to stay at their schools, Lurie and company moved onto the next phase. Brian Kelly was in the mix, but he, too, chose to stay at his university.
Even before the Eagles met with Bradley, he was considered a serious contender. The second interview confirms that he is a finalist, at the very least. Whisenhunt, Gruden and Smith are legitimate adversaries. They may not get a follow-up interview, however, if the Eagles seal the deal with Bradley over the next 24 hours.
Until then, hang on for the rest of the ride.


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7. | butterball | ||
Buttnaked shorty got butterball quick
1. | butterball | ||
A over weight girl that has always wear tight clothing. and the fat is oozing out of her clothing. Amanda is a fuckin butterball. she's so fucking fat that her clothing doesn't want to stay on her body.
2. | butterball | ||
Someone who is quite large in size, but not in an overly grotesque way! Look at that butterball, he takes up two seats in the cafeteria.
3. | Butterball | ||
A sex act wherein the man shaves off all of his pubic hair so that his flaccid genitals resemble a dead bird, and coats his crotch in butter. He then drags his testicles across the face of his sleeping significant other, whilst gobbling like a turkey. Especially popular during the holiday season. Autumn was angry when Patrick woke her on Thanksgiving morning with an especially greasy butterball.
4. | Butterball | ||
The opposite of "butterface", meaning a female who is extremely attractive from the neck up, yet it has an exceptionally unattractive figure or disfigurement not affecting the facial appearance. Dude 1: "Hey, did you see that 'butterface' Aj took home last night?
Dude 2: "Yeah, but did you see her 'butterball' friend? Dude 3: "Hell yeah. That's a huge bitch." |
5. | butterball | ||
Slang for an intravenous shot of meth or any other similar uppers like dexedrine, ephedrine, or benzedrine. David- "Hey whats goin on Jesus?
Jesus- "I'm about to do a big fat butterball then watch porn for five hours." |
6. | Butterball | ||
A precious little person who squeaks. La dee dee do. Butterball was precious today. She squeaked when I tickled her. So I fed her a cracker.


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As below I'm a 90kg intermediate long term surfer. I've had a 6'8" Alt which I got as I was coming back into the water after a long layoff. While it's fine I feel I can do with a touch less volume. I recently bought a 6'4" Futura which paddles fine. While it hasn't got float for the absolutely most gutless waves, it has enough for most conditions. Copunterbalancing that, as I'm getting older I feel like I can benefit from a touch more width than is probably "standard" on my boards.
The board would be used typically in head high plus beach break, reef break and point conditions. While there is no doubt a lot of overlap with the Alt and the Futura, so far I'm finding the Alt just a touch more responsive.
So I was wondering what views there were around me doing a CBD customisation on a 6'6" by making only one change, namely bringing the width out to somewhere between 20" and 20.25". The latter width is exactly the same as the 6'8" which I like, and indeed provided that's not considered too extreme that's probably what I'd do. It'd probably replace the 6'8" but I may keep the 6'8" for a while just out of caution.


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I give the staff a five! I do have to say that even after getting a special rate I can not see how this place should ever be over 100$ a night. The design is laid out like an apartment complex and gave me a bit of a unsafe feel. something about walking down stairs where no one can see... More
- Also Known As:
- Residence Inn Kansas City Downtown/Union Hill Hotel
- Residence Inn Kansas City Downtown/Union Hill Hotel Kansas City
- Residence Inn Kansas City
- Kansas City Residence Inn
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- TripAdvisor is proud to partner with Travelocity, Expedia, Booking.com, Marriott, Olotels, Hotels.com, Venere, Cheap Tickets, Agoda, Priceline, HotelsClick and Tingo so you can book your Residence Inn Kansas City Downtown/Union Hill reservations with confidence. We help millions of travellers each month to find the perfect hotel for both holiday and business trips, always with the best discounts and special offers.


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Rock Hall of Fame to open Rolling Stones exhibit
CLEVELAND (AP) — The story of The Rolling Stones is so huge it takes 2½ floors of The Rock and Roll Hall of Fame and Museum to tell.
The Cleveland-based museum will open "Rolling Stones: 50 Years of Satisfaction," an exclusive exhibit celebrating the archetypal rock band, on May 24.
The exhibit will be open until March 2014 and will include personal and collected items that have never before been seen by the public along with film, text and interactive components and periodic lectures on the band's 50-year career. The entire exhibit will take up more than two floors of the museum.
Mick Jagger, Keith Richards and The Stones recently held a series of concerts to celebrate their 50th year together and there have been rumors of more activity.
Online: http://rockhall.org
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Stayed here for a few days in march. Very basic hotel, no bar, small rooms but very clean, friendly staff and ideal for staying whilst at the rugby sevens. Free wifi!! Everything you need is right outside the hotel, food, drink and the metro so excellent location and will be staying there again next march!
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