RESUMEN
We report two rare cases of an anomalous origin of the left pulmonary artery (AOLPA) from the ascending aorta, associated with pulmonary atresia, a ventricular septal defect and a left aortic arch. The cases are unusual because AOLPA is more commonly associated with a right aortic arch and it is more usual for the right pulmonary artery to originate anomalously from the ascending aorta. The pulmonary blood supply to the right lung in both patients was absent and provided instead by major aorto-pulmonary collateral arteries which were stenosed at multiple levels. The AOLPA in both patients originated from the postero-lateral aspect of the ascending aorta just distal to the sino-tubular junction. Only one patient showed the more common association of an unusual aortic arch branching pattern in the form of an anomalous right subclavian artery. Neither patient was in heart failure and the chest X-ray in both revealed differential pulmonary perfusion with prominent vascularity of the left lung. Cardiac catheterisation showed systemic pressures within the anomalous left pulmonary artery. Karyotyping revealed normal chromosomes, and fluorescent in-situ hybridisation done in one patient was negative for chromosome 22q11.2 microdeletion. Both patients have been managed conservatively.
Asunto(s)
Anomalías Múltiples , Aorta/anomalías , Circulación Colateral , Defectos del Tabique Interventricular/complicaciones , Arteria Pulmonar/anomalías , Atresia Pulmonar/complicaciones , Circulación Pulmonar , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Aortografía , Cateterismo Cardíaco , Niño , Ecocardiografía Doppler en Color , Femenino , Defectos del Tabique Interventricular/diagnóstico , Defectos del Tabique Interventricular/fisiopatología , Humanos , Lactante , Masculino , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Atresia Pulmonar/diagnóstico , Atresia Pulmonar/fisiopatologíaRESUMEN
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder occurring in male and occasional female carriers of a premutation expansion (55-200 CGG repeats) of the fragile X mental retardation 1 gene (FMR1). This study assessed the relationship between hippocampal volume and psychological symptoms in carriers, both with and without FXTAS, and controls. Volumetric MRI measures, clinical staging, cognitive testing, molecular analysis, and measures of psychological symptoms were performed for female premutation carriers both with FXTAS (n = 16, age: 57.50 + or - 12.46) and without FXTAS (n = 17, age: 44.94 + or - 11.23), in genetically normal female controls (n = 8, age: 50.63 + or - 11.43), male carriers with FXTAS (n = 34, age: 66.44 + or - 6.77) and without FXTAS (n = 21, age: 52.38 + or - 12.11), and genetically normal male controls (n = 30, age: 57.20 + or - 14.12). We examined the relationship between psychological symptom severity and hippocampal volume, as well as correlations with molecular data. We found a significant negative correlation between total hippocampal volume and anxiety in female carriers, with and without FXTAS. This finding was mainly driven by the significant negative correlation between right hippocampal volume and anxiety. Other anxiety-related subscales also correlated with the right hippocampus in females. In male carriers with and without FXTAS, only paranoid ideation negatively correlated with hippocampal volume. Female premutation carriers demonstrated a negative association between hippocampal volume and the severity of anxiety-related psychological symptoms. Though the presentation of FXTAS symptoms is less common in females, anxiety-related problems are common both prior to and after the onset of FXTAS, and may be related to hippocampal changes.
Asunto(s)
Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/psicología , Heterocigoto , Hipocampo/patología , Mutación/genética , Adulto , Anciano , Ansiedad/psicología , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los ÓrganosRESUMEN
BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder occurring in male and rare female carriers of a premutation expansion (55 to 200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. METHODS: Volumetric MRI studies, clinical staging, cognitive testing, and molecular analysis were conducted in 15 female premutation carriers affected by FXTAS (age 59.5 +/- 10.3 years), 20 unaffected female carriers (43.3 +/- 11.2 years), 11 genetically normal female controls (51.0 +/- 10.3 years), 36 affected male carriers (65.0 +/- 5.6 years), 25 unaffected male carriers (53.5 +/- 12.5 years), and 39 male controls (58.0 +/- 15.0 years). Female and male carriers with FXTAS were matched on duration of disease. RESULTS: We found less pronounced reductions of cerebellar volume and a lower incidence of involvement (symmetric high T2 signal) of the middle cerebellar peduncles (MCP sign) in females affected by FXTAS (13%) compared with affected males (58%). We found reduced brain volumes and increased white matter disease associated with the presence of FXTAS in females compared with female controls. We also observed significant associations between reduced cerebellar volume and both increased severity of FXTAS symptoms and increased length of the CGG repeat expansion in male premutation carriers, but not in females. CONCLUSIONS: Females affected by fragile X-associated tremor/ataxia syndrome (FXTAS) demonstrated milder brain changes than affected males, although they showed a similar pattern of radiologic findings consistent with brain atrophy and white matter disease. FXTAS should be considered (by ordering fragile X DNA testing) in females who present with late-onset ataxia, action tremor, or neuropathy, particularly in those with a family history of mental retardation, autism, or premature ovarian failure.
Asunto(s)
Ataxia/patología , Atrofia/patología , Enfermedades Cerebelosas/patología , Síndrome del Cromosoma X Frágil/patología , Caracteres Sexuales , Temblor/patología , Adulto , Anciano , Ataxia/genética , Ataxia/fisiopatología , Atrofia/genética , Enfermedades Cerebelosas/genética , Enfermedades Cerebelosas/fisiopatología , Análisis Mutacional de ADN , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/fisiopatología , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/patología , Temblor/genética , Temblor/fisiopatología , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
OBJECTIVE: Several measures can quantify thoracic kyphosis from radiographs, yet their suitability for people with osteoporosis remains uncertain. The aim of this study was to examine the validity and reliability of the vertebral centroid and Cobb angles in people with osteoporosis. DESIGN AND PATIENTS: Lateral radiographs of the thoracic spine were captured in 31 elderly women with osteoporosis. Thoracic kyphosis was measured globally (T1-T12) and regionally (T4-T9) using Cobb and vertebral centroid angles. Multisegmental curvature was also measured by fitting polynomial functions to the thoracic curvature profile. Canonical and Pearson correlations were used to examine correspondence; agreement between measures was examined with linear regression. RESULTS: Moderate to high intra- and inter-rater reliability was achieved (SEM = 0.9-4.0 degrees ). Concurrent validity of the simple measures was established against multisegmental curvature (r = 0.88-0.98). Strong association was observed between the Cobb and centroid angles globally (r = 0.84) and regionally (r = 0.83). Correspondence between measures was moderate for the Cobb method r = 0.72), yet stronger for the centroid method (r = 0.80). The Cobb angle was 20% greater for regional measures due to the influence of endplate tilt. CONCLUSIONS: Regional Cobb and centroid angles are valid and reliable measures of thoracic kyphosis in people with osteoporosis. However, the Cobb angle is biased by endplate tilt, suggesting that the centroid angle is more appropriate for this population.
Asunto(s)
Cifosis/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Interpretación Estadística de Datos , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Cifosis/etiología , Persona de Mediana Edad , Variaciones Dependientes del Observador , Osteoporosis/complicaciones , Radiografía , Reproducibilidad de los Resultados , Fracturas de la Columna Vertebral/etiología , Vértebras Torácicas/lesionesRESUMEN
An assay method for identification of metabolites from in vitro microsomal incubations was developed for use in the early stage of drug discovery. We have developed a practical approach which involves integrated sample generation, sample preparation, bioanalysis, and data handling to maximize sample throughput and speed up the process for identification of metabolites. The assay system consisted of a robotic liquid handler (Genesis workstation) to generate and process samples, PALLAS MetabolExpert software to predict possible metabolites, exact mass measurement via a tandem quadrupole time-of-flight mass spectrometer (QTOF-MS) coupled with liquid chromatography to analyze samples, MetaboLynx software to find potential metabolites and Advanced Chemistry Development/MS (ACD/MS) software to provide guidance to the most likely hypothetical metabolite chemical structures. For purposes of evaluating this new method, dextromethorphan, alprenolol, and propranolol were incubated separately for up to 60 minutes with rat and human hepatic microsomes. The incubation and sample preparation were carried out in 96-well plates using the Genesis workstation. The bioanalysis was performed by LC-MS/MS using QTOF with MetaboLynx software to find metabolites. Metabolic products formed in vitro by rat and human microsomes were separated using an analytical column C18 with gradient elution at flow rate of 250 micro l/min. The internal mass calibration was performed by continuous postcolumn infusion of Haloperidol. The mass spectra from incubations containing NADPH were compared to those without NADPH (control) using the MetaboLynx software to find potential metabolites. Finally, the MS/MS spectra were processed by the ACD/MS software to predict the chemical structure. MetaboLynx software successfully identified metabolites for each of the drugs studied by automatically discerning expected metabolites. Exact differences in masses between each metabolite and parent drug were measured from five replicate sample injections. All measured values are accurate to less than 0.001Da or 3.8 ppm with the standard deviation within 0.0015 Da, which allowed good prediction/confirmation of empirical formulae. Hypothetical chemical structures were achieved by the ACD/MS software and provided a useful tool to assist in prediction of the metabolic pathways of the drugs. The metabolites identified were in good agreement with previously published results for all three compounds. This new method will greatly enhance throughput, which in turn will facilitate our ability to rapidly provide this guidance to the synthetic chemist.
Asunto(s)
Espectrometría de Masas/métodos , Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Robótica/métodos , Alprenolol/química , Alprenolol/metabolismo , Alprenolol/farmacocinética , Animales , Cromatografía Liquida/métodos , Dextrometorfano/química , Dextrometorfano/metabolismo , Dextrometorfano/farmacocinética , Diseño de Fármacos , Humanos , Técnicas In Vitro , Masculino , Microsomas Hepáticos/metabolismo , Propranolol/química , Propranolol/metabolismo , Propranolol/farmacocinética , Ratas , Reproducibilidad de los Resultados , Robótica/instrumentación , Sensibilidad y Especificidad , Programas InformáticosRESUMEN
1. The effect of a new rifamycin derivative, rifalazil (KRM-1648), on liver microsomal enzyme induction was studied in rat and dog with repeated oral administration of the compound. Relative liver weight, cytochrome b5 and P450 contents, enzyme activities of NADPH-cytochrome c reductase, aniline hydroxylase, p-nitroanisole O-demethylase, aminopyrine N-demethylase, and erythromycin N-demethylase were measured. 2. In rat, rifalazil treatment at 300 mg/kg/day for 10 days increased cytochrome b5 content but it did not affect liver weight, P450 content or enzyme activities. In contrast, rifampicin and rifabutin increased relative liver weights, cytochrome contents and enzyme activities under similar conditions. 3. In dog, rifalazil did not affect any parameters at 30 or 300 mg/kg/day for 13 weeks. 4. These findings indicate that rifalazil is not an enzyme inducer in rat and dog. This property differs from other rifamycin derivatives such as rifampicin and rifabutin.
Asunto(s)
Antibióticos Antituberculosos/farmacología , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/enzimología , Oxigenasas de Función Mixta/biosíntesis , Rifamicinas/farmacología , Animales , Sistema Enzimático del Citocromo P-450/biosíntesis , Sistema Enzimático del Citocromo P-450/metabolismo , Citocromos b5/biosíntesis , Citocromos b5/metabolismo , Perros , Inducción Enzimática/efectos de los fármacos , Femenino , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Masculino , Oxigenasas de Función Mixta/metabolismo , NADPH-Ferrihemoproteína Reductasa/biosíntesis , NADPH-Ferrihemoproteína Reductasa/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Rifabutina/farmacología , Rifampin/farmacologíaRESUMEN
1. 14C-sulphadimethoxine (4-amino-N-(2,6-dimethoxy-4-pyrimidinyl)benzene-[U-14C]-sulphonamide; 14C-SDM) was given orally (60 mg/kg body weight) to eight swine (weight 27-32 kg). Urine and faeces were collected from 0 to 72 h after dosing and tissue samples were collected from animals exsanguinated at 12, 24, 48 and 72 h after dosing. The concentration of total 14C-labelled residues (14C-SDM equivalents) in tissues other than the gastrointestinal tract ranged from 99-1 ppm (plasma) to 13.8 ppm (adipose tissue) 12 h after dosing. Seventy-two hours after dosing tissue concentrations ranged from 5.4 ppm (plasma) to 0.5 ppm (skeletal muscle). The concentration in the large intestine was substantially higher (10.4 ppm) than in the stomach (2.8 ppm) and small intestine (1.4 ppm) 72 h after dosing. 2. Of the 14C, 77% was excreted in the urine from 0 to 72 h after dosing with 14C-SDM, mostly in the 0-24-h collection. Fifteen percent was excreted in the faeces from 0 to 72 h after dosing, with most of this occurring 36-72 h post-dosing. 3. 14C-SDM accounted for 24% (liver) to 66% (adipose tissue) and the N4-acetyl derivative of SDM (N4-Ac-SDM) accounted for 10% (skeletal muscle) to 35% (kidney) of the total 14C in the tissues 12 h after dosing. The N4-glucose conjugate of SDM (G-SDM) was a major 14C-labelled compound in skeletal muscle (21% of total) and liver (28%) but it was not detected in adipose tissue or kidney. The N4-glucuronic acid conjugate of SDM (GA-SDM) was a minor metabolite in kidney, but was not detected in other tissues collected 12 h after dosing. Desamino SDM was a minor metabolite in the kidney. A minor metabolite in plasma was identified as the sulphate ester of 3-hydroxysulphadimethoxine. 4. 14C-labelled fractions isolated from 0 to 6-h urine included N4-Ac-SDM (82%), SDM (3%) and GA-SDM (6%).
Asunto(s)
Sulfadimetoxina/metabolismo , Administración Oral , Animales , Cromatografía Líquida de Alta Presión , Heces/química , Masculino , Tasa de Depuración Metabólica , Sulfadimetoxina/administración & dosificación , Porcinos , Distribución TisularRESUMEN
To establish the usefulness of liver slices as predictive models for in vivo metabolism and toxicity, acetaminophen was used as a model hepatotoxicant for which the role of metabolism in toxicity is well documented. Acetaminophen was incubated with liver slices prepared from the rat and hamster since these species differ in susceptibility to acetaminophen-induced hepatotoxicity. Formation of acetaminophen metabolites (sulfate, glucuronide, and glutathione conjugate), slice glutathione levels, and slice histopathology were assessed. Acetaminophen (0.5, 1, and 2 mM) induced a dose-dependent depletion of glutathione in hamster slices (sensitive species) but not rat slices (insensitive species). Formation of the acetaminophen toxic metabolite, as measured by glutathione conjugate formation, was much lower in rat slices compared with hamster slices. Rat slices also showed greater activity of the nontoxic sulfation and glucuronidation pathways. These data predicted an 11-fold greater susceptibility to toxicity in the hamster based on the proportion of the dose metabolized to the reactive species. In vivo data, using hepatic glutathione depletion as an indicator of toxic metabolite formation, would predict a similar difference (13.3-fold) between the hamster and the rat. To ascertain if the characteristic centrilobular lesion induced by acetaminophen in vivo could be reproduced in vitro, liver slice histopathology was assessed 6 and 12 hr after a 2-hr treatment with acetaminophen (2 mM). Discrete damage to the centrilobular regions of the liver were noted in hamster but not rat slices. Overall, based on metabolite formation, glutathione depletion, and slice histopathology, the liver slices were excellent predictors of acetaminophen hepatotoxicity in vivo.
Asunto(s)
Acetaminofén/metabolismo , Acetaminofén/toxicidad , Hígado/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Animales , Cricetinae , ADN/análisis , Glucuronatos/metabolismo , Glutatión/metabolismo , Técnicas In Vitro , L-Lactato Deshidrogenasa/metabolismo , Hígado/metabolismo , Masculino , Mesocricetus , Ratas , Ratas Sprague-Dawley , Sulfatos/metabolismoRESUMEN
The authors describe how operations of an inpatient admitting service for interventional radiology were improved by developing a clinic and hiring a physician's assistant. The service, begun in 1982, was managed by a senior radiologist and fellows. Because of increasing admissions (from a mean of 52 per year in 1982-1985 to 110 per year in 1985-1987), a 1/2-day, twice-weekly clinic was created in 1985 to evaluate new patients and perform follow-up examinations. In 1986 a physician's assistant was hired to assist in the clinic and during patient admissions. Use of the clinic and physician's assistant streamlined patient flow and management during hospitalization. This resulted in a decrease in mean length of stay for patients undergoing angioplasty (from 3.74 days in 1982-1983 to 2.41 days in 1986-1987). This decrease means cost savings for the hospital under the prospective payment system. Other benefits include improved physician-patient relationships and follow-up, new patients for colleagues (15% of patients had anatomy unsuitable for interventional procedures and were referred to staff surgeons), and increased professional fees.
Asunto(s)
Departamentos de Hospitales/organización & administración , Admisión del Paciente , Servicio de Radiología en Hospital/organización & administración , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/economía , Embolización Terapéutica , Honorarios Médicos , Humanos , Tiempo de Internación , Asistentes Médicos , Derivación y ConsultaRESUMEN
The pharmacokinetic disposition of florfenicol was studied in male veal calves given 11 mg of florfenicol/kg of body weight, IV and 11 mg of florfenicol/kg PO every 12 hours for 7 doses. After florfenicol administration IV, the median elimination half-life was 222.8 minutes, whereas the median half-life of the distribution phase was 7.94 minutes. Median body clearance and apparent volume of distribution were 2.87 ml/kg/min and 0.907 L/kg, respectively. After florfenicol administration, PO, there was a wide variation in the calculated half-life, which was attributed to variation in the rate of florfenicol absorption. The half-life was 167.4 to 534.9 minutes after the first oral dose and 190 to 808.8 minutes after the seventh dose. The median bioavailability after the first oral dose was 0.8888. Peak and trough concentrations of florfenicol were increased after subsequent doses were administered, compared with those after the first oral dose. The percentage of protein binding in serum from one adult cow was 22% to 26%. Florfenicol concentrations in tissues and body fluids of male veal calves were studied after the seventh dose of 11 mg of florfenicol/kg. High concentrations of florfenicol were measured in the urine, kidney, and bile. Low concentrations were measured in the brain, CSF, and aqueous humor. Concentrations in all other tissues and fluids studied were similar to the concurrent serum concentration.
Asunto(s)
Antibacterianos/farmacocinética , Bovinos/metabolismo , Tianfenicol/análogos & derivados , Administración Oral , Animales , Antibacterianos/administración & dosificación , Esquema de Medicación , Inyecciones Intravenosas , Masculino , Tianfenicol/administración & dosificación , Tianfenicol/farmacocinética , Distribución TisularRESUMEN
The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22-mg/kg dose intravenously, orally after a 12-h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half-life was 171.9 min while the half-life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 l/kg, respectively. Following oral administration the median bio-availability (f) was 0.88 for calves dosed after a 12-h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.
Asunto(s)
Tianfenicol/análogos & derivados , Administración Oral , Animales , Disponibilidad Biológica , Bovinos , Femenino , Inyecciones Intravenosas , Absorción Intestinal , Cinética , Tasa de Depuración Metabólica , Tianfenicol/administración & dosificación , Tianfenicol/sangre , Tianfenicol/metabolismoRESUMEN
Silicone tubes in 2-F increments from 12 to 20 F were developed for long term external-internal drainage of benign and malignant biliary obstructions. Passed coaxially over Teflon catheters and a guidewire, the silicone stents were softer and had larger sideholes than conventional drainage tubes. Once the acute track had matured (two weeks or longer), a silicone stent, 2 F larger than the preceding one, could be placed at each succeeding tube change. We have placed these tubes in 50 patients, 24 of whom had initially placed percutaneous catheters and 26 of whom had surgically placed stents. These tubes remain patent at least as long as conventional catheters and all patients have reported increased comfort using these catheters compared with standard ones.
Asunto(s)
Colestasis/terapia , Drenaje/instrumentación , Cateterismo/instrumentación , Humanos , Punciones , SiliconasAsunto(s)
Enfermedades de los Conductos Biliares/terapia , Intubación , Elastómeros de Silicona , Enfermedades de los Conductos Biliares/diagnóstico por imagen , Colangitis/terapia , Colestasis Extrahepática/terapia , Conducto Hepático Común , Humanos , Intubación/efectos adversos , Radiografía , Factores de TiempoRESUMEN
Testicular varicocele is the single most common cause of male infertility. Varicoceles are due to either absent or nonfunctioning valves that permit retrograde flow in the internal spermatic vein resulting in increased temperature within the scrotum and interfering with spermatogenesis. Our method to treat varicoceles is occlusion of the spermatic vein with detachable silicone balloons. In our first 70 patients, this has proven to be a safe and effective nonsurgical method of occluding varicoceles in outpatients with results similar to those of surgery.
Asunto(s)
Embolización Terapéutica/instrumentación , Varicocele/terapia , Embolización Terapéutica/métodos , Humanos , Masculino , Testículo/irrigación sanguínea , VenasRESUMEN
At the Johns Hopkins Hospital, a cardiovascular radiology "clinical assistant" position was created to assist the radiologist in performing interventional radiology procedures. It was soon apparent that the clinical assistant could contribute a great deal to patient management before and after the procedure. Additionally, patient and housestaff education was facilitated, and continuity of care was maintained. The clinical assistant has become an indispensable part of the health care team in interventional radiology.
Asunto(s)
Grupo de Atención al Paciente , Asistentes Médicos , Radiología , Maryland , Servicio de Radiología en Hospital , Recursos HumanosRESUMEN
Intra-arterial pressure measurements and ankle pressure indices (determined by Doppler ultrasound) were used to evaluate the hemodynamic response after transluminal angioplasty of the iliac and superficial femoral arteries. Intra-arterial pressure was the best determinant of the end point and technical success of the procedure, while improvement in the ankle pressure index was a good predictor of clinical success. Patients with clinical improvement had a significant increase in ankle pressure regardless of the status of peripheral runoff, while those without improvement did not; they demonstrated impaired distal runoff and required further surgical intervention. Peripheral Doppler pressures also provided a convenient noninvasive method of long-term follow-up.