Cannabis and driving: results from a general population survey.

The role of illicit drugs on driving, and particularly of cannabis and driving, is the object of increasing awareness. While there is increasing evidence of their effect on psychomotor performance and increased risk of involvement in traffic accidents, limited information is available concerning factors that can predict the likelihood of driving under the influence of cannabis. The present study aims to determine the past year prevalence of driving under the influence of cannabis, and of being a passenger in a vehicle driven by a person under the influence of cannabis, as well as to examine the correlations with a broad range of potential risk factors. A total of 2500 people, aged between 14 and 70 and living in Castille and Leon (Spain), were surveyed in 2004 with regard to their consumption of alcohol and illicit drugs. Among those who reported cannabis use in the previous year, further assessment was carried out. 15.7% of those surveyed reported cannabis consumption in the previous 12 months, of whom 9.7% reported driving a vehicle under the influence of cannabis during this period, on average eight times. One out of five (19.9%) reported being a passenger in a vehicle driven by a person under the influence of cannabis, on average five times in the previous 12 months. The predictors of driving under the influence of cannabis were the population size of community, the number of drugs consumed, reference to cannabis-related problems and to being a passenger in a vehicle driven by a person under the influence of alcohol. The data show that cannabis consumption and driving is common, and requires more attention from policy makers.

Cytosolic levels of neuron-specific enolase in squamous cell carcinomas of the lung.

To study the behavior and possible correlations of neuron-specific enolase (NSE) with other clinicobiological parameters, we measured the cytosolic levels of this marker by means of an immunoradiometric assay (IRMA) in 95 squamous cell lung carcinoma samples. We also analyzed the levels of pS2, tissue-type plasminogen activator (t-PA), hyaluronic acid (HA), free beta subunit of human chorionic gonadotropin (beta-HCG), CYFRA 21.1 and CA 125 in cytosol. On the cell surface we analyzed the concentrations of epidermal growth factor receptor (EGFR), HA, erbB-2 oncoprotein, CD44s, CD44v5 and CD44v6. Other parameters considered were clinical stage, lymph node involvement, histological grade (HG), ploidy and the cellular S-phase fraction measured by flow cytometry on nuclei obtained from fresh tissues. In the 95 squamous cell carcinomas the cytosolic levels of NSE varied from 4.5 to 2235 ng/mg protein (median: 267) and were significantly higher (p < 0.001) than those observed in 38 samples of normal pulmonary tissue obtained from the same patients (range: 56-657; median: 141.5). When classifying tumors according to the different parameters analyzed, we observed that the levels of NSE were higher in aneuploid than in diploid cases (p = 0.046) and in those that were HG3 than in those that were HG2 (p < 0.001). Tumors with high NSE levels (> 422 ng/mg protein; 75th percentile) were more likely to have high S-phase values (p = 0.012) and were more frequently aneuploid (p = 0.038) and HG3 (p < 0.001) than those with low levels of NSE (< 180 ng/mg protein; 25th percentile). These results lead us to the following conclusions: 1) the cytosolic concentrations of NSE are significantly higher in squamous cell carcinomas than in healthy pulmonary tissue, and 2) the cytosolic concentrations of NSE are not correlated with clinical stage or nodal involvement. However, in our study higher levels of the enzyme were statistically correlated with aneuploidy, histological grade 3 and S-phase. This may explain its association with poorer outcome and progression, but also the more favorable response of tumors with elevated NSE to chemotherapy, as suggested by other groups.

Medication and fitness to drive.

PURPOSE: The aim of this study is to analyze the consumption patterns of medicaments among motor vehicle drivers who attend 'Medical Driving Test Centres' and the relation between habitual consumption of medicaments and fitness to drive. METHODS: The study was carried out on 8043 drivers who attended 25 Medical Driving Test Centres. RESULTS: 24.7% of drivers chronically consume medicaments while 6.8% consume medicaments along with alcohol every day. Of those who chronically consume medicaments with a warning about the medications on driving, 65.8% were considered 'fit' to drive, 27.3% 'fit with restrictions', 5.1% 'suspended' and 0.4% 'unfit'. CONCLUSIONS: The results show how frequent the consumption of medicaments along with alcohol is and that the great majority of drivers who take medicaments are considered fit to drive.

[Estimating the costs associated with nosocomial urinary tract infection. A case-control study]. / Estimación de los costes asociados a la infección urinaria nosocomial. Un estudio de casos y controles.

BACKGROUND: Nosocomial infection (NI) is associated with increased resource use. The current study addressed the cost excess attributable to nosocomial urinary tract infection (NUTI). METHODS: Case-control study conducted in a cohort population. For matching, the Diagnostic Related Group (DRG) to which the episode of case patient was ascribed was used. Then, a further search was conducted in the hospital discharge database with the following parameters: DRG, gender, age, admission date, department, comparison of length of stays, main diagnosis, co-morbidities, number of secondary diagnoses and procedures. Matching was achieved for 64 episodes (71%), and upon them an estimation of costs was performed. RESULTS: The mean length of stay for cases were 15.3 (median: 12) and 12.3 (median: 11) days for cases and controls, respectively (p = 0.0001). The excess of length of stay attributable to NUTI was 3 days (95% CI 1.6-4.7), longer for patients admitted to Medical Departments (5.3 days) than for patients admitted to Surgical Departments (2 days) (p = 0,03). The use of diagnostic resources was significantly higher for bacteriological testing only. The use of antibiotics and fluid therapy was higher among infected patients. Out of the total excess of the estimated costs per episode, 132,047 ptas, 93% corresponded to the increase in hospital stay. Ten patients (15.6%) were responsible for 68% of the total of extra-costs. In 17 occasions (26.6%), the control patient used more resources than the infected patient. CONCLUSIONS: Nosocomial urinary tract infection is associated with a resource use directly related to its presence. For the most part, it is related to the prolongation of hospital stay.

[CD44s Cell surface expression in 55 lung adenocarcinomas. Negative correlation with tumor size and CA125 cytosolic levels]. / Estudio de la expresión de CD44s en 55 adenocarcinomas pulmonares. Correlación inversa con el tamaño y las concentraciones citosólicas de CA125.

INTRODUCTION: CD44s belongs to a family of cell adhesion molecules involved in cell adhesion, migration and cell-extracellular matrix interactions. In this work we attempt to study CD44s expression in lung adenocarcinomas and its possible correlation with other clinicobiological parameters. MATERIAL AND METHODS: Using an EIA, cell surface CD44s levels were determined in 55 lung adenocarcinomas, classified according to clinical stage, histological grade, ploidy and cellular S-phase fraction. CA125 cytosolic concentrations were also assayed. RESULTS: Forty two adenocarcinomas (76.4%) showed CD44s concentrations > 80 ng/mg prot, and did not differ significantly from those observed in 16 normal samples (93.7%). There were no differences in CD44s expression when clinical stage (I: 24/28, II: 6/9 and III: 12/17), lymph node involvement (N = 245/29, N+: 18/26), ploidy (diploid: 3/5, aneuploid: 32/39), histological grade (I: 6/7, III: 18/26) and cellular S-phase (> 8.8%: 24/31, < or = 8.8%: 17/24) were considered. Positive CD44s tumors had lower CA125 (p: 0.0072) cytosolic levels and a reduced tumor size (p: 0.0093). CONCLUSIONS: CD44s expressions in lung adenocarcinomas did not correlate with any clinicobiological parameters, but there was a negative correlation between this and reduced tumor size and lower CA125 cytosolic levels.

Estimación de los costes asociados a la infección urinaria nosocomial. Un estudio de casos y controles / Estimating the costs associated with nosocomial urinary tract infection. A case-control study

Fundamento. La infección nosocomial (IN) se acompaña de un incremento en el consumo de recursos. En el presente estudio se estima el exceso de costes atribuible a la infección urinaria nosocomial (IUN).Métodos. Se realizó un estudio de casos y controles anidado en un estudio de cohortes. Para el apareamiento se partió del Grupo Relacionado con el Diagnóstico (GRD) al que se adscribió el episodio del paciente caso, con una búsqueda ulterior en la base de datos de altas hospitalarias utilizando las siguientes variables: GRD, sexo, edad, fecha de ingreso, servicio, comparación de estancias, diagnóstico principal, comorbilidad, número de diagnósticos secundarios y procedimientos. Se logró el apareamiento en 64 episodios (71 por ciento), sobre los que se realizó la estimación de costes. Resultados. La estancia media fue para los casos de 15,3 días (mediana: 12) y para los controles de 12,3 días (mediana: 11); p = 0,0001. El exceso de estancia atribuible a la IUN fue de 3 días (IC 95 por ciento: 1,6-4,7), mayor para los pacientes ingresados en los servicios médicos, 5,3 días, que en aquellos que sufrieron intervenciones quirúrgicas, 2 días; p = 0,03. El consumo de recursos diagnósticos fue significativamante más elevado únicamente en pruebas bacteriológicas. El consumo de antibióticos y fluidoterapia fue mayor en los pacientes infectados. Del exceso total del coste estimado por episodio, 132.048 pesetas, el 93 por ciento corresponde al incremento de estancias. Diez pacientes (15,6 por ciento) fueron responsables del 68 por ciento del total de costes extras. En 17 ocasiones (26,6 por ciento) el paciente control consumió más recursos que el paciente infectado. Conclusiones. La infección urinaria nosocomial se acompaña de un consumo de recursos directamente relacionado con su existencia. En su mayor parte está relacionado con la prolongación de la estancia hospitalaria (AU)

[CYFRA 21.1 cytosol levels in lung adenocarcinomas. Correlation with other clinico-biological parameters]. / Estudio de las concentraciones citosólicas de CYFRA 21.1 en adenocarcinomas de pulmón, correlación con otros parámetros clinicobiológicos.

INTRODUCTION: Cyfra 21.1 are soluble cytokeratin 19 fragments present in several biological fluids. The aim of this work was to study cyfra 21.1 cytosolic levels in lung adenocarcinomas and their possible correlation with other clinical-biological parameters. PATIENTS AND METHODS: Cyfra 21.1 was determined, using an immunoradiometric assay (CIS BioInternational. France), in 58 tissue samples of lung adenocarcinomas patients. Other parameters included in the study were the following: clinical stage, histological grade, ploidy, S-phase cellular fraction, as well as cathepsin D, CA 125 and hyaluronic acid levels in cytosols. Likewise, AH, erbB2 oncoprotein, CD44s, CD44v5 and CD44v6 levels in cell surfaces were assayed. RESULTS: Cyfra 21.1 cytosolic levels oscillated between 24.8 and 6,774 ng/mg prot. (median 1,147.5) and were higher (p:0.00074) than those observed in 16 normal lung samples of the same patients. We did not observe any statistically significant differences in cyfra 21.1 values when clinical stage, ploidy, S-phase and histological grade were considered. When lung adenocarcinomas were classified according to cyfra 21.1 positivity, using 1,499 ng/mg prot. as cut-off, which represents the 75th percentile of the whole group, we noted that positive cases had higher levels of cathepsin D (p:0.00218), cytosolic hyaluronic acid (p:0.02947), erbB2 protein (p:0.06272) and CA 125 (p:0.07243) than negative carcinomas. CONCLUSIONS: These results suggest the possibility that high cytosolic cyfra 21.1 levels could be associated with a poor outcome in lung adenocarcinomas.

[Cytosolic pS2 levels in 154 non-small-cell lung carcinomas. Correlation with other clinical and biological parameters]. / Estudio de la concentración citosólica de pS2 en 154 carcinomas pulmonares no microcíticos. Correlación con otros parámetros clínico-biológicos.

INTRODUCTION: pS2 was first identified as an estrogen induced molecule in a breast cancer cell line, but its gene responds to several growth factors and oncogenic proteins. Its main clinical application lies in breast carcinomas, where it is a molecular marker to identify breast cancer patients who will respond to hormone therapy. This study was performed to evaluate the significance of the pS2 cytosolic levels in non small cell lung carcinomas classified according to different clinical and biological parameters. Likewise, the results obtained were correlated with those observed in normal tissues. MATERIAL AND METHODS: The study group included 154 non small cell lung carcinomas (59 adenocarcinomas and 95 squamous carcinomas) and 54 normal lung samples. Cathepsin D, pS2, neuron specific enolase (NSE) and CA125 cytosolic concentrations were determined, as well as those of epidermal growth factor receptor (EGFR), erbB2 protein, CD44s, CD44v5 and CD44v6 on cell surface membranes. Likewise, clinical stage, histological grade, ploidy and cellular S-phase fraction were also considered as variables of the study. RESULTS: We observed cytosolic pS2 values greater than 1 ng/mg protein (positive cutoff) in 18/59 adenocarcinomas and in 10/95 squamous carcinomas (p:0.00177). In adenocarcinomas, pS2 positivity was not correlated with any clinical and biological parameters, but positive cases had lower EGFR (p:0.03770) concentrations and higher CA125 (p:0.01902) levels. In squamous carcinomas, pS2 positivity was associated with lower EGFR (p:0.02270) levels and higher erbB2 protein (p:0,00563) concentrations. CONCLUSIONS: Our results led us to suggest the following: 1) cytosolic pS2 concentrations are higher in tumoral than in normal samples; 2) adenoarcinomas had higher levels than squamous lung carcinomas; 3) in adenocarcinomas, positivity for pS2 is associated with lower EGFR levels and higher CA125 concentrations suggesting a worse outcome, and 4) in squamous lung tumors, positivity for pS2 was associated with lower EGFR and higher erbB2 oncoprotein concentrations, it not being possible to establish its clinical significance, although it may be correlated with a poor prognosis.

[Infiltrating ductal carcinomas of the breast in women over 60 years of age. Association with higher cellular proliferation and lower PS2, cell surface and cytosolic hyaluronic acid concentrations]. / Carcinomas ductales infiltrantes de mama en mujeres mayores de 60 años. Asociación con mayor proliferación celular y menores concentraciones de pS2 y ácido hialurónico citosólico y de membrana.

INTRODUCTION: There are several discrepancies in the literature concerning breast cancer behavior in elderly women. For this reason, we decided to study the possible clinical-biological differences between infiltrating ductal breast carcinomas in women older than 60 and those between 41 and 60 years old. PATIENTS AND METHODS: The study group included 161 women with infiltrating ductal carcinomas of the breast, 90 of whom were women over 60 years and 71 whose ages ranged from 41 to 60 years old. Estrogen receptors (ER), progesterone receptors (PR), pS2, cathepsin D, tissue-type plasminogen activator (t-PA) and hyaluronic acid (HA) cytosolic concentrations were analyzed in addition to those of the epidermal growth factor receptor (EGFR), HA and erbB2/neuoncoprotein in cell surfaces. Size, axillary lymph node involvement, distant metastases, histological grade, ploidy and cellular S-phase fraction were also considered as study variables. RESULTS: Infiltrating ductal carcinomas of the breast in women over 60 had lower pS2 concentrations (p: 0.0367), cell surface (p: 0.021) and cytosolic hyaluronic acid (p: 0.0019) levels than those of women whose ages ranged from 41 to 60 years old. Furthermore, the former had higher S-phase values (p: 0.0345) and percentage of cases with S-phase >7% (p: 0.0483). CONCLUSIONS: The results obtained (higher cellular proliferation and lower pS2, cell surface and cytosolic hyaluronic acid concentrations) suggest that the infiltrating ductal carcinomas of the breast in women older than 60 could have a worse behavior, as has been suggested by other authors, even though further studies with more patients would be needed in order to observe if these biological differences still persist.

Histological grade in breast cancer: association with clinical and biological features in a series of 229 patients.

In order to study the association of histological grade (HG) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast (IDC), we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor (ER), progesterone receptor (PR), pS2, cathepsin D, hyaluronic acid (HA) and tissue-type plasminogen activator (t-PA), as well as those of the erbB2 oncoprotein, epidermal growth factor receptor (EGFR), HA, CD44v5 and CD44v6 in the cell membrane fraction. Likewise, we considered size, ploidy, S-phase fraction and axillary node involvement as variables of the study. The transition from HG1 to HG2 and from HG2 to HG3 was accompanied by a number of common features: global increase in size, greater number of tumors >2.0 cm, decrease in membrane hyaluronic acid concentrations, increased cell proliferation (S-phase >7%) and greater aneuploidy. Other events observed during the transition from HG2 to HG3 were a decrease in ER, PR, t-PA and cytosolic hyaluronic acid. These results led us to consider that HG is associated with certain clinical-biological changes that may help explain its value as a prognostic factor in breast carcinomas.

[Clinico-biological impact of pS2 positivity in estrogen receptor negative-infiltrating ductal carcinomas of the breast]. / Impacto clínico-biológico de la positividad de la pS2 en carcinomas ductales infiltrantes de mama receptor de estrógenos negativos.

UNLABELLED: The pS2 protein is regulated by estrogens, but it can also be expressed in hormone independent breast carcincomas. We have carried out the present study in order to analyze the clinical-biological impact of pS2 positivity (>2 ng/mg prt.) in negative estrogen receptors (< 10 fmol/mg prt.) infiltrating ductal breast carcinomas (IDC). MATERIAL AND METHODS: 97 negative ER-IDC have been included in our study. We established the doses of the cytosol levels of pS2, progesterone receptors (PR), cathepsin D, tissue -type plasminogen activator (t-PA) and hyaluronic acid (HA), as well as the levels of HA, epidermal growth factor receptor (EGFR), CD44v5 and CD44v6 in cell surface membranes. We also considered the menopausal status, histological grade, ploidy, cellular synthesis phase, tumor size, axillary lymph node involvement and the existence of distant metastasis. The same results were obtained when the progesterone receptor status was also considered. RESULTS: ER-/pS2+ IDC presented higher (p <0,05) PR, t-PA and HA cytosol level, as well as lower EGFR concentrations, S-phase > 7% and S-phase >14% and lower N+>10 percentages and aneuploidy. They were also more frequently CD44v6+. The same results were observed when the positivity of the progesterone receptors was considered. CONCLUSIONS: The above results lead us to consider that the positivity for pS2 in ER- IDC is associated with hormone-dependent parameters, good differentiation and lower cellular proliferation, which can explain a better clinical outcome.

[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases]. / La expresión de la molécula de adhesión CD44v6 en carcinomas ductales infiltrantes de mama se asocia con la hormonodependencia. Nuestra experiencia con 168 casos.

In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.

The effects on lipid and apolipoprotein serum levels of long-term carbamazepine, valproic acid and phenobarbital therapy in children with epilepsy.

The aim of the present study was to assess the effect of long-term carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PB) treatment on serum lipids and apolipoproteins in epileptic children. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TGs) were measured and the LDL-C/HDL-C and TC/HDL-C ratios were calculated in 320 children and adolescents (129 receiving CBZ, 127 receiving VPA and 64 receiving PB) suffering from various types of epilepsy. Additionally, in a subgroup of 181 children (68 CBZ; 78 VPA; 35 PB) apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), HDL2-C and HDL3-C were measured and apoA-I/apoB and HDL2-C/HDL3-C ratios were calculated. Results of the measurements were compared with those of 169 age-and sex-matched healthy controls. None of the variables considered was significantly correlated with time elapsed since start of treatment or with drug concentration in serum. TC and LDL-C serum levels were high in children receiving CBZ or PB and low in those treated with VPA. Serum LDL-C level exceeded 130 mg/dl in 27.9% of CBZ-group, 31.8% of the subjects receiving PB, but only in 7% of those receiving VPA and in 11.8% of control group subjects. CBZ-treated children also showed high HDL-C and HDL3-C values. In the group receiving VPA, HDL2-C, HDL2-C/HDL3-C ratio and apo B were significantly lower than in the control group. Mean apoA-I levels were low in all treated groups: by contrast, in neither group did TGs, VLDL-C levels and TC/HDL-C or LDL-C/HDL-C ratios differ significantly from the corresponding control group. Our results suggest that the effects of long-term AED therapy on lipid profile and, particularly, on apolipoprotein serum levels increase risk of atherosclerosis-related disease. Moreover, these results confirm our previously reported increased risk in CBZ and PB-treated patients.

Alcohol use among fatally injured drivers in Spain.

Blood from 285 fatally injured drivers in Northern Spain was collected and tested for the presence of alcohol and drugs. Alcohol was detected in 50.5% of all fatalities. Alcohol alone was detected in 44.2% of all samples and in the remaining 6.3% another substance was found together with alcohol. Blood alcohol concentration was classified in different levels. It has been observed that in 35.4% of the cases the blood alcohol level was > or = 0.8 g/l, the legal limit in Spain for car drivers. Alcohol together with other substances was encountered in 18 cases, with medication in 22.2% (4 out of 18), alcohol with illegal drugs in 66.6% of the cases (12 out of 18), and alcohol with medicines and illegal drugs in 11.1% (2 out of 18). Cocaine was the most commonly detected drug. The study shows how widespread the incidence of a high level of alcohol concentration among drivers involved in fatal accidents in Spain.