RESUMEN
PURPOSE: The efficacy of voriconazole against fungal central nervous system (CNS) infections was examined retrospectively. METHODS: Voriconazole-treated patients with proven (137) or probable (55) CNS infections were identified in the voriconazole database (114) and the literature (78). Investigator-determined success was a complete or partial response. Survival was calculated from the start of voriconazole therapy. RESULTS: The patients' age range was <1-81 years (median 43) and 127 (66%) were male. Aspergillus spp. (63%) and Scedosporium spp. (18%) predominated, but 12 other genera were recorded. Underlying conditions were haematopoietic stem cell transplantation (HSCT, 35), haematologic malignancy (HM, 35), solid-organ transplantation (SOT, 25), chronic immunosuppression (CI, 40) and other conditions (OC, 57). The median voriconazole therapy duration was 93 days (range 1-1,128), with success in 93 patients (48%). Only 35 patients received primary therapy, with success in 63% versus 45% for salvage (p = 0.06 NS). Underlying conditions influenced success; HSCT 14%, HM 54%, SOT 40%, CI 45% and OC 72% (p < 0.001). Additional antifungal combination therapy (37 patients) gave a trend towards an improved response rate (p = 0.09) and superior survival (p = 0.0149), while patients receiving neurosurgical interventions (72) showed superior responses (p = 0.0174) and survival (p = 0.0399). In all, 49% of patients died, 71% (67/94) due to fungal infection. The overall median survival was 297 days (range 3 to >2,000). Paediatric (p = 0.014) and literature patients (p < 0.001) exhibited superior survival compared with adults and voriconazole database patients, respectively. CONCLUSIONS: Voriconazole shows encouraging efficacy against various CNS fungal infections. Combination therapy and/or CNS surgery may improve outcomes.
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Antifúngicos/uso terapéutico , Infecciones Fúngicas del Sistema Nervioso Central/tratamiento farmacológico , Infecciones Fúngicas del Sistema Nervioso Central/microbiología , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aspergilosis/tratamiento farmacológico , Aspergilosis/microbiología , Aspergillus/patogenicidad , Infecciones Fúngicas del Sistema Nervioso Central/patología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Scedosporium/patogenicidad , Resultado del Tratamiento , Voriconazol , Adulto JovenRESUMEN
Tolerability of azithromycin oral suspension, 10 mg/kg once daily for 3 days, was assessed in paediatric patients (< or = 18 years) with respiratory or skin and soft-tissue infections. Of 2425 patients evaluated, 1213 received azithromycin and 1212 received standard regimens of amoxycillin/clavulanic acid, cefaclor, cefixime, ceftriaxone, clarithromycin, erythromycin, or penicillin V. The incidence of treatment-related adverse events was significantly lower in patients receiving azithromycin than comparators (7.9 vs. 11.5%, P=0.003), while discontinuation rates were similar (1.0 and 1.1%, respectively). Significantly fewer gastrointestinal events were recorded for azithromycin than comparators (6.5 vs. 9.9%, P=0.002), and their duration was significantly shorter (mean 2.3 vs. 5.0 days, P=0.0001). Azithromycin paediatric oral suspension is well tolerated and associated with significantly fewer adverse events than comparators.
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Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infecciones de los Tejidos Blandos/tratamiento farmacológicoRESUMEN
Recently psychologists have questioned the traditional model of grief, arguing that the continuation of bonds with the deceased spouse is generally adaptive. Continuing bonds can be seen as attempts to cope with the loss of a spouse but also with the shattering of the normal illusory basic assumptions about the self, the world, and the future. At this time, however, scholarship has provided few concepts to understand how continuing bonds and illusions express adaptive or maladaptive forms of grief. Therefore, the purpose of this article is to identify, in the context of the illusory basic assumptions, the circumstances by which the bond with the deceased is adaptive or maladaptive. So Epstein (1980) distinguished between higher order postulates and lower order postulates. Higher order postulates are an abstract form of schemas, or generalized theories about the self, the world, and the future, that are resistant to changes. On the other hand, lower order postulates are a concrete form of schemas normally flexible and responsive to the changes in the reality of the new situation. On the basis of this distinction, the author argues that higher order bonds or symbolic bonds are adaptive, whereas lower order bonds or concrete bonds are maladaptive.
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Adaptación Psicológica , Pesar , Ilusiones , Relaciones Interpersonales , Esposos , Femenino , Humanos , Ilusiones/psicología , Masculino , Esposos/psicología , Estados UnidosRESUMEN
BACKGROUND: Morning report, a cornerstone of inter nal medicine residency programs for many years, involves a diverse group of teachers and learners with heterogeneous learning goals. METHODS: We distributed a self-administered, cross sectional survey to internal medicine residents to clarify the objectives of the learners at morning report. We selected a convenience sample of internal medicine residents at community- and university-based programs Questions were answered in a Likert scale or multiple-choice format. RESULTS: Residents from 13 residency programs in 7 states participated. We received 356 completed surveys, which represented a 63% response rate. The house staff in our sample preferred that half of the guest attending physicians be generalists. They indicated that the primary function of morning report should be educational, and preferred to discuss the management of a few interesting cases rather than review all patients admitted the previous day. The majority of respondents (60.8%) favored a stepwise presentation of cases to simulate the chronology of receiving information. Disease process, diagnostic workup, and evaluation of tests and procedures were all considered important topics for discussion, while medical ethics and research methods were viewed as less important. Responses varied little when stratified by sex, postgraduate year, type of residency program, subspecialty fellowship plans, or location of medical school. CONCLUSIONS: Residents from a diverse group of programs expressed remarkably similar opinions about morning report. Consistent with the recently increased emphasis on ambulatory care and general internal medicine in residency training, they expressed a desire for about 50% of the guest attending physicians to be generalists. In addition, they preferred a style in which challenging cases were presented in a stepwise manner.
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Medicina Interna/educación , Internado y Residencia/normas , Enseñanza/normas , Adulto , Atención Ambulatoria , Estudios Transversales , Femenino , Humanos , Masculino , Aprendizaje Basado en Problemas/normas , Encuestas y Cuestionarios , Enseñanza/métodos , Estados Unidos , Recursos HumanosRESUMEN
To determine how internists would respond to out-of-hospital emergency medical situations, we surveyed internal medicine residents and attending physicians at urban academic medical centers regarding their willingness to help in five such scenarios. For those scenarios in which they were reluctant to help, they were asked why. Knowledge of Good Samaritan statutes was also assessed. Respondents were most likely to give aid, including mouth-to-mouth resuscitation if necessary, in scenarios involving a man complaining of chest pain in a restaurant (69%) and a call for help on an airplane (54%), and least likely to help a disheveled man lying on the sidewalk (2%). The most common reasons for not helping were a reluctance to perform mouth-to-mouth resuscitation, feeling that it was not one's responsibility to help, and concern about infectious disease. Knowledge of New York's Good Samaritan law was not associated with willingness to help.
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Reanimación Cardiopulmonar , Urgencias Médicas , Conocimientos, Actitudes y Práctica en Salud , Medicina Interna , Adulto , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Based on prior results in large cell lymphoma (LCL) with COPBLAM (Cyclophosphamide, Oncovin, Prednisone, Bleomycin, Adriamycin, Matulane) I and COPBLAM III, CODBLAM (Cyclophosphamide, Oncovin, Dexamethasone, Bleomycin, Adriamycin, Matulane) IV was developed to intensify treatment further by utilizing four sequential cycles of infusional chemotherapy followed by high-dose chemotherapy and cycle active agents. METHODS: Sixty-one patients with LCL, mostly B-cell lymphoma, with 54% >60 years of age, were treated with daily continuous infusion of vincristine 1.0 mg/m2 days 1-2, bleomycin 4 mg/m2 i.v. push x 1 only followed by daily infusion 4 mg/m2 days 1-5, dexamethasone 10 mg/m2 days 1-5, procarbazine 100 mg/m2 orally days 1-5, doxorubicin 35 mg/m2 i.v. push day 1 (escalated), and cyclophosphamide 350 mg/m2 i.v. push day 1 (escalated), all given every 3 weeks for four cycles. After infusions, patients were restaged and treated with single courses of doxorubicin 90 mg/ m2 i.v. push followed at 3 weeks with cyclophosphamide 1500 mg/m2 i.v. push (both with concomitant vincristine 1 mg/m2 i.v. push and dexamethasone 10 mg/m2 p.o. daily for 5 days). Remaining treatment consisted of methotrexate 120 mg/m2 i.v. push with citrovorum rescue, cytarabine 250 mg/m2 i.v. push, and etoposide 100 mg/m2 i.v. infusion over 1 h, all given every 10 days for six cycles. RESULTS: The overall complete response (CR) rate was 88%. Of all patients, 36 (59%) are sustained disease free at a median follow-up time of 55 months. In patients age < or = 60 years, 89% achieved CR and 85% of patients age >60 years attained CR. CR was achieved in 83% of patients with constitutional B-type symptoms, 69% of patients with bulky adenopathy, and 86% of patients with immunoblastic histology. Toxicity was primarily pulmonary, occuring in 15% of patients. One toxic death was observed. CONCLUSIONS: Infusional CODBLAM IV may represent an effective and unique treatment for LCL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Procarbazina/administración & dosificación , Inducción de Remisión , Análisis de Supervivencia , Vincristina/administración & dosificaciónRESUMEN
Elevated constitutive expression of major histocompatibility (MHC) class II antigens occurs in the enterocytes of patients with IBD. It has been suggested that this aberrant expression of class II molecules may play a role in the pathogenesis of IBD. We examined two possible reasons for such a finding. 1) Heightened sensitivity of IBD enterocytes to endogenous gamma interferon (gamma IFN) and 2) enhanced endogenous secretion of gamma interferon by intestinal cells in close proximity to the enterocytes (lamina propria lymphocytes). Constitutive and gamma interferon stimulated HLA-DR and DP density on intestinal epithelial cells (IEC) and peripheral blood monocytes (PBM) from UC patients (IEC n = 13; PBM n = 20), CD patients (IEC n = 14; PBM n = 18) and non-IBD controls (IEC n = 12; PBM n = 20) were measured via flow cytometry (mean channel fluorescence). gamma IFN production by PHA stimulated and unstimulated lamina propria lymphocyte (LPL) cultures of UC patients (n = 11) CD patients (n = 8) and non-IBD controls (n = 11) was measured using a vesicular stomatitis virus/WISH cell bioassay. We found significantly greater gamma IFN secretion by IBD-derived PHA stimulated LPL than from non-IBD stimulated controls (CD = 39.4 +/- 12.4u; UC41.5 +/- 6.8u; NL = 22.4 +/- 8.3u, p less than 0.05) while gamma IFN induced HLA-DR and DP upregulation was no greater in IBD-derived IEC and PBM than in non-IBD controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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Antígenos de Histocompatibilidad Clase II/biosíntesis , Enfermedades Inflamatorias del Intestino/inmunología , Intestinos/inmunología , Monocitos/inmunología , Asma/inmunología , Autoinmunidad , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Relación Dosis-Respuesta a Droga , Epitelio/inmunología , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica/efectos de los fármacos , Antígenos HLA-DP/biosíntesis , Antígenos HLA-DR/biosíntesis , Humanos , Técnicas In Vitro , Interferón gamma/biosíntesis , Interferón gamma/farmacología , Mucosa Intestinal/metabolismoRESUMEN
Three hundred thirty-one women with metastatic breast cancer were randomized to receive combination chemotherapy with either cyclophosphamide, Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ), and fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and fluorouracil (CAF). Patients could not have had prior chemotherapy, although adjuvant chemotherapy was acceptable. Initial doses were 500 mg/m2 of cyclophosphamide and 500 mg/m2 of fluorouracil with either 10 mg/m2 of mitoxantrone or 50 mg/m2 of doxorubicin, administered intravenously (IV) on day 1 and repeated every 3 weeks. There were no statistically significant differences in pretreatment or prior therapy characteristics between the groups. For patients assigned to the CNF and CAF groups, respectively, 25 (18%) were premenopausal, 39 (40%) were estrogen receptor (ER) negative, 39 (38%) had a disease-free interval less than 1 year, and 24 (26%) had received prior adjuvant chemotherapy. All patients were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. None of these parameters were statistically significant favoring one regimen over the other. The response rate (complete [CR] and partial response [PR]) was 29% for the CNF group (95% confidence interval of 22% to 37%) and 37% for the CAF group (95% confidence interval of 29% to 45%). The median response duration and TTF were 171 days and 125 days for the CNF group and 254 days and 147 days for the CAF group, respectively. The median survival times for the CNF group and the CAF group were 377 and 385 days, respectively. The major dose-limiting toxicity for both regimens was leukopenia, manifested as granulocytopenia. The incidence of stomatitis/mucositis was 10% in the CNF group and 19% in the CAF group. Alopecia occurred in 49% of CNF patients (severely for 4%) and in 86% of CAF patients (severely for 39%). Nausea/vomiting occurred in 80% of CNF patients and in 81% of CAF patients; the degree of severity was also comparable. There was significantly less cardiotoxicity observed in the CNF group compared with the CAF group. Although CNF is somewhat less effective in overall response rate, survival curves are identical. CNF can be offered to patients who reject anthracycline-containing regimens because of fear of alopecia.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama , Carcinoma/secundario , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma/tratamiento farmacológico , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Estudios Multicéntricos como Asunto , Pronóstico , Estudios Prospectivos , Calidad de Vida , Distribución Aleatoria , Autoevaluación (Psicología)RESUMEN
The cyclophosphamide, vincristine, prednisone, bleomycin, doxorubicin, procarbazine (COP-BLAM) programs of combination chemotherapy were administered to patients with advanced diffuse large cell lymphoma. The original COP-BLAM programs were designed to deliver intense multidrug therapy maximizing tumor kill. COP-BLAM programs IA and IB, easily administered on an outpatient basis, produced identical 73% complete remissions (CRs) and 55% long-term, disease-free survival (DFS). COP-BLAM III, an outgrowth of studies using infusional therapy, differed from COP-BLAM by using infusional bleomycin and vincristine alternated with bolus vincristine. With COP-BLAM III, 84% CRs, 76% "potential cures," and a 65% DFS were produced at a median follow-up time of 50 months. COD-BLAM IV, using four sequential cycles of infusional chemotherapy, high-dose alternating myelosuppressives (doxorubicin, cyclophosphamide), and cycle-active agents (methotrexate, cytarabine, and etoposide) produced 88% CRs, 67% potential cures, and a 64% DFS at a median follow-up of 24 months. COP-BLAM V employs four to six sequential cycles of infusional chemotherapy tailored to the rapidity of response. Preliminary results in patients with high-risk Hodgkin's disease suggest COP-BLAM V may be effective despite the shortened treatment time. In all programs, prognostic factors were critical determinants in the results achieved, particularly age and rapidity of response.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Evaluación de Medicamentos , Humanos , Infusiones Intravenosas , Prednisona/administración & dosificación , Prednisona/efectos adversos , Procarbazina/administración & dosificación , Procarbazina/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.
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Antraquinonas/uso terapéutico , Antineoplásicos , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Adulto , Anciano , Antraquinonas/efectos adversos , Antineoplásicos/efectos adversos , Gasto Cardíaco/efectos de los fármacos , Ensayos Clínicos como Asunto , Doxorrubicina/efectos adversos , Femenino , Corazón/efectos de los fármacos , Humanos , Leucopenia/inducido químicamente , Menopausia , Persona de Mediana Edad , Mitoxantrona , Estadificación de Neoplasias , Recuento de Plaquetas/efectos de los fármacos , Distribución Aleatoria , Receptores de Estrógenos/análisisRESUMEN
We evaluated the effect of mitoxantrone (Novantrone; dihydroxyanthracenedione) in the treatment of refractory acute leukemia and acute leukemia in relapse. In this study, 70 patients are currently evaluable. Of the 25 patients who received mitoxantrone 10 mg/m2 X 5, two of 10 with ANLL in relapse, one of five with ALL in relapse achieved complete remission, and one of seven with blastic phase CML responded. At a dose of 12 mg/m2 X 5, nine of 22 patients with ANLL in relapse, one of five patients with blastic phase CML and none of the nine patients with ALL responded. At this dose all remissions occurred after one course of treatment. None of the patients with ANLL or ALL refractory to primary therapy achieved a remission. Toxicities encountered with both dose levels were comparable. However, second courses at 12 mg/m2 X 5 led to severe stomatitis and prolonged cytopenia. We conclude that mitoxantrone is effective therapy for ANLL in relapse and that 12 mg/m2 per day X 5 is the optimal dose schedule. A randomized trial comparing daunorubicin with mitoxantrone in combination with cytarabine in untreated patients with ANLL should answer whether mitoxantrone is less toxic and whether it should replace daunorubicin in standard induction therapy in ANLL.
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Antraquinonas/uso terapéutico , Antineoplásicos , Leucemia/tratamiento farmacológico , Enfermedad Aguda , Adulto , Anciano , Antraquinonas/efectos adversos , Antineoplásicos/efectos adversos , Sistema Digestivo/efectos de los fármacos , Evaluación de Medicamentos , Femenino , Corazón/efectos de los fármacos , Humanos , Leucemia Linfoide/tratamiento farmacológico , Leucemia Mieloide/tratamiento farmacológico , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , MitoxantronaAsunto(s)
Aberraciones Cromosómicas , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Médula Ósea/ultraestructura , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana EdadRESUMEN
A time-honored industrial engineering technique, job evaluation, which was developed to set rates for manual labor, was used in the design of new teams for delivering primary health care in Latin America. The technique was used both in writing job descriptions for new allied health personnel and in designing the curriculums needed to train the personnel.
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Técnicos Medios en Salud , Perfil Laboral , Administración de Personal , Atención Primaria de Salud/métodos , Países en Desarrollo , Humanos , América Latina , México , Trastornos Nutricionales/terapia , Análisis y Desempeño de TareasRESUMEN
Patients with advanced ovarian carcinoma, Stage III or IV (International Federation of Gynaecology and Obstetrics), were randomized to primary chemotherapy with doxorubicin (Adriamycin) and cisplatin plus or minus hexamethylmelamine, and cyclophosphamide (CHAP). The four-drug CHAP regimen produced a 57% complete clinical response rate and a 26% partial response rate for clinically evaluable patients. The median survival of CHAP patients is 25 months. The two-drug Adriamycin-cisplatin (AP) regimen produced a 43% complete response rate and a 35% partial response rate. The median survival is 18 months. The four-drug regimen produced a significantly longer median survival (28 versus 18 months) for patients with poorly differentiated tumors than for patients with well-differentiated tumors on either treatment. Examination of treatment failure or death by treatment, histology, and size of largest residual tumor and comparison to similar patients treated with AP in this and two preceding controlled trials also suggest that CHAP is superior to AP for patients with poorly differentiated tumors.