Cincuenta años del Departamento de Medicina del Dolor y Paliativa del Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼ / Fifty anniversary of the department of pain and palliative medicine at the Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼

Resumen: Introducción: En México, la primera clínica especializada en el alivio del dolor fue fundada en 1972 por el Dr. Ramón De Lille Fuentes en el Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼ (INCMNSZ). Material y métodos: Se realizó una búsqueda histórica documental y entrevistas a quienes han colaborado con el Departamento de Medicina del Dolor y Paliativa del INCMNSZ desde su fundación. Resultados: Nuestra visión es ofrecer atención del dolor, cuidados paliativos y apoyo continuo. Para ello, documentamos nuestra historia y los logros del departamento. Conclusiones: A 50 años de su fundación, el Departamento de Medicina del Dolor y Paliativa del INCMNSZ es un foro de desarrollo científico y de formación de capital humano con un enfoque humanista.

Abstract: Introduction: In Mexico, the first clinic specializing in pain relief was founded in 1972 by Dr. Ramón De Lille Fuentes at the Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán¼ (INCMNSZ). Material and methods: A historical documentary search and interviews were carried out with those who have collaborated with the Department of Pain and Palliative Medicine of the INCMNSZ since its foundation. Results: Our vision is to offer pain management, palliative care, and ongoing support. To do this, we document the history and achievements of the department. Conclusions: 50 years after its foundation, the INCMNSZ Department of Pain and Palliative Medicine is a forum for scientific development and human capital training with a humanistic approach.

Experimental display of generalized wave-particle duality.

The quantification of wave-particle duality (WPD) by means of measurable features associated to it, such as fringe visibility ($\mathcal {V}$) and path distinguishability ($\mathcal {D}$), led to the establishment of the constraint $\mathcal {V}^{2}+\mathcal {D}^{2} \leq \,1$. The two involved quantities refer to so-called "quantons", physical objects that are capable of generating an interferometric pattern, while being at least partially localizable. Any quanton's internal degree of freedom (DOF) can in principle be used as a path-marker. When the quanton and its internal DOF are simultaneously engaged, new constraints can be derived and experimentally tested. Generalized constraints show how $\mathcal {V}$ and $\mathcal {D}$ relate to other quantifiers and bring to light coherences that might remain otherwise hidden in both quantum and classical light. We submitted two-qubit constraints to experimental tests, using optical light beams. This shows that, despite the rather contrived nature of the constraints, linear optics setups are appropriate to test them. Our experimental results are in very good agreement with theoretical predictions related to the tested constraints. Our results also show that quantifiers such as $\mathcal {V}$ and $\mathcal {D}$ help not only to quantify, but also to generalize the concept of WPD.

Sleep architecture and the absence of trapezius muscle atonia in women with chronic whiplash-associated disorder: a pilot study.

Sleep disturbances frequently occur in people with whiplash-associated disorder (WAD) and have been evaluated using questionnaires or actigraphy. It is not clear whether sleep architecture, as assessed by polysomnography (PSG), is altered in individuals with WAD. Additionally, in people with WAD, muscle dysfunction is observed during tasks performed during wakefulness. Thus, this study aimed to analyze the sleep architecture of patients with chronic WAD as well as to evaluate trapezius muscle activity during sleep. Nine women with chronic WAD and nine healthy age-matched women participated in the study. Two PSG recordings were conducted for each participant. Surface electromyography signal samples of the right and left trapezius, and mentonian muscles were obtained from N2, N3, and REM sleep stages for analysis. Significant differences were found in the percentages of total sleep time in the N1 and N2 stages between the two groups. While the muscle tone of the three muscles analyzed decreased progressively across the sleep stages in the healthy group, in the chronic WAD group, this decrement was observed only in the mentonian muscle, and the trapezius muscle continued to exhibit the same muscle tone throughout the sleep stages without atonia during REM sleep. The absence of trapezius muscle atonia during REM sleep in the WAD patients may be related to dysfunction of the mechanisms that regulate motor activity.

Apexificación en una cita utilizando material biocerámico como tapón apical / Apexification in a single appointment using a bioceramic material as an apical plug

El objetivo fue realizar una técnica de apexificación en una cita, evaluando clínica y radiográficamente la formación de barrera dura apical, con seguimiento a nueve meses, al utilizar material biocerámico en dien-tes permanentes jóvenes. Se trataron 30 incisivos su-periores permanentes con ápice abierto y anteceden-tes de trauma, en pacientes de ambos géneros y 18-40 años. Las piezas (n=30) se dividieron en dos grupos (n=15). Grupo experimental: tratamiento de apexifica-ción con EndoSequence Root Repair Material (EERR), y grupo control: tratamiento con impresión apical. Se determinaron distribuciones de frecuencias y esta-dísticas descriptivas para cada variable, según es-cala de medición y distribución. Se realizaron IC 95%, test de Chi cuadrado con cálculo de residuos estan-darizados ajustados y test de Fisher. Se fijó nivel de significación p=0.05. Las diferencias de manifestacio-nes preoperatorias y postoperatorias según grupo fueron no significativas (p Fisher = 0.9140) y (p Fisher = 0.992), respectivamente. No se hallaron diferencias entre proporciones de hallazgos radiológicos preope-ratorios según grupo. Medidas trimestralmente, no hubo diferencias significativas entre proporciones de piezas con continuidad de cortical ósea y radiolucidez periapical postoperatoria según grupo, (p Fisher = 0.7780) y (p Fisher = 0.7909), respectivamente. Debi-do la escasa cantidad de trabajos que reportan el uso de EERR para esta técnica, se requiere de nuevos en-sayos clínicos con tamaños muestrales amplios, para compararlo con otros materiales y técnicas, y deter-minar si su tasa de éxito a largo plazo es mayor que a de los materiales y técnicas usadas actualmente (AU)

To perform apexification technique in one appointment, clinically and radiographically evaluating the formation of apical hard barrier, with follow-up at nine months, when using bioceramic material in young permanent teeth. Materials and methods: 30 permanent upper incisors with open apex and history of trauma were treated, in patients of both genders and 18-40 years of ages. The teeth (n=30) were divided into two groups (n=15). Experimental group: apexification treatment was performed with EndoSequence Root Repair Material (EERR), control group: treatment with apical impression. Frequency distributions and descriptive statistics were determined for each variable according to scale of measurement and distribution. 95% CI, Chi-square test with calculation of adjusted standardized residuals and Fisher's test were performed. The level of significance p=0.05 was set. The differences in preoperative and postoperative manifestations according to group were not statistically significant (Fisher's p = 0.9140) and (Fisher's p = 0.992), respectively. No differences were found between proportions of preoperative radiological findings according to group. Measured quarterly, there were no significant differences between proportions of teeth with bone cortical continuity and with postoperative periapical radiolucency according to group, (p Fisher = 0.7780) and (p Fisher = 0.7909), respectively. Due to the small number of works that report its use for this technique, is necessary to carry out new clinical trials with larger sample sizes, to compare it with other materials and techniques, and determine if its success rate in the long term is greater than that of currently used materials and techniques (AU)

Deterministic Generation of Large Fock States.

We present a protocol to deterministically prepare the electromagnetic field in a large photon number state. The field starts in a coherent state and, through resonant interaction with one or few two-level systems, it evolves into a coherently displaced Fock state without any postselection. We show the feasibility of the scheme under realistic parameters. The presented method opens a door to reach Fock states, with n∼100 and optimal fidelities above 70%, blurring the line between macroscopic and quantum states of the field.

MET phosphorylation predicts poor outcome in small cell lung carcinoma and its inhibition blocks HGF-induced effects in MET mutant cell lines.

BACKGROUND: Small cell lung carcinoma (SCLC) has poor prognosis and remains orphan from targeted therapy. MET is activated in several tumour types and may be a promising therapeutic target. METHODS: To evaluate the role of MET in SCLC, MET gene status and protein expression were evaluated in a panel of SCLC cell lines. The MET inhibitor PHA-665752 was used to study effects of pathway inhibition in basal and hepatocyte growth factor (HGF)-stimulated conditions. Immunohistochemistry for MET and p-MET was performed in human SCLC samples and association with outcome was assessed. RESULTS: In MET mutant SCLC cells, HGF induced MET phosphorylation, increased proliferation, invasiveness and clonogenic growth. PHA-665752 blocked MET phosphorylation and counteracted HGF-induced effects. In clinical samples, total MET and p-MET overexpression were detected in 54% and 43% SCLC tumours (n = 77), respectively. MET phosphorylation was associated with poor median overall survival (132 days) vs p-MET negative cases (287 days) (P < 0.001). Phospho-MET retained its prognostic value in a multivariate analysis. CONCLUSIONS: MET activation resulted in a more aggressive phenotype in MET mutant SCLC cells and its inhibition by PHA-665752 reversed this phenotype. In patients with SCLC, MET activation was associated with worse prognosis, suggesting a role in the adverse clinical behaviour in this disease.

Displasias vertebrales múltiples asociadas a Síndrome de Rokitansky: una causa poco frecuente de escoliosis congénita. A propósito de un caso / Multiple vertebral dysplasia associated with Rokitansky Syndrome: un uncommon cause of congenital scoliosis. Case report

Las displasias vertebrales son defectos del desarrollo que afectan principalmente a los cuerpos vertebrales, dando lugar a graves deformidades de la columna vertebral y de la caja torácica, en forma de escoliosis y cifoescoliosis congénitas. Pueden ser clasificadas en fallos de la formación, fallos de la segmentación o combinación de ambos. La localización y el tipo de defecto vertebral determinarán la gravedad de la curva patológica. Dichas anomalías pueden aparecer aisladas o asociadas a defectos neurales, viscerales y/o en las extremidades que deben ser descartados en el momento del diagnóstico, solicitando estudios genéticos y de imagen adicionales. El diagnostico precoz, así como el tratamiento rehabilitador con un exhaustivo seguimiento, son de vital importancia para prevenir la progresión de la escoliosis y las posibles complicaciones pulmonares. Presentamos un caso clínico muy poco frecuente, de múltiples anomalías vertebrales asociado a Síndrome de Rokitansky en una mujer que desarrolló escoliosis durante la pubertad (AU)

Vertebral dysplasia is a developmental defect, mainly of the vertebral bodies that cause severe spinal column and thoracic deformity that include congenital scoliosis and kyphoscoliosis. These vertebral anomalies can be classified as failure of formation, failure of segmentation, or a combination of both. The location and type of the vertebral defect determines the severity of the scoliosis. Is mandatory known that these abnormalities may be isolated or associated with concurrent neural, limb or visceral anomalies, which must be ruled out. Therefore additional imaging and genetical studies are necessary to provide evidence of these associated defects. Early diagnosis and rehabilitation treatment with exhaustive expectant watching are vital to prevent development of sever deformities and possible pulmonary complications. We report a representative case of multiple vertebral anomalies associated with Rokitansky Syndrome in a female who develops scoliosis during her puberty (AU)

C-MET as a new therapeutic target for the development of novel anticancer drugs.

MET is a tyrosine kinase receptor that, upon binding of its natural ligand, the hepatocyte growth factor (HGF), is phosphorylated and subsequently activates different signalling pathways involved in proliferation, motility, migration and invasion. MET has been found to be aberrantly activated in human cancer via mutation, amplification or protein overexpression. MET expression and activation have been associated with prognosis in a number of tumour types and predict response to MET inhibitors in preclinical models. Here we review the HGF/MET signalling pathway, its role in human cancer and the different inhibitory strategies that have been developed for therapeutic use.

C-MET as a new therapeutic target for the development of novel anticancer drugs

MET is a tyrosine kinase receptor that, upon binding of its natural ligand, the hepatocyte growth factor (HGF), is phosphorylated and subsequently activates different signalling pathways involved in proliferation, motility, migration and invasion. MET has been found to be aberrantly activated in human cancer via mutation, amplification or protein overexpression. MET expression and activation have been associated with prognosis in a number of tumour types and predict response to MET inhibitors in preclinical models. Here we review the HGF/MET signalling pathway, its role in human cancer and the different inhibitory strategies that have been developed for therapeutic use (AU)

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Sequencing of the porB gene: a step toward a true characterization of Neisseria meningitidis.

Variations in class 2/3 (PorB) proteins form the basis for meningococcal serotyping. Antibodies against these proteins are bactericidal, making serotyping results useful not only for epidemiological surveillance of meningococcal disease but also for identifying potential vaccine components. A total of 20 to 60% of meningococcal B and C isolates from any given population are nontypeable (NT) using a panel of monoclonal antibodies. To analyze the mechanisms responsible for the nonserotypeability characteristic in Neisseria meningitidis, we (i) established the nucleotide sequences of porB gene in 146 meningococcal strains (95 not recognized by the serotyping panel), (ii) identified 18 new allelic variants of the porB gene, (iii) correlated allelic variants with serotypes, (iv) suggest the nontypeability characteristic in those 95 NT strains, and (v) reject the possibility of variation in the levels of PorB expression.

Cell populations in the pineal gland of the viscacha (Lagostomus maximus). Seasonal variations.

Pineal samples of the viscacha, which were taken in winter and in summer, were analysed using both light and electron microscopy. The differences found between the two seasons were few in number but significant. The parenchyma showed two main cell populations. Type I cells occupied the largest volume of the pineal and showed the characteristics of typical pinealocytes. Many processes, some of which were filled with vesicles, could be seen in intimate contact with the neighbouring cells. The presence in the winter samples of "synaptic" ribbons and spherules, which were almost absent in the summer pineals, suggests a seasonal rhythm. These synaptic-like structures, as well as the abundant subsurface cisterns present in type I cells, appeared as basic differential features which allowed these cells to be distinguished from type II cells. These latter cells, which can be classified as interstitial cells, showed some other distinguishing features, such as irregular-shaped nuclei, abundant deposits of glycogen-like particles and structures of unknown function consisting of concentric cisterns surrounding a dense body. In the summer, interstitial cells displayed numerous large round bodies, which contributed to increase the cellular volume slightly. Regarding other constituents, like glial cell processes, vessels of non-fenestrated endothelium and sympathetic innervation, no qualitative differences were observed between the two seasons studied. We have presented here some morphological evidences of the circannual rhythm of the viscacha pineal, as well as ultrastructural criteria for distinguishing the main cell populations of this organ, which could be useful for studies carried out in other mammals.

Ultrastructural morphometry of nucleoli: potential usefulness for objective grading of clear cell renal cell carcinoma.

The authors attempted to determine the potential prognostic value of several ultrastructural morphometric parameters, including nuclear, nucleolar, and cytoplasmic features, that could be used in the objective and reproducible histological grading of clear cell renal cell carcinoma. Several nuclear and cytoplasmic parameters were assessed by ultrastructural morphometry in 26 consecutive cases of clear cell renal cell carcinoma. The nuclear and nucleolar sizes, the number of nucleoli per nuclear section and the number of marginated nucleoli, Fuhrman's nuclear grade, and Robson's stage were recorded. In addition, the proportion of cytoplasmic components was semiquantitatively estimated and compared to light microscopic appearance. Follow-up ranged from 5 to 15 years (mean = 10 years). Statistical evaluations were performed by means of the Pearson or Spearman correlation coefficient tests, and differences in survival were estimated, using the Mantel-Cox proportional risk method. Differences in survival among patients with a mean nuclear area over and under 160 microm2, and among those with a mean nucleolar area over and under 10 microm2, were statistically significant. (Cutoff points were selected at the median value for both parameters; Mantel-Cox test: chi2 = 7.102, p < .01; and chi2 = 11.096, p < .001, respectively). Fuhrman's nuclear grade (p < .01) and tumor stage at diagnosis (p < .001) were also related to survival. These data suggest that, out of all the ultrastructural morphometric features, nucleolar area is the most useful in the reproducible and accurate grading of clear cell renal cell carcinoma.

Age-related morphometric changes in the pineal gland. A comparative study between C57BL/6J and CBA mice.

Relatively little is known about the effects of melatonin on the aging of the pineal, the organ which is the main place for synthesis of this hormone. Using simple morphometric methods, some parameters of the pineal gland, such as total volume, number of pinealocytes and pinealocyte volume were estimated in two mice strains: normal CBA and melatonin-deficient C57BL/6J. Two age groups, 6 weeks and 10 months, were studied in order to evaluate possible differential age-related changes between both strains. Pineals of both strains have similar morphometric and morphological features at 6 weeks of age. This suggests that pineal development, which has already concluded at 6 weeks of age, is not affected by the absence of melatonin synthesis in the pinealocytes. Later on, CBA pineal showed an increase in size caused by cellular hypertrophy. In contrast, the C57BL/6J pineal volume decreased by loss of pinealocytes in the same period of time. Semithin sections analysed by light microscopy did not show that this cell death was evident in the C57BL/6J strain at any of the ages studied. Thus, a gradual loss of pinealocytes could be hypothesised in these pineals. These results suggest that pineal melatonin could have a role in the maintenance of pinealocyte viability and the increase of pineal size which takes place after development. The abnormal pattern observed in the C57BL/6J pineal should be taken into account in future studies on this gland.

Size and degeneration increase in herring bodies during aging in hamsters.

The hypothalamo-neurohypophysial tract of young, adult and aged male hamsters was studied at lateral and ventral regions of hypothalamus by means of electron microscopy. Neurosecretory swelling axons (Herring bodies) were usually found as classically described containing abundant neurosecretory granules, mitochondria, few microtubules and profiles of smooth endoplasmic reticulum in all groups of age. However, in aged hamsters, starting at 18-month-old subjects, we observed that the size of some neurosecretory axons was highly increased. Autophagic and degenerative features were seen in the larger ones. These data could suggest abnormal axonal storage or axonal transport blocked during aging. The implications in the role of hypothalamus-neurohypophysial system during aging are discussed.

Legal abortion in Asturias (Spain) after the 1985 law: sociodemographic characteristics of women applying for abortion.

STUDY OBJECTIVE: To describe the use of induced abortion (IA) in Asturias after its legalisation as well as the socio-demographic characteristics of women applying for abortion. DESIGN AND SETTING: Descriptive study, population-based, using data collected by the regional abortion surveillance system for the period 1988 1994. MAIN RESULTS: The number of IA and the abortion rate (AR) (10 per 1000 women aged 15-49) have been stable in Asturias during the study period. The highest ARs were found for women in the age group 20-34, for divorced/separated, for women with a higher educational level and for women with only one child. The proportion of pregnancies which ended in abortion was one in four; for teenagers and women over 34 years it was one in two. This proportion was also higher for women not married, students and women with two or more children. Ninety-eight percent of all abortions took place in private clinics, the woman's physical/mental health being the medical indication for these abortions. Abortion was most often performed within eight weeks of gestation (65%). Late abortion ocurred more frequently among teenagers and women of low educational level. Eighteen percent of women had repeated abortions. A high proportion (61%) of women applying for abortion had not used the Family Planning (FP) services in the previous two years; adolescents and women of low educational level had the lowest frequencies of FP use. CONCLUSIONS: Compared with that of other European countries, the AR in Asturias was intermediate. The results regarding adolescents show the need for evaluation and promotion of sex education and contraceptive programmes. The lower and later use of abortion by women of low educational level shows inequalities that call for specific action.

Quantitative ultrastructural evidences suggest no age-related changes in biosynthesis and processing within parvocellular cells of the paraventricular nucleus in hamsters.

The parvocellular neurons of the parvocellular division of the paraventricular nucleus (PVPA) were studied in hamsters at six point ages (from 3 to 30 months old). Standard manual morphometric techniques were used to obtain data of parvocellular activity including nuclear and nucleolar size, as well as the percentage of the cell occupied by Golgi apparatus (GA), mitochondria and rough endoplasmic reticulum (RER). Other directly age-related parameters like amounts of nuclear invagination and lipofuscin have also been studied. No significant differences in the measured subcellular components were detected among groups studied, except slight increases in lipofuscin. No age-related changes were found in the synthesizing apparatus, but a significant decrease in the cell area was observed in older groups. This finding could suggest a reduction in absolute terms in the protein synthesis of the parvocellular neurons during aging. Ultrastructural morphometric observations in parvocellular neurons are discussed in relation to synthesizing activity and hormone production during aging.

The magnocellular neurosecretory system of the hamster hypothalamus: an ultrastructural and morphometric study during lifetime.

A quantitative study regarding the age-related changes occurring in the nucleus and the somatic organelles of neurosecretory magnocellular neurons of the hypothalamo neurohypophyseal system (HNS) was carried out in the hamster at six age-points during animal life. The magnocellular cells of both parts of the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of male Syrian hamsters between 3 and 30 months of age were examined ultrastructurally. Cells of all age groups present the same morphological ultrastructure. Standard manual morphometric techniques are used to calculate the following parameters related directly or indirectly with cellular activity: nuclear area, nucleolar area, nuclear invagination index and volumetric fractions of some intracellular structures (Golgi apparatus, mitochondria, rough endoplasmic reticulum and lipofuscin). With respect to the cell nucleus, the parameters are not modified during aging. No significant differences in the volume density of subcellular components, except lipofuscin, were detected at the age groups studies. However, there is a positive linear trend among all parameters and age except for the rough endoplasmic reticulum. Our results suggest maintenance of the synthetic activity of the magnocellular neurons in the hamster during aging but in no case an increase in their metabolic activity.