By E. Renwik. Jones International University.

Antimetabolites agents Some agents of this group specifically inhibit essential metabolic steps that are essential to microorganisms generic soma 350mg without prescription. Examples of anti-infective of this group include sulfonamides (sulfisoxazole buy soma 500 mg lowest price, sulfacetamide) and the combination trimethroprim-sulfamethoxazole [34 buy 350 mg soma fast delivery, 35] cheap soma 500mg overnight delivery. Other agents directly affect nucleic st acid metabolism, such as the fluoroquinolones of 1 generation (norfloxacin), nd rd 2 generation (ciprofloxacin and ofloxacin), 3 generation (levofloxacin) and th 4 generation (moxifloxacin) [36]. Sulfonamides are active against Gram-positive and negative organisms, Chlamydia spp. Fluoroquinolones are effective in the treatment of 8 infections of the urogenital and gastrointestinal tracts caused by Gram- negative organisms, including E. However, the use should be avoided during the first trimester and late in gestation, respectively [37]. Fluoroquinolones have been associated to the development of arthropathy in immature animals and are not recommended for routine use during pregnancy [30-32]. Antimycobacterial drugs Agents of this class are active against Mycobacterium spp. During pregnancy, these drugs are used against tuberculosis, leprosy and atypical mycobacterium infections [30, 31]. Miscellaneous and Urinary anti-infective agents Metronidazole, nitrofurantoin and nalidixic acid are the most important agents of this class. Nalidixic acid and Nitrofurantoin are active against many urinary tract pathogens, but not Proteus spp. Metronidazol is used for the treatment of bacterial vaginosis and trichomoniasis during pregnancy. Nitrofurantoin is used for the as a second- line treatment for asymptomatic bacteriuria and cystitis during pregnancy [30- 32]. Other less prevalent conditons include sexually transmitted infections, malaria, tuberculosis and cutaneous bacterial infections [40-42]. A more detailed description of the most important gestational infections can be found in the section 2. Epidemiology of anti-infective drug use during pregnancy The question of whether to prescribe anti-infective drugs to pregnant women is a dilemma faced by health care providers on a daily basis. Physicians have been reluctant to prescribe anti-infective drugs for pregnant women because a few of them are on the list of human teratogens (e. There is discrepancy in results of the studies that investigated the use of anti- infective drugs during pregnancy. Therefore, useful comparisons between studies and interpretation of results can be challenging [45]. The use of medications by pregnant women was recorded in South Africa, and the results showed that the most commonly used medicines were analgesics, antibiotics, laxatives and antacids [46]. In Brazil, a retrospective cohort study showed that antibiotics were the third most common group of medications used during pregnancy [47]. In Finland, penicillin, erythromycin and pivmecillinam were the most often used antibiotics during pregnancy comprising together 65. Antibiotics were the most commonly prescribed medications in a study conducted in Australia [51]. High incidence of anti-infective use in pregnancy was also observed in the United States [4, 52], where the use of nitrofurantoin, sulfonamides was considered excessive [53]. In the United Kingdom, 30% of women were exposed to at least one anti-infective drug during gestation [54]. Respiratory infections diagnosed during pregnancy are mostly of viral etiology [59-61]. In this thesis, we focus on anti- infective drugs used to treat bacterial infections. These infections are characterized by the presence of microorganisms in the genito-urinary tract that cannot be explained by contamination. These agents have the potential to invade the tissues of the urinary tract and adjacent structures. The infection may be limited to the growth of bacteria in the urine (which frequently doesn’t produce symptoms) or it can result in several syndromes associated with an inflammatory response to remove the bacterial invasion. Although the incidence of acute cystitis in pregnant women is similar to that in their nonpregnant counterparts, 12 the incidence of acute pyelonephritis in pregnant women with bacteriuria is significantly increased, compared with nonpregnant women [66]. Many studies have reported that pyelonephritis is more common during the second half of pregnancy, with an incidence peak during the last two trimesters of pregnancy [67-69]. The prevalence is also markedly increased if women present certain pre-existing medical conditions, such as diabetes mellitus, sickle cell disease, immunodeficiency states, urinary tract anatomic anomalies, spinal cord injuries and psychiatric illnesses [70]. Organisms causing bacteriuria are similar in both pregnant and nonpregnant women [66]. Asymptomatic bacteriuria is defined by 8 two consecutive clean-catch urine cultures with more than 10 colonies of bacteria/L of urine, with a single type of bacteria [74]. Urethritis is characterized by urethral colonization 13 resulting in dysuria and polyuria. Common clinical manifestations are dysuria, polyuria, suprapubic discomfort, and in some cases, hematuria [37]. Clinical signs and symptoms of pyelonephritis include flank pain or abdominal pain, fever, anorexia, nausea and vomiting often associated with variable degrees of dehydration, chills, headache, and tachypinea. Intrauterine infections are thought to be responsible for up to 50% of extreme preterm births of less than 28 weeks of gestation, where both neonatal mortality and morbidity are high [83]. As a consequence, the initial antibiotic therapy has the drawback of being empirical, and a variety of different antimicrobial agents can be used for treatment [86]. Urinary Treatment Treatment options Comments tract regimen infection Asymp- Current standard Cephalexin 250-500 mg, Single-dose tomatic of practice is to po, qid. Although the infection is present in almost 20% of pregnant women, it is difficult to know the exact prevalence of this condition, because many cases are asymptomatic or naturally occur at regular times during the menstrual cycle [96]. The infection is clinically characterized by the presence of three of the five following Amsel criteria [101]: release of the amine fishy odour, release of amine odour after addition of potassium hydroxide, vaginal pH greater than 4. Available evidence does not suggest any benefit in screening and treating asymptomatic pregnant women if the aim of therapy is to prevent preterm birth [107]. Topical intra-vaginal treatment with clindamycin is not recommended, given that the use of this drug is associated with an increased risk of low birth 21 weight and neonatal infections [32, 102, 109-111]. This agent is able to cross the placenta throughout gestation, and data from animal studies suggests teratogenic properties for this drug [112]. However, there is no evidence that using metronidazole during pregnancy increases the rate of major birth defects or that there are any detectable adverse effects on fetuses [113]. Some studies suggest that the use of metronidazole during the last two trimesters of pregnancy may result in a qualitative imbalance of the normal vaginal flora [114, 115]. One of its consequences is the growth of harmful microorganisms, leading to ascending infection, stimulation of the local inflammatory process and early delivery. Therefore, the use of metronidazole during pregnancy has been controversial [113]. Bacterial Treatment Treatment Comments vaginosis regimen options Metronidazole Current standard 500 mg po bid for Topical of practice is to 7 days. However, as with the use of other medications, the potential benefits of use need to be weighed against the risk for the fetus [31].

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Another antipsoric remedy which may be ever so useful effective soma 350 mg, but is prescribed too early and before the cessation of the action of the present remedy purchase soma 500mg on line, or a new dose of the same remedy which is still usefully acting generic soma 500mg without prescription, can in no case replace the good effect which has been lost through the interruption of the complete action of the preceding remedy buy discount soma 500mg on line, which was acting usefully, and which can hardly be again replaced. It is a fundamental rule in the treatment of chronic diseases: To let the action of the remedy, selected in a mode homoeopathically appropriate to the case of disease which has been carefully investigated as to its symptoms, come to an undisturbed conclusion, so long as it visibly advances the care and the while improvement still perceptibly progresses. This method forbids any new prescription, any interruption by another medicine and forbids as well the immediate repetition of the same remedy. Nor can there be anything more desirable for the physician than to see the improvement of the patient proceed to its completion unhindered and perceptibly. There are not a few cases, where the practiced careful Homoeopath sees a single dose of his remedy, selected so as to be perfectly homoeopathic, even in a very severe chronic disease, continue uninterruptedly to diminish the ailment for several weeks, yea, months, up to recovery; a thing which could not have been expected better in any other way, and could not have been effected by treating with several doses or with several medicines. To make the possibility of this process in some way intelligible, we may assume, what is not very unlikely, that an antipsoric remedy selected most accurately according to homoeopathic principles, even in the smallest dose of a high or the highest potency can manifest so long- continued a curative force, and at last cure, probably, only by means of a certain infection with a very similar medicinal disease which overpowers the original disease, by the process of nature itself, according to which (Organon, ¤ 5, Fifth Edition,) two diseases which are different, indeed, in their kind but very similar in their manifestations and effects, as also in the ailments and symptoms caused by it, when they meet together in the organism, the stronger disease (which is always the one caused by the medicine, ¤33, ibid. In this case every new medicine and also a new dose of the same medicine, would interrupt the work of improvement and cause new ailments, an interference which often cannot be repaired for a long time. Yet when a sudden great and striking improvement of a tedious great ailment follows immediately on the first dose of a medicine, there justly arises much suspicion that the remedy has only acted palliatively, and therefore must never be given again, even after the intervention of several others remedies. Nevertheless there are cases which make an exception to the rule, but which not every beginner should risk finding out. We may declare it once, that the practice of late, which has even been recommended in public journals of giving the patient several doses of the same medicine to take with him, so that he may take them himself at certain intervals, without considering whether this repetition may affect him injuriously, seems to show a negligent empiricism, and to be unworthy of a homoeopathic physician, who should not allow a new dose of a medicine to be taken or given without convincing himself in every case beforehand as to its usefulness. This is rare in chronic diseases, but in acute diseases and in chronic diseases that rise into an acute state it is frequently the case. It is only then, as a practiced observer may recognize - when the peculiar symptoms of the disease to be treated, after fourteen, ten, seven, and even fewer days, visibly cease to diminish, so that the improvement manifestly has come to a stop, without any disturbance of the mind and without the appearance of any new troublesome symptoms, so that the former medicine would still be perfectly homoeopathically suitable, only then, if say, is it useful, and probably necessary to give a dose of the same medicine of a similarly small amount, but most safely in a different degree of dynamic potency. To adduce an example: a freshly arisen eruption of itch belongs to those diseases which might soonest permit the repetition of the dose (sulphur), and which does permit it the more frequently, the sooner after the infection the itch is received for treatment, as it then approaches the nature of an acute disorder, and demands its remedies in more frequent doses than when it has been standing on the skin for some time. But this repetition should be permitted only when the preceding dose has largely exhausted its action (after six, eight or ten days), and the dose should be just as small as the preceding one, and be given in a different potency. Nevertheless it is in such a case often serviceable, in answer to a slight change of symptoms, to interpose between the doses of pure sulphur, a small dose of Hepar sulphuris calcareum. This also should be given in various potencies, if several doses should be needed from time to time. Often also, according to circumstances, a dose of Nux voinica (x) or one of mercury (x)** may be used between. A dose of medicine may also have been suddenly counteracted and annihilated by a grave error in the regimen of the patient, when perhaps a dose of the former serviceable medicine might again be given with the modification mentioned above. Thereby the remedy seeing to take a deeper hold on the organism and hasten the restoration in patients who are vigorous and not too sensitive. Indeed it is hardly ever needed in chronic diseases, as we have a goodly supply of antipsoric remedies at our disposal, so that as soon as one well selected remedy has completed its action, and a change of symptoms, i. Nevertheless in very tedious and complex cases, which are mostly such as have been mismanaged by allopathic treatment, it is nearly always necessary to give again from time to time during the treatment, a dose of Sulphur or of Hepar (according to the symptoms), even to the patients who have been before dosed with large allopathic doses of Sulphur and with sulphur-baths; but then only after a previous dose of Mercury (x). Where, as is usually the case in chronic diseases, various antipsoric remedies are necessary, the more frequent sudden change of them is a sign that the physician has selected neither the one nor the other in an appropriately homoeopathic manner, and had not properly investigated the leading symptoms of the case before prescribing a new remedy. This is a frequent fault into which the homoeopathic physician falls in urgent cases of chronic diseases, but oftener still in acute diseases from overhaste, especially when the patient is a person very dear to his heart. Then the patient naturally falls into such an irritated state that, as we say, no medicine acts, or shows its effect,* yea, so that the power of response in the patient is in danger of flaring up and expiring at the least further dose of medicine. In such a case no further benefit can be had through medicine, but there may be in use a calming mesmeric stroke made from the crown of the head (on which both the extended hands should rest for about a minute) slowly down over the body, passing over the throat, shoulders, arms, hands, knees and legs down over the feet and toes. A dose of homoeopathic medicine may also be moderated and softened by allowing the patient to smell a small pellet moistened with the selected remedy in a high potency, and placed in a vial the mouth of which is held to the nostril of the patient, who draws in only a momentary little whiff of it. By such an inhalation the powers of any potentized medicine may be communicated to the patient in any degree of strength. One or more such medicated pellets, and even those of a larger size may be in the smelling-bottle, and by allowing the patient to take longer or stronger whiffs, the dose may be increased a hundred fold as compared with the smallest first mentioned. The period of action of the power of a potentized medicine taken in by such inhalation and spread over so large a surface (as that of the nostrils and of the lungs) last as long as that of a small massive dose taken through the mouth and the fauces. From this it follows that the nerves possessing merely the sense of touch receive the salutary impression and communicate it unfailingly to the whole nervous system. This method of allowing the patient to be acted upon by smelling the potentized medicine has great advantages in the manifold mishaps which often obstruct and interrupt the treatment of chronic diseases. The antidote to remove these mishaps as quickly as possible the patient may also best receive in greater or less strength through inhalation, which acts most quickly on the nerves and so also affords the most prompt assistance, by which also the continuation of the treatment of the chronic disease is least delayed. When the mishap has thus been obviated most speedily, the antipsoric medicine before taken frequently continues its interrupted action for some time. But the dose of the inhaled medicine must be so apportioned to the morbid interruption that its effect just suffices to extinguish the disadvantage arising from the mishap, without going any deeper or being able to continue its operation any further. I remark here, that I consider the sugar of milk thus used as an invaluable gift of God. So also the homoeopathic physician cannot avoid allowing a new chronic patient to take at least one little powder a day; the difference between this and the many medicinal doses of allopaths is still very great. During this daily taking of a powder, following the numbers, it will be a great benefit to the poor patient who is often intimidated by slanderers of the better medical art, if he does not know whether there is a dose of medicine in every powder, nor again, in which one of them? If he knew the latter, and should know, that to-dayÕs number contains the medicine of which he expects so much, his fancy would often play him an evil trick, and he would imagine that he feels sensations and changes in his body, which do not exist; he would note imaginary symptoms and live in a continual inquietude of mind; but if he daily takes a dose, and daily notices no evil assault on his health, he becomes more equable in disposition (being taught by experience), expects no ill effects, and will then quietly note the changes in his state which are actually present, and therefore can only report the truth to his physician. On this account it is best that he should daily take his powder, without knowing whether there is medicine in all or in a certain powder; thus he will not expect more from to-dayÕs powder than from yesterdayÕs or that of the day before. But this is a vain, utterly unfounded fear, as I have determined by very exact experiments. We may use the crude, pure sugar of milk as a food, and partake of considerable quantities of it, without any change in the health, and so also the triturated sugar. But to destroy at the same time the fear to which utterance has been given by some hypochondriacs, that through a long trituration of the sugar of milk alone, or in the potentizing of medicines, something might rub off from the porcelain mortar (silica), which being potentized by this same trituration would be bound to become strongly acting Silicea( ), I took a new porcelain triturating bowl in which the glazing 1 had been rubbed off, with a new porcelain pestle, and had one hundred grains of pure sugar of milk, divided into portions of thirty-three grains, triturated eighteen times for six minutes at a time and as frequently scraped for four minutes with a porcelain spatula, in order to develop by this three hours strong trituration a medicinal power either of the sugar of milk or of the silica or of both; but my preparation remained as indifferent and unmedicinal as the crude, merely nutritive sugar of milk, of which I convinced myself by experiments on very sensitive persons. This deceptive effect shows that the medicine here acts enantiopathically as an opposite or palliative, and that in the days following we cannot expect anything from this remedy but an aggravation of the original disease. As soon then as this deceptive improvement within a few days begins again to turn to aggravation, it is high time to give either the antidote to this medicine, or, when this cannot be had, a medicine which is homoeopathically more appropriate. In such cases we may also successfully use, for the ailments following after a few days from such an antipathic remedy, one of the remaining medicines from the considerable store laid down in Materia Medica Pura, in the ÒArchiv der homoeopathischen HeilkunstÓ or in the ÒAnnalen. Among the mishaps which disturb the treatment only in a temporary way, I enumerate: overloading the stomach (this may be remedied by hunger, i. Here the other homoeopathic remedies will have to be used, wherefore I shall not enter upon this here, except to say that the antipsoric treatment will have for the time to be totally discontinued, so long as the, treatment of the epidemic disease which has also seized our (chronic) patient may last, even if a few weeks in the worst cases may thus be lost. But here also, if the disease is not too severe, the above mentioned method of applying the medicine by smelling a moistened pellet is often sufficient to help, and the cure of the acute disease may thus he extraordinarily shortened. The intelligent homoeopathic physician will soon note the point of time when his remedies have completed the cure of the epidemic intermediate disease * and when the peculiar course of the chronic (psoric) malady is continued. There are fevers of various kinds, a continuous acute fever, or a slow remittent, or an intermittent fever.

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Aggravating factors include old age generic 500 mg soma visa, obesity buy soma 500 mg lowest price, re- current trauma order 350 mg soma, immobility and joint problems 350mg soma mastercard. Aetiology The aetiology of most congenital heart disease is un- Pathophysiology known, and associations are as follows: r Genetic factors: Down, Turner, Marfan syndromes. Chronic venous ulceration is the last stage of lipo- r Environmental factors: Teratogenic effects of drugs dermatosclerosis(the skin changes of oedema, fibrosis around veins and eczema, which occurs in venous sta- and alcohol. Pathophysiology Clinical features Normally in postnatal life the right ventricle pumps de- Distinguishable from arterial ulcers by clinical features oxygenated blood to lungs and the left ventricle pumps and a history of chronic venous insufficiency (see Table oxygenatedbloodatsystemicbloodpressuretotheaorta, 2. Investigations Congenital heart lesions can be considered according Phlebography is performed to assess the underlying state to one or more of of the veins. Blood from the left side of the heart is re- Management turned to the lungs instead of going to the systemic Healing often takes weeks, possibly months. Skin grafts may speed healing, but only if venous pres- Clinically lesions can be divided into two categories: sure is reduced, e. Surgery to remove r Acyanotic heart disease, which include the left to right incompetent veins before ulceration occurs. Definition Prevalence Abnormal defect in the ventricular septum allowing pas- Up to 1% of live born infants are affected by some form sage of blood flow between the ventricles. Chapter 2: Congenital heart disease 85 Age continued large left to right shunt, the combination of Congenital increased pulmonary blood volume and high-pressure shear forces causes hypertrophy and deposition of col- Sex lagen in the walls of pulmonary arterioles. Eventually M = F these changes become irreversible and pulmonary hy- pertension develops, usually during childhood. The re- sultant high pressure in the right side of the heart causes Aetiology areductionand eventual reversal of the shunt with as- In most cases the aetiology is unknown but may include sociated development of cyanosis termed Eisenmenger maternal alcohol abuse. On ex- r Small defects result in little blood crossing to the right amination there is usually a pulmonary ejection mur- sideoftheheartandnohaemodynamiccompromise– mur and there may be tachypnoea and tachycardia if ‘maladie de Roger’. The murmur is, however, causes a loud pulmonary component to the second quieter as there is less turbulent flow. Initially increased pulmonary blood flow does not cause arise in pressures within the pulmonary circulation Investigations due to the vascular compliance. If, however, there is a r Chest X-ray: Abnormalities are only seen with large defects when cardiomegaly and prominent pul- monary vasculature may be seen. Measurement of the size of the defect and the blood flow allows prediction of the outcome. The shunting of blood from left to right increases the volume of blood passing through the right side of the Incidence heart leading to right ventricular volume overload and 10% of congenital heart defects. Prolongedhigh volume blood flow through lungs can occasionally lead Sex to pulmonary hypertension due to changes in the pul- F > M monary vasculature similar to ventricular septal defects (see page 84). Aetiology Defects in the ostium primum occur in patients with Clinical features Down syndrome often as part of an atrioventricular sep- Atrialseptaldefectsareoftenasymptomaticinchildhood tal defect. On examination Pathophysiology there is a fixed widely split second heart sound due to the The atrial septum is embryologically made up of two high volumes flowing through the right side of the heart parts: the ostium primum and the ostium secundum, and the equalisation of right and left pressures during which forms a flap over the defect in the ostium pri- respiration. A diastolic murmur may through the fossa ovalis and hence shunts blood away also occur due to flow across the tricuspid valve. In normal individuals Rarely patients may present with paradoxical emboli at birth the vasculature within the lungs dilate at birth (where thrombus from a deep vein thrombosis crosses and hence the right heart pressures fall. Once the left the atrial septal defect and causes stroke or peripheral atrial pressure exceeds the right, the ostium secundum arterial occlusion). Ostium secundum tends to produce right axis Chapter 2: Congenital heart disease 87 deviation, whereas ostium primum produces left axis Neonatal coarctation is often associated with a patent deviation. Eighty per cent of cases occur in association with a Management bicuspid aortic valve. The defect may be closed using an umbrella-shaped Clinical features occluder placed at cardiac catheterisation. Traditional Proximal hypertension may cause headache and dizzi- open surgical repair requires cardiopulmonary bypass ness, distal hypotension results in weakness and poor pe- and may use a pericardial or Dacron patch to close the ripheral circulation. Surgicalinterventioninostiumprimumdefectsis are weak or absent and there is radiofemoral delay. Four- morecomplexduetoinvolvementoftheatrioventricular limb blood pressure measurement will demonstrate the valves. Coarctation of the aorta Investigations Definition r Chest X-ray may show left ventricular hypertrophy Localised narrowing of the descending aorta close to the and rib notching due to dilated intercostal arteries site of the ductus arteriosus. Pathophysiology Coarctation of the aorta tends to occur at the site of the ductus/ligamentus arteriosus, which is usually opposite Management the origin of the left subclavian artery (see Fig. The Surgical treatment is used in the majority of cases and left ventricle hypertrophies to overcome the obstruction is an emergency in coarctation complicated by a patent and cardiac failure may occur. The chest is opened by left lateral tho- develops with hypotension in the lower body. Prognosis Without treatment 50% of patients die within the first year of life from cardiac failure and complications of hypertension such as intracranial bleeds. This reduces the right to left intracardiac shunt and provides some symptomatic relief. On auscultation there is initially a long systolic murmur across the pulmonary valve, which shortens as cyanosis develops. Spasm of the infundibular muscle in the right ven- tricular outflow tract results in further compromises the right cardiac outflow causing worsening cyanosis and often loss of consciousness. Investigations ChestX-rayoftenshowsaheartofnormalsizebuttheleft heartborderisconcave(bootshape)duetothesmallpul- r Right ventricular outflow obstruction (pulmonary monary trunk. Aetiology Embryological hypoplasia of the conus, which gives rise tothemembranousventricularseptum. OccursinDown Management r Symptomatic infants may require a Blalock–Taussig syndrome and as part of fetal alcohol syndrome. This provides a left to The pulmonary stenosis results in high right ventricular rightshunt replacing the duct as it closes. The degree of pulmonary stenosis isvariable(rangingfrommildtoatresia),thustheclinical picture ranges in severity. The right ventricular outflow Cardiovascular oncology tract obstruction is often progressive. Clinical features Atrial myxoma In rare severe cases cyanosis develops within days as the Definition pulmonary circulation is dependent on a patent ductus An atrial myxoma is a benign primary tumour of the arteriosus. More commonly presentation is later with heart most commonly arising in the left atrium. Initially it may only be present on exertion, but as the right ventricu- lar outflow obstruction is progressive cyanosis becomes Incidence evident at rest, and the characteristic squatting position Primarytumoursoftheheartarerare,butatrialmyxoma may be adopted. Chapter 2: Cardiovascular oncology 89 Aetiology Carotid body tumours The aetiology of atrial myxoma is unknown. Definition Tumour arising from chemoreceptors at the bifurcation Pathophysiology of the carotid artery. The tumour is usually located on a pedicle arising from the atrial septum, and can grow up to about 8 cm Incidence across. The pedicle allows the tumour to move within Rare the atrium resulting in various symptom complexes. If the tumour obstructs the mitral valve a picture similar to Aetiology mitral stenosis will occur.

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Firstly generic soma 350mg without prescription, statins may not cause autoimmunity by themselves but may promote a pre- existing autoimmune-prone condition to progress towards clinically manifest diseases generic 350 mg soma with mastercard. Secondly buy cheap soma 500 mg on line, one can argue whether we have used the most relevant outcome defnitions and confounders cheap 350 mg soma. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Principles and methods for assessing autoimmunity associated with exposure to chemicals: Environmental Health Criteria. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies. Vasculitis and antineutrophil cytoplasmic autoantibodies associated with propylthiouracil therapy. Quantifying effect of statins on low density lipoprotein cholesterol, 6 ischaemic heart disease, and stroke: systematic review and meta-analysis. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis factor and interleukin 1 by human peripheral blood mononuclear cells. Angiotensin converting enzyme inhibitors suppress production of tumor necrosis factor-alpha in vitro and in vivo. Captopril and lisinopril suppress production of interleukin-12 by human peripheral blood mononuclear cells. Angiotensin receptor blockers reduce erythrocyte sedimentation rate levels in patients with rheumatoid arthritis. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Accelerated atherosclerosis in systemic lupus erythematosus: role of proinfammatory cytokines and therapeutic approaches. Balancing early market access to new drugs with the need for beneft/risk data: a mounting dilemma. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuti- cals for Human Use. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuti- cals for Human Use. Lupus erythematosus and other autoimmune diseases related to statin therapy: a systematic review. Statin adverse effects : a review of the literature and evidence for a mitochondrial mechanism. Statin-induced lupus: a case/non-case study in a nationwide pharmacovigi- lance database. Persistence with statins and onset of rheumatoid arthritis: a population-based cohort study. Effect of statins on a wide range of health outcomes: a cohort study validated by comparison with randomized trials. Frequency of development of connective tissue disease in statin-users versus nonusers. The central role of the propensity score in observational studies for causal effects. Angiotensin-converting enzyme inhibitor-induced pemphigus: three case reports and literature review. Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy. Angiotensin receptor blockers suppress antigen-spe- cifc T cell responses and ameliorate collagen-induced arthritis in mice. The non-thiol angiotensin-converting enzyme inhibitor quinapril suppresses infammatory arthritis. Involvement of the renin-angiotensin system in the development of vascular damage in a rat model of arthritis: effect of angiotensin receptor blockers. Effects of Angiotensin-converting enzyme inhibition and statin treatment on infammatory markers and endothelial functions in patients with longterm rheumatoid arthritis. Association of statins with infammatory cytokines: a population-based Colaus study. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. Simvastatin promotes Th2-type responses through the induction of the chitinase family member Ym1 in dendritic cells. Adverse effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors associated with elevated serum IgE and eosinophilia. The effect of aggressive versus conventional lipid-lowering therapy on markers of infammatory and oxidative stress. Secondary prevention with 6 fuvastatin decreases levels of adhesion molecules, neopterin and C-reactive protein. Assessment of the effcacy of different statins in murine collagen-induced arthritis. Protein geranylgeranylation regulates the balance between Th17 cells and Foxp3 regulatory T cells. Atorvastatin up-regulates regulatory T-cell and improves clinical disease activity in patients with rheumatoid arthritis. Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo. Heterogeneity of natural Foxp3+ T cells: a committed regulatory T-cell lineage and an uncommitted minor population retaining plasticity. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Drug insight: Immunomodulatory effects of statins--potential benefts for renal patients? Targeting Rac1 by the Yersinia effector protein YopE inhibits caspase-1-mediated maturation and release of interleukin-1be- ta.

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