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Causes include rheumatic heart disease (now itor the clinical effect of the valve lesion is to measure rare in the United Kingdom) order cialis 10mg without prescription erectile dysfunction drugs in nigeria, infective endocarditis the left ventricular dimension purchase cialis paypal erectile dysfunction vacuum pumps. An end systolic dimen- occurring on a previously damaged or bicuspid aor- sion of over 5 cm indicates decompensation. Causes include se- infective endocarditis should be administered when vere hypertension, dissecting aneurysm and Marfan’s appropriate. It is only when volume overload is heart size or diminishing left ventricular function are excessive and chronic that the left ventricle fails. The indications for surgical intervention usually by valve first sign of this decompensation is a reduction in the replacement. There is also reduced coronary artery perfusion with associated increased risk of myocardial ischaemia. Prognosis Mild or moderate aortic regurgitation has a relatively good prognosis and thus surgical intervention is not Clinical features required. However, it is important to perform surgical Aortic regurgitation is asymptomatic until left ventricu- correction before irreversible left ventricular failure lar failure develops. Onexamination there is a large volume pulse, which is collapsing in char- acter (see page 27). The blood pressure has a wide pulse Aortic stenosis pressure (high systolic and low diastolic pressure). Various signs of the high-velocity blood flow Aortic stenosis is a pathological narrowing of the aortic have been described but are rare. There is however turbulent r Echocardiography is diagnostic, often showing cusp flow across these valves, which become thickened and thickening and calcification. Severe stenosis may develop over a period of the degree of stenosis and can measure left ventricular 20–30 years. It may lead to thicken- r Treatment includes management of angina and car- ing and calcification of the aortic valve, which is often diac failure. This pres- r Severe stenosis (pressure gradient over 60 mmHg) or sure overload results in left ventricular hypertrophy and symptomatic stenosis are indications for surgery (see arelative ischaemia of the myocardium with associ- page 30). As the stenosis becomes more severe, re- but this is increased if coronary artery bypass is also duced coronary artery perfusion exacerbates myocardial required. Balloon valvuloplasty may be used in pa- ischaemia even if the coronary arteries are normal. Im- tients unfit for surgery or to improve cardiac function paired left ventricular emptying is most apparent dur- prior to surgery. Ischaemia and hypertrophy of the left ventricle may lead Prognosis to arrhythmias and left ventricular failure. Clinical features Patients are asymptomatic until there is severe steno- sis when they present with exercise-induced syncope, Pulmonary stenosis angina or dyspnoea. Narrowing of the pulmonary valve, resulting in pressure On examination the pulse is low volume and slow ris- overload of the right ventricle. On palpation there may be an aortic systolic thrill felt in the right second intercostal space. Aetiology The apex is slow and thrusting in nature but not dis- This is almost invariably a congenital lesion either as an placed. On auscultation there may be a systolic ejection isolated lesion or as part of the tetralogy of Fallot. Rarely click, followed by a mid-systolic ejection murmur heard itmaybeanacquiredlesionsecondarytorheumaticfever best in the right second intercostal space and radiating or the carcinoid syndrome. The murmur is best heard with the patient leaning forward with breath held in expiration. Pathophysiology The obstruction to right ventricular emptying results Investigations in right ventricular hypertrophy and hence decreased r Chest X-ray may show a post-stenotic dilation of the ventricular compliance, which leads to right atrial ascending aorta and left ventricular hypertrophy. If severe, the condition leads to right Chapter 2: Rheumatic fever and valve disease 47 ventricular failure, often with accompanying regurgita- Aetiology tion of the tricuspid valve and signs of right-sided heart Tricuspid regurgitation can be divided into functional, failure. Patients with mild r Organic tricuspid regurgitation occurs with rheuma- pulmonary stenosis are asymptomatic (diagnosed inci- tic mitral valve disease, infective endocarditis and the dentally from the presence of a murmur or the presence carcinoid syndrome. Patients the tricuspid valve is seen particularly in intravenous mayhavenon-specificsymptomssuchasfatigueordysp- drug abusers. Syncope is a sign of critical stenosis, which requires plasia of the tricuspid valve with abnormal valve urgent treatment. Auscultation reveals a click and harsh Pathophysiology mid-systolic ejection murmur heard best on inspiration Regurgitation of blood into the right atrium during sys- in the left second intercostal space often associated with tole results in high right atrial pressures and hence right a thrill. A left parasternal heave may also be felt due to atrial hypertrophy and dilatation. In the chronic un- cases intervention is required before decompensation of treated patient there can be hepatic cirrhosis from the the right ventricle occurs. Echocardiography is diagnostic and is also essential to assess right ventricular function. Tricuspid regurgitation Definition Management Retrograde blood flow from the right ventricle to the Functional tricuspid regurgitation usually resolves with rightatrium during systole. Severe organic tricuspid 48 Chapter 2: Cardiovascular system regurgitation or refractory functional regurgitation may Sinus nodal arrhythmias require operative repair (or rarely replacement). Cardiac arrhythmias A cardiac arrhythmia is a disturbance of the nor- Aetiology mal rhythm of the heart. Tachycardias are also subdivided according to their Clinical features origin: Most patients are asymptomatic but occasionally post- r Sinustachycardia. If bradycardia is episodic and severe, syncope r Ventricular tachyarrhythmias such as ventricular may occur. However, in patients with bundle branch block Most cases do not require treatment other than with- and in cases where the rapid rate of supraventricu- drawal of drugs or treatment of any underlying cause. Chapter 2: Cardiac arrhythmias 49 Sinus tachycardia rate may be regular, bradycardic, tachycardic or variable with pauses. Carotid sinus massage typically leads to a Definition sudden and sometimes prolonged sinus pause. Aetiology/pathophysiology Sinustachycardia is a physiological response to main- tain tissue perfusion and oxygenation. Causes include Complications exercise, fever, anaemia, hypovolaemia, hypoxia, heart The most important complication is cardiac syncope, as failure, hyperthyroidism, pulmonary embolism, drugs in other forms of bradycardia. Clinical features Investigations Palpitations with an associated rapid, regular pulse rate. In addition anti-arrhythmic drugs may be required to Management controlanytachycardia. Atrial arrhythmias Sinus node disease Atrial ectopic beats Definition Sinusnode disease or sick sinus syndrome is a tachy- Definition cardia/bradycardia resulting from damage to the sinus Atrial ectopic beats include extrasystoles and premature node.

This alone can greatly reduce the dose to the patient population purchase cialis discount erectile dysfunction depression treatment, especially in younger patients where the radiation is more pertinent to their lifetime accumulation to cancer risk buy cialis 2.5mg line erectile dysfunction medication free samples. Caesium iodide or cadmium zinc telluride have proven to be very expensive but improve sensitivity and energy resolution. Generally, cameras that use 3-D mode need less of a radioisotope than cameras that have to operate in 2-D mode. Operating in 3-D mode makes it possible to decrease the dose to the patient to as much as 1. If there is a cyclotron in the hospital, and ammonia can be used, an even lower dose could be given as in 3-D mode only about 10 mCi is needed, which puts the effective dose at roughly 1. There are studies that report that, with list-mode and the right use of processing software, one dynamic study can be acquired and the software can be used to create the gated and perfusion images. With this type of hardware and software, the effective radiation dose to the patient can again be reduced just by eliminating extra acquisition scans. Older cameras that do not have this type of hardware and software would require that four doses be injected to achieve both the dynamic study for coronary flow and another for the gated imaging. Rubidium can be produced in a generator every four, five or six weeks depending on the number of patients. Technically, the technologist can also influence the exposure to a patient by adjusting several of the components of the cardiac study. First of all, if the energy window is widened, there can be an impact on the counts acquired in a study. As a technologist, it is necessary to note the downside of widening the window, as it will also increase the scatter, which reduces image contrast. If the camera has iterative scatter correction, there will be less of a problem with this reduction in image contrast. Generally, step-and-shoot reconstruction algorithms are set up to input data that are collected at distinct angles. With continuous acquisitions, many more counts can be received, which allows the reduction in dose. Both of these last two recommendations, in theory, will reduce the effective radiation dose a patient receives. There may still need to be further research on the parameters to implement this in practice. Occupational monitoring in nuclear medicine, thus, includes assessment of both external irradiation of the body and internal exposure due to inhalation or ingestion of radioactive substances. When appropriate radiation protection measures are applied, the annual effective dose to nuclear medicine staff is low (around 2–3 mSv). However, hand doses can be very high and can even exceed the regulatory limit for skin equivalent dose, without workers being aware of it. Secondly, the procedures require the handling of radiopharmaceuticals in contact with, or very close to the extremities (hands, fingers). Nuclear medicine workers are, thus, potentially exposed to external radiation and to internal contamination in case of accidental intake. If adequate protocols are used, in general, contamination leads to negligible exposure of staff. However, the exposure of the extremities during preparation and administration of radiopharmaceuticals can be high. The hands often remain unprotected and, thus, fingertips can receive high doses which are likely to exceed the dose limit for extremities whenever the level of radiation protection is insufficient or the workload is too high. One of the main difficulties 2 is that the dose limit of 500 mSv per year is valid for the 1 cm of skin that is most exposed. This location of maximum dose is not known in advance and can vary for each exposure. Not much data are available yet on eye lens doses in nuclear medicine, but it can be expected that they are of the same order of magnitude as the whole body doses [1]. Monitoring of internal exposure for nuclear medicine workers requires frequent measurements due to the short physical half-lives of most radionuclides used in this field. The intakes from ingestion and inhalation are usually negligible, provided that adequate protection measures are applied. However, when volatile radionuclides such as iodine are used, it is recommended that workplace conditions be monitored, in particular to control contamination levels in the air. It included 139 workers from 35 nuclear medicine departments in 7 European countries (Belgium, France, Germany, Italy, Slovakia, Spain and Switzerland) [3]. The experimental data were complemented with Monte Carlo simulations to better determine the main parameters that influence extremity exposure, the effectiveness of different radiation protection measures and the degree of variability that could be ‘intrinsically related’ to each monitored procedure. For the measurement campaign, a common protocol was established to be able to compare and evaluate the data from the different hospitals. Measurements were performed separately for each radionuclide and independently for preparation and administration. For each worker, a set of 4–5 measurements were taken, except for therapy, where this was not always achievable. The least exposed positions were found to be the wrists, followed by the bases of the fingers. A clear trend was observed for the non-dominant hand to be more exposed than the dominant hand, in particular for radionuclide preparation. For therapy, spatial dose inhomogeneity is usually much more pronounced, but generally also the same positions as for diagnostics were the most exposed. In most cases, the index tip of the non-dominant hand is the most exposed specific position. It is shown that preparation of radiopharmaceuticals involves higher finger doses per unit activity than administration because the procedures take longer and there are more steps requiring manipulations of the vials and/or syringes with higher activities, some of them without a shield. Therapy procedures involve generally higher mean 18 normalized skin dose to the hands than diagnostics. Within diagnostics, F 99m involves higher skin doses per unit activity than Tc because of the different dose rates at contact. The Monte Carlo simulation sensitivity study revealed that short source displacements (of up to a few centimetres), orientation and volume changes (of up to 3 mL) can increase the maximum dose by a factor of three to five depending on the source. Shielding was found to be the most important parameter affecting skin dose levels, both for diagnostics and especially for therapy. Even though the use of shields slows down the whole procedure, increases the difficulty of visualizing the required volume and offers less comfort, especially for heavy and thick shields, it provides a protection which mostly cannot be replaced by increasing working speed. Often, staff are not aware that near the bottom of a shielded syringe the dose rate is very high. Using tweezers is a very effective means of dose reduction when vials or syringes have to be held without a shield and also during connecting and separating the syringe to or from needles or butterflies. The ratios between the highest dose and the dose at the most common monitoring positions were calculated and are summarized in Table 2. It is shown that even with the exclusion of outliers, the distribution of ratios is very wide.

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How does the disease Eggs shed in the faeces and urine of infected animals and humans spread between groups of contaminate water sources inhabited by snail intermediate hosts buy cialis 5 mg without a prescription erectile dysfunction foods to avoid, which in animals? Risk of infection is exacerbated by increased host density and by the wide definitive host range of schistosome species order cialis 5mg without a prescription erectile dysfunction causes prescription drugs. How is the disease In contaminated freshwater bodies, infective schistosome cercariae transmitted to humans? Schistosome infections are maintained by a range of mammals, however, field transmission is increased when water sources such as dams and irrigation ditches are shared with infected human populations (e. Herein lies the potential for a human settlement with poor sanitation to significantly impact on the health of surrounding livestock and wildlife. Human population displacement and refugee movements can introduce the disease to new areas (e. The infective cercariae of these non- human species can penetrate the skin of humans but rarely develop further. Recommended action if Contact and seek assistance from human and animal health professionals suspected immediately if there is suspected infection in people and/or livestock. Diagnosis Diagnosis is based on identification of characteristic schistosome eggs by microscopic examination of faeces and urine samples, or biopsy specimens. Serological tests may be sensitive and specific but do not provide information about the size of worm burden or clinical status. In areas where mammalian host density is low, this high fecundity enables the parasite to maintain a low level population without causing disease in humans or livestock. In environments where water sources supporting populations of susceptible snails are contaminated with high levels of infected human and livestock excreta, rates of transmission will also rise along with the probability and severity of disease. Control measures should therefore focus on preventing contamination of water sources through improved sanitation, as well as public health education, large scale medical treatment of infected individuals [► Humans], ring-fencing contaminated water bodies and reducing snail populations. Vector control - snail control Strategies should be implemented with specific knowledge of the ecology of the causative snail. Alter flow rate and water levels to disturb snail habitats and their food sources: Include V-shaped banks in irrigation channels. Remove vegetation/silt in channels to avoid a drop in velocity which may lead to further vegetation growth and good habitat for snails. Note that personnel involved in the manual removal of vegetation are increasing their exposure to snails. Flow rate should only be addressed with knowledge of the ecology of the snail in question e. Expose snail habitat: Remove littoral vegetation from the sides of canals feeding irrigation projects to expose snail habitat. Thought should be given to downstream conditions and the potential for the liberated snails to recolonise new habitat. Where possible dry out littoral zones to strand snail populations, however take into account the specific ecology and the resilience of the target species. Chemical control: Use of molluscicides may cause environmental damage and should be avoided. Applications are usually restricted to places frequently used by people for swimming, bathing etc. Biological control of intermediate snail hosts using larger, more voracious aquatic snails which do not harbour schistosome infection and out-compete local snails, has also been successful but should only be used after expert consultation due to their effects on local biodiversity. Livestock Prevention of contamination of wetland habitat with livestock excreta should be the main priority. To reduce the risk of infection, susceptible livestock should be removed from wetlands and replaced with non-susceptible species (or by farm machinery if the purpose of livestock is mechanical management). Infected and susceptible livestock should be treated with flukicides such as praziquantel. However, re-infection may occur quickly if the source of contamination is left uncontrolled. Wildlife High density populations of susceptible wildlife increase the potential for disease transmission. Interaction between livestock and wildlife should be prevented wherever possible and supplementary feeding of wild animals close to water sources should also be avoided. Humans The following practices may help reduce the likelihood of infection in humans: Avoiding contact with snail-infested waters and using water supplied from covered pipes or pit-wells. It is safest to consider all freshwater bodies in endemic areas as potential transmission sites if sites are otherwise unidentified. For agricultural workers at constant risk of infection, periodic examination and treatment may be the most feasible approach to disease control. A clean water supply and improved sanitation (including for people onboard boats) must be provided to stop human excrement entering wetlands. Treat infected individuals Anthelmintics such as praziquantel and oxamniquine (for S. If the local economic situation allows, consider mass treatment programmes for non-infected individuals following episodes of flooding. It is important that anthelmintic treatment be applied in conjunction with sanitation improvements to prevent widespread re-infection and subsequent cycles of treatment/re-infection thus increasing the potential for drug resistance to develop. Schistosomes contain cross- reacting antigens and vaccine development programmes are currently in progress. Frequent exposure of humans to schistosomes of domesticated animals can impart a degree of immunity to disease-causing species. Public health education Many countries and regions may lack funds for public education especially to isolated human settlements. However, an informed public are able to make personal decisions over their contact and use of standing water and thus reduce the risk of infection to themselves and their livestock. Problems may arise in areas where wildlife mixes with high density livestock and/or human populations. Effect on livestock An estimated 165 million animals are infected in Africa and Asia. In these regions most infections are subclinical but, depending on the schistosome species, can still cause serious morbidity and mortality (e. Worldwide, 207 million people are infected with schistosomiasis and it is especially important because of its prevalence in children and capacity to hinder growth and learning. Similarly, schistosomiasis impacts on economic development in developing countries by reducing the productivity of human workforces. Eradication programmes including widespread administration of praziquantel and implementation of improved sanitation are costly and beyond the means of many developing nations. These blood-feeding ectoparasites are found in almost every region of the world, typically in grassy, wooded habitat. They can act as vectors and/or reservoirs of disease, transmitting pathogens from an infected vertebrate to another susceptible animal, or human, whilst feeding. There are two major tick families: the Argasidae (soft ticks) and the Ixodidae (hard ticks), the latter (Ixodidae) having a number of attributes that enhance their potential to transmit disease, including long feeding durations (often days), firm attachment whilst feeding, a usually painless bite and the utilisation of a variety of hosts. Aside from disease transmission, ticks are also responsible for severe toxic conditions (tick paralysis or toxicosis), irritation, secondary infections and physical damage associated with their bites.

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Decoction: Decoctions are herbs/botanicals prepared in boiling water used primarily for compresses and syrups cialis 20mg discount best erectile dysfunction drug review. Use approximately a heaping palmful of dried discount 5mg cialis free shipping erectile dysfunction drugs in nigeria, crushed (not powdered) herb per pint of water. Boil together for about 15 minutes, cool, strain and add sufficient water to bring the volume back to a pint. Put 1-2 hands full of dried, crushed (not powdered) herb or fresh (best if available as whole leaf) into a large pot filled with water. Bring the water to a boil with the herbs in the water, place pot on a table, cover the head and pot with a towel, hang head over the pot, and breathe deep. When the herbs no longer have a scent in the stream you can add more and continue the treatment until desired relief is achieved. Tinctures: Tinctures are an alcohol-based extraction that is medicinally the most potent herbal treatment. When you dry herbs/botanicals the medicinal components are concentrated with the removal of the water. Soaking (tincturing) the dried herb/botanical in alcohol extracts those concentrated medicinal components and makes them available. An additional bonus is that alcohol-based tinctures are medicinally potent for years if stored in dark bottles or jars. We tincture most of our herbs and botanicals so they are immediately available for use, and we can be confident they are potent in an acute situation. We also keep dried herbs available for infant/child usage as teas, and also particular dried herbs available for poultices, and compress, and topical usage. To prepare the tincture you need quart canning jars with lids, dried herbs/botanicals, and at least 90 proof Vodka. Everclear is excellent to use also and in a pinch you could use another grain-based product. You want the alcohol to become saturated with the medicinal components of the herb/botanical, and other alcohol liquors/whiskey have components already saturating the alcohol so it probably won’t be as medicinally potent, but it would still have more potency that other preparation methods. Fill the quart jar about 1/3 full of dried herb/botanical, chopped root, or crushed (not powdered) leaf, fill the jar to the "shoulder" with vodka/Everclear, secure the lid, shake, and put in a dark cool place. In 10-14 days strain the liquid into dark bottles or jars, cap tightly, and label. The commonly accepted tincture dosage is 1-2 eye droppers full, 1 dropper full equals approximately 1/2 teaspoon. Alternatively, you can use the dropper to place the tincture in gelatine capsules. You can buy empty gelatine capsules in health food stores by the capsule or by the bag of 1000. Just pop the capsule apart, fill the larger section with finely crushed (powdered) dried herb, put - 70 - Survival and Austere Medicine: An Introduction back together, and take with water. Poultice: A poultice is warm, mashed, fresh, or finely crushed dried herb applied directly to the skin to relieve inflammation, bites, eruptions, boils, and abscesses. Depending on the size of the area to be treated put enough herbs in a glass dish/pot, cover with enough olive oil, or water, or decoction of the same herb to thoroughly saturate the herb, heat gently until a comfortable temperature to the skin, apply directly to the area to be treated covering it completely, and then cover with a sterile bandage. Bolus/Suppository: These are made using vegetable glycerine or cocoa butter mixed with a dried powdered herb to the consistency of bread dough. This method allows the herb to be in direct contact with the area needing treatment. Syrup: To about a pint of decoction you add enough honey and/or eatable glycerine to thicken slightly. Especially good for children to treat coughs, congestions, and sore throat as it will coat these areas slightly ,and keep the medicinal components in direct contact with the tissues. Specific Herbs and Botanicals We have tried to refine a list of herbs/botanicals, both wildcrafted and home grown, that would be most useful in treating the most common illnesses or diseases that may manifest in a survival situation. From the reading you have been doing in your newly acquired herb information books you now realize the vast amount of information and herbs available for use. Just use this list as a starting point to adjust and personalize according to your needs and medical situations. Wildcrafting: The following 7 herbs and botanicals grow almost universally all over the U. It has a blood cleanser effect (detoxifier) and is nutritive to the liver; also mildly diuretic. Dandelion (Taraxacum officinale): Harvest 2nd year roots in the spring or fall; young leaves in the spring for fresh eating. The root has been used for centuries to treat jaundice as it has a powerful alterative effect on the liver. Echinacea (Echinacea angustifolia): Harvest 2nd and 3rd year roots in early winter after the plant has totally died back (see, you do need your map! Echinacea purpurea: Harvest flower heads with seeds before petals drop in late summer. Tincture, water infusion, oil infusion, decoction, poultice, compress, bolus, syrup, capsule. Using these two varieties together gives increases the potency of your treatments. For strengthening the immune system dosage suggested is a dropper full (1/2 tsp) daily for a 10-day course, no herb for 7 days, then repeat the 10-day course, etc. One option now is to purchase 1# of cut and sifted Echinacea angustifolia root (currently $23/lb), tincture half of it right now, and save half for future decoctions and poultices. This will give you some time to gather your own root, and the tincture will be medicinally potent for at least 10 years. Echinacea root tincture has activity against influenza, herpes, and other viruses which includes virus which cause the common colds. Just soak a cotton ball or swab in the decoction and apply directly to the gums twice daily until the disease is resolved. Mullein (Verbascum thapsus): Harvest leaves before flowering taking no more than 1/3 of the total. It has expectorant action, soothes the throat, has bactericidal activity, and helps stop muscle spasms that trigger coughs. It seems to give mucous membranes a protective coating that allergens cannot penetrate. A 1 tsp dose protects against allergy symptoms for 4-5 hours with no negative side effects. Mullein has been stated to have narcotic properties without being habit forming or - 72 - Survival and Austere Medicine: An Introduction poisonous. Plantain is primarily a proven healer of injured skin cells, hence the topical usage. A salve or compress of plantain applied appropriately is known to reduce hemorrhoid swelling and pain. The New England Journal of Medicine carried a study reporting that poultices made from plantain leaves can help control the itching of poison ivy exposures, it is also good for poison oak also.

Polydextrose serves as a bulking agent in foods and sometimes as a sugar substitute buy discount cialis on-line erectile dysfunction injections trimix. Polydextrose is not digested or absorbed in the small intestine and is partially fermented in the large intestine purchase cialis 2.5 mg with amex erectile dysfunction medications, with the remaining excreted in the feces. Psyllium refers to the husk of psyllium seeds and is a very viscous mucilage in aqueous solution. The psyllium seed, also known as plantago or flea seed, is small, dark, reddish-brown, odorless, and nearly tasteless. Indigestible components of starch hydrolysates, as a result of heat and enzymatic treatment, yield indigestible dextrins that are also called resistant maltodextrins. Unlike gums, which have a high viscosity that can lead to problems in food processing and unpleasant organoleptic properties, resistant maltodextrins are easily added to foods and have a good mouth feel. Resistant maltodextrins are produced by heat/acid treat- ment of cornstarch, followed by enzymatic (amylase) treatment. The average molecular weight of resistant maltodextrins is 2,000 daltons and consists of polymers of glucose containing α-(1-4) and α-(1-6) glucosidic bonds, as well as 1-2 and 1-3 linkages. Resistant dextrins can potentially be classified as Functional Fibers when sufficient data on physiological benefits in humans are documented. Resistant starch is naturally occurring, but can also be produced by the modification of starch during the processing of foods. Resistant starch is estimated to be approximately 10 percent (2 to 20 percent) of the amount of starch consumed in the Western diet (Stephen et al. Along the gastrointestinal tract, properties of fiber result in differ- ent physiological effects. Effect on Gastric Emptying and Satiety Consumption of viscous fibers delays gastric emptying (Low, 1990; Roberfroid, 1993) and expands the effective unstirred layer, thus slowing the process of absorption once in the small intestine (Blackburn et al. A slower emptying rate means delayed digestion and absorp- tion of nutrients (Jenkins et al. For example, Stevens and coworkers (1987) showed an 11 percent reduction in energy intake with psyllium gum intake. Postprandial glucose concentration in the blood is thus lower after the consumption of viscous fiber than after consumption of digestible carbohydrate alone (Benini et al. The extended presence of nutrients in the upper small intestine may promote satiety (Sepple and Read, 1989). Fermentation Fibers may be fermented by the colonic microflora to carbon dioxide, methane, hydrogen, and short-chain fatty acids (primarily acetate, propi- onate, and butyrate). Foods rich in hemicelluloses and pectins, such as fruits and vegetables, contain Dietary Fiber that is more completely ferment- able than foods rich in celluloses, such as cereals (Cummings, 1984; Cummings and Englyst, 1987; McBurney and Thompson, 1990). There appears to be no relationship between the level of Dietary Fiber intake and fermentability up to very high levels (Livesey, 1990). Butyrate, a four-carbon, short-chain fatty acid, is the preferred energy source for colon cells (Roediger, 1982), and lack of butyrate production, absorption, or metabo- lism is thought by some to contribute to ulcerative colitis (Roediger, 1980; Roediger et al. Others have suggested that butyrate may be protec- tive against colon cancer (see “Dietary Fiber and the Prevention of Colon Cancer”). However, the relationship between butyrate and colon cancer is controversial and the subject of ongoing investigation (Lupton, 1995). Once absorbed into the colon cells, butyrate can be used as an energy source by colonocytes (Roediger, 1982); acetate and propionate travel through the portal vein to the liver, where propionate is then utilized by the liver. A small proportion of energy from fermented fiber is used for bacterial growth and mainte- nance, and bacteria are excreted in feces, which also contain short-chain fatty acids (Cummings and Branch, 1986). Differences in food composi- tion, patterns of food consumption, the administered dose of fiber, the metabolic status of the individual (e. Because the process of fermentation is anaerobic, less energy is recovered from fiber than the 4 kcal/g that is recovered from carbohy- drate. While it is still unclear as to the energy yield of fibers in humans, current data indicate that the yield is in the range of 1. Physiological Effects of Isolated and Synthetic Fibers This section summarizes the fibers for which there is a sufficient data- base that documents their beneficial physiological human effects, which is the rationale for categorizing them as Functional Fibers. It is important to note that discussions on the potential benefits of what might eventually be classified as Functional Fibers should not be construed as endorsements of those fibers. While plant-based foods are a good source of Dietary Fiber, isolated or synthetic fibers have been developed for their use as food ingredients and because of their beneficial role in human health. In 1988 Health Canada published guidelines for what they considered to be “novel fiber sources” and food products containing them that could be labeled as a source of fiber in addition to those included in their 1985 definition (Health Canada, 1988). The rationale for these guidelines was that there were safety issues unique to novel sources of fiber, and if a product was represented as containing fiber, it should have the beneficial physiological effects associated with dietary fiber that the public expects. The guidelines indicated that both safety and efficacy of the fiber source had to be estab- lished in order for the product to be identified as a source of dietary fiber in Canada, and this had to be done through experiments using humans. Detailed guidelines were later produced for the clinical studies required to assess laxation effects, as this was the physiological function most often used by industry when seeking approval for a novel fiber source (Health Canada, 1997). For each of the fiber sources discussed below, studies will be summarized that relate to one of the three measures of efficacy identified by Health Canada, as these are the three most commonly accepted beneficial effects of fibers. A more complete discussion of these three measures of efficacy may be found later in this chapter. In addition, other potentially efficacious effects will be noted where studies are available. As interest has increased in fiber, manufacturers have isolated various types of fiber from a wide range of carbohydrate sources added to foods. Many of these isolated materials are used as food additives based on func- tional properties such as thickening or fat reduction. As enzymatic and other technologies evolve, many types of polysaccharides will continue to be designed and manufactured using plant and animal synthetic enzymes. Examples in this category include modified cellulose, in which the hydroxyl groups on the glucose residues have been substituted to varying degrees with alkyl groups such as methyl and propyl; fructooligosaccharides manu- factured from sucrose; and polydextrose synthesized from glucose. In some instances, fibers isolated from plants or manufactured chemically or synthetically have demonstrated more powerful beneficial physiological effects than a food source of the fiber polysaccharide. From a meta-analysis of about 100 studies of changes in stool weight with various fiber sources, investigators have calculated the increase in fecal weight due to fiber ingestion (Cummings, 1993). As noted later in this chapter, an increase in fecal weight does not necessarily equate with enhanced laxation, so this needs to be considered in interpreting the results of fecal bulking studies. In a randomized, crossover study designed to compare the effects of supplemental pectin (12 g/d), cellulose (15 g/d), and lignin (12 g/d) on stool characteristics of healthy volunteers, cellulose was the only fiber that significantly decreased (–27 percent) mean stool transit time and increased mean wet stool weight (+57 percent) (Hillman et al. Cellulose is often used as the placebo in studies designed to test the efficacy of fibers on decreasing serum cholesterol concentrations. Cellulose is either neutral with respect to blood cholesterol concentrations (Hillman et al. Similar to the relationship between cellulose and serum cholesterol concentrations, cellulose is also often used as a placebo in studies that evaluate the effect of fiber on blood glucose and insulin concentrations. Cellulose is ineffective in decreasing the postprandial glucose response (Librenti et al. There are a number of animal studies that have suggested that chitin and chitosan may decrease lipid absorption and thus the amount of fat entering the blood (Gallaher et al. Therefore, blood cholesterol and triacylglycerol concentrations have been shown to be reduced with chitosan intake in animals (Chiang et al.

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Current approaches to informed consent for research rely on long buy cheap cialis online erectile dysfunction consult doctor, complex consent forms that may deter participation while doing little to help participants understand the nature of the research order discount cialis on line erectile dysfunction causes in young men. Public participation in biobanks and research projects would build trust (Levy et al. Although a waiver of authorization to use identifiable health information may be granted under certain circumstances, many health care organizations are reluctant to participate. Thirdly, requirements for “accounting” to patients for research uses of data are burdensome and discourage data sharing. These regulations are strong deterrents to the kinds of pilot projects envisaged in this report. A biobank might serve as a trusted intermediary for the pilot projects described above, giving researchers only data and materials without overt identifiers but retaining a key to coded samples so they could update clinical information or re-contact patients or donors when appropriate. The Committee envisages that best practices and ultimately consensus standards will emerge from the different models of consent and return of clinically significant results to participants. The research needed to build the Information Commons, which will require projects involving vast amounts of data from large numbers of patients, will proceed more efficiently if such collaborations can be developed both between academia and industry and among for-profit companies that have historically been competitors (Altshuler et al. These collaborations could include developing common standards and database formats and building infrastructure to facilitate data sharing. Consortia might be organized to share upstream research findings widely that have no immediate market potential but are critical to downstream product development. Examples of such upstream research include the identification and validation of biomarkers and predictors of adverse drug reactions. To build a flourishing culture of pre-competitive collaboration, drug companies will need to overcome their reluctance to share all data from completed clinical trials, not just the selected data relevant to regulatory proceedings. Finally, and most significantly, guidelines for intellectual property need to be clarified and concerns about loss of intellectual-property rights addressed. Precompetitive collaborations will only emerge if individuals and organizations have incentives to join them (Vargas et al. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 59 with its attendant benefits in improved health outcomes and reduced health-care costs, can become a widespread reality. Similar principles apply whether the collaborations involve commercial entities or are confined to academia. To encourage the collection of materials and data, organizations and researchers who collect them should have first access to their use for research, while still ensuring their timely availability to others. The Committee does not envision the desirability or need, in the context of the research required to populate the Information Commons with data and derive a Knowledge Network from it, for the instant-data-release model adopted during the Human Genome Project. However, it does believe that timely, unrestricted access to data sets by researchers with no connections to the investigators who created them will be essential. The cost of populating the Information Commons with data precludes extensive redundancy in publicly financed research projects. At the same time, the size and complexity of these data sets—as well as the need for diverse, competitive inputs to their analysis—precludes giving any one group prolonged control over them. They must be regarded as public resources available for widespread and diverse research into ways to improve health care and to increase the efficiency of health care delivery. Because the Committee is skeptical that one-size-fits-all policies can accommodate the conflicting values associated with incentivizing researchers and insuring adequate access to data, it believes that pilot projects of increasing scope and scale should put substantial emphasis on addressing the challenges associated with data-sharing, rather than focusing exclusively on data collection and analysis. Competition and sharing in the health-care system A distinct and critical question is whether payers, such as health insurance companies, will provide access to their vast databases of patient and outcomes data and whether they will be willing to integrate these data with data from other companies and researchers with the goal of creating Knowledge Networks such as those described in Chapter 3. On one hand, these organizations recognize the potential value and cost saving that could emerge from such an effort. One of the main impediments is cultural: many of these organizations view their data as a propriety asset to be used in efforts to generate competitive advantages relative to other organizations. For example, large health-care systems and insurance providers are interested in developing decision support tools for physicians that would cut down on the substantial waste caused by misdiagnosis or inappropriate treatment decisions. Integration of biological data, patient data, and outcomes information into Knowledge Networks that aggregate data from many sources could dramatically accelerate such efforts. However, if the data and the research results are shared, it would undermine one type of competitive advantage that large data providers might otherwise have. In this way, there is a tension between the sharing that would be good for the health-care system as a whole and the short-term competitive instincts of individual providers and payers. Apart from the culture of competition there are other impediments related to cost pressures. Cost pressures within the health-care system are such that providers and payers are unlikely to be willing to invest substantially (or in some cases, at all) in the collection of biological data for research purposes. Over the long-term, once such data have been shown to yield clinically useful information, it will become justifiable to expend health care resources on the collection of actionable data, just as is presently done for standard diagnostic tests. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 60 Commons will become populated by biological data (such as genome sequences) acquired from providers and payers. Similarly, the information technology challenges associated with integration of large data sets and new disease classification systems are substantial. While the goals of integrating data sets and changing classification systems are achievable in principle, they will be beyond the technical capacity of all but the largest and most technologically sophisticated providers and payers. Thus, the transition to non- proprietary Knowledge Networks into which all data would be deposited would have to involve strong incentives for payers and providers. This may mean that the government will ultimately need to require participation in such Knowledge Networks for reimbursement of health care expenses. At an even more fundamental level, the longstanding issue of equity in access to a sufficiently advanced level of healthcare should also be addressed if the data in the Knowledge Network is to adequately represent the diversity of our society. The Development of a Knowledge Network of Disease will require and inform the education of health-care providers at all levels Decision-making based on a Knowledge Network of Disease and the New Taxonomy, which will incorporate a multitude of parameters, will represent a significant adjustment in the practical work of the primary care physician. Given the demands on the time of physicians and other care-givers in the present health-care environment, few are likely to have the time or to feel qualified to interpret the results of “omics”-scale analyses of their patients. The importance of this issue will escalate over time as the Knowledge Network and its linked molecular-based taxonomy evolve into a system whose sheer complexity greatly exceeds current approaches to disease classification. One concern is that the infusion of large molecular datasets into clinical records will reinforce a tendency many perceive as already crediting genetic and other molecular findings with more weight than they deserve. In extreme cases, this cultural bias has enabled the promoting and marketing of “omic” tests with no clinical value whatsoever (Kolata 2011). In other cases genetic or “omic” tests with real value in specific contexts may be over-interpreted and thereby occlude consideration of other relevant clinical data. To develop the Knowledge Network of Disease and the New Taxonomy that will be derived from it, health-care providers will need to develop much greater literacy in the interpretation and application of molecular data. To meet these challenges, health-care providers will require both decision-support systems and new training paradigms. The decision-support systems will need to provide useful information about the propensity of patients to develop disease, facilitate a correct diagnosis, guide selection of the most appropriate strategies for disease prevention or treatment, inform the patient about the prognosis and management of the disease, and provide the opportunity for both physicians and patients to access more detailed information about the disease on an “as interested” or “as needed” basis. Whenever possible, such decision-support systems should enable shared decision-making by patients and their care-givers.