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X-chromosome inactivation takes place in every cell Despite the absence of angiokeratoma, cutaneous biopsy is 3,23 at the start of embryogenesis. Parents should be informed about the cytes, smooth muscle cells, conduction system cells, and 39,40 likelihood that siblings, relatives, and future children will valvular brocytes. Affected mothers have a 50% chance of Brain alterations result from lipid deposits that can be passing the defective gene on to all offspring whether boys found in the sympathetic ganglions of the autonomic ner or girls. Sons who inherit the gene will be affected; her daugh vous system, brainstem, hypothalamus, amygdala, hippo 41,42 ters may display a spectrum of clinical involvement. Previously, unrecognized pneumocytes and epithelial cells of the bronchial membrane. Currently, prenatal diagnosis can peritubular myoblasts, and deposits in vascular endothelium 1 be established in boys via a-Gal A de ciency testing using and perivascular cells. With age, the reddish purple, nonblanching vascular lesions pro Neurological Manifestations gressively increase in number and size. Hair may be become 1 Patients with Fabry disease present peripheral and central thicker with a coarse texture. Neuropathic pain is often the rst manifesta Although angiokeratomas are often regarded as being tion of loss of small, unmyelinated nerve ber function and synonymous with Fabry disease, they may also be present 29,30 in patients with other enzymatic de ciencies, for example, can present in 2 forms. Episodes may last for days Ophthalmologic Manifestations 58 or weeks and are generally accompanied by fever and elevated Generally, ocular lesions do not affect vision. Unfortunately, acroparesthe ually evolves into spiral streaks in the corneal epithelium sias are often misdiagnosed as growing pains or malingering. Corneal verticillata is not pathognomonic for Fabry dis 45 ease because it may also be encountered in patients using can lead to patients becoming depressed in adulthood. Peripheral neuropathy also manifests as autonomic dys phenothiazine, chloroquine, indomethacin, or amiodar 1,60 function causing hypohidrosis or anhidrosis (inability to one. The opacities are believed to be caused by accumula sweat), orthostatic hypotension, and bowel disturbances tion of glycosphingolipids at the level of the Bowman layer 46 and anterior stroma. Sensory losses, especially loss of thermal sensation, due to Narrowing of arterioles, dilation of veins, exaggerated autonomic dysfunction and loss of small peripheral sensory tortuosity of retinal and conjunctival vessels, and capsular 29,30 deposits in the anterior or posterior lens may occur, particu neurons, are particularly prominent. Central retinal artery occlusion and 64 ischemic and/or hemorrhagic cerebrovascular accidents, tran ischemic optic neuropathy are rare. Hemipare sis, paraparesis or monoparesis, hyper exia, ataxia, vertigo or Renal Manifestations dizziness, and complications secondary to vascular alterations Renal involvement may occur as early as in childhood or ad (eg, diplopia, dysarthria, nystagmus, hemiataxia, and memory olescence, and rst signs include microalbuminuria, impair 37,65 de cits) may develop. Cranial nerve damage may cause ment in urinary concentration ability, and lipiduria. Similarly to that seen in di Depending on the location of the central nervous system abetic nephropathy, glomerular hyper ltration may occur at 37 lesions, other neurologic syndromes may present including an early stage. Rapid onset of kidney failure occurs if a crit 25 frontal lobe syndrome with disturbances in behavior and/ ical number of nephrons has been damaged. Males with the classic form of Fabry disease prog 47,51 ress to end-stage renal disease and, if untreated, the average spheres. The posterior cerebral artery territory seems 48 life expectancy is severely reduced to approximately 50 susceptible to vascular lesions and perfusion disturbances. A signi cant proportion of females Cutaneous lesion is a common feature and may rst be no had progressed to moderate to severe kidney involvement ticed in childhood (boys) or adolescence (girls) usually in occurring at the same mean age as in males. In Pulmonary complications (eg, chronic cough, dyspnea with 43,81 patients over 40 years of age, 45% of males and 20% of fe exercise, wheezing) may present in adulthood. Both in males and females, the prev cise intolerance is attributed to hypohidrosis, pulmonary dis 82 alence and magnitude of proteinuria was higher in those in ease, or cardiomyopathy and may begin in childhood. Proteinuria values were signif Gastrointestinal Involvement icantly correlated with systolic blood pressure in both sexes. Early satiety, strated renal progression during the Phase 3 extension postprandial bloating, nausea, and vomiting also occur clinical trial with agalsidase-b shared a common clinical pro frequently. Acute 1 le, including age >40 years, signi cant baseline proteinuria abdominal pain can mimic appendicitis or renal colic. Rheumatologic and Vascular Manifestations Cardiovascular Manifestations Vasospastic disturbances characterized by episodes of With age, cardiovascular anomalies increase in severity, more changes in color of ngers and toes (Raynaud phenomenon), 70 accompanied by paresthesias and pain triggered by tempera often and earlier in males than in females, and become a key 71 72 cause of morbidity. The earliest ndings include sinus node dysfunction and Joint pain accompanied by fever may occur in hands and conduction system abnormalities. Shortening of the P-R inter feet (interphalangeal, metacarpophalangeal, metatarsal 1 val is seen in young patients, and later, atrio-ventricular blocks joints) and is frequently misdiagnosed as rheumatic fever, 85 and sinus node dysfunction may develop. Patients may also report bradycardia, ventricular tachycardia) can result in sudden pain in the elbows, shoulders, or knees. Late signs and symptoms include arterial hyperten sion due to renal insuf ciency and vascular Fabry pathology, neuropathic endothelium at nerve endings of joint structures and angina pectoris. Myocardial infarction resulting from in Muscle pain may contribute to the limitation in exercise volvement of the coronary vascular bed, predominantly of the tolerance, together with hypohidrosis, pulmonary disease, 82 small penetrating vessels, congestive heart failure, and heart and cardiomyopathy. Osteopenia 89,90 abnormalities can be detected using modalities such as strain has been reported in a major fraction of patients, and 75,76 1 rate imaging. Of the valvulopathies, mitral insuf ciency growth retardation and delayed puberty are not uncommon. Patients with Fabry disease are at risk of developing throm Results from Fabry Registry analyses indicate that left botic and thromboembolic complications due to the general ventricular mean wall thickness increases progressively with ized prothrombotic or in ammatory state and endothelial 70 26,27 decreasing renal function in both male and female patients. In addition, interstitial myocardial brosis appears to be 77,78 Psychosocial Aspects correlated with progression of renal insuf ciency. Perception of 76,79 painful stimuli can be modi ed quantitatively and qualita of cardiac dysfunction in patients with Fabry disease. Lymphedema, particularly of the lower extremities, may tively depending on a series of factors relating to the individ occur in classically affected patients and presumably re ects ual or the environment. In the case of acute pain, the derailment of the balance between vasodilatative and vaso perception acts as a signal that induces the person to adopt 80 a behavior which aims at warding off, reducing or constrictive mechanisms. In contrast to other lysosomal dis Chronic pain and subsequent alterations in behavior of ease, Fabry disease is not associated with mental retardation sufferers can be in uenced by environmental factors. Shortly after diagnosis and genetic counseling, the patient may express shock, anger, denial, feeling of being cheated, de Fabry Disease Characteristics in the pression, and or acceptance of the new situation; therefore Brazilian Patient Cohort the patient should be constantly monitored as patients are 45,91-93 prone to become chronically depressed. Our analyses (June 2008, unpublished) of natural history data from Brazilian patients with Fabry enrolled in the Fabry Clinical Manifestations in Female Registry, a voluntary observational database, con rm that Heterozygotes symptoms generally present at pediatric age in both males and females. The conception of the expression of Fabry disease in females Among the 53 male (median age, 38 years) and 56 female has drastically changed over the last decade. The most common rst symptoms were severity of symptoms but also to the range of tissues affected reported at the following median ages: neurologic pain at 9 and onset of symptomatology. Onset of rst symptoms and and 11 years for males and females, respectively, angiokera adulthood complications generally occur at a later age as 2-4 toma at 9 and 19. Disabling and life-threatening renal, cardiac, (transient ischemic attack, stroke) were 40 (n = 13) and 37 and cerebrovascular manifestations also occur in heterozy 2-4,68 (n = 1), 44. Onset though fewer female patients with Fabry disease had major of cerebrovascular and cardiovascular events occurred at clinical events, the ages at which clinical events occurred a median age of 43 and 47 years, respectively, thus later appear to be quite similar in both sexes. Patients usually present in childhood or adoles nosed (Table I), and delays between onset and accurate diag cence with symptoms re ecting progressive loss of function nosis exceeding 10 years have been reported in both 55,96 of small, unmyelinated nerve bers of the somatosensory sexes. Also in the Brazilian cohort of patients, there 28 and autonomous nervous systems. Although rst symptoms clude chronic neuropathic pain and/or acute pain attacks; generally presented during childhood, diagnosis occurred at lack of or decreased sweating; tinnitus; heat, cold, and exer a median age of 32. If cise intolerance; gastrointestinal disturbances (eg, diarrhea, a carefully taken medical history, physical examination, lab abdominal discomfort, nausea, vomiting); and dif culty oratory tests, and imaging procedures trigger the suspicion of gaining weight. Furthermore, skin lesions (angiokeratomas), Fabry disease, the diagnosis should be con rmed by analysis corneal opacities with unaffected vision, and discrete pro of a-Gal A activity and, particularly in females, by molecular teinuria (in male adolescents), are among the rst manifesta analysis.

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This Act also permits Gardai to seize syringes and penalise individuals who abandon syringes where others are likely to be endangered. In these cases the District Court penalties are the same as for attacks but on indictment the maximum jail sentence is 7 years. The penalty for someone found guilty in the District Court is a fne of 1,905 or 12 months or both. On indictment such as in the Circuit Court there may be a fne or 3 years in jail or both fne and jail sentence. Criminal Justice (Public Order) Act 1994 the Criminal Justice (Public Order) Act 1994 makes it an ofence for a person to be intoxicated in a public place to such an extent as to be a danger to themselves or others. The Act also allows Gardai to seize any bottle or container that they have reasonable cause to suspect contains an intoxicating substance, They can also indicate, in relation to certain events, that those in possession of intoxicating liquor are liable to have that alcohol confscated. Merchant Shipping Act 1992 the Merchant Shipping Act 1992 (Section 24 Subsection 2) makes it an ofence for the master or a crew member of a ship to be under the in uence of alcohol or any other drug while on duty, to such an extent that his ability to discharge his duties is impaired. Intoxicating Liquor Acts 1988 & 2000 the supply, possession and consumption of alcohol and tobacco by adults are permitted, but at the same time availability is afected by taxation and various laws, some of which are designed to discourage young people from drinking and smoking. The Intoxicating 11 Psychoactive Substances Liquor Act 1988 not only prohibits the sale of alcohol to those under 18, but also makes it an ofence for a person under 18 to buy alcohol or to drink alcohol in a public place. In an amendment to the 1988 Act the Intoxicating Liquor Act 2000 allows District Court Justices to order the temporary closure of licensed premises where an ofence of illegal supply to a person under 18 is proven. The closure can be for 7 days for a frst ofence and up to a month for a second ofence. Tobacco (Health Promotion and Protection) Act 1988 the Tobacco (Health Promotion and Protection) Act 1988 reinforces the prohibition on the sale of cigarettes to those under 16. This Act also bans the sale of smokeless tobacco products such as Skoal Bandits and enabled the Minister for Health to introduce Regulations in 1990 prohibiting or restricting the use of tobacco in a large number of public areas including cinemas, theatres, trains, schools and public buildings. The Health (Miscellaneous Provisions) Act 2000 amended the 1988 Act by increasing the age Iimit of those to whom tobacco may be sold from l6 to 18 and increases the fne to 1,905. Included in this group is cafeine contained in drinks such as tea, cofee and cola. The supply of organic solvents in the form of glues and aerosols is prohibited under Section 74 of the Child Care Act 1991, where there is reasonable cause to believe the substance will be inhaled by a person under 18 for the purpose of causing intoxication. However a member of the Gardai Siochana may seize a substance that is being inhaled by a person under 18. The penalty for supplying such products to those under 18 may include a fne of up to 1,270 or 12 months in jail. Informal Controls It is said that the non-medical use of all drugs is subject to informal controls arising from custom and culture and from the requirements of everyday Iife. These controls are more likely to be efective with drugs that are a familiar part of the culture. This may explain why cofee and tea are made available during the working day, while alcohol is generally reserved for after work. However, it has been pointed out that the level of acceptance of excessive alcohol consumption is very high in Ireland. Strengthening of informal controls such as the increasing unacceptability of drunken driving or the hardening of attitudes to incompetence at work due to alcohol, may be as important as legal controls in preventing excessive, harmful or inappropriate use of drugs. Contains no Contains no Betel Nut Stimulant controlled controlled substances substances Contains no Contains no Sedative Bitter Orange controlled controlled Stimulant substances substances this is also Hallucinogen Contains Safrole a controlled Black Pepper Aphrodisiac which is a category precursor within Stimulant 1 precursor. Hallucinogen Brugmansia Aphrodisiac Sedative Mescaline is a scheduled substance in Ireland. Making it this is also Cacti containing Hallucinogen illegal to supply scheduled within Mescaline Aphrodisiac and possess. Contains 2 these are also Hypnotic Californian poppy scheduled 1 controlled within Sedative substances. Contains Cathoine, a schedule 1 Aphrodisiac Illegal in most substance and Khat Hallucinogen countries ephedrine, Stimulat internationally norpseudoephedrine which are schedule 3 substances Contains no Contains no Klipp Dagga Relaxant controlled controlled substances substances Contains no Contains no Aphrodisiac Kola Nut controlled controlled Stimulant substances substances Illegal in Thailand, Not a controlled Australia, Burma Kratom Sedative substance in and Vietnam. Also Morning Glory Hallucinogen contains lysergide derivatives which are a schedule 1 controlled substance Illegal to own, process and Illegal across the Mescaline Hallucinogen supply. Common Names: Bufalo Swallow Wattle, Maidens Wattle, Umbrella Acacias, Wattle, Yellow Fever Acacia. Drug E ects: the Acacia genus includes more than 1,200 Classifcation: Depressant, Sedative species of owering trees and shrubs. Classifcation: Narcotic, Pain Reliever Short Term E ects: In uence mood & dreaming, visionary Classifcation: Hallucinogen, Psychedelic perceptions, weight loss properties, reduce stress. Classifcation: Aphrodisiac, Stimulant Long Term E ects: Anthelmintic, anti-catarrhal, antidiabetic, anti-diarrhoeal, antifungal, antihemorrhagic, anti in ammatory, anti-malarial, antimicrobial, antioxidant, antiseptic, astringent, diuretic. Negative/Overdose Risk: Asthma, bloating, constipation, dizziness, gas, hallucinations, loose stools, rash, weakness, mild gastrointestinal symptoms. Contraindications / Interactions: Use cautiously in patients taking Amoxicillin or Iron, patients with Respiratory Disorders. Classifcation: Narcotic, Pain Reliever Drug E ects: Drunk by Shamans for divination and diagnosis and as a hallucinogen. They respect it as very Classifcation: Hallucinogen, Psychedelic powerful plant and use it cautiously because it is said to be Classifcation: Aphrodisiac, Stimulant able to cause permanent insanity. Long Term E ects: Anaesthetic, antiarrhythmic, anticholinergic, anticonvulsant, antideliriant, antidote, antiemetic, anti-in ammatory, antispasmodic, antitumor, antiviral, carminative, hyperkinetic, intoxicant, vasodilator, vermifuge. Negative/Overdose Risk: Blurred visions, coma, delusions, difculty swallowing, dilated pupils, disorientation, dry mouth, headache, hot dry skin, incoherent speech, paralysis restless fatigue, vomiting. Psychoactive Ingredient In: Beer, Toxic Honey, Ayahuasca, Snuf, Enema, Smoking Blends. Drug E ects: this vine has been used with admixture plants for thousands of years to make sacred medicinal drinks Ayahuasca, Natema, Yahe etc. Classifcation: Hallucinogen, Psychedelic Short Term E ects: Calming, feelings of tranquillity, cns stimulant, euphoric, fantasy increasing, increased colour, Classifcation: Aphrodisiac, Stimulant size changes, mood enhancing, visionary experiences. Long Term E ects: Anaesthetic, anthelmintic, antibacterial, antimalarial, antitrypanosomic, cardiovascular, cytotoxic, desmutagenic, hyperkinetic, phototoxic, uteroactive, hypotensive. Dependency: Studies on the consumption of Ayahuasca within a controlled context shows it not to be addictive. Withdrawal: the consumption of Ayahuasca within a controlled context does not produce any withdrawal syndrome, that is to say that people do not show any symptom of abstinence when they stop consuming it. Active Constituents: Bufotenine (5-Hydroxy-N,N-Dimethyltryptamine), 5-Meo-Dmt (5-Methoxy N,N-Dimethyltryptamine), Acetylnorharmine, Dihydroshihunine, Harmaline, Harmalinic Acid, Harmalol, Harmanamide, Harmic-Acid-Methylester, Harmic-Amide, Harmine-N-Oxide, Harmine, Ketotetrahydronorharmine, N,N-Dimethyltryptamine, N-Methyltryptamine, Saponin, Shihunine, Tetrahydroharmine. Drug E ects: Baybean is smoked on the Gulf Coast of Mexico as Marijuana substitute. Long Term E ects: Anticancer, antifertility, anti-in ammatory, antimicrobial, antioxidant, antispas modic, antitumor, anti-ulcer, antiviral, tonic. Psychoactive Ingredient In: Marijuana Substitute, Ex-Ses, Spike, Ice Bud, Blueberry Haze, Dream Incense, Dutch Haze. Method of Use: Smoke, Tea or Eating Berries, Alcoholic Extracts, Liniments, Ointment, Suppositories. Classifcation: Depressant, Sedative Drug E ects:The belladonna alkaloids should only be used with great caution and rarely for pleasure as Classifcation: Narcotic, Pain Reliever hallucinations can be threatening, dark, demonic and profoundly terrifying. Extremely toxic, even moderate Classifcation: Deliriant, Poison, Hallucinogen doses could be fatal. Long Term E ects: Anaesthetic, antidote, antiemetic, anti-in ammatory, antineuralgic, antispasmodic, calmative, diuretic, laxative, excessive use may cause brain decomposition. Negative/Overdose Risk: Confusion, convulsions, crying, death, depression, difculty swallowing, dilated pupils, drowsiness, dry mouth, fever, frenzy, hallucinations, headache, paralysis, rapid pulse, red face, sweat inducing, screaming, temporary memory loss, toxic.

Diseases

  • Agyria
  • Neuronal intestinal pseudoobstruction
  • Amelogenesis imperfecta
  • Porencephaly
  • Thrombocytopenic purpura, autoimmune
  • Primary sclerosing cholangitis
  • Tracheobronchomalacia
  • Horton disease

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Ketoconazole, fluconazole, intra acute primary, chronic cavitary, and progressive conazole, and amphotericin B are effective drugs. The acute primary form, which is more common, is characterized by constitutional symptoms (low-grade fever, malaise, chills, myal gias, etc. The chronic cavitary form is characterized exclusively by pulmonary signs and symptoms. Clinically, it is characterized by constitutional symptoms and hepatosplenomegaly, lymphadenopathy, bone marrow involvement, pulmonary radiologic find ings, gastrointestinal disorders, adrenal insuffi ciency, and oral and pharyngeal manifestations. Fungal Infections Paracoccidioidomycosis form is the most common inasmuch as signs and symptoms from oral, cranial, and facial structures Paracoccidioidomycosis (South American blas account for 40-70 % of all reported cases. The dis grade fever, headache, malaise, sinus pain, bloody ease is particularly restricted to Brazil and other nasal discharge, periorbital or perinasal swelling countries of South and Central America. Three and edema, ptosis of the eyelid, extraocular mus forms of the disease are recognized: pulmonary, cle paresis, and progressive lethargy. Palatal ulceration and terized by weight loss, fever, dyspnea, cough, necrosis are the most characteristic oral lesions. The mucosa surrounding the ulcer is usually Clinical, oral lesions usually present as a thickened. Orbital and intracranial invasion is a chronic irregular ulcer with a granular surface common complication. Perforation of the hard palate associ the differential diagnosis of oral lesions should ated with pain may be seen in severe cases. Computerized axial tomography may be useful to demonstrate the extent of bone destruction. Serologic test by underlying predisposing conditions is also impor immunodiffusion or the complement fixation is tant. Intravenous amphotericin B, keto conazole, and intraconazole are effective drugs. Mucormycosis Mucormycosis (zygomycosis, phycomycosis) is a rare, often fatal, acute opportunistic fungal infec tion which usually involves debilitated individuals. Fungi of the family Mucoraceae, mainly rhizopus and rhizomucor, and rarely other species are the cause of the disease. The most common predispos ing condition is poorly controlled diabetes mellitus with ketoacidosis. The fungus is acquired from the environment and characteristi cally erodes arteries, causing thrombosis, ischemia, and finally necrosis of the surrounding tissues. Four clinical forms of mucormycosis are recognized: rhinocerebral, pulmonary, gastro intestinal, and disseminated. Other Infections Cutaneous Leishmaniasis Sarcoidosis Leishmaniasis is a parasitic infection caused by Sarcoidosis is a systemic granulomatous disease organisms of the genus Leishmania. Members of affecting the lungs, lymph nodes, spleen, liver, the genus Phlebotomus transfer the parasite from and central nervous system. The entities have been described: Cutaneous leish disease is seen most frequently in women, usually maniasis (Oriental sore) caused by Leishmania between 20 and 50 years of age. The exact cause of tropica, Mucocutaneous leishmaniasis (American the disease is not known, although evidence exists leishmaniasis) caused by Leishmania brasiliensis, that a depression of cell-mediated immunity and and Systemic leishmaniasis (Kala-azar) caused by an overactivity of B cells care associated with Leishmania donovani. Cutaneous leishmaniasis is endemic in the trop the typical skin lesions of sarcoidosis consist of ical and subtropical zones and around the multiple purple-brown macules, papules, or Mediterranean. Lupus pernio, erythema nodosum, usually occur on the face or other exposed parts of scars, and persistent plaques are common skin the skin. Initially, a small papule forms that of patients and may be the only manifestations. A red or brownish-red painless the oral mucosa is rarely involved and the lips, nodule with smooth and glistering surface then tongue, and gingiva are the most commonly develops and progresses to ulceration (Fig. Clinical manifestations include A brown-gray crust covers the ulcer, and the small or large deep red nodules, which may rarely surrounding tissues are inflamed. The salivary glands the differential diagnosis includes basal cell car and the jaw bones may also be involved. All cinoma, squamous cell carcinoma, keratoacan lesions are usually associated with lymph thoma, syphilitic chancre, and erysipelas. Laboratory tests helpful in establishing the diag Treatment includes administration of methyl nosis include histopathologic examination, glucamine antimoniate (glucantime), antimala rials, local use of steroids, and rarely surgical Kveim-Siltzbach skin test, and chest radiograph. Steroids, azathioprine, levamisole, oxyphenbutazone, and cyclosporine may be helpful. Histopathologic examination is form of sarcoidosis characterized by bilateral, helpful in establishing the diagnosis. Kveim-Siltz firm, painless enlargement of the parotid glands, bach skin test, and chest radiograph may be uveitis, facial nerve paralysis and low-grade fever. The sublingual and submandibular salivary glands and the lacrimal glands may also be affected (Fig. Lymph node enlarge ment, erythema nodosum, and cutaneous nodules complete the clinical picture. Diseases with Possible Immunopathogenesis Recurrent Aphthous Ulcers Minor Aphthous Ulcers Recurrent aphthous ulcers are the most common Minor aphthous ulcers are the most common form lesions of the oral mucosa and affect 10 to 30% of the disease. The exact cause remains quently in females than in males during the second unknown, although numerous possible etiologic and third decades, although they may appear at factors have been suggested, such as iron, vitamin any age. A prodromal burning sensation 24 to 48 B12 or folic acid deficiency, and viral or bacterial hours before the appearance of the ulcer is recog infection, especially with Streptococcus species nized. A vesic may occur in a cyclic pattern a few days before ular stage does not exist. Recent evidence supports the con Ulcers can be single or multiple (2 to 6); they cept that cell-mediated and humoral immunity to generally persist 5 to 8 days and gradually heal oral mucosal antigens play a primary role in the with no evidence of scarring. They recur usually at pathogenesis of recurrent aphthous ulcers and 1 to 5-month intervals. Recurrent aphthous ulcers occurrence are the nonkeratinized (movable) oral have been classified into four varieties based on mucosa (buccal mucosa, lips, tongue, mucolabial clinical criteria: minor, major, herpetiform ulcers, and mucobuccal folds). Diseases with Possible Immonopathogenesis Major Aphthous Ulcers Herpetiform Ulcers Major aphthous ulcers are currently believed to be Herpetifom ulcers, or herpetiform stomatitis, a more severe form of aphthous ulcerations. These histologic, microbiologic, and immunologic differ ulcers are usually one to five in number and 1 to ences. The disease presents as multiple (10 to 100 2cm in diameter each, deep, and extremely pain in number) small shallow ulcers, 1 to 2 mm in ful (Figs. The most common sites of diameter, with a thin red halo, which gradually occurrence are the lip, buccal mucosa, tongue, coalesce to larger irregular lesions (Fig. They may persist for 3 to 6 weeks, lesions are very painful and may occur at any site leave a scar on healing in cases of very deep of the oral mucosa, where they persist for 1 to 2 ulcers, and recur, often at 1 to 3-month intervals. Although the exact nature of the gens are found with slightly increased frequency in disease is unknown, it is considered appropriate to patients with aphthous ulcers. The differential diagnosis of minor and major aphthous ulcers should include herpes simplex, the differential diagnosis includes primary herpet hand-foot-and-mouth disease, syphilitic chancre ic gingivostomatitis, herpangina, and erythema and mucous patches of secondary syphilis, cyclic multiforme. Low doses of cortico quently stomatitis venenata and medicamentosa, steroids (15 to 20 mg prednisone) for 5 to 7 days and rarely malignant ulcers. Topical application of a steroid oint ment reduces discomfort and decreases the dura tion of the lesions. In severe cases, intralesional steroid injection or systemic steroids in a low dose (10 to 20 mg prednisone) for 5 to 10 days reduce the pain dramatically. The dis ease is five to ten times more common in males, with a mean age at onset of 20 to 30 years. These criteria are: a) recurrent oral ulceration; b) recurrent gen ital ulceration; c) eye lesions; d) skin lesions, and e) positive pathergy test. The oral mucosa is invariably involved and very often oral lesions precede other clinical manifestations. They vary in size and number, recur quite fre quently, and may develop anywhere in the mouth (Figs. The syndrome may follow an enteric infection with Salmonella or cases and consist of papules, pustules, erythema Yersinia species, or a nongonococcal urethritis nodosum, ulcers, and rarely necrotic lesions (Fig. Clin Diagnosis is based exclusively on the history ical characteristics include nongonococcal ure thritis, conjunctivitis (Fig. They appear as diffuse the differential diagnosis should include recurrent erythema and slightly painful superficial erosions. When mation occur in serologic and routine hematologic these lesions appear on the tongue, they mimic studies.

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Peptides have very low immunogenicity themselves but can be used for induction of Abs, when coupled to a carrier protein, which can provide T cell epitopes for induction of Abs. The conjugation also limits the conformational exibility of the peptides, which makes them more immunogenic/antigenic. Due to their structure and composite antigen binding sites (complementarity-determining regions), Abs are very speci c recognition molecules and interact with their epitopes through multiple bonds, which gives them high a nity and speci city. Moreover, they can be obtained fairly easily and go through multiple rounds of a nity maturation during immunization, which makes them highly valuable and, until now, irreplaceable reagents for diagnostics and therapy. The advantage of using peptide antibodies are that they, in theory, can be directed to any target. However, peptide antibodies may be di cult to generate with su ciently high titers. Another limitation when producing antibodies for therapeutic uses are the production costs. The use of a very large culture of mammalian cells and extensive puri cation steps limit the use of antibodies. Another naturally inherent limitation of natural and synthetic Abs for therapy is the ability of pathogens to mutate and evade antibody responses and the inherent immunogenicity of proteins, even in the form of fully human or humanized Abs. Abs also have some inherent limitations due to size and other physical properties, and, therefore, many attempts have been made at developing other molecule types with equally high a nity and speci city. Alternative protein-based sca olds relying on Ab-derived principles for selection have been developed and are beginning to complement Abs. However, in terms of therapy, such binders can be expected to su er from equal or even higher problems with immunogenicity as Abs. However, despite much research and development, very few aptamers are of commercial importance today. Hopefully, in the future, new and more advanced recognition molecules will be generated, which may complement Abs and have diagnostic as well as therapeutic uses. Native chemical ligation and extended methods: Mechanisms, catalysis, scope, and limitations. Synthesis, biological activity and solution structure of new analogues of the antimicrobial Gramicidin S. Synthesis of a biological active beta-hairpin peptide by addition of two structural motifs. The conformation and assignment of the proton nmr spectrum in water of dx600, a bioactive peptide with a random coil conformation. Visualizing the cellular route of entry of a cystine-knot peptide with xfect transfection reagent by electron microscopy. X-ray crystallographic structure of a teixobactin derivative reveals amyloid-like assembly. Antibodies to a strain-speci c citrullinated epstein-barr virus peptide diagnoses rheumatoid arthritis. Identi cation of continuous epitopes of hud antibodies related to paraneoplastic diseases/small cell lung cancer. Identi cation and mapping of a linear epitope of centromere protein f using monoclonal antibodies. Erratum: Sorafenib promotes graft-versus-leukemia activity in mice and humans through il-15 production in t3-itd-mutant leukemia cells. Computational analysis of dengue virus envelope protein (e) reveals an epitope with avivirus immunodiagnostic potential in peptide microarrays. Kinetic and thermodynamic characterisation of hiv-protease inhibitors against e35d upward arrowg upward arrows mutant in the south african hiv-1 subtype c protease. Targeting chronic lymphocytic leukemia with n-methylated thrombospondin-1-derived peptides overcomes drug resistance. Comparison of 2 monoclonal antibodies for immunohistochemical detection of braf v600e mutation in malignant melanoma, pulmonary carcinoma, gastrointestinal carcinoma, thyroid carcinoma, and gliomas. Peptide-based polyclonal antibody production against p110 protein of mycoplasma genitalium. Fine mapping of a monoclonal antibody to the n-methyl d-aspartate receptor reveals a short linear epitope. Fine mapping of glutamate decarboxylase 65 epitopes reveals dependency on hydrophobic amino acids for speci c interactions. The use of synthetic peptides for detection of anti-citrullinated protein antibodies in rheumatoid arthritis. Application of synthetic peptides for detection of anti-citrullinated peptide antibodies. Evaluation of the inova diagnostics enzyme-linked immunosorbent assay kits for measuring serum immunoglobulin g (igg) and iga to deamidated gliadin peptides. Development of an improved time-resolved uoroimmunoassay for simultaneous quanti cation of c-peptide and insulin in human serum. Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. The three-dimensional structure of an intact monoclonal antibody for canine lymphoma. Crystal structure of an intact human igg: Antibody asymmetry, exibility, and a guide for hiv-1 vaccine design. Structure of a therapeutic full-length anti-npra igg4 antibody: Dissecting conformational diversity. Production and characterization of murine monoclonal antibody against synthetic peptide of cd34. Production of anti-cd14 monoclonal antibody using synthetic peptide of human cd14 as immunizing antigen. Development and characterization of monoclonal antibodies against human cd20 in balb/c mice. Immunohistochemistry as a quick screening method for clinical detection of braf(v600e) mutation in melanoma patients. Egfr mutant-speci c immunohistochemistry has high speci city and sensitivity for detecting targeted activating egfr mutations in lung adenocarcinoma. Role of homologous fc fragment in the potency and e cacy of anti-botulinum antibody preparations. Tumour necrosis factor as a therapeutic target in rheumatoid arthritis and other chronic in ammatory diseases: the clinical experience with in iximab (remicade). Anti-egfr monoclonal antibody panitumumab for the treatment of patients with metastatic colorectal cancer: An overview of current practice and future perspectives. E cacy of anti-interleukin-2 receptor antibody (daclizumab) in reducing the incidence of acute rejection after renal transplantation. A single dose of antibody-drug conjugate cures a stage 1 model of african trypanosomiasis. Successes and challenges for preventing measles, mumps and rubella by vaccination. Fully liquid dtap-ipv-hib pediatric combination vaccine (pediacel): A review of 18 years of clinical experience. Dtap-ipv-hepb-hib vaccine (hexyon((r))): An updated review of its use in primary and booster vaccination. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Aluminum hydroxide adjuvant di erentially activates the three complement pathways with major involvement of the alternative pathway. Optimization of sequence, display, and mode of operation of igg-binding peptide ligands to develop robust, high-capacity a nity adsorbents that a ord high igg product quality. Spotlight proteomics-a igg-enrichment phenotype pro ling approach with clinical implications. Characterization of continuous b-cell epitopes in the n-terminus of glutamate decarboxylase67 using monoclonal antibodies. Identi cation of a linear epitope recognized by a monoclonal antibody directed to the heterogeneous nucleoriboprotein a2. A nity liquid chromatography method for the quanti cation of immunoglobulin g in bovine colostrum powders. Speci c detection and quantitation of bovine igg in bioreactor derived mouse mab preparations. A hapten-speci c chimaeric ige antibody with human physiological e ector function.

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Fever is absent unless a laboratory diagnostic capacity in many Control measures complicating infection occurs. The illness typically begins Australia National Notifiable Diseases techniques about cooking time, pressure, with constipation followed by lethargy, Surveillance System). The absence of a bulging lid on difficulty in swallowing and generalised potential bioterrorist agent. Spores have been found in marine sediments and the intestinal tracts of animals, including fish. Environmental health officers and food Suspected cases should immediately be safety officers should coordinate the referred for specialist care and trivalent appropriate disposal of implicated food. Recall any implicated food immediately and send samples to For wound botulism, in addition to the Microbiological Diagnostic Unit for antitoxin the wound should be debrided analysis. Take sera and faeces from or drained, and appropriate antibiotic cases as well as exposed but prophylaxis against other potential asymptomatic persons for analysis, infections should be administered. Isolation or quarantine is not needed but Undertake efforts to recover and test hand washing is indicated after handling implicated foods. Usual sanitary disposal of coordinated through Food Standards faeces from infant cases is acceptable. Any implicated food should be retained for collection and investigation by public health authorities. Control of contacts Those who have eaten incriminated food should be purged with emetics, gastric lavage or high enemas. Administration of polyvalent antitoxin to asymptomatic individuals should be considered carefully, assessing potential protection against the risk of sensitisation and severe reactions to horse serum. The blue book: Guidelines forthe control of infectious diseases 19 Brucellosis (undulant fever, Malta fever) Victorian statutory requirement test (Rose Bengal and seroagglutination) Mode of transmission Brucellosis (Group B disease) must be detecting agglutinating antibodies (IgM, Brucellosis can be transmitted by notified in writing within five days of IgG and IgA) with others detecting non contact with infected tissues, blood, diagnosis. Subclinical and unrecognised feral pigs in Queensland and represents infections are frequent. Susceptibility and resistance a risk to people who hunt and butcher Everyone is susceptible to infection. Notifications of brucellosis in Severity and duration of clinical illness may be associated with a variety of other Victoria are now rare and generally are subject to wide variation. The Control measures osteomyelitis and endocarditis are less sources of infection and responsible Preventive measures common. The case-fatality rate in organism vary according to geographic Educate the public, particularly travellers, untreated brucellosis is approximately area. Affected regions include the against drinking unpasteurised milk or 2%, mostly due to endocarditis from Mediterranean countries, North and East eating dairy products produced from B. Laboratory confirmation of the diagnosis Reservoir is made by isolating the infectious agent Educate farmers and handlers of the most important reservoirs for human from blood, bone marrow, other tissues or potentially infected animals such as feral infection are cattle, swine, goats, sheep discharges of the patient. Infections may also occur in testing for Brucella is useful but often care in handling placentae, discharges other wild ungulates. Consult the current version of Therapeutic guidelines: antibiotic (Therapeutic Guidelines Limited) and seek expert infectious diseases. Control of contacts Although there is no person to person transmission of brucellosis, contact tracing is done as part of the case investigation to identify those people who have been exposed to the same implicated source of Brucella infection as the case. These people are advised of the early signs and symptoms of brucellosis to aid early diagnosis and treatment. Control of environment the Department of Primary Industries is notified of any new, non-imported case of brucellosis so that appropriate animal investigations and control measures can commence. Restriction on the distribution of unpasteurised milk and milk products is enforced. Outbreak measures Trace source of infection such as contaminated unpasteurised milk products and institute appropriate control measures. School exclusion: exclude cases from and occurrence child care and school until after Campylobacter infections are now the Susceptibility and resistance diarrhoea has ceased. The incidence of Infectious agent Control measures infection appears to be increasing, a the most common types of Preventive measures trend observed internationally. All age Campylobacter species that cause Prevention is dependent on good groups are affected. Most cases in Australia appear sporadic but food and refrigerated after cooking, especially Identification water-borne outbreaks occur and it is poultry. Wash utensils used to prepare Clinical features likely that many outbreaks are not raw meats and poultry in hot soapy Campylobacter infection may be detected. Symptoms usually last two to five animals are another possible source of encourage hand washing after handling days. Campylobacter infection has been Control of case associated with rare sequelae including Mode of transmission Treatment is largely symptomatic. Human infection ingestion of the organism via severe illness or where prompt with C. Antibiotics are not indicated for particularly in immunosuppressed Person to person transmission via the diarrhoeal disease in which the causative persons. Infection pathogen is not known, except in some may also occur through contact with Method of diagnosis very severe illnesses when empirical infected animals. Health care workers, child care workers, food handlers and children in school and child care centres should be excluded from work or school until diarrhoea has ceased. Isolation is not required for hospitalised patients and standard precautions apply. Control of environment Isolation is not required for hospitalised patients and standard precautions apply. Outbreak measures Two or more related cases should be reported immediately, particularly in institutions. Obtain food histories and investigate other recognised vehicles of infection such as pets or farm animals to identify a common source. The blue book: Guidelines forthe control of infectious diseases 23 Chickenpox or shingles (varicella/herpes zoster) Victorian statutory requirement Complications include secondary Method of diagnosis Notification is not required. The rash is often more immunoglobulin administration as Identification widespread and persistent in passive immunisation against varicella. Public health significance Varicella (chickenpox) Patients must be carefully evaluated to and occurrence Chickenpox generally presents with a ensure that there is no eye involvement Chickenpox is a highly contagious but low-grade fever, malaise and a rash. The when the rash involves the ophthalmic generally mild disease and is endemic in rash is firstly maculopapular then area of the face. It becomes epidemic becomes vesicular (blistered) and mandatory in this case as blindness can among susceptible individuals mainly progresses to crusted lesions over about result. Lesions appear in three or four Incidence increases with age and 90% of cases are children under 15 years crops. A debilitating complication of herpes to the reactivation of latent virus from the zoster in many (especially elderly) dorsal root ganglia. Rarely, the disease patients is prolonged pain (post-herpetic Reservoir may be fatal. Indirect contact In Australia, the varicella vaccine is patients with severe disease and in occurs through articles freshly soiled by recommended for non-immune, healthy normal patients with complications of discharges from vesicles of infected individuals aged 12 months or older. Consult the current version of It is usually communicable for one to two Therapeutic guidelines: antibiotic Non-immune individuals who should be days (up to five days) before the onset of (Therapeutic Guidelines Limited).

Syndromes

  • Do you have allergies or a post nasal drip?
  • Osteoporosis
  • Dehydration (such as from severe diarrhea)
  • The Lupus Foundation of America - www.lupus.org
  • Murine typhus occurs in the southern United States, particularly California and Texas. It is often seen during the summer and fall. It is rarely deadly. You are more likely to get this type of typhus if you are around rats feces or fleas, and other animals  such as cats, opossums, raccoons, and skunks.
  • Histiocytosis X
  • Cancer of the renal pelvis or ureter

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The Statute of Artificers was thus supplemented by the Poor Laws, a most confusing term in modern ears, to which "poor" and "pauper" sound much alike. Actually, the gentlemen of England judged all per sons poor who did not command an income sufficient to keep them in leisure. Hence the term "poor" meant all people who were in need and all the people, if and when they were in need. The aged, the infirm, the orphans had to be taken care of in a society which claimed that within its confines there was a place for every Christian. But over and above, there were the able-bodied poor, whom we would call the unemployed, on the as sumption that they could earn their living by manual work if only they could find employment. Beggary was severely punished; vagrancy, in case of repetition, was a capital offense. The Poor Law of 1601 decreed that the able-bodied poor should be put to work so as to earn their keep, which the parish was to supply; the burden of relief was squarely put on the parish, which was empowered to raise the necessary sums by local taxes or rates. These were to be levied upon all householders and tenants, rich and nonrich alike, according to the rental of the land or houses they occupied. The Statute of Artificers and the Poor Law together provided what might be called a Code of Labor. Many parishes had no poorhouses; a great many more had no reasonable provisions for the useful occupation of the able-bodied; there was an endless vari [ 92 ] the Great Transformation ety of ways in which the sluggardliness of the local ratepayers, the in difference of the overseers of the poor, the callousness of the interests centering on pauperism vitiated the working of the law. Still, by and large, the nearly sixteen thousand Poor Law authorities of the country managed to keep the social fabric of village life unbroken and un damaged. Yet under a national system of labor, the local organization of un employment and poor relief was a patent anomaly. The greater the va riety of local provisions for the poor, the greater the danger to the well kept parish that it would be swamped by the professional pauper. After the Restoration the Act of Settlement and Removal was passed to pro tect the "better" parishes from the influx of paupers. More than a century later, Adam Smith inveighed against this act because it im mobilized the people, and thus prevented them from finding useful employment as it prevented the capitalist from finding employees. Only with the goodwill of the local magistrate and the parish authori ties could a man stay in any other but his home parish; everywhere else he was liable to expulsion even though in good standing and em ployed. The legal status of the people was therefore that of freedom and equality subject to incisive limitations. But they were not free to choose their occupations or those of their children; they were not free to settle where they pleased; and they were forced to labor. The two great Eliza bethan Statutes and the Act of Settlement together were a charter of liberty to the common people as well as a seal of their disabilities. The Industrial Revolution was well on the way, when in 1795, under the pressure of the needs of industry, the Act of 1662 was partially re pealed, parish serfdom was abolished, and the physical mobility of the laborer was restored. But in the very same year, as we know, a practice of Poor Law administration was introduced which meant the reversal of the Elizabethan principle of enforced labor. Speenhamland ensured the "right to live"; grants in aid-of-wages were made general; family allow ances were superadded; and all this was to be given in outdoor relief, i. This was a return to regulationism and paternalism with a vengeance just as, it would seem, the steam engine was clamoring for freedom and the machines were crying out for human hands. Yet the Speenhamland Antecedents and Consequences [ 93 ] Law coincided in time with the withdrawal of the Act of Settlement. The contradiction was patent; the Act of Settlement was being re pealed because the Industrial Revolution demanded a national supply of laborers who would offer to work for wages, while Speenhamland proclaimed the principle that no man need fear to starve and that the parish would keep him and his family, however little he earned. There was stark contradiction between the two industrial policies; what else but a social enormity could be expected from their simultaneous con tinued application. On the eve of the greatest industrial revolution in history, no signs and portents were forthcoming. No one had forecast the development of a machine industry; it came as a complete surprise. For some time England had been actu ally expecting a permanent recession of foreign trade when the dam burst, and the old world was swept away in one indomitable surge to ward a planetary economy. In the retrospect it may seem as if they had not only attempted the impossible but had done so by means the inner contradictions of which should have been ap parent to them. Actually, they were successful in achieving their aim of protecting the village against dislocation, while the effects of their policy were all the more disastrous in other, unforeseen directions. Speenhamland policy was the outcome of a definite phase in the devel opment of a market for labor power and should be understood in the light of the views taken of that situation by those in the position to shape policy. From this angle the allowance system will appear as a de vice contrived by squirearchy to meet a situation in which physical mobility could no longer be denied to labor, while the squire wished to avoid such unsettlement of local conditions, including higher wages, as was involved in the acceptance of a free national labor market. The connection between rural poverty and the impact of [ 94 ] the Great Transformation world trade was anything but obvious. Contemporaries had no reason to link the number of the village poor with the development of com merce in the Seven Seas. The inexplicable increase in the number of the poor was almost generally put down to the method of Poor Law administration, and not without some good cause. Actually, beneath the surface, the ominous growth of rural pauperism was directly linked with the trend of general economic history. Scores of writers probed into the channels by which the poor trickled into the village, and the number as well as the variety of reasons adduced for their appearance was amazing. And yet only a few contemporary writers pointed to those symptoms of the dislocation which we are used to connect with the In dustrial Revolution. Up to 1785 the English public was unaware of any major change in economic life, except for a fitful increase of trade and the growth of pauperism. The causes of pauperism and the means of combating it could hardly be ex pected to be kept apart in a literature which was inspired by the con viction that if only the most apparent evils of pauperism could be sufficiently alleviated it would cease to exist altogether. On one point there appears to have been general agreement, namely, on the great va riety of causes that accounted for the fact of the increase. Some writers blamed a new type of large sheep; others, horses which should be replaced by oxen; still oth ers urged the keeping of fewer dogs. Some writers believed that the poor should eat less, or no, bread, while others thought that even feed ing on the "best bread should not be charged against them. Forty years later Harriet Martineau still believed in preaching the advantages of drop Antecedents and Consequences [ 95 ] ping the tea habit for the sake of relieving pauperism. Yet on the whole, the impression prevails that pauperism was regarded as a phenomenon sui generis, a social disease which was caused by a variety of reasons, most of which be came active only through the failure of the Poor Law to apply the right remedy. The true answer almost certainly was that the aggravation of pau perism and the higher rates were due to an increase in what we would today call invisible unemployment. Such a fact would not be obvious at a time when even employment was, as a rule, invisible, as it necessar ily was up to a point under cottage industry. Still there remain these questions: How to account for this increase in the number of the un employed and underemployed. And why did the signs of imminent changes in industry escape the notice even of observant contempo raries. The explanations lies primarily in the excessive fluctuations of trade in early times which tended to cover up the absolute increase in trade. While the latter accounted for the rise in employment, the fluc tuations accounted for the much bigger rise in unemployment. But while the increase in the general level of employment was slow, the in crease in unemployment and underemployment would tend to be fast. Thus the building up of what Friedrich Engels called the indus trial reserve army outweighted by much the creation of the industrial army proper. This had the important consequence that the connection between unemployment and the rise of total trade could be easily overlooked. While it was often remarked that the rise in unemployment was due to the great fluctuations in trade, it escaped notice that these fluctuations formed part of an underlying process of even greater amplitude, namely, a general growth of commerce increasingly based on manu factures. For the contemporaries there seemed to be no connection between the mainly urban manufactories and the great increase of the poor in the countryside. The increase in the aggregate of trade naturally swelled the volume of employment while territorial division of labor combined with * Martineau, H. The distant rumor of large wages made the poor dissatisfied with those which agriculture could afford, and it created a dislike for that labor as poorly recompensed. The industrial regions of that age resembled a new country, like another America, at tracting immigrants by the thousand. That such a reflux toward the village must have taken place seems to find support also in the fact that no absolute decrease of the rural population was noted.

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It was clear that brains and spinal cord should not be eaten, but what about livers and kidneys. Even the parts that were not eaten, such as thyroid, pan creas and adrenal glands, were frequently used to produce medicines and over the-counter nutritional supplements. Cow pituitary glands produced drugs prescribed to help human beings control their blood pressure and heart rate. Spleens were consumed for food and also used went into medicines used to induce blood clotting. All meat is laced with microscopic nerve tissue needed to stimulate muscle actions. They took those organs out, because they had to take something out that might be dangerous, so they selected only those organs that caused the minimal commercial loss. Like most medically-trained professionals of his generation, Lacey grew up thinking of vegetarians as misguided cranks. I am not sure exactly why I was so appalled, but I must have been aware then of the sheer inefficiency of meat pro duction from the point of wasted energy and basic nutrients. However, it was not until the 1980s that my professional work and knowledge began to impinge to any real extent on what I ate, and in retrospect, I cannot understand why it took so long. In defense, I can offer the excuse that I was trained as a doctor and doctors were themselves indoctrinated to preach the need for meat. In 1986 he was appointed to the Veterinary Products Committee, a scientific panel that advises the British Minister of Agriculture on matters concerning the use of drugs in animals, birds and fish. My presence would therefore counteract the view that much antibiotic resistance was due to the use of antibi otics in animals. I would not say that this is exactly my view today, but the appointment to this committee did let me see how the inside of the U. The controversy began when Edwina Currie, a junior health minister, made the mistake of mention ing publicly that eggs infected with salmonella had poisoned over 1,000 people that year. Currie was quickly humbled and forced to resign over her remarks, but Lacey took up her defense, insisting that England was indeed experienc ing its worst-ever outbreak of salmonella, with 300 cases reported each week. Taking into account the fact that many cases passed as flu and went under reported, he estimated that 150,000 people per year were getting salmonella food poisoning from eggs. Currie has been made a scapegoat by the egg producers, by the Ministry of Agriculture and by all those trying to find someone to blame. Previously, officials had tallied about 1,000 cases per year of poisoning by the phage 4 strain, but in 1988 the number leapt to 14,000 cases. The root of the problem was the system of modern factory farming, which packed chickens together in overcrowded quar ters and relied on antibiotics rather than good hygiene to control infection. In addition, chickens had been highly inbred and selected for their egg-laying characteristics. These facts were not news to me, but the more I looked into the causes of food contamination, the more revolted I became. I soon began to write about general matters of food, using my basic med ical and nutritional knowledge in addition to my microbiological training. In an attempt to restore consumer confidence, the government hastily introduced a $45 million agricultural assistance package to subsidize the slaughter of four million at-risk chickens. Tim Lang of the London Food Commission, an independent food watchdog organization. Lacey had purchased 24 samples of microwaveable dinners from grocery stores and found that six of them contained listeria, a bacteria that can cause fatal blood poisoning, meningitis, and miscarriages in pregnant women. Moreover, the microwaving instructions on the package were insufficient to heat the food adequately. Lacey cooked the meals according to instructions and found that in most cases the listeria survived. A week after he announced his findings, the story flared into a full-scale food scare focusing on the death of a baby girl who had acquired listeria in the womb when her mother ate a packet of chicken sandwiches and soft cheeses from a supermarket. In April, the head of food microbiology at Nottingham Uni versity noted that the number of cases of salmonella-related food poisoning in England had doubled since 1985 and warned that the number of cases could reach one million a year by the end of the century. Worst-case Scenario 127 Bernard Rowe, director of the Public Health Laboratory Service. According to the World Health Organization, Europe as a whole was probably already seeing at least a million cases of salmonella and several hundred deaths per year. Critics, however, charged that the hormone was bad for animal health, suspect for human health, and poten tially harmful to the environment. In any case it was becoming increasingly difficult to criticize an organization that I had respon sibility to advise. These results show that the disease can be transmitted using unnat ural methods of infection, which can only be done experimentally in labora tory conditions and which would never happen in the field. If the exposure method was too unnatural to give meaningful results, why had they bothered with the exper iment in the first place. The spongiform encephalopathies varied widely in their impact on susceptible populations. Scrapie, on the other hand, was endemic in sheep, and kuru had devastated the Fore tribes people of New Guinea. With transmissible mink encephalopathy, there were well-documented cases in which almost 100% of all mink on a ranch suc cumbed following exposure to contaminated feed. Other people were also reading between the lines and drawing worried conclusions from the new announcement. In March 1990, more bad news came when the Times of London reported the previously unpublicized fact that five types of antelope had died in British zoos from spongiform encephalopathies. Zoo officials confirmed that the affected animals had been fed com mercial cattle feed. He had become ill earlier in the year, and veterinarians spent several weeks testing him but could do nothing to help. In all likelihood, other cats with the disease were going undetected, since most cat deaths did not undergo the level of scrutiny that Max had received. Cats had not succumbed when exposed to sheep scrapie, but experiments had shown that they were easily susceptible to Creutzfeldt-Jakob Disease. I agreed, little realizing that the Andrew Neil in question was Andrew Neil, the editor of the Sunday Times. Next day, a jour nalist from the Sunday Times telephoned and I repeated these comments.

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By the middle of the 1930s France and some other states still ad hering to gold were actually forced off the standard by the Treasuries of Great Britian and the United States, formerly jealous guardians of the liberal creed. Al though Great Britain and the United States departed from monetary orthodoxy, they retained the principles and methods of liberalism in industry and commerce, the general organization of their economic life. This was to prove a factor in precipitating the war and a handicap in fighting it, since economic liberalism had created and fostered the illusion that dictatorships were bound for economic catastrophe. By virtue of this creed, democratic governments were the last to under stand the implications of managed currencies and directed trade, even when they happened by force of circumstances to be practicing these methods themselves; also, the legacy of economic liberalism barred the way to timely rearmament in the name of balanced budgets and stable exchanges, which were supposed to provide the only secure foundations of economic strength in war. But for the stubborn and impassioned insistence of economic liberals on their fallacies, the leaders of the race as well as the masses of free men would have been better equipped for the ordeal of the age and might perhaps even have been able to avoid it altogether. But secular tenets of social organization embracing the whole civi lized world are not dislodged by the events of a decade. Both in Great Britain and in the United States millions of independent business units derived their existence from the principle of laissez-faire. In deed, its partial eclipse may have even strengthened its hold since it en abled its defenders to argue that the incomplete application of its prin ciples was the reason for every and any difficulty laid to its charge. Its apologists are repeating in endless variations that but for the policies advocated by its critics, liberalism would have delivered the goods; that not the competitive system and the self-regulating market, but interference with that system and interventions with that market are responsible for our ills. And this argument does not find support in innumerable recent infringements of economic freedom only, but also in the indubitable fact that the movement to spread the system of self-regulating markets was met in the second half of the nineteenth century by a persistent countermove obstructing the free working of such an economy. The economic liberal is thus enabled to formulate a case which links the present with the past in one coherent whole. For who could deny that government intervention in business may undermine con fidence. Who could deny that unemployment would sometimes be less if it were not for out-of-work benefit provided by law. The root of all evil, the liberal insists, was precisely this interference with the freedom of employment, trade and currencies practiced by the various schools of social, national, and monopolistic protectionism since the third quarter of the nineteenth century; but for the unholy alliance of trade unions and labor parties with monopolistic manu facturers and agrarian interests, which in their shortsighted greed joined forces to frustrate economic liberty, the world would be en joying today the fruits of an almost automatic system of creating ma terial welfare. Liberal leaders never weary of repeating that the tragedy Birth of the Liberal Creed [151] of the nineteenth century sprang from the incapacity of man to re main faithful to the inspiration of the early liberals; that the generous initiative of our ancestors was frustrated by the passions of national ism and class war, vested interests, and monopolists, and above all, by the blindness of the working people to the ultimate beneficence of un restricted economic freedom to all human interests, including their own. A great intellectual and moral advance was thus, it is claimed; frustrated by the intellectual and moral weaknesses of the mass of the people; what the spirit of Enlightenment had achieved was put to nought by the forces of selfishness. Unless it is refuted, he will continue to hold the floor in the contest of arguments. It is agreed that the liberal movement, intent on the spreading of the market system, was met by a protective coun termovement tending toward its restriction; such an assumption, in deed, underlies our own thesis of the double movement. But while we assert that the application of the absurd notion of a self-regulating market system would have inevitably destroyed society, the liberal ac cuses the most various elements of having wrecked a great initiative. Unable to adduce evidence of any such concerted effort to thwart the liberal movement, he falls back on the practically irrefutable hypothe sis of covert action. This is the myth of the anti-liberal conspiracy which in one form or another is common to all liberal interpretations of the events of the 1870s and 1880s. Thus in its most spiritualized form the liberal doctrine hypostasizes the working of some dialectical law in modern society stultifying the en deavors of enlightened reason, while in its crudest version it reduces it self to an attack on political democracy, as the alleged mainspring of interventionism. The great variety of forms in which the "collectivist" countermovement appeared was not due to any preference for socialism or nationalism on the part of con certed interests, but exclusively to the broad range of the vital social in terests affected by the expanding market mechanism. This accounts for the all but universal reaction of predominantly practical character [ 152 ] the Great Transformation called forth by the expansion of that mechanism. Intellectual fashion played no role whatever in this process; there was, accordingly, no room for the prejudice which the liberal regards as the ideological force behind the anti-liberal development. Although it is true that the 1870s and 1880s saw the end of orthodox liberalism, and that all crucial problems of the present can be traced back to that period, it is incor rect to say that the change to social and national protectionism was due to any other cause than the manifestation of the weaknesses and perils inherent in a self-regulating market system. Firstly, there is the amazing diversity of the matters on which ac tion was taken. Let us cite from a list of interventions which Herbert Spencer compiled in 1884, when charging liberals with having deserted their principles for the sake of "restrictive legislation. In i860 authority was given to provide "analysts of food and drink to be paid out of local rates"; there fol lowed an Act providing "the inspection of gas works"; an extension of the Mines Act "making it penal to employ boys under twelve not at tending schools and unable to read or write. And yet each of these acts dealt with some problem arising out of mod * Spencer, H. Birth of the Liberal Creed [ 153 ] ern industrial conditions and was aimed at the safeguarding of some public interest against dangers inherent either in such conditions or, at any rate, in the market method of dealing with them. To an unbi ased mind they proved the purely practical and pragmatic nature of the "collectivist" countermove. Most of those who carried these mea sures were convinced supporters of laissez-faire, and certainly did not wish their consent to the establishment of a fire brigade in London to imply a protest against the principles of economic liberalism. On the contrary, the sponsors of these legislative acts were as a rule uncom promising opponents of socialism, or any other form of collectivism. Secondly, the change from liberal to "collectivist" solutions hap pened sometimes over night and without any consciousness on the part of those engaged in the process of legislative rumination. The history of the various acts em bodying this idea, since 1880, showed consistent adherence to the indi vidualist principle that the responsibility of the employer to his em ployee must be regulated in a manner strictly identical with that governing his responsibility to others. With hardly any change in opinion, in 1897, the employer was suddenly made the in surer of his workmen against any damage incurred in the course of their employment, a "thoroughly collectivistic legislation," as Dicey justly remarked. No better proof could be adduced that no change either in the type of interests involved, or in the tendency of the opin ions brought to bear on the matter, caused the supplanting of a liberal principle by an anti-liberal one, but exclusively the evolving condi tions under which the problem arose and a solution was sought. Thirdly, there is the indirect, but most striking proof provided by a comparison of the development in various countries of a widely dis similar political and ideological configuration. Victorian England and the Prussia of Bismarck were poles apart, and both were very much un like the France of the Third Republic or the Empire of the Hapsburgs. Yet each of them passed through a period of free trade and laissez faire, followed by a period of anti-liberal legislation in regard to public health, factory conditions, municipal trading, social insurance, ship ping subsidies, public utilities, trade associations, and so on. It would be easy to produce a regular calendar setting out the years in which analogous changes occurred in the various countries. The supporting forces were in some cases violently reactionary and antiso cialist as in Vienna, at other times "radical imperialist" as in Birming ham, or of the purest liberal hue as with the Frenchman, Edouard Her riot, Mayor of Lyons. In Protestant England, Conservative and Liberal cabinets labored intermittently at the completion of factory legisla tion. In Germany, Roman Catholics and Social Democrats took part in its achievement; in Austria, the Church and its most militant support ers; in France, enemies of the Church and ardent anticlericals were re sponsible for the enactment of almost identical laws. Thus under the most varied slogans, with very different motivations a multitude of parties and social strata put into effect almost exactly the same mea sures in a series of countries in respect of a large number of compli cated subjects. There is, on the face of it, nothing more absurd than to infer that they were secretly actuated by the same ideological precon ceptions or narrow group interests as the legend of the antiliberal con spiracy would have it. On the contrary, everything tends to support the assumption that objective reasons of a stringent nature forced the hands of the legislators. Fourthly, there is the significant fact that at various times eco nomic liberals themselves advocated restrictions on the freedom of contract and on laissez-faire in a number of well-defined cases of great theoretical and practical importance. We have in mind the principle of the association of labor on the one hand, the law of business corpo rations on the other. The first refers to the right of workers to combine for the purpose of raising their wages; the latter, to the right of trusts, cartels, or other forms of capitalistic combines, to raise prices. It was justly charged in both cases that freedom of contract or laissez-faire was being used in restraint of trade. It is highly significant that in either case consistent liberals from Lloyd George and Theodore Roosevelt to Thurman Arnold and Walter Lipp mann subordinated laissez-faire to the demand for a free competitive market; they pressed for regulations and restrictions, for penal laws and compulsion, arguing as any "collectivist" would that the freedom of contract was being "abused" by trade unions, or corporations, whichever it was. Theoretically, laissez-faire or freedom of contract implied the freedom of workers to withhold their labor either individ ually or jointly, if they so decided; it implied also the freedom of busi nessmen to concert on selling prices irrespective of the wishes of the consumers. But in practice such freedom conflicted with the institu tion of a self-regulating market, and in such a conflict the self-regulating market was invariably accorded precedence.

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Transplacental Toxoplasmosis acquired after birth severe complications for the foetus. Period of communicability Infection may be diagnosed by Toxoplasmosis is not transmitted from visualisation of the protozoa in biopsy person to person spread except in-utero. Infection in the They may remain infective in water or water to dispose of the oocysts before first trimester results in a low foetal moist soil for over a year. Infection later in Tissue cysts in meat remain infective for Cats should only be fed with dry, canned pregnancy results in a higher infection as long as the meat is edible and under or boiled food and should be discouraged rate but generally less severe disease. However, direct contact with cats is rarely the Diagnosis and treatment during Susceptibility and resistance cause of infection. Cats are generally pregnancy appears to reduce the effects Everyone is susceptible to infection. About 75% of women of childbearing age oocysts for two weeks after their original False positive IgM antibody test (and less are susceptible. Where infection of the immunosuppressive therapy, in particular mother is confirmed, treatment is Control of case for haematological malignancies, or indicated. Immunosuppressed persons may also infection during pregnancy or active Pregnant women and require prophylactic treatment for the infection, and immunosuppressed immunosuppressed people should be duration of their immunosuppression. It is communicable as long as typhoid or School exclusion: exclude until approved Incubation period paratyphoid bacilli are present in excreta. Public health significance recognised serovars A, B and C are the and occurrence Control measures infectious agents. Typhoid and paratyphoid infections occur Preventive measures Identification worldwide. Outbreaks occur in areas with Vaccination is not routinely Clinical features poor sanitation and inadequate sewerage recommended, except for travellers who Typhoid fever (enteric fever) is a systems. Vaccination should be considered for Reservoir Complications such as intestinal laboratory workers in potential contact Reservoirs for typhoid and paratyphoid haemorrhage or perforation can develop with Salmonella typhi. A combination hepatitis A and typhoid Method of diagnosis Mode of transmission injectable vaccine is also available. All Diagnosis is made by culture of typhoid or Salmonella is transmitted by formulations are equally effective. Serology in the form of the water used), raw vegetables, salads and advised to exercise care in selecting food Widal test is no longer routinely used. A history of travel to an about personal hygiene, especially they should be advised to cease work until endemic area is usually found. If there is no history of travel, local the Department arranges the collection sources of infection are investigated to Control of case and testing of weekly faecal specimens identify further cases, asymptomatic Hospitalisation is usually required for for S. Food preparation, the Department will ciprofloxacin, ceftriaxone, handlers and workers in high risk determine the appropriate management chloramphenicol, amoxycillin or co professions are generally excluded from of the workplace on an individual basis. However, strains resistant to high risk work or patient care until they chloramphenicol, amoxycillin and co have had three consecutive negative Outbreak measures trimoxazole are common in south Asia. All cases are intensively investigated, Failure to respond to ciprofloxacin has Control of contacts whether sporadic or part of a cluster. Education should be given to the patient food-handlers or in a high risk Widespread use of typhoid vaccine is not regarding the importance of completing profession. Follow-up of all patients is conducted by Use of typhoid vaccine for contacts is the Department of Human Services to Additional sources of information not generally recommended. The blue book: Guidelines forthe control of infectious diseases 231 Verotoxin producing E. Humans serve as dysenteriae type 1 are the causative in the presence of the following: reservoirs for person to person agents. Fever is usually the incubation period is two to eight meat or mince, is a source of infection. Asymptomatic infection days, with an average of three to four Other known food sources have included can occur. Collect samples of precautions should be strictly observed potentially implicated food and send to in the management of hospitalised the Microbiological Diagnostic Unit for cases. The blue book: Guidelines forthe control of infectious diseases 233 Viral gastroenteritis (not rotavirus) Victorian statutory requirement Incubation period person to person contact. Explosive outbreaks have considered infectious until at least 48 adenoviruses are the infective agents. Identification centres, cruise ships, restaurants and Shedding of norovirus in the absence of Clinical features following catered functions. Vomiting High secondary attack rates result in Everyone is susceptible to infection and is relatively more prevalent among outbreaks that are often prolonged and infection is not known to confer lifelong children. Although rare, severe detected throughout the year but are Prevention is dependent on attention to dehydration caused by viral more common in the period from late good food and personal hygiene, gastroenteritis can be fatal in persons winter to early summer. Healthcare workers and food handlers be visualised and distinguished by Reservoir should be excluded from work until at electron microscopy. Children should be to detect norovirus genome are a excluded from school or childcare sensitive and specific tool for outbreak Mode of transmission centres until after symptoms have investigations. Nucleotide sequencing Viral gastroenteritis is predominantly ceased or a medical certificate of provides a classification of the viruses n spread via the faecal-oral route. Residents of observed,and is an important tool in Transmission is facilitated through institutions should be isolated until establishing links to contaminated contaminated food (particularly raw diarrhoea has ceased. Outbreak measures An outbreak is defined as two or more related cases of gastroenteritis. The primary aim is to prevent further disease by identifying the source, cleaning contaminated environments and isolating cases. Special settings Specific protocols for the management of outbreaks in special settings are available from the Communicable Diseases Section of the Department of Human Services. Public health significance rate of 1% of infected cases but 25% of and occurrence School exclusion: until medical hospitalised cases. Appropriate specimens Dengue haemorrhagic fever and yellow are: and treatment is commenced as early as fever are discussed elsewhere. Fever is typically insidious in onset and accompanied by severe Incubation period Reservoir headache, myalgia and malaise. Other the incubation period varies according to the reservoir for Lassa fever virus is a symptoms include retrosternal chest pain, the causative agent: rodent known as the multimammate rat cough, abdominal pain, diarrhoea, of the genus Mastomys spp.

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For example, red wine has received a lot of attention due to its health benefits (see above). Some researchers have linked this to the powerful antioxidant capacity of red wine and in particular to the activity of resveratrol (Whitehead et al. Corrected for abundance in red wine, catechin is found to contribute 38% to the total antioxidant ability of red wine, whereas resveratrol contributes only 0. This suggests that any health benefit attributed to resveratrol is probably not due to its antioxidant capacity. Similarly, when discussing the antioxidant potential of any one antioxidant in plasma, its relative abundance must also be taken into consideration. The total antioxidant capacity has been measured in a variety of samples including fluids obtained from healthy and diseased individuals, and beverages (Table 4. Decreased antioxidant capacity is found in many but by no means all diseases and conditions (Table 4. Its use as a marker of oxidative stress and possibly disease outcome must be made with caution. Some are relatively quick to perform and take only a few minutes, whereas others take a couple of hours. A few techniques measure peroxyl radical antioxidant activity only and ignore other aspects. Unfortunately, many approaches suffer from several important issues including poor quantitation, different antioxidants show different quenching kinetics, the antioxidant capacity of some antioxidants. For many assays albumin can contribute as much as 45% of the measured antioxidant capacity. It is therefore surprising that the antioxidant capacity is significantly altered in different clinical states. To overcome some of the problems associated with antioxidant capacity assays Cao et al. This is the only method that takes free radical action to completion and uses an area under-curve approach for quantitation. It combines both percentage inhibition and duration of inhibition time of an antioxidant into a single quantity. Consequently, both the contribution of individual antioxidants and the total antioxidant capacity of a plant sample can readily be obtained from a coulometric array chromatogram. The coulometric array approach can also be used to profile water-soluble and fat-soluble antioxidants in animal tissues (see above). So far it has been used to study diseases and conditions that markedly affect blood chemistry but can the assay be refined to monitor diseases that affect the blood much less. If the ultimate total antioxidant capacity method is developed then maybe it will be of practical use to the clinician in predicting and treating disease. The oxidation of foods resulting from their handling, processing and cooking is a major problem and can lead to nutrient loss, rancidity, spoilage and the production of potentially toxic compounds. Foods, especially those high in unsaturated fats, are particularly susceptible to oxidation (Donnelly and Robinson (1995)). Furthermore, the processing of meat and fish can release iron ions and heme proteins that act as pro-oxidants (Harel et al. The correct choice of antioxidant, natural or synthetic, is dependent upon the type of food being stabilized, carry-through from oil to final cooked products, solubility and dispersion in fat, presence of metals, possible discoloration, severity and degree of processing, and, in the United States, the maximum amount allowed by the Food and Drug Administration. Mobile phase A: Water that contained 25 mM sodium acetate and 25 mM citric acid methanol; 95:5 (v/v). Gradient Conditions: Initial conditions of 25% B with linear increase to 100% B over 12 minutes; hold at 100% B for 8 minutes; return to initial conditions of 25% B; and hold for 10 minutes. Irradiation of food by accelerated electrons, gamma rays or x-rays is currently being used by the food industry to delay fruit ripening, eliminate pathogens and produce sterile, shelf-stable products (Donnelly and Robinson (1995)). Unfortunately, irradiation cannot be used to treat foods high in fats as hydroxyl free radicals can initiate lipid peroxidation, thereby causing the formation of undesirable flavors. Furthermore, there is concern, especially amongst the public that irradiation can lead to the production of potentially toxic compounds. At best, irradiation represents a compromise between destruction of pathogens and the potential loss of micronutrients. Analytes measured include volatile lipid-derived compounds (tetradecene and alkylcyclobutanone), amino acid and protein oxidation products. So far not one technique has proven to be completely accurate so usually a suite of approaches is employed. Fluorometric determination of phylloquinone and menaquinone-4 in biological materials using high-performance liquid chromatography. Identification and determination of phenolic constituents in natural beverages and plant extracts by means of a coulometric electrode array system. The Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, Chicago, Illinois. Western diet and western diseases: some hormonal and biochemical mechanisms and associations. Quantitative determination of lignans and isoflavonoids in plasma of omnivorous and vegetarian women by isotope dilution gas chromatography-mass spectrometry. Antioxidant actions of thymol, cavacrol, 6-gingerol, zingerone and hydroxytyrosol. Metal-independent putative superoxide dismutase mimics in chemistry, biology and medicine. Correlation between mechanistic biotransformation and biochemical toxicology of some antihypertensive drugs. Uric acid provides an antioxidant defense in humans against oxidant and radical-caused aging and cancer: A hypothesis. A compilation of specific bimolecular rate constants for the reaction of hydrated electrons, hydrogen atoms and hydroxyl radicals with inorganic and organic compounds in aqueous solution. Structure-property relationships of the trimetazidine derivatives and model compounds as potential antioxidants. Phenotypic heterogeneity in motor neuron disease patients with CuZn-superoxide dismutase mutations in Scandinavia. Determination of indoles and catechols in rat brain and pineal using liquid chromatography with fluorometric and amperometric determination. Effects of thiol oxidation and thiol export from erythrocytes on determination of redox status of homocysteine and other thiols in plasma from healthy subjects and patients with cerebral infarction. Ascorbate-stimulated lipid peroxidation in human brain is dependent on iron but not on hydroxyl radical. Neurohormone melatonin prevents cell damage: Effect on gene expression for antioxidant enzymes. Postmortem changes of uric acid in various rat tissues: Determination of uric acid by reversed-phase high-performance liquid chromatography with electrochemical detection. Effects of inhibitors of hydroxymethylglutaryl coenzyme A reductase on coenzyme Q and dolichol biosynthesis. Dehydroepiandrosterone protects tissues of streptozotocin-treated rats against oxidative stress. Oxypurinol, a xanthine oxidase inhibitor and a superoxide scavenger, did not attenuate ischemic neuronal damage in gerbils. Retinoic acid affects the cell cycle and increases total protein content in epithelial cells. Function of thioredoxin reductase as a peroxynitrite reductase using selenocystine or ebselen. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide and hypochlorous acid. Antioxidant action of ergothioneine: Assessment of its ability to scavenge peroxynitrite. A high-performance liquid chromatography method for the measurement of oxidized glutathione in biological samples. Involvement of lipid peroxidation in necrosis of skin flaps and its suppression by ellagic acid. Concurrent on-line sampling of melatonin in pineal microdialysates from conscious rat and its analysis by high-performance liquid chromatography with electrochemical detection.

References:

  • https://www.uchealth.com/wp-content/uploads/2013/01/PE-LP_UCNI.pdf
  • https://www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/Brochure-MS-for-the-Physician-Assistant_-A-Practical-Primer.pdf
  • https://main.mohfw.gov.in/sites/default/files/7966072180.pdf
  • http://downloads.hindawi.com/journals/specialissues/924519.pdf

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