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This suspended cell technique of the Maitlands was applied extensively by multiple investigators to the study of viral growth symptoms you are pregnant cheap zofran 8mg fast delivery. Then in 1936 medications known to cause miscarriage cheap zofran on line, Albert Sabin and Peter Olitsky attempted to grow poliomyelitis viruses in Maitland cultures of tissues from chick symptoms testicular cancer buy zofran visa, mouse administering medications 7th edition buy zofran 4 mg lowest price, monkey treatment hepatitis b purchase zofran us, and human embryos treatment hypercalcemia purchase zofran line. However, they found that only in human embryonic brain tissue would the virus replicate. For their studies, Sabin and Olitsky used a poliovirus obtained from Simon Flexner of the Rockefeller Institute that was likely already adapted for and restricted to growth in nerve cells because of its multiple passages through the monkey nervous system. They tried a different source of poliovirus and successfully infected these embryonic cells (33,34). John Franklin Enders was born in 1897 to a family of means in West Hartford, Connecticut. Beginning in a graduate program of English at Harvard, he focused on English and Celtic literature. However, impressed by a lecture and teachings of Hans Zinsser, Chairman of Bacteriology and Immunology at the Harvard Medical School, Enders decided to change careers and pursue a Ph. Three years later, at age thirty-three, he received his doctoral degree in bacteriology and immunology and became an instructor at Harvard Medical School. Like most microbiologists of his generation, he worked on techniques to control tuberculosis and pneumococci infections. Enders, with William Hayman, showed that the cats had a disease caused by a filterable agent and that this agent could transmit the disease. These observations on what proved to be panleukemia virus of cats provided Enders with his first real experience in virology, led to his first publication in this field, and focused the remainder of his career on this discipline. The major theme of his endeavors was to be the application of tissue culture techniques to virology and the extension of his findings to diagnosis and vaccination. He showed that poliomyelitis viruses grew not only in brain tissue but also in cultured cells from the skin, muscles, and intestines. He then proved that viruses produced in this way caused recognizable cytopathology (cell destruction) and that serum from the blood of individuals who were immune to poliovirus could block such cell destruction. Now Enders was able to supply virologists with a tool as important as the one Pasteur and Koch had provided for bacteriologists by developing defined culture media. Fifty years before Edward Jenner (35) showed that cowpox inoculation protected humans against smallpox and introduced the concept of vaccination, and thirty years after Lady Mary Montagu had her son variolated in Constantinople (36), a Scottish physician, Francis Home (37), drew on the same idea and attempted to produce mild measles by mimicking the variolation process. Similarly, by taking blood from an infected patient and inoculating it through the skin of an uninfected recipient, Home was able to transfer measles to ten of twelve patients. This experiment clearly demonstrated the presence of measles virus in human blood nearly 100 years before Frosch and Loeffier described the first animal virus (38). Next, they grew these viruses in epithelial cells obtained from kidneys of humans and monkeys (39). Subsequently, the same viruses grown in human kidneys, human amnionic fiuid, fertile hen eggs, and chick embryo cell cultures became the progenitors for the vaccines used today. For recognizing and adapting the culture method of replicating viruses, mainly poliomyelitis virus, Enders, with his colleagues Frederick Robbins and Thomas Weller, received the Nobel Prize in 1954 (30). The safety of cultured and attenuated viruses in producing immunity but not disease was demonstrated first in monkeys. Viruses passed in cultured cells were selected for their diminished ability to harm recipients while still inducing an immune response upon inoculation. When these viruses were inoculated into monkeys intracerebrally (into the brain), no disease or tissue damage occurred. By contrast, monkeys not first immunized developed severe measles virus infections when exposed to the virus. After this success, the attenuated Measles Virus 153 virus was tested in humans, first by inoculating the vaccine into immune adults in whom it was safe. The next step was a bigger clinical trial using children in several American cities. In 1961 Enders and his colleagues reported that measles virus infection could be prevented through vaccination (6). Shortly thereafter, in September 1961, an editorial appeared in the New York Times enthusiastically complimenting Enders on his accomplishment in developing the vaccine for measles and his work leading to the development of the poliomyelitis vaccine (40). For the sake of accuracy, however, I would emphasize the fact that whatever may have been accomplished represents the joint product of many co-workers supported by several institutions. In the studies on measles virus and vaccine, essential contributions were made by Thomas C. To me it seems most desirable that the collaborative character of these investigations should be understood, not solely for personal reasons but because much of all modern medical research is conducted in this way. First, Edmonston and his wife, owing to their personal philosophy, resisted any vaccination of their 154 Viruses, Plagues, and History own children. Second, a favorite toy of children around the globe is called Thomas the Tank Engine. Awdry wrote the story in the 1940s, with publication in 1945, while caring for his son Christopher who was laid up with the measles. Nevertheless, despite the stance of Edmonston and others of like opinion, the widespread vaccination of children in the United States and around the world has dramatically decreased the incidence of measles virus and its sometimes severe complications. A single exposure to the measles virus vaccine results in the production of antimeasles virus antibodies in greater than 80 to 85 percent of susceptible individuals. However, an unsolved problem remaining has been those infants infected with measles virus before their ninth month of age (6). This early infection occurs in a number of countries where the virus continues to circulate widely, particularly in the sub-Saharan African nations. Whether this dilemma will be overcome by immunization of all susceptible children and adults, thereby reducing the circulating virus pool, or design of a new vaccine that can provide protection but avoid neutralization by maternal antibody, remains to be determined. This confiict is currently being hotly debated among experts on measles virus infection (in favor of developing new vaccines that are not neutralized by maternal antibody) and epidemiologists (mainly in favor of using the current vaccine only). The outcome will have an important impact on the goal of possibly eradicating the measles virus. In addition to the large numbers of infants under a year of age who are susceptible to infection, a considerable population of children and adults lack immunity to the measles virus. The virus circulates in a community until its chain of transmission is broken by a massive vaccination program. However, as documented in Gambia from 1967 through 1970, such control is possible. In that small country, a year before the onset of mass vaccinations, 1,248 cases were recorded, but in 1969 and 1970 that number dropped to zero following a series of universal vaccinations done each year. What is clear from such examples is that a commitment by all nations to enforce universal immunization with the current vaccine will clearly reduce or potentially eliminate the presence of circulating virus in virtually every area of the world. Another problem still remaining is the low but significant number of vaccine recipients who fail to respond to the initial inoculation. To counteract this difficulty, many countries have instituted a two-dose schedule, with a second dose given at varying times after the first one. With such a strategy, measles has been eliminated entirely in Finland, Sweden, and Cuba, and the annual number of reported cases in the United States decreased from more than two million per year to now less than a handful. However, this highly contagious virus still travels beyond the borders of countries where vaccination is universal to those where it is not widely practiced, and measles viruses continue to infect those who remain susceptible. In Japan, despite some difficulties experienced with the side effects of a Japanese-manufactured measles virus vaccine, 156 Viruses, Plagues, and History the vast majority of their people have been vaccinated and, until recently, outbreaks of the infection numbered less than a few thousand per year. In Third World countries, measles has been more difficult to eliminate than in developed countries because the contact rates as well as reproduction rates are higher and the infrastructure is less well organized to provide vaccinations. India currently has more measles-related deaths than any other country and yet, at the time of writing this book, has not made measles vaccination a national priority. Even in highly industrialized European countries or the United States, measles has not been eliminated. The causes are inadequate vaccination coverage in preschool-age children, the approximately 5 percent primary vaccine failure rate, apathy, and concern that individuals not government agencies should decide whether to vaccinate. Further, objections that children are receiving too many vaccines and that the measles vaccine is often harmful, even a major cause of autism, although untrue, nevertheless block some vaccinations. Over time, vaccinations to prevent measles sank to 85 percent of the population or below in the United Kingdom in the late 1990s and early 2000s (reviewed in 43,44). As one would predict, soon afterward, outbreaks of measles followed with some devastating aftereffects. Autism, first recognized as a distinct disease in the 1940s, results in children who cannot relate to themselves or to other people and situations. Although its cause was not known in the 1990s and still is not Measles Virus 157 completely understood, the initial reports clearly indicated that autistic children frequently had parents who were highly motivated and career oriented. Further, the incidence of autism increased at the same time that mandatory vaccinations were initiated for infants. According to the paper, of twelve children who had autism and chronic enterocolitis (bowel disease), eight had been given the vaccine and one had a measles virus infection before the onset of autism. No virologic evidence was provided for the measles virus infection, nor was there any stringent epidemiologic evidence to link the infection or other events to autism. First Horton, despite the doubts of his reviewers, published the measles-autism article presumably to increase reader interest in the Lancet. Later, the financial confiicts-of-interest of some authors of the Lancet paper along with questions over lack of informed consent for the children were uncovered and resulted in most, but not all, of the authors retracting the paper six years after its publication. Horton further advocated obtaining financial and confiict-of-interest statements from all authors, which one would consider an absolute condition for any scientific publication. Such synapses are junctions across which neurons communicate, and they are required for sensory perception, movement, coordination, learning, memory, and likely social interaction. Measles, once the scourge of all lands, is now controlled in most countries, although it still kills millions in developing countries. The strategy for elimination of this virus depends on the dedication of every government to do so. The will to save these 500,000-plus lives per year rests solely on the dedication, responsibility, and commitment of the more fortunate nations, of all citizens on this planet, and, in turn, on the politicians and legislatures positioned to set the necessary priorities. Whether measles-related deaths will continue for over 100 years after the development of the measles virus vaccine, as was true for the smallpox vaccine, will largely be determined by the kind of society present in the twenty-first century. At the time of the World Health Assembly declaration of intent in 1988, more than 1,000 people per day developed polio. One hundred and twenty-five countries worldwide reported cases of poliomyelitis, among the oldest and most ferocious of maladies. Eradication of this dread disease was deemed possible due to successful development of the effective vaccines against polio: the inactivated killed vaccine of Salk in 1955 and the oral attenuated live virus vaccine by Sabin in the early 1960s. The United States, and then most other Western countries, discontinued use of the Sabin vaccine in 2000 because no new cases of poliovirus appeared spontaneously (wild-type). However, vaccine-induced polio developed in some geographically scattered individuals whose attenuated poliovirus inocula reverted to a virulent form.

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The highest level of use seems to be among 67%) treatment 3 antifungal buy generic zofran 4mg on line, whereas curative patients used herbal remedies much Asians (48 medicine yeast infection purchase 8 mg zofran with mastercard. More worryingly crohns medications 6mp zofran 8 mg lowest price, many adults were longinteractions was assessed in a Medicare population symptoms 2 weeks pregnant discount generic zofran uk, using a term users and most did not discuss this practice with their retrospective analysis of Cardiovascular Health Study interdoctor treatment 5th metatarsal stress fracture purchase cheap zofran on line. The authors suggested that most patients are elderly are those concerned with ameliorating degenerative not asked specifically about herbal consumption by their or age-related conditions treatment 02 academy purchase zofran 8mg overnight delivery. The prevalence of complementary/alternative medicine in cancer: each year from 1994 to 1999 for an average of 359 male a systematic review. Trends in complementary/alternative medicine use by breast cancer survivors: comparing survey data from 1998 and 2005. Complementary/ (non-vitamin, non-mineral) supplement followed by ginkgo, alternative medicine use in a comprehensive cancer center and the implications for chondroitin and garlic. Herbal use among cancer patients during alpha-lipoic acid, ginkgo and grapeseed extract showed a palliative or curative chemotherapy treatment in Norway. In the rural community 92% used concurrently in 20% of the patients and 15% were took herbal medicines with conventional medicines, compared with 70% of the urban community. Potential interactions of drug-natural everyday remedies used in the home; and women take more health products and natural health products-natural health products among children. Nonvitamin, nonmineral supplement use over a 12-month period by adult members of a large health maintenance suggested that women are at least twice as likely to take organization. Prevalence of complementary and alternative medicine use in cancer patients during treatment. Use of nonprescription dietary supplements for weight loss is take herbal and nutritional supplements. The practice of polypharmacy involving herbal and prescription medicines in the treatment of diabetes product, 88% had at least 1 year of college education. This serious under-reporting by patients may probably be this definition is obviously as true for conventional because they consider herbal medicines safe, even if taken at medicines as it is for herbal medicines. A the disapproval of the physician and, since they consider the reduction in efficacy due to an interaction can sometimes medicines to be safe, see no reason for inviting problems by be just as harmful as an increase. The practice of polypharmacy involving herbal and prescription medicines in the treatment of diabetes Echinacea purpurea extract mildly inhibited the cytochrome mellitus, hypertension and gastrointestinal disorders in Jamaica. For example, a mixture General considerations 7 of dietary soya isoflavones containing genistein was found to dealt with here as though they occur in isolation. Although a few drugs are cleared from the body simply by being excreted unchanged in the urine, most are chemically Mechanisms of drug interactions altered within the body to less lipid-soluble compounds, Some drugs interact together in totally unique ways, but, as which are more easily excreted by the kidneys. If this were the many examples in this publication amply illustrate, there not so, many drugs would persist in the body and continue to are certain mechanisms of interaction that are encountered exert their effects for a long time. Some of these isoenzymes concert, although for clarity most of the mechanisms are are also found in the gut wall. Note inhibition also Lidocaine oral, Propafenone, Quinidine) greatly between products) reported) Ginkgo (in vitro studies supported by clinical data, Anticholinesterases, centrally acting Bitter orange (juice known to have clinically but any effect modest. Note induction also reported) Azoles (Itraconazole, Voriconazole) Feverfew (in vitro evidence only) Benzodiazepines and related drugs Garlic (effects in vitro are probably not clinically (Alprazolam, Triazolam, Midazolam; Buspirone, relevant) Zolpidem, Zopiclone) Calcium-channel blockers (Diltiazem, Ginkgo (in vitro studies supported by clinical data, Felodipine, Lercanidipine) but any effect modest. Some herbal medicines can have a marked effect on the extent of first-pass metabolism of conventional drugs by (c) Predicting interactions involving cytochrome P450 inducing the cytochrome P450 isoenzymes in the gut wall or in the liver. Those that appear to responsible for the metabolism of drugs because by doing in cause clinically relevant induction of specific isoenzymes are vitro tests with human liver enzymes it is often possible to grouped in a series of tables, along with the conventional explain why and how some drugs interact. Unlike enzyme induction, which Drug transporter proteins may take several days or even weeks to develop fully, Drugs and endogenous substances are known to cross enzyme inhibition can occur within 2 to 3 days, resulting in biological membranes, not just by passive diffusion, but also the rapid development of toxicity. This may result in a fall in the plasma levels of more drugs (so-called serotonergic or serotomimetic drugs) digoxin. The characteristic symptoms fall into three some extracts of danshen appear to inhibit the activity of main areas, namely altered mental status (agitation, confuP-glycoprotein, and may therefore increase digoxin levels. It is for this reason that it is used as a probe another without allowing a long enough washout period in substrate for P-glycoprotein activity, and the effects of herbal between, and the problem usually resolves within about medicines on this particular drug have been studied. However, the effects of problems, while a very small number develop this serious many herbal medicines and drugs on these transporters are toxic reaction, but it certainly suggests that there are other less well understood than those of P-glycoprotein, and thus, factors involved that have yet to be identified. It has been proposed that the vitamin K content of herbal medicines may be sufficient (a) Additive or synergistic interactions to provoke this interaction, but in most cases of normal If two drugs that have the same pharmacological effect are intake of the herb, this seems unlikely. The human population is a total mixture, unlike selected theoretical additive nephrotoxicity, see Ginkgo + Aminoglybatches of laboratory animals (same age, weight, sex, strain, cosides, page 209). These words make-up, ethnic background, sex, renal and hepatic funchave precise pharmacological definitions but they are often tions, diseases and nutritional states, ages and other factors used rather loosely as synonyms because in practice it is (the route of administration, for example) all contribute often very difficult to know the extent of the increased towards the heterogeneity of our responses. The based on what has been seen in other patients: the more reasons for this effect are not fully understood, but the extensive the data, the firmer the predictions. Be on the alert with any drugs that have a narrow especially as evidence regarding interactions between herbal therapeutic window or where it is necessary to keep serum medicines is often only of an experimental nature. Consider the think what might happen if drugs that affect the same facts and conclusions, and then set the whole against the receptors are used together. Keep in mind that the elderly are at risk because of decide to do is well thought out and soundly based. We do reduced liver and renal function on which drug clearance not usually have the luxury of knowing absolutely all the depends. A cido philus Lactobacillus acidophilus (Lactobacillaceae) Use and indications Pharmacokinetics Lactobacillus acidophilus are lactic-acid producing bacterial No relevant pharmacokinetic data found. Acidophilus supplements are primarily taken as a probiotic, Interactions overview to restore or maintain healthy microbial flora. Antibacterials and yeast-based infections (such as those caused by Candida drugs that are dependent on bacterial degradation to release albicans), and for general digestive problems. It is available active constituents, namely sulfasalazine, may also be in various forms ranging from capsules to yoghurts. The authors A the interaction between acidophilus and antibacterials is based hypothesised that increasing the populations of bacteria, by using on experimental evidence only. For more information on the interactions of isoflavones with sulbactam,3 benzylpenicillin,2,3 cefalotin,1 chloramphenicol,2,3 in general, see under isoflavones, page 258. Plasma cycline,3 penicillin,1 quinupristin/dalfopristin,3 streptomycin,3 tetraphytoestrogensarenot altered byprobioticconsumptionin postmenopausalwomenwith cycline2 and vancomycin3 have been found to inhibit acidophilus and without a history of breast cancer. Mechanism Antibacterials kill or inhibit the growth of bacterial populations through various different mechanisms. Importance and management Acidophilus + Immunosuppressants Depending on the particular strain of acidophilus and the antibacterial dose, the desired therapeutic effect of acidophilus An isolated case report describes fatal septicaemia in an may be significantly reduced or even abolished by these antiimmunosuppressed woman taking cyclophosphamide and flubacterials. Susceptibility of 40 lactobacilli to six rhamnosus, which is closely related to acidophilus. Antimicrobial susceptibilities of Lactobacillus rhamnosus septicaemia, which proved to be fatal, Lactobacillus, Pediococcus and Lactococcus human isolates and cultures intended for probiotic or nutritional use. Mechanism Acidophilus + Food the immunosuppressed nature of the patient is thought to have provided a more conducive environment for the introduced bacteria No interactions found. Importance and management Although not a drug interaction in the strictest sense, it would be sensible to assume that introducing bacteria in the form of a probiotic to an immunosuppressed patient should be undertaken with Acidophilus + Herbal medicines; Soya great care or perhaps avoided: note that patients who have isoflavones undergone a transplantation and who are immunosuppressed are often advised to avoid foods such as live yoghurts. Remember that, as immunosuppression secondary to corticosterAcidophilus does not generally affect the metabolism of soya oid use is dependent on numerous factors related to the dosage and isoflavones. In a randomised study 20 women who had been successfully treated for breast cancer and 20 women without a history of cancer were 1. Yoghurt biotherapy: contraindicated in given a soya protein isolate containing 640micrograms/kg of immunosuppressed patientsfi The azo link of sulfasalazine is split by anaerobic bacteria in the It should be noted, however, that this is a rather old experimental colon to release sulfapyridine and 5-aminosalicylic acid, the latter study that appears to be the only one of its kind in the literature. Taking all this into account, this the bacterial cell by passive diffusion across the cell membrane. Constituents Agnus castus is usually standardised to the content of the Interactions overview flavonoid casticin (dried ripe fruit and powdered extracts A comprehensive systematic review of data from spontancontain a minimum of 0. Other major case reports was carried out in September 2004 to investigate constituents are the labdane and clerodane diterpenes the safety of agnus castus extracts. However, agnus castus has dopamine agonist properties, and may therefore interact with drugs with either dopamine Use and indications agonist or dopamine antagonist actions. Traditional use of the dried ripe fruit of agnus castus focuses Agnus castus contains oestrogenic compounds but it is on menstrual disorders in women resulting from corpus unclear whether the effects of these compounds are additive, luteum deficiency, such as amenorrhoea, metrorrhagia and or antagonistic, to oestrogens and oestrogen antagonists. Vitex agnus castus: a systematic No relevant pharmacokinetic data for agnus castus found. The agnus castus was In a double-blind study in women suffering from mastalgia, agnus stopped and she experienced symptoms suggestive of mild ovarian castus extracts reduced serum prolactin levels (by about 4nanohyperstimulation syndrome in the luteal phase. Mechanism Active compounds of agnus castus may compete for the same Importance and management oestrogen receptor as hormonal drugs and treatment. The in vitro evidence suggests oestrogenic use of agnus castus and dopaminergics that act at the D2-receptor, activity. For dopamine agonists such as bromocriptine and apomorphine, additive effects and toxicity is a theoretical Importance and management possibility. Ergebnisse einer randomisierten, receptor as conventional hormonal drugs, with the outcome of either plazebo-kontrollierten Doppelblindstudie. In vitro assays for bioactivity-guided hormonally active herbal medicines, unless under the advice of an isolation of endocrine active compounds in Vitex agnus-castus. In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus. The interaction between agnus castus and opioids is based on experimental evidence only. Agnus castus + Oestrogens or Oestrogen Experimental evidence antagonists Various agnus castus extracts have been shown to have an affinity to opioid receptors in an in vitro study. Pharmacological activities of Active compounds of agnus castus and opioids may have additive Vitex agnus-castus extracts in vitro. Other constituents include flavonoids, Information on the interactions of flavonoid supplements are based on quercetin, kaempferol, apigenin, catechins, epicacovered under flavonoids, page 186, but note that it is techins and procyanidins; various phenolic acids; triterpenes unlikely that agrimony would be taken in doses large enough including fi-amyrin, ursolic and euscapic acids, phytosterols; to give the levels of individual flavonoids used in the salicylic and silicic acids. It the dried flowering tops are used as a mild astringent and may therefore be expected to interact with conventional diuretic. A Experimental evidence the interaction between agrimony and antidiabetics is based on experimental evidence only. One study in rats found that agrimony had little significant diuretic activity,1 and Clinical evidence another in cats found that intravenous agrimony decreased blood pressure over a period of 20minutes. Experimental evidence Mechanism In various in vitro and animal studies, high-dose agrimony has It is possible that the herb will have weak antihypertensive effects, stimulated insulin secretion and reduced hyperglycaemia. Medicago afghanica Vass, Medicago grandiflora A possible association between alfalfa and systemic lupus (Grossh. For information on the the main active constituents of alfalfa are the isoflavones, pharmacokinetics of its isoflavone constituents genistein, which include biochanin A, formononetin, daidzein and daidzein and biochanin A, see isoflavones, page 258. Other components include the toxic amino acid canavanine; Although it has been suggested that alfalfa may interact with natural coumarins such as coumestrol, lucernol, medicagol, antidiabetic medicines and anticoagulants, evidence for this sativol and daphnoretin; the sterols campestrol and betais largely lacking. Alfalfa + Immunosuppressants Alfalfa + Antidiabetics An isolated report describes acute rejection and vasculitis with alfalfa and/or black cohosh in a renal transplant recipient taking ciclosporin. An isolated case describes a marked reduction in blood-glucose levels in a diabetic patient who took an alfalfa extract. Clinical evidence Clinical evidence A stable kidney transplant recipient taking azathioprine 50mg daily and ciclosporin 75mg twice daily began to take alfalfa and black A case report describes a young man with poorly controlled diabetes cohosh supplements (specific products not stated) on medical advice (reportedly requiring large doses of insulin for even moderately for severe menopausal symptoms.

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Alagiakrishnan K treatment coordinator buy generic zofran from india, Sankaralingam S medicine ethics buy zofran amex, Ghosh M treatment 4 pink eye purchase zofran online from canada, of high blood pressure in adults: report from the abetes medicine dictionary prescription drugs buy discount zofran 4 mg online, insulin administration may be Mereu L medications hyperthyroidism order zofran 4 mg online, Senior P symptoms nausea fatigue order zofran 8 mg line. Prev Chronic Dis 2012;9:E100 S126 Diabetes Care Volume 41, Supplement 1, January 2018 American Diabetes Association 12. Attention to family dynamics, developmental stages, and physiological differences related to sexual maturity are all essential in developing and implementing an optimal diabetes treatment plan (4). Due to the nature of clinical research in children, the recommendations for children and adolescents are less likely to be based on clinical trial evidence. A multidisciplinary team of specialists trained in pediatric diabetes management Suggested citation: American Diabetes Associaand sensitive to the challenges of children and adolescents with type 1 diabetes and tion. Children and adolescents: Standards of their families should provide care for this population. The appropriate balance between adult supervision and independent selfmation is available at. Furthermore, the compact adherence to diabetes manthe adolescent gradually becomes an plexities of diabetes management require agement and provide appropriate emerging young adult. E tween the growing child/teen and parent c Mental health professionals should Recommendation in order to maintain adherence and to prebe considered integral members of c Youthwithtype1diabetesand vent deterioration in glycemic control the pediatric diabetes multidisciparents/caregivers (for patients (16,17). E aged,18 years) should receive fiict is related to poorer adherence and c Encourage developmentally approculturally sensitive and developglycemic control, it is appropriate to inquire priate family involvement in diabementally appropriate individualized about such confiict during visits and to eites management tasks for children diabetes self-management educather help to negotiate a plan for resolution and adolescents, recognizing that tion and support according to naor refer to an appropriate mental health premature transfer of diabetes care tional standards at diagnosis and specialist (18). Monitoring of social adjustto the child can result in nonadherroutinely thereafter. B ment (peer relationships) and school perence and deterioration in glycemic formance can facilitate both well-being control. Subopmen, it can only be effective if the family c Providers should consider asking timal glycemic control is a risk factor for and/or affected individuals are able to youthand theirparentsabout social below average school performance and implement it. Familyinvolvementisavital adjustment (peer relationships) and increased absenteeism (20). Health care providers (the ponents and self-management behaviors diabetes care team) who care for chilc Assess youth with diabetes for psycan improve diabetes self-efficacy, addren and adolescents must be capable of chosocial and diabetes-related disherence, and metabolic outcomes (21). E Beginning at the onset of puberty or at necessary toassessthe educationalneeds c Offer adolescents time by themselves diagnosis of diabetes, all adolescent girls and skills of day care providers, school with their care provider(s) starting at and women with childbearing potential nurses,orotherschoolpersonnelwhoparage 12 years, or when developmenshould receive education about the risks ticipate in the care of the young child with tally appropriate. A Preconception counseling using develin school, close communication with and opmentally appropriate educational tools the cooperation of school or day care perenables adolescent girls to make wellsonnel are essential for optimal diabetes Rapid and dynamic cognitive, developinformed decisions (23). Preconception management, safety, and maximal acamental, and emotional changes occur counseling resources tailored for adolesdemic opportunities. Screening for psychosocial distress and Early detection of depression, anxiety, mental health problems is an important Recommendations eating disorders, and learning disabilities component of ongoing care. It is imporc At diagnosis and during routine followcan facilitate effective treatment optant to consider the impact of diabetes on up care, assess psychosocial issues tions and help minimize adverse effects quality of life as well as the development S128 Children and Adolescents Diabetes Care Volume 41, Supplement 1, January 2018 of mental health problems related to dithat near normalization of blood glucose improve glycemic control. Benefits abetes distress, fear of hypoglycemia (and levels was more difficult to achieve in adof continuous glucose monitoring hyperglycemia), symptoms ofanxiety, disolescents than in adults. Nevertheless, correlate with adherence to ongoordered eating behaviors as well as eating the increased use of basal-bolus regimens, ing use of the device. B disorders, and symptoms of depression insulin pumps, frequent blood glucose c Automated insulin delivery systems (25). Consider assessing youth for diabemonitoring, goal setting, and improved paimprove glycemic control and retes distress, generally starting at 7 or tient education in youth from infancy duce hypoglycemia in adolescents 8 years of age (15). Consider screening through adolescence have been associaand should be considered in adolesfor depression and disordered eating beted with more children reaching the blood cents with type 1 diabetes. E unique and dangerous disordered eating diabetes participate jointly to perform the behavior of insulin omission for weight required diabetes-related tasks. The presmore, studies documenting neurocognitive agement refiect the need to lower gluence of a mental health professional on imaging differences related to hyperglycecose as safely as possible. This should be pediatric multidisciplinary teams highmia in children provide another motivation done with stepwise goals. When establights the importance of attending to for lowering glycemic targets (2). In selecting glycemic goals, the longspecial consideration should be given to these psychosocial factors are signifiterm health benefits of achieving a lower theriskofhypoglycemiainyoungchildren cantly related to nonadherence, suboptimal A1C should be balanced against the risks (aged,6 years) who are often unable glycemic control, reduced quality of life, of hypoglycemia and the developmental to recognize, articulate, and/or manage and higher rates of acute and chronic diburdens of intensive regimens in children hypoglycemia. In addition, achieving lower Type 1 diabetes can be associated with A1C levels is more likely to be related to Glycemic Control adverse effects on cognition during childsetting lower A1C targets (46,47). Factors that Recommendations and blood glucose goals are presented contribute to adverse effects on brain c the majority of children and adolesin Table 12. HowRecommendation injections or continuous subcutaneever, meticulous use of new therapeutic c Assess for the presence of autoimous insulin infusion. A modalities, such as rapidand long-acting mune conditions associated with c All children and adolescents with insulin analogs, technological advances type 1 diabetes soon after the ditype 1 diabetes should self-monitor. B blood glucose levels multiple times glucose suspend insulin pumps, and audaily, including premeal, prebedtomated insulin delivery systems), and Because of the increased frequency of time, and as needed for safety in intensive self-management education other autoimmune diseases in type 1 dispecific clinical situations such as now make it more feasible to achieve exabetes, screening for thyroid dysfunction exercise, driving, or for symptoms cellent glycemic control while reducing and celiac disease should be considered of hypoglycemia. Asymptomatic suring IgA tissue transglutaminase and monitored as clinically indicated. The challenging dietype 1 diabetes for antithyroid perc Repeat screening within 2 years of tary restrictions associated with having oxidase and antithyroglobulin andiabetes diagnosis and then again both type 1 diabetes and celiac disease tibodies soon after the diagnosis. E quent screening in children who Therefore, a biopsy to confirm the diagc Measure thyroid-stimulating horhave symptoms or a first-degree nosis of celiac disease is recommended, mone concentrations at diagnosis relative with celiac disease. B especially in asymptomatic children, bewhen clinically stable or soon after c Individuals with biopsy-confirmed fore endorsing significant dietary changes. B Risk Factors megaly, an abnormal growth rate, Celiacdiseaseisanimmune-mediateddisHypertension or an unexplained glycemic variation. A order that occurs with increased freRecommendations quency in patients with type 1 diabetes Screening (1. At the time of diagnosis, about 25% tissue transglutaminase antibodies, or, forage,sex,andheight)orhyof children with type 1 diabetes have thywith IgA deficiency, screening can include pertension (systolic blood pressure roid autoantibodies (51); their presence measuring IgG tissue transglutaminase anor diastolic blood pressure $95th is predictive of thyroid dysfunctiond tibodies or IgG deamidated gliadin peptide percentile for age, sex, and height) most commonly hypothyroidism, alantibodies. Because most cases of celiac should have elevated blood though hyperthyroidism occurs in;0. For thyroid autoantibodies, a recent tes, screening should be considered at the study from Sweden indicated antithyroid Treatment time of diagnosis and repeated at 2 and peroxidase antibodies were more predicc Initial treatment of high-normal then 5 years (58). Thyroid funcsure or diastolic blood pressure nosed more than 10 years after diabetes tion tests may be misleading (euthyroid consistently $90th percentile for diagnosis, there are insufficient data after sick syndrome) if performed at the time age, sex, and height) includes die5 years to determine the optimal screenof diagnosis owing to the effect of previous tary modification and increased ing frequency. Measurement of tissue hyperglycemia, ketosis or ketoacidosis, transglutaminase antibody should be conexercise, if appropriate, aimed at weight loss, etc. A small-bowel biopsy in antibodysoon after a period of metabolic stability vention, pharmacologic treatment positive children is recommended to confirm and good glycemic control. European guidelines hypothyroidism may be associated with c In addition to lifestyle modification, on screening for celiac disease in chilincreased risk of symptomatic hypoglycepharmacologic treatment of hyperdren (not specifictochildrenwithtype1 mia (55) and reduced linear growth rate. Abnormal results from a random tor blockers may be considered for one or more cardiovascular disease lipid panel should be confirmed with a the treatment of elevated (. If ablevels (74); likewise, a lifestyle intervennormal, repeat lipid profile after tion trial with 6 months of exercise in adSmoking fasting. E olescents demonstrated improvement in Recommendation c If lipids are abnormal, annual monilipid levels (75). Despite this, smoktimizing glucose control and mediHeart Associationdiet, whichrestricts sating rates are significantly higher among cal nutrition therapy using a Step urated fat to 7% of total calories and reyouth with diabetes than among youth 2 American Heart Association diet stricts dietary cholesterol to 200 mg/day. In youth with to decrease the amount of satuData from randomized clinical trials in diabetes, it is important to avoid addirated fat in the diet. Smoking increases c After the age of 10 years, addition dicate that this diet is safe and does not the risk of onset of albuminuria; thereof a statin is suggested in patients interfere with normal growth and develfore, smoking avoidance is important to who, despite medical nutrition theropment (77). E in youth is different not only from type 1 performed at puberty or at age $10 diabetes but also from type 2 diabetes in Retinopathy (like albuminuria) most comyears, whichever is earlier, once the adults and has unique features, such as a monly occurs after the onset of puberty child has had diabetes for 5 years. Type 2 c When persistently elevated urinary professionals with expertise in diabetic diabetes disproportionately impacts albumin-to-creatinine ratio (. The c Consider an annual comprehensive family history ofdiabetes,female sex, and urine samples should be obtained foot exam at the start of puberty or low socioeconomic status (96). A comprehensive portance of routine screening to ensure c Risk-based screening for prediabefoot exam, including inspection, palpation early diagnosis and timely treatment of tes and/or type 2 diabetes should of dorsalis pedis and posterior tibial be considered in children and adoalbuminuria (84). B weight management for children their families should receive compreand adolescents with type 2 diabetes, hensive diabetes self-management Inthe last decade, the incidence and prevlifestyle intervention should be based education and support that is specific alence of type 2 diabetes in adolescents on a chronic care model and offered to youth with type 2 diabetes and has increased dramatically, especially in rain the context of diabetes care. A c Youth with diabetes, like all chilfew recent studies suggest oral glucose dren, should be encouraged to the general treatment goals for youth tolerance tests or fasting plasma glucose participate in at least 60 min of with type 2 diabetes are the same as values as more suitable diagnostic tests moderate to vigorous physical acthose for youth with type 1 diabetes. A than A1C in the pediatric population, estivity per day (and strength training multidisciplinary diabetes team, including pecially among certain ethnicities (98). C istered dietitian, and psychologist or social recognize that diabetes diagnostic criteria c Nutrition for youth with type 2 diworker,isessential. Inadditiontoblood are based on long-term health outcomes, abetes, like all children, should foglucose control, initial treatment must inand validations are not currently available cus on healthy eating patterns that clude management of comorbidities such in the pediatric population (99). A1C for diagnosing type 2 diabetes in childecreased consumption of calorieCurrent treatment options for youthdren and adolescents. Although A1C is dense, nutrient-poor foods, particonset type 2 diabetes are limited to two not recommended for diagnosis of diabeularly sugar-added beverages. B approved drugsdinsulin and metformin tesin childrenwith cystic fibrosis orsymp(95). Metformin therapy to recommend A1C for diagnosis of type2 c In metabolically stable patients may be used as an adjunct after resoludiabetes in this population (100,101). Initial treatmetformin is the initial pharmacoment should also be with insulin when the Diagnostic Challenges logic treatment of choice if renal distinction between type 1 diabetes and Given the current obesity epidemic, distin2 function is. A type 2 diabetes is unclear and in patients guishing between type 1 and type 2 diabec Youth with marked hyperglycemia who have random blood glucose concentes in children can be difficult. E abetes, individual-level lifestyle intervenManagement c In patients initially treated with tions may not be sufficient to target the Recommendations basal insulin and metformin who complex interplay of family dynamics, are meeting glucose targets based mental health, community readiness, and Lifestyle Management on home blood glucose monitoring, the broader environmental system (95). B Alterations in white matter structure in young youth with type 2 diabetes; the combinachildren with type 1 diabetes. Neurological conseSmall retrospectiveanalyses and a recent from parents and other adults to the youth quences of diabetic ketoacidosis at initial presentawith type 1 or type 2 diabetes throughout tion of type 1 diabetes in a prospective cohort study prospective multicenter nonrandomized of children. Developsurgery may have similar benefits in obese pediatric to adult health care providers, mental changes in the roles of patients and families adolescents with type 2 diabetes compared however, often occurs abruptly as the older intype1diabetesmanagement. Type 1 diadiabetes remission, and improvement of which is a critical period for young people betes through the life span: a position statement cardiometabolic risk factors for at least who have diabetes. Type 1 diabetes in children and adolescents: a position effectiveness and safety of surgery to must become fully responsible for their statement by the American Diabetes Association.

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Especially in Kaduna symptoms tonsillitis order zofran uk, Plateau and Nasarawa States treatment modalities order zofran cheap online, many of the chiefs are twentieth century creations treatment restless leg syndrome trusted zofran 8 mg. This is not to say some of these communities did not have ritual leaders prior to 1900 medications used for anxiety buy generic zofran from india, but these individuals did not have a category of political authority corresponding to the notion of chiefship medications ending in pril order 8 mg zofran. The key factors in advancing a claim for chiefship were the proximity of the Hausa chiefdoms and the early impact of missionary education symptoms influenza generic zofran 8mg overnight delivery. As a consequence, the possession of a traditional ruler was seen as a sine qua non of political identity, and regalia were often appropriated from Islam, even where the area was wholly Christian. For example, the ruler of the Ninkyob 17 people in southern Kaduna State, who was only appointed in 2005, has surrounded himself with Islamic regalia, despite the fact that the area has almost no Muslims at all. The rise in political awareness in the Middle Belt has accelerated the evolution of Christian or unaffiliated rulers, who take their model of kingship from their Muslim neighbours. Part of the impact of the colonial system was to formalise the extent of the territory over which a traditional ruler exercised power. The colonial provinces were transformed into States in 1967, at which time there was a rough correspondence between the larger northern Emirates and the relevant states. However, with increasing population, greater awareness of individual ethnic groups, and improved communications, came demands for more states and local governments. This was undoubtedly also powered by a mistaken belief that if a state split into two, it would have the same income from Federal Government as the former larger unit. In the window of democracy in the early 1990s, this was a persuasive view and states such as Sokoto were first divided in 1991, with the creation of Kebbi state and then again in 1996 with the creation of Zamfara. Local rulers in the new states increased their authority and that of the Sultan of Sokoto was correspondingly reduced. In the Middle Belt, the situation was somewhat different since there were no large pre-colonial polities. Created and extended chiefdoms began to claim authority over regions that traditionally had no rulers at all. Very often this involved trying to enfold minorities into a larger ethnic grouping in order to do this, and very often this was reflected in attempts to control Local Goverments. This has sometimes been responsible for violent local riots, such as the problems in Shendam in 2006, but on the whole has been accepted, since such 17 Visit to Ninkyob, Roger Blench, July 2006. Individual states may demonstrate a mixture of both Islamic and non-Islamic systems. The typical Hausa/Fulfie Emirates stretching from Sokoto to Gombe and parts of Adamawa/Taraba are fairly uniform in administration and regalia. But where there is an articulate population of Christians, Emirs must operate with a fair degree of subtlety. In 1985, the Emir was dethroned following land misappropriation and a new one is still to be appointed following protests from the dominant non-Islamic inhabitants. A combination of a painful historical record and a background population with acephalous social structures probably means that Muri Emirate will never now revive. Main towns and locations of traditional chiefdoms featured in the text the focus on Northern Nigeria reflects the fact that the institution of traditional rulers in the South is very different in character. The traditional kingdoms of the Yoruba were as follows (Table 3); 22 Traditional leaders in Nigeria, Main text of Final Report Table 3. Kingdoms of the Yoruba Location Kingdoms Primary Ife, Oyo Eastern Ijesha, Ekiti, Igbomina, Owfi, Ondo Western Ketu, Shabe, Dassa Southern Ijebu, Egba, Egbado, Lagos Islamic Ilorin Source: Smith (1988) the non-Islamic kingdoms were as much ritual entities as political institutions which probably explains their very different fates in the twentieth century. The colonial authorities saw no reason to prop them up in the same way as Northern Emirates and they were never integrated into a system of indirect rule. As a consequence, none have retained the type of authority that is common in Islamic areas and those that have retained power have achieved it through savvy political and financial manoeuvrings. In the Niger Delta, the patchy nature of aquatic resources prior to outside contact resulted in an acephalous social structure until trade and guns changed the equations of power. When Clapperton entered Kano in 1824 he estimated the population at just 30-40,000 (Denham, Clapperton & Oudney 1826). Although many of the pre-Jihad states were broadly of Islamic orientation, the Jihad of Shehu Uthman Dan Fodio that began in 1804 and was initially intended as a movement for reform soon became a military adventure. Dan Fodio and his followers imposed the emirate system throughout most of what is now Northern Nigeria and the ruling Hausa dynasties were replaced by Fulfie. Although these families were initially Fulfulde-speaking, they had little in common with the Fulfie cattle-herders in rural areas. Over time, almost all of them took on the language and culture of the peoples they ruled. Thus most of the northern rulers became Hausa-speaking whereas those among the Nupe 18 Cf. What baffles everyone, is that why would the traditional rulers, the custodian of the culture and morals of the society now show examples in line with the mood of the democratic nature of the country. So one is not surprised at the struggle to stay in office when the term of office of the executive has extended. Nonetheless, a claim to Fulfie ancestry remains highly prestigious, even today, when hardly any trace of Fulfie culture remains among the ruling classes. The one exception to this in Nigeria was the Lamidate of Adamawa, based in Yola, which has remained Fulfulde-speaking, as have some of the chiefdoms across the border in neighbouring Cameroun. The flag-bearers of the Jihad were given the task of conquering seven crucial polities and seven deemed less important, the so-called Hausa Bakwai and the Banza Bakwai (Table 4); Table 4. Emirates conquered following the 1804 Jihad Hausa Bakwai Banza Bakwai Kano Gombe Katsina Kazaure Zaria Daura Bauchi Hadejia Adamawa Misau Nupe Katagum Ilorin Borno [not conquered] Today, only a vestige of the Sokoto Empire exists, as the Sokoto Sultanate has no supervisory role over any emirate or chiefdom. The Sultan of Sokoto still functions primarily as the paramount leader of the traditional institutions in Sokoto state. However, his supreme authority in Islamic matters still transcends territorial boundaries as he is considered the overall leader of Nigerian Muslims. However, they can appoint officials directly as well as allotting titles to individuals who then become advisors to the ruler. One of the most important duties of traditional rulers is to be present at government occasions such as foundation laying ceremonies, project commissioning, welcoming visiting government officials and so on. From the point of view of government, this has the advantage of reducing pressure on civil servants, but also gives an impression (sometimes false) that traditional rulers fully support government activities. In some matrimonial cases for instance, rulers provide hospitality to a woman perceived to be suffering injustice from both religious and judicial point of view, for the period of arbitration. A relic of the Native Authority structure of the Colonial and post-Independence eras that persists in most Emirates are the Senior Councillors. Individuals with this title have no portfolios in the local government system although they are honorary officials of Emirs with considerable influence. They are generally members of the ruling family whose function is to guarantee the Emir is seen not to have arrogated power to himself alone. This system is re-interpreted in the complex multi-ethnic Middle Belt chiefdoms as a mechanism for sharing out power between political sub-units in order to defuse rivalry. For example, one clan of the ethnic group might provide the Galadima, another the Madaki, yet another the Waziri to assist the chief. This type of delegation frees up the chief for more important tasks but also distributes 24 Traditional leaders in Nigeria, Main text of Final Report responsibility for controversial actions. These titles have no very fixed authority and may vary from one chiefdom to another. Table 5 shows the typical portfolio councillor system as at July 1962 in Northern Nigeria; Table 5. Kingdoms such as the Nupe, with a mixed linguistic heritage may adopt some Hausa titles while retaining indigenous titles from their own system. The Sultan of Sokoto has the title Sarkin Musulmi, Commander of the Faithful, 19 and he is considered the most senior of the first class chiefs in Northern Nigeria. The Sultan announces the sighting of the moon to mark the month of Ramadan and the beginning and end of the annual fast. The pre-eminence of Sokoto itself dates only to the beginning of the nineteenth century. Prior to that, a complex of states controlled by different ethnic groups controlled the Sokoto-Rima system (cf. Two kinglists compete for the prehistory of the Sultanate, that of the kings of Zamfara, said to stretch back to the thirteenth century and those of Gobir, located in Arabia and the Sudan, and thus more evidently in a mythical realm. Following the battle of Tabkin Kwatto in 1804, when the forces of the Jihad defeated the Gobirawa, Uthman Dan Fodio conferred flags and titles on the local chiefs. Namoda was made Sarkin Zamfara and the Sarkin Zamfara of Zurmi and the Sarkin Kiawa of Kaura Namoda are descended from him. Mojiju became Sarkin Kebbi of Yabo, a title 19 During the field visit to Sokoto, Sultan Alhaji Muhammadu Maccido personally met with the research th team before directing the Senior Councillor of the Sultanate to grant the rest of the interview on 18 February 2006. The titles of Ardo Ding Yadi and Ardo Shuni (Dangara) are still held by descendants of the first titleholders, and the Sarkin Yaki of Binji descended from the original Sarkin Yaki, Aliyu Jedo. The Waziri of Sokoto surrendered to Lord Lugard in 1903 and until the 1930s, the British authorities appointed a succession of weak rulers. The one ruler who did not bend to their will, Sultan Muhammadu Tambari, was repudiated by his own people for occult activities, deposed and banished to Wukari in 1931. However, when the power to appoint officeholders was returned to the kingmakers, the Sultanate began to gain in eminence again. A continuing lack of support for Dasuki made it imperative for the Federal Government to get rid of him, and in 1996, during the Abacha era, the Military Administrator of Sokoto deposed Alhaji Dasuki and installed Alhaji Muhammadu Maccido. The justification for this was that Dasuki had been involved in financial misdeeds, although clearly this was little more than a pretext. The rather evident ease with which the Federal Government could replace and appoint the Sultan has undoubtedly led to an overall decline in the political authority of the Sultanate and a rise of scepticism among its subjects. Another aspect of this decline is that although Sokoto was once the capital of a substantial empire the area of its suzerainty has been much reduced. Sokoto State, created in 1967, was roughly coterminous with the previous domain of the Sultanate. But the characteristic process of states creation during the 1990s gradually broke up its territorial coherence. The fragmentation of Sokoto state into the present Sokoto, Kebbi and Zamfara states in 1991 and 1996, also weakened the authority of the Sultan. This political decline has been partly counterbalanced by an increased emphasis on religious leadership. The engagement of the Sultan with spiritual and administrative matters at the national level that day-to-day administration is delegated to 20 official titleholders both at the palace and in the districts. However, in spite of the wrangling in the Sultanate palace, district, village and ward heads and councillors still continue to resolve issues affecting their communities. In view of his leadership role, the Sultan is often the first leader called when religious crises occur. He has mediated by meeting with different groups and government functionaries; for example, during the Tiv-Jukun crisis in 1992, Tafawa-Balewa crisis in 1995, Jos crisis in 2001-2004, Kafanchan crisis of 1999 and ZangonKataf crisis of 1997 in Taraba, Bauchi, Plateau and Kaduna states respectively. In November 2002, when some incautious remarks by a newspaper columnist concerning the Miss World Beauty pageant led to a severe crisis in Kaduna, with significant loss of life, the Sultan appealed for calm and met with Muslim leaders to contain the situation. The strong identification of the Sultan with Muslim interests makes it more difficult to mediate effectively in an inter-religious crisis. Emirs and chiefs in Kebbi state are given full recognition and assigned important roles. Although they have been 20 Fieldwork was conducted in Wamako, Kuane, Goronyo, Rabbah and Isah districts. The founder of Gwandu, Abdullahi, in 1808 was the guardian of the administration of the western part of Sokoto Emirate. Shortly after this the capital of Gwandu was moved permanently to Birnin Kebbi, where it is based today, a move that is responsible for the location of modern Kebbi State. Unlike Sokoto, Kebbi includes a substantial population of non-Muslims in the southern Local Governments and traditional rulers have to move much more carefully to avoid sparking conflicts. Gwandu Emirate council has jurisdiction throughout the territorial boundaries of the historic Emirate. The Emirate council was established ostensibly to reconcile the traditional rulers, although is now accepted that Emirate or Traditional council cannot veto any decision of local government. The Emirate council has the responsibility of holding Chieftaincy, Traditional and customary matters. The Emir has certain specific responsibilities including the settlement of crises, the maintenance of law and order, assistance in tax and rate collection and the compilation of nominal rolls, the settlement of disputes and to provide leadership to the people, especially in national activities.

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