Participation of TLR2 and TLR4 in Cytokines Production by Patients with Symptomatic and Asymptomatic Chronic Chagas Disease.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a serious public health issue. Its evolution involves an acute stage, characterized by no specific symptoms, and the chronic stage during most individuals are asymptomatic, but about 30-40% of them become symptomatic presenting the cardiac or digestive disease. Host immune response mechanisms involved in symptomatic or asymptomatic chronic disease are not fully understood. The pro-inflammatory cytokines are crucial in host resistance. However, a fine control of this inflammatory process, by action of anti-inflammatory cytokines, is necessary to avoid tissue injury. This control was found to be responsible for no clinical manifestations in asymptomatic individuals. Toll-like receptors (TLRs) are extremely important in defining the cytokine profile released in response to a micro-organism. We found that patients with the cardiac form predominantly released the pro-inflammatory cytokines: IFN-γ, TNF-α and IL-17 with the involvement of both, TLR2 and TLR4. In contrast, patients with asymptomatic disease release predominantly the anti-inflammatory cytokines IL-10 and TGF-ß, but also with TLR2 and TLR4 participation. The mechanisms by which stimulation of the same TLRs results in release of different pattern of cytokines, depending on the patients group that is being evaluated, are discussed.

Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate.

Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.

Gilles de la Tourette syndrome: clinical features of 75 cases from Argentina.

A series of 75 cases of Gilles de la Tourette syndrome (GTS) from Argentina, whose ages ranged from 6 to 55 with a mean of 20.02, were evaluated to compare findings with those reported for other countries. Mean age at onset was 7.44 years and mean overall duration of symptoms was 12.58 years; 6.7% of cases were mild, 49% moderate and 44.3% severe. Most frequent presenting motor tics were excessive blinking in 41 followed by head jerking in 16 and eye winking in six, while phonic tics included coprolalia in 28.0%, echolalia in 17.5% and palilalia in 10.8%. Abnormal perinatal events were reported in 40.5%, while positive family history for tics was present in 26.66%. Obsessive-compulsive behaviour was evident in 66% and attention deficit disorder in 16% of cases. Self-injurious behaviour comprised onychophagia in 28 patients, lip-biting in seven and self-slapping in eight cases. Almost half of our patients were initially interpreted as having a psychogenic disorder indicating that GTS in Argentina is most likely underdiagnosed. It may be concluded that the overall pattern of GTS is not dissimilar to that described for European, Asian and American populations, thus highlighting the previously recognized cross-cultural uniformity.

L-dopa malabsorption in a parkinsonian patient with Strongyloides stercoralis duodenitis.

We report a parkinsonian patient initially responding to L-dopa who developed a severe loss of drug efficacy due to Strongyloides stercoralis duodenitis. The patient was put on mebendazole and metronidazole, and the parasitosis abated, allowing L-dopa reduction by 33%. Our patient illustrates the advisability of searching for Strongyloides stercoralis when L-dopa malabsorption is suspected in Parkinson's disease.

Distonías craneales: perfil clínico y neurofarmacológico en 123 casos / Cranial dystonias: clinical and neuropharmacological profile in 123 cases

El blefaroespasmo aislado (BE) y/o asociado a distonía oromadibular (DOM) constituye una de las formas más frecuentes de distonía focal/segmentaria de inicio en la edad adulta. En los últimos 10 años evaluamos 123 pacientes con BE y BE + DOM. Observamos una predominancia de 3 a 1 en mujeres sobre varones, con una edad promedio de inicio de los síntomas de 52 años. Si bien algunos pacientes presentaron un comienzo unilateral, todos evolucionaron en forma bilateral. La remisión espontánea de los síntomas ocurrió en sólo 3 pacientes. El error diagnóstico más frecuente consistió en interpretar este cuadro como psicógeno u ocular. Los estudios por imágenes (TC y MRI) demostraron anormalidades en 12 casos que correspondieron a lesiones en ganglios basales en 6 de los mismos. En nuestra serie, 4 pacientes presentaron historia familiar de distonía craneal. El tratamiento de elección fue la administración local por vía subcutánea de toxina botulínica. Estos hallazgos son homologables a otras series internacionales. Creemos que el reconocimiento clínico-epidemiológico de esta afección, a menudo incapacitante, facilitará un mejor y más rápido diagnóstico y ofrecerá una posibilidad terapéutica sencilla que demuestra un alto grado de seguridad y eficacia (AU)

Distonías craneales: perfil clínico y neurofarmacológico en 123 casos / Cranial dystonias: clinical and neuropharmacological profile in 123 cases

El blefaroespasmo aislado (BE) y/o asociado a distonía oromadibular (DOM) constituye una de las formas más frecuentes de distonía focal/segmentaria de inicio en la edad adulta. En los últimos 10 años evaluamos 123 pacientes con BE y BE + DOM. Observamos una predominancia de 3 a 1 en mujeres sobre varones, con una edad promedio de inicio de los síntomas de 52 años. Si bien algunos pacientes presentaron un comienzo unilateral, todos evolucionaron en forma bilateral. La remisión espontánea de los síntomas ocurrió en sólo 3 pacientes. El error diagnóstico más frecuente consistió en interpretar este cuadro como psicógeno u ocular. Los estudios por imágenes (TC y MRI) demostraron anormalidades en 12 casos que correspondieron a lesiones en ganglios basales en 6 de los mismos. En nuestra serie, 4 pacientes presentaron historia familiar de distonía craneal. El tratamiento de elección fue la administración local por vía subcutánea de toxina botulínica. Estos hallazgos son homologables a otras series internacionales. Creemos que el reconocimiento clínico-epidemiológico de esta afección, a menudo incapacitante, facilitará un mejor y más rápido diagnóstico y ofrecerá una posibilidad terapéutica sencilla que demuestra un alto grado de seguridad y eficacia

Bruxism secondary to chronic antidopaminergic drug exposure.

Eight cases of diurnal bruxism (DB) secondary to long-term antidopaminergic drug exposure are reported. Five exhibited a grinding pattern, one a clenching form, and two a mixed type. An odontological etiology was absent throughout. EMG recordings disclosed two distinct patterns of muscle activity, one with brief rhythmic, forceful contractions and the other featuring sustained prolonged contractions. Surface EMG and EEG monitoring during a 24-h period confirmed the absence of bruxism during sleep. Several drug trials failed to provide relief. Our findings support DB as a focal tardive dystonia syndrome.

Hemiballism in a patient with partial motor status epilepticus treated with phenytoin.

A 13-year-old girl developed left partial motor status epilepticus with severe postictal hemiparesis. Magnetic resonance imaging showed a right frontoparietal hyperintense T2 weighted signal. Treated with phenytoin, carbamazepine and phenobarbital, seizures subsided but left choreic-like flinging movements, consistent with hemiballism, presented 2 days later. On phenytoin withdrawal, symptoms gradually remitted with mild residual dystonia at 14 months follow-up. It is speculated that the lesion might have rendered the cortex more susceptible to phenytoin, inducing unilateral toxicity.

Treatment of Tourette's syndrome with calcium antagonists.

Six males and one female with chronic tic disorders, whose ages ranged from 12 to 31 years, were evaluated before treatment, after 1 month on placebo, after a single 10 mg nifedipine dose (three patients), and monthly while on flunarizine 10-15 mg (mean dose of 13 mg). None of the patients receiving nifedipine improved, but treatment with flunarizine significantly decreased both motor and phonic tic severity and frequency in all but one patient. Side effects included mild transient headaches in one patient, depression in one, and bradykinesia in two. Although a double-blind study is essential to validate our findings, results suggest that flunarizine is a useful drug in the treatment of Gilles de la Tourette syndrome.

[Treatment of blepharospasm with botulinum toxin]. / Tratamiento del blefaroespasmo con toxina botulínica.

Blepharospasm is a relatively frequent cranial dystonia which may be seen either alone or related to orofacial-mandibular dystonia (Meige's syndrome). In its maximum degree it can cause functional blindness.Twelve patients with blepharospasm (4 essential and 8 Meige's syndrome) who had been previously treated unsuccessfully with drugs (trihexyphenidyl, biperiden, carbamazepine, lithium, baclofen, lisuride, imipramine, clonazepam and butyrophenones) were treated for 12 months with periocular injections of botulinum toxin (BOTOX). A "low" dose of 12,5 U per eye was employed. With this dose, eleven out of twelve patients experienced significant improvement which lasted from five to fifteen weeks. The only nonresponder obtained complete relief upon duplicating the dose. The only side effect was uni or bilateral ptosis in six patients which improved completely in seven to twenty one days. One patient developed a peripheral facial palsy with complete remission in nineteen days. No systemic side effects were noted. There was only one desertion from this study due to depression enhanced by prolonged (21 days) ptosis. All patients (including the deserter) agreed that treatment with BOTOX provided more relief than any other previous therapeutic method. Our results confirm those obtained by others but a more prolonged study is needed to better evaluate long term effects.

Blepharoclonus and parkinsonism associated with aqueductal stenosis.

A 28-year-old man with a history of congenital hydrocephalus due to aqueductal stenosis shunted at 45 days of age is presented. At age 4 years the valve had to be removed because of septicemia. Twenty-three years later he developed parkinsonian signs and abnormal, involuntary rhythmic contractions of the eyelids. The latter were elicited on gentle eye closure. Parkinsonism promptly improved after ventriculoperitoneal shunting, but blepharoclonus persisted unchanged.

Tratamiento del blefaroespasmo con toxina botulínica / Treatment of blepharospam with botulinum toxin

El blefaroespasmo, ya sea aislado o en el contexto de una disquinesia oro-facio-mandibular (síndrome de Meige) es una distonía cranial relativamente frecuente. En su máxima expresión puede dar origen a marcada minusvalía e incluso ceguera funcional. Doce pacientes con respuesta poco satisfactoria a tratamientos medicamentosos (trihexifenidilo, hiperideno, imipramina, carbamazepina, baclofén, litio, lisuride, clonazepam, butirofenonas) fueron tratados con inyecciones perioculares de toxina botulínica (Botox), utilizando una dosis "baja" de 12,5 UI por ojo. Once de los doce pacientes obtuvieron mejoria significativa que duró entre cinco y quince semanas. Una sola paciente no respondió y lo hizo al duplicar la dosis de toxina inyectada. Los únicos efectos secundarios observados fueron ptosis uni o bilateral en 6 pacientes, reversible antes de los 21 días de la inyección y no se observaron efectos secundarios sistemáticos. Una paciente tuvo una parálisis facial periférica de 19 días de duración con remisión completa. Hubo una sola deserción del estudio en una paciente depresiva con ptosis prolongada (21 días). Todos los pacientes (inclusive la desertora) coincidieron en que el tratamiento con Botox fue más eficaz que cualquier ensayo medicamentoso previo. A pesar que estos resultados son similares a comunicaciones previas, creemos aconsejable acumular experiencia para evaluar los resultados a largo plazo

Tratamiento del blefaroespasmo con toxina botulínica. / [Treatment of blepharospasm with botulinum toxin]

Blepharospasm is a relatively frequent cranial dystonia which may be seen either alone or related to orofacial-mandibular dystonia (Meiges syndrome). In its maximum degree it can cause functional blindness.Twelve patients with blepharospasm (4 essential and 8 Meiges syndrome) who had been previously treated unsuccessfully with drugs (trihexyphenidyl, biperiden, carbamazepine, lithium, baclofen, lisuride, imipramine, clonazepam and butyrophenones) were treated for 12 months with periocular injections of botulinum toxin (BOTOX). A [quot ]low[quot ] dose of 12,5 U per eye was employed. With this dose, eleven out of twelve patients experienced significant improvement which lasted from five to fifteen weeks. The only nonresponder obtained complete relief upon duplicating the dose. The only side effect was uni or bilateral ptosis in six patients which improved completely in seven to twenty one days. One patient developed a peripheral facial palsy with complete remission in nineteen days. No systemic side effects were noted. There was only one desertion from this study due to depression enhanced by prolonged (21 days) ptosis. All patients (including the deserter) agreed that treatment with BOTOX provided more relief than any other previous therapeutic method. Our results confirm those obtained by others but a more prolonged study is needed to better evaluate long term effects.

Tratamiento del blefaroespasmo con toxina botulínica / Treatment of blepharospam with botulinum toxin

El blefaroespasmo, ya sea aislado o en el contexto de una disquinesia oro-facio-mandibular (síndrome de Meige) es una distonía cranial relativamente frecuente. En su máxima expresión puede dar origen a marcada minusvalía e incluso ceguera funcional. Doce pacientes con respuesta poco satisfactoria a tratamientos medicamentosos (trihexifenidilo, hiperideno, imipramina, carbamazepina, baclofén, litio, lisuride, clonazepam, butirofenonas) fueron tratados con inyecciones perioculares de toxina botulínica (Botox), utilizando una dosis "baja" de 12,5 UI por ojo. Once de los doce pacientes obtuvieron mejoria significativa que duró entre cinco y quince semanas. Una sola paciente no respondió y lo hizo al duplicar la dosis de toxina inyectada. Los únicos efectos secundarios observados fueron ptosis uni o bilateral en 6 pacientes, reversible antes de los 21 días de la inyección y no se observaron efectos secundarios sistemáticos. Una paciente tuvo una parálisis facial periférica de 19 días de duración con remisión completa. Hubo una sola deserción del estudio en una paciente depresiva con ptosis prolongada (21 días). Todos los pacientes (inclusive la desertora) coincidieron en que el tratamiento con Botox fue más eficaz que cualquier ensayo medicamentoso previo. A pesar que estos resultados son similares a comunicaciones previas, creemos aconsejable acumular experiencia para evaluar los resultados a largo plazo (AU)

Movement disorders and depression due to flunarizine and cinnarizine.

Over the last few years, cases of movement disorders induced by flunarizine and cinnarizine have been increasingly reported. We describe a series of 101 patients, whose ages ranged from 37 to 84 years (mean 69.1), developing abnormal movements frequently associated with depression, secondary to treatment with either or both drugs. Symptoms closely resembled those induced by neuroleptic drugs and remitted on drug discontinuance in all but five cases after 5-22 months' follow-up. Whether or not such undesirable side effects are attributable to calcium antagonism and/or dopamine receptor blockade, long-term treatment with flunarizine or cinnarizine should be discouraged, particularly in the elderly.

Treatment of Parkinson's disease with subcutaneous lisuride infusions.

Four patients with Parkinson's disease and severe fluctuating responses to levodopa and oral dopamine agonists were treated with continuous administration of lisuride infusions, administered by means of an externally worn pump. Levodopa dosage ranged from 300 to 687 mg/day and was kept stable throughout the study. In addition increasing doses of lisuride were injected subcutaneously in the abdomen. Lisuride doses ranged from 41 to 104 micrograms/h. A marked improvement in mobility was observed in every patient while severe biphasic dyskinesais almost remitted in one of them. The most common side-effect was the presence of subcutaneous nodules appearing at the injection site. Two cases had mild hemorrhagic complications and one initially had nausea. One patient developed acute psychiatric disturbances severe enough to be excluded from the study. Our findings suggest that lisuride subcutaneous infusions can be useful in severily handicapped parkinsonian patients, however local and psychiatric side-effects may be a serious threat in the long-term care.

Ectasis de las arterias intracraneales / Ectasia of intracraneal arteries

Se presentan 10 pacientes con ectasias sintomáticas de arterias cerebrales. Todos los pacientes son de sexo masculino y padecían de hipertensión arterial leve o moderada. Las ectasias estaban presentes en la arteria basilar en el 20%, en las arterias carótidas en el 20% y en ambos sistemas en el 60% restante. Predominaron los síntomas motores y sensitivos, ataxia, diplopía y demencia. Asismismo se presenta el segundo caso en la literatura con hemorragia subaracnoidea a partir de la ruptura de una arteria basilar ectásia. Se discute la presencia de trastornos autonómicos en un paciente con severo compromiso neurológico por compresión del tronco encefálico. Todos los pacientes fueron estudiados con tomografía computada cerebral con infusión de sustancia de constraste y arteriografía cerebral de los cuatro vasos. En uno de los casos la tomografía cerebral resultó insuficiente para el diagmnóstico de ectasia, sugiriendo un tumor del ángulo pontocerebeloso. Cinco pacientes fueron tratados con antiagregantes plaquetarios y dos pacientes recibieron anticoagulación. La evolución clínica fue desfavorable, no observándose benefício aparente en los casos tratados (AU)