Screening Medications for the Treatment of Cannabis Use Disorder.

Cannabis use has been increasingly accepted legally and in public opinion. However, cannabis has the potential to produce adverse physical and mental health effects, and cannabis use disorder (CUD) occurs in a substantial percentage of both occasional and daily cannabis users. Many people have difficulty discontinuing use despite receiving treatment. Therefore, it would be beneficial to develop safe and effective medications for treating CUD. To achieve this, methods have been developed for screening and evaluating potential medications using animal models and controlled experimental protocols in human volunteers. In this chapter, we describe: (1) animal models available for assessing the effect of potential medications on specific aspects of CUD, (2) the main findings obtained so far with these animal models, (3) the approaches used to assess potential medications in humans in laboratory experiments and clinical trials, and (4) the effectiveness of several potential pharmacotherapies on particular aspects of CUD modeled in these human studies.

[Assessment of the efficiency of the clinical management of neuropathic pain in specialist clinics compared to general clinics in neurology health care units in Spain]. / Evaluación de la eficiencia del manejo clínico del dolor neuropático en consultas especializadas frente a consultas generales en unidades asistenciales de neurología en España.

OBJECTIVES: To analyse the cost-consequences of chronic neuropathic pain (NeP) outpatients care comparing management in general clinics (GC) versus specialised pain clinics (SPC) in neurology settings in Spain. METHODS: A 6-month retrospective, cross-sectional, comparative observational study including NeP subjects was designed. Sociodemographics and clinical characteristics of subjects along with pain-related healthcare and non healthcare resources utilization were recorded. Lost-work-days equivalent missed as a consequence of pain were also collected to compute indirect costs. Costs to society were calculated in euros for the year 2008. Severity and interference of pain were used for the main effectiveness evaluation. RESULTS: A total of 234 patients (53% in SPC), 56.8% women, and 59.3+/-14.7 years were included. Patients were allocated according to usual administrative procedures in each participant centre, consecutively and independently of the diagnosis and clinical status of patients. Yearly indirect costs were euro1,299+/-2,804 in SPC compared to euro1,483+/-3,452 in GC (p=0.660), while annual direct costs were, euro2,911+/-3,335 and euro3,563+/-4,797, respectively (p=0.239), with total costs of euro4,210+/-4,654 and euro5,060+/-6,250, respectively (p=0.249). Mean pain severity at the time of evaluation was 3.8+/-2.3 in subjects in SPC vs. 5.2+/-2 in GC (p<0.001), while the average interference of pain on daily activities were 3.3+/-2 and 4.7+/-2.5, respectively (p<0.001). CONCLUSIONS: In neurology settings in Spain, the outpatient clinical management of chronic NeP in SPC was a dominant alternative compared with GC healthcare, since it has shown better patients healthcare outcomes with less severity and interference of pain on daily activities, while maintaining a similar level of costs. These results could help health decision makers when planning the use of health care resources.

[Encephalitis caused by Rickettsia conorii without exanthema]. / Encefalitis por Rickettsia conorii sin exantema.

INTRODUCTION: Mediterranean boutonneuse fever, caused by Rickettsia conorii, is an endemic disease in the Mediterranean area. The serious forms of the disease, which include encephalitis, are infrequent but are associated with a high mortality rate. Diagnostic suspicion is backed up by the development of exanthema. We report the case of a patient who developed encephalitis caused by Rickettsia conorii without exanthema. Clinical case. A 27 year old woman who had nauseas, headache, fever, abdominal upset and generalised pain during the days before being admitted to hospital. On the day she was admitted, she noticed reduced strength in the left limbs, together with numbness and pins and needles in the left side of the body. In the casualty department she presented tonic seizures in the left extremities and later generalised tonic clonic seizures. Exploration showed facial paresis and 4/5 hemiparesis on the left side. Complementary tests carried out in casualty, including cerebrospinal fluid (CSF), did not reveal any significant findings. She was admitted after a loading dose of phenytoin. After 48 hours she presented fever and repeated complex partial seizures. A new CSF analysis was normal. She was treated with valproate, clonazepam, ceftriaxone, doxycycline and acyclovir. An electroencephalogram (EEG) showed theta activity in the left centroparietal areas and slow delta waves in the right temporal regions. Magnetic resonance imaging (MRI) of the brain showed contrast enhancement in the meninges. 24 later, due to the frequency of the seizures, phenobarbital and methylprednisolone were added, which enabled the seizures to be controlled. The posterior brain MRI revealed a right parasylvian lesion. Serological Rickettsia conorii IgM +, IgG 1/256 was administered. After eight months, she has presented no seizures or neurological deficit. CONCLUSIONS: There are cases of encephalitis from Rickettsia conorii that can present without exanthema. This means that in endemic areas early treatment with doxycycline could be advisable when faced with encephalitis of unknown aetiology, bearing in mind the high mortality rate that occurs when no early treatment is administered and the good tolerance to doxycycline.

[Modification of the immune response in the elderly with nutritional treatments]. / Modificación de la respuesta inmune en los ancianos con tratamientos nutricionales.

The aging associates to it unites alteration of the immune response, this is well documented. This alteration can contribute to much of the illnesses associated to the age like repetition infections, cancer and illnesses autoinmunes. Is in the immunity mediated by cells where the main dysfunction resides, although with accuracy it is not clarified which is the intimate cause that produces it, although certainly the smallest presence in a co-estimulative of the recognition and the immune response as the receiver CD28, seem to play a key paper between to the descent of the thymic activity. The relationship between immunity and nutrition is known, as well as the high nutritional deficit prevalence in the elderly. In this work we pass reviews to that published in relation to the possibilities of improving the immune response in the elderly with nutritional treatments.

Modificación de la respuesta inmune en los ancianos con tratamientos nutricionales / Modification of the immune response in the elderly with nutritional treatments

Está bien documentado que se produce una alteración de la respuesta inmune asociada al envejecimiento. Este declinar puede contribuir a mucha de las enfermedades asociadas a la vejez como infecciones de repetición, cáncer y enfermedades autoinmunes. Es en la inmunidad mediada por células donde radica la principal disfunción, aunque con exactitud no está aclarada cual es la causa íntima que la produce, aunque ciertamente la menor presencia de un coestimulador del reconocimiento y la respuesta inmune como el receptor CD28, parece jugar un papel clave junto al descenso de la actividad tímica. La relación entre inmunidad y nutrición es conocida, así como la alta prevalencia de déficit nutricionales en los ancianos. En este trabajo pasamos revista a lo publicado en relación a las posibilidades de mejorar la respuesta inmune en el anciano con tratamientos nutricionales (AU)

The aging associates to it unites alteration of the immune response, this is well documented. This alteration can contribute to much of the illnesses associated to the age like repetition infections, cancer and illnesses autoinmunes. Is in the immunity mediated by cells where the main dysfunction resides, although with accuracy it is not clarified which is the intimate cause that produces it, although certainly the smallest presence in a co-estimulative of the recognition and the immune response as the receiver CD28, seem to play a key paper between to the descent of the thymic activity. The relationship between immunity and nutrition is known, as well as the high nutritional deficit prevalence in the elderly. In this work we pass reviews to that published in relation to the possibilities of improving the immune response in the elderly with nutritional treatments (AU)

Discharge profiles of abducens, accessory abducens, and orbicularis oculi motoneurons during reflex and conditioned blinks in alert cats.

The discharge profiles of identified abducens, accessory abducens, and orbicularis oculi motoneurons have been recorded extra- and intracellularly in alert behaving cats during spontaneous, reflexively evoked, and classically conditioned eyelid responses. The movement of the upper lid and the electromyographic activity of the orbicularis oculi muscle also were recorded. Animals were conditioned by short, weak air puffs or 350-ms tones as conditioned stimuli (CS) and long, strong air puffs as unconditioned stimulus (US) using both trace and delayed conditioning paradigms. Motoneurons were identified by antidromic activation from their respective cranial nerves. Orbicularis oculi and accessory abducens motoneurons fired an early, double burst of action potentials (at 4-6 and 10-16 ms) in response to air puffs or to the electrical stimulation of the supraorbital nerve. Orbicularis oculi, but not accessory abducens, motoneurons fired in response to flash and tone presentations. Only 10-15% of recorded abducens motoneurons fired a late, weak burst after air puff, supraorbital nerve, and flash stimulations. Spontaneous fasciculations of the orbicularis oculi muscle and the activity of single orbicularis oculi motoneurons that generated them also were recorded. The activation of orbicularis oculi motoneurons during the acquisition of classically conditioned eyelid responses happened in a gradual, sequential manner. Initially, some putative excitatory synaptic potentials were observed in the time window corresponding to the CS-US interval; by the second to the fourth conditioning session, some isolated action potentials appeared that increased in number until some small movements were noticed in eyelid position traces. No accessory abducens motoneuron fired and no abducens motoneuron modified their discharge rate for conditioned eyelid responses. The firing of orbicularis oculi motoneurons was related linearly to lid velocity during reflex blinks but to lid position during conditioned responses, a fact indicating the different neural origin and coding of both types of motor commands. The power spectra of both reflex and conditioned lid responses showed a dominant peak at approximately 20 Hz. The wavy appearance of both reflex and conditioned eyelid responses was clearly the result of the high phasic activity of orbicularis oculi motor units. Orbicularis oculi motoneuron membrane potentials oscillated at approximately 20 Hz after supraorbital nerve stimulation and during other reflex and conditioned eyelid movements. The oscillation seemed to be the result of both intrinsic (spike afterhyperpolarization lasting approximately 50 ms, and late depolarizations) and extrinsic properties of the motoneuronal pool and of the circuits involved in eye blinks.

Lack of ability of ciprofloxacin-rifampin prophylaxis to decrease infection-related morbidity in neutropenic patients given cytotoxic therapy and peripheral blood stem cell transplants.

We compared ciprofloxacin alone with ciprofloxacin plus rifampin (C + R) as a prophylactic antibacterial regimen for 40 patients with solid tumors treated with high-dose chemotherapy and autologous stem cell transplantation support. No differences were found between groups in the time elapsed to the onset of fever, incidence of febrile episodes, amphotericin B use, and length of hospital stay. However, C + R combination prophylaxis significantly reduced the incidence of gram-positive bacteremia (five versus zero episodes) but was associated with a higher incidence of drug-related side effects.