Validez de un registro poblacional automatizado de demencia basado en las bases de datos clínicas / Validity of a computerized population registry of dementia based on clinical databases

Introducción: El manejo de la información mediante soportes digitales permite abordajes innovadores de la identificación de los casos de demencia mediante búsquedas automatizadas en las bases de datos clínicas con sistemas de codificación de los diagnósticos. El objetivo de este trabajo fue analizar la validez de un registro de demencia en Gipuzkoa basado en los sistemas de registro administrativos y clínicos existentes en el Servicio Vasco de Salud.MétodosEs un estudio descriptivo basado en la evaluación de las fuentes de datos disponibles. Primero, mediante revisión de historias clínicas se evaluó la validez diagnóstica en 2 muestras de casos identificados y no identificados como demencia. Se midió la sensibilidad, especificidad y valor predictivo positivo y negativo del diagnóstico de demencia. Posteriormente se buscaron los casos de demencia vivos a fecha 31 de diciembre de 2016 en toda la población guipuzcoana y se recogieron variables sociodemográficas y clínicas.ResultadosLas 2 muestras de validación incluyeron 986 casos y 327 no casos. La sensibilidad calculada fue del 80,2% y la especificidad del 99,9%. El valor predictivo negativo fue del 99,4% y el positivo del 95,1%. Los casos registrados en toda la población guipuzcoana fueron 10.551 que supone un 65% de los casos previstos según la literatura. Un 40% tomaban medicación antisicótica. La población institucionalizada fue del 25%.ConclusionesUn registro de demencias basado en las bases de datos clínicas y administrativas es válido y factible. Su principal aportación es mostrar la dimensión que tiene la demencia en el ámbito del sistema sanitario. (AU)

Introduction: The handling of information through digital media allows innovative approaches for identifying cases of dementia through computerized searches within the clinical databases that include systems for coding diagnoses. The aim of this study was to analyze the validity of a dementia registry in Gipuzkoa based on the administrative and clinical databases existing in the Basque Health Service.MethodsThis is a descriptive study based on the evaluation of available data sources. First, through review of medical records, the diagnostic validity was evaluated in 2 samples of cases identified and not identified as dementia. The sensitivity, specificity and positive and negative predictive value of the diagnosis of dementia were measured. Subsequently, the cases of living dementia in December 31, 2016 were searched in the entire Gipuzkoa population to collect sociodemographic and clinical variables.ResultsThe validation samples included 986 cases and 327 no cases. The calculated sensitivity was 80.2% and the specificity was 99.9%. The negative predictive value was 99.4% and positive value was 95.1%. The cases in Gipuzkoa were 10,551, representing 65% of the cases predicted according to the literature. Antipsychotic medication were taken by a 40% and a 25% of the cases were institutionalized.ConclusionsA registry of dementias based on clinical and administrative databases is valid and feasible. Its main contribution is to show the dimension of dementia in the health system. (AU)

Validity of a computerised population registry of dementia based on clinical databases.

INTRODUCTION: The handling of information through digital media allows innovative approaches for identifying cases of dementia through computerised searches within the clinical databases that include systems for coding diagnoses. The aim of this study was to analyse the validity of a dementia registry in Gipuzkoa based on the administrative and clinical databases existing in the Basque Health Service. METHODS: This is a descriptive study based on the evaluation of available data sources. First, through review of medical records, the diagnostic validity was evaluated in two samples of cases identified and not identified as dementia. The sensitivity, specificity and positive and negative predictive value of the diagnosis of dementia were measured. Subsequently, the cases of living dementia in December 31, 2016 were searched in the entire Gipuzkoa population to collect sociodemographic and clinical variables. RESULTS: The validation samples included 986 cases and 327 no cases. The calculated sensitivity was 80.2% and the specificity was 99.9%. The negative predictive value was 99.4% and positive value was 95.1%. The cases in Gipuzkoa were 10 551, representing 65% of the cases predicted according to the literature. Antipsychotic medication were taken by a 40% and a 25% of the cases were institutionalised. CONCLUSIONS: A registry of dementias based on clinical and administrative databases is valid and feasible. Its main contribution is to show the dimension of dementia in the health system.

Internalizing and externalizing symptoms and suicidal behaviour in young people: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To assess internalizing and externalizing symptoms as risk factors for suicidal behaviour and suicide among adolescents and young adults. METHOD: We conducted a systematic review of articles published until January 2017. We identified 26 883 potential papers; 1701 full-text articles were assessed for eligibility, of which 1479 were excluded because of methodological reasons. Diverse meta-analyses were performed for each group of symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CI) or beta coefficients for categorical variables, and effect size (ES) were calculated for continuous variables. RESULTS: Finally, 41 studies were included, involving participants aged 12-26 years for a systematic review, and 24 articles were included for meta-analysis. The meta-analysis showed that youths with any internalizing (ES = 0.93) or externalizing symptoms (ES = 0.76 and OR = 2.59) were more likely to attempt suicide in future. This effect was also seen in depression symptoms (OR = 6.58 and ES = 1.00), legal problems (OR = 3.36), and anxiety (ES = 0.65). CONCLUSION: Reported internalizing and externalizing symptoms are predictors of suicide behaviour in young people; therefore, the detection and management of these symptoms in young populations could be a crucial strategy for preventing suicidality in this group.

[Extensive encephalomyelitis due to Borrelia: an atypical form of neuroborreliosis]. / Encefalomielitis extensa por Borrelia: una forma atipica de neuroborreliosis.

TITLE: Encefalomielitis extensa por Borrelia: una forma atipica de neuroborreliosis.

Sexual orientation and suicidal behaviour in adolescents and young adults: systematic review and meta-analysis.

BackgroundResearch suggests that lesbian, gay and bisexual (LGB) adolescents have a higher risk of suicidal behaviours than their heterosexual peers, but little is known about specific risk factors.AimsTo assess sexual orientation as a risk factor for suicidal behaviours, and to identify other risk factors among LGB adolescents and young adults.MethodA systematic search was made of six databases up to June 2015, including a grey literature search. Population-based longitudinal studies considering non-clinical populations aged 12-26 years and assessing being LGB as a risk factor for suicidal behaviour compared with being heterosexual, or evaluating risk factors for suicidal behaviour within LGB populations, were included. Random effect models were used in meta-analysis.ResultsSexual orientation was significantly associated with suicide attempts in adolescents and youths (OR = 2.26, 95% CI 1.60-3.20). Gay or bisexual men were more likely to report suicide attempts compared with heterosexual men (OR = 2.21, 95% CI 1.21-4.04). Based on two studies, a non-significant positive association was found between depression and suicide attempts in LGB groups.ConclusionsSexual orientation is associated with a higher risk of suicide attempt in young people. Further research is needed to assess completed suicide, and specific risk factors affecting the LGB population.

Longitudinal association between self-injurious thoughts and behaviors and suicidal behavior in adolescents and young adults: A systematic review with meta-analysis.

BACKGROUND: Adolescents with previous self-injurious thoughts and behaviors (SITB) have over 2-fold risk of dying by suicide, higher than older ages. This meta-analysis aims to disentangle the association of each SITB with subsequent suicidal behavior in adolescence/young adulthood, the contribution of each SITB, and the proportion of suicide deaths with no previous suicide attempt. METHODS: We searched 6 databases until June 2015. INCLUSION CRITERIA: 1. Assessment of any previous SITB [a) suicidal thoughts and behaviors (ideation; threat/gesture; plan; attempt); b) non-suicidal thoughts and behaviors (thoughts; threat/gesture; self-injury); c) self-harm] as a risk factor of suicide attempt or suicide death; 2. Case-control or cohort studies; 3. Subjects aged 12-26y. Random effect models, metaregression analyses including mental health and environmental variables, and population attributable risks (PAR)s were estimated. RESULTS: From 23,682 potentially eligible articles, 29 were included in the meta-analysis (1,122,054 individuals). While 68% of all youth suicide deaths had no previous suicide attempt, suicide death was very strongly associated with any previous SITB (OR=22.53, 95%CI: 18.40-27.58). Suicide attempts were also associated with a history of previous SITB (OR=3.48, 95%CI: 2.71-4.43). There were no moderating effects for mental health and environmental features. The PAR of previous SITB to suicide attempts is 26%. LIMITATIONS: There is considerable heterogeneity between the available studies. Due to limitations in the original studies, an over-estimation of the proportion dying at their first attempt cannot be ruled out, since they might have missed unrecognized previous suicide attempts. CONCLUSIONS: Although more than two thirds of suicide deaths in adolescence/young adulthood have occurred with no previous suicidal behavior, previous SITBs have a much higher risk of dying by suicide than previously reported in this age group.

Exposure to violence, a risk for suicide in youths and young adults. A meta-analysis of longitudinal studies.

OBJECTIVE: To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults. METHOD: We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment [childhood physical, sexual, emotional abuse, neglect], (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population-based case-control or cohort studies; and (3) subjects aged 12-26 years. Random models were used for meta-analyses (Reg: CRD42013005775). RESULTS: From 23 682 articles, 29 articles with 143 730 subjects for meta-analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73-2.28); for child maltreatment, 2.25 (95% CI: 1.85-2.73); for bullying, 2.39 (95% CI: 1.89-3.01); for dating violence, 1.65 (95% CI: 1.40-1.94); and for community violence, 1.48 (95% CI: 1.16-1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46-25.07). CONCLUSION: Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.

Brain RGS4 and RGS10 protein expression in schizophrenia and depression. Effect of drug treatment.

RATIONALE: Regulator of G-protein signaling (RGS) proteins, RGS4 and RGS10, may be involved in the pathophysiology of schizophrenia. RGS4 has attracted special interest since the reports of genetic association between SNPs in RGS4 and schizophrenia. However, there is no information about the subcellular distribution of RGS4 and RGS10 proteins in psychiatric disorders. OBJECTIVES: Plasma membrane RGS4 and cytosolic RGS10 protein immunoreactivity in prefrontal cortex from schizophrenic subjects (n = 25), non-diagnosed suicides (n = 13), and control subjects (n = 35), matched by age, gender, and postmortem delay, was analyzed by western blot. A second group of depressed subjects (n = 25) and control subjects (n = 25) was evaluated. The effect of the antipsychotic or antidepressant treatments was also assessed. RESULTS: No significant differences in plasma membrane RGS4 and cytosolic RGS10 protein expression were observed between schizophrenic subjects, non-diagnosed suicides, and control subjects. However, RGS4 immunoreactivity was significantly higher (Δ = 33 ± 10 %, p < 0.05) in the antipsychotic-treated subgroup (n = 12) than in the antipsychotic-free subgroup (n = 13). Immunodensities of plasma membrane RGS4 and cytosolic RGS10 proteins did not differ between depressed and matched control subjects. CONCLUSIONS: Expression of RGS4 and RGS10 proteins at their predominant subcellular location was studied in the postmortem brain of subjects with psychiatric disorders. The results suggest unaltered membrane RGS4 and cytosolic RGS10 proteins levels in schizophrenia and major depression. Antipsychotic treatment seems to increase membrane RGS4 immunoreactivity. Further studies are needed to elucidate RGS4 and RGS10 functional status.

Análisis de la prescripción inducida en una comarca de atención primaria / Analysis of the induced prescription in a primary care region

Objetivos. Conocer la prevalencia, el origen y el gasto atribuible de la prescripción inducida (PI) en atención primaria (AP) en la Comarca Oeste de Gipuzkoa, determinar el grado de acuerdo de los médicos de AP con respecto a la PI y analizar la adecuación de la PI a los indicadores del contrato de gestión clínica de la AP. Material y métodos. Diseño: estudio descriptivo, transversal y multicéntrico. Ámbito: AP, 38 médicos pertenecientes a 17 unidades de AP de la Comarca Oeste de Gipuzkoa. Participantes: prescripciones farmacéuticas financiables realizadas durante 2 días en consulta a demanda y crónicas generadas por el programa informático Osabide. Variables analizadas: tipo de prescripción, origen, especialidad del prescriptor, diagnóstico, precio y grado de acuerdo. Resultados. Se realizaron 6.919 prescripciones y el 44% fueron PI (intervalo de confianza del 95%: 42,8–45,1). El 62,2% del gasto total se atribuyó a la PI, con un precio medio por receta de 22,3€ para la PI y de 10,6€ para la prescripción propia. Los subgrupos terapéuticos de mayor gasto fueron los hipolipidemiantes y los broncodilatadores. Resultados. El grado de desacuerdo de los médicos participantes con la PI fue del 28,8%. La adecuación de los indicadores de calidad de la prescripción fue mayor en la prescripción propia que en la PI. Conclusiones. Existe un porcentaje elevado de PI asociado a un gasto elevado que se atribuye a la AP. El porcentaje de desacuerdo en AP con respecto a la PI es importante. Se observa una influencia elevada de la PI en la evaluación de los indicadores de calidad establecidos en la AP(AU)

Objectives. To find out the prevalence, origin and cost associated with Induced Prescription (IP) in Primary Health Care (PHC) in the West of Gipuzkoa (WG). To find out the extent to which PHC doctors agree with IP. To analyse the adaptation of IP to PHC clinical management contract indicators. Materials and methods. Design descriptive multi-centre cross-study. Location. Primary Health Care, 38 doctors from 17 WG PHC units. Participants. Pharmaceutical prescriptions eligible for finance over a period of two days in outpatients and chronic diseases generated by the Osabide computer application. Participants. Variables analysed: type of prescription, origin, prescriber, diagnosis, price and level of agreement. Results. A total of 6.919 prescriptions were made out, with 44% (95% CI: 42.8–45.1) being IP. Of the total cost, 62.2% was put down to IP, with an average price per prescription of €22.3,and in non-induced prescription (NIP) it was €10.62. The therapeutic subgroups with the highest cost were lipid lowering and bronchodilator drugs. The level of disagreement of the doctors taking part in IP was 28.8%. The adaptation to the quality indicators of the prescription was higher in NIP than in IP. Conclusions. There is a high percentage of IP associated with high costs attributed to PHC. The percentage of disagreement in PHC with regard to IP is significant. There is a high influence of IP on the evaluation of the quality indicators established in PHC(AU)

[Analysis of the induced prescription in a primary care region]. / Análisis de la prescripción inducida en una comarca de atención primaria.

OBJECTIVES: To find out the prevalence, origin and cost associated with Induced Prescription (IP) in Primary Health Care (PHC) in the West of Gipuzkoa (WG). To find out the extent to which PHC doctors agree with IP. To analyse the adaptation of IP to PHC clinical management contract indicators. MATERIALS AND METHODS: Design descriptive multi-centre cross-study. LOCATION: Primary Health Care, 38 doctors from 17 WG PHC units. PARTICIPANTS: Pharmaceutical prescriptions eligible for finance over a period of two days in outpatients and chronic diseases generated by the Osabide computer application. Variables analysed: type of prescription, origin, prescriber, diagnosis, price and level of agreement. RESULTS: A total of 6.919 prescriptions were made out, with 44% (95% CI: 42.8-45.1) being IP. Of the total cost, 62.2% was put down to IP, with an average price per prescription of €22.3,and in non-induced prescription (NIP) it was €10.62. The therapeutic subgroups with the highest cost were lipid lowering and bronchodilator drugs. The level of disagreement of the doctors taking part in IP was 28.8%. The adaptation to the quality indicators of the prescription was higher in NIP than in IP. CONCLUSIONS: There is a high percentage of IP associated with high costs attributed to PHC. The percentage of disagreement in PHC with regard to IP is significant. There is a high influence of IP on the evaluation of the quality indicators established in PHC.

"Frontotemporoparietal" dementia: clinical phenotype associated with the c.709-1G>A PGRN mutation.

BACKGROUND: Mutations in the progranulin gene (PGRN) are a major cause of frontotemporal lobar degeneration with tau-negative and ubiquitin-positive neuronal inclusions. Most previous studies aimed at characterizing the clinical and neuropsychological phenotype of PGRN mutation carriers included patients with different PGRN mutations, assuming that the common proposed pathogenetic mechanism of haploinsufficiency will lead to a comparable phenotype. METHODS: We studied 21 patients with a single pathogenic splicing mutation in the PGRN gene (c.709-1G>A) in the same tertiary referral center using homogenous diagnostic criteria and protocols. All patients were of Basque descent. RESULTS: Patients exhibited a variable phenotype both in age at onset and initial symptoms. Behavioral variant frontotemporal dementia (52.4%) and progressive nonfluent aphasia (23.8%) were the most common presenting syndromes. Apathy was the most common behavioral symptom. Patients developed a relatively rapidly progressive dementia with features that led to a secondary diagnosis in 61.9% of cases 2 years after primary diagnosis. Notably, this secondary or tertiary diagnosis was corticobasal syndrome in 47.6% of cases, which confirmed the neuropsychological features of parietal lobe dysfunction seen at the initial assessment in 81.8% of patients. CONCLUSIONS: Patients carrying the c.709-1G>A mutation in the PGRN gene showed heterogeneous clinical and neuropsychological features and commonly developed corticobasal syndrome as the disease progressed.

Estimulación del nervio vago. ¿Un nuevo tratamiento biológico para la depresión? / Vagus nerve stimulation: a new biological treatment for depression?

No disponible

Characterization of receptor-mediated [35S]GTPgammaS binding to cortical membranes from postmortem human brain.

The [35S]GTPgammaS binding assay represents a functional approach to assess the coupling between receptors and G-proteins. The optimal conditions for [35S]GTPgammaS binding to human brain homogenates were established in postmortem samples of prefrontal cortex. The influence of protein content, incubation time, GDP, Mg(2+), and NaCl concentrations on the [35S]GTPgammaS binding were assessed in the absence and presence of the alpha(2)-adrenoceptor agonist UK14304 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine). In conditions of 50 microM GDP and 100 mM NaCl, UK14304 increased the apparent affinity of the specific [35S]GTPgammaS binding without changing the apparent density. Concentration-response curves to agonists of alpha(2)-adrenoceptors, mu-opioid, 5-HT(1A), cholinergic muscarinic, and GABA(B) receptors displayed, in the presence of NaCl, maximal stimulations between 24% and 61% with EC(50) values in the micromolar range. Selective antagonists shifted to the right the agonist-induced stimulation curves. The G(i)/G(o)-protein alkylating agent N-ethylmaleimide decreased basal [35S]GTPgammaS binding in a concentration-dependent manner and inhibited the stimulation induced by the different agonists. In cortical sections, [35S]GTPgammaS binding to gray matter was stimulated by the agonist UK14304. The present study demonstrates that functional studies of the receptor coupling to G(i)/G(o)-proteins can be performed in postmortem human brain samples.

Differential modulation of alpha2-adrenoceptor subtypes in rat kidney by chronic desipramine treatment.

The profile of [3H]RX821002 (2-methoxy idazoxan) binding to alpha2-adrenoceptor subtypes in rat kidney membranes was evaluated in controls and after chronic treatment with desipramine (10 mg/kg, i.p., every 12 h, 7 days) or clorgyline (2 mg/kg, i.p., every 24 h, 21 days). [3H]RX821002 recognized with high affinity (Kd=1.5+/-0.2 nM in controls) a single and saturable population of binding sites (Bmax=57+/-5 fmol/mg protein in controls). The competitions by (-)-adrenaline, the alpha2B-adrenoceptor selective drug ARC239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3 (2H,4H)-isoquinolindione) and the alpha2A-adrenoceptor selective drug BRL44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidaz ole) suggested the existence of both alpha2A- and alpha2B-adrenoceptors together with a non-adrenoceptor binding site. After chronic desipramine but not after chronic clorgyline treatments, the density (Bmax) of alpha2-adrenoceptors was increased (46%). In the presence of ARC239 (50 nM), the density of alpha2A-adrenoceptors increased (44%) in the desipramine-treated group without changes in the clorgyline-treated group. Conversely, in the presence of BRL44408 (100 nM), the density of alpha2B-adrenoceptors was not affected by the treatments. The selective upregulation of the alpha2A-adrenoceptor subtype following chronic desipramine administration is compatible with a differential location and function of the alpha2-adrenoceptor subtypes in the rat kidney.

A dileucine motif in the C terminus of the beta2-adrenergic receptor is involved in receptor internalization.

The cytoplasmic C terminus of the beta2-adrenergic receptor and many other G protein-coupled receptors contains a dileucine sequence that has been implicated in endosome/lysosome targeting of diverse proteins. In the present study, we provide evidence for an essential role of this motif in the agonist-induced internalization of the beta2-adrenergic receptor. Mutation of Leu-339 and/or Leu-340 to Ala caused little changes in surface expression, ligand binding, G protein coupling, and signaling to adenylyl cyclase, when these receptors were transiently or stably expressed in CHO or HEK-293 cells. However, agonist-induced receptor internalization was markedly impaired in the L339,340A double mutant and reduced in the two single mutants. This impairment in receptor internalization was seen by using various approaches to determine internalization: binding of hydrophobic vs. hydrophilic ligands, loss of surface beta2-adrenergic receptor immunoreactivity, and immunofluorescence microscopy. The selective effects of these mutations suggest that the C-terminal dileucine motif is involved in agonist-induced internalization of the beta2-adrenergic receptor.

[3H]RX821002 (2-methoxyidazoxan) binds to alpha 2-adrenoceptor subtypes and a non-adrenoceptor imidazoline binding site in rat kidney.

The binding of [3H]RX821002 (2-methoxyidazoxan) was evaluated in rat kidney membranes. [3H]RX821002 (0.13-16 nM) recognized a single, saturable binding site with high affinity. Different binding site densities were calculated depending on non-specific binding as defined by (-)-adrenaline or RX821002 (10 microM). Competition assays using (-)-adrenaline and the subtype-selective drugs ARC 239 (2-[2-[4-(o-methoxyphenyl)-piperazin-1-yl]-ethyl]-4,4-dimethyl-1,3 (2H,4H)-isoquinolindione), BRL 44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5-dihydroimidaz ole), oxymetazoline or prazosin for [3H]RX821002 binding sites revealed the presence of alpha 2B-adrenoceptors (33-51%), alpha 2D-adrenoceptors (15-28%) and an adrenaline-insensitive population (34-40%), sensitive to imidazolines. After the addition of (-)-adrenaline (3 microM) to mask alpha 2-adrenoceptors, [3H]RX821002 specifically identified a saturable binding site with high affinity (Kd = 4.9 +/- 1.5 nM). The pharmacological profile of this non-adrenoceptor, [3H]RX821002 binding site (potencies: efaroxan > clonidine > guanabenz > BRL 44408 > ARC 239 > BU 224 (2-(4,5-dihydroimidaz-2-yl)quinoline) > moxonidine > (-)-nor-adrenaline > cimetidine) is different to that of imidazoline I1 or imidazoline I2 binding sites. Alternative incubation in the presence of ARC 239 (50 nM) to mask alpha 2B-adrenoceptors or BRL 44408 (100 nM) to mask alpha 2D-adrenoceptors confirmed the existence of both alpha 2-adrenoceptor subtypes and a non-adrenoceptor imidazoline binding site.

Mutations of Tyr326 in the beta 2-adrenoceptor disrupt multiple receptor functions.

A tyrosine residue at the cytoplasmic end of the seventh transmembrane helix is conserved in many G-protein-coupled receptors. In the human beta 2-adrenoceptor, this tyrosine (Tyr326) has been proposed to be a specific determinant for agonist-induced receptor sequestration. In order to probe its contribution to the sequestration process we have replaced this tyrosine by alanine (Y326A) or phenylalanine (Y326F). Wild-type and mutant receptors were stably expressed in Chinese hamster ovary cells. Agonist-induced sequestration was essentially abolished in Y326A receptors and only slightly reduced in Y326F receptors. However, cells expressing Y326A receptors displayed a high percentage of internal receptors under basal conditions while cells expressing wild-type receptors did not. In addition, high-affinity agonist binding and the ability to activate adenylyl cyclase were markedly reduced in Y326A receptors and slightly reduced in Y326F receptors. We conclude that Tyr326 is required for the functional integrity of the beta 2-adrenoceptor and that it may be involved in multiple agonist-induced effects.

Incidence of Vibrio cholerae O1 diarrhea in children at the onset of cholera epidemic in periurban Lima, Peru.

OBJECTIVE: To determine the incidence of Vibrio cholerae O1-associated diarrhea in children during the onset of the 1991 cholera epidemic in Peru. METHODS: Stool cultures were obtained from children (mean age, 26 months) participating in a prospective community-based study of diarrhea in a periurban community in Lima between February and May, 1991. RESULTS: Of the 409 diarrheal episodes cultured V. cholerae O1 was isolated in 14 (3.4%) episodes. This represented an incidence of 0.11 episode per child year, higher than previously reported rates in children from endemic cholera areas. Most cases were mild; only 1 case required hospitalization. CONCLUSIONS: Our study indicates that from the beginning of this epidemic, V. cholerae O1 caused diarrhea in children as well as adults and should therefore be considered as one of the possible pathogens when children from a cholera-affected area develop diarrhea.