Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance.

BACKGROUND: Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. METHODS: Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. RESULTS: Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. CONCLUSIONS: Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.

[Characteristics of status epilepticus in MELAS. Analysis of four cases]. / Características del estado del mal epiléptico en MELAS. Análisis de cuatro casos.

INTRODUCTION: Clinical characteristics of status epilepticus (SE) as a first manifestation in patients with MELAS who had not previously epileptic episode has been studied little in the literature. OBJECTIVES: Our aim was to analyse precipitating factors, clinical characteristics, EEG and difficulties in the treatment of SE in MELAS. PATIENTS AND METHODS: We studied four cases with ages between 27 an 41 years who began with SE and they had been diagnosed with MELAS during the episode. Case 3 was confirmed by autopsy. Cases 1, 2 and 4 showed a 3243 mtDNA mutation in the lymphocytes. Epileptic seizures had not been present in any previous status case. The precipitating factor in cases 1 and 3 was fever and in case 2 and 4 stress by headache. Moreover in case 2 second status was caused by stress in hyperglycaemic ketoacidosis. All cases were studied with EEG and a brain CT or MRI. RESULTS: All patients started with epilepsia partialis continua that began with partial motor simple seizures, but sometimes progressed to partial complex seizures or secondary tonic clonic seizures. In two cases the initial symptom was migraine with aura, in two cases fever with cephalalgia and in one case diabetes mellitus decompensation. The EEG during a seizure presented a complex pseudoperiodic complex in the temporal-occipital contralateral region that spread to all hemisphere when myoclonus was increased. CONCLUSIONS: SE in MELAS appears in cell stress situation precipitated by hypermetabolic conditions and it provokes claudication in ill mitochondria. In fact, events such as fever, glycemic alterations, hypoxemia or headache that could change the normal mechanism of sequester mitochondrial calcium in the neuron are able to trigger SE. Optimal evolution depends on an improvement of basal metabolic conditions that could precipitate the status. Supplementary folic acid, riboflavin and coenzyme Q 10 can be useful.

Características del estado del mal epiléptico en MELAS. Análisis de cuatro casos / Characteristics of status epilepticus in MELAS. Analysis of four cases

Introducción. El estado de mal epiléptico (EE) como primera manifestación en pacientes con MELAS que previamente no habían tenido crisis epilépticas ha sido escasamente analizado en la literatura.Objetivos. Nuestro propósito ha sido analizar los factores precipitantes, las características electroclínicas y las dificultades en el tratamiento del EE en el MELAS.Pacientes y métodos. Analizamos cuatro casos diagnosticados de MELAS, con edades comprendidas entre 27 y 41 años, que se inician con un EE y son diagnosticados de MELAS durante el episodio. El diagnóstico se realizó en los casos 1, 2 Y 4 analizando en una muestra de sangre periférica el ADN mitocondrial, obteniéndose en todos ellos la mutación 3243 en el ADN linfocitario. El caso 3 se confirmó por necropsia. Ninguno de los pacientes había presentado crisis epilépticas previamente. El factor desencadenante en los casos 1 y 3 fue la fiebre, mientras que los casos 2 y 4 se asociaron a migraña con aura. El estrés provocado por la hiperglucemia cetoacidótica desencadenó el segundo episodio en el caso 2. Todos los casos fueron estudiados con EEG, TC o RM craneal.Resultados. Clínica mente todos los pacientes empezaron con una epilepsia parcial continua que comenzó con crisis parciales motoras simples, pudiendo progresar a crisis parciales complejas o a crisis tonicoclónicas secundariamente generalizadas. En dos ocasiones se asoció a migraña con aura, en dos casos a fiebre con cefalea y en uno a descompensación diabética. El EEG durante las crisis mostraba complejos seudoperiódicos en la región temporo-occipital que se difundían a todo el hemisferio o contra lateralmente cuando se incrementaban las mioclonías.Conclusiones. El EE en el MELAS aparece en situaciones de estrés celular, desencadenado por situaciones hipermetabólicas que hacen claudicar a las mitocondrias enfermas. De esta manera efectos como fiebre, alteraciones de la glucemia o crisis migrañosas que puedan modificar el mecanismo habitual de secuestro del calcio mitocondrial en la neurona son capaces de desencadenarlo. El pronóstico dependerá en parte de la mejoría de las condiciones metabólicas basa les que lo han precipitado

Introduction. Clinical characteristics of status epilepticus (SE) as a first manifestation in patients with MELAS who had not previously epileptic episode has been studied little in the literature.Objectives. Our aim was to analyse precipitating factors, clinical characteristics, EEG and difficulties in the treatment of SE in MELAS.Patients and methods. We studied four cases with ages between 27 an 41 years who began with SE and they had been diagnosed with MELAS during the episode. Case 3 was confirmed by autopsy. Cases 1, 2 and 4 showed a 3243 mtDNA mutation in the lymphocytes. Epileptic seizures had not been present in any previous status case. The precipitating factor in cases 1 and 3 was fever and in case 2 and 4 stress by headache. Moreover in case 2 second status was caused by stress in hyperglycaemic ketoacidosis. AlI cases were studied with EEG and a brain CT or MRI.Results. All patients started with epilepsia partialis continua that began with partial motor simple seizures, but sometimes progressed to partial complex seizures or secondary tonic clonic seizures. In two cases the initial symptom was migraine with aura, in two cases fever with cephalalgia and in one case diabetes mellitus decompensation. The EEG during a seizure presented a complex pseudoperiodic complex in the temporal-occipital contralateral region that spread to all hemisphere when myoclonus was increased.Conclusions. SE in MELAS appears in cell stress situation precipitated by hypermetabolic conditions and it provokes claudication in ill mitochondria. In fact, events such as fever, glycemic alterations, hypoxemia or headache that could change the normal mechanism of sequester mitochondrial calcium in the neuron are able to trigger SE. Optimal evolution depends on an improvement of basal metabolic conditions that could precipitate the status. Supplementary folic acid, riboflavin and coenzyme Q 10 can be useful

Synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active cyclooxygenase-2 inhibitors.

A series of 3,4-diaryloxazolones were prepared and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). Extensive structure-activity relationship work was carried out within this series, and a number of potent and selective COX-2 inhibitors were identified. The replacement of the methyl sulfone group on the 4-phenyl ring by a sulfonamide moiety resulted in compounds with superior in vivo antiinflammatory properties. In the sulfonamide series, the introduction of a methyl group at the 5-position of the oxazolone ring gave rise to very COX-2-selective compounds but with decreased in vivo activity. Selected 3,4-diaryloxazolones exhibited excellent activities in experimental models of arthritis and hyperalgesia. The in vivo activity of these compounds was confirmed with the evaluation of their antipyretic effectiveness and their ability to inhibit migration of proinflammatory cells. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 4-day treatment of 100 mg/kg/day. Within this novel series, sulfonamides 9-11 have been selected for further preclinical evaluation.

Tratamiento del paciente cannábico / Cannabic patient treatment

Se ofrece el tratamiento sintomático de las consecuencias psiquiátricas del consumo de cannabis, el tratamiento de cesación del hábito, y la significación de los controles de orina. Sobre el tratamiento sintomático se compara la semivida de eliminación de los cannabinoides y la de algunos antipsicóticos. Por vez primera, al menos en español, se sistematiza la terapia de cesación del hábito cannábico, teniendo como referencia su homóloga del hábito tabáquico. Se alude al contexto de uso recreativo, a la importancia del ambiente de consumo, y a las interacciones farmacológicas deseadas por los policonsumidores. Se define la cesación del hábito cannábico como terapia psicológica ambulatoria basada en el counselling. Comprende los abordajes individual, grupal y familiar. En este último se distingue entre intervención informativa e intervención terapéutica. Por último, se considera la significación de los controles de orina en el proceso terapéutico. Las conclusiones son: que además de ofrecer tratamiento psiquiátrico sintomático hay que ofrecer tratamiento de cesación del hábito. Que este último requiere competencias profesionales de tipo counselling e incluso psicoterapia, y que los controles de orina son válidos como complemento con fines terapéuticos, pero nunca fiscalizadores por la lenta eliminación de los cannabinoides (AU)

The symptomatic psychiatric treatment of cannabis abuse, the cessation treatment of the habit, and the significance of urinalysis are described. The respective elimination half-lifes of both cannabinoids and some antipsychotics are compared. At least in Spanish, this is the first time when the cessation treatment of the cannabis habit is proposed and systematised. The reference is clearly its homologous in tobaccoism. Context factors as recreative use, relevance of the setting in which cannabis use takes place, and the desired drug interactions of polyusers are considered. Cannabis habit cessation treatment is defined as psychological outpatient therapy technically based on counselling. Individual, group and family approaches are described. The latter includes information and/or therapy interventions. The significance of urinalysis in the treatment process is considered. Conclusions are: besides psychiatric treatment of the symptoms caused by cannabis abuse, cessation treatment of the cannabis habit must be offered. The latter requires as well specific professional competence, to be defined as counselling or even psychotherapy. Urinalysis controls are useful as a complementary treatment instrument, but given the slow elimination of cannabionids they are not indicated for surveillance purposes (AU)

[Unstable detrusor: usefulness of biofeedback]. / Detrusor inestable: utilidad del biofeedback.

Presentation of results of treatment using Biofeedback in two conditions which quite frequently associate vesical instability and incontinence: 65 cases of enuresis and 39 of urinary stress incontinence in females. The method was effective and achieved disappearance of detrusor instability in 78.2% of enuretic cases and 58.9% of urinary stress female incontinence. Outcome for incontinence was less favourable since disappearance was only achieved in 70.5% of enuretics and 20.5% cases of female incontinence. A brief description of the method and instrumentation used is done, which can be easily conveyed to any electromiographic device with real time output. The paper substantiates the authors' views relative to the likely pathogeny of the instability in both processes and the mechanism of action of Biofeedback techniques.

Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine.

A double-blind, randomised, parallel group, multicentre, multinational study compared the effects of 12 months' treatment with lisinopril (10-20 mg once daily) or nifedipine retard tablets (20-40 mg twice daily) in 239 males (aged 18-75 years) and 96 post-menopausal females (aged 40-75 years). They all had a history of clinically stable type II diabetes > 3 months, microalbuminuria and early diabetic nephropathy (a urinary albumin excretion (UAE) rate ranging from 20 to 300 micrograms/min) and a sitting diastolic blood pressure (DBP) 90-100 mm Hg (Korotkoff phase V) inclusive at both entry and after 3-4 weeks' placebo treatment. The aim of treatment was to achieve a reduction in sitting DBP to < 90 mm Hg 24-30 h after the last dose of lisinopril or 12-18 hours after the last dose of nifedipine and to evaluate the effect of these treatments on UAE over 12 months. The effect of the two treatments on ambulatory blood pressure (BP) was also evaluated in a subset of patients. Management of diabetes with oral hypoglycaemic drugs, diet and insulin alone or in combination was permitted. Median UAE fell on lisinopril from 65.5 (range 20-297) micrograms/min at baseline to 39.0 (2-510) micrograms/min after 12 months. On nifedipine median UAE fell from 63.0 (range 20-289) micrograms/min at baseline to 58.0 (9-1192) micrograms/min after 12 months. The estimated median difference between the effects of the two treatments was 20 micrograms/min (P = 0.0006). Over 12 months both treatments produced similar falls in sitting BP from 163 +/- 17/99 +/- 6 mm Hg (mean +/- s.d.) to 147 +/- 18/88 +/- 10 mm Hg for lisinopril and from 161 +/- 18/97 +/- 5 mm Hg to 150 +/- 18/88 +/- 9 mm Hg for nifedipine. Ambulatory BP was assessed in a subset of patients and using areas under the BP-time curve (AUC) a comparison of the effects of the two treatments showed no between-treatment differences. Creatinine clearance, glycaemic control (HbA1c) and lipid profiles did not change significantly during either treatment. Frequency of withdrawals and adverse events were similar for both treatments. We conclude that lisinopril has a significantly more beneficial effect on UAE than nifedipine despite similar effects on both BP and glycaemic control in type II diabetic patients with hypertension.

[Nuclear syndrome of the oculomotor nerve caused by a mesencephalic infarction confirmed by MRI]. / Síndrome "nuclear" del motor ocular común por infarto mesencefálico confirmado con RM.

The nuclear syndrome of the third nerve was first described in 1981. It has the very characteristic disturbance of an ophthalmoplegia with complete ipsilateral third nerve palsy associated with paresis of elevation in contralateral eye. This particularly presentation is due to the innervation of the superior rectus which comes mainly from the contralateral oculomotor nucleus. As associated signs were described contralateral cerebellar and or pyramidal syndromes, uni or bilateral parasympathetic disfunction and sometimes gaze disorders. The etiology es usually a vascular damage (ischemic most frequently) located in mesencephalon. We report on a case of a 60 years old man who developed acute nuclear ophthalmoplegia of the third right nerve accompanied with cerebellar and pyramidal syndrome and focal asterixis in left extremities. MRI showed an ischemic lesion in right paramedial mesencephalic territory with extension to the ipsilateral thalamic region. Pyramidal and cerebellar syndromes and asterixis disappeared in a few weeks, while ophthalmoplegia remained unchanged. Semiologic characteristics and anatomic basis of the nuclear oculomotor syndrome which allow to make the differential diagnosis between this syndrome and intra-axial fascicular disturbances of the third nerve (Weber, Claude and Benedikt syndromes) are discuss.

[Effect of muscle relaxation in hypertensive patients]. / Efecto de la relajación muscular en pacientes hipertensos.

The efficacy of muscle relaxation in the treatment of hypertension has been described by several authors. Our experience with this type of technique is analyzed in this report. The clinical histories of 38 individuals who have taken part in the relaxation program since the end of 1984 (relaxation group: RG) with at least 6 months of follow up, have been reviewed. For each RG patient, two sex, age, and initial diastolic blood pressure (DBP) matched controls were found, obtaining thus a control group (CG) consisting of 70 hypertensive patients who were not participating in any relaxation program. The final efficacy of the program was evaluated recording the systolic blood pressure (SBP), the DBP, and heart rate (HR) 6 and 12 months after the initiation of the program also considering the drop outs and the need of drugs (evaluated with a therapeutic index: TI). There were no differences in the initial parameters between the two groups except for the TI (uncontrollable variable) which was higher in the RG. The final values in the RG showed a slightly lower blood pressure (RG = 135.2/86.9 mm Hg; CG = 139.4/90.4 mm Hg, p = 0.082 for the DBP) as well as a lower number of drop outs (RG = 18.4%); CG = 32.9%, p less than 0.1). 10 patients in the RG while none in the CG were medically discharged. (p = 0.000). The only significant difference found was the increase in TI in the CG (p = 0.000), while the increase observed in the RG was not statistically significant.

Renal tubular acidosis in recurrent renal stone formers.

Renal tubular acidosis (RTA) is a well-known metabolic disturbance that may promote recurrent renal stone formation. However, its incidence, screening criteria and association with other lithogenic metabolic abnormalities are not established in recurrent nephrolithiasis. 10 of 50 consecutive recurrent renal stone formers had a persistent fasting morning urinary pH above 6.0 and/or a basal plasma bicarbonate concentration below 20.0 mM. Acid and alkaline loads disclosed RTA in 3 patients: 1 patient had incomplete type-1 distal RTA in addition to hyperoxaluria; a second patient showed complete type-2 proximal RTA, hyperoxaluria and renal hypercaliuria; and a third patient had incomplete proximal RTA without any other metabolic derangement. These results reinforce the importance of RTA as an isolated metabolic abnormality among recurrent renal stone formers. In addition, RTA appears to be more commonly associated with other lithogenic metabolic derangements than has been previously suspected. The extensive metabolic protocol used in this study provides a useful tool in the diagnosis and therapeutic considerations of recurrent nephrolithiasis.

[Tubular function and renal acidifying in juvenile diabetes mellitus of short evolution]. / Estudio de la función tubular y capacidad renal de acidificación en la diabetes mellitus infanto-juvenil de corta evolución.

The fractional excretion of uric acid, calcium, phosphorus, magnesium and other ions, and the urinary acidifying capacity were studied in then patients with juvenile diabetes of short evolution and in a control group matched for age, sex, and body surface. The diabetic patients showed a hyperexcretion of uric acid, sodium, potassium, chloride and ammonium which was unrelated to the increment of glomerular filtration rate or to glucosuria, and could not be ascribed to diet. The pathophysiologic interpretation of these findings is discussed, concluding that they might be the result of an increase in the filtered load and the behaviour of the tubules in front of the glomerular hyperfunction or metabolic disturbance inherent to the diabetic condition.