RESUMEN
OBJECTIVE: To evaluate the efficacy and safety of topical alitretinoin gel (9-cis-retinoic acid [LGD1057], Panretin gel; Ligand Pharmaceuticals, Inc, San Diego, Calif) in cutaneous Kaposi sarcoma (KS). DESIGN: Open-label, within-patient, controlled, dose-escalating phase 1 and 2 clinical trials. In all patients, 1 or more cutaneous KS lesions were treated with alitretinoin gel, and at least 2 other lesions served as untreated controls for up to 16 weeks. Alitretinoin (0.05% or 0.1% gel) was applied twice daily for the first 2 weeks and up to 4 times daily thereafter, if tolerated. SETTING: Nine academic clinical centers. PATIENTS: One hundred fifteen patients with biopsy-proven acquired immunodeficiency syndrome (AIDS)-related KS. MAIN OUTCOME MEASURES: AIDS Clinical Trials Group response criteria. RESULTS: Statistically significant clinical responses were observed in 31 (27%) of 115 patients for the group of treated index lesions compared with 13 (11%) for the group of untreated control lesions (P<.001). Responses occurred with low CD4(+) lymphocyte counts (<200 cells/microL) and in some patients with refractory response to previous systemic anti-KS therapy. The incidence of disease progression was significantly lower for treated index lesions compared with untreated control lesions (39/115 [34%] vs 53/115 [46%]; P =.02). Alitretinoin gel generally was well tolerated, with 90% of treatment-related adverse events confined to the application site and only mild or moderate in severity. CONCLUSIONS: Alitretinoin gel has significant antitumor activity as a topical treatment for AIDS-related KS lesions, substantially reduces the incidence of disease progression in treated lesions, and is generally well tolerated.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Sarcoma de Kaposi/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Tretinoina/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/patología , Administración Cutánea , Adulto , Alitretinoína , Antineoplásicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Geles , Humanos , Masculino , Persona de Mediana Edad , Sarcoma de Kaposi/patología , Neoplasias Cutáneas/patología , Resultado del Tratamiento , Tretinoina/administración & dosificación , Estados UnidosRESUMEN
Thymopentin, 50 mg subcutaneously (s.c.) 3 times per week, was evaluated in a double-blind, randomized, placebo-controlled trial of zidovudine (AZT)-treated asymptomatic human immunodeficiency virus (HIV)-infected subjects with 200-500 CD4 cells/mm3 at entry. The 352 subjects were prestratified by prior AZT use into stratum I (235 subjects, > 6 months AZT at entry) and stratum II (117 subjects, < or = 6 months AZT at entry). Clinical end points, CD4 cell counts, serum p24, serum immune complex dissociated (ICD) p24, and safety variables were evaluated through 48 weeks, using an intent-to-treat analysis. The two strata were analyzed individually because they yielded different clinical outcomes, with a statistically significant treatment-by-stratum interaction. In stratum I (mean, 16 months AZT at entry) two AIDS or death events occurred in thymopentin and 10 in placebo recipients (p = 0.024; relative risk (RR) estimate, 4.9 [95% confidence limit (CI), 1.1 to 22.2]). There were three AIDS-related complex (ARC), AIDS, or death events in thymopentin and 18 in placebo recipients [p = 0.001; RR estimate, 5.9 (95% CI, 1.7 to 20.0)]. In stratum II (mean, 3 months AZT at entry), four AIDS or death events occurred in thymopentin and none in placebo recipients (p = 0.11), and four ARC, AIDS, or death events occurred in thymopentin and two in placebo recipients (p = 0.79). The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities. Thus, AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC, AIDS, or death, and these rates were reduced by thymopentin treatment. In contrast, placebo-treated subjects with little prior AZT experience had low progression rates; these were not significantly changed by thymopentin treatment. There was no increase in the incidence of adverse reactions with thymopentin.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Timopentina/uso terapéutico , Zidovudina/uso terapéutico , Adulto , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Método Doble Ciego , Farmacorresistencia Microbiana/genética , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , VIH/efectos de los fármacos , VIH/genética , Proteína p24 del Núcleo del VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Pentamidina/uso terapéutico , Neumonía por Pneumocystis/prevención & control , Pronóstico , Modelos de Riesgos Proporcionales , Timopentina/administración & dosificación , Timopentina/efectos adversos , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoAsunto(s)
Protocolos Clínicos , Fibroblastos/trasplante , Productos del Gen env/genética , Productos del Gen env/inmunología , Infecciones por VIH/terapia , VIH-1 , Adulto , Determinación de la Elegibilidad , Femenino , Estudios de Seguimiento , Productos del Gen env/administración & dosificación , Técnicas de Transferencia de Gen , Terapia Genética , Infecciones por VIH/inmunología , Humanos , Inmunización Secundaria , Inmunoterapia , Masculino , Factores de Riesgo , Seguridad , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Zidovudina/efectos adversos , Adulto , Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Transfusión Sanguínea , Médula Ósea/efectos de los fármacos , Método Doble Ciego , Eritropoyetina/administración & dosificación , Eritropoyetina/análisis , Femenino , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Zidovudina/administración & dosificación , Zidovudina/uso terapéuticoRESUMEN
Several neurologic syndromes (including Guillain-Barré) complicated Mycoplasma pneumoniae pneumonitis in a young man. At onset of neurologic disease, buffy coat and cerebrospinal fluid cultures on inert media were negative for M. pneumoniae. However, metabolically active mycoplasma were identified in both body fluids by enhanced uptake of 14C-uracil versus 3H-uridine, with marked reduction in normal uridine-to-uracil uptake ratios (> 1000:1) in tissue culture. Uridine-to-uracil ratios were 8.5:1 and 15:1 for buffy coat and cerebrospinal fluid, respectively. Indirect fluorescent antibody (FA) studies confirmed the species as M. pneumoniae. In convalescence, uridine-to-uracil ratios and FA studies of buffy coat normalized, indicating clearance of M. pneumoniae from blood. Cell lines inoculated with "convalescent" cerebrospinal fluid showed slightly increased uracil uptake, slightly decreased uptake ratios, and persistent FA staining of approximately 5% of cells, indicating incomplete clearance of M. pneumoniae. Immune complexes were undetectable in either buffy coat or spinal fluid. This indicates that certain M. pneumoniae-associated neurologic disorders may be related to direct neural infection and not immunologically mediated as has been suggested.
Asunto(s)
Mycoplasma pneumoniae/aislamiento & purificación , Neumonía por Mycoplasma/complicaciones , Polirradiculoneuropatía/etiología , Adulto , Radioisótopos de Carbono , Línea Celular , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Mycoplasma pneumoniae/metabolismo , Neumonía por Mycoplasma/líquido cefalorraquídeo , Polirradiculoneuropatía/líquido cefalorraquídeo , Polirradiculoneuropatía/diagnóstico , Tritio , Uracilo/metabolismo , Uridina/metabolismoRESUMEN
Fourteen patients are described with a syndrome of methicillin-induced interstitial nephritis. In all patients severe renal dysfunction developed with an average peak serum creatinine of 8 mg/100 ml. An increased total peripheral eosinophil count was found in all patients. All patients had sterile pyuria and each of nine patients studied by Wright's stain of urine sediment had marked eosinophiluria. These findings are suggestive of methicillin-induced interstitial nephritis, although proteinura was a variable finding in our patients. Eight of 14 patients in our study received prednisone therapy for their interstitial nephritis, and the time lapse between maximal and final base line serum creatinine levels was statistically less in the prednisone-treated compared to the nontreated groups. Clinical manifestations of this syndrome are discussed, and the light and electron microscopic and immunofluorescent findings on renal biospy are described.
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Meticilina/efectos adversos , Nefritis Intersticial/inducido químicamente , Adulto , Femenino , Humanos , Riñón/patología , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Nefritis Intersticial/diagnóstico , Nefritis Intersticial/tratamiento farmacológico , Prednisona/uso terapéuticoRESUMEN
Treatment of cutaneous Herpesvirus hominis type 2 infection in albino guinea pigs with 8-methoxypsoralen plus long-wave ultraviolet light was evaluated by clinical assessment and quantitative viral cultures. There was a statistically significant difference between the treated animals and the controls in relation to vesicular development, rate of healing, and viral titers. The treatment was effective after the appearance of lesions, when viral multiplication has already begun.
Asunto(s)
Herpes Simple/terapia , Metoxaleno/uso terapéutico , Fotoquimioterapia , Enfermedades Cutáneas Infecciosas/terapia , Terapia Ultravioleta , Animales , Modelos Animales de Enfermedad , Cobayas , Factores de TiempoRESUMEN
Bacteremia was documented in 19 (76%) of 24 patients with sepsis caused solely by decubitus ulcers, persisted in all but two, and was polymicrobial in 10 (42%). Obligate anaerobes were isolated from 12 patients (63%) and included Bacteroides fragilis in 11 (58%). Aerobes, primarily Proteus (21%) and Staphylococcus (16%), were isolated in nine patients (47%). Therapy was judged appropriate when the microbial isolates were susceptible in vitro to the antibiotic used. Nineteen patients received clindamycin plus gentamicin, which was considered appropriate for all but one patient. Four patients received cephalothin plus kanamycin, which was inappropriate for three patients. One patient received appropriate treatment with methicillin, gentamicin, and chloramphenicol. Patients who received appropriate antibiotics and had surgical intervention had the lowest mortality rate (14%); in those treated with appropriate antibiotics but without surgical intervention, the incidence of death was 67% (P less than 0.05). Patients who received inappropriate antibiotics, whether or not there was surgical intervention, had a 75% mortality rate (P less than 0.05). Surgical debridement and antibiotic therapy effective against aerobic as well as anaerobic bacteria are important factors in the treatment of sepsis caused by decubitus ulcers.
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Infecciones Bacterianas/tratamiento farmacológico , Clindamicina/uso terapéutico , Úlcera por Presión/complicaciones , Aerobiosis , Anaerobiosis , Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Infecciones Bacterianas/etiología , Infecciones Bacterianas/microbiología , Sangre/microbiología , Humanos , Especificidad de la EspecieAsunto(s)
Urgencias Médicas , Síndrome de Dificultad Respiratoria del Recién Nacido/diagnóstico , Absceso/diagnóstico , Adolescente , Adulto , Anciano , Obstrucción de las Vías Aéreas/diagnóstico , Infecciones Bacterianas/diagnóstico , Niño , Preescolar , Difteria/diagnóstico , Femenino , Hemoneumotórax/diagnóstico , Humanos , Hipoventilación/diagnóstico , Hipoxia/diagnóstico , Lactante , Recién Nacido , Laringitis/diagnóstico , Masculino , Persona de Mediana Edad , Micosis/diagnóstico , Enfermedades Faríngeas/diagnóstico , Neumonía/microbiología , Polineuropatías/diagnóstico , Rabia/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Tétanos/diagnóstico , Parálisis por Garrapatas/diagnóstico , Virosis/diagnósticoRESUMEN
Thirty-one patients with Candida isolated from peritoneal fluid were examined. Twenty-two were considered to have Candida peritonitis. The data on these 22 patients, plus 12 additional patients described in the literature, were reviewed. This infection was observed as a complication of peritoneal dialysis, gastrointestinal surgery or perforation of an abdominal viscus. Recent antibiotic administration seemed to be an important predisposing factor. The disease usually remained localized intra-abdominally, although disseminated candidiasis was also noted in three cases. Clinically significant infection could be differentiated from peritoneal contamination with Candida by the presence and persistence of fever, peritoneal signs, peripheral leukocytosis, positive peritoneal cultures for Candida, abnormal films of the abdomen and purulent ascitic fluid. Surgical interventions and removal of infected peritoneal fluid were the cornerstones of therapy. Short-term, low-dose systemic and/or intraperitoneally administered amphotericin B appeared promising in the treatment of unremitting infection. Mortality in treated patients was low and was comparable to that in patients with bacterial peritonitis.
Asunto(s)
Candidiasis , Peritonitis , Adulto , Anfotericina B/uso terapéutico , Candidiasis/etiología , Candidiasis/mortalidad , Candidiasis/terapia , Femenino , Humanos , Masculino , Diálisis Peritoneal/efectos adversos , Peritonitis/etiología , Peritonitis/mortalidad , Peritonitis/terapia , Complicaciones Posoperatorias , Pronóstico , Irrigación TerapéuticaRESUMEN
Among 21 patients with sepsis attributed solely to decubitus ulcers, bacteremia was documented in 16 (76 per cent)9 Bacteremia involved obligate anaerobes in eight patients (50 per cent) and was polymicrobial in eight patients (50 per cent). Twelve of 17 patients who received antibiotics had persistent bacteremia; in five patients, bacteremia was terminated only after surgical debridement. Ten of these 21 patients died, eight despite appropirate antibiotics. Among 14 patients who underwent surgical debridement, only four patients died. Surgical debridement and antibiotics effective against aerobic as well as anaerobic bacteria are both important in the treatment of this serious complication.
Asunto(s)
Úlcera por Presión/complicaciones , Sepsis/etiología , Adulto , Anciano , Antibacterianos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Úlcera por Presión/microbiología , Sepsis/tratamiento farmacológico , Sepsis/microbiologíaAsunto(s)
Coccidioidomicosis/diagnóstico , Adulto , Anciano , Artritis Infecciosa/microbiología , Coccidioides/aislamiento & purificación , Coccidioidomicosis/terapia , Dermatomicosis/microbiología , Femenino , Humanos , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Persona de Mediana Edad , Micetoma/microbiología , Osteomielitis/microbiología , Pericarditis/microbiología , Sinovitis/microbiologíaRESUMEN
Clostridia are rare causes of pleuropulmonary infections in the absence of penetrating chest injuries; only 10 previous cases have been reported from civilian practice. An additional case of a rapidly progressive, necrotizing pneumonia and empyema is reported. Clostridial pneumonia is more likely to occur in patients with underlying pleuropulmonary disease. Unlike clostridial myonecrosis, it is rarely associated with toxemia; its mortality rate is comparable to that of nonclostridial pleuropulmonary infections. Appropriate antimicrobial therapy with surgical drainage of the empyema is the treatment of choice. Among the cases reviewed, an iatrogenic cause of infection involving an invasive procedure into the pleural cavity could be identified in seven of 11 cases. Aspiration of oropharyngeal contents was the likely route of infection in three other cases. In the remaining case, bacteremic seeding of the pleural cavity was the most probable mode of infection.
Asunto(s)
Infecciones por Clostridium , Clostridium perfringens , Empiema/microbiología , Neumonía/microbiología , Clostridium perfringens/aislamiento & purificación , Humanos , Enfermedad Iatrogénica , Masculino , Persona de Mediana Edad , Necrosis , Neumonía/etiología , Neumonía/patologíaRESUMEN
A patient with meningococcal pneumonia which developed following therapy for an earlier episode of pneumococcal pneumonia is presented. This entity is most frequently associated with an antecedent viral respiratory illness and/or a concurrent infection with Hemophilus influenzae or diplococcus pneumoniae. The characteristics of this disease are discussed and the possible pathogenetic mechanisms reviewed.