Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 83
Filter
1.
Rev. neurol. (Ed. impr.) ; 75(7): 165-171, Oct 1, 2022. tab, graf
Article in Spanish | IBECS | ID: ibc-209612

ABSTRACT

Introducción: La narcolepsia de tipo 1 es una enfermedad incapacitante que requiere tratamiento continuo, que no siempre es eficaz. El pitolisant es un nuevo fármaco con un mecanismo de acción diferente que ofrece una nueva opción de tratamiento. El objetivo del estudio fue analizar la efectividad y la seguridad del pitolisant en pacientes con narcolepsia de tipo 1 que no hubieran respondido o tolerado previamente los tratamientos habituales. Pacientes y métodos: Estudio observacional descriptivo multicéntrico de vida real que incluyó a pacientes diagnosticados de narcolepsia de tipo 1 no respondedores a tratamientos previos que iniciaron tratamiento con pitolisant. El estudio evaluó tres momentos: el inicio del tratamiento, la estabilización del tratamiento con pitolisant y los tres meses posteriores. Resultados: En 32 pacientes incluidos (media de edad, 44 años; 37,5% de mujeres), la media de la escala de somnolencia de Epworth se redujo de 17,1 a 13,5; un 47,8% de los pacientes mejoró subjetivamente de su cataplejía; un 65% de los pacientes mejoró su impresión clínica global a criterio médico y a criterio del paciente; y se redujo la media de medicamentos consumidos de 2,0 a 1,4. El efecto adverso más frecuente fue el insomnio, en un 43,8% de los pacientes. De los 32 pacientes, 23 mantuvieron el tratamiento durante los tres meses de seguimiento. Conclusiones: En pacientes con narcolepsia de tipo 1 que no responden a o no toleran los tratamientos disponibles, el pitolisant puede mejorar su situación clínica y reducir su consumo de medicamentos. Son necesarios estudios de mayor nivel de evidencia para confirmar estos resultados.(AU)


INTRODUCTION: Type 1 narcolepsy is a disabling disease that requires continuous treatment, which is not always effective. Pitolisant is a new drug with a different mechanism of action that offers a new treatment option. The objective of the study was to analyse the effectiveness and safety of pitolisant in patients with type 1 narcolepsy that did not respond to or tolerate previous standard treatments. PATIENTS AND METHODS: Real-life multicentre descriptive observational study that included patients diagnosed with type 1 narcolepsy who did not respond to or tolerate previous treatments and started treatment with pitolisant. The study evaluated three different moments: the start of treatment, the stabilization of treatment with pitolisant and the three months after. RESULTS: In 32 patients included (mean age, 44 years; 37.5% women) the mean of the Epworth Sleepiness Scale was reduced from 17.1 to 13.5; 47.8% of the patients improved from their cataplexy; 65% of the patients improved their clinical global impression at the physician’s and at the patient’s discretion and the mean number of medications consumed was reduced from 2.0 to 1.4. The most frequent adverse effect was insomnia in 43.8% of patients. Of the 32 patients, 23 continued with the treatment during the 3-month follow-up period. CONCLUSIONS: In patients with type I narcolepsy who do not respond to or do not tolerate the available treatments, pitolisant can improve their clinical situation and reduce their medication consumption. Studies with a higher level of evidence are needed to confirm these results.(AU)


Subject(s)
Humans , Male , Female , Narcolepsy/diagnosis , Narcolepsy/drug therapy , Sleepiness , Treatment Outcome , Cataplexy/diagnosis , Cataplexy/drug therapy , Sleep Wake Disorders , Patients , Epidemiology, Descriptive , Retrospective Studies , Neurology
2.
Rev Neurol ; 75(7): 165-171, 2022 10 01.
Article in Spanish | MEDLINE | ID: mdl-36169322

ABSTRACT

INTRODUCTION: Type 1 narcolepsy is a disabling disease that requires continuous treatment, which is not always effective. Pitolisant is a new drug with a different mechanism of action that offers a new treatment option. The objective of the study was to analyse the effectiveness and safety of pitolisant in patients with type 1 narcolepsy that did not respond to or tolerate previous standard treatments. PATIENTS AND METHODS: Real-life multicentre descriptive observational study that included patients diagnosed with type 1 narcolepsy who did not respond to or tolerate previous treatments and started treatment with pitolisant. The study evaluated three different moments: the start of treatment, the stabilization of treatment with pitolisant and the three months after. RESULTS: In 32 patients included (mean age, 44 years; 37.5% women) the mean of the Epworth Sleepiness Scale was reduced from 17.1 to 13.5; 47.8% of the patients improved from their cataplexy; 65% of the patients improved their clinical global impression at the physician's and at the patient's discretion and the mean number of medications consumed was reduced from 2.0 to 1.4. The most frequent adverse effect was insomnia in 43.8% of patients. Of the 32 patients, 23 continued with the treatment during the 3-month follow-up period. CONCLUSIONS: In patients with type I narcolepsy who do not respond to or do not tolerate the available treatments, pitolisant can improve their clinical situation and reduce their medication consumption. Studies with a higher level of evidence are needed to confirm these results.


TITLE: Estudio WAKE de vida real en pacientes con narcolepsia con cataplejía tratados con pitolisant no respondedores a tratamientos previos.Introducción. La narcolepsia de tipo 1 es una enfermedad incapacitante que requiere tratamiento continuo, que no siempre es eficaz. El pitolisant es un nuevo fármaco con un mecanismo de acción diferente que ofrece una nueva opción de tratamiento. El objetivo del estudio fue analizar la efectividad y la seguridad del pitolisant en pacientes con narcolepsia de tipo 1 que no hubieran respondido o tolerado previamente los tratamientos habituales. Pacientes y métodos. Estudio observacional descriptivo multicéntrico de vida real que incluyó a pacientes diagnosticados de narcolepsia de tipo 1 no respondedores a tratamientos previos que iniciaron tratamiento con pitolisant. El estudio evaluó tres momentos: el inicio del tratamiento, la estabilización del tratamiento con pitolisant y los tres meses posteriores. Resultados. En 32 pacientes incluidos (media de edad, 44 años; 37,5% de mujeres), la media de la escala de somnolencia de Epworth se redujo de 17,1 a 13,5; un 47,8% de los pacientes mejoró subjetivamente de su cataplejía; un 65% de los pacientes mejoró su impresión clínica global a criterio médico y a criterio del paciente; y se redujo la media de medicamentos consumidos de 2,0 a 1,4. El efecto adverso más frecuente fue el insomnio, en un 43,8% de los pacientes. De los 32 pacientes, 23 mantuvieron el tratamiento durante los tres meses de seguimiento. Conclusiones. En pacientes con narcolepsia de tipo 1 que no responden a o no toleran los tratamientos disponibles, el pitolisant puede mejorar su situación clínica y reducir su consumo de medicamentos. Son necesarios estudios de mayor nivel de evidencia para confirmar estos resultados.


Subject(s)
Cataplexy , Narcolepsy , Sleep Initiation and Maintenance Disorders , Adult , Cataplexy/drug therapy , Female , Humans , Male , Narcolepsy/drug therapy , Piperidines/adverse effects
3.
Osteoporos Int ; 32(10): 2125-2129, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33928403

ABSTRACT

Osteoporosis is a disease of low bone mass which leads to an increased risk of fracture. The prevalence of osteoporosis is greatest amongst postmenopausal women who also form a large portion of patients with osteoarthritis presenting for total knee arthroplasty. We present a case of a 77-year-old female with knee osteoarthritis and osteoporosis on denosumab who underwent robotic-assisted total knee arthroplasty. Postoperatively, she suffered an atraumatic midshaft femur fracture at the pin site associated with the use of intraoperative robotic technology. This is a unique complication related to the use of robotics which requires additional skeletal fixation versus standard arthroplasty surgical technique. We recommend caution and further study regarding the use of robotics in total knee arthroplasty in the setting of osteoporosis and denosumab use.


Subject(s)
Arthroplasty, Replacement, Knee , Femoral Fractures , Osteoarthritis, Knee , Osteoporotic Fractures , Aged , Arthroplasty, Replacement, Knee/adverse effects , Female , Femoral Fractures/etiology , Femoral Fractures/surgery , Femur/surgery , Humans , Osteoarthritis, Knee/surgery , Osteoporotic Fractures/etiology
4.
Int J Oral Maxillofac Surg ; 50(6): 733-739, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33279376

ABSTRACT

Bone scintigraphy is an extremely valuable technique in diagnosis and treatment planning for patients with condylar hyperplasia (CH). The main objective of this study was to develop an approach to determine normal activity values in the mandibular condyles, adjusted to age and sex, through quantitative analysis of bone single-photon emission computed tomography (SPECT) on a condyle-by-condyle basis and to compare these values with those of a control group comprising patients with confirmed CH. Technetium 99 m-methylene diphosphonate (99mTc-MDP) SPECT studies of the mandibular condyles were performed in patients with no mandibular pathology for quantitative analysis. Regions of interest were drawn on slices representing the upper, middle, and inferior thirds of each condyle and on the summation of transaxial slices representing the whole condyle (three-dimensional approach). The clivus was used for internal validation and the condyle to clivus ratios were calculated. These ratios were compared between 'normal' and 'diseased' condyles. A total 144 condyles in normal patients and 25 in confirmed CH patients were analysed. Differences between the ratios were evaluated through the coefficient of variation. In normal patients, the ratios to the clivus on the summed condyle image showed the lowest variability: range 0.3-1.28 (median 0.74). The quantile regression model showed significant differences with respect to sex, but not to age. The Mann-Whitney test showed significant differences in the ratios to clivus between normal and diseased condyles (P<0.0001).


Subject(s)
Mandibular Condyle , Tomography, Emission-Computed, Single-Photon , Humans , Hyperplasia/pathology , Mandible , Mandibular Condyle/diagnostic imaging , Mandibular Condyle/pathology , Reference Values , Technetium Tc 99m Medronate
5.
Cir Cir ; 88(6): 765-771, 2020.
Article in English | MEDLINE | ID: mdl-33254179

ABSTRACT

ANTECEDENTES: Los efectos antiinflamatorios de la dafnetina (7,8-dihidroxicumarina) han sido bien documentados, pero su potencial como agente anticanceroso es controversial y no se ha explorado suficientemente. MATERIAL Y MÉTODOS: En este trabajo se evalúa el efecto antiproliferativo in vitro de la dafnetina en tres líneas celulares mediante ensayos de MTT, así como su efecto antitumoral in vivo en cuatro diferentes tipos de tumores en ratones. RESULTADOS: Con una correlación entre los resultados in vitro e in vivo, los tipos de células probadas tienen diferente sensibilidad al compuesto. Las siguientes líneas celulares están ordenadas de acuerdo con la potencia antiproliferativa in vitro de la dafnetina: células de melanoma B16 (IC50 = 54 ± 2.8 µM) > células de adenocarcinoma de mama MXT (IC50 = 74 ± 6.4 µM) > células de carcinoma de colon C26 (IC50 = 108 ± 7.3 µM). In vivo, la dosis antitumoral óptima de dafnetina fue de 40 mg/kg, y las magnitudes de inhibición fueron las siguientes: tumor B16 (48%) > tumor MXT (40%) > tumor fibrosarcoma S180 (30%) > tumor C26 (20%). CONCLUSIÓN: Los resultados indican que la dafnetina podría tener un impacto como adyuvante para mejorar la efectividad de la quimioterapia convencional.


BACKGROUND: The anti-inflammatory effects of daphnetin (7,8-dihidroxicoumarin) have been well-documented, but the potential of daphnetin as an anticancer agent is controversial and remains insufficiently explored. MATERIAL AND METHODS: In this work, we evaluated the in vitro anti-proliferative effect of daphnetin in three cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, as well as its in vivo antitumor effect in four different types of mouse tumor. RESULTS: With a correlation between in vitro and in vivo results, the tested cell types have different sensitivity to the compound. The following cell lines are arranged according to the in vitro anti-proliferative potency of daphnetin: B16 melanoma cells (inhibitory concentrations 50 [IC50] = 54 ± 2.8 µM) > mitoxantrone (MXT) breast adenocarcinoma cells (IC50 = 74 ± 6.4 µM) > C26 colon carcinoma cells (IC50 = 108 ± 7.3 µM). In vivo, the optimal antitumor dose of daphnetin was 40 mg/kg and the magnitudes of inhibition were the following: B16 tumor (48%) > MXT tumor (40%) > S180 fibrosarcoma tumor (30%) > C26 tumor (20%). CONCLUSION: Our results indicate that daphnetin might have an impact as adjuvant to improve the effectiveness of conventional chemotherapy.


Subject(s)
Adenocarcinoma , Colonic Neoplasms , Humans , Umbelliferones
6.
J Pharmacol Toxicol Methods ; 103: 106684, 2020.
Article in English | MEDLINE | ID: mdl-32173560

ABSTRACT

The pre-marketing testing of drugs and chemicals is now a paradigm of contribution to the safeguard of public health. As pointed out by the ICH concept paper E14/S7B, there is a need for science-based frameworks that allow a better design, conduction, and interpretation of nonclinical and toxicity tests, particularly, in order for those assays to influence nonclinical and clinical evaluations and decisions better. Critical issues related to the performance and predictive values of nonclinical testing were highlighted and discussed in this article, specifically, to help pharmacologists, toxicologists, and regulators in the evaluation of the reliability of such tests, and basing the prospective decisions on the true predictivity of selected screening tests. This review addressed two common mistakes in drug and chemical testing, namely, (a) the assumption of either sensitivity or specificity as automatically "predictive," and (b) the reporting of the predictive values disregarding a truly representative prevalence. This review also discussed a statistical basis to apply for (industry standpoint) or grant (regulatory standpoint) authorization for the waiving of selected nonclinical tests. Furthermore, this review can be guiding for those who are entering into the field of drug and chemical testing. Through application, investigation, and enhancement of the conceptual framework discussed in this review, nonclinical testing is expected to provide a higher contribution to drug and chemical development, regulatory science, and public health.


Subject(s)
Drug Evaluation, Preclinical/trends , Animals , Drug-Related Side Effects and Adverse Reactions , Humans , Long QT Syndrome , Safety , Substance-Related Disorders , Toxicity Tests
7.
Transplant Proc ; 50(2): 478-484, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29579832

ABSTRACT

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.


Subject(s)
End Stage Liver Disease/surgery , Liver Transplantation/statistics & numerical data , Adult , Aged , Argentina , Cohort Studies , Female , Graft Rejection/epidemiology , Humans , Liver Transplantation/mortality , Male , Middle Aged , Postoperative Complications/epidemiology , Waiting Lists
8.
J Wound Care ; 20(12): 592-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22240886

ABSTRACT

OBJECTIVE: To test the hypothesis that topically applied calcium glycerophosphate (CGP) would improve the appearance of the wound following bilateral knee replacement. METHOD: Healthy patients, aged 45-75 years, scheduled for bilateral total-knee replacement surgery were recruited into the study. One knee was randomly assigned to the treatment group, while the contralateral knee was designated the control (standard care). Subjects were instructed to apply a preparation of 10% CGP in an aqueous lotion to the treated knee once daily for 42 days, starting at the third postoperative day. Functional sealing and cosmetic appearance of the incision were evaluated by two surgeons by direct examination of the patient and then by two experienced assessors from photographs. The investigators qualitatively scored the intensity and extent of erythema along the incision and over the entire knee, the appearance of visible oedema along the incision and over the knee, and the overall clinical impression of wound healing. All four assessors were blinded to the subjects' allocation and the latter two assessors to the initial investigators' assessments. Subjects were also followed up for an additional 46 weeks, giving a total study duration of 12 months. RESULTS: Twenty patients completed the study. Statistical analysis showed that both the area and intensity of erythema along the incision were significantly reduced in the treated vs untreated knee over the entire study period. The analysis further showed that treatment significantly reduced oedema, both along the incision and across the entire knee. The differences were most marked at the seventh postoperative day and diminished with time. No adverse effects were observed for any patient, in either treated or untreated knees. CONCLUSION: These data demonstrate that postoperative application of 10% CGP could improve the appearance of the wound following total knee arthroplasty.


Subject(s)
Arthroplasty, Replacement, Knee , Glycerophosphates/administration & dosage , Wound Healing/drug effects , Administration, Topical , Aged , Cicatrix/prevention & control , Erythema/prevention & control , Female , Humans , Knee Joint/physiopathology , Male , Middle Aged , Pain Measurement , Range of Motion, Articular , Wound Healing/physiology
9.
Arch Environ Contam Toxicol ; 57(3): 561-70, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19198751

ABSTRACT

The present study examines the induction of mixed-function oxidase (MFO) enzymes, including CYP content CYP1A (EROD) activity and alcohol dehydrogenase activity (ADH), in an endemic Mexican fish species, the black-fin goodeid Girardinichthys viviparus, exposed to the water of two localities, Lake Texcoco (LTX) and Lake Zumpango, and to the same matrices enriched in polychlorinated biphenyls (PCBs) to simulate the potential toxic effects of sublethal increases in these xenobiotics. Fishes of both sexes born in the laboratory were exposed for 1, 2, 4, 8, and 16 days. Water from the two types of localities of the black-fin goodeid contains MFO inducers. Of the two, the most contaminated is LTX water, which also contains PCBs. EROD activity was higher in all treatments with female compared with male fish. This suggests greater metabolic compromise in female fish as a response to damage caused by these xenobiotics. In this species, CYP induction displayed two patterns that were not always concurrent with higher CYP1A activity. In the enriched matrix system, biotransformation processes were notably altered. Increased ADH may indicate that this enzyme is involved in the biotransformation of PCBs and their metabolites, particularly in male fish, and provides at least a part of reductive power required by the MFO enzymes; however, specific studies are needed to clarify this point.


Subject(s)
Fresh Water/analysis , Killifishes/metabolism , Liver/enzymology , Mixed Function Oxygenases/biosynthesis , Polychlorinated Biphenyls/analysis , Water Pollutants, Chemical/analysis , Alcohol Dehydrogenase/biosynthesis , Animals , Biomarkers/analysis , Cytochrome P-450 CYP1A1/biosynthesis , Endangered Species , Environmental Exposure/analysis , Enzyme Induction , Female , Liver/drug effects , Male , Metabolic Detoxication, Phase I , Mexico , Polychlorinated Biphenyls/pharmacokinetics , Polychlorinated Biphenyls/toxicity , Water Pollutants, Chemical/pharmacokinetics , Water Pollutants, Chemical/toxicity
10.
Environ Toxicol Chem ; 27(4): 963-9, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18333695

ABSTRACT

The present study examines the relationships between cytochrome P4501A (CYP1A) activity and vitellogenin (VTG) induction in Ameca splendens elicited by a polychlorinated biphenyl (PCB) mixture. Ethoxyresorufin-O-deethylase (EROD) activity, mRNA levels of VTG, and VTG induction were evaluated in male and female fish exposed for 1, 2, 4, 8, and 16 d to a commercial PCB mixture. Polychlorinated biphenyls induced higher EROD in both sexes and this induction was higher in females than in males. Maximum EROD and VTG induction occurred on day 1 in females, while in males these maxima occurred on days 8 and 16. A correlation between EROD and VTG induction was found only in males (p<0.001), and VTG induction was also higher in males than in females (p<0.01). Exposure to PCBs elicited increases in VTG expression and induction over time in males, while in females these decreased at the end of the exposure period. Deficiencies in the feedback mechanisms of male A. splendens exposed in the wild to xenoestrogens such as PCBs have probably contributed to alter the sex ratio of wild populations of this species.


Subject(s)
Cytochrome P-450 CYP1A1/metabolism , Estrogens/toxicity , Polychlorinated Biphenyls/toxicity , Water Pollutants, Chemical/toxicity , Animals , Fishes , Liver/enzymology , Vitellogenins/biosynthesis
11.
Todo hosp ; (240): 580-587, oct. 2007. ilus, tab
Article in Spanish | IBECS | ID: ibc-61910

ABSTRACT

El objetivo principal del estudio es un análisis descriptivo general de las visitas y de la calidad asistencial ORL en el Servicio de Urgencias Hospitalarias (SUH) durante el mes de septiembre de 2005. Para la valoración de las visitas se analizó la actividad según los diagnósticos emitidos en SUH (CIE-9), según variables temporales y según gravedad. Para la valoración de la calidad asistencial se han evaluado el índice de reincidencias (4,3%) y el porcentaje de fugas (3,6%). Los diagnósticos más frecuentes fueron otitis externa (10%), amigdalitis aguda (7,4%) y epitaxis (5,9%). El 50% de las visitas se consideraron de tipo ambulatorio de acuerdo a la gravedad (AU)


A describe study is made of the visits and nursing quality of the ENT Service in the Hospital Casualty Department of the Hospital Clínic during the month of September 2005. The visits are analysed according to the diagnosis given, time variables and the severity. The conclusions indicate that the most frequently diagnosed given, time variables and the severity. The conclusions indicate that the most frequently diagnosed pathologies in this Service were otitis externa, acute tonsillitis and nose bleeds. 50% of the visits are considered as outpatient´s department type according to the severity (AU)


Subject(s)
Humans , Male , Female , Emergencies/epidemiology , Emergency Medicine/organization & administration , Recurrence , Otolaryngology/organization & administration , Otolaryngology/trends , /organization & administration , Quality of Health Care/organization & administration , Otitis , Otitis Externa/epidemiology , Tonsillitis/epidemiology , Otorhinolaryngologic Diseases/epidemiology
12.
Comp Biochem Physiol C Toxicol Pharmacol ; 145(3): 394-403, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17317326

ABSTRACT

Girardinichthys viviparus is a Mexican endangered endemic fish species living only in Lake Texcoco (LTX), one of two extant type localities for this species. The other type locality is Lake Zumpango (LZ). LTX and LZ are fed by wastewater treated at secondary level that contains several endocrine disrupting chemicals. Our goal was to assess the estrogenic and anti-estrogenic effects elicited in G. viviparus by water from the two type localities and by these same matrices enriched with PCBs in order to understand potential damage due to increased xenobiotic levels. Estrogenic and anti-estrogenic effects were evaluated in vitro by E-screen assay in MCF-7 cells and cytotoxicity by MTT assay. PCBs were quantified in type localities. In vivo vitellogenin (VTG) induction was determined by a hybrid ELISA in adult laboratory-born fish exposed during 1, 2, 4, 8 and 16 days to LTX or LZ water in static exposure systems, and by the same matrices enriched with PCBs. We found PCBs only in LTX, but the water from both type localities elicit estrogenic and anti-estrogenic effects in vitro. Cytotoxicity was not observed in MCF-7 cells exposed to LTX or LZ water. VTG induction was higher with LTX water than with LZ water; also the response of males was greater than in females. In the PCB-enriched matrices, VTG induction in both sexes exposed to LTX water was reduced compared to un-enriched matrices. Thus, the sublethal increases in PCB levels may be hazardous to both sexes since they are linked probably to hepatotoxicity.


Subject(s)
Endocrine Disruptors/toxicity , Estrogen Antagonists/toxicity , Estrogens/toxicity , Water Pollutants, Chemical/toxicity , Animals , Cell Line, Tumor , Cell Survival/drug effects , Female , Fishes , Male , Polychlorinated Biphenyls/toxicity , Vitellogenins/biosynthesis , Waste Disposal, Fluid , Water Purification
13.
Lung Cancer ; 34(2): 185-94, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11679177

ABSTRACT

Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.


Subject(s)
Adenocarcinoma/pathology , Antineoplastic Agents/pharmacology , Cell Cycle/drug effects , Coumarins/pharmacology , Cyclin D1/biosynthesis , Gene Expression Regulation, Neoplastic , Lung Neoplasms/pathology , Umbelliferones/pharmacology , Biotransformation , Cell Division , Dose-Response Relationship, Drug , Humans , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Tumor Cells, Cultured
14.
J Arthroplasty ; 16(4): 415-21, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11402402

ABSTRACT

Sixty-two total hip arthroplasties in 49 patients with a diagnosis of rheumatoid arthritis were performed between November 1986 and December 1992. All components were titanium alloy with a circumferential plasma-spray porous coating. Four patients (4 hips) died before 5-year follow-up, and 6 patients (8 hips) were lost to follow-up, leaving 39 patients (50 hips) for review at a minimum 5-year follow-up after surgery (mean, 8 years; range, 5-12 years). There were 12 men and 27 women, with a mean age at time of surgery of 55 years (range, 25-77 years) and a mean weight of 69 kg (range, 42-109 kg). Compared with the preoperative Charnley scores, there was significant improvement in the postoperative scores: pain, from 2.7 to 5.7, and function, from 3.2 to 5.3. Thigh pain was present in 1 patient (1 hip) (2.0%). No femoral fractures occurred intraoperatively with the insertion of the prosthesis. Spot welds consistent with bone ingrowth were identified in all of the femoral components. No femoral components showed evidence of radiographic loosening or required revision for aseptic loosening or incapacitating thigh pain, but 7 acetabular revisions were performed. Uncemented femoral fixation with this component design in rheumatoid patients appears to be a promising treatment.


Subject(s)
Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement, Hip , Adult , Aged , Cementation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prosthesis Design , Treatment Outcome
17.
J Bone Joint Surg Am ; 83(3): 359-63, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11263639

ABSTRACT

BACKGROUND: Cementless total hip arthroplasty is an accepted alternative to total hip arthroplasty with cement in younger patients, but it remains controversial for elderly patients. The purpose of this study was to evaluate the clinical and radiographic outcomes of cementless total hip arthroplasty with use of a proximally coated stem in patients who were at least eighty years of age at the time of the operation. METHODS: One hundred and twenty-three cementless total hip replacements were performed for the treatment of osteoarthritis in 114 patients between the ages of eighty and eighty-nine years. Seven patients (eight hips) died within two years after the surgery, seventeen patients (eighteen hips) died more than two years postoperatively but were not followed for at least two years, and five hips were lost to follow-up; this left ninety-two hips in eighty-six patients for review. The mean duration of follow-up was five years (range, two to eleven years). For the clinical evaluation, the Charnley modification of the Merle d'Aubigné and Postel scale was used. In addition, preoperative and postoperative Harris hip scores were available for sixty-nine hips. Seventy-eight hips were followed radiographically for two years or more. The focus of the radiographic evaluation was the status of the fixation of the femoral and acetabular components as well as cup wear. RESULTS: Perioperative medical complications occurred in association with 24% (thirty) of the 123 operations, but there were no deaths. The mean Charnley scores for pain and function for the ninety-two hips that were followed clinically for at least two years improved by 3.0 and 1.4 points, respectively. The sixty-nine hips for which preoperative and postoperative Harris hip scores were available had a mean improvement of 42 points, with a mean score of 82 points at the last follow-up evaluation. Mild thigh pain was present in four patients, but it did not limit their activity. There were no femoral component revisions. All of the femoral components were radiographically stable and had bone ingrowth. No acetabular component failed by loosening, but 41% (thirty) of the seventy-three hips with radiographs available for measurement of wear showed polyethylene wear. Of the seventy-eight cups that were followed radiographically for two years or more, 4% (three) were associated with lysis, but none had been revised. CONCLUSIONS: Cementless fixation in the elderly is safe, effective, and durable at the time of two to eleven-year follow-up.


Subject(s)
Arthroplasty, Replacement, Hip , Osteoarthritis, Hip/surgery , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Pain, Postoperative , Postoperative Complications , Treatment Outcome
19.
J Arthroplasty ; 15(8): 1059-63, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11112203

ABSTRACT

We report 4 cases of polyethylene wear in modular cementless sockets presenting as recurrent dislocation. Before the onset of the dislocations, the patients were functioning without symptoms. This is the first report in the literature of this phenomenon.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Dislocation/etiology , Hip Prosthesis , Polyethylenes , Prosthesis Failure , Adult , Aged , Aged, 80 and over , Cementation , Female , Humans , Male , Middle Aged , Recurrence , Reoperation
20.
Vigilia sueño ; 12(supl.1): 75-78, mar. 2000.
Article in Es | IBECS | ID: ibc-26582

ABSTRACT

La taquipnea neurógena ligada al sueño (TNLS) es un raro trastorno sobre el que existen muy pocas referencias en la literatura, y con una etiopatogenia no aclarada. Se define como un incremento sostenido de la frecuencia respiratoria durante el sueño, que se mantiene durante el mismo y revierte con el despertar. Algunos pacientes presentan excesiva somnolencia diurna como síntoma de consulta, y en otros es completamente asintomática. Se ha asociado a trastornos respiratorios (ronquido, apneas) y con diferentes patologías del SNC. Se presentan en este trabajo tres pacientes con TNLS estudiados en nuestra unidad, que presentaron características clínicas y polisomnográficas similares a las descritas. Con este motivo se realiza una discusión sobre las posibles causas de este trastorno, con especial énfasis en el papel de la formación reticular (AU)


Subject(s)
Sleep Wake Disorders/complications , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/therapy
SELECTION OF CITATIONS
SEARCH DETAIL
...