Description of a novel technique for ultrasound-based planning for gynaecological 3D brachytherapy and comparison between plans of this technique and 2D with fluoroscopy.

With the purpose of implementing a way to obtain volumes from ultrasound axial images, a novel method for 3D gynaecologic brachytherapy was assessed, with a 3D-printed attachment for a commercial stepper (for prostate brachytherapy). It allowed the acquisition of a transabdominal axial image series by ultrasound; these images were uploaded to a treatment planning system where high-risk clinical tumour volume (HR-CTV) and risk organs were contoured. A dose administration plan was developed with orthogonal X-ray images (0° and 270° incidences), using International Commission on Radiation Units and Measurements (ICRU) 38 points. The same plan was applied in the ultrasound images' sequence and their respective volumes; differences were noted. In the 20 cases analysed, with a given point A dose, its corresponding dose delivered to 90% of HR-CTV percentage was highly variable (mean = 104.2, SD = 26.01). There is a significant variation of this percentage when point A falls outside the HR-CTV than when it falls inside (p < 0.00001). There is a significant correlation in terms of the bladder point dose ICRU 38 and the Maximum dose to 2cc of organ or target volume (D2cc) bladder (p = 0.021); however, there is no such correlation when we relate the rectum point dose ICRU 38 to the D2cc rectum (p = 0.327). There was a negative correlation between HR-CTV and D2cc bladder and D2cc rectum; both were statistically significant. There were significant differences comparing ICRU points and dose to prescription and organ at risk volumes, pointing out that there is room for optimisation of plans using the latter technique. So, it is proposed to further test this image modality and compare it to other imaging techniques that allow the creation of volumes, such as computed tomography or magnetic resonance imaging.

[Primary ciliary dyskinesia in children. Role of electron microscopy in countries with medium economic resources]. / Discinesia ciliar primaria en niños. Rol de la microscopia electrónica en países de medianos recursos económicos.

Primary ciliary dyskinesia (PCD) is a rare genetic disease that produces functional and structural de fects in the cilia. In Peru, no cases of this disease have been reported in the pediatric population. OBJECTIVE: To describe the clinical, radiological and ciliary ultrastructure characteristics in children with PCD, in a country with medium economic resources. CLINICAL CASE: We report 5 patients with PCD treated at the Instituto Nacional de Salud del Niño-Breña (Peru). Age range 1 to 5 years (median 3 years). Three patients were male. The most frequent clinical manifestations were chronic wet cough, rhonchi, coarse crackles, recurrent bronchial obstructive syndrome, and recurrent pneumonia. All patients had atelectasis, three had bronchiectasis, and two had dextrocardia with situs inversus. Two patients had undergone lobectomy. Other causes of recurrent pneumonias were ruled out with im munodeficiency study, chlorine test and pulmonary aspiration The electron microscopy showed ab sence of the inner arm of dynein as the most frequent pattern. All patients received treatment with antibiotics, nebulization with hypertonic saline, and respiratory physiotherapy with good adherence. CONCLUSION: In medium incomes countries, electron microscopy associated with clinical and radio logical characteristics plays an important role in the early diagnosis of this disease. This is the first Peruvian report that contributes to the casuistry and epidemiology of this rare pathology.

[Surfactant protein C dysfunction in pediatric patients: Clinical Case]. / Disfunción de la proteína surfactante C en pacientes pediátricos: Caso Clínico.

Pulmonary surfactant dysfunction disorders are caused by genetic defects that alter pulmonary surfactant metabolism. They are rare disorders and cause significant morbidity and mortality in the neonatal and pediatric populations. OBJECTIVE: To describe the clinical, histopathological, and ultrastructural findings of the lamellar body that suggest surfactant protein C (SP-C) dysfunction, where confirmatory genetic studies are not available. CLINICAL CASE: We report three pediatric cases of pul monary surfactant dysfunction disorders from a pediatric hospital in Peru. Video-assisted lung biop sy was performed in all cases. Ultrastructural studies of the lamellar body were compatible with type- C pulmonary surfactant dysfunction. The treatment used was methylprednisolone pulses monthly for six months, then every two months, varying the duration according to the clinical evolution. They also received daily hydroxychloroquine and azithromycin three times a week. Clinical evaluations, eye fundus, echocardiogram, electrocardiogram, and biochemistry were performed periodically. At follow-up, there was a good response to treatment and no adverse effects were observed. One case died despite the therapies received. CONCLUSIONS: In 3 patients with type-C surfactant dysfunction, treatment with corticosteroids, hydroxychloroquine, and azithromycin was successful in 2 of them. This is one of the first case series reported in Peru that contributes to the study of these diseases, es pecially in low- and medium-income countries.

Haloperidol-based conditioned increase in locomotor activity is disrupted by latent inhibition and extended interstimulus interval.

Previous research have shown that repeated administration of 0.5 mg/kg of haloperidol in a given context gives rise to an increase in activity when spontaneous locomotor activity is recorded in a drug-free test conducted in such context. In order to confirm whether this type of response is based on processes of a Pavlovian nature, we conducted two experiments involving two manipulations that disrupt conditioning in typical classical conditioning procedures: preexposure of the to-be-conditioned stimulus (latent inhibition), and an increase in the length of the inter-stimulus interval. The results revealed that both manipulations were effective in reducing the conditioned increase of the locomotor response. This kind of conditioning can be explained in terms of the differential effects of low vs. high doses of haloperidol, and the temporal dynamics of conditioned response.

Conditioned increase of locomotor activity induced by haloperidol.

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol can act as an unconditioned stimulus, we carried out two experiments in which the administration of haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase in locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.

Reward devaluation disrupts latent inhibition in fear conditioning.

Three experiments explored the link between reward shifts and latent inhibition (LI). Using consummatory procedures, rewards were either downshifted from 32% to 4% sucrose (Experiments 1-2), or upshifted from 4% to 32% sucrose (Experiment 3). In both cases, appropriate unshifted controls were also included. LI was implemented in terms of fear conditioning involving a single tone-shock pairing after extensive tone-only preexposure. Nonpreexposed controls were also included. Experiment 1 demonstrated a typical LI effect (i.e., disruption of fear conditioning after preexposure to the tone) in animals previously exposed only to 4% sucrose. However, the LI effect was eliminated by preexposure to a 32%-to-4% sucrose devaluation. Experiment 2 replicated this effect when the LI protocol was administered immediately after the reward devaluation event. However, LI was restored when preexposure was administered after a 60-min retention interval. Finally, Experiment 3 showed that a reward upshift did not affect LI. These results point to a significant role of negative emotion related to reward devaluation in the enhancement of stimulus processing despite extensive nonreinforced preexposure experience.

Effect of stress and attention on startle response and prepulse inhibition.

The startle reflex magnitude can be modulated when a weak stimulus is presented before the onset of the startle stimulus, a phenomenon termed prepulse inhibition (PPI). Previous research has demonstrated that emotional processes can modulate PPI and startle intensity, but the available evidence is inconclusive. In order to obtain additional evidence in this domain, we conducted two experiments intended to analyze the effect of induced stress and attentional load on PPI and startle magnitude. Specifically, in Experiment 1 we used a between subject strategy to evaluate the effect on startle response and PPI magnitude of performing a difficult task intended to induce stress in the participants, as compared to a group exposed to a control task. In Experiment 2 we evaluated the effect of diverting attention from the acoustic stimulus on startle and PPI intensity. The results seem to indicate that induced stress can reduce PPI, and that startle reflex intensity is reduced when attention is directed away from the auditory stimulus that induces the reflex.

Rapid-onset antidepressant efficacy of glutamatergic system modulators: the neural plasticity hypothesis of depression.

Depression is a devastating psychiatric disorder widely attributed to deficient monoaminergic signaling in the central nervous system. However, most clinical antidepressants enhance monoaminergic neurotransmission with little delay but require 4-8 weeks to reach therapeutic efficacy, a paradox suggesting that the monoaminergic hypothesis of depression is an oversimplification. In contrast to the antidepressants targeting the monoaminergic system, a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine produces rapid (within 2 h) and sustained (over 7 days) antidepressant efficacy in treatment-resistant patients. Glutamatergic transmission mediated by NMDARs is critical for experience-dependent synaptic plasticity and learning, processes that can be modified indirectly by the monoaminergic system. To better understand the mechanisms of action of the new antidepressants like ketamine, we review and compare the monoaminergic and glutamatergic antidepressants, with emphasis on neural plasticity. The pathogenesis of depression may involve maladaptive neural plasticity in glutamatergic circuits that may serve as a new class of targets to produce rapid antidepressant effects.

Comportamiento del PPD en niños con diagnostico de tuberculosis pulmonar, Servicio de Neumología - INSN / Behavior of the PPD in children with diagnosis of pulmonary tuberculosis, Service of Pneumology - INSN

El diagnóstico de TBC en niños sigue siendo difícil a pesar de los actuales adelantos científicos, debido a su naturaleza paucibacilar y mayores formas extrapulmonares. Su enfoque radica principalmente en la Historia de Contactos, radiografía de tórax y PPD. Este último, sin embargo no discrimina entre infección latente y enfermedad activa. El presente estudio, describe el comportamiento del PPD en pacientes diagnosticados de TBC pulmonar, su reactividad en relación a la baciloscopía. MATERIAL Y METODOS: Es un estudio descriptivo de cohorte transversal. Se revisó las fichas de seguimiento de todos los pacientes diagnosticados de TBC Pulmonar durante los años 2009 - 2010 en el Instituto Nacional de Salud del Niño, Lima - Perú. Los datos recolectados se analizaron por el sistema SPSS V15.0. RESULTADOS: Se encontraron 209 casos (56 por ciento fueron varones), clasificados por grupos etáreos: 6.7 por ciento (menor 1 año), 27.3 por ciento (1 a 4 años), 24.9 por ciento (5 a 9 años) y 41.1 por ciento (mayores de 10 años). Los casos más frecuentes provinieron de los distritos de Lima Este (22 por ciento), Centro (22 por ciento) y Sur (20 por ciento). Predominó la TBC Pulmonar Activo evolutiva (87.6 por ciento) sobre las otras formas. La positividad de las baciloscopías fue del 22 por ciento, el grupo mayor a 10 años presentó mayor frecuencia de baciloscopías positivas (41 por ciento). La positividad al PPD se observó en el 78 por ciento de los casos estudiados y existió contacto bacilífero conocido en un 45 por ciento del total. No se observó que una mayor medida del PPD se relacione a mayor posibilidad de encontrar una baciloscopía positiva. Además los pacientes mayores de 10 años reaccionaron más al PPD que los otros grupos. CONCLUSIONES: La prueba de Tuberculina (PPD) es una herramienta útil en el enfoque diagnóstico de la TBC en niños, su mayor medida no se relaciona a una mayor frecuencia de baciloscopías positivas, y está relacionada a una mejor respuesta inmune frente al MBT

Removal of synaptic Ca²+-permeable AMPA receptors during sleep.

There is accumulating evidence that sleep contributes to memory formation and learning, but the underlying cellular mechanisms are incompletely understood. To investigate the impact of sleep on excitatory synaptic transmission, we obtained whole-cell patch-clamp recordings from layer V pyramidal neurons in acute slices of somatosensory cortex of juvenile rats (postnatal days 21-25). In animals after the dark period, philanthotoxin 74 (PhTx)-sensitive calcium-permeable AMPA receptors (CP-AMPARs) accounted for ∼25% of total EPSP size, and current-voltage (I-V) relationships of the underlying EPSCs showed inward rectification. In contrast, in similar experiments after the light period, EPSPs were PhTx insensitive with linear I-V characteristics, indicating that CP-AMPARs were less abundant. Combined EEG and EMG recordings confirmed that slow-wave sleep-associated delta wave power peaked at the onset of the more quiescent, lights-on phase of the cycle. Subsequently, we show that burst firing, a characteristic action potential discharge mode of layer V pyramidal neurons during slow-wave sleep has a dual impact on synaptic AMPA receptor composition: repetitive burst firing without synaptic stimulation eliminated CP-AMPARs by activating serine/threonine phosphatases. Additionally, repetitive burst-firing paired with EPSPs led to input-specific long-term depression (LTD), affecting Ca(2+) impermeable AMPARs via protein kinase C signaling. In agreement with two parallel mechanisms, simple bursts were ineffective after the light period but paired bursts induced robust LTD. In contrast, incremental LTD was generated by both conditioning protocols after the dark cycle. Together, our results demonstrate qualitative changes at neocortical glutamatergic synapses that can be induced by discharge patterns characteristic of non-rapid eye movement sleep.

[Primary pneumonic plague with nosocomial transmission in La Libertad, Peru 2010]. / Peste neumónica primaria con transmisión intrahospitalaria en La Libertad, Perú 2010.

UNLABELLED: Pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of Yersinia pestis coming from an animal or from person to person. OBJECTIVE: To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. MATERIALS AND METHODS: The clinical records of the confirmed cases of primary pneumonic plague presenting in an outbreak occurring in La Libertad, in July 2010, were reviewed, also the search and contact investigation was performed. RESULTS: The index case was identified, as well as three additional cases, out of these, two were nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50% (2/4). CONCLUSION: Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.

Peste neumónica primaria con transmisión intrahospitalaria en La Libertad, Perú 2010 / Primary pneumonic plague with nosocomial transmission in La libertad, Peru 2010

La peste neumónica es una forma clínica de peste, de baja frecuencia y alta letalidad, transmitida por la inhalación directa de Yersinia pestis proveniente de un animal o de persona a persona. Objetivo: Describir las características clínicas y epidemiológicas de los casos de un brote de peste neumónica primaria humana en el norte de Perú. Materiales y Métodos. Se revisaron las historias clínicas de los casos confirmados de peste neumónica primaria presentados en un brote ocurrido en la región de La Libertad, en el mes de julio de 2010, asimismo, se efectuó la búsqueda e investigación de contactos. Resultados: Se identificó el caso Índice y tres casos adicionales, de estos últimos, dos fueron infecciones intrahospitalarias relacionadas con el caso índice. La presentación clínica inicial se caracterizó por fiebre de inicio súbito, escalofríos, mialgias y dolor torácico y evolución en menos de 24 horas a hipotensión arterial y cianosis. El inicio del tratamiento específico varió de 2 a 12 días, observándose que los casos con inicio precoz de tratamiento tuvieron un mejor resultado clínico. La lealtad fue de 50 por ciento (2/4). Conclusión: Se evidenció la transmisión intrahospitalaria de peste neumónica en el Perú con manifestaciones graves y alta letalidad.

Pneumonic plague is one of the clinical forms of plague, of low frequency and high mortality, transmitted by direct inhalation of Yersinia pestis coming from an animal or from person to person. Objective. To describe the clinical and epidemiological characteristics of the cases of primary pneumonic plague in an outbreak in the north of Peru. Materials and methods. The clinical records of the confirmed cases of primary pneumonic plague presenting in an outbreak occurring in La Libertad, in July 2010, were reviewed, also the search and contact investigation was performed. Results. The index case was identified, as well as three additional cases, out of these, two were nosocomial infections related to the index case. The initial clinical presentation was characterized by sudden onset of fever, chills, myalgia and chest pain, which in less than 24 hours evolved to hypotension and cyanosis. The initiation of specific treatment varied from 2 to 12 days, and cases with prompt initiation of treatment had a better clinical outcome. The lethality was 50 percent (2/4). Conclusion. Nosocomial transmission of pneumonic plague in Peru is evidenced, with severe clinical manifestations and high lethality.

Penile erection and micturition events triggered by electrical stimulation of the mesopontine tegmental area.

The cholinergic neurons in the laterodorsal tegmental nucleus (LDT) play a crucial role in the regulation of rapid eye movement (REM) sleep. Because penile erection occurs during REM sleep, the involvement of the LDT in penile erection was examined in unanesthetized head-restrained rats. To detect penile erection, corpus spongiosum of the penis (CSP) pressure was measured through a telemetric device with simultaneous bulbospongiosum (BS) muscle EMG recording through stainless wires. Electrical stimulation in and around the LDT induced the following three CSP pressure patterns: 1) a full erection pattern indistinguishable from the nonevoked or spontaneous erection, characterized by a slow increase in CSP pressure with additional sharp CSP peaks associated with BS muscle bursts, 2) a muscular pattern characterized by sharp CSP pressure peaks but in the absence of a vascular component, i.e., without an increase in baseline CSP pressure, and 3) a mixed-type response characterized by high-frequency CSP pressure peaks followed by a full erection response. Full erections were evoked in and around the LDT, including more medially and ventrally. The sites for inducing mixed-type events were intermingled with the sites that triggered full erections in the anterior half of the LDT, whereas they were separated in the posterior half. The sites for muscular responses were lateral to the sites for full erections. Finally, a CSP pressure response identical to micturition was evoked in and around the Barrington's nucleus and in the dorsal raphe nucleus. These results suggest that the LDT and surrounding region are involved in the regulation of penile erection. Moreover, different anatomical areas in the mesopontine tegmentum may have specific roles in the regulation of penile erection and micturition.