RESUMEN
The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.
Asunto(s)
Heterosexualidad/estadística & datos numéricos , Uso de la Marihuana/epidemiología , Conducta Sexual/estadística & datos numéricos , Minorías Sexuales y de Género/estadística & datos numéricos , Trastornos Relacionados con Sustancias/epidemiología , Adolescente , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Estimulantes del Sistema Nervioso Central , Estudios Transversales , Femenino , Francia/epidemiología , Infecciones por VIH/epidemiología , Alucinógenos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Asunción de Riesgos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVES: Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based practice used to identify, reduce and prevent problematic use and abuse of, and dependence on, tobacco, alcohol and psychoactive substances. To date, the pertinence of this practice among people living with HIV (PLHIV) is unknown. In this pilot study, we aimed to assess the acceptability of SBIRT in a cohort of HIV-infected out-patients who were asked about their consumption of alcohol, tobacco and psychoactive substances. METHODS: A monocentric study was performed at the University Hospital of Montpellier. In a 6-month period, 20 trained physicians screened for the consumption of alcohol [using the Alcohol Use Disorders Identification Test (AUDIT)], tobacco (using the Short Fagerstrom Test) and psychoactive substances [using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) V3.0] via an auto-questionnaire and proposed a brief intervention to patients with misusage. RESULTS: One thousand and eighteen PLHIV completed the questionnaire, and 861 [84.6%; 95% confidence interval (CI) 82.2-86.7%] PLHIV returned it to the physician. Among the latter, 650 patients wished to discuss the answers with their physician (75.5%; 95% CI 72.5-78.3%), and brief interventions were realized in 405 patients (62.3%). CONCLUSIONS: SBIRT is a simple screening and harm reduction tool that is well accepted by PLHIV in out-patient clinics. This method could be implemented in routine HIV care to screen and manage patients systematically for harmful substance use.
Asunto(s)
Infecciones por VIH , Tamizaje Masivo/métodos , Aceptación de la Atención de Salud , Prevención Primaria/métodos , Trastornos Relacionados con Sustancias , Adulto , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/prevención & control , Adulto JovenRESUMEN
A combined hepatitis A and B vaccine is available since 1996. Two separate open-label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17-43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long-term persistence of anti-HAV and anti-HBs antibodies. The subjects whose antibody concentrations fell below the cut-offs between Year 11 and Year 15 (anti-HAV: <15 mIU/ml; anti-HBs: <10 mIU/ml) were offered an additional dose of the appropriate monovalent hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti-HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti-HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine-related serious adverse events were reported. This study confirms the long-term immunogenicity of the three-dose regimen of the combined hepatitis A and B vaccine, as eliciting long-term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination.
Asunto(s)
Anticuerpos de Hepatitis A/sangre , Vacunas contra la Hepatitis A/inmunología , Anticuerpos contra la Hepatitis B/sangre , Memoria Inmunológica , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Vacunas contra la Hepatitis A/administración & dosificación , Humanos , Inmunización Secundaria/métodos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Vacunación/métodos , Adulto JovenRESUMEN
Vaccination against hepatitis B virus (HBV) immediately after birth prevents neonatal infection by vertical transmission from HBV carrier mothers. There is an ongoing debate whether infant vaccination is sufficient to protect against infection when exposed to HBV later in life. We studied 222 Thai infants born to HBsAg -/+ and HBeAg -/+ mothers who were vaccinated with recombinant hepatitis B vaccine at 0-1-2-12 months of age. A subset of 100 subjects received a booster dose at age 5 years. Blood samples collected yearly for 20 years were examined for anti-HBs antibodies and serological markers of hepatitis B infection (anti-HBc, HBsAg, and in selected cases HBeAg, anti-HBe, HBV DNA). During the 20-year follow-up, no subject acquired new chronic HBV infection or clinical hepatitis B disease. During the first decade, possible subclinical breakthrough HBV infection (anti-HBc seroconversion) was only observed in subjects born to HBsAg +/HBeAg + mothers (6/49 [12.2%]). During the second decade, breakthrough HBV infections were detected in all groups (18/140 [12.8%]). Increases in anti-HBs concentrations that were unrelated to additional HBV vaccination or infection were detected in approximately 10% of subjects in each decade. Primary infant vaccination with a recombinant hepatitis B vaccine confers long-term protection against clinical disease and new chronic hepatitis B infection despite confirmed hepatitis B exposure.
Asunto(s)
Portador Sano/prevención & control , Enfermedades Endémicas/prevención & control , Vacunas contra Hepatitis B/administración & dosificación , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/prevención & control , Adolescente , Portador Sano/epidemiología , Portador Sano/inmunología , Niño , Preescolar , ADN Viral/sangre , Femenino , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/inmunología , Antígenos e de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Inmunización Secundaria , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Estudios Longitudinales , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/virología , Tailandia/epidemiología , Adulto JovenRESUMEN
The immunogenicity and reactogenicity of booster vaccination with GSK Biologicals' hexavalent DTPa-HBV-IPV/Hib vaccine was assessed in toddlers aged 12-18 months previously primed with the same combination (N=341), or with DTPa-IPV/Hib and HBV administered separately (N=102; Trials 217744/059 and 217744/096). Antibody persistence at age 4-6 years was also assessed in children who had received a 4th consecutive dose of DTPa-HBV-IPV/Hib vaccine or separate DTPa-IPV/Hib and HBV vaccines in this study and in another study conducted under similar conditions in Germany. Prior to booster vaccination in the second year of life, antibody concentrations and seroprotection rates were similar irrespective of the primary vaccine used. One month after boosting with DTPa-HBV-IPV/Hib, substantial antibody increases were observed against all vaccine antigens indicative of previous immune priming. Seropositivity and booster response rates against all antigens were 97.4-100%. Reactogenicity following booster vaccination with DTPa-HBV-IPV/Hib was similar regardless of the primary regimen used. Three to four years after administration of the 4th DTPa-HBV-IPV/Hib dose, >90% vaccinees had persistent protective antibody concentrations against diphtheria, hepatitis B, Hib and the three poliovirus types. Anti-tetanus antibody concentrations were > or = 0.1 IU/ml in 76.4% subjects and seropositivity for pertussis antibodies ranged from 34.5% for PT to 98.9% for FHA. In conclusion, the combined hexavalent DTPa-HBV-IPV/Hib vaccine is immunogenic and safe when used for boosting in the second year of life, regardless of the primary vaccine used, and offers sustained protection during early childhood and beyond.
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Hepatitis B/administración & dosificación , Inmunización Secundaria/tendencias , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Niño , Preescolar , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Femenino , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Humanos , Memoria Inmunológica/inmunología , Lactante , Masculino , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunologíaRESUMEN
This study evaluated GSK's combined DTPa-IPV vaccine (Infanrix-IPV) given as a fifth consecutive acellular pertussis booster dose in conjunction with the second dose of MMR vaccine (Priorix) in children aged 4-6 years. The immunogenicity and reactogenicity of this vaccine regimen was compared with separate injections of DTPa and IPV when given concomitantly with MMR. A cohort of 362 children previously primed with four doses of DTPa and OPV, and a single dose of MMR were randomized to receive either DTPa-IPV+MMR (N=181) or DTPa+IPV+MMR (N=181). Antibody concentrations were measured prior to and 1 month after the booster dose. After immunisation all subjects from both groups had seroprotective antibody levels against diphtheria, tetanus and the three poliovirus serotypes, > or = 96% showed vaccine response to PT, FHA and PRN, all were seropositive to mumps and rubella, and all but one subject were seropositive to measles. Immunogenicity results for each component antigen were similar for DTPa-IPV and separately co-administered DTPa and IPV. Local reactions were common with 24.0% and 31.1% of children experiencing swelling >50mm at the DTPa-IPV and DTPa injection sites, respectively. The DTPa-IPV combination did not increase the incidence or intensity of adverse events compared with separately administered DTPa+IPV. The response to the concomitantly administered MMR vaccine was similar in the two groups and similar to previously reported responses for a second dose of MMR. This combined DTPa-IPV vaccine has a similar reactogenicity profile to DTPa, is immunogenic when given as a booster dose at 4-6 years of age, and has no impact on the immunogenicity of a co-administered second dose of MMR vaccine.
Asunto(s)
Anticuerpos/sangre , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Inmunización Secundaria/métodos , Vacuna contra el Sarampión-Parotiditis-Rubéola/administración & dosificación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Niño , Preescolar , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Vacuna contra el Sarampión-Parotiditis-Rubéola/efectos adversos , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunología , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunologíaRESUMEN
A combined DTPa-IPV booster vaccine was administered as a 4th or 5th dose after DTPa or DTPw priming. Over 99% vaccines developed antibody levels considered to be protective to diphtheria, tetanus and poliovirus, and >95% mounted a response to acellular pertussis antigens. Rectal temperature >39.5 degrees C was observed in at most 3.2% of vaccinees. Swelling >50 mm occurred in 24% of DTPa-primed compared to 5.5% of DTPw-primed children. Large swelling involving the entire upper arm (extending to involve the elbow joint) was reported for up to 1.2% of DTPa-primed subjects, which is consistent with literature reports for other DTPa vaccines.
Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Vacunas Combinadas/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Niño , Preescolar , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Humanos , Inmunización Secundaria , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacunas Combinadas/efectos adversosRESUMEN
1. The Muscovy duck of equatorial origin, is photosensitive and its sexual maturation can be advanced by long days. The aim of this study was to investigate the photorefractory nature of the seasonal sexual rest in this species. 2. Sixty males were allocated to three groups of 20 birds each after completion of one full reproductive cycle in long days (16L:8D). Group A was transferred to longer days (20L:4D). Group B remained in 16L:8D. Group C was transferred to short days (6L:18D) for 9 weeks and then returned to 16L:8D. 3. Group B spontaneously redeveloped their testes and recrudescence, indicated by increased plasma concentrations of luteinising hormone and testosterone, started between the 4th and 10th week after total regression. Longer days (in group A accelerated recrudescence. Shorter days (in group C) delayed it, but the return to long days restored reproductive function. 4. In group C, the transfer to short days increased the hypothalamic content of luteinising hormone-releasing hormone. LHRH and secretion of the neuropeptide in vitro. The pituitary sensitivity to LHRH was increased in that group after the return to long days. 5. These effects show that the birds were photosensitive when daylength was changed 8 weeks after the completion of regression, and that short days were not necessary for the birds to regain photosensitivity. 6. The shortness of the regressed period and the spontaneous recrudescence in long days are more typical of equatorial birds than temperate zone species, which are more dependent on photoperiodic changes. The Muscovy duck probably retains features of its wild ancestor, which, living in equatorial latitudes, was more subject to non-photic synchronisers.
Asunto(s)
Patos/fisiología , Glándulas Endocrinas/fisiología , Sistemas Neurosecretores/fisiología , Fotoperiodo , Reproducción/fisiología , Maduración Sexual/fisiología , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Patos/sangre , Hormona Liberadora de Gonadotropina/análisis , Hormona Liberadora de Gonadotropina/metabolismo , Hormona Liberadora de Gonadotropina/farmacología , Hipotálamo/química , Técnicas In Vitro , Hormona Luteinizante/sangre , Masculino , Muda/fisiología , Hipófisis/efectos de los fármacos , Hipófisis/fisiología , Radiografía , Radioinmunoensayo/métodos , Radioinmunoensayo/veterinaria , Estaciones del Año , Testículo/anatomía & histología , Testículo/diagnóstico por imagen , Testículo/fisiología , Testosterona/sangre , Factores de TiempoRESUMEN
The influence of photoperiodic control on reproductive development was investigated in Muscovy drakes by the use of night-interruption photoschedules consisting of a main photofraction of 6 hr and a secondary photofraction of 1 hr, interrupting the dark period 6 hr (Group A), 8 hr (Group B), 10 hr (Group C), and 12 hr (Group D) after dawn. Sexual maturity, assessed by the increase in plasma concentrations of luteinising hormone (LH) and testosterone, was achieved in all groups by Week 34. However, significant differences in the precocity of the rate of sexual maturation were evident on Week 27. At this time, plasma testosterone concentrations, relative to those at Week 15, had increased by 2.02, 0.29, 0.89, and 2.68 ng/ml in Groups A, B, C, and D respectively. Increases in LH concentrations followed a similar pattern. The more pronounced increases in LH and testosterone concentrations observed from Group B to Group D indicate that long days stimulate reproductive development in the Muscovy duck via a diurnal rhythm of photosensitivity. However, the nonphotostimulated increase in hormonal concentrations observed in Group A implies that a factor other than photostimulation may be involved. The dissipation of juvenile photorefractoriness by long-term short-day exposure and subsequent passive sexual maturation may explain these results. We hypothesize that the rate of sexual maturation results from a balance between the dissipation of juvenile photorefractoriness by short days and the relative strength of the photoperiodic drive as the result of long days.
Asunto(s)
Patos/fisiología , Fotoperiodo , Maduración Sexual/fisiología , Animales , Ritmo Circadiano/fisiología , Patos/metabolismo , Luz , Hormona Luteinizante/sangre , Masculino , Radioinmunoensayo , Testosterona/sangre , Factores de TiempoRESUMEN
An in vitro system for the incubation of mediobasal hypothalami (MBH) of cockerels and a radioimmunoassay for chicken luteinising hormone-releasing hormone-I (cLHRH-I) were developed. The size of the hypothalamic fragment (MBH including the median eminence) and the incubation conditions used (40 degrees C, under constant shaking and gassing) preserved the physiological properties of the tissue. It was possible to maintain the MBH in vitro and to study the LHRH release for several hours. The assay proved sensitive enough (ED80 = 0.794 pmol/tube, ie 4.59 pg/ml) and sufficiently precise (within-assay coefficient of variation = 4.4% and between-assay coefficient of variation = 10.2%) to measure the amounts of peptide released in the incubation medium. The use of this incubation system provided the first evidence of the stimulating effect of the excitatory amino acids glutamate, NMDA and kainate on the secretion of cLHRH-I in birds. Our results suggest that the effect on the NMDA receptor is predominant.
Asunto(s)
Aminoácidos/farmacología , Pollos/fisiología , Hormona Liberadora de Gonadotropina/análogos & derivados , Hipotálamo Medio/metabolismo , Animales , Glutamatos/farmacología , Ácido Glutámico , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo Medio/efectos de los fármacos , Técnicas In Vitro , Ácido Kaínico/farmacología , Masculino , N-Metilaspartato/farmacología , Ácido Pirrolidona Carboxílico/análogos & derivados , RadioinmunoensayoRESUMEN
1. The ability of a moult-inducing procedure to restore high levels of sperm production was assessed, in two experiments, using cockerels with reduced sperm production. The moulting procedure consisted of a period of food and light restriction for 6 weeks. The moulted birds were compared with control birds for 20 weeks. 2. Moult induction resulted in decreased daily sperm output (DSO) and plasma testosterone concentration, from weeks 3 to 7. In the first experiment, plasma luteinising hormone (LH) concentration in moulted birds was reduced on week 5. 3. No change in pituitary sensitivity to chicken luteinising hormone-releasing hormone-I (cLHRH-I) was detected at week 3 in moulted cockerels. In moulted birds, a transient increase in plasma thyroxine concentration was detected. 4. After the end of moult induction, testosterone concentrations increased, plasma LH showed a rebound at week 7 and the pituitary sensitivity to LHRH was increased at week 9. 5. This increased activity of the pituitary-testicular axis resulted for a short time in an increase in DSO of moulted birds compared with that of controls. Although amelioration was moderate, this result indicates the possibility of improving sperm production in the cockerel by using an induced moulting procedure.
Asunto(s)
Pollos/fisiología , Hormona Liberadora de Gonadotropina/fisiología , Hormona Luteinizante/sangre , Espermatozoides/fisiología , Testosterona/sangre , Tiroxina/sangre , Animales , Masculino , Hipófisis/fisiología , Recuento de EspermatozoidesRESUMEN
1. The effect of thyroxine (T4) on reproductive function in the adult cockerel was followed for 11 weeks. Broiler cockerels aged 96 weeks were fed on diets containing either 0, 2 or 5 mg T4/kg for 4 weeks. 2. Daily sperm output (DSO) was significantly reduced (P < 0.01) in the T4-treated groups compared with that of controls at weeks 5 and 7. In the group given 5 mg T4/kg, plasma testosterone concentration was significantly reduced (P < 0.01) compared with that in controls during the T4 treatment, in spite of the fact that there was a decrease in concentration in both control and experimental birds. Plasma luteinising hormone (LH) concentration was significantly decreased (P < 0.05) in both of the groups given T4 treatments after 3 weeks. 3. Plasma testosterone concentrations and DSO had returned to control values at weeks 5 and 11 respectively, while plasma LH showed a transient but significant (P < 0.001) rebound after removal of thyroxine from the food. 4. In contrast to other variables, the pituitary responsivity to cLHRH-I injections, was not decreased during the feeding of the T4 diet but was, on the contrary, significantly increased (P < 0.05) during treatment with 5 mg T4/kg diet, and after the end of the treatment with 2 mg T4/kg diet. 5. These results provide some evidence for an inhibitory effect of large doses of T4 on the reproductive function in the adult cockerel. Although the possibility of a direct effect of T4 on the testes cannot be excluded, T4 is likely to act, at least in part, at the hypothalamo-pituitary level, and not through a reduction in the pituitary sensitivity to LHRH.
Asunto(s)
Pollos/fisiología , Hormona Liberadora de Gonadotropina/fisiología , Hormona Luteinizante/sangre , Hipófisis/fisiología , Testículo/fisiología , Tiroxina/fisiología , Animales , Peso Corporal , Masculino , Espermatozoides/fisiología , Testosterona/sangre , Tiroxina/sangreRESUMEN
A high-performance liquid chromatographic method with spectrofluorometric detection has been developed for the analysis of doxorubicin (DOX), pirarubicin (PIRA) and their metabolite, doxorubicinol, in plasma. The detection was performed at 480 nm for excitation, and 590 nm for emission. The proposed technique is selective, reliable, and sensitive. The limit of quantification was 2 ng ml-1 for DOX and 5 ng ml-1 for PIRA. The reproducibility of the analytical method through statistical coefficients is approximately 5%. The accuracy of the method is good; the relative error is less than 5%.
Asunto(s)
Antibióticos Antineoplásicos/análisis , Doxorrubicina/análogos & derivados , Doxorrubicina/análisis , Cromatografía Líquida de Alta PresiónRESUMEN
The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography with fluorescence detection. As reported previously, a wide range of plasma levels were found among our patients. It appears that in addition to being quickly cleared from the plasma, both DOX and DOXol are excreted in detectable amounts in parotid saliva, a route of elimination that has been given little attention, if any. Excretion in the saliva exposes the mucosa of the upper gastrointestinal tract to drug and may play a role in causing stomatitis in patients receiving DOX by the i.v. route. Since huge interindividual and pronounced intraindividual differences were found in S/P ratios that mostly were not systematically related to the plasma drug concentration, the concentration in parotid saliva was not useful in predicting the level of free DOX and DOXol in plasma. For the parent drug and its metabolite, the S/P ratios increased significantly with time during the 48-h period after dosing.
Asunto(s)
Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Glándula Parótida/metabolismo , Saliva/metabolismo , Adulto , Anciano , Doxorrubicina/sangre , Doxorrubicina/uso terapéutico , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológicoRESUMEN
Doxorubicin was given by brief i.v. infusion (doses ranging from 25 to 72 mg/m2) to 28 patients for 2-7 successive courses of chemotherapy (68 courses studied in all). A Bayesian approach was developed to determine the individual pharmacokinetic parameters of doxorubicin. Statistical characteristics of the population pharmacokinetic parameters were first evaluated for 19 patients and a total of 30 courses, which, when combined with 4 individual plasma concentrations of drug, led to a Bayesian estimation of individual pharmacokinetic parameters for the remaining 38 courses. The estimated parameters for the elimination phase (A3/V1 and t1/2 elimination) and the residual plasma level at 48 h as computed by Bayesian estimation on this reduced sub-optimal sampling protocol were compared with a maximal likelihood estimation of these parameters. No statistically significant differences were found. Performance of the developed methodology was evaluated by computing bias and precision. The mean errors were -0.0315 x 10(-4) l-1 for A3/V1, 0.0839 h for t1/2 elimination, and -0.22 ng/ml for c(48 h). The precision of the prediction of these three parameters (0.304 x 10(-5) l-1, 3.34 h, and 0.659 ng/ml, respectively) remained lower than the interindividual standard deviation (1.42 x 10(-4) l-1, 14.9 h, and 4.54 ng/ml, respectively). This procedure enables the estimation of individual pharmacokinetic parameters for doxorubicin at minimal cost and minimal disturbance of the patient.
Asunto(s)
Doxorrubicina/farmacocinética , Teorema de Bayes , Cromatografía Líquida de Alta Presión/métodos , Doxorrubicina/administración & dosificación , Doxorrubicina/sangre , Estudios de Evaluación como Asunto , Humanos , Infusiones Intravenosas , Funciones de Verosimilitud , Factores de TiempoRESUMEN
Doxorubicin was given by short i.v. infusion (dose range 25-72 mg/m2) to 18 patients who underwent three to seven successive courses of chemotherapy (total, 57 courses). Plasma levels of doxorubicin and its major metabolite doxorubicinol were determined by high-performance liquid chromatography over a 48-h period after the infusion. Pharmacokinetic parameters for the parent drug and its metabolite were calculated for each course of treatment. The results show considerable inter- and intraindividual variations for most parameters. The coefficients of variation (CV) ranged from 37% to 93% (inter-individual) and from 6% to 59% (intra-individual). Nevertheless, we observed a good stability over successive courses for terminal half-life in six patients (CV, 6%-25%) and for clearance and AUC in four subjects (CV, 10%-22%). The ratio of the AUCs for doxorubicinol: doxorubicin averaged 0.514. The pharmacokinetic pattern of doxorubicinol was biphasic in plasma of the majority of patients. We propose a model for curve-fitting of these metabolite plasma concentrations that is based on two successive releases of the compound in the plasma compartment, separated by a lag time.
Asunto(s)
Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Adulto , Anciano , Femenino , Humanos , Individualidad , Masculino , Persona de Mediana EdadRESUMEN
Experiments in minks, as in a number of other seasonal breeders, clearly demonstrate that the pineal gland is essential for the photoperiodic control of reproduction. While maintenance of pineal-intact minks under natural photoperiods results in a set of seasonally appropriate changes in testicular activity, pinealectomized minks undergo none of these changes but rather remain sexually inactive as under long-day conditions. Thus, the consequences of pinealectomy differ from one photoperiodic species to another, but the unifying feature is the organism's need for the pineal gland to respond appropriately to changes in day length. Although the precise mechanism by which the pineal regulates hypothalamic-pituitary gonadal function remains unknown, the results of the present study indicate that, in the mink, luteinizing hormone-releasing hormone axonal transport is affected by pinealectomy. Furthermore, our results suggest that the pineal does not act exclusively upon the neuroendocrine-gonadal system but also acts on other functions that are influenced by photoperiod. Pinealectomized minks left in natural conditions cannot adjust their prolactin secretion in response to either long or short photoperiods. Operated animals continued to have plasma prolactin variations but at irregular intervals and with no apparent relation to the time of the year. The data strengthen the hypothesis that melatonin may act at some point on the hypothalamic neuroendocrine systems, which regulate the two functions differently, and that melatonin is not an anti- or progonadal substance but rather a seasonal transducer.
Asunto(s)
Hormona Liberadora de Gonadotropina/fisiología , Visón/fisiología , Glándula Pineal/fisiología , Prolactina/sangre , Testículo/fisiología , Animales , MasculinoRESUMEN
It has been demonstrated that an endogenous mechanism is involved in photoperiodic time measurement in the mink, a short-day-breeding mannal. A study of testicular activity (testicular volume, plasma testosterone concentration) and plasma prolactin level was carried out in sexually resting minks (the experiment began in November). Groups of minks were kept in the natural photoperiod or subjected to different resonance light-dark (LD) cycles (LD 4:8, LD 4:20, LD 4:32, LD 4:44); an additional group of animals was reared in an ahemeral photoperiod (LD 4:16). A rapid increase of testicular activity was observed in control animals or those kept in LD 4:20 (T 24) and LD 4:44 (T 48). In the other groups of animals, those kept in LD 4:8 (T 12), LD 4:32 (T 36), and LD 4:16 (T 20), testicular function remained at rest. Prolactin secretion was, in contrast, stimulated in the groups kept in LD 4:8 (T 12). LD 4:32 (T 36), and LD 4:16 (T 20), and remained low in the groups kept in LD 4:20 (T 24) and LD 4:44 (T 48). These results show that the effects of the different photoperiodic regimens do not depend on the duration of the photophase, but rather on the period of the LD cycles. The LD cycles that allow an increase of testicular function are those that are inhibitory to reproduction in birds and long-day-breeding mammals. To explain these results, it is suggested that in the mink exposure to light during the circadian photosensitive phase induces inhibition of testicular activity and stimulation of prolactin secretion. To explain the opposite effects of a single photoperiod on testicular function and secretion of prolactin, the hypothesis has been advanced that, in the mink, long days might simultaneously inhibit hypothalamic luteinizing-hormone-releasing hormone (LH-RH) activity and prolactin-inhibiting factor (PIF) activity.
Asunto(s)
Ritmo Circadiano/fisiología , Visón/fisiología , Animales , Luz , Masculino , Prolactina/metabolismo , Estaciones del Año , Testículo/crecimiento & desarrollo , Testículo/fisiología , Testosterona/metabolismoRESUMEN
The possible role of thyroid hormones in the setting of sexual quiescence was investigated in the mink, since levels of thyroid hormones were earlier shown to rise while testicular activity decreased. When performed at the beginning of the sexual period, thyroidectomy transiently stimulated testosterone production, and significantly prolonged the duration of maximal testicular development. These results indicate that mink conforms to a pattern of inhibitory thyroid-testis interactions similar to that previously described in several species of birds and mammals. Thyroidectomy was unable, however, to prevent ultimately the installation of sexual quiescence which also appears independent of the photoperiod. On the other hand, thyroidectomy did not modify, from February to October, the general pattern of prolactin secretion, even though the vernal stimulation of prolactin secretion, induced by increasing daylength, was significantly enhanced in the absence of thyroid hormones.