Delivery of glutamine synthetase gene by baculovirus vectors: a proof of concept for the treatment of acute hyperammonemia.

Hyperammonemia, a condition present in patients with urea cycle disorders (UCDs) or liver diseases, can cause neuropsychiatric complications, which in the worst cases result in brain damage, coma or death. Diverse treatments exist for the treatment of hyperammonemia, but they have limited efficacy, adverse effects and elevated cost. Gene therapy is a promising alternative that is explored here. A baculovirus, termed Bac-GS, containing the glutamine synthetase (GS) gene was constructed for the in vitro and in vivo treatment of hyperammonemia. Transduction of MA104 epithelial or L6 myoblast/myotubes cells with Bac-GS resulted in a high expression of the GS gene, an increase in GS concentration, and a reduction of almost half of exogenously added ammonia. When Bac-GS was tested in an acute hyperammonemia rat model by intramuscularly injecting the rear legs, the concentration of ammonia in blood decreased 351 µM, in comparison with controls. A high GS concentration was detected in gastrocnemius muscles from the rats transduced with Bac-GS. These results show that gene delivery for overexpressing GS in muscle tissue is a promising alternative for the treatment of hyperammonemia in patients with acute or chronic liver diseases and hepatic encephalopathy or UCD.

[Who monitors patients treated with psychotropic drugs in primary care?]. / 'Quién controla a los enfermos tratados con fármacos psicotropos en atención primaria?

OBJECTIVE: To analyse the degree of monitoring by doctors, nurses, and other health professionals of patients taking psychotropic medication. DESIGN. Retrospective, observational study of patients of both sexes and over 15 years old, who took psychotropic medication and had attended a minimum of ten times the same doctor-nurse primary care unit (PCU). Their monitoring during 2 year-long periods was studied: a first period (the first year after diagnosis) and a second period from October 2001 to October 2002. SETTING: Primary care in the Raval Sud District, Barcelona, Spain. PARTICIPANTS: A total of 730 clinical histories were reviewed, of which 200 (27%) met inclusion criteria. RESULTS: The most common diagnosis was anxiety-depression disorder (58%), and 14.5% of patients had no recorded diagnosis. 35.5% were patients taking more than one medicine. The most common drug group was the benzodiazepines (60.4%). Significant differences in the number of controls were found between the 2 periods and between different PCUs. The mean difference between periods was -0.5, with 95% CI at -1.0: clearly the degree of monitoring drops over time. CONCLUSIONS: These patients' follow-up was not monitored well, which poses the need to create clear aims and protocols for the doctor-nurse team, to thus assist the treatment of patients with mental health problems.

¿Quién controla a los enfermos tratados con fármacos psicotropos en atención primaria? / Who monitors patients treated with psychotropic drugs in primary care?

Objetivo. Analizar el grado de seguimiento realizado por médicos, enfermeras y otros profesionales de la salud sobre los enfermos consumidores de fármacos psicotropos. Diseño. Estudio observacional retrospectivo en el que se seleccionó a pacientes de ambos sexos mayores de 15 años, con consumo de fármacos psicotropos y visitados un mínimo de 10 veces por la misma unidad básica de atención médico-enfermera (UBA). Se estudió su seguimiento durante 2 períodos de un año: el primer año después del diagnóstico y el período octubre de 2001-octubre de 2002. Emplazamiento. Atención primaria en el Área Básica de Salud (ABS) Raval Sud, Barcelona. Participantes. Se revisaron 730 historiales de pacientes, de los cuales 200 (27%) cumplieron criterios de inclusión. Resultados. El diagnóstico más frecuente fue el trastorno de ansiedad-depresión (58%), y destacaba que un 14,5% de los pacientes no tenían un diagnóstico registrado. El 35,5% correspondió a pacientes que recibieron más de un fármaco y el grupo farmacológico más frecuente fue el de las benzodiacepinas (60,4%). Se detectaron diferencias significativas en el número de controles entre los 2 períodos, y entre las diferentes UBA. La mediana de la diferencia de períodos fue ­0,5 y su intervalo de confianza del 95%, ­1,0; se evidencia que el grado de control disminuye con el tiempo. Conclusiones. En estos pacientes se observa poco control en su seguimiento, lo que indica la necesidad de crear unos objetivos y unos protocolos claros dirigidos al equipo médico-enfermera, para así facilitar el tratamiento del paciente con problemas de salud mental

Objective. To analyse the degree of monitoring by doctors, nurses, and other health professionals of patients taking psychotropic medication. Design. Retrospective, observational study of patients of both sexes and over 15 years old, who took psychotropic medication and had attended a minimum of ten times the same doctor-nurse primary care unit (PCU). Their monitoring during 2 year-long periods was studied: a first period (the first year after diagnosis) and a second period from October 2001 to October 2002. Setting. Primary care in the Raval Sud District, Barcelona, Spain. Participants. A total of 730 clinical histories were reviewed, of which 200 (27%) met inclusion criteria. Results. The most common diagnosis was anxiety-depression disorder (58%), and 14.5% of patients had no recorded diagnosis. 35.5% were patients taking more than one medicine. The most common drug group was the benzodiazepines (60.4%). Significant differences in the number of controls were found between the 2 periods and between different PCUs. The mean difference between periods was ­0.5, with 95% CI at ­1.0: clearly the degree of monitoring drops over time. Conclusions. These patients' follow-up was not monitored well, which poses the need to create clear aims and protocols for the doctor-nurse team, to thus assist the treatment of patients with mental health problems

Tracking of body mass index during childhood: a 15-year prospective population-based family study in eastern Finland.

OBJECTIVES: To investigate the tracking of body mass index (BMI) during childhood. The effect of birth weight and family history of obesity on BMI development during childhood was also evaluated. METHODS: All children born during 1981-1982 in a rural community of eastern Finland were followed at ages 6 months, 7 and 15 y (-6 m, -7y, -15y). Out of 205 children, 138 completed the full follow-up period, of which 100 (45 girls) were included in the analysis with complete data. RESULTS: BMI-6 m was significantly associated with BMI-7y (r=0.320; P-value=0.001), but no longer with BMI-15y. BMI-7y was significantly associated with BMI-15y (r=0.686; P-value <0.001). Children in the highest tertile of BMI-6 m did not have a higher risk of being in the highest tertile of either BMI-7y or BMI-15y compared with children in other tertiles of BMI-6 m. Children in the highest tertile of BMI-7y had a significantly higher risk of being in the highest tertile of BMI-15y (relative risk=3.6 (2.0-6.3)) compared with children in other tertiles of BMI-7y. BMI-7y was predicted negatively by parents' education and male gender and positively by BMI-6 m. BMI-15y was predicted positively by BMI-7y, the difference in BMI between ages 7 y and 6 months and the mean of BMI between ages 6 months and 7 y. Birth weight was not a good predictor of BMI during childhood. Children with at least one obese parent seemed to have higher BMI during childhood; however, this association did not reach a significant level. CONCLUSION: The study confirmed the tracking of BMI during childhood. Neither birth weight nor family history of obesity was found a good predictor of BMI during childhood. The risk of obesity in adolescence can be determined during middle childhood and obese children may be targeted in lifestyle advice to reverse this trend. Parental education may have a key role in the prevention of obesity during childhood.

Tracking of serum total cholesterol during childhood: an 8-year follow-up population-based family study in eastern Finland.

AIM: To investigate the tracking of serum total cholesterol (TC) during childhood. METHODS: All children born during 1981-1982 in a rural community of eastern Finland were followed at 6 mo, 7 y and 15 y of age. The full follow-up period was completed by 138 out of 205 children, of whom 82 (33 girls) had TC measured at 7 y and 15 y of age (-7 y, -15 y). The main outcome measurement was TC (mmol/L). RESULTS: TC-7 y was significantly associated with TC-15 y (r = 0.655; p-value < 0.001). This correlation did not change significantly after accounting for confounders. Children in the highest tertile of TC-7 y had a significantly higher risk of being in the highest tertile of TC-15 y compared with children in other tertiles of TC-7 y (relative risk = 6.4 (2.9-13.9)). TC-15 y was predicted positively by TC-7 y (linear regression beta = 0.63; p-value < 0.001) and parental high TC (TC > or = 5.0 mmol/L in at least one parent) (beta = 0.58; p-value = 0.030). Birthweight had no significant association with TC during childhood. CONCLUSION: The study confirmed the tracking of TC during childhood. The identification of children at risk of developing high TC during adolescence should take into consideration the child's previous TC values during childhood and parental TC status.

Familial aggregation of body mass index: a population-based family study in eastern Finland.

In this study, we investigated the familial aggregation of body mass index (BMI) in a sample of families with young offspring from eastern Finland. 15-year-olds were examined from 1996 to 1997, and their biological parents were examined from 1993 to 1994. 224 children were invited; 184 families participated, and 144 were included in the analysis with complete data. Significant positive correlations were found for mother-offspring pairs (correlation [r] = 0.31, p < 0.001, n = 140), father-offspring (r = 0.23, p = 0.017, n = 107), mother-daughter (r = 0.26, p = 0.044, n = 63) and mother-son (r = 0.36, p = 0.001, n = 77). Adjustment for confounding variables did not alter these results. There was a higher proportion of children in the highest quartile of BMI when the mother was obese (odds ratio [OR] = 3.0, 95 % CI = 1.4 - 6.7, n = 140) and when one or both parents were obese (OR = 2.8, 95 % CI = 1.0 - 8.0 when one parent was obese; OR = 4.6, 95 % CI = 1.1 - 20.0 when both parents were obese; n = 103). The study confirmed familial BMI aggregation. The consistent obesity relationship between mother and offspring may indicate the key role of the mother in primary obesity prevention.

Familial aggregation of serum total cholesterol: a population-based family study in eastern Finland.

BACKGROUND: The Finnish population has a high risk of coronary heart disease, which is associated to a high population level of serum total cholesterol (CHOL) already evident at early ages. The study investigated the familial aggregation of CHOL in a sample of families with young offspring from eastern Finland. METHODS: Fifteen-year-old offspring were examined during 1996-1997 and their biological parents were examined during 1993-1994. A total of 224 children were invited and 184 families participated, of which 123 were included in the analysis with complete data. The main outcome measure was the CHOL (millimoles per liter). RESULTS: Significant positive familial correlations of CHOL were found for the pairs of mother/offspring (r = 0.35, P < 0.001, n = 111), father/offspring (r = 0.29, P = 0.007, n = 82), mother/daughter (r = 0.46, P = 0.001, n = 49), mother/son (r = 0.27, P = 0.036, n = 62), and father/daughter (r = 0.35, P = 0.035, n = 36). The adjustments for the offspring's gender and body mass index (BMI) and the parent's age, BMI, education, and family history of acute myocardial infarction did not alter these results. There was a higher proportion of the offspring in the highest quartile of CHOL when the mother had CHOL > or =5 mmol/L (OR = 3.26, 95% CI = 1.2-8.9, n = 111). CONCLUSIONS: The study confirmed the familial aggregation of CHOL. The consistent CHOL association between the mother and the offspring may indicate the key role of the mother for the primary prevention of hypercholesterolemia.

Familial aggregation of blood pressure: a population-based family study in eastern Finland.

Blood pressure (BP) levels in the Finnish population are amongst the highest in the world, despite favourable changes at the national level in the past two decades. The study evaluates the familial aggregation of BP and the association of some environmental factors to the familial aggregation of BP as a primary epidemiological approach of the genetics of hypertension in a sample of families with young offspring from eastern Finland. Offspring aged 15 years were examined between 1996 and 1997 and their biological parents were examined between 1993 and 1994. A total of 224 children were invited, 184 families participated, from which 144 were included in the analysis with complete data. Systolic (SBP), diastolic (DBP) and mean (MAP) arterial BPs were the main outcome measurements. After the offspring's gender and body mass index (BMI) and the parent's age and BMI were controlled for, the mother/offspring correlation of SBP and the father/offspring correlation of MAP were statistically significant (r = 0.18, P = 0.039, n = 134 and r = 0.20, P = 0.048, n = 99, respectively). The additional adjustment for the parent's education and family history of acute myocardial infarction did not change these results. There was a higher proportion of offspring in the highest quartile of SBP and MAP when the mother had a history of hypertension (OR = 3.4, 95% CI = 1.4-8.5, n = 139, and OR = 2.6, 95% CI = 1.0-6.5, n = 139, respectively). The study confirmed the familial aggregation of BP. The consistent BP association between the mother and the offspring may indicate the key role of the mother in the primary prevention of hypertension.