Coalescing beneficial host and deleterious antiparasitic actions as an antischistosomal strategy.

Conventional approaches for antiparasitic drug discovery center upon discovering selective agents that adversely impact parasites with minimal host side effects. Here, we show that agents with a broad polypharmacology, often considered 'dirtier' drugs, can have unique efficacy if they combine deleterious effects on the parasite with beneficial actions in the host. This principle is evidenced through a screen for drugs to treat schistosomiasis, a parasitic flatworm disease that impacts over 230 million people. A target-based screen of a Schistosoma serotoninergic G protein coupled receptor yielded the potent agonist, ergotamine, which disrupted worm movement. In vivo, ergotamine decreased mortality, parasite load and intestinal egg counts but also uniquely reduced organ pathology through engagement of host GPCRs that repressed hepatic stellate cell activation, inflammatory damage and fibrosis. The unique ability of ergotamine to engage both host and parasite GPCRs evidences a future strategy for anthelmintic drug design that coalesces deleterious antiparasitic activity with beneficial host effects.

Ergotamine-induced vasospastic ischemia mimicking arterial embolism: unusual case.

Ergotamine toxicity is an important and rare condition, including tachycardia, arterial spasm which occurring as a result of accidental overdosing or drug interactions. We assessed the consequences of delayed diagnosis of peripheral arterial vasoconstriction occurring after simultaneous macrolide use by a 35-year-old woman using an ergot-derived drug for migraine. Diagnosis of ergotamine intoxication begins with suspicion. Interventional radiologists and surgeons should be aware of this acute dangerous condition.

A case report of multiple fractures with arterial vasospasm associated with ergotamine use.

Vasospasm that develops in association with ergotamine use is a rarely seen but well-understood complication. A case is presented here of multiple fractures in which arteriospasm affecting all the arteries of the lower limb on the same side occurred 10 days post-trauma. In this case, the arteriospasm resulting from ergotamine addiction and high doses of ergotamine, which may be confused with post-traumatic angiospasm, was treated with a marcaine infusion by epidural catheter and heparin, iliomedin and nitronal infusion intravenously. This clinical condition should be borne in mind for all trauma cases determined to have arterial vasospasm, and the use of ergotamine must be queried when taking the anamnesis from the patient.

[Digital necrosis in hand by uncommon mechanism]. / Necrosis digital en la mano por mecanismo infrecuente.

A 43-year-old, non-smoking man presented with acute ischemic lesions of his left hand. He had been taking beta-blockers for his arterial hypertension. The day before the occurrence of these acute lesions, he self medicated with a drug containing ergotamine and caffeine because of a headache. About one hour after mild trauma to the hand, he noticed intense cyanosis accompanied by severe pain in the fingers that progressed to digital necrosis. Hematological tests, hand radiography, echo Doppler, and nailfold videocapillaroscopy were performed. Digital necrosis owing to an unusual combination of ischemic mechanisms is assumed.

Trigeminal autonomic cephalalgias. Part 1: cluster headache.

Cluster headache is characterized by severe, strictly unilateral pain attacks lasting 15 to 180 minutes localized to orbital, temporal, and midface areas accompanied by ipsilateral autonomic features. It represents 1 of 3 primary headaches classified as trigeminal autonomic cephalalgias. While its prevalence is small, it is not uncommon for cluster headache patients to present at dental offices seeking relief for their pain. It is important for oral health care providers to recognize cluster headache and render an accurate diagnosis. This will avoid the pitfall of implementing unnecessary and inappropriate traditional dental treatments in hopes of alleviating this neurovascular pain. The following article is part 1 of a review on trigeminal autonomic cephalalgias and focuses on cluster headache. Aspects of cluster headache including its prevalence and incidence, genetics, pathophysiology, clinical presentation, classification and variants, diagnosis, medical management, and dental considerations are discussed.

Migraine development, treatments, research advances, and anesthesia implications.

The purpose of this course is to update anesthesia providers on the phenomenology and biological mechanisms underlying migraines. As experts in pain management who encounter this common ailment, anesthesia providers frequently are consulted to assist in patient care. Effective assessment and treatment of migraine will lead to better anesthesia management. Knowledge of preventive measures of surgical patients with migraine history can avoid events that can elicit a headache attack. The clinical implications of migraine disorder--and each patient's preventive medication profile--is relevant to safe, accommodative anesthesia nursing care. Research advances in migraine treatment may profoundly improve our current pain relief measures. Adequate knowledge of the development, treatments, and research advances concerning migraine will improve patient care.

Reactive nodular fibrous pseudotumor involving the pelvic and abdominal cavity: a case report and review of literature.

There are several entities that can present with multiple nodular lesions within the peritoneal cavity, such as "disseminated peritoneal leiomyomatosis," "peritoneal fibrosis," "calcifying fibrous pseudotumor," and the recently described lesion of "reactive nodular fibrous pseudotumor of the gastrointestinal tract and mesentery." Here we present one such lesion in a 28-year-old woman with a history of dysmenorrhea and ergotamine use for migraine attacks. Intraoperative exploration of our patient disclosed numerous nodules located throughout the pelvic and abdominal peritoneum. Histopathologically, these lesions were fibrocollagenous nodules composed of sparse wavy spindle cells within hyalinized "keloid-like" collagen surrounded by an inflammatory infiltrate. Some of the nodules were associated with small foci of endometriosis. We believe this lesion is best described by the term "reactive nodular fibrous pseudotumor" and that endometriosis and the use of ergotamine derivatives may be contributing factors.

Lower-half facial migraine: a report of 11 cases.

PURPOSE: Vascular pain of the face constitutes a variant of pain of the head, and includes migraine, cluster headache, paroxysmal hemicrania, and a facial variant of the so-called lower-half migraine. Lower-half facial migraine is a condition difficult to classify; according to the international classifications it could not be found as an individual entity. The objective of the present study is to determine the difficulties we encountered in diagnosis, the ineffective treatments provided, and the pharmacologic treatment effect. PATIENTS AND METHODS: A study is made of 11 cases of lower-half facial migraine, corresponding to 10 women and 1 man (mean age, 35 years), commenting on the clinical characteristics of the disorder and its treatment options. The location of the pain often mimics dental pain, and can lead to a mistaken diagnosis and to the application of inappropriate therapeutic measures. Forty-five percent of the patients had a history of endodontic treatment before the development of pain in the initially affected quadrant. Once the pain had developed, extractions were carried out in 36% of cases in an unsuccessful attempt to secure symptom relief. Our pharmacologic treatment consisted of ergotamine in 9 cases and the remaining 2 patients received indomethacin. RESULTS: Nine patients (82%) improved as a result of treatment, with an important reduction in the frequency of the pain episodes and intensity of pain. One patient failed to respond to ergotamine, while another patient failed to improve with indomethacin. Both were prescribed only minor analgesics. CONCLUSION: The treatment of migraine occurring in the face is no different than that provided for pain occurring in the head.

[Treatment of cluster headache]. / Le traitement de l'algie vasculaire de la face.

INTRODUCTION: The cluster headache (CH) is one of the most severe types of head pain. It is a typical example of a periodic disease and the International Headache Society classification recognizes two forms of this disease: episodic and chronic CH. Its prevalence is about 0.1 to 0.4% in the general population. PATHOPHYSIOLOGY: A global hypothesis is still lacking to explain the pain, the vasodilation, the autonomic features (ipsilateral lacrimation, conjunctiva injection, rhinorrhea, partial Horner syndrome, etc.) and the periodicity of the CH. Pain and vasodilation seem secondary to an activation of the trigeminal vascular system and the periodicity of the attacks is thought to be due to a dysfunction of hypothalamic biologic clock mechanisms. Treatment of acute CH attacks. The most effective agents are oxygen inhalation and subcutaneous sumatriptan, a 5HT1B and D receptor agonist which has vasoconstrictor and anti-neurogenic inflammation properties by blocking the release from the trigeminal-sensitive fibers of neuropeptides such as CGRP and substance P. With subcutaneous sumatriptan, headache relief is very rapid, within 5 to 10 min. Prophylactic treatment of CH: The number of attacks per day varies from one to three, but some patients can have four to eight per day and acute treatments fail to provide sufficient relief or give rise to side-effects. Several different regimens have been proven effective. FUTURE PROSPECTS AND PROJECTS: Contraindications and side-effects of the drugs limit the choice of the prophylactic treatment: corticosteroids in a tapering course, verapamil and methysergide are the most useful treatments of the episodic form. Lithium carbonate is more effective for the chronic stage of CH, but side-effects are often troublesome. Numerous other medications have been used for prophylaxis: valproate, capsaicin, beta-blockers. Unfortunately, double-blind studies are often lacking and are difficult to realize due to spontaneous variable remission of episodic CH. When adequate trials of drug therapies show a total resistance to the treatments, surgery may be considered. Radiofrequency trigeminal rhizotomy is the treatment of choice with 70% of beneficial effects. Risks and complications have to be discussed in balance with the benefit of the different surgical procedures.

Tratamento farmacológico da migrânea: uma revisäo / Pharmacological treatment of migraine: a review

Migrânea é uma desordem caracterizada por cefaléias episódicas associadas a sintomas com náuseas, vômitos, fotofobia, fonofobia e fraqueza. Ë uma das queixas mais comuns encontradas por médicos gerais e neurologistas, com prevalência estimada em 12 por cento da populaçäo e predomínio em mulheres. Ë um distúrbio que pode incapacitar os pacientes de realizar atividades usuais, determinando significante impacto econômico. Há três formas principais de manejo desta doença: evitar os potenciais fatores desencadeantes da cefaléia, tratamento efetivo das crises agudas com medicaçöes adequadas e uso regular das medicaçöes preventivas. Apesar de mudanças no estilo de vida e alternativas näo farmacológicas podem ajudar a impedir algumas crises, o suporte principal é o uso precoce das medicaçöes. Atualmente, há uma grande variedade de drogas disponíveis, abrangendo desde os antiinflamatórios näo esteróides (AINEs) até novas drogas mais efetivas, como os agonistas serotoninérgicos 5HTIB/ID ou triptanos. O objetivo desta revisäo é sumarizar as informaçöes presentes na literatura a respeito dos mais diversos esquemas farmacológicos disponíveis para o tratamento agudo e preventivo migrânea

[Roles of arterial dysplasia, chronic ergotism and other factors in a case multiple spontaneous arterial dissections]. / Rôles d'une dysplasie artérielle, d'un ergotisme chronique et d'autres facteurs dans un cas de dissections artérielles multiples spontanées.

INTRODUCTION: Spontaneous dissection of cervical and visceral arteries are rare and usually associated with an underlying arterial disease. EXEGESIS: The authors report the unusual case of a 50-year-old woman with high blood pressure who presented spontaneous dissection of cervico-cephalic, renal and hepatic arteries and of the descending aorta. She had been taking ergotamine tartrate for ten years for migraine. She also suffered from Raynaud's syndrome worsened by treatment. CONCLUSION: The respective roles of arterial dysplasia, chronic ergotism, renovascular hypertension and migraine are discussed.

[Intractable vomiting, convulsions and megaloblastic anemia: anamnesis, key to diagnosis]. / Vomissements incoercibles, convulsions et anémie mégaloblastique: l'anamnèse, clé du diagnostic.

In July 1996 a 43-year-old illiterate Hispanic woman presented with uncontrollable vomiting, palpitations and confusion. In 1994, despite several hospitalisations in other medical centres where a cerebral CT-scan, oesogastroduodenoscopy, colonoscopy and abdominal ultrasound were performed, no satisfactory diagnosis could be found. A psychiatric origin was finally considered. On admission, the laboratory findings showed severe metabolic alkalosis with associated hypokalaemia, confirmatory evidence of vomiting. The ECG showed tremendous P waves (5 mV) in the standard derivations, which can be explained by the hypokalaemia, with multiple supraventricular extrasystoles. Echocardiography and pulmonary scintigraphy ruled out pulmonary hypertension and a pulmonary embolus. After additional discussion with her daughter we discovered that the patient had been treating chronic headaches for years with 4-5 Cafergot-PB suppositories per day. This drug contains 2 mg ergotamine tartrate, 100 mg butalbital, 100 mg caffeine and 0.25 mg belladona alkaloids. As is known, vomiting is a classical symptom of ergotamine intoxication. After rehydration we discovered a megaloblastic anaemia with a folate deficiency compatible with chronic barbiturate intoxication. Folate and iron supplementation allowed a rapid normalisation of the haemoglobin values. Five months after having stopped the Cafergot-PB, the patient was well and did not vomit anymore. The headaches were treated with chlorpromazine with a good result. Despite sophisticated technical means, the diagnosis could only be established after a thorough history taking. This message should be heard in times when high tech medicine tends to obscure the place of a good history taking!

Cefaléias: diagnóstico e conduta no serviço de emergência / Headache: diagnostic and management at emergence service

A cefaléia é um dos sintomas mais comuns nos serviços médicos de emergência, sendo manifestaçäo de doença sistêmica ou neurológica. o objetivo deste estudo é conhecer os principais quadros clínicos, o diagnóstico diferencial e o tratamento.

Coexistence of migraine and idiopathic intracranial hypertension without papilledema.

Eighty-five patients with refractory transformed migraine type of chronic daily headache (CDH) had spinal tap as a part of diagnostic work-up. Twelve had increased intracranial pressure without papilledema, transient visual obscurations, or visual field defects. The headache profile of these 12 patients was not different from that of transformed migraine type of CDH. Acute headache exacerbations responded to specific antimigraine agents such as ergotamine, dihydroergotamine (DHE), and sumatriptan, whereas prophylactic antimigraine medications were only partially helpful. Addition of agents such as acetazolamide and furosemide, after the diagnosis of increased intracranial pressure, resulted in better control of symptoms. These observations suggest a link between migraine and idiopathic intracranial hypertension that needs further research. In refractory CDH with migrainous features, a spinal tap to exclude coexistent idiopathic intracranial hypertension without papilledema may be indicated.

Aortic and mitral valve disease induced by ergotamine therapy for migraine: a case report and review of the literature.

A case of aortic and mitral valve disease associated with ergotamine abuse is reported. A 34-year-old woman presented with dyspnea after a long standing history of peripheral vascular pathology associated with ergotamine abuse. Cardiac dysfunction was rapidly progressive. At surgery, nodular thickening of both valves and fusion of the posterior leaflet of the mitral valve were seen. Microscopy revealed proliferation of myofibroblasts with little destruction of normal valvular elements. The similarity to lesions in carcinoid heart disease and in methysergide-associated valvular disease suggests direct stimulation of myofibroblast growth by serotonin agonist effect.