E. Irmak. Henderson State Univerisity.
The basic naturopathic training in botanicals includes historical use order cialis jelly 20mg line, disease indications discount cialis jelly 20 mg amex, mechanism of action (if known), active constituents (if known), adverse reactions and contraindications, and drug interactions (if known) of about 200 botanicals. This is important, as many naturopaths continue to produce their own formulations of herbal tinctures. They may use a single herb or a combination of herbs to treat a particular disease condition. Combinations of two to five herbs are often used in a formula for either acute or chronic conditions. Siberian ginseng (Eleuthrococcus sinensis) and gotu kola (Centella asiastica) might be considered stimulant nervines. The adaptogens, mostly from Asian traditions (the ginsengs, Withania somnifera), are also considered tonic nervines. This tonic function of herbs is common across herbal traditions and is a class of mechanisms perhaps inadequately attended to among pharmaceutical approaches to neurological disorders. Diet (clinical nutrition) Naturopaths attend to dietary assessment including macro- and micro-nutrient content in foods, individual responses to diets and specific foods and in the application of a variety of therapeutic diets. The use of diet to improve health is a therapeutic foundation in naturopathic medicine as it encompasses aspects of all six of the naturopathic principles. The types of diet that NDs use are highly variable and may include, on a case-by-case basis, low fat, elimination and challenge (hypoallergenic), glutenfree, dairy-free, blood type diet, vegetarian and fasting (juice, water). Clinical evidence evaluating the influence of diet in neurological disease includes the following examples. Epilepsy: the ketogenic diet The ketogenic diet is a high-fat, low-carbohydrate diet that was developed decades ago but which has recently come under consideration in intractable cases. There have been many studies reporting a sig- nificant decrease in seizures of children with severe epilepsy that were 10–12 treated with the ketogenic diet. Although the diet is highly successful in decreasing seizures in difficult-to-treat epileptic children, compliance with the diet is often an 13 issue. There is evidence that it may increase the frequency of kidney stone formation in 14 those on the diet. Migraine headaches: hypoallergenic diets (elimination/challenge diet) The rationale for use of this type of diet for migraine headaches is that food allergies cause platelet degranulation and histamine release that can precipitate vasomotor 15 instability and subsequent migraine. There are a number of studies that have reported a benefit in subjects who suffer from migraines and have eliminated foods that might elicit 16–20 a migraine. The elimination diet requires that a person go on various versions of an oligoallergenic restricted diet (a typical diet may be primarily lamb and rice for a period of 7–10 days) after which they systematically re-introduce food groups to identify foods that will elicit a migraine. Once a food that triggers a migraine is identified, the food is taken out of the diet for a period of time and is re-introduced in smaller quantities. The strategy is not to stay on a highly restricted diet but to identify allergenic foods and to decrease the amounts and frequency of these foods consumed. Naturopathic medicine in neurological disorders 159 Multiple sclerosis: the Swank diet There have been a number of epidemiological studies assessing associations between dietary factors and the risk of developing multiple sclerosis (MS). A number of epidemiological studies have reported a significant positive association between risk of 21,22 MS and consumption of animal fat. Dr Roy Swank has provided evidence that a diet low in saturated fats (less than 15 g/day) combined with cod liver oil supplementation, maintained over a long period of time, tends to retard the disease process, reduce the 23,24 number of attacks and decrease mortality. Oneopen-label pilot clinical trial evaluated the effects of a diet low in saturated fats supplemented with fish oil, vitamin B-complex 25 and vitamin C in subjects with newly diagnosed relapsing-remitting MS. After 2 years of this regimen the study reported a significant decrease from baseline values of relapse rates and disability scores. Preliminary reports from a recent randomized placebo- controlled pilot study evaluating a diet very low in saturated fat (less than 15%) supplemented with fish oil capsules found that, when compared with subjects following the American Heart Diet (less than 30% saturated fat) supplemented with placebo oil capsules, the treatment group had a significant decrease in relapse rate, disability and a 26 decrease in two inflammatory cytokines. These studies suggest that a diet very low in fat combined with fish oil supplementation may help to decrease relapse rates and increase time to disability in people with MS. Nutritional/dietary supplementation Many naturopaths use a variety of nutritional supplements usually as an adjunct to fundamental lifestyle therapies, such as diet, exercise and stress reduction (counseling) to address a specific symptom or condition. Under the DSHEA, dietary supplements are considered foods and not drugs and therefore regulated by the FDA as foods. Examples of substances that are considered dietary supplements include: fish, flax, evening primrose and borage oils, glandulars (usually made from animal sources), enzymes, melatonin and dehydroepiandrosterone (DHEA) (although these are hormones they are regulated and sold as dietary supplements in the USA), garlic capsules, soluble fiber, coenzyme Q10 (CoQ-10), L-carnitine, 5-hydroxytryptophan (5-HTP), etc. Obviously this is just a small fraction of the number and types of existing dietary supplements; the associated effects indicated below are rarely definitive. Cold-water fish and fish oil contain a high proportion of the omega-3 fatty acids and therefore contain a higher relative proportion of DHA and eicosapentaenoic acid. There have been at least two clinical trials evaluating the effectiveness of essential fatty acids (EFA) and DHA supplementation for dementia. The treatment group was given a mix of omega-6/ omega-3 fatty acids at a 4:1 ratio in which they received about 0. There were no cognitive measures in this study, and subjects were rated on 12 behavioral variables by their guardian. Although this study showed a positive benefit from short term EFA supplementation there were no objective measures in this study and no standard testing of cognitive function (e. The second, a double- blind placebo-controlled pilot study, evaluated the effects of 1 year of supplementation of 0. A significant increase in MMSE score was reported after 6 months of supplementation (control=19. There was a significant increase in both serum DHA and eicosapentaenoic acid levels after 3 months of supplementation. Amyotrophic lateral sclerosis: creatine Seven days of supplementation with creatine 20 g resulted in a transient increase in 35 maximal voluntary isometric muscular contraction and fatigue in 28 patients. Naturopathic medicine in neurological disorders 161 Bipolar disorder Four months of treatment with 9. Depression: ethyl-eicosapentaenoic acid There are two double-blind placebo-controlled pilot studies that have reported a significant improvement in depression in people on stable doses of antidepressants after 36,37 1–3 months of ethyl-eicosapentaenoic acid (E-EPA) supplementation.
Some fetal cardiac ar- rhythmias purchase cialis jelly 20mg line, such as supraventricular tachycardia order cialis jelly 20 mg amex, are suc- DRUG DISPOSITION IN PEDIATRIC cessfully managed by treating the mother during preg- PATIENTS nancy. Since most drugs cross the placenta, the infant In spite of recent advances in this area, knowledge of has the potential to be affected by drugs that the the disposition and actions of drugs in children is lim- mother takes. This lack of information has made drug therapy for sponsibility of the fetus, as the placenta and the mater- them difﬁcult and dangerous. There are two major ob- nal liver and kidneys contribute signiﬁcantly to drug stacles to clinical drug studies in children. At birth, term infants can metabolize and eliminate The second obstacle is inherent to children; they grow drugs. Drug studies must be performed on during fetal life and therefore even at birth are not very children at each stage of their development to deter- efﬁcient. The ability to absorb and infants, term infants from birth through the ﬁrst month eliminate drugs increases slowly over the ﬁrst month of of life, children 1 month to 2 years of age, children 2 to life. Acid Renal blood ﬂow 5–12 mo initially is secreted within the ﬁrst few hours after birth, reaching peak levels within the ﬁrst 10 days of life. Maternally administered drugs also may affect in- Gastric acid secretion approaches the lower limits of fants who are breast-fed. However, several drugs secretion is often delayed in infants with delayed initia- can reach concentrations sufﬁcient to adversely affect tion of oral feedings, such as extreme preemies and the newborn. Formulas garding risks to the infant from drug in breast milk is containing long-chain fatty acids will delay gastric emp- not available. Both gastric emptying time and small-intestine The period from 1 month to 2 years of age is a time peristalsis tend to be slow until the later part of the ﬁrst of rapid growth and maturation. Paradoxically, tying time dramatically increases, as does splanchnic between 2 and 12 years of age drug clearance greatly in- blood ﬂow. Half-lives are drug absorption and increased peak blood concentra- shorter and dosing requirements are frequently greater tions of drug. These differences are often associated with a in the neonatal period, drugs administered intramuscu- decreased drug absorption and elimination in the fe- larly are absorbed erratically. Females have less gastric Percutaneous drug absorption can present special acidity and an increased gastric emptying time. Cyclic changes in glomerular ﬁltra- preterm infant will not have this protective barrier until tion are noted during the menstrual cycle. Absorption of hexachlorophene soap used to Absorption bathe newborns has resulted in brain damage and Oral absorption of drugs is inﬂuenced by gastric acidity death. Gastric acid is rarely found in the cyanosis secondary to methemoglobinemia, and EMLA (lidocaine/prilocaine) cream may cause methemoglo- binemia when administered to infants less than 3 months of age. This increased total body water increases the Decreased albumin concentration and binding volume of drug distribution for water-soluble com- Decreased total plasma protein pounds. As a consequence, there is a need to administer 58 I GENERAL PRINCIPLES OF PHARMACOLOGY loading doses of some drugs. Differences in total body Excretion water are basically insigniﬁcant after the ﬁrst year of Renal blood ﬂow, glomerular ﬁltration rate, and tubular life. Newborns have decreased body fat and therefore function are reduced in both preterm and term less storage ability for fat-soluble drugs. Aminoglycosides are administered In addition, albumin from these patients shows a de- every 8 hours in older children, every 12 hours in new- creased drug-binding afﬁnity. This may result in increased borns, and every 24 hours in extremely premature in- plasma levels of free drug and the potential for toxicity. The glomerular ﬁltration rate of the term newborn the past, concerns were raised that certain drugs, such as is approximately 50% less than the adult level but sulfonamides, could displace endogenous substances, like reaches adult values by 1 year of age. Tubular secretory functions mature at a slower rate than Although this belief has been challenged recently, reluc- does glomerular ﬁltration. Renal elimination of drugs appears to play a greater role than As with adults, the primary organ responsible for drug does metabolism in newborns. Phase I oxidation reactions and demethylation enzyme systems are signif- Drug Action icantly reduced at birth. However, the reductive enzyme Most drugs are administered to infants and children for systems approach adult levels and the methylation the same therapeutic indications as for adults. Among to the production of different metabolites in newborns these are theophylline and caffeine, which are used to from those in adults. For example, newborns metabolize treat apnea of prematurity; indomethacin, which closes a approximately 30% of theophylline to caffeine rather patent ductus arteriosus; and prostaglandin E1, which than to uric acid derivatives, as occurs in adults. Para- most phase I enzymes have reached adult levels by 6 doxically, drugs such as phenobarbital, which have a months of age, alcohol dehydrogenase activity appears sedating action on adults, may produce hyperactivity in around 2 months of age and approaches adult levels children, and some adult stimulant drugs, such as methyl- only by age 5 years. Phase II synthetic enzyme reactions are responsible for the elimination of endogenous compounds, such as bilirubin, and many exogenous substances. The immatu- Adverse Reactions rity of the glucuronidation pathway was responsible for Children may display adverse reactions different from the development of gray baby syndrome (see Chapter those noted in adult patients. The plasma half-life was found to be 26 hours in Several problems unique to pediatric drug therapy de- these patients compared with 4 hours in older children. For example, most medications Infants and children have a greater capacity to carry are commercially available only in adult dose forms. For example, Preparing pediatric doses from adult tablets or capsules acetaminophen is excreted predominantly as a sulfate can be very difﬁcult and may require special skill on the conjugate in children as opposed to a glucuronide con- part of the pharmacist. This enhanced sulfation of acetamino- administer the intravenous (IV) preparation orally than phen, along with decreased metabolism via cytochrome to develop a preparation from the oral medication. P450 pathways and increased glutathione turnover, are IV drug administration is most effective in children thought to explain the decreased hepatotoxicity caused when given via a pump infusion system close to the site by this analgesic in children under 6 years of age.
Translated into movements order 20 mg cialis jelly free shipping, this means that in real life there is virtually no such thing as a single muscle/single joint movement for which it would make sense to implement a segregated representation cheap cialis jelly 20mg on-line. This does not mean that single neurons cannot elicit motor actions, but only that it is virtually impossible to hardwire functional demands into the response properties of single neurons (see however Brecht et al. A classical debate in motor control research has been whether muscles or movements are “represented” in the primary motor cortex. In a way, this is equivalent to asking whether a piano functions by playing a sonata or striking chords. In other words, this debate is conceptually related to the debate about “grandmother neurons” in the visual system. In a more contemporary view, func- tionally meaningful motor acts arise from the concerted activity of many neural units, just as a sonata arises from the effect of playing a certain complex pattern of piano keys. However, in contrast with the concert pianist, we do not know which sonata is on the program today and under which biophysical circumstances we will need to play it. These prospective uncertainties impose on the motor control system the need to retain a high ﬂexibility that permits adaptation to variable demands by virtue of ﬂexibly associating the available neural units into a customized pattern that will yield the required action result. If we assume that movements and their direction are coded by population activity, the functional performance of such constantly regrouped populations would beneﬁt from single keys striking several chords and single chords being accessible via several keys, i. The probability for interactions is higher within limbs than across limbs, and facial movements will again be fairly independent of those in upper and lower extremities. This is not to say that for instance ballistic arm movements will not require coor- dinated output to trunk and leg muscles, but just that the predictability is lower than for within-limb coordination. The functional anatomical consequences of this pseudo-segregation have lured many researchers into the jargon of face, arm/hand, Copyright © 2005 CRC Press LLC and leg “areas,” as if these were strictly segregated distinct representations. The data available only suggest that embedded into one continuous motor representation a greater degree of spatial separation and a lower degree of overlap can be found for the representation of different movements across than within these body parts. The next question is whether within an upper limb representation the probability distribution of interactions is ﬂat. This is clearly not the case, and may account for the relative ease with which it has been found that proximal movements elicit more medial activation than distal movements, and vice versa. It should be noted that in natural contexts these movements differ not only in terms of the musculature involved, but also in terms of movement type and purpose. This is no longer the case when considering different types of hand and ﬁnger movements. Lesions of the primary motor hand representation affect our capability for performing individuated ﬁnger movements. At the same time, there is evidence, recently conﬁrmed by magnetoencephalography,65 that in quantitative terms, or when ana- lyzed as the center of gravity, thumb movements are represented more laterally than index movements, and index movements more laterally than little ﬁnger movements. The degree of separation is not sufﬁcient to make isolated or even predominant ﬁnger paresis after focal motor cortex lesions a frequent clinical observation. The observation of such cases is in accordance with our general reasoning here because the radial nerve innervates muscles that implement extension across several joints of the arm (elbow, wrist, phalanges), and the synergy of these movements in natural contexts may result in a higher degree of interaction of the underlying neural units. Yet, this association is orthogonal to the general notion of somatotopy because it spans proximal to distal upper limb movements. It must be emphasized that the observation of within-hand somatotopy does not depend on the body parts containing the muscles involved. Relatively isolated ﬁnger move- ments can be performed using either forearm or small hand muscles. If somatotopy were to code for whether the muscles are more proximal or more distal one would not expect this ﬁnding. Conversely, the detection of somatotopy is related to which part of the body will manifest the effects of coordinated muscular activity. The question then is whether this aspect inﬂuences the probability distribution of inter- actions. We believe that it does, not in the sense of pure motor interactions (for the reasons outlined above), but in the sense of sensorimotor interactions. The functional signiﬁcance of distal upper extremity movements lies in estab- lishing our proﬁciency in ﬁnely graded manipulations. These manipulations rely heavily on feedback from cutaneous and proprioceptive sensory afferents, and Copyright © 2005 CRC Press LLC accordingly there are dense ﬁber connections from the primary somatosensory to the primary motor cortex. Following the general reasoning of optimizing interaction by minimizing the associative ﬁber path lengths, one would expect a bias to cluster those neural units in the primary motor cortex that may engender, for instance, thumb movements (and concomitant sensory thumb stimulation) in spatial proximity to those neural units in M1 that will receive and process this sensory stimulation and thus be informative for optimizing the muscular activity pattern. Experimental sup- port for this notion comes from ﬁndings in the forelimb representation of the nonhuman primate motor cortex. Using electrodes both for the recording of responses to somatosensory stimulation and for eliciting movements by stimulation, Rosén and Asanuma68 observed that in roughly half of the units that could be driven by somatosensory stimuli, the receptive ﬁelds of these units colocalized to the parts of the hand displaying the motor response when this unit was stimulated. In the view presented here, the feature of within-hand somatotopy in the primary motor cortex arises merely as a repercussion of functional principles that guide the somatotopical layout of the primary somatosensory cortex. In fact, one concern with those fMRI data that have shown an inﬂuence of somatotopy on the activation patterns in the primary motor hand representation has been that this might reﬂect concomitant tactile activation from the usual ﬁnger-tapping type task used in these studies. In that case, the results would be driven by the fraction of neurons in M1 that have somatosensory response properties. However, this could be made unlikely by a study in which ﬁnger opposition with and without actual touch were compared and no difference between the two activation patterns was observed in M1. Yet, this mechanism would not explain the aforementioned ﬁndings from intracortical microstimulation exper- iments or magnetoencephalography,65 and it thus appears more likely that there is also a somatotopical gradient in the movement-related functional architecture of M1. We believe that the view presented in the previous paragraph, albeit speculative, accounts for the entirety of the currently available experimental observations. It should be noted that the contribution of interactions with primary somatosensory cortex to the probability distribution of interactions for neural units in the motor hand representation is only one of several factors. It can be seen to compete with other factors related to movement execution which in their own right do not drive the connectivity and thus the functional cortical architecture toward a somatotopical layout. Since somatotopical segregation is not compatible with fundamental features of motor control, the effect of this somatosensory factor can only be a somatotopical gradient superimposed onto a more complex layout.
In that sense buy cialis jelly 20 mg fast delivery, this approach resembled those used in the visual system for retinotopic mapping where there is continuous visual stimulation that slowly changes its position in the visual ﬁeld discount cialis jelly 20mg with visa. Because we found no segregation but only relative predominance, we proposed to think of the contribution of somatatopy to functional organization of M1 as a “gradient. We believe that such a description presents a safeguard not only against overinterpreting the historical homunculus cartoons, but also against seeing more segregation in contemporary fractured or mosaic patterns obtained in nonhu- man primates than the methods applied in those studies can positively afﬁrm. The ﬁnding of a somatotopic gradient in the M1 hand representation has since been revisited and reproduced by several research groups. In one case, there was a claim of somatotopy but the actual layout found did not correspond to the classical homunculus cartoon,50 with index movements represented more laterally than thumb movements. Alternatively, this can be seen to reﬂect the degree to which we manage to move a single ﬁnger in as much isolation as possible. Although each of these studies added some aspect of reﬁnement or some degree of more detailed quantiﬁ- cation and thus further corroborated the experimental proof and characterization of somatotopy in the motor hand representation, none of these studies advanced our understanding from a functional perspective of why this should be the case. The unanswered question is what good does it serve the brain to represent information in a topographical fashion. One of the potential beneﬁts from such a functional architecture is segregation, and this makes sense for unique solutions. In the visual system for instance, a dot that is present in one spot of the visual ﬁeld is not present in another spot, and accordingly the processing of this information may be aided by spatially separating the neural populations that code for these different spots in the visual ﬁeld. Because a dot may have a certain size and thus cover a certain extent of the visual ﬁeld, it also makes sense to organize those representations that code for one spot in the immediate vicinity of those coding for the adjacent spots. This in itself presents a sufﬁcient functional beneﬁt to justify a retinotopic layout of the primary visual cortex, but does this predict any such beneﬁt for the motor system? The example in Copyright © 2005 CRC Press LLC the visual system deals with unambiguous information in the physical environment as collapsed into a two-dimensional visual ﬁeld that is ﬁrst (and most precisely) represented by virtue of a mere optical projection at the retinal level. In fact, the propagation of a veridical primary retinotopic representation into the central nervous system progressively degrades, distorts, and fractures the relative contribution of retinotopy to the individual neural response properties. Seeking the analogy with the visual system may be good for the somatosensory system, and the studies on somatosensory somatotopy provide experimental evidence in favor of this notion. In fact, from a motor control perspective, a somatotopic layout does not make a lot of sense for the hand representation. Motor acts involve concerted activity changes across a wide range of different muscles. Many of these muscles affect movements of more than one joint, and movement in many joints is affected by more than one muscle. Accordingly, the neural pathways involved display high degrees of divergence and convergence. In compiling the functional beneﬁt from topical organization as above for the sensory systems, we have not yet mentioned one additional important factor. Man is in motion and so are objects in the world, and one of the cardinal functions of the sensory and motor systems is to optimize the related neural processes. Using the visual system again for illustration, if we think of a dot at one spot in the visual ﬁeld and assume that it is moving, then it will be at another spot of the visual ﬁeld at a later time point. To reconstruct the trajectory of the dot requires interactions of those neurons that code the spot where it is ﬁrst, with those that code where it appears thereafter. Obviously, mere connection of these neuronal units is a prerequisite, but is not in itself sufﬁcient for the perceptual success of this functional interaction. In addition, the preservation of precise temporal information is required to determine whether the dot moved one way or the other or whether these are in fact the two ends of a bar that just appeared behind an occluding surface. The preservation of temporal infor- mation can be achieved by a high speed of information relay between neuronal units, and the nervous system has two ways of doing this. One involves the degree of myelination, and works well for instance for the corticospinal tract. However, this strategy is costly in terms of the volume required by such a heavily myelinated pathway. In projection pathways, this may not pose a constraint, but for intra- or inter-areal associative communication pathways this may be disadvantageous. Alter- natively, short pathways offer a strategy of rapid communication that is less costly but that cannot be applied uniformly if it has to deal with interconnecting each position with every other position for a two-dimensional cortical sheet. To achieve the best functional result despite this problem requires knowledge of which neural units must be closely connected and which neural units can interact by sparser or longer association ﬁbers. If we think of the dot again that appears sequentially at different positions of the visual ﬁeld, there is no absolute prediction of its subsequent position by means of its previous one. The subsequent position Copyright © 2005 CRC Press LLC could be anywhere in the visual ﬁeld, but there is an obvious probability distribution of where this will be. This probability distribution provides a meaningful a priori hypothesis for how to wire the horizontal interactions in a visual area, and it corresponds to a retinotopic map layout. This teleological consideration is also related to theoretical work that has addressed the connectivity patterns by which neural elements can serve the functional needs of segregation and of integration while maximizing their proﬁciency (or complexity) in information processing. The fundamental difference between the motor system and the visual (or somatosensory) system is that in the former there is almost no functional beneﬁt from segregation. In other words, for a given neural unit the probability distribution of interactions with other neural units does not present distinct peaks, as in sensory systems. Translated into movements, this means that in real life there is virtually no such thing as a single muscle/single joint movement for which it would make sense to implement a segregated representation. This does not mean that single neurons cannot elicit motor actions, but only that it is virtually impossible to hardwire functional demands into the response properties of single neurons (see however Brecht et al. A classical debate in motor control research has been whether muscles or movements are “represented” in the primary motor cortex. In a way, this is equivalent to asking whether a piano functions by playing a sonata or striking chords. In other words, this debate is conceptually related to the debate about “grandmother neurons” in the visual system.
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