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1.
Acute Med ; 13(2): 68-71, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24940569

RESUMEN

An 80 year old man presented subacutely with drowsiness and confusion. Subsequent MRI brain imaging demonstrated multiple posterior circulation infarcts. Extracranial vasculitis was suspected when his ESR was found to be high and vascular imaging showed multifocal irregular narrowing of both vertebral arteries. This was confirmed by targeted temporal artery biopsy, which showed chronic granulomatous inflammation typical of giant cell arteritis (GCA). The patient made a significant recovery following treatment with prednisolone.


Asunto(s)
Arteritis de Células Gigantes/diagnóstico , Accidente Cerebrovascular/etiología , Anciano de 80 o más Años , Sedimentación Sanguínea , Encéfalo/patología , Arteritis de Células Gigantes/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Humanos , Angiografía por Resonancia Magnética , Imagen por Resonancia Magnética , Masculino , Prednisolona/uso terapéutico , Arterias Temporales/patología
2.
Br J Surg ; 99(2): 209-16, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22190246

RESUMEN

BACKGROUND: Carotid endarterectomy (CEA) reduces the risk of stroke in patients with internal carotid stenosis of 50-99 per cent. This study assessed national surgical practice through audit of CEA procedures and outcomes. METHODS: This was a prospective cohort study of UK surgeons performing CEA, using clinical audit data collected continuously and reported in two rounds, covering operations from December 2005 to December 2007, and January 2008 to September 2009. RESULTS: Some 352 (92·6 per cent) of 380 eligible surgeons contributed data. Of 19,935 CEAs recorded by Hospital Episode Statistics, 12,496 (62·7 per cent) were submitted to the audit. A total of 10,452 operations (83·6 per cent) were performed for symptomatic carotid stenosis; among these patients, the presenting symptoms were transient ischaemic attack in 4507 (43·1 per cent), stroke in 3572 (34·2 per cent) and amaurosis fugax in 1965 (18·8 per cent). The 30-day mortality rate was 1·0 per cent (48 of 4944) in round 1 and 0·8 per cent (50 of 6151) in round 2; the most common cause of death was stroke, followed by myocardial infarction. The rate of death or stroke within 30 days of surgery was 2·5 per cent (124 of 4918) in round 1 and 1·8 per cent (112 of 6135) in round 2. CONCLUSION: CEA is performed less commonly in the UK than in other European countries and probably remains underutilized in the prevention of stroke. Increasing the number of CEAs done in the UK, together with reducing surgical waiting times, could prevent more strokes.


Asunto(s)
Estenosis Carotídea/cirugía , Endarterectomía Carotidea/métodos , Práctica Profesional , Anciano , Amaurosis Fugax/etiología , Diagnóstico Tardío , Femenino , Humanos , Ataque Isquémico Transitorio/etiología , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/etiología , Cuidados Preoperatorios/métodos , Estudios Prospectivos , Derivación y Consulta , Accidente Cerebrovascular/etiología
3.
Disabil Rehabil ; 44(10): 1959-1967, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-32960114

RESUMEN

PURPOSE: In search of Kipling's six honest serving men in upper limb rehabilitation after stroke, we sought to investigate clinicians' perspective of when and where to begin therapy, how much and what therapy to provide, and who and why (or not) to provide therapy.Materials & methods: Within-participant case cross-over experiments were nested within an anonymous web-based questionnaire (21 questions, three cases). Graph theory-based voting to produce ranked ordered lists and mixed-effect logistic regression were performed. RESULTS: In total, 225 Australian stroke clinicians responded: 53% occupational therapists, 61% working in acute/inpatient stroke setting. Most respondents indicated they did not have a protocol/expectation regarding when (62%), how much (84%) or what (60%) therapy to provide in their setting. Respondents ranked 24-h to 7-days post-stroke as the optimal time to commence therapy, and 30- to 60-min per day as the optimal dose to provide. Within-participant experiments demonstrated that greater motor recovery as time progressed increased the odds of offering therapy, while lack of motor recovery, shoulder pain, neurological decline and sole therapist reduced the odds. CONCLUSION: We need to develop an evidence base concerning Kipling's six honest serving men and equip clinicians with clinical decision-making skills aligned with this focus.IMPLICATIONS FOR REHABILITATIONMost clinicians did not have access to a protocol / clinical pathway which defines when, how much and what upper limb therapy to provide after stroke, which may be improved by providing individual clinicians with organisational support to make therapy decisions.To improve the personalisation of upper limb rehabilitation in clinical practice, we need to understand when and where after stroke to begin therapy, how much and what therapy to provide, as well as who and why (clinical decision-making) to provide therapy.Clinicians perceive clinical trials as successful if the therapy can demonstrate recovery that is greater than a minimal clinical important difference (MCID).


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Australia , Humanos , Internet , Masculino , Recuperación de la Función , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/métodos , Encuestas y Cuestionarios , Extremidad Superior
4.
Nat Med ; 4(11): 1302-7, 1998 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-9809555

RESUMEN

T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels. All four subjects receiving 100 mg twice daily had a decline in plasma HIV RNA to less than 500 copies/ml, by bDNA assay. A sensitive RT-PCR assay (detection threshold 40 copies/ml) demonstrated that, although undetectable levels were not achieved in the 14-day dosing period, there was a 1.96 log10 median decline in plasma HIV RNA in these subjects. This study provides proof-of-concept that viral entry can be successfully blocked in vivo. Short-term administration of T-20 seems safe and provides potent inhibition of HIV replication comparable to anti-retroviral regimens approved at present.


Asunto(s)
Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Proteína gp41 de Envoltorio del VIH/sangre , Proteína gp41 de Envoltorio del VIH/fisiología , Proteína gp41 de Envoltorio del VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Fragmentos de Péptidos/sangre , Fragmentos de Péptidos/uso terapéutico , Replicación Viral/efectos de los fármacos , Adulto , Fármacos Anti-VIH/sangre , Recuento de Linfocito CD4 , Relación Dosis-Respuesta a Droga , Enfuvirtida , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Semivida , Humanos , Tasa de Depuración Metabólica
5.
Clin Rehabil ; 24(5): 471-8, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20237174

RESUMEN

OBJECTIVE: To describe a treatment protocol for the upper limb that standardizes intensity of therapy input regardless of the severity of presentation. DESIGN: The protocol is described (Part 1) and feasibility and effect explored (Part 2). SUBJECTS: Participants (n = 11) had a single ischaemic stroke in the middle cerebral artery territory more than one year previously, and had residual weakness of the hand with some extension present at the wrist and the ability to grasp. INTERVENTIONS: Following two baseline assessments, participants attended therapy for 1 hour a day for 10 consecutive working days. Treatment consisted of a combination of strength and functional task training. Outcomes were measured immediately after training, at one month and three months. OUTCOME MEASURES: Intensity was measured with Borg Rating of Perceived Exertion. Secondary outcome measures included Action Research Arm Test (ARAT), nine-hole peg test, and Goal Attainment Scale. RESULTS: Borg scores indicated that the level of intensity was appropriate and similar across all participants despite individual differences in the severity of their initial presentation (median (interquartile range) = 14 (13-15)). The mean ARAT score significantly increased by 6.8 points (chi(2)(3) = 15.618, P<0.001), and was maintained at three-month follow-up (z = - 2.384, P = 0.016). The nine-hole peg test also showed a main effect of time and 88% of goals set were achieved. CONCLUSIONS: The physiotherapy protocol standardized intensity of treatment by grading exercise and task-related practice according to the person's residual ability, rather than simply standardizing treatment times. It was feasible and well tolerated in this group.


Asunto(s)
Debilidad Muscular/rehabilitación , Modalidades de Fisioterapia/normas , Rehabilitación/normas , Rehabilitación de Accidente Cerebrovascular , Análisis y Desempeño de Tareas , Extremidad Superior/fisiopatología , Actividades Cotidianas , Animales , Objetivos , Fuerza de la Mano , Humanos , Actividad Motora/fisiología , Debilidad Muscular/fisiopatología , Proyectos Piloto , Calidad de Vida , Ratas , Recuperación de la Función , Rehabilitación/métodos , Resultado del Tratamiento
6.
Clin Pharmacol Ther ; 81(6): 867-72, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17392728

RESUMEN

Cytomegalovirus (CMV) is the most common viral congenital infection, producing both sensorineural hearing loss and mental retardation. Our objective was to assess the population pharmacokinetics of a research-grade oral valganciclovir solution in neonates with symptomatic congenital CMV disease. Twenty-four neonates received 6 weeks of antiviral therapy. Ganciclovir and valganciclovir were measured by liquid chromatography/tandem mass spectroscopy. NONMEM version VI beta was used for population analyses. All profiles were consistent with a one-compartment model. Postnatal age, body surface area, and gender did not improve the model fit after body weight was taken into account. The typical value of clearance (l/h), distribution volume (l), and bioavailability of ganciclovir were 0.146 x body weight (WT)(1.68), 1.15 x WT, and 53.6%, respectively. Although these results cannot be extrapolated to extemporaneously compounded valganciclovir preparations, they provide the foundation on which a commercial-grade valganciclovir oral solution may be a viable option for administration to neonates.


Asunto(s)
Antivirales/farmacocinética , Infecciones por Citomegalovirus/tratamiento farmacológico , Ganciclovir/análogos & derivados , Ganciclovir/farmacocinética , Administración Oral , Antivirales/sangre , Antivirales/uso terapéutico , Área Bajo la Curva , Peso Corporal , Cromatografía Líquida de Alta Presión , Femenino , Ganciclovir/sangre , Ganciclovir/uso terapéutico , Humanos , Lactante , Recién Nacido , Enfermedades del Recién Nacido/tratamiento farmacológico , Inyecciones Intravenosas , Masculino , Espectrometría de Masas en Tándem , Valganciclovir
7.
J Neurol Neurosurg Psychiatry ; 78(11): 1218-25, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17287234

RESUMEN

BACKGROUND AND PURPOSE: Posterior circulation stroke accounts for 20% of ischaemic strokes. Recent data suggest that the early stroke recurrence risk is high and comparable with carotid artery disease. Vertebral artery stenosis accounts for approximately 20% of posterior circulation stroke, and with endovascular treatment available accurate diagnostic imaging is important. We performed a systematic literature review to validate the accuracy of the non-invasive imaging techniques Duplex ultrasound (DUS), magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) in detecting severe vertebral artery stenosis, with intra-arterial angiography (IAA) as the reference standard. METHODS: We identified studies that used non-invasive imaging and IAA as the reference standard to determine vertebral artery stenosis and provided adequate data to calculate sensitivity and specificity. We analysed the quality of these studies, looked for evidence of heterogeneity and performed subgroup analysis for different degrees of stenosis. RESULTS: 11 studies categorised stenosis into 50-99%. The sensitivity of CTA (single study) and pooled sensitivities of contrast enhanced MRA (CE-MRA) and colour duplex were 100% (95% CI 15.8 to 100), 93.9% (79.8 to 99.3) and 70.2% (54.2 to 83.3), respectively. The specificities for CTA, CE-MRA and colour duplex were 95.2% (83.8 to 99.4), 94.8% (91.1 to 97.3) and 97.7% (95.2 to 99.1). However, specificities for CE-MRA and colour duplex demonstrated significant heterogeneity (p = 0.003 and p = 0.002, respectively). CONCLUSIONS: CE-MRA and possibly CTA may be more sensitive in diagnosing vertebral artery stenosis than DUS. However, data are limited and further high quality studies comparing DUS, MRA and CTA with IAA are required.


Asunto(s)
Angiografía Cerebral , Angiografía por Resonancia Magnética , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler Dúplex , Insuficiencia Vertebrobasilar/diagnóstico , Medios de Contraste , Humanos , Aumento de la Imagen , Sensibilidad y Especificidad
8.
Int J Stroke ; 12(1): 9-12, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27694315

RESUMEN

Systemic thrombolysis with rt-PA is contraindicated in patients with acute ischemic stroke anticoagulated with dabigatran. This expert opinion provides guidance on the use of the specific reversal agent idarucizumab followed by rt-PA and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran. The use of idarucizumab followed by rt-PA is covered by the label of both drugs.


Asunto(s)
Antitrombinas/uso terapéutico , Isquemia Encefálica/terapia , Dabigatrán/uso terapéutico , Accidente Cerebrovascular/terapia , Trombectomía , Terapia Trombolítica , Isquemia Encefálica/prevención & control , Humanos , Accidente Cerebrovascular/prevención & control
9.
J Clin Oncol ; 1(11): 720-6, 1983 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-6668490

RESUMEN

A multifactorial analysis was used to identify the dominant prognostic variables predicting survival rates of 175 patients with hepatic metastases from colorectal carcinoma. Seven of 22 parameters examined simultaneously were found to independently influence the median survival rate in these patients: (1) elevated alkaline phosphatase (p = 0.0004), (2) elevated serum bilirubin level (p = 0.0005), (3) location of hepatic metastases (unilateral or bilateral, p = 0.0022), (4) number of metastatic nodes involved (0, 1-5, greater than 5; p = 0.0148), (5) depressed serum albumin (p = 0.0217), (6) whether or not the primary colorectal tumor was resected (p = 0.0013), and (7) chemotherapy (given or withheld, p = 0.0439). The prothrombin time, serum lactic dehydrogenase, and the number of hepatic metastases also correlated with survival, but they did not independently predict survival rates after other more dominant factors were accounted for. A mathematical equation for predicting an individual patient's clinical course once they developed hepatic metastases was derived from this statistical analysis. In addition, a simple and clinically useful guide for predicting outcome was developed that integrated the two most important risk factors, alkaline phosphatase and bilirubin.


Asunto(s)
Neoplasias del Colon/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias del Recto/mortalidad , Anciano , Fosfatasa Alcalina/sangre , Análisis de Varianza , Antineoplásicos/uso terapéutico , Bilirrubina/sangre , Pruebas Enzimáticas Clínicas , Colectomía , Neoplasias del Colon/terapia , Terapia Combinada , Femenino , Humanos , Pruebas de Función Hepática , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Neoplasias del Recto/terapia
10.
Medicine (Baltimore) ; 72(4): 207-24, 1993 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8341139

RESUMEN

We have reviewed our experience with 17 of our own patients with cryptococcal meningitis and 32 cases from the literature. Although this complication is an uncommon event, patients with cryptococcal meningitis may develop visual loss in the absence of other ocular lesions (endophthalmitis or cryptococcomas in the visual pathway) that could explain the visual symptoms. There are 2 distinct patterns of visual loss: rapid visual loss and slow visual loss. Rapid visual loss is characterized by onset of profound visual loss over a period as short as 12 hours before or early in the course of therapy and a clinical syndrome that is strongly suggestive of optic neuritis. Direct invasion of the optic nerve by C. neoformans is demonstrated by cases in this and other reports. Slow visual loss is characterized by slow but progressive visual loss which typically begins later during therapy and may be due to the effects of increased intracranial pressure. While the initial deficit may be mild, patients with slow visual loss can progress to severe visual loss over weeks to months. The only factors that appear to predict either pattern of visual loss are the presence of papilledema, an elevated CSF opening pressure, and a positive CSF India ink preparation. In the 25 visual loss patients for whom data were available for all 3 items, 10 (40%) were positive for all 3, as opposed to only 4 of 114 (3.5%) from a reference group of cryptococcal meningitis patients without visual loss (p < 0.00001). The only therapeutic measures with any degree of consistent success were those directed at reducing intracranial pressure. When begun early and used aggressively, such therapy halted and sometimes even reversed the course of visual loss, particularly in the slow visual loss group. Corticosteroids did not appear to be of value in the small number of patients who received them.


Asunto(s)
Meningitis Criptocócica/complicaciones , Trastornos de la Visión/etiología , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Antifúngicos/uso terapéutico , Femenino , Humanos , Presión Intracraneal , Masculino , Persona de Mediana Edad , Neuritis Óptica/complicaciones , Seudotumor Cerebral/complicaciones , Punción Espinal , Factores de Tiempo , Trastornos de la Visión/fisiopatología , Trastornos de la Visión/terapia
11.
J Immunol Methods ; 94(1-2): 247-55, 1986 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-3782814

RESUMEN

A novel flow cytometry method for the evaluation of cell-mediated cytotoxicity is described. This method uses flow cytometry analysis to distinguish target cells from effector cells by differences in volume and light scatter characteristics. Non-viable target cells, following their interaction with effector cells, are determined via propidium iodide (PI) dye exclusion and then expressed as a percentage of the total target cell population. This assay is suitable both for analysis of systems which allow recycling of cytotoxic effector cells (total cell cytotoxicity assays, TCCA), and of systems in which recycling does not occur (single cell cytotoxicity assays, SCCA). Natural killer (NK) cell-mediated cytotoxicity evaluated by flow cytometry is significantly correlated with the standard 51Cr release assay. Flow cytometry can also be used to evaluate the competitive inhibition that certain cell types exert on the cell-mediated killing of NK-sensitive targets. A prerequisite for this assay is that competitor cells and target cells are distinguishable through their volume and light scatter characteristics. Advantages and pitfalls of the flow cytometry method are discussed, in comparison with the 51Cr-release assay.


Asunto(s)
Pruebas Inmunológicas de Citotoxicidad/métodos , Citometría de Flujo , Adulto , Línea Celular , Supervivencia Celular , Radioisótopos de Cromo , Humanos , Células Asesinas Naturales/inmunología , Propidio
12.
Am J Med ; 84(3 Pt 2): 603-10, 1988 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3279775

RESUMEN

One hundred and twelve patients with progressive pulmonary, skeletal, or soft tissue infections caused by Coccidioides immitis were randomly assigned to treatment with 400 or 800 mg per day dosages of ketoconazole. During therapy, if response was unsatisfactory, the protocol provided for treatment with higher doses. With 400 mg, ketoconazole resulted in 23.2 percent successes, which was similar to 32.1 percent successes with 800-mg treatments (p = 0.29). An additional six of 23 patients in whom initial therapy failed and who later received 1,200 or 1,600 mg per day of ketoconazole also showed improvement. However, among patients completing successful courses of therapy, relapses were more frequent in those requiring higher than 400-mg dosages for their success. From these studies, it is concluded that ketoconazole in doses above those currently recommended offer little or no benefit for most patients with non-meningeal forms of coccidioidomycosis.


Asunto(s)
Coccidioidomicosis/tratamiento farmacológico , Cetoconazol/administración & dosificación , Adulto , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Cetoconazol/uso terapéutico , Masculino , Distribución Aleatoria
13.
Am J Med ; 89(3): 282-90, 1990 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2168126

RESUMEN

PURPOSE: The purpose of this study was to assess the tolerance and efficacy of itraconazole in the treatment of coccidioidomycosis. PATIENTS AND METHODS: Fifty-one patients with nonmeningeal coccidioidomycosis were considered for treatment with intraconazole. Forty-nine patients who met study criteria were treated with itraconazole given orally in doses of 100 to 400 mg/day for periods up to 39 months. Of these patients, 12 had osteoarticular disease, 23 had chronic pulmonary disease, and 14 had skin or soft tissue disease. Clinical response was evaluated using a scoring system accounting for lesion number and size, symptoms, culture, and serologic titer. Remission was defined as reduction of the pretreatment score by 50% or more. RESULTS: Patients with osteoarticular, chronic pulmonary, and soft tissue disease improved at similar rates. Because two patients had no scoring assessment for efficacy, they were considered inassessable for efficacy. Forty-seven patients are evaluable. Of these patients, 44 have completed therapy, and three are still receiving itraconazole. Of the 44 patients no longer receiving therapy, 25 (57%) achieved remission. Of the 25 patients achieving remission, four later experienced a relapse. Therapy failed in 19 patients (43%). Of these cases, 16 (36%) were clinical failures and three (7%) developed drug intolerance that precluded continuation of treatment. Evaluation of culture conversions was of limited value in the osteoarticular patients, fewer than half of whom had follow-up biopsies. However, culture conversions were a useful index of response in patients with chronic pulmonary disease. During the course of treatment, serologic titers declined in the two groups with extrapulmonary disease, but not in patients with pulmonary coccidioidomycosis. Possible toxicities were generally mild. CONCLUSION: Itraconazole appears efficacious and very well tolerated in patients with coccidioidomycosis.


Asunto(s)
Antifúngicos/uso terapéutico , Coccidioidomicosis/tratamiento farmacológico , Cetoconazol/análogos & derivados , Adolescente , Adulto , Anciano , Antifúngicos/administración & dosificación , Antifúngicos/toxicidad , Enfermedades Óseas/tratamiento farmacológico , Dermatomicosis/tratamiento farmacológico , Farmacorresistencia Microbiana , Femenino , Estudios de Seguimiento , Humanos , Itraconazol , Artropatías/tratamiento farmacológico , Cetoconazol/administración & dosificación , Cetoconazol/uso terapéutico , Cetoconazol/toxicidad , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Recurrencia , Inducción de Remisión
14.
Am J Med ; 83(2): 236-42, 1987 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-3303926

RESUMEN

A multicenter prospective randomized trial of four versus six weeks of amphotericin B, 0.3 mg/kg per day, plus flucytosine, 150 mg/kg per day, was performed with 194 patients with cryptococcal meningitis. One or more toxic drug reactions developed in 103 patients: azotemia (51), renal tubular acidosis (two), leukopenia (30), thrombocytopenia (22), diarrhea (26), nausea/vomiting (10), and hepatitis (13). The four- and six-week regimens were complicated by toxicity in 44 percent and 43 percent of cases, respectively. Toxicity appeared during the first two weeks of therapy in 56 percent and during the first four weeks in 87 percent. Azotemia did not occur more frequently in renal transplant recipients or diabetic patients. Cytopenias did not appear more often in patients with hematologic malignancies or those receiving immunosuppressive therapies. Toxic reactions that contributed to death developed in five patients (two with azotemia, one with pancytopenia, one with hepatitis, one with ileus). Amphotericin B-induced azotemia was not a significant risk factor for the subsequent development of bone marrow, gastrointestinal, or hepatic toxicity attributable to flucytosine. Flucytosine toxicity was associated with peak serum flucytosine levels of 100 micrograms/ml or more during two or more weeks of therapy (p = 0.005). Peak 5-fluorouracil levels were not predictive of toxicity. An initial dose of flucytosine is recommended based on the creatinine clearance: 150 mg/kg per day at a creatinine clearance above 50 ml/minute, 75 mg/kg per day at a creatinine clearance of 26 to 50 ml/minute, and 37 mg/kg per day at a creatinine clearance of 13 to 25 ml/minute. The serum creatinine level should be monitored twice weekly and the creatinine clearance weekly during therapy in order to anticipate changes in serum flucytosine concentration. In addition, it is recommended that the serum flucytosine level be determined two hours after an oral dose once a week, and that the dose be adjusted to maintain a level of 50 to 100 micrograms/ml.


Asunto(s)
Anfotericina B/efectos adversos , Criptococosis/tratamiento farmacológico , Flucitosina/efectos adversos , Meningitis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anfotericina B/administración & dosificación , Niño , Ensayos Clínicos como Asunto , Creatinina/sangre , Criptococosis/sangre , Criptococosis/complicaciones , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Flucitosina/administración & dosificación , Humanos , Masculino , Meningitis/sangre , Meningitis/complicaciones , Persona de Mediana Edad , Estudios Prospectivos , Distribución Aleatoria , Factores de Tiempo
15.
Am J Med ; 95(3): 279-85, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8396321

RESUMEN

PURPOSE: To describe the clinical presentation and outcomes of treatment with itraconazole in patients with sporotrichosis. METHODS: A culture for Sporothrix schenckii or compatible histopathology was required for inclusion in the study. Patients with both cutaneous and systemic sporotrichosis were treated. Patients received from 100 to 600 mg of itraconazole daily for 3 to 18 months. Patients were classified as responders or nonresponders. Responders were further classified as remaining on treatment, relapsed, or free of disease. Nonresponders included patients who failed to respond or progressed during treatment with itraconazole. RESULTS: Twenty-seven patients (mean age: 53 years) were treated with 30 courses of itraconazole. Diabetes mellitus and alcoholism were present in eight and seven patients, respectively. Sites of involvement included lymphocutaneous alone in 9 patients, articular/osseous in 15 (multifocal in 3), and lung in 3. Prior therapy was unsuccessful in 11 patients. Among the 30 courses, there were 25 responders and 5 nonresponders. All 5 nonresponders received at least 200 mg daily of itraconazole for durations that ranged from 6 to 18 months. Of the 25 responders, 7 relapsed 1 to 7 months after treatment durations of 6 to 18 months. Of the 7 who relapsed, 2 are responding to a second course. One responder was lost to follow-up after 10 months of treatment with itraconazole. Of the remaining 17 responders, 3 remain on treatment, and 14 are free of disease over follow-up durations of 6 to 42 months (mean: 17.6 months). Itraconazole was well tolerated with few side effects noted. CONCLUSIONS: These results document the efficacy of itraconazole in the treatment of cutaneous and systemic sporotrichosis.


Asunto(s)
Antifúngicos/uso terapéutico , Cetoconazol/análogos & derivados , Esporotricosis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Femenino , Humanos , Itraconazol , Cetoconazol/administración & dosificación , Cetoconazol/efectos adversos , Cetoconazol/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
16.
Am J Med ; 98(3): 249-56, 1995 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-7872341

RESUMEN

PURPOSE: To determine the efficacy and safety of fluconazole as treatment for coccidioidomycosis. PATIENTS AND METHODS: This was a multicenter, open-label, single-arm study. Of 78 patients enrolled, 22 had soft-tissue, 42 had chronic pulmonary, and 14 had skeletal coccidioidomycosis. Forty-nine had at least one concomitant disease, 7 of whom had HIV infection. Patients were given oral fluconazole 200 mg/d. Nonresponders were increased to 400 mg/d. Treatment courses were long: a mean of 323 +/- 230 days at 200 mg and 433 +/- 178 days at 400 mg. Predefined assessment of disease-related abnormalities was performed at the time of enrollment and repeated at least every 4 months. A satisfactory response was defined as any reduction of baseline abnormality by month 4 and at least 51% reduction by month 8. RESULTS: Among 75 evaluable patients, a satisfactory response was observed in 12 (86%) of the 14 patients with skeletal, 22 (55%) of the 40 patients with chronic pulmonary, and 16 (76%) of the 21 patients with soft-tissue disease. Five patients (7%) required modification of treatment due to toxicity. Forty-one patients who responded were followed off drug. Fifteen (37%) of them experienced reactivation of infection. CONCLUSION: Fluconazole 200 or 400 mg/d is well tolerated and a moderately effective treatment for chronic pulmonary or nonmeningeal disseminated coccidioidomycosis. The relapse rate following therapy is high. Treatment trials with higher doses appear warranted. The relative efficacy of fluconazole versus other azoles or amphotericin B remains unknown.


Asunto(s)
Coccidioidomicosis/tratamiento farmacológico , Fluconazol/uso terapéutico , Enfermedades Pulmonares Fúngicas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Fluconazol/efectos adversos , Humanos , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
17.
Am J Med ; 93(5): 489-97, 1992 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1332471

RESUMEN

OBJECTIVE: To assess the efficacy and toxicity of orally administered itraconazole in the treatment of nonmeningeal, nonlife-threatening forms of blastomycosis and histoplasmosis. DESIGN: Prospective, nonrandomized, open trial. SETTING: Multicenter trial at 14 university referral centers. PATIENTS: Eighty-five patients with culture or histopathologic evidence of blastomycosis (48 patients) or histoplasmosis (37 patients). Patients receiving other systemic antifungal therapy were excluded. INTERVENTIONS: Itraconazole was administered orally at doses of 200 to 400 mg/d. Patients in whom treatment was considered a success were treated for a median duration of 6.2 months (blastomycosis) and 9.0 months (histoplasmosis). Disease activity was assessed at baseline; drug efficacy and toxicity were evaluated at monthly intervals during therapy, and efficacy was evaluated at regular follow-up visits after completion of therapy. The median duration of posttreatment evaluation for successfully treated patients was 11.9 months (blastomycosis) and 12.1 months (histoplasmosis). MEASUREMENTS AND MAIN RESULTS: Among the 48 patients with blastomycosis, success was documented in 43 (90%). The success rate for patients treated for more than 2 months was 95% (38 of 40). Among the 37 patients with histoplasmosis, success was documented in 30 (81%). The success rate for patients treated for more than 2 months was 86% (30 of 35). All patients with histoplasmosis in whom treatment failed had chronic cavitary pulmonary disease. Toxicity was minor; only 25 (29%) patients experienced any side effects, and itraconazole toxicity necessitated stopping therapy in only 1 patient. CONCLUSIONS: Itraconazole is a highly effective therapy for nonmeningeal, nonlife-threatening blastomycosis and histoplasmosis. The drug is associated with minimal toxicity.


Asunto(s)
Antifúngicos/uso terapéutico , Blastomicosis/tratamiento farmacológico , Histoplasmosis/tratamiento farmacológico , Cetoconazol/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/efectos adversos , Femenino , Humanos , Itraconazol , Cetoconazol/efectos adversos , Cetoconazol/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
18.
Pediatrics ; 79(1): 76-83, 1987 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-3025807

RESUMEN

A total of 205 infants who were hospitalized when younger than 3 months of age for pneumonitis were followed longitudinally. Of these patients, 145 (70%) had evidence of infection with one or more pathogens. The most common etiologic agents were Chlamydia trachomatis 61/193 (36%), respiratory syncytial virus 33/142 (23%), cytomegalovirus 42/203 (20%), Pneumocystis carinii 30/171 (17%), and Ureaplasma urealyticum 21/125 (16%). The initial clinical presentation was characterized by cough, rales, normal temperature, and diffuse obstructive airways disease by chest roentgenogram. Regardless of etiology, significant association occurred for cough and cytomegalovirus, apnea and Pneumocystis, and conjunctivitis and Chlamydia. Longitudinal follow-up demonstrates a mortality of 7/205 (3.4%). Morbidity was manifest as recurrent wheezing episodes in 86/187 (46%) patients, persistently abnormal chest roentgenographic findings for at least 12 months in 17/109 (15%) patients, and abnormal pulmonary functions in 15/25 (60%) patients. These abnormalities occurred irrespective of prematurity, atopy, or the initial etiologic agent associated with the pneumonitis. These data add further evidence that respiratory infections during infancy may well be predecessors of obstructive airways disease in later life.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Infecciones por Citomegalovirus/diagnóstico , Neumonía por Pneumocystis/diagnóstico , Neumonía Viral/etiología , Neumonía/etiología , Chlamydia trachomatis/aislamiento & purificación , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Factores de Tiempo , Ureaplasma/aislamiento & purificación
19.
Pediatr Infect Dis J ; 9(7): 465-70, 1990 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1973533

RESUMEN

Child care workers are potentially at risk for occupational exposure to cytomegalovirus, the leading cause of congenital infection in the United States. Preschool children often shed cytomegalovirus and commonly transmit virus to peers and parents. Workers from 32 day care centers were enrolled and tested for serum antibody to cytomegalovirus; 318 (62.5%) were seropositive. By logistic regression analysis the only variables significantly (P less than 0.05) associated with seropositivity at enrollment were older age and nonwhite race, though contact with younger children (less than 2 years of age) attained a P value of 0.06. Follow-up sera were obtained at 6-month intervals from 82 initially seronegative workers; 19 seroconverted in a median interval of 14 months, a rate of 20%/year, approximately 10-fold higher than the expected rate. The only demographic or employment variable associated with seroconversion was contact with children younger than 3 years of age for at least 20 hours per week (P = 0.03). Day care center workers have a markedly increased risk for acquisition of cytomegalovirus; those who could become pregnant should be appropriately counseled regarding prevention and consequences of cytomegalovirus infection during pregnancy.


Asunto(s)
Guarderías Infantiles , Infecciones por Citomegalovirus/epidemiología , Enfermedades Profesionales/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Alabama/epidemiología , Anticuerpos Antivirales/análisis , Niño , Preescolar , Citomegalovirus/genética , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/transmisión , ADN Viral/análisis , Femenino , Estudios de Seguimiento , Humanos , Lactante , Estudios Longitudinales , Persona de Mediana Edad , Enfermedades Profesionales/inmunología , Enfermedades Profesionales/prevención & control , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Regresión , Factores de Riesgo , Recursos Humanos
20.
Pediatr Infect Dis J ; 9(3): 170-5, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2159611

RESUMEN

Cytomegalovirus (CMV) is the most common viral agent causing congenital infection in humans, affecting 0.2 to 2.4% of all live births. Symptomatic congenital CMV infection has previously been shown to cause low birth weight and prematurity. Whether or not asymptomatic congenital CMV infection, which represents the majority of cases (90 to 95%), affects intrauterine growth or gestational duration is unknown. Using a population of 146 infants with asymptomatic congenital CMV infection and 1419 controls from two socioeconomically diverse populations (biracial low income and white mid- to upper income), determinants of body size (birth weight and crown-heel length) were investigated using multiple regression techniques. We found that congenital infection following the transmission of maternal primary and "unknown" CMV infection resulted in a significant mean birth weight deficit of 163 g (P less than 0.04) for the low income term infants (blacks and whites), but not in the mid- to upper income white infants. Newborns with congenital infection following the transmission of maternal reactivated (recurrent) CMV infection were significantly shorter by a mean of 1 cm (P less than 0.03) than controls, a finding that was consistent regardless of socioeconomic status or race.


Asunto(s)
Constitución Corporal , Infecciones por Citomegalovirus/congénito , Edad Gestacional , Peso al Nacer , Estatura , Estudios de Casos y Controles , Infecciones por Citomegalovirus/complicaciones , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo , Estudios Prospectivos , Factores Socioeconómicos , Factores de Tiempo
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