Clinical guide for the diagnosis and follow-up of myotonic dystrophy type 1, MD1 or Steinert's disease. / Guía clínica para el diagnóstico y seguimiento de la distrofia miotónica tipo 1, DM1 o enfermedad de Steinert.

BACKGROUND AND OBJECTIVES: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1. MATERIAL AND METHODS: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide. RECOMMENDATIONS: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives. CONCLUSION: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up.

Imaging the molecular channel in acetaldehyde photodissociation: roaming and transition state mechanisms.

The roaming dynamics in the photodissociation of acetaldehyde is studied through the first absorption band, in the wavelength interval ranging from 230 nm to 325 nm. Using a combination of the velocity-map imaging technique and rotational resonance enhanced multiphoton ionization (REMPI) spectroscopy of the CO fragment, the branching ratio between the canonical transition state and roaming dissociation mechanisms is obtained at each of the photolysis wavelengths studied. Upon one photon absorption, the molecule is excited to the first singlet excited S(1) state, which, depending on the excitation wavelength, either converts back to highly vibrationally excited ground S(0) state or undergoes intersystem crossing to the first excited triplet T(1) state, from where the molecule can dissociate over two main channels: the radical (CH(3) + HCO) and the molecular (CO + CH(4)) channels. Three dynamical regions are characterized: in the red edge of the absorption band, at excitation energies below the T(1) barrier, the ratio of the roaming dissociation channel increases, largely surpassing the transition state contribution. As the excitation wavelength is increased, the roaming propensity decreases reaching a minimum at wavelengths ∼308 nm. Towards the blue edge, at 230 nm, an upper limit of ∼50% has been estimated for the contribution of the roaming channel. The experimental results are interpreted in terms of the interaction between the different potential energy surfaces involved by means of ab initio stationary points and intrinsic reaction coordinate paths calculations.

Imaging the radical channel in acetaldehyde photodissociation: competing mechanisms at energies close to the triplet exit barrier.

The photodissociation of acetaldehyde in the radical channel has been studied at wavelengths between 315 and 325 nm using the velocity-map imaging technique. Upon one-photon absorption at 315 nm, the molecule is excited to the first singlet excited state S(1), which, in turn, undergoes intersystem crossing to the first excited triplet state T(1). On the triplet surface, the molecule dissociates into CH(3) and HCO radicals with large kinetic energy release (KER), in accordance with the well characterized exit barrier on T(1). However, at longer wavelengths (>320 nm), which correspond to excitation energies just below the triplet barrier, a sudden change in KER is observed. At these photolysis wavelengths, there is not enough energy to surpass the exit barrier on the triplet state, which leaves the possibility of unimolecular dissociation on S(0) after internal conversion from S(1). We have characterized the fragments' KER at these wavelengths, as well as determined the energy partitioning for the radical fragments. A new accurate estimate of the barrier height on T(1) is presented.

The photodissociation of CH(3)I in the red edge of the A-band: Comparison between slice imaging experiments and multisurface wave packet calculations.

The photodissociation of methyl iodide at different wavelengths in the red edge of the A-band (286-333 nm) has been studied using a combination of slice imaging and resonance enhanced multiphoton ionization detection of the methyl fragment in the vibrational ground state (nu=0). The kinetic energy distributions (KED) of the produced CH(3)(nu=0) fragments show a vibrational structure, both in the I((2)P(3/2)) and I( *)((2)P(1/2)) channels, due to the contribution to the overall process of initial vibrational excitation in the nu(3)(C-I) mode of the parent CH(3)I. The structures observed in the KEDs shift toward upper vibrational excited levels of CH(3)I when the photolysis wavelength is increased. The I((2)P(3/2))/I( *)((2)P(1/2)) branching ratios, photofragment anisotropies, and the contribution of vibrational excitation of the parent CH(3)I are explained in terms of the contribution of the three excited surfaces involved in the photodissociation process, (3)Q(0), (1)Q(1), and (3)Q(1), as well as the probability of nonadiabatic curve crossing (1)Q(1)<--(3)Q(0). The experimental results are compared with multisurface wave packet calculations carried out using the available ab initio potential energy surfaces, transition moments, and nonadiabatic couplings, employing a reduced dimensionality (pseudotriatomic) model. A general qualitative good agreement has been found between theory and experiment, the most important discrepancies being in the I((2)P(3/2))/[I((2)P(3/2))+I( *)((2)P(1/2))] branching ratios. Inaccuracies of the available potential energy surfaces are the main reason for the discrepancies.

Acute necrotizing pancreatitis and severe hepatic failure: description of three cases.

INTRODUCTION: Acute pancreatitis is not uncommon in fulminant hepatic failure (FHF) as confirmed by histology or serology. A few reports exist of symptomatic pancreatitis in the setting of acute viral hepatitis; the diagnosis is usually made intraoperatively or postmortem. We report three cases of liver transplant (OLT) recipients with severe acute liver failure and severe acute pancreatitis as an intraoperative finding. METHODS: We undertook a retrospective review among a large cohort of liver transplant recipients to define the impact of this problem. RESULTS: Between 1999 and 2007, 293. LTs were performed including 15 (5%) who had severe acute liver failure (nine with FHF and six with an emergency retransplantation [ER]). Among this group, three patients were diagnosed intraoperatively with acute necrotizing pancreatitis (ANP): two patients with associated FHF and one with an ER due to ABO incompatibility. None of the patients had symptoms of pancreatitis. In all, ANP was classified as Balthazar CT grade D-E, which determined the outcome. All the patients developed a pseudocyst and abscess, which required surgical drains. CONCLUSION: ANP was diagnosed as an intraoperative finding in patients with FHF. The mechanism of pancreatitis in patients with FHF is unknown. It may be multifactorial (virus, acute liver failure, hypotension, infection, drug-induced lesion,). This association leads to a worse outcome due to the complications.

Slice imaging of the photodissociation of acetaldehyde at 248 nm. Evidence of a roaming mechanism.

The photodissociation of acetaldehyde in the molecular channel yielding CO and CH(4) at 248 nm has been studied, probing different rotational states of the CO(nu = 0) fragment by slice ion imaging using a 2+1 REMPI scheme at around 230 nm. From the slice images, clear evidence of the co-existence of two different mechanisms has been obtained. One of the mechanisms is consistent with the well-studied conventional transition state in which CO products appear rotationally excited, and the second is consistent with a roaming mechanism. This roaming mechanism is characterized by a low rotational energy disposal into the CO fragment as well as by a very low kinetic energy release, corresponding to a high internal energy in the CH(4) counter-fragment.

[Epidemiology in inflammatory bowel disease in five areas of Asturias. Spain]. / Epidemiología de la enfermedad inflamaroria intestinal crónica en cinco áreas de Asturias. España.

AIMS: The epidemiologic analysis inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology. IBD has been reported to have varying frequencies in different parts of the world, and there seem to be significant differences in the disease pattern and clinical course. The aim of the present study was to assess the disease pattern of IBD in Asturias (Spain). PATIENTS AND METHODS: A descriptive epidemiological population based study, retrospective (1954-1993) and prospective (1994-97), was performed to study 1018 patients found, bigger than 14 years, to have IBD, in five areas of Asturias (Spain) (461.965 inhabitants). RESULTS: During the period of time studied, we diagnosed 1018 IBD [565 ulcerative colitis (55.5%), 415 (40.8%) Crohn's disease and 38(3.7%) indeterminate colitis], with 482 females (47.2%), 536 males (52.8%), and male/female: 1.11. Age at diagnosis were 39.49 +/- 1.08 (95% CI : 38.41 +/- 40.57); (UC: 43.95 +/- 1.47; CD: 33.53 +/- 1.51; IC: 38.26 +/- 5.14. p = 0.000. Age at onset previously at diagnosis for UC: 42.84 +/- 1.34; CD: 30.68 +/- 1.40; IC: 36.74 +/- 4.86 (p = 0.000). Diagnosis criteria: UC: syntomatic 97.34% (p = ns), endoscopy 96.63% (p = 0.000 pathology 90.26% (p = 0.000). CD: radiology 83.61% (p =0.000). Study level in CD: 57.57 (p = 0.0005). Family history: 8.4%. The most frequent involvement at diagnosis of UC was proctitis only, in 13.6%, 269% rectum and sigmoid 26% let colitis, 20% pancolitis, and in CD colon only, in 16.7%, 30.3% terminal ileum, 41.3% ileo-colon of the patients. This also helps to explain the differences in severity, need for surgery, and survival noted between community based studies. CONCLUSIONS: We highlight the uniformity of distribution of the inflammatory bowel disease in relation to types and sex. The high frequency of familial Crohn's disease suggests a genetic predisposition. Highlighting a bigger morbilidad for the Crohn's Disease reflected in the surgical requirements, but however with smaller mortality that in ulcerative colitis.

[Incidence and prevalence of inflammatory bowel disease. Asturian study in 5 areas (EIICEA). Spain]. / Incidencia y prevalencia en enfermedad inflamatoria intestinal crónica. Estudio asturiano en cinco áreas (EIICEA). España.

AIMS: To know and to compare Inflammatory Bowel Disease (IBD) Incidence and Prevalence rates in in five areas of Asturias (Spain). We conducted a prospective epidemiologic study of IBD in the Province of Liege (1 million inhabitants). PATIENT AND METHODS: We conducted a descriptive, populational, collaborative epidemiologic study, retrospective between 1954 and 1993 and prospective between 1994 and 1997. All patients diagnosed according to a standard protocol for case ascertainment and definition of IBD, aged 14 years or more are included, in five areas of Asturias (Spain) (461,965 inhabitants). RESULTS: For the period 1954 to 1997, 1018 IBD have been diagnosed [565 ulcerative colitis (UC) (55.5%), 415 Crohn's disease (CD) (40.8%) and 38 undefined IBD (IC) (3.7%)]; [482 women (47.2%), 536 males (52.8%)]. In the 4 year-prospective period, 306 cases were collected: 176 UC (57.51%), 110 CD (35.94) and 20 IC (6.53%); UC/CD: 1.6. Without appreciable and significant differences between Frequency of illness groups and sexes. IBD incidence rate (per 100,000 per year) (1954-97) is 5.12 (95% CI = 3.05-7.18) (UC: 2.84; CD: 2.08; IC: 0.19; UC/CD 1.36). In the 4 years- prospective study, IBD incidence rate is 16.55 (95% CI = 12.84-20.25), (UC: 9.52; CD: 5.95; IC: 1.08; UC/CD: 1.6). IBD prevalence rate in 1997 is 205.21 (95% CI = 182.14-227.29), (UC: 109.96; CD: 87.45; IC: 7.79). Comparisons have settled down among the studied areas, without finding differences statistically significant. CONCLUSIONS: Inflammatory Bowel Disease incidence and prevalence rates of in our region are homogeneous between the cities investigated and superior than those historically reported in Spanish studies. These results were similar to those observed in European studies.

[Epidemiology of chronic inflammatory bowel disease in Gijón, Asturias]. / Epidemiología de la enfermedad inflamatoria intestinal crónica en Gijón. Asturias.

AIMS: To determine several aspects of the epidemiology of chronic inflammatory bowel disease (IBD), including distribution of the various forms of IBD, sex, age at diagnosis considering lag-time to diagnosis, criteria used in the diagnosis, the relationship between educational level and activity, familial aggregation, phenotype (site and clinical type), number of admissions and mean hospital stay/year, surgical requirements and mortality. PATIENTS AND METHODS: We carried out a retrospective (1954-1993) and prospective (1994-97) descriptive epidemiologic population study, in the fifth health district of Gijón in Asturias (Spain), with 225,798 inhabitants. A total of 595 patients diagnosed with chronic IBD according to the diagnostic criteria described by Lennard-Jones and Truelove for Crohn's disease (CD) and ulcerative colitis (UC) and according to Ashley B. Price's criteria for indeterminate colitis (IC) were studied. In all patients a complete clinical follow-up was performed. RESULTS: During the study period, we diagnosed 595 patients with IBD [305 patients with UC (51.3%), 272 (45.7%) patients with CD and 18 (3%) with IC]. Sex distribution was 287 females (48.2%) and 308 males (51.8%), with a male/female ratio of 1.07. Mean age at presentation was 38.79 +/- 17.44 years (UC: 43.37 +/- 17.55; CD: 33.98 +/- 16.16; IC: 33.73 +/- 13.48), p = 0.000. Age at onset prior to diagnosis was as follows: UC: 42.03; CD: 30.47; IC: 30.99 (p = 0.000). Diagnostic criteria used in UC was symptomatic in 99.01% (p = ns), endoscopic in 95.04% (p = 0.000), and pathologic in 87.21% (p = 0.000); in CD diagnostic criteria used was radiologic in 85.29% (p = 0.000). A total of 29.1% of patients with UC and 66.7% of those with CD had higher education (p = 0.0005). Family history was found in 9.8%. Anatomical site was as follows: in UC: rectum 21%, 28.2% rectum and sigmoid, 22.3% left colitis, 4.2% distal to hepatic flexure and 24% pancolitis; in CD: 32.72% terminal ileum, 19.11% colon, 37.13% ileo-colon, 11.02% extensive intestinal and 3.67% gastro-duodenal. A total of 8.37% of patients with UC and 14.51% of those with CD had been hospitalized during the previous 4 years; mean hospital stay was 1.63 days in UC and 2.27 days in CD. The mean surgical requirements were 0.54 +/- 1.08 (31.59%); UC: 0.11 +/- 0.36 (10.2%); CD: 1.04 +/- 1.38 (56.25%), p = 0.000. The mortality rate was 48.73 deaths/1,000 inhabitants (UC: T = 65.57; CD: T = 33.08; IC:T= 0) p = ns. The standardized mortality ratio was 4.83 (UC: 6.51; CD: 3.28). CONCLUSIONS: We highlight the uniformity of the distribution of IBD in relation to types of disease and sex. Patients with CD had a higher level of education. Genetic components play an important role in these diseases and familial aggregation was high, especially in CD. Complicated situations are infrequent in this group of patients. Morbidity was higher in patients with CD as reflected by surgical requirements and hospital stay. Mortality was lower in CD than in UC.

Energetic metabolism in mouse cerebral cortex during chronic hypoxia.

We measured the activities of Na(+)K(+) ATPase and of enzymes of the glycolytic pathway, Krebs cycle, and the respiratory chain in cerebral cortex of mice exposed to chronic hypoxia for three weeks and compared their values with those of sea level controls. There were no differences in Na(+)K(+) ATPase activity or in the activity of glycolytic enzymes. In the Krebs cycle, a 66% increase of succinate dehydrogenase activity was found due to a lower Km. In contrast, respiratory chain cytochrome oxidase activity was reduced by 12% in mice exposed to hypoxia. This suggested that the metabolic demand would be satisfied despite the respiratory chain depression (cytochrome oxidase), probably due to anaerobic energy production within the mitochondria (succinate dehydrogenase).

[Incidence and prevalence of inflammatory bowel disease in Gijon, Asturias, Spain]. / Incidencia y prevalencia de la enfermedad inflamatoria intestinal en Gijón (Asturias).

AIM: To determine the incidence and prevalence of inflammatory bowel disease in our area and to compare our results with those of other series from Spain and other parts of the world. PATIENTS AND METHODS: Descriptive epidemiologic population study, retrospective (1954-1993) and prospective (1994-1997) in health district V of Gijón in Asturias (Spain) with 225,798 inhabitants. Diagnostic criteria used were those described by Lennard-Jones and Truelove for Crohn's disease and ulcerative colitis and those described by Ashley B. Price for indeterminate colitis. Annual incidence was expressed per 100,000 inhabitants. Prevalence was calculated excluding cured patients: proctocolectomized in ulcerative colitis (10 cases) and deaths (29 cases). RESULTS: During the period studied, 595 patients were diagnosed with bowel disease (305 patients with ulcerative colitis, 272 with Crohn's disease and 18 with indeterminate colitis). Mean annual incidence (1954-1997) was 6.128 (95% CI: 2.90-9.36). In the 4-year prospective study the incidence was 15.49 (95% CI: 11.19-21.79), 9.36 for ulcerative colitis, 6.08 for Crohn's disease and 0.77 for indeterminate colitis (UC/CD: 1.58). Prevalence was 246.23 (95% CI: 225.6-226.70, 212.79 for ulcerative colitis, 116.47 for Crohn's disease and 7.97 for indeterminate colitis. CONCLUSIONS: Incidence and prevalence obtained in our environment were higher than those described in other areas of Spain and were similar to those found in areas of Europe and other parts of the world with a higher incidence. Incidence and prevalence have increased since 1980, probably due to the widespread use of endoscopy as a diagnostic technique. Rates were higher in the prospective study than in the retrospective one.

[Study of incidence of osteoporotic fractures in a cohort of individuals older than 50 years from Asturias, Spain, after a 6 year follow-up period]. / Estudio de incidencia de fracturas osteoporóticas en una cohorte mayor de 50 años durante un período de 6 años de seguimiento.

BACKGROUND: The present work, performed as follow-up of the prevalence study of vertebral fractures (EVOS Study), evaluates in a 6 year period the incidence of vertebral fractures and other osteoporotic fractures in Oviedo (Asturias, Spain) in people older than 50 years. SUBJECTS AND METHODS: The study was performed in a cohort from the Oviedo's local registry in 1986. 624 men and women were followed by 3 postal questionnaires. The first questionnaire referred to the history of falls and fractures that happened during the follow-up period performed. Between the 2nd and 3rd follow-up subjects were invited to repeat the X-rays previously performed in the initial study. RESULTS: The incidence of osteoporotic fractures was higher in women than in men. In both sexes, vertebral fracture was the one which reached the highest incidence. Compared with men, Colles' fracture in women occurred earlier, with 5 times higher incidence. The incidence of hip fracture was twice higher in women than in men. A prevalent vertebral fractures increased until 5 times the incidence of vertebral and hip fracture. CONCLUSIONS: Among the osteoporotic fractures, vertebral fracture had a highest incidence values in both sexes. Although vertebral and hip fractures were twice incident in women compared with men, the incidence of Colles fracture was five times higher in women. A pre-existing vertebral fracture is an important risk factor to develop a new vertebral or hip fracture.

Increased brain capillaries in chronic hypoxia.

The effect of chronic hypobaric hypoxia (28 days, 455 Torr) on the organization of brain vessels was studied in Balb/c mice. In comparison to age-matched controls kept at sea level, emulsion-perfused capillaries in hypoxic mice showed marked dilation in all brain areas studied. Capillary length per unit volume of tissue (Lv) was increased in the cerebellar granular layer, the caudate nucleus, the globus pallidus, the substantia nigra, the superior colliculus, and the dentate gyrus. There was a selective increase of Lv in the hippocampus (CA1 strata pyramidale and lacunosum and CA3 strata pyramidale and oriens) and in somatosensory cortex layers V and VI, motor cortex layers II, III, V, and VI, and auditory cortex layers II and III. An increase in capillary surface area per unit volume of tissue was also determined in several brain areas, including layer IV of somatosensory cortex, where Lv was not significantly increased. The O2 diffusion conductance and PO2 in the tissues were estimated with a mathematical model. The remodeling of capillary diameter and length during chronic hypoxia accounts for the significant increase of O2 conductance to neural tissues. Also the estimated tissue PO2 in chronic brain hypoxia is markedly increased in the caudate nucleus and the substantia nigra compared with acute hypoxia. These results suggest that formation of new capillaries is an important mechanism to restore the O2 deficit in chronic brain hypoxia and that local rates of energy utilization may influence angiogenesis in different areas of the brain.

[Incidence and risk factors in fractures of the proximal femur due to osteoporosis]. / Incidencia y factores de riesgo de la fractura de fémur proximal por osteoporosis.

Every year more than one million fractures of the proximal femur occur in the world, especially in older persons. Given the continuous aging experienced by populations, such fractures will become more frequent from year to year and will constitute a growing public health problem. The largest increase is expected to occur in countries of Latin America around the year 2050. Since nearly 70% of all atraumatic fractures in persons over 45 are due to osteoporosis, a case-control study was conducted in the city of Mar del Plata, Argentina, for the purpose of investigating the incidence of and the risk factors associated with proximal femur fractures due to osteoporosis. Between 1 August 1992 and 31 July 1993, a record was kept of all fractures of the proximal femur due to osteoporosis in persons over 50 years of age that visited any of the city's 30 public and private health centers. A total of 246 cases was recorded. The incidence rate per 100,000 inhabitants in the above-50 population was 259 among women and 92 among men, for a ratio of 2.8:1. The incidence was consistently higher in the older age groups, especially in persons over 75. Factors associated with a statistically significant increased risk of fracture of the proximal femur were: a history of neurologic disorders, psychotherapeutic drug use, alcohol consumption, previous fractures, cardiovascular disease, and a decreased intake of milk products. There were no observed differences between cases and controls with respect to age at menopause, weight, height, previous activity, smoking habits, or sun exposure, nor were such differences detected in terms of the percentage of women who had undergone oophorectomy.

Increase in succinate dehydrogenase activity in mice brain during chronic hypoxia

Se midió la actividad de la succinato deshidrogenasa (SDH) en siete regiones cerebrales de ratones expuestos a tres semanas de hipoxia hipobárica (450 torr, 4380 metros por encima del nivel del mar), y se comparó con los controles normóxicos de nivel del mar. En el grupo hipóxico se encontró un aumento del 40 por ciento en la actividad de la SDH en la corteza y el hipocampo. Este podría ser un mecanismo compensatorio frente a la disminución de la actividad de otros componentes de la cadena respiratoria en condiciones de hipoxia hipobárica, como una estrategia para mantener la producción normal de ATP.

Chronic hypoxia induces modification of the N-methyl-D-aspartate receptor in rat brain.

This study examined [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor in membranes prepared from cerebral cortex, hippocampus and corpus striatum of 3 week old rats exposed to 10 weeks of intermittent hypobaric hypoxia (4300 m; 450 Torr) and compared results with those of normoxic controls. The cortex, hippocampus and striatum of hypoxic animals had a 36, 35 and 31% reduction in binding sites (Bmax) and a 29, 32 and 17% decrease (reflecting increased affinity) in the dissociation constant (Kd) when compared to controls. In the cerebral cortex, both glutamate (100 microM) and glycine (10 microM) enhanced 3[H]MK-801 binding by two to 3-fold. Coagonist glutamate, however, had a higher EC50 (0.44 microM) in the hypoxic cortical membranes when compared to controls (0.28 microM). No significant differences were found in the EC50 of glycine. The results show that the NMDA receptor is altered in several brain regions of rats developing in a hypoxic environment.