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In suggested that the efcacy shown in the blinded studies was main- North America a broader defnition is ofen used than in Europe discount 80 mg super cialis overnight delivery erectile dysfunction vacuum pump medicare. The populations studied included chil- 1 discount super cialis online american express erectile dysfunction treatment toronto,5-benzodiazepines (such as clonazepam) are efcacious, particu- dren and adults, used broad defnitions of the syndrome and had larly for myoclonic seizures, although tonic status may be precipitat- maintenance phases of, at most, only a few months. Clobazam (a 1,5-benzodiazepine) was evaluated was not shown to be superior to placebo [102]. Twenty-fve – felbamate, lamotrigine, topiramate, rufnamide and clobazam – experienced a >50% reduction in seizures [118]. Drug Population Intervention Key outcomes Felbamate 73 subjects aged 4–36 years Felbamate versus placebo Mean change in total seizure frequency: 19% decrease versus having at least 180 atonic (maximum of 45 mg/ 4% increasea or atypical absences in 8 kg/day or 3600 mg/day, Responder rate for total seizures: 50% versus 11%a weeks prior to baseline whichever lower) for Mean change in atonic seizure frequency: 34% decrease versus 70 days 9% decreasea Responder rate for atonic seizures: 57% versus 9%a Discontinuations due to adverse events: 1 versus 1 Lamotrigine 169 subjects aged 3–25 Lamotrigine versus placebo Median change in major seizure frequency: 32% decrease years with at least one (dose dependent on versus 9% decreasea seizure every 2 days concomitant valproate Responder rate for major seizures: 33% versus 16%a therapy and body Median change in drop attack frequency: 34% decrease versus weight) for 16 weeks 9% decreasea Responder rate for drop attacks: 37% versus 22%a Discontinuations due to adverse events: 3 versus 7 Topiramate 98 subjects aged 1–30 years Topiramate versus placebo Median change in major seizure frequency: 26% decrease with at least 60 seizures in (target dose approx versus 5% decreasea month prior to baseline 6 mg/kg/day) for 11 Responder rate for major seizures: 33% versus 8%a weeks Median change in drop attack frequency: 15% decrease versus 5% decreasea Responder rate for drop attacks: 28% versus 14% Discontinuations due to adverse events: none Rufnamide 138 subjects aged 4–37 Rufnamide versus placebo Median change in total seizure frequency: 33% decrease versus years with at least 90 (target dose 45 mg/kg/ 12% decreasea seizures (including drop day) for 84 days Median change in tonic–atonic seizure frequency: 43% attacks and atypical decrease versus 1% increasea absences) in month prior Responder rate for tonic–atonic seizures: 43% versus 17%a to baseline Discontinuations due to adverse events: 6 versus 0 Clobazam 217 subjects aged 2–60 Clobazam versus placebo Reduction in drop attacks: 12. Other studies have shown that, although the initial efect are no data from randomized, double-blind, controlled trials and is ofen good, relapse is common. Although regular benzodiaze- than 10 days, although 10 subsequently relapsed within 6 months pines may be helpful, their usefulness for treatment of episodes of [126]. However, there is evidence that clobazam may be supe- view [128] found no evidence to support the use of steroids in the rior to other options [138]. Carbamazepine, phenytoin, oxcarbaze- treatment of childhood epilepsy, other than West syndrome. However, a subsequent single-blind placebo study lacosamide might do likewise [139]. Patients were randomized to receive appears to achieve nothing and, in a few cases, it is appropriate to the diet immediately or afer 3 months. Tirty-eight per cent on the diet had a >50% reduction Doose syndrome in seizures compared with 6% not on the diet. Numbers were too Tere are no randomized controlled studies of any treatment for small to analyse by syndrome but there was no signifcant diference Doose syndrome and the best evidence available is from case series. Corpus callosotomy can be used for the treatment of atonic lamotrigine, sometimes combined with sodium valproate, is ofen and tonic drop attacks, seizure types that characteristically occur in used. A study from Taiwan reported that 68% of patients (children became seizure-free on lamotrigine and there are no reports of lam- and adults) had at least a 50% reduction in seizures following ante- otrigine exacerbating seizures in Doose syndrome [140]. Indeed, it rior callosotomy and that this was not dependent on whether West was found to be efective in 6 out of 10 patients who were hitherto Management of Childhood Epilepsy Syndromes 189 pharmacoresistent [141]. Because this is an area of eloquent cortex, 3 months and in six out of eight patients at 6 months. However, the technique of mul- particularly efective against myoclonic–astatic seizures [143]. However, even in those children who re- syndrome, 11 of whom were treated with the ketogenic diet. At 18 spond quickly, age-appropriate language appears to be only occa- months, six remained on the diet, two were seizure-free, two had sionally achieved. Reports suggest that earlier surgery is associated a 75–99% reduction in seizures and two experienced a 50–74% with a better functional impact. Treatment of this rare syndrome is guided by information from case Treatment with no other drug (including levetiracetam, carbamaz- series. Tere is one report of myoclonic status epilepticus in Doose zure control is said to be associated with a better long-term cognitive syndrome apparently provoked by levetiracetam [147]. Both are rare and there References are no randomized controlled trials to help guide their manage- 1. This and other drugs, such as oxcarbazepine, vigabatrin, ti- tiepileptic drugs, I: treatment of new onset epilepsy: report of the Treatment and agabine and gabapentin, are probably best avoided. It is sometimes Technology Assessment Subcommittee and the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Efcacy and tolerability of the new an- or two of them before trying other treatment modalities. The diagnosis and management of the ethosuximide, benzodiazepines (administered rectally) and sulth- epilepsies in adults and children in primary and secondary care. Treatment of pediatric It is usually advocated that they should be tried early on the clinical epilepsy: European expert opinion, 2007. Epilepsy and evidence-based medicine: a vote of conf- dence in expert opinion from the National Institute for Clinical Excellence? Stiripentol in severe myoclonic epilepsy Success is also claimed for the use of intravenous immunoglobulins in infancy: a randomised placebo-controlled syndrome-dedicated trial. Human herpesvirus 6 and 7 in febrile withdrawal of such treatment can usually be achieved. Intermittent oral diazepam prophylaxis in an unblinded randomised controlled trial. J Pediatr trolled trial of ibuprofen syrup administered during febrile illnesses to prevent 1961; 58: 211–218. Clobazam in treatment of refractory the recurrence of febrile seizures in children? A systematic review of randomized epilepsy: the Canadian experience – a retrospective study. Lamotrigine as frst-line drug in child- on Febrile Seizures American Academy of Pediatrics. Febrile seizures: clinical hood absence epilepsy: a clinical and neurophysiological study. Brain Dev 2004; practice guideline for the long-term management of the child with simple febrile 26: 26–29. Lack of efcacy of phenytoin in children pre- frst-line monotherapy in newly diagnosed typical absence seizures: an open-label, senting with febrile status epilepticus. Lamotrigine for patients with juvenile intravenous diazepam for treating febrile seizures in children: prospective ran- myoclonic epilepsy following prior treatment with valproate: results of an open-la- domised study. Exacerbation of juvenile myoclonic epilepsy with lam- trigine for absence seizures in children and adolescents. Ethosuximide, valproic acid, and lamotrig- lamotrigine in juvenile myoclonic epilepsy in adults: a prospective, unblinded ran- ine in childhood absence epilepsy. Topiramate monotherapy for childhood absence seizures: an open label ine in childhood absence epilepsy: initial monotherapy outcome at 12 months. Benefcial efect of antiepileptic medication pathic generalized epilepsy with myoclonic seizures. The efects on cognitive function and behavioural topiramate in Lennox–Gastaut syndrome. Neurolo- problems of topiramate compared with carbamazepine as monotherapy for chil- gy 1999; 52: 1882–1887. Felbamate in the treatment of Lennox–Gastaut syndrome: results benign childhood epilepsy with centrotemporal spikes: a clinical and cognitive of a 12-month open-label study following a randomized clinical trial. Topiramate in Lennox–Gastaut racetam monotherapy to improve language dysfunction associated with benign syndrome: open-label treatment of patients completing a randomized controlled rolandic epilepsy. Anticonvulsant-induced status epilepticus in Len- opoulos syndrome: a case report. Clobazam for the treatment of intractable childhood epilep- by carbamazepine in Panayiotopoulos syndrome.

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This chapter prior to undertaking definitive surgical repair of the fistula will focus on the ligation of intersphincteric fistula tract and many of the other series do so as well purchase super cialis 80 mg without prescription erectile dysfunction 19 years old. The operation is appropriate for and super cialis 80 mg discount erectile dysfunction doctors northern va, in many cases, easier to dissect free from the surround- transsphincteric fistulas with length sufficient enough to per- ing tissues ensuring a successful ligation [3 , 6 ]. The fibers of the internal and external sphincter lithotomy position, under either regional or general anesthe- are separated and the intersphincteric groove is entered. Some surgeons use lithotomy or prone jackknife position the fistula tract is identified (Fig. Bowel prepara- lated, severed, and suture ligated at both ends and severed tion consists of two phospho soda enemas the day before after removal of the fistula probe (Fig. Patients are administered only a single dose of ligature obliterates the internal opening. If the tract length appropriate peri-operative antibiotics intravenously, usually warrants, a portion of the tract may be excised, increasing the cefoxitin, or ciprofloxacin/metronidazole if the patient is distance between the two suture-ligated ends (Fig. At the end of the procedure, a dibucaine- the internal and external sphincter are reapproximated; coated piece of gelfoam is rolled and gently inserted into the the skin is closed loosely. The patients are not admitted for and left open to drain and heal secondarily (Fig. Results/Discussion We prefer to remove a portion of the tract if the length allows it [3]. There was no reported incontinence Department of Surgery, University of Minnesota, 1055 Westgate Drive, Ste 190 , St. Reprinted with wound is closed loosely, and external opening of the tract is enlarged to permission [3 ]. Dissection of intersphincteric groove and identification of fibrotic Drawings courtesy of Russell K. These early reports sug- illustrates the desirable points of any novel sphincter sparing gested a healing rate of 57–82 % at 9–24 weeks follow-up, technique, i. In patients in whom endo- anal ultrasound revealed failure resulting in a simple fistula, Failures the patients were successfully treated with application of silver nitrate or fistulotomy. The series reports an over- categories: early (procedural failure) and late (recurrence). Including these patients in the overall randomized trials is hindered by the suitability of the healing percentage, they observed a 100 % healing rate. No Furthermore, the incontinence score after 6 months was “gold-standard” sphincter sparing technique exists [21 ]. Like other sphincter sparing later studies are minimal and on par with other sphincter techniques, the operation itself is very much dependent on sparing techniques. Subsequent studies have validated the success rates of the initial technique (see Table 16. Total series have varying healing rates; however, they are small anal sphincter saving technique for fistula-in-ano; the ligation of series and none of them have been validated or duplicated. Ligation of intersphincteric Conclusion fistula tract: early results of a pilot study. Does ligation ceric fistula tract compared with advancement flap for complex of the intersphincteric fistula tract raise the bar in fistula surgery? Fibrin glue treatment intersphincteric fistula tract in low transsphincteric fistulas: a new of complex anal fistulas has low success rate. Outcomes with the use of bioprosthetic grafts to reinforce successful closure with anal fistula plug in cryptoglandular fistulas. Ligation of the intersphincteric improve the outcome of transanal advancement flap repair for high fistula tract: an effective new technique for complex fistulas. Dis transsphincteric fistulas by additional ligation of the intersphinc- Colon Rectum. Letter to the editor on “The management of fistula-in- ligation of the intersphincteric fistula tract procedure: the Western ano: a plea for randomized trials and standard reporting of a case Hospital experience. Which tap is used depends on the position of the technique performed for the surgical treatment of complex fistula. Also in the kit are a semicircular or linear stapler and anal fistulas and their recurrences. The optimal nary gentle probing of the tract in order to explore it and to patient positioning is the lithotomic position. The fistuloscope is connected to the Karl Storz of “putting an eye” on the probe and exploring the tract from equipment and to the washing solution bag. This allows precise identifica- tion of secondary tracts and abscess cavities and minimizes the risk of creating false passages on the way to reaching the the Diagnostic Phase internal opening. After this a diatermocoagulation of the fis- tula walls and a hermetic closure of the internal opening are the purpose of this phase is to find the main and secondary performed. The accurate anatomic definition and the precise tracts and abscess cavities and to correctly locate the internal identification of the internal opening, the drainage of associ- fistula opening. At the beginning of the procedure insert a ated sepsis, the destruction of the tract, and the closure of the syringe in the external orifice and inject low-pressure saline internal opening itself are the rationale principles of anal fis- solution in order to obtain a fistula tract dilatation. This technique tissue around the external opening can be removed by elec- comprises two phases: (1) a diagnostic one and (2) an opera- trosurgical knife for ease of entry of the fistuloscope tip and tive one. During the insertion, the washing solution is already running, providing a clear view of the fistula pathway, which Materials appears on the screen (Figs. At this point, it is very important to be patient and wait for an adequate dila- Karl Storz GmbH Video Equipment (Tuttlingen, Germany) tion of the tract. The operating kit includes a fistuloscope guide it using a trans-anally inserted finger. The fistuloscope has an external opening, allows it to be straightened by a counter 8° angled eyepiece, its diameter is 3. Blocking tissue in the tract can be removed using the equipped with an optical channel and also a working and 2 mm forceps to facilitate the progression of the fistuloscope. The operative length is 18 cm without a the orientation of the fistuloscope is correct when the obtu- rator appears in the lower part of the screen. The surgeon follows the fistula pathway using slow left-right and up- down movements. Mori by the complete relaxation of the surrounding tissue induced fistuloscope exits through the internal opening, the rectal by the spinal anesthesia. The fistuloscope helps to straighten the fistula tract by combined movements usually goes out through the internal opening but sometimes between the finger and the fistuloscope. Optimum vision of it is not so easy, as the internal opening might be very narrow: the inside of the fistula is assured by the continuous jet of the in that case, its location is found by viewing the fistuloscope washing solution to the point where you reach the end of the light behind the rectal mucosa. At this point, it’s useful to put fistula pathway which is the internal fistula opening (Fig. Dimming the lights in the operating theatre enables an easy localization of the fistuloscope light in the rectum.

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Opiate agonists-antagonists like buprenorphine are good for moderate analgesia but not recommended for use in critically ill patients cheap 80mg super cialis erectile dysfunction pills over the counter. Ketamine: A powerful analgesic agent which has a good safety profile when used in a variety of conditions cheap super cialis 80 mg mastercard intracavernosal injections erectile dysfunction. It has no hemodynamic depressive action and can be used in septic shock, cardiac disease and across all ages. Combined with sedatives, the dose required comes down and the triple goals of anxiolysis, hypnosis and amnesia can also be met. They also exhibit muscle relaxant and anticonvulsant effects but lack analgesic properties. The ideal level of sedation varies, but in most cases we try to maintain a child who is sleepy and tranquil but easily arousable on verbal stimulus. The right balance needs to be achieved and the risks of both over and under-sedation are real. Dose related hypoventilation and hypotension may be seen but is usually rare under appropriate monitoring. It is also the least lipid-soluble and hence has a delayed onset and prolonged action. It is water soluble at low pH but becomes lipid soluble at body pH and hence is marketed as a solution. The cardiovascular ad respiratory depressive effects are lower with continuous dosing as the peak levels attained are lower than with bolus dosing. Propofol: This is an anesthetic agent which has anxiolytic, hypnotic, sedative and amnestic properties at sub-anesthetic doses. In another study, sedation with propofol was more effective in achieving patient-ventilator synchrony than that with midazolam. Patients sedated with propofol awoke more rapidly and with less variability that those patients sedated with midazolam. Discontinuation results in a 50% drop in serum levels in 10 minutes and the accumulated drug as it comes out of the compartments of distribution, does not attain a therapeutic level. As it reduces the cerebral oxygen consumption, it is also used in place of barbiturates for this purpose. Side effects: the rate of metabolism is prolonged by hepatic dysfunction, age and other sedatives. Infection and acidosis have also been reported and meticulous handling of the solution and lines is necessary. The prolonged sedative and depressive effects and hemodynamic compromise they cause have many intensivists switching to Propofol. Pentobarbital not being available, we use Thiopental, which has greater propensity for myocardial depression with subsequent hypotension which is self defeating when trying to maintain a high mean arterial pressure. This is a neuroleptic agent and associated with several minor and major side effects including the often-fatal neuroleptic malignant syndrome. Hence, the safety profile needs to be considered before routine use is recommended. Another study in children with burns, 9 assessed the adverse effects or reactions after the administration of the drug. This result suggests that the use of haloperidol to treat the acutely agitated and delirious pediatric burn patients is fraught with a number of difficulties and is not completely safe and effective. Although the drug is widely used for adults, it has not gained popularity fro children. Atracurium and Cisatracurium are intermediate acting and do not depend on any end-organ metabolism for their elimination. Vercuronium, an intermediate acting agent has minimal cardiovascular side effects. However, several side effects have been recently reported: delayed recovery, muscle necrosis, accumulation in renal dysfunction. Because of its side effects- hyperkalemia, fasiculations, raised intraocular and intragastric pressure, malignant hyperthermia in muscular disorders bradycardia, prolonged paralysis–it has been replaced by non-depolarizing agents like Rocuronium/Mivicurium, which are fairly short acting. The patient can breathe spontaneously and trigger the ventilator, thereby dictating rate, flow and breath cycling on any patient triggered mode. In certain ventilator strategies, it has been suggested that the non-physiological nature of the intervention may cause agitation and patient ventilator dys-synchrony. In a controlled study, Kahn showed that low tidal volume ventilation was not associated with increased dose or duration of sedatives in patients with acute lung injury. They therefore concluded that sedation administration should not be considered a barrier to implementing a lung-protective ventilation strategy. Here too, continuous infusions may actually result in smoother sedation without ups and downs in the patient’s settings and may actually result in lesser total dosages. Inadequate sedation and pain relief will cause greater patient discomfort, which will go unrecognized by the care giver. Time to wean will be longer and prolonged paralysis may lead to poor respiratory muscle function compounding the problem. These agents should therefore be used when gas exchange is inadequate without full control; when the patient is on settings incompatible with any degree of comfort e. In any of these situations, the agents should be withdrawn at the earliest and all methods of establishing a patient triggered mode explored. However, continuous infusions of sedative drugs in the intensive care unit may prolong the duration of mechanical ventilation, prolong the length of stay in the intensive care unit and the hospital, impede efforts to perform daily neurologic examinations, and increase the need for tests to assess alterations in mental status. He concluded that in patients receiving mechanical ventilation, daily interruption of sedative-drug infusions decreases the duration of mechanical ventilation and the length of stay in the intensive care unit. Standardized protocols and medical treatment pathways, using guidelines formulated by using the best available medical knowledge, provide a systematic approach to providing less variable medical care that can decrease errors and improve the effectiveness of treatment. Sedation and weaning are two areas in which recent clinical studies have demonstrated the ability of protocols to improve patient outcome. In one trial dexmedetomidine infusions (1) did not result in clinically significant respiratory depression, (2) decreased rather than increased the apnea/hypopnea index, and (3) exhibited some similarity with natural sleep. This is a noninvasive marker of deep sleep with values from 0 (no brain activity) to 100 (full consciousness). The accuracy of monitoring is said to result in lower doses of drugs and more complete lack of awareness for the procedures done. No physician should use a drug he or she is unfamiliar with or whose side effects cannot be recognized and controlled. Sedation, analgesia and paralysis are strictly meant for the patient’s comfort not that of the doctor or nursing staff. The art and science of sedation is an integral part of the training of any intensivist. The minimum dosage and duration required can be maintained with periodic assessments. The drugs used are only one of many that the patient will receive and interactions should be kept in mind. Finally, a happy patient is one who remembers little or nothing of the entire period of ventilation. Continuous intravenous infusion of lorazepam and midazolam in the treatment of acute agitation syndromes during mechanical ventilatory support.

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Miller demonstrated the role of the thymus in immu- T and B lymphocytes cooperate with one another in the pro- nity while in pursuit of Gross leukemia virus in neonatal duction of an immune response super cialis 80mg sale impotence risk factors. Good and associates helped establish the role of the produced some of the frst evidence that T and B cells act thymus in the education of lymphocytes and made fundamen- synergistically in the humoral response order super cialis uk erectile dysfunction treatment sydney. Various phenomena, tal contributions to understanding the ontogeny and phylog- such as the switch from forming one class of immunoglobu- eny of immunity. B cells stimulated by antigen in which no cell signal His insight that the lymphocytes recirculate via the thoracic was given continued to produce IgM antibody. Such antigens duct made radical changes in the understanding of the role of were referred to as thymic-independent antigens, and others lymphocytes. In 1966, Harris, Hummeler, and Harris clearly requiring T-cell participation as thymic-dependent antigens. Thus, immune regulation was considered investigator whose principal contribution to immunology was to depend in part upon a delicate balance between helper T the demonstration that lymphocytes recirculate via the tho- lymphocytes and these T-suppressor cells. Later advances in racic duct, which radically changed the understanding of the molecular biology cast some doubt on the suppressor con- role lymphocytes play in immune reactions. The Astrid Elsa Fagraeus-Wallbom (1913– ), Swedish inves- suppressor T cell was described as a subpopulation of lym- tigator noted for her doctoral thesis which provided the frst phocytes that diminish or suppress antibody formation by B clear evidence that immunoglobulins are made in plasma cells. The inability to confrm the pres- National Bacteriological Laboratory, and in 1965, professor of ence of receptor molecules on their surface has cast a cloud immunology at the Karolinska Institute in Stockholm. She also over the suppressor cell; however, functional suppressor-cell investigated cell membrane antigens and contributed to the effects are indisputable. Antibody Production in Relation to the Development of Plasma Cells, Stockholm, 1948. In 1975, Köhler and Milstein successfully fused splenic lym- phocytes from mice forming antibody with tumor cells to Milan Hasek (1925–1985), Czechoslovakian scientist whose produce what they called a hybridoma. The spleen cells con- contributions to immunology include investigations of immu- ferred the antibody-forming capacity, while the tumor cells nologic tolerance and the development of chick embryo provided the capability for immortality or endless reproduc- parabiosis. At the 1980 International Congress of became interested in the bursa of the chicken and removed Immunology held in Paris, Henry Kaplan and Lennart Olsson the organ from the cloacas of some test animals for study. Glick and associates sent an article to Science, which was refused, so they published their fnd- ing in Poultry Science. Harold Wolfe, at the University of Wisconsin, Madison, understood the importance of this fact, and the hunt began to identify the two big classes of lympho- cytes, T and B cells, the latter being so called because they are “bursa derived. Davies in London con- ducted studies with lethally irradiated mice, which proved that both bursa-derived and thymus-derived lymphocytes were needed to produce an immune response, T and B cooperation. Much of his work focused on immunodefciency diseases and the role of the thymus and the bursa of Fabricius in immunity. He and his colleagues demonstrated the role of the thymus in the education of lymphocytes. History of Immunology 37 Phenomenon of Local Tissue Reactivity in 1937 that the injection of one dose of endotoxin into a tumor site followed 24 h later by an intravenous injection of endotoxin resulted in a local Shwartzman reaction, leading to hemorrhage and necrosis in the tumor. Studies on transplantable tumors in inbred strains of mice are discussed elsewhere in this volume. They postulated that somatic mutations of cells with the potential to develop into malignant tumors are recognized as alien by antigenic determinants not present on normal cells, and are destroyed by immunocytes that police the bodily tissues to eliminate cells not recognized as self by seek-and-destroy tactics. They theorized that failure of the immune system to carry out this function could lead to proliferation of these aberrant cells into a tumor mass too great to be eliminated by immunological figure 1. Indirect evidence offered in support of such a concept included the increased frequency of tumors in children with proposed an altered-self concept and dual recognition by T immunodefciency of the T-cell system, tumors that appear cells. Further in transplant patients, and the increase in tumor incidence investigations of T cells have proceeded at an unprecedented with advancing age. Björkman described a prominent groove defned by Kaliss as the “successful establishment of a tumor on the upper surface of the molecule which, surprisingly, contained antigen even after purifcation. TumOr immuniTy It has long been the dream of medical scientists to be able to resist cancer by immunological methods. William Coley, in 1891, observed that cancer patients who developed cer- tain infections derived benefcial results. This led him to inject mixtures of bacterial toxins into cancer patients in an attempt to alter the pathogenesis of their malignant dis- ease. His efforts met with success in 1893 when an inoper- able tumor in a 16-year-old boy receiving bacterial toxin regressed and disappeared over several months of treat- ment. Coley applied his treatment to 250 other cancer vic- tims whose survival ranged from 5 to 72 years. Perhaps because of the unavailability of suffcient immunological information to understand Coley’s experiments at the time, their signifcance was not appreciated until years later. This host) as a consequence of the tumor’s contact with specifc appears to have an immunologic basis. It should be pointed out that a comprehensive or exhaustive review of the literature of autoimmunity was not our intention. Snell and associates studied tumor enhancement using inbred By contrast, we only outline the milestones in the development strains of mice of known genetic constitution. These investi- of autoimmunity, which has signifcance not only for selected gators aimed at solving the mechanism and other aspects of disease mechanisms but also for many features of normal immunological enhancement. Karl and Ingegerd self-antigens failed to elicit an immune response in the autol- Hellström demonstrated immune complexes that acted as ogous host. On discovering that goats immunized with their blocking factors in the serum of certain cancer patients. They own erythrocytes failed to produce autoantibodies, Ehrlich subsequently discovered unblocking factors capable of elimi- formulated a concept of “horror autotoxicus” to explain the nating complexes that interfere with the immune system of the animal body’s failure to mount an immune response against tumor-bearing host. Nevertheless, he recognized also that autoimmunity treatment occurred following the demonstration that tumor- might occur as an aberration and lead to disease. He found that immunity could constitute a part of the etiopathogenesis of ligation and atrophy of methylcholanthrene-induced sarcoma selected disease states. An investigator of rare genius and in mice of the C3H-He pure line were followed by immunity. At frst Subsequently, Donath and Landsteiner showed that autoanti- there was great hope that the detection of this antigen in the bodies were responsible for paroxysmal cold hemaglobinuria blood sera of patients might aid in the diagnosis of cancer. Wassermann and colleagues reported a diagnostic Unfortunately, patients with other types of cancer as well as serologic test for syphilis based on autoantibodies. Meanwhile, certain nonneoplastic diseases may experience derepression many claims were made that one type of disease process or of α gene encoding its formation. For many years immunologists accepted Ehrlich’s have undergone surgical excision of colonic cancer, to signal dictum that the animal body would not form harmful immu- any recurrence or metastasis of the malignancy. Burkitt lymphoma, a B-cell malig- Once early investigators began to use antigens from diverse nancy, which shows strong evidence of association with the sources, Metchnikoff and other pathfnders in immunology History of Immunology 39 reported the development of cytotoxic antibodies in animals 3. Associated with this response, the animal develops immunized with spermatozoa and tissue cells, thereby initiat- pathological changes that are basically similar to ing the concept of autoallergy in which an animal mounts an those of the human; autoimmune response against its own self-antigens.