Tcf4 transgenic female mice display delayed adaptation in an auditory latent inhibition paradigm.

Schizophrenia (SZ) is a severe mental disorder affecting about 1 % of the human population. Patients show severe deficits in cognitive processing often characterized by an improper filtering of environmental stimuli. Independent genome-wide association studies confirmed a number of risk variants for SZ including several associated with the gene encoding the transcription factor 4 (TCF4). TCF4 is widely expressed in the central nervous system of mice and humans and seems to be important for brain development. Transgenic mice overexpressing murine Tcf4 (Tcf4tg) in the adult brain display cognitive impairments and sensorimotor gating disturbances. To address the question of whether increased Tcf4 gene dosage may affect cognitive flexibility in an auditory associative task, we tested latent inhibition (LI) in female Tcf4tg mice. LI is a widely accepted translational endophenotype of SZ and results from a maladaptive delay in switching a response to a previously unconditioned stimulus when this becomes conditioned. Using an Audiobox, we pre-exposed Tcf4tg mice and their wild-type littermates to either a 3- or a 12-kHz tone before conditioning them to a 12-kHz tone. Tcf4tg animals pre-exposed to a 12-kHz tone showed significantly delayed conditioning when the previously unconditioned tone became associated with an air puff. These results support findings that associate TCF4 dysfunction with cognitive inflexibility and improper filtering of sensory stimuli observed in SZ patients.

[Evolution of the prevalence of HIV infection and risk behavior of drug injection among intravenous drug users infected or not infected by HIV in 3 Spanish cities. Working Group of Physicians of the World for the monitoring of HIV infection and risk behaviors in intravenous drug users]. / Evolución de la prevalencia de infección por VIH y de prácticas de riesgo de inyección entre inyectores de drogas infectados o no por el VIH de tres ciudades españolas. Grupo de Trabajo de Médicos del Mundo para la monitorización de la infección por VIH y las prácticas de riesgo en usuarios de drogas inyectables.

OBJECTIVE: To know the evolution of HIV prevalence and risk behavior practices of drug injection in three spanish cities on the basis of the serologic status of injecting drug users. METHODS: Cross-sectional surveys among users in syringe interchange programmes. RESULTS: HIV prevalence (self-reported) decreased in Madrid from 50% (1992) down to 41% (1996) (p = 0.01) and did not change in Seville and Valencia from 1994 to 1996. Among HIV-positive injecting drug users, a decrease was observed in the practice of giving and taking used syringes in the three cities, although this decrease reached a statistically significance (p = 0.006) only for giving in Valencia from 1994 to 1996 and was almost significant (p = 0.08) for taking in Madrid from 1993 to 1996. Among HIV-negative injecting drug users, no decreases were observed in the practice of giving and taking used syringes and even a significant increase in giving syringes in Seville was recorded (p = 0.01) from 1994 to 1996. CONCLUSIONS: HIV prevalence among injecting drug users is stabilized or decreasing in the three studied cities. The prevalence of injecting risk behavior evolves differently according to the serologic status.

Evolución de la prevalencia de infección por VIH y de prácticas de riesgo de inyección entre inyectores de drogas infectados o no por el VIH de tres ciudades españolas / Evolution of the prevalence of HIV infection and risk behavior of drug injection among HIV+ and HIV- drug users in three spanish cities

Fundamento. Conocer la evolución de la prevalencia del virus de la inmunodeficiencia humana (VIH) y las prácticas de riesgo con drogas por vía intravenosa en tres ciudades españolas según el estado serológico de los inyectores. Métodos. Encuestas transversales a usuarios de programas de intercambio de jeringuillas. Resultados. La prevalencia de VIH (autoinformada) descendió en Madrid del 50 por ciento (1992) al 41 por ciento (1996) (p = 0,01) y no se modificó en Sevilla y Valencia entre 1994 y 1996. Entre los inyectores de drogas infectados por el VIH disminuyó la práctica de dar y la de recibir jeringuillas usadas en las tres ciudades, aunque este descenso sólo alcanzó significación estadística (p = 0,006) para dar en Valencia entre 1994-1996 y la rozó (p = 0,08) en Madrid para recibir entre 1993-1996. Entre los no infectados por el VIH no se aprecian descensos en la práctica de recibir ni en la de dar jeringuillas usadas, registrándose incluso un incremento significativo de dar en Sevilla (p = 0,01) entre 1994-1996.Conclusiones. La prevalencia del VIH entre inyectores de drogas está estabilizada o en descenso en las ciudades estudiadas. La prevalencia de prácticas de riesgo de inyección evoluciona diferencialmente según el estado serológico (AU)

Reversible neural inactivation reveals hippocampal participation in several memory processes.

Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes-encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

[Drug injection method risky for transmission of blood-borne diseases: are we careful enough?]. / Estamos estudiando adecuadamente las prácticas de inyección de drogas que implican riesgo de transmisión de enfermedades por vía parenteral?

In the last 20 years, research on the determinants of the HIV epidemic among drug users has focused mainly on studies of risk behaviour for drug injection. Studies involving human behaviour present special methodological problems. This paper presents a review of 1) the most important features that make this field different from the study of blood-borne diseases in other populations, and 2) the basic variables used in epidemiology to analyse injecting risk behaviour. Alternatives to improve research planning and results are proposed based on collaborating with other disciplines and improving the methodological resources of epidemiology.

[Emergency room admissions in cocaine users in Spanish hospitals: first evidences of acute complications related to crack use. Work Group for the Study of Emergencies from Psychostimulants]. / Urgencias en consumidores de cocaína en varios hospitales españoles: primeras evidencias de complicaciones agudas por consumo de crack. Grupo de Trabajo para el Estudio de Urgencias por Psicoestimulantes.

BACKGROUND: Acute complications of cocaine are increasing in Spain, nevertheless little information is available on its clinical and toxicological characteristics. MATERIAL AND METHOD: Records from medical emergency rooms of 14 hospitals from Madrid, Valencia and Gran Canaria were reviewed. Records were selected if the term "cocaine" was mentioned, excluding those related with injuries or obstetric, gynecologic and pediatric problems. Emergency room episodes were classified in three groups according its relation with cocaine use. RESULTS: 223 episodes were directly related to cocaine, some of these simultaneously related to heroin (36%) or alcohol. The proportion of all emergency room episodes related to cocaine was threefold higher in Gran Canaria than in Madrid and Valencia. In Gran Canaria most of episodes (72%) were related to cocaine smoking, generally crack, but in Madrid and Valencia most were due to intravenous cocaine use. The most common signs and symptoms were anxiety, mydriasis, syncope, tachycardia, shortness of breath, confusion or coma, agitation, chest pain and palpitations. Mental disorders were the most common diagnoses. 13% of patients were admitted as inpatients to hospital or were referred to another hospital (23.6, 17.3 and 2.2%, if cocaine was smoked, injected and sniffed, respectively). Cardiovascular diagnosis were less frequent in episodes simultaneously related to opioids than in not opioids-related episodes (1.1% vs 10.7%; p = 0.005). Furthermore, 219 not cocaine-related episodes were identified. The relation to cocaine could not be established in other 275 episodes. CONCLUSIONS: This work show for the first time in Spain the presence of crack-related emergency episodes and suggests that injecting and smoking cocaine has a greater impact on public health than sniffing this drug.

Contingent versus incidental context processing during conditioning: dissociation after excitotoxic hippocampal plus dentate gyrus lesions.

This experiment explored whether excitotoxic hippocampus plus dentate gyrus (HPC/DG) lesions in rats would dissociate the differential processing of contextual cues during the performance of learned associations when (1) their processing during training is incidental to successful learning or (2) the solution of a discrimination problem is contingent on their processing. A series of training stages were conducted, beginning with appetitive conditioning to two stimuli (X and Y), each of which was trained in one of two different contexts (operant chambers A and B) (i.e., AX+, BY+). Conditioning was indexed as appetitive responding. The animals were then trained on a biconditional contextual discrimination with these same stimuli (AX+, AY-; BY+, BX-). The next stage involved conditioning trials to two new stimuli (W and Z), one in each context, while the animals were actively discriminating contexts A and B by continuing to perform the original biconditional discrimination (AX+, AY-, AW+; BY+, BX-, BZ+). Finally, they were trained on a second biconditional discrimination involving these new stimuli (AX+, AY-, AW+, AZ-; BY+, BX-, BZ+, BW-). The incidental use of context cues was examined by looking at the rate of conditioned responding to cues X, Y, W, and Z in their original training contexts or a different context; HPC/DG lesioned rats differed from controls in being unaffected by a change of context. The contingent use of context cues was examined by looking at performance of each of the two biconditional tasks; HPC/DG lesioned rats reached levels of conditional performance indistinguishable from those of controls. These findings point to two distinct ways in which contextual information is processed in the brain, revealing a dissociation between incidental and contingent processing of contextual cues after HPC/DG lesions.

[Epidemiology of designer drug use in Spain]. / Epidemiología del consumo de drogas de diseño en España.

BACKGROUND: To provide epidemiological information on the extent of design drug use in Spain, the characteristics of users, and the types of substances consumed. MATERIALS AND METHODS: We analyzed two surveys on drug use carried out in 1993 and 1994 (one in the general population older than 15 years and the other in heroin and/or cocaine users who were not in treatment) as well as data on designer drug seizures confiscated by the General Police Headquarters and Ministry of Health laboratories. RESULTS: According to the general population survey, 4.5% of persons 16-40 years of age have tried design drugs at some time, 2.1% more than once, and 0.6% are current users. Design drug use is associated with age of 20-24 years and use of crack (odds ratio [OR] = 28.6), cannabis (OR = 12.5), cocaine (OR = 7.6) or heroin (OR = 3.8). According to the survey of heroin/cocaine users, 25% of cocaine users have used design drugs in the last 30 days, 11% of heroin users, and 18% of those who use both substances. Use is associated with the use of hallucinogens (OR = 4.8), non-use of the injected route (OR = 2), and having been interviewed in recreational areas (OR = 1.8). Police data reflect a stability in the quantities of amphetamines confiscated, a large increase in those of MDMA, and an absence of MDA and MDEA. Ministry of Health laboratories show an increase in confiscations of amphetamines and the presence of MDA, MDMA and MDEA in all years and areas studied, as well as the appearance of MBDB in 1994. CONCLUSIONS: The occasional use of different design drugs has spread to some degree among young people, varies considerably by geographic region, and is associated with the use of other legal and illegal substances, specially stimulants.

[Patterns of cocaine use among cocaine users who do not use heroin recruited outside of treatment centers]. / Patrones de uso de cocaína en un grupo de consumidores de esta droga sin consumo de heroína captados fuera de los servicios asistenciales.

BACKGROUND: In Spain cocaine use, although relatively widespread, has produced few health problems, most likely because there is a preponderance of non-intensive intranasal use. To obtain data in this regard, we investigated the history and patterns of use in a group of cocaine users. SUBJECTS AND METHODS: Cross-sectional survey carried out in 1993 among 381 cocaine users (289 men and 92 women) who did not use heroin and had not received treatment for drug dependence, recruited by non-probabilistic sampling outside of treatment centers in 35 Spanish cities. The results are presented separately for men and women. RESULTS: The persons interviewed predominantly took cocaine sporadically, during the weekend, in moderate amounts (less than 0.4 g/day) and by the intranasal route. For only 7.2% was it very difficult or impossible to give up cocaine. These characteristics had persisted throughout the users' history; few users (18.1%) had taken cocaine more than 3 times a week in any period or had used a main route other than the intranasal route (10.8%). The proportion of those interviewed who used other drugs, mainly alcohol, tobacco and cannabis, was larger than in the general population in the same age group; interviewees also had a higher educational level and a lower level of unemployment. Women used cocaine, alcohol and tobacco in smaller amounts than men, and a smaller proportion of women stated that it was very difficult or impossible to give up cocaine. CONCLUSIONS: In Spain, the cocaine users who do not use heroin have better educational and employment levels than general population, and generally they use cocaine sporadically, in moderate amounts and by the intranasal route. These circumstances may contribute to explain the relative scarcity of health problems associated to cocaine use.

[Emergencies associated with the consumption of designer drugs, hallucinogens and amphetamines treated at 15 Spanish hospitals in 1994. Work Group on the Study of Emergencies due to Psychostimulants]. / Urgencias relacionadas con el consumo de drogas de diseño, alucinógenos y anfetaminas atendidas en quince hospitales españoles durante 1994. Grupo de Trabajo para el Estudio de las Urgencias por Psicoestimulantes.

The clinical records of patients attended at emergency hospitals in fifteen hospitals in Madrid, Valencia and Gran Canaria during 1994 were retrospectively analyzed. Seventy-three emergencies related to the consumption of design drugs, hallucinogens or amphetamines (100 times lower than because of opiates or cocaine) were recorded. Apart from the responsible drug for the emergency visit, in most cases the usual consumption of other substances was mentioned. Acute psychopathological reactions predominated. Three patients were admitted and five were derived to other hospitals; the remaining patients improved and were discharged. The number of emergencies on account of these drugs is relatively low, with a proportion of less than one in 10,000 emergencies attended in these areas and might not radically change if the current predominant consumption pattern is maintained.

[Risk behaviors for HIV transmission among the recent clients of a syringe-exchange program in Madrid, 1993]. / Conductas de riesgo para transmisión del VIH entre los usuarios recientes de un programa de intercambio de jeringas en Madrid, 1993.

OBJECTIVE: To determine the prevalence of the major risk behavior in HIV transmission (syringe sharing and failure to use condoms) and associated factors among drug injectors recruited for a syringe exchange program (PIJ) in the city of Madrid. METHODS: Cross-section study. All the information was obtained in 1993 through structured interviews with 441 users who had injected drugs during the previous month and had resorted to the PIJ five times, at most. The reference period for drug use and risk behaviour was the month prior to the interview. The statistical analysis included bivariate methods and logistical regression techniques. RESULTS: 29.2% shared syringes (18% passing and 21.7% taking used syringes) and of those that had sexual intercourse (49.4%), 42.5% always used a condom. 89.5% had an HIV antibody test and of those that knew the results, 48.6% were HIV-positive. Multivariate analysis showed that the association between certain behaviour patterns was significant; i.e., taking used syringes and: passing used syringes (odds ratio -OR- = 6.1; 95% confidence interval -CI- = 3.0-12.5), being HIV-positive (OR = 4.1; CI = 1.8-9.1), being unaware of HIV antibody test status (OR = 4.2; CI = 1.7-10.2) and having used intravenous drugs for 5-9 years (OR = 2.9; CI = 1.1-7.9); the association was significant between passing used syringes and: using a mixture of heroin and cocaine (OR = 2.7; CI = 1.1-6.4) and being unaware of HIV antibody test status (OR = 2.5; CI = 1.1-6.0). In the sample as a whole, the association between not using condoms ever and consuming cocaine (OR = 1.7; CI = 1.1-2.9) or crack (OR = 3.0; CI = 1.5-5.9) was significant; furthermore, among those that had sexual intercourse, the association was significant between not using condoms ever and: having been in jail (OR = 2.9; CI = 1.3-6.4), injecting drugs 2-4 times a day (OR = 2.4; CI = 1.0-5.8), having sexual intercourse with drug injectors (OR = 2.6; CI = 1.2-5.9) and having intercourse with two or more partners (OR = 0.4; CI = 0.2-0.9). CONCLUSIONS: The prevalence of HIV infection and risk behavior in the transmission of this virus remain high among drug injectors in Madrid. The habit of sharing syringes is still common, especially among HIV-positive drug injectors (a high percentage take used syringe) and among those who are unaware of their HIV antibody test status. The use of condoms is less frequent among those who have sexual intercourse with other drug injectors or with only one partner.

The epidemiology of cocaine use in Spain.

Trends and patterns of cocaine use in Spain are described with the aid of different information sources such as population surveys, the State Information System on Drug Abuse, and anthropological studies. In recent years the magnitude of cocaine supply indicators has increased greatly. High levels of last-month prevalence of cocaine use have been detected among the general population--consistently higher than those for heroin-- and cocaine consumption among heroin users has increased. Although the frequency of some health problems related to cocaine use--treatment admissions, hospital emergency admissions--has increased, it is still 30 times less than for heroin. Various hypotheses to explain these discrepancies are discussed.

[Quality of the certification of death due to acute reaction to opiates and cocaine among inhabitants of the City of Madrid]. / Calidad de la certificación de la muerte por reacción aguda a opiáceos y cocaína entre residentes del municipio de Madrid.

BACKGROUND: Deaths by acute reaction from drugs consumption (RAD) particularly heroine or cocaine, collected in routine morality statistics, have not changed substantially during the last ten years, whereas an specific collection system (State Information System on Drug-Abuse SISD) presented a great increase. For this reason, we try to measure the validity of drug-related deaths certificate. METHODS: The cause of death, corresponding to the persons, from 15 to 39 years of age, decreased in 1988 and residing in the Municipality of Madrid, registered in the Civil Register Decease Book and in the death Statistics Bulletins (DSB) was compared with the cause present in the autopsy report. RESULTS: A detection rate of 2.45% for the CR and 3.27% for the DSB were obtained. With the consequent correction, the RAD for this age group would be the second cause of mortality in the Municipality of Madrid and deaths related to circulatory and respiratory system would decrease in a great measure. CONCLUSIONS: It is necessary to improve substantially the collection of this cause of death in mortality statistics if we want a correct measurement of drug abuse lethal effects and the effectiveness of control programmes on this health problem.

[Influence of diabetes mellitus in hospital emergencies]. / Influencia de la diabetes mellitus en la Urgencia Hospitalaria.

A study performed at the Internal Medicine Emergency Department of the General Hospital "La Paz" (Madrid) over a six month period is presented. Its goal was to check the problems of the diabetic patient at his entrance to the medical emergency. We review the emergency pathological causes and we established that vascular (32%) and acute metabolic (17%) alterations were the most common pathologies, both in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. We analyzed the acute metabolic alterations considering that they can be foreseeable with an adequate knowledge of the disease. We point out an aspect that to our knowledge is basic: the diabetological information-education of diabetic patients (only 5% had a good knowledge of the disease and, furthermore, only 18% declared to have received some diabetological information). We also highlight the overuse that diabetic patients do of the hospital emergency departments, as a consequence of the previously mentioned poor information received which also reflects the insufficient or inadequate medical assistance in Primary Care Centers.