A study on the bioequivalence of lithium and valproate salivary and blood levels in the treatment of bipolar disorder.

Lithium (Li) and valproate (VPA) are used in the treatment of bipolar disorder (BD), with narrow therapeutic window requiring periodic control of serum levels. This prevents intoxication, lack of efficacy due to low serum concentrations, and allows monitoring adherence. We aimed at evaluating the bioequivalence of salivary and blood levels of LI or VPA in a sample of adult BD patients. Secondarily, lithium bioequivalence was evaluated across different patients' lifespans. BD patients treated with either Li or VPA underwent contemporary standard serum and salivary measurements. Blood levels of both drugs were taken according to standard procedures. Li salivary levels were performed by an adapted potentiometric method on the AVL9180 electrolyte analyzer. VPA salivary levels were taken with an immune-assay method with turbidimetric inhibition. A total of 50 patients (38 on Li, 12 on VPA) were enrolled. Blood-saliva bioequivalence for VPA was not found due to a high variability in salivary measures. Li measures resulted in a high correlation (r=0.767, p<0.001), showing no partial correlation with age (r=0.147, p=0.380). Li salivary test is a reliable method of measuring Li availability and is equivalent to serum levels. Potential advantages of Li salivary testing are its non-invasive nature and the possibility of doing the test during the usual appointment with the psychiatrist.

Effect of CYP2D6, CYP2C9 and ABCB1 genotypes on fluoxetine plasma concentrations and clinical improvement in children and adolescent patients.

There is little known about pharmacogenetic of fluoxetine in children and adolescents. In this study, we evaluate, for the first time, the influence of CYP2D6, CYP2C9 and ABCB1 genotypes on the steady-state plasma concentrations of fluoxetine and its active metabolite (S)-norfluoxetine, and on the clinical improvement in children and adolescent patients receiving fluoxetine treatment. The assessment was performed in 83 patients after 8 and 12 weeks of treatment. Fluoxetine/(S)-norfluoxetine ratio was negatively correlated with the number of active CYP2D6 alleles (r: -0.450; P<0.001). Regarding the G2677T ABCB1 polymorphism, T allele carriers showed significantly higher improvements on the majority of scales including the Clinical Global Impression-Improvement scale (P<0.001). Our results confirm the influence of CYP2D6 genetic variants in fluoxetine pharmacokinetics and provide evidence for the potential effect of the ABCB1 genotype on the clinical improvement in children and adolescent patients treated with fluoxetine.

Evaluation of the VersaTREK system compared to the Bactec MGIT 960 system for first-line drug susceptibility testing of Mycobacterium tuberculosis.

The aim of this study was to evaluate the reliability of the VersaTREK system for Mycobacterium tuberculosis drug susceptibility testing compared with results obtained with the Bactec MGIT 960 system. A total of 67 strains were evaluated. Overall agreement was at 98.5%. Kappa indexes were 1.0 for isoniazid, rifampin, and ethambutol, 0.937 for pyrazinamide, and 0.907 for streptomycin. The VersaTREK system is validated for M. tuberculosis drug susceptibility testing.

Prolonged bisphosphonate release after treatment in women with osteoporosis. Relationship with bone turnover.

Bisphosphonates (BP), especially alendronate and risedronate, are the drugs most commonly used for osteoporosis treatment, being incorporated into the skeleton where they inhibit bone resorption and are thereafter slowly released during bone turnover. However, there are few data on the release of BP in patients who have received treatment with these drugs for osteoporosis. This information is essential for evaluating the possibility of BP cyclic therapy in these patients and for controlling their long-term presence in bone tissue. This study evaluated the urinary excretion of alendronate and risedronate in patients treated with these drugs for osteoporosis and analysed its relationship with bone turnover, time of previous drug exposure and time of treatment discontinuation. We included 43 women (aged 65±9.4 years) previously treated with alendronate (36) or risedronate (7) during a mean of 51±3 and 53±3 months, respectively, who had not been treated with other antiosteoporotic treatment and with a median time of discontinuation of 13.5 and 14 months, respectively. Both BP were detected in 24-hour urine by HPLC. In addition, bone formation (PINP) and resorption (NTx) markers were analysed. Both BP were also determined in a control group of women during treatment. Alendronate was detected in 41% of women previously treated with this drug whereas no patient previously treated with risedronate showed detectable urinary values. All control patients showed detectable values of both BP. In patients with detectable alendronate levels, the time of drug cessation was shorter than in patients with undetectable values (12 [6-19] versus 31 [7-72] months, p<0.001). Alendronate was not detected in any patient 19 months after treatment cessation. Alendronate levels were inversely related to time of treatment discontinuation (r=-0.403, p=0.01) and the latter was directly related to NTx (r=0.394, p=0.02). No relationship was observed with age, length of drug exposure, renal function or weight. In conclusion, contrary to risedronate, which was not detected in patients after cessation of treatment, alendronate was frequently detected in women previously treated with this agent up to 19 months after discontinuation of therapy. The relationship between alendronate levels and both bone resorption and time of treatment cessation further indicates a residual effect of this drug in bone, despite treatment discontinuation.

The PFA-100 detects sub-optimal antiplatelet responses in patients on aspirin.

Although it is suspected that some patients with acute coronary syndromes (ACS) could have a sub-optimal response to aspirin (SASAR), currently a fixed dose of ASA is long-term used in all individuals. This study was designed to determine SASAR and whether a SASAR is a predictor for recurrence of ischemic events in patients on low-dose ASA with a previous ACS. One hundred patients taking ASA 100 mg/day were assessed at 1 and 6 months after a first ACS. SASAR was initially defined as a failure of the ASA treatment to significantly prolong the closure time in the Platelet Function Analyzer (PFA-100). SASAR in these samples was reconfirmed by conventional aggregometry. TXB2 levels were determined in plasma. At one month 49 patients showed SASAR in the PFA-100; only 25 of them showed SASAR by conventional aggregometry. At six months, 39 of 81 patients showed SASAR by PFA-100, but conventional aggregometry detected SASAR in only 12 of the 39 patients. TXB2 levels were significantly higher in patients with SASAR. Five patients with SASAR, by both tests, died during follow-up (p = 0.013). The PFA-100 detected a high rate of SASAR in patients with ACS. This instrument could be used to screen for suboptimal response to the antiplatelet action of ASA. Whether persistence of SASAR could relate to a higher risk of recurrence and how adjusting the dose of ASA could reduce the rate of SASAR are issues that deserve further investigations.

[Ponderal evolution in the Girona population, 1989-1999]. / Evolución ponderal en la población de Girona, 1989-1999.

BACKGROUND AND OBJECTIVE: Despite the number of plans leading to lose weight among individuals in the developed countries, the prevalence of obesity has increased since 1980. The knowledge of ponderal evolution in a given population is very important because the adverse effects of obesity vary greatly among individuals and populations. The objective of the present paper was to determine the modifications in the different degrees of body adiposity in a population in Catalunya. PATIENTS AND METHODS: A measurement was made of weight and height of 24554 users aged over 14 years (10595 males and 13959 females) attended at four basic health areas (BHA): Girona 1, Girona 4, Salt and Camprodon, and a Primary Health Center (PHC) in the Girona province, for a five-year period, 1995-1999. The prevalence of the different degrees of obesity was compared with that obtained in a previous study with 6373 individuals during the 1986-1989 period (4,579 males and 1794 females). RESULTS: The prevalence of women with overweight (defined as a body mass index [BMI] > 25 kg/m2) increased from 7.3% (1986-1989, study 0) to 17.6% (1995-1999, study 1) for women aged 15 to 24 years ( p < 0.001), from 17.9 % to 28.1% for women aged 25 to 34 years (p < 0.001), and from 37.5% to 44.7 % for women aged 35 to 44 years (p < 0.001). In the latter age group, the proportion of women with obesity (BMI > 30 kg/m2) increased from 6.9% to 12.9%. Similar trends were observed among men, and the change in the 35-44 year age group (from 10.5 % of obese men to 16% [p < 0.001]), and 55 to 65 years (from 16.6% of obese men to 22.7% [p < 0.001] was particularly significant. And lastly, it is also noteworthy the proportion of individuals with low weight (BMI < 18.5 kg/m2) which increased from 7.3% to 11.6% for women aged 15 to 24 years, and from 0.3% to 2.2% for women aged 35 to 44 years. This trend was also observed for men aged 15 to 24 years (11% to 17.2%). CONCLUSIONS: The relative increase in the prevalence of overweight and obesity runs in parallel to that found in other surrounding countries. Also, it is worth mentioning that among women aged 15 to 24 years the increase in the prevalence of low weight and obesity is almost identical, which invalidates the mean and median values as a means to assess the ponderal evolution in this population. The current compartmentalization between the extreme BMIs, particularly among the youngest portion of population should be addressed from a multidisciplinary perspective.

Evolución ponderal en la población de Girona, 1989-1999 / Ponderal evolution in the Girona population, 1989-1999

Introducción y objetivo. A pesar de los numerosos planes encaminados a perder peso en los países desarrollados, la prevalencia de obesidad se ha incrementado desde 1980. El conocimiento de la evolución ponderal de una población dada es muy importante porque los efectos adversos de la obesidad son muy variables entre individuos y entre poblaciones. El objetivo de este estudio fue determinar las modificaciones de los diferentes grados de adiposidad corporal en población catalana. Pacientes y métodos. Se midió el peso y la talla a 24.554 usuarios mayores de 14 años (10.595 hombres y 13.959 mujeres) atendidos en cuatro áreas básicas de salud (ABS): Girona 1, Girona 4, Salt y Camprodon y un Centro de Atención Primaria (CAP) de la provincia de Girona, durante un período de 5 años, 1995-1999. La prevalencia de los diferentes grados de obesidad se comparó con la obtenida en un estudio previo sobre 6.373 sujetos durante el período 1986-1989 (4.579 hombres y 1.794 mujeres).Resultados. La prevalencia de las mujeres que presentaban sobrepeso (definido como un índice de masa corporal [IMC] > 25 kg/m2) creció de un 7,3 por ciento (1986-1989, estudio 0) a un 17,6 por ciento (1995-1999, estudio 1) entre las mujeres de 15 a 24 años ( p 30 kg/m2) pasó del 6,9 por ciento al 12,9 por ciento. En los hombres se observaron tendencias similares, siendo especialmente significativo el cambio en la década de 35 a 44 años (de un 10,5 por ciento de hombres obesos a un 16 por ciento [p < 0,001]) y de 55 a 65 años (de un 16,6 por ciento de hombres obesos a un 22,7 por ciento [p < 0,001]). Por último, también es de destacar el cambio en la proporción de sujetos con bajo peso (IMC < 18,5 kg/m2), que creció de un 7,3 por ciento a un 11,6 por ciento en las mujeres de 15 a 24 años y de un 0,3 por ciento a un 2,2 por ciento en las mujeres de 35 a 44 años. Esta tendencia también se observó entre los hombres de 15 a 24 años (11 por ciento a 17,2 por ciento). Conclusiones. El crecimiento relativo de la prevalencia de sobrepeso y de obesidad es paralela a la de otros países de nuestro entorno. Además es de destacar que en el caso de las mujeres de 15 a 24 años el aumento de la prevelancia de bajo peso y de obesidad es casi idéntico, lo que invalida a la media y mediana de IMC como medio de valorar la evolución ponderal en esta población. Es necesario abordar desde una perspectiva multidisciplinaria la tendencia a la compartimentalización actual entre los IMC extremos, especialmente en el segmento más joven de la población (AU)

Biological monitoring of environmental exposure to manganese in blood samples from residents of the city of Barcelona, Spain.

Serum manganese levels were determined in 250 healthy subjects (122 men and 128 women) living in Barcelona in northeastern Spain. The study was designed to assess the reference levels for serum manganese and to investigate its relationship to age and sex. The age distribution ranged from 15 to 90 years. The assays were performed by means of a graphite furnace atomic absorption spectrometry. The geometric mean of serum manganese concentration was 1.1 microg/l, ranging from 0.3 microg/l to 2.5 microg/l. In almost every case, the 95th upper percentiles of this element were < 1.8 microg/l. No correlation between the concentration of manganese and sex could be established, but in the younger population the manganese levels were nearly three times higher than the results obtained in the older population.

[Prevalence of obesity in the population assisted at primary health care services in Girona, 1995-1999]. / Prevalencia de la obesidad en la población atendida en asistencia primaria de Girona, 1995-1999.

OBJECTIVES: To estimate the prevalence of obesity and overweight in the population of Girona (Spain) between 1995 and 1999 and to divide the prevalences in geographical areas according to age and sex. METHODS: Height and weight were directly measures in 24,554 health care consumers older than 14 years (10,595 men and 13,959 women) treated in four primary health care areas: Girona 1, Girona 4, Salt and Camprodon and in one primary health care center in the province of Girona. Body mas index (BMI) was calcuted by dividing weight in kilograms bye height in meters squared. Obesity was defined as grades II and III of Garrow's index (BMI >= 30 kg/m2) and overweight as degree I (25 kg/m2 >= BMI < 30 kg/m2). Because the sample was not randomized, the prevalences were adequately weighted. The comparison between prevalences in two different primary health care areas for each sex (in the same Garrow's index and age group) was carried out using a parametric test of differences in proportions (Student's t-test). A hierarchical logistic regression was used to compare prevalences in the same grade Garrow's index, controlling for age and sex. RESULTS: The prevalence of obesity was estimated as 15.6% in men aged from 20-74 years (from 14.0% in Girona 1 to 22.4% in Camprodon) and 17.5% for women (15.6% in Girona 1, 22.7% in Camprodon). The weighted mean was 16.7%. The prevalence of overweight was 44% in men and 33% in women and the weighted mean was 37.8%. The prevalence of obesity was graduated with statistically significant differences between Girona 1, Salt, Girona 4, Camprodon and Sils. CONCLUSIONS: The estimates of the prevalences of obesity and overweight obtained in this study were closer to those of other studies in similar populations than previously believed. Indeed, the prevalences may be similar to those of the European Union and, in some age groups, to those of the United States.

Prevalencia de la obesidad en la población atendida en asistencia primaria de Girona, 1995-1999 / Prevalence of obesity in the population of Girona, Spain, 1995-1999

Objetivos: Estimar y comparar la prevalencia de la obesidad y el sobrepeso en la población de Girona, entre 1995 y 1999, estratificando geográficamente por sexo y edad. Métodos: Medidas directas de talla y peso correspondientes a 24.554 usuarios mayores de 14 años (10.595 varones y 13.959 mujeres) atendidos en cuatro áreas básicas de salud (ABS): Girona 1, Girona 4, Salt y Camprodon, así como en un centro de atención primaria (CAP) de la provincia de Girona. Se calculó el índice de masa corporal (IMC) como el cociente entre el peso y la talla al cuadrado. La obesidad se define como los grados II y III del índice de Garrow (IMC 30 kg/m2) y el sobrepeso como el grado I (25 kg/m2 IMC < 30 kg/m2). Al no utilizarse una muestra aleatoria de sujetos, el cálculo de prevalencias y de sus errores estándar se corrigió mediante el uso de ponderaciones adecuadas. La comparación de las prevalencias entre dos ABS distintas para cada sexo se realizó utilizando un contraste paramétrico de diferencia de proporciones La comparación entre las prevalencias de un determinado grado del índice de Garrow, controlando por sexo y edad, se llevó a cabo utilizando una regresión logística j árquica. Resultados: La prevalencia de la obesidad se estimó en 15,6 por ciento entre los varones de 20 a 74 años (desde el 14,0 por ciento en Girona 1 hasta el 22,4 por ciento en Camprodon) y en un 17,5 por ciento entre las mujeres (un 15,6 por ciento en Girona 1 y un 22,7 por ciento en Camprodon), un 16,7 por ciento de promedio ponderado. La prevalencia del sobrepeso se sitúa en el 44 por ciento en varones y en un 33 por ciento en mujeres, un 37,8 por ciento de promedio ponderado. Existe una gradación en las prevalencias de la obesidad, con diferencias estadísticamente significativas: Girona 1, Salt, Girona 4, Camprodon y Sils (AU)

Dietary micronutrients/antioxidants and their relationship with bronchial asthma severity.

BACKGROUND: Because little is known about micronutrient/antioxidant intake and asthma severity, we investigated dietary intake and plasma/serum levels of micronutrients/antioxidants in a group of asthma patients with various degrees of severity, and compared the results with healthy subjects. METHODS: A case control study was carried out on 118 asthma patients and 121 healthy subjects. The severity of the disease was classified by division of patients into four groups. Normal dietary micronutrient/antioxidant intake was estimated from a food frequency questionnaire. Plasma/serum levels of vitamins C, E, and A, selenium, magnesium, zinc, and platelet glutathione peroxidase (GSH-Px) activity were also determined. RESULTS: No differences in daily micronutrient/antioxidant intake were seen between patients and healthy subjects. The severity of the disease showed no significant relationship with micronutrient/antioxidant intake. There were no differences in plasma/serum levels in any of the micronutrients/antioxidants between healthy subjects and asthmatics. Nor were any differences found between asthma groups in severity in the biochemical measures, except in platelet GSH-Px activity, which was significantly lower in the most severe groups. CONCLUSIONS: In this study, we found no evidence of any association between micronutrient/antioxidant intake or plasma/serum levels of micronutrients/antioxidants and asthma. Reduction of platelet GSH-Px activity in the most severe patients suggests that these patients have a diminished capacity to restore part of the antioxidant defences.

Optimized procedure for lamotrigine analysis in serum by high-performance liquid chromatography without interferences from other frequently coadministered anticonvulsants.

The authors have developed a simple isocratic high-pressure liquid chromatographic (HPLC) assay for the simultaneous determination of lamotrigine and other frequently coadministered antiepileptic drugs in serum samples. Lamotrigine extraction was performed on a reversed-phase Oasis HBL preparation column. The eluates containing butalbital as internal standard were separated with a 7-microm Chromsystems C18 250 x 4.0 mm I.D. reversed-phase column at a temperature of 40 degrees C using a mobile phase consisting of pH 3.8 phosphate-acetonitrile buffer (55:45, v/v), at a flow rate of 0.8 mL/min. Ultraviolet detection was carried out at 210 nm. Measurement of the peak:height ratio allowed quantitative determination of the samples. The method was linear over a concentration range of 0.2 to 20 microg/mL for lamotrigine. Recovery was >90%. Within-day and between-day coefficients of variation ranged from 1.8% to 6.7%. The mean lamotrigine concentration was 8.01 +/- 5.63 microg/mL. After studying sera from 130 patients treated with lamotrigine the authors confirmed that associated antiepileptic therapy affected the serum lamotrigine levels, which were significantly higher in patients under valproic acid treatment.

Cyclical etidronate versus sodium fluoride in established postmenopausal osteoporosis: a randomized 3 year trial.

To compare the effects of sodium fluoride and etidronate in severe postmenopausal osteoporosis, we conducted a 3 year, prospective, trial in 118 postmenopausal osteoporotic women with at least one vertebral fracture, who were randomly assigned to receive sodium fluoride (25 mg twice daily, as enteric-coated tablets) plus calcium (1000 mg/day) or intermittent etidronate (400 mg/day for 14 days) followed by calcium (1000 mg/day for 76 days). Lateral spine X-ray films and dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and proximal femur were performed at enrollment and yearly. Nonvertebral fractures were recorded every 6 months. Thirty-one women in the fluoride group and 47 in the etidronate group completed the trial. At 36 months, the mean change from baseline of the lumbar bone density in the fluoride group was 8.5 +/- 2.04% (p = 0.001) and in the etidronate group was of 3.6 +/- 0. 84% (p < 0.001). The changes in the fluoride group were significantly higher than in the etidronate group (p = 0.01). Both groups showed nonsignificant changes in femoral neck bone density. There was no significant difference between groups in the cumulative proportion of women with new vertebral fractures, with an incidence in the fluoride group of 16% vs. 17% in the etidronate group. However, the number of new vertebral fractures was significantly lower in the fluoride group (6 fractures) than in the etidronate group (19 fractures) (p = 0.05). The number of patients with nonvertebral fractures was similar in both groups. A high incidence of side effects, mainly gastrointestinal symptoms and lower extremity pain syndrome, was observed in the fluoride group. Etidronate was well tolerated. We conclude that, in women with severe osteoporosis, although sodium fluoride is more favorable than cyclical etidronate for increasing lumbar bone mass, no differences were observed in the incidence of fractures.

Alpha-1-acid glycoprotein in major depressive disorder. Relationships to severity, response to treatment and imipramine plasma levels.

BACKGROUND: Increased plasma levels of alpha-1-acid glycoprotein (AGP) were reported in major depressive disorder. However, the relationship between AGP levels, severity of depression, treatment response and antidepressant levels are still unclear. METHODS: Plasma AGP levels were measured in 36 subjects with major depressive disorder before and after a 6-week treatment with imipramine and in 30 controls. Free imipramine plasma levels of depressed patients were measured at 6 weeks. Comparative analysis between depressed patients and controls, between non-responders (N = 12) and responders (N = 24), and between severely depressed patients (N = 14) and moderately depressed patients (N = 22) were made. RESULTS: Depressed patients had significantly higher mean values of AGP than control subjects. Imipramine non-responders and specially severely depressed patients had significantly greater increases of AGP levels during treatment than other depressed subgroups. There was no correlation between baseline AGP levels and severity of depression or free imipramine levels. LIMITATIONS: The most significant limitations of this study are the small sample size and the fact that all the subjects were out-patients. Results should not be generalized to in-patient populations. CONCLUSIONS: Depressed patients showed high baseline concentrations of AGP. AGP levels did not predict either free imipramine plasma levels or differential response after 6 weeks of treatment with imipramine. A greater increase of AGP during treatment was associated with severity of depression and treatment non-response. CLINICAL IMPLICATIONS: The relationship between high plasma levels of AGP, severity of depression and lack of treatment response is clarified. The influence of imipramine levels is minimized.

Blood chromium determination in assessing reference values in an unexposed Mediterranean population.

Plasma chromium levels were determined in 243 healthy subjects. The study group consisted of 134 men and 109 women, ages 19-71 yr, all residing in Barcelona in northeastern Spain. The study was designed to assess the reference levels for plasma chromium and to investigate its relationships to age and sex. The assays were performed by means of a graphite-furnace atomic absorption spectrometer. The mean plasma chromium concentration was 3.01 +/- 1.45 nmol/L, ranging from 0.6 to 6 nmol/L. The upper reference values in the 0.95 percentile for this population was 5 nmol/L. No significant differences were observed with respect to the subjects' sex.

Serum and urine fluoride concentration: relationships to age, sex and renal function in a non-fluoridated population.

Serum and urine fluoride levels were determined in 250 healthy subjects (15-90 years, 122 men and 128 women) residing in Catalonia, Spain, and in 150 patients (20-81 years, 84 men and 66 women) with chronic renal failure undergoing regular dialysis treatment, living in the same geographical area, to determine normal range and to investigate its relationships to age, sex and renal function. Serum and urine fluoride were determined by a fluoride ion specific electrode system. Mean (+/- S.D.) serum fluoride concentration was 17.5 +/- 9.5 micrograms/l, ranging from 1 to 47 micrograms/l, in the control group and 58 +/- 31 micrograms/l, ranging from 28 to 185 micrograms/l, in renal patients. Urine fluoride concentration in the healthy group was 671 +/- 373 micrograms/24 h, ranging from 156 to 1900 micrograms/24 h. Fluoride status in the patient group was significantly greater than the control group. There was significant correlation between serum fluoride and age. No sex related difference was found.