Gold glyconanoparticles coupled to listeriolysin O 91-99 peptide serve as adjuvant therapy against melanoma.

Dendritic cell-based (DC-based) vaccines are promising immunotherapies for cancer. However, several factors, such as the lack of efficient targeted delivery and the sources and types of DCs, have limited the efficacy of DCs and their clinical potential. We propose an alternative nanotechnology-based vaccine platform with antibacterial prophylactic abilities that uses gold glyconanoparticles coupled to listeriolysin O 91-99 peptide (GNP-LLO91-99), which acts as a novel adjuvant for cancer therapy. GNP-LLO91-99, when used to vaccinate mice, exhibited dual antitumour activities, namely, the inhibition of tumour migration and growth and adjuvant activity for recruiting and activating DCs, including those from melanoma patients. GNP-LLO91-99 nanoparticles caused tumour apoptosis and induced antigen- and melanoma-specific cytotoxic Th1 responses (P ≤ 0.5). We propose this adjuvant nanotherapy for preventing the progression of the first stages of melanoma.

Botulinum toxin A in management of cerebral palsy.

The efficacy of local injection of botulinum toxin A in selected skeletal muscles to relieve muscle hypertonia and muscle contracture, and increase range of motion in children with cerebral palsy was studied in an open ABA (baseline-treatment-posttreatment phase) type of study. The first 6 months were the baseline phase, the day of injection the treatment phase, and the next 6 months the posttreatment phase. The patients acted as their own controls. Fifteen children with cerebral palsy (mean age: 6 years, 8 months) were included in the study. All had limb deformities associated with non-fixed joint contractures that had not responded to physical therapy. Clinical assessment of passive and active muscle tone was performed using a modified Ashworth scale. The range of motion to passive movement was measured with a manual goniometer. Botulinum toxin was injected directly into the muscle at several sites. The postinjection scores of muscle hypertonia were significantly lower (P < .01) and the range-of-motion values demonstrated a significant increase (P < .001). Functional improvement was measured by decreased scissoring on standing in all 6 children with adductor muscles injected; all 6 children with knee flexor muscles injected were able to straighten the knees. The 3 children with injected gastrocnemius muscles were able to achieve heel-strike while bare-footed. The study provides evidence that the intramuscular injection of botulinum toxin A in selected skeletal muscles decreases muscle tone and contractures, and increases range of motion and motor function.

[Controversial or arguable therapies in neurodevelopmental disorders]. / Terapias de controversia o polémicas en los trastornos del neurodesarrollo.

OBJECTIVE: To analyze the therapies and methods not scientifically documented that more frequently are offer and used for the treatment of neurodevelopmental disorders. DEVELOPMENT: These therapies are divided into three main groups: a) Therapies directed upon brain functioning; b) Therapies directed upon nutritional needs, and c) Others. Parents and close relatives of children with developmental disorders are vulnerable to any person, institution or method that offers a quick and easy solution to their problem. It is a priority that all health professionals are familiar with the unproven therapies, that are offered for the therapy of developmental disorders, so that they can inform, educate and advise correctly to parents and close relatives of their patients. To deal with unproven treatments involves more than analyzing the available scientific data. It is required a comprehension and understanding of the personal and family dynamics in front of a threat of illness or disfunction. CONCLUSION: Responsible and well informed parents in relation to an unproven therapy should be free and have the right to decide whether or not to use a controversial procedure prior to a scientific determination of its validity; they also must keep in mind that at least some procedures, beside of not been useful, could be harmful for the physical, emotional and economical well-being of the patient and/or his family.

[Prevention of mental retardation]. / Prevención del retraso mental.

OBJECTIVE: To present within the general field of the conditions causing mental retardation, the preventive strategies for specific application available at the present time. DEVELOPMENT: In spite of the fact that in the majority of cases of mental retardation the etiology is unknown, and for that reason, in them it is not possible to establish preventive strategies, within the last three decades, important research advances have helped to prevent thousands of cases of mental retardation of illnesses caused by Haemophilus influenzae B, measles encephalitis, Rh disease and severe jaundice in newborn infants, congenital hypothyroidism, phenylketonuria and congenital rubella; as well as removing lead from the environment, intervention programs for the proper use of seat belts, child safety seats, and motorcycle and bicycle helmets; early and adequate prenatal care, dietary supplementation with folic acid beginning before conception to reduce the risk of neural tube defects, avoidance of toxic substances during pregnancy like alcohol, and the use of newborn screening tests. CONCLUSION: The primary and secondary prevention of conditions that cause mental retardation continue being a challenge. Require of a review of the present strategies, that frequently inform about the problem, but are not practice in an every day bases (ej. intake of alcohol during pregnancy, the universal use of seat belt and child safety seats during automobile travel). In the future we may have the possibility of prenatal gene therapy.

[Clinical treatment (non surgical) of spasticity in cerebral palsy]. / Tratamiento clínico (no quirúrgico) de la espasticidad en parálisis cerebral.

OBJECTIVE: A review about the procedures used in the non surgical management of spasticity in children with cerebral palsy. DEVELOPMENT: Therapeutic modalities for the management of spasticity in cerebral palsy include: (1) elimination of factors aggravating spasticity: pain, fatigue, stress, excitement, cold, illness, sleep disturbance, immobility, and hormonal changes; (2) rehabilitative therapies, there are four major groups: (a) biomechanical approach, (b) neurophysiologic approach, (c) developmental approach and (d) sensory approach; (3) orthosis; (4) oral pharmacotherapy: baclofen, tizanidine, diacepam and dantroleno; (5) chemical denervation: phenol injections and botulinum toxin injections. The medical management of spasticity in cerebral palsy is based on: 1. Oral pharmacotherapy: (a) baclofen, binds GABAB receptors of spinal interneurons presynaptically, inhibits release of excitatory neurotransmitters in the spinal cord; (b) tizanidine, binds alfa 2 adrenergic receptors presinaptically, inhibits release of excitatory neurotransmitters in the spinal cord; (c) diacepam, augments GABA mediated inhibition in the spinal cord and supraspinally;(d) dantrolene, inhibits release of calcium from sarcoplasmic reticulum in muscle, weakens muscle contraction in response to myofiber excitation. 2. Chemical denervation: (a) phenol injection perineurally or into the motor point disrupts efferent signals from hyperexcitable anterior horn cells causing necrosis of axons or muscle; (b) botulinum toxin injection in selected muscles blocks the release of acetylcholine presynaptically and weakens the force of muscle contraction produced by hyperexcitable motoneurons. CONCLUSIONS: At the present time, there is not irrefutable evidence of a sustain benefit of physical rehabilitation in the management of spasticity. There are few studies with oral pharmacological agents involving children with cerebral palsy to define its role. On the other hand, botulinum toxin A is effective, well tolerated, and safe in the treatment of spasticity in children with cerebral palsy.

[Treatment of spasticity in cerebral palsy with botulinum toxin]. / Tratamiento de la espasticidad en parálisis cerebral con toxina botulínica.

OBJECTIVE: A review of the pathophysiological and developmental basis, measurement scales and the usefulness of botulinum toxin A injections in selected muscles for the treatment of spasticity in children with cerebral palsy. DEVELOPMENT: Cerebral palsy is the most common cause of spasticity in children. The increase in muscle length is achieved through the addition of sarcomeres in series at the level of the muscle tendinous junction. The regulation of the number of sarcomeres seems to be determined by the lengthening of the muscle. The muscle contracture is a shortening of the length of a muscle as a result of a decrease in the number of sarcomeres. Spasticity and motor function assessment scales used in children with cerebral palsy: a) Modified Ashworth scale for the assessment of spasticity; b) modified Tardieu scale for the assessment of dynamic muscle length; c) muscle spasms frequency scale; d) modified Medical Research Council scale for muscle strength; e) hip adductor muscle tone scale; f) global pain scale with affective facial expression represented in a drawing; g) goniometric measurement of the joint range of movement; h) Palisano gross motor function measure; i) observational video gait analysis scale. Recommended guidelines for dosing the botulinum toxin A: 1. Total maximum dose administered per visit up to 15 U/kg or a total of 400 U; 2. Dose range of large muscles 3 to 6 U/kg per visit; 3. Dose range of small muscles 1 to 3 U/kg per visit; 4. Maximum dose per injection site: 50 U dividing the total planned unit dose/muscle into equal amounts/injection site; 5. Frequency: no more than one injection every 3 months, frequently once every 6 or more months. CONCLUSION: Botulinum toxin A injection is a well tolerated, safe and effective procedure in the treatment of children with spastic cerebral palsy.

[Gilles de la tourette syndrome: clinical spectrum and management]. / Sindrome de Gilles de la Tourette: espectro clínico y tratamiento.

OBJECTIVE: To present the current concepts of the clinical phenomenology and natural history of Gilles de la Tourette syndrome (GTS), differential diagnosis with other involuntary movements, its pathogenesis and current management. DEVELOPMENT: GTS is a disorder characterized by a spectrum of both motor and sonic tics, and a spectrum of behavioral disorders. There is not a biological marker that confirms or refutes the diagnosis of GTS, so this diagnosis remains purely clinical. It has been found to be present in 1 to 3% of school population. An specific cause for GTS is unknown, though most cases appear to occur on an hereditary polygenetic basis. Observations that drugs increasing dopamine neurotransmission, including levodopa and the dopamine receptor agonist pergolide lessen tics, have called into question the dopamine receptor supersensibility hypothesis. The hypothesis proposing basal ganglia and frontostriatal pathways involvement in the pathophysiology of the disorder is the most likely. Frequently, disruption due to tics is overshadowed by comorbid conditions, like obsessive compulsive behaviors, attention deficit hyperactivity disorder, other behavioral disorders and learning disabilities, so the management should be targeted to them. CONCLUSION: The knowledge about the basic mechanisms and the integral definition of the clinical spectrum of tics and neurobehavioral manifestations, and its natural history in a patient with GTS, allow us to establish a more rational approach for management and prognosis

[The clinical phenomenology of Rett's syndrome]. / Fenomenología clínica del síndrome de Rett.

The work was done to facilitate the clinical diagnosis and understanding of Rett syndrome (RS) by grouping the symptoms and signs in areas of neurological disfunction. This is a retrospective, longitudinal and observational study of 30 young females whose clinical manifestations were grouped using a modified Fitzgerald et al. scale for motor and behavior evaluation of patients with RS. All patients were videotaped at least during one or several appointments during their follow-up for a period of 1 to 10 years. All patients and videotapes were reviewed independently by the three authors. We followed the clinical diagnostic criteria of classic RS, and grouped the symptoms and signs in 12 groups of clinical phenomenology that represented specific areas of central or peripheral nervous system involvement: 1) dementia syndrome (fronto-temporo-parietal and limbic dysfunction); 2) extrapyramidal syndrome (basal ganglia dysfunction); 3) respiratory function disorders (brain stem reticular system disfunction); 4) sleep disorders (reticular system and limbic dysfunction); 5) epilepsy (cortico-subcortical paroxysmal bioelectrical dysfunction); 6) lower motor neuron syndrome (neuropathic dysfunction and/or peripheral neuropathy); 7) body growth retardation; 8) tonic-postural skeletal deformities; 9) deficit of pain sensation (nociceptive deficit); 10) pseudobulbar dysfunction; 11) autonomic dysfunction and 12) others (microcephaly and bruxism). In clinical practice, we recommend the use of this grouping of symptoms and signs because it makes facilities the clinical study, definition of areas of dysfunction and diagnosis of the patient with RS.

[Autism in tuberous sclerosis]. / Autismo en la esclerosis tuberosa.

During the last five years, it has been recognized a very high incidence of autism in children affected by tuberous sclerosis; we believe that this association may be more than just a coincidence and that it may be that the autistic behavior spectrum is related to a great extent, to the anatomic localization of tubers in the frontal and temporoparietal areas. In this study we report our experience with 27 consecutive children, 12 boys and 15 girls with a diagnosis of tuberous sclerosis confirmed by clinical and MRI and or CT findings according to the diagnostic criteria developed by the Diagnosis Criteria Committee of the National Tuberous Sclerosis Association. They were studied during the period of 1988 to 1990. Ages range from 18 months to 16 years (mean: 6.5 years). Twenty-four had epilepsy and were receiving antiepileptic treatment. Seven of the 27 children (25.9 per cent) fulfilled the diagnostic criteria for autistic disorder according to the DSM-III-R. The autistic behavior was evident in all of them by three and half years. The seven children had mental retardation. MRI and CT findings with subependymal calcifications and cortical tubers of frontal and temporoparietal predominance were seen in five of the seven autistic children. In one child, CT was normal and in the other it was not performed. Five were girls and all had West syndrome; two were boys and neither had seizures. Most of the reported cases of children with tuberous sclerosis and autism had experiences West syndrome. In our patients, five of the seven children with autism had west syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Migraine. Various current concepts]. / Migraña. Algunos conceptos actuales.

Migraine is a common disorder in children with a prevalence of 2.5% under seven years of age, 5% in those between the ages of seven and puberty and in postpuberal females it may be as prevalent as 10%. It is transmitted as an autosomally dominant trait and is frequently caused by precipitating factors. The vascular theory which stated that the aura was due to an intracranial vessel constriction and that the headache was due to an extracranial vasodilation has now be questioned due to new clinical and experimental data. Recently it is believed to be due to an unstable inherited serotonigenic neurotransmission which favors an increase in the frequency of neuronal discharge of the mid-brain raphe. Included is a classification and the diagnostic headache criteria used by the International Headache Society (1988). Treatment for migraine can be: a) abortive and b) preventive. Propranolol at a dosage of 2 mg/kg per day taken divided into three has shown to be the most beneficial in the prevention of migraine headaches. Certain calcium channel blockers, particularly flunarizine seem to have prophylactic value.

[Conductive education in integral rehabilitation of patients with cerebral palsy]. / "Educación conducida" en la rehabilitación integral del paciente con parálisis cerebral.

"Conductive education" was thought out and developed by Andres Peto in Budapest. Its main goal is "orthofunction". Such a system was used in 22 children with cerebral palsy. These children were divided in two groups, one with 10 pre-school and school age children and the other of "parents and babies" with 12 infants. From the first group, six children had received physiotherapy in our Center following an eclectic method at least for one year and from the second group seven infants had received also physiotherapy at least for six months; these children were used as controls. The rest of the children were new admissions. A special evaluating scale was developed to evaluate all the children involved. In the control group the evaluation was performed before the initiation of the program (12 and six months respectively), at the beginning in all of them and at 12 and 16 months in the pre-school and school age group, and at six and 12 months in the infants of the "parents and babies" group. The results showed a definite advantage in both groups of Conductive education in the motor, cognitive and social areas compared with the results with physiotherapy in the control group.

[Emergency management of convulsions and prevention of status epilepticus with rectal diazepam administered by parents]. / Manejo de emergencia de convulsiones y prevención de estado epiléptico con diazepan rectal administrado por los padres.

The parents of 17 children with a history of convulsions, were shown how to administer liquid diazepam through the rectum using a 1 mL insulin syringe, in order to alleviate a convulsion at home or any where ever this may occur. Eight of the children had suffered from repetitive and/or prolonged non-temperature related convulsions, four had epileptic status and five had suffered from simple fever related convulsions, complicated in four and in a convulsive status in 1; the number of fever-related convulsions ranged between 1 and 6 per child and those non temperature related ranged from one daily to once a month. The observation of the children was done in an 88 month period (between 1 and nine months per child, averaging 5.2 months). In seven of the children, it was required of the parents to administer rectal diazepam a total of 90 times (fluctuating between 2 and 25 doses per child), with no complications, a dose of 0.5 mg/kg was administered in those patients whose convulsions lasted over 5 minutes or more. In 75 occasions, the convulsion stopped within a period of 2 to 5 minutes, in 12 other times there was a need for repeated dosages and in 2 occasions, a third doses was needed. Only in one occasion was hospital management needed. Therefore, we conclude that the administration of rectal diazepam by parents--at home--is a useful and secure method to prevent prolonged convulsions and the epileptic status; it gives parents security and tranquility using an instrument which can be used in any circumstance therefore reducing anguish and the cost of hospital care.(ABSTRACT TRUNCATED AT 250 WORDS)

[Congenital myasthenia gravis. Presentation of a case with dysphagia as the only clinical manifestation]. / Miastenia gravis congénita. Presentación de un caso de disfagia como única manifestación clínica.

Myasthenia gravis is an infrequent disease seen at the neonatal stage. Two main groups are identified: a) one with a genetic origin which can be secondary to pre- or postsynaptic defects and b) of an acquired origin, as transitory neonatal myasthenia seen in 10-15% of those children with myasthenic mothers. Few cases with a genetic origin have been reported in the literature; the most common symptoms being bilateral eyelid ptosis, ophtalmoparesis, easy fatigability, respiratory and feeding difficulties. This is a report of a genetic neonatal case of myasthenia gravis with dysphagia as the only clinical manifestation seen since the first days of the child's life, confirming the diagnosis using a repetitive supramaximal stimulation test and obtaining excellent results with pyridostigmine. We conclude that, although this a rare form of the disease, genetic neonatal myasthenia gravis should be considered in the differential diagnosis of newborns with difficulties to swallow. The repetitive supramaximal stimulation test is the diagnostic procedure of first choice to be used in the neonatal period.

[Febrile convulsion. A clinical study of 303 patients]. / Convulsiones febriles. Estudio clínico de 303 pacientes.

The clinical characteristics of 303 patients who had episodes of feverish convulsions (FC) were retrospectively reviewed. No preference was seen for either sex (1.3/1). In 75.3% of the cases, the convulsions occurred in children under two. There was some predominance of tonic-clonic crisis and generalized clonic-tonic convulsions (85.5%) with 21.8% of complex partial crisis. In 44.8% of the cases a perinatal history of high risk was noted. A comparative investigation was carried out in a subgroup of 244 children in who FC vs non-febrile convulsions (NFC) were during two years. In 35.2% of the patients neurological abnormalities were found associated, among them were language difficulties (27.4%) and psychomotor retardation (11.9%). In 36.4% of the cases, the EEG was found to be abnormal, and paroxysmal in 27%. The predominating perinatal pathological complications were perinatal hypoxia-anoxia and prematurity. In 84% of the patients, anti-convulsive medication was administered. Of the 244 patients, 62 (25.4) of them had NFC which were directly related to the number of risk factors and their characteristics. Among those risk factors were partial convulsions, neurological deficit, abnormal EEG, convulsions lasting over 10 minutes and a previous family history of epilepsy. It is noteworthy that 15.7% of the patients had no risk factors related to epilepsy. In those patients who suffered from convulsions from an early age, who had convulsions of a partial--complex type, which lasted over 20 minutes and repeated frequently--were seen to be the most likely to develop epilepsy. The medications prescribed prevented the occurrence of the FC but did not significantly diminish the development of epilepsy. Febrile convulsions; epilepsy; perinatal.