RESUMEN
To compare frequent measurement with infrequent measurement of human immunodeficiency virus (HIV) RNA levels in the management of antiretroviral therapy, we conducted a clinical strategy study of 206 HIV-infected patients who had <500 CD4 cells/mm(3). Patients were randomized (1.5:1) to undergo frequent monitoring (at baseline and every 2 months) or infrequent monitoring (at baseline and twice yearly), with CD4 cell counts determined every 2 months. Patients received unrestricted antiretroviral therapy. In the primary analysis (at month 6), the frequent group had a mean HIV RNA reduction (+/- standard deviation) of 0.93+/-0.79 log(10) copies/mL, versus 0.48+/-0.83 log(10) copies/mL for the infrequent group (P=.0002). A trend (P=.1) toward improved survival was seen in the frequent group. Given this improved virological response, more frequent HIV RNA measurement than is recommended in published guidelines (every 3-4 months) may be appropriate.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , ARN Viral/sangre , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/virología , VIH-1/fisiología , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Claritromicina/uso terapéutico , Complejo Mycobacterium avium/efectos de los fármacos , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Adulto , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Claritromicina/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Quimioterapia Combinada/uso terapéutico , Etambutol/uso terapéutico , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Masculino , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
In some countries, excessive non-measles-related mortality has been observed among female recipients of high-titer measles vaccines. We determined if differences in the immune response to measles vaccines underlie the excessive female mortality by measuring the measles virus (MV)-specific antibody-dependent cellular cytotoxicity (ADCC) antibody response in 65 3-year-old Gambian children immunized with Edmonston-Zagreb medium-titer (EZ) or Schwarz standard vaccines during infancy. Among the 20 females and 22 males with undetectable anti-MV antibodies at the time of immunization, females had significantly lower ADCC than males (median cytotoxicities of 1/100 serum dilutions = 8.4 and 12%, respectively; P = 0.04). This sex-associated difference was present only among the six female and seven male recipients of EZ vaccine (median cytotoxicities = 5.1 and 19.0%, respectively; P = 0.02). There were no significant sex-associated differences in neutralizing antibody activity. Decreased ADCC antibody activity may contribute to the lower survival rate observed in females receiving high-titer measles vaccination.
Asunto(s)
Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Vacuna Antisarampión/efectos adversos , Vacuna Antisarampión/inmunología , Virus del Sarampión/inmunología , Preescolar , Femenino , Gambia , Humanos , Masculino , Pruebas de Neutralización , Caracteres SexualesRESUMEN
The exact immune defects leading to human immunodeficiency virus (HIV)-associated opportunistic infections, malignancies, and death are unknown. In this study, the relationship between survival and 2 immune functions, cytomegalovirus-specific antibody-dependent cellular cytotoxicity (ADCC) and natural killer (NK) activity, was determined by using peripheral blood mononuclear cells from 39 severely immunocompromised patients (median CD4 count, 7). Median follow-up was 414 days; 15 subjects died and 24 remained alive. In a Kaplan-Meier analysis, high baseline ADCC (>median) was associated with improved survival (P=.05). A similar trend was observed for NK activity (P=.1). In a multivariate model controlling for baseline CD4 cell count, HIV RNA, and use of protease inhibitors during follow-up, high ADCC, but not high NK activity, remained significantly associated with a lower risk of death (relative risk, 0.18; 95% confidence interval, 0.05-0.75). ADCC may be an important determinant of disease progression independently of anti-retroviral therapy, CD4 cell count, and HIV RNA.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Citotoxicidad Celular Dependiente de Anticuerpos , Infecciones por Citomegalovirus/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/mortalidad , Adulto , Anciano , Recuento de Linfocito CD4 , Estudios de Cohortes , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/mortalidad , Retinitis por Citomegalovirus/inmunología , Retinitis por Citomegalovirus/mortalidad , Femenino , Humanos , Huésped Inmunocomprometido , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , ARN Viral/sangre , Tasa de Supervivencia , Factores de TiempoRESUMEN
During a randomized study of clarithromycin plus clofazimine with or without ethambutol in patients with AIDS and Mycobacterium avium complex (MAC) bacteremia, eight participants received additional antimycobacterial drugs following the detection of a clarithromycin-resistant isolate (MIC, > 8 micrograms/mL). A macrolide (seven received clarithromycin, one azithromycin) and clofazimine were continued; additional treatment included various combinations of ethambutol, ciprofloxacin, amikacin, and rifabutin. After the detection of a resistant isolate and before receipt of additional antimycobacterials, the median peak MAC colony count in blood was 105 cfu/mL (range, 8-81,500 cfu/mL). After additional antimycobacterials, the median nadir MAC colony count was 5 cfu/mL (range, 0-110 cfu/mL). Five (63%) of eight patients had a > or = 1 log10 decrease, including two who achieved negative blood cultures; all of these responses occurred in patients originally assigned to clarithromycin plus clofazimine. Treatment of clarithromycin-resistant MAC bacteremia that emerges during clarithromycin-based treatment can decrease levels of bacteremia and transiently sterilize blood cultures.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Bacteriemia/tratamiento farmacológico , Quimioterapia Combinada/uso terapéutico , Complejo Mycobacterium avium/efectos de los fármacos , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Bacteriemia/microbiología , Ciprofloxacina/uso terapéutico , Claritromicina/farmacología , Clofazimina/uso terapéutico , Farmacorresistencia Microbiana , Etambutol/uso terapéutico , Humanos , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/microbiología , Rifabutina/uso terapéuticoRESUMEN
The pathophysiology of chronic hepatitis in rabbits infected with coxsackievirus B5 (CVB5), (strain Mitchell) was investigated. Three-week-old male New Zealand White rabbits were inoculated intraperitoneally with 1 x 10(5) plaque forming units of virus. Every 3 months for 15 months postinoculation (p.i.) groups of animals were sacrificed for the following tests: interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-beta cytokine levels by enzyme-linked immunosorbent assay (ELISA); splenic natural killer (NK) cell function; sequence of a 154-bp section of the 5' noncoding region; antihepatocyte autoantibodies; histologic examination; in situ polymerase chain reaction (ISPCR) of the liver; neutralizing antibody response to CVB5; and viral cultures of liver, spleen, blood, brain, heart, skeletal muscle, and pancreas samples. Histologic evidence of hepatocyte necrosis was evident at each time point, although few inflammatory cells were seen. Liver samples were positive at each time by ISPCR, with viral nucleic acid localized to hepatocyte cytoplasm. Other cells in the liver did not stain. No hepatocyte autoantibodies were detected, and there was no elevation of intrahepatic cytokine levels compared to uninfected controls. There were no mutations in the virus over time. A vigorous neutralizing antibody response to CVB5, Mitchell was generated, but splenic natural killer (NK) function and numbers of splenic NK cells were significantly decreased. Virus culture was positive at 3 months, but negative at further time points. Cultures were negative at 3 months for the other tissues tested. Thus, CVB5, Mitchell causes a chronic hepatitis in rabbits, with virus limited to hepatocyte cytoplasm and no evidence of autoimmunity.
Asunto(s)
Infecciones por Coxsackievirus/inmunología , Enterovirus Humano B , Hepatitis Crónica/inmunología , Hepatitis Viral Animal/inmunología , Hígado/inmunología , Animales , Autoanticuerpos/análisis , Infecciones por Coxsackievirus/patología , Infecciones por Coxsackievirus/virología , Enterovirus Humano B/inmunología , Enterovirus Humano B/aislamiento & purificación , Enterovirus Humano B/fisiología , Hepatitis Crónica/patología , Hepatitis Crónica/virología , Hepatitis Viral Animal/patología , Hepatitis Viral Animal/virología , Células Asesinas Naturales , Hígado/patología , Hígado/virología , Masculino , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/análisis , Conejos , Bazo/inmunologíaRESUMEN
In humans, eight monosaccharides are required for the synthesis of glycoproteins. Dietary supplements that supply these crucial sugars are known as glyconutrients. A glyconutrient compound was added to Peripheral Blood Mononuclear Cells (PBMC) isolated from normal controls and patients with the Chronic Fatigue Syndrome (CFS), a disease associated with immune dysregulation. The in vitro immunomodulatory effects were investigated. Cell surface expression of the glycoproteins CD5, CD8, and CD11a were significantly lower in patients with CFS compared to normal controls. Addition of glyconutrient homogenate to PBMC from patients with CFS stimulated with phytohemagglutinin significantly increased the expression of each glycoprotein. Furthermore, natural killer (NK) cell function was reduced in CFS patients. The glyconutrient preparation significantly enhanced NK cell activity versus human herpes virus 6 (HHV-6)-infected H9 cells in an 8 h 51Cr release assay compared to placebo for PBMC from patients with CFS (p< .01). Finally, apoptosis was significantly higher in patients with CFS. The percentage of apoptotic cells was significantly decreased in PBMC from patients with CFS that had been incubated for 48 h with glyconutrients. Thus, glyconutrients improved abnormal immune parameters in vitro in patients with CFS.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Síndrome de Fatiga Crónica/inmunología , Monocitos/inmunología , Adulto , Antígenos de Superficie/metabolismo , Apoptosis/fisiología , Radioisótopos de Cromo , Síndrome de Fatiga Crónica/tratamiento farmacológico , Femenino , Humanos , Células Asesinas Naturales/inmunología , Cinética , Masculino , Monocitos/efectos de los fármacosRESUMEN
Combined hepatitis B surface antigen and hepatitis C antigen were encapsulated into 1, 2, and 5 microm discrete liposomes and then lyophilized. Groups of adolescent CD-1 mice were given a single 0.3 mL oral dose of these liposomes containing 50 microg/mL hepatitis B surface antigen and hepatitis C antigen, 50 microg/mL of the same antigens or liposomes alone. Animals in each group were sacrificed every 2 weeks for 10 weeks and the humoral response investigated by enzyme-linked immunosorbent assay (ELISA) and the cellular response by splenic lymphocyte proliferation to 10 microg of either antigen. Seroconversion to both antigens in the mice receiving liposomal antigens occurred in 87.5% of animals sacrificed at 4 weeks and later. One animal (12.5%) receiving antigen alone seroconverted to hepatitis B virus at 6 weeks, but all animals receiving liposomes alone remained negative. Proliferation indexes (PI) greater than 3 were observed in all animals receiving liposomal antigens, with the greatest response seen at 10 weeks. PI was less than 2 for all animals in the other two groups. Thus, a single oral dose of liposomes of three sizes containing both hepatitis B and C antigens given to mice resulted in rapid seroconversion and a progressive robust cellular immune response, whereas the antigens alone or liposomes without antigen did not.
Asunto(s)
Vacunas contra Hepatitis B/inmunología , Vacunas contra Hepatitis Viral/inmunología , Animales , Formación de Anticuerpos , Portadores de Fármacos , Inmunidad Celular , Liposomas , Masculino , RatonesRESUMEN
Serologic case-control studies have suggested an association between coxsasckie group B viruses and insulin-dependent diabetes mellitus (IDDM). New investigations have identified enteroviral nucleic acid in the peripheral blood mononuclear cells of newly-diagnosed patients with IDDM. The disease pathogenesis is dependent on several factors. including the genetics of the host, strain of virus, activation status of autoreactive T-cells, upregulation of pancreatic MHC-1 antigens, molecular mimicry between viral and beta cell epitopes and direct islet cell destruction by viral cytolysis. Epitopes (IDDM-E1 and E2) on glutamate decarboxylase 65 (GAD65) are the most common targets for antibody and cellular-mediated autoimmune beta cell destruction.
Asunto(s)
Infecciones por Coxsackievirus/fisiopatología , Diabetes Mellitus Tipo 1/virología , Enterovirus Humano B/inmunología , Animales , Autoinmunidad , Infecciones por Coxsackievirus/inmunología , Diabetes Mellitus Tipo 1/inmunología , Glutamato Descarboxilasa/inmunología , Humanos , Islotes PancreáticosRESUMEN
Patients with AIDS and Mycobacterium avium complex (MAC) bacteremia are at high risk for relapse and emergence of resistant isolates during monotherapy with clarithromycin. Ninety-five AIDS patients with MAC bacteremia received clarithromycin plus clofazimine, with or without ethambutol, in a prospective, multicenter, randomized open-label trial. Of 80 patients with positive baseline cultures, sterilization or a 2 log10 reduction in colony-forming units of MAC in two consecutive blood cultures occurred in 69% of both groups. There were nine relapses in the two-drug arm and three in the three-drug arm. Kaplan-Meier estimates of risk of relapse at 36 weeks were 68% and 12%, respectively (P = .004). All relapse isolates were resistant to clarithromycin. Median time to clarithromycin resistance was 16 weeks with two drugs and 40 weeks with three drugs (P = .004). Ethambutol reduced relapses and emergence of clarithromycin resistance and should be considered an essential component of clarithromycin-based therapies for MAC bacteremia.
Asunto(s)
Antibacterianos/administración & dosificación , Antituberculosos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Claritromicina/administración & dosificación , Etambutol/administración & dosificación , Infección por Mycobacterium avium-intracellulare/tratamiento farmacológico , Adulto , Claritromicina/efectos adversos , Farmacorresistencia Microbiana , Quimioterapia Combinada , Etambutol/efectos adversos , Femenino , Humanos , Masculino , Estudios Prospectivos , RecurrenciaRESUMEN
It was observed that 23-day-old New Zealand white rabbits came down with acute hepatitis demonstrable 3 days after intraperitoneal injection with 12 coxsackievirus group B strains. The model was used to evaluate a polyvalent, formalin-inactivated virus vaccine prepared with prototype strains of coxsackievirus groups B1-6. Seven-day-old animals received one intraperitoneal and two subcutaneous injections containing the vaccine or placebo. The regimen was repeated at 15 days of age. At 23 days of age, groups of rabbits were challenged with 1 x 10(5) plaque-forming units of a clinical strain of group B coxsackievirus and sacrificed 3 days later. The mean neutralizing antibody titer for the 12 strains tested (log2) was 4.5 +/- 1.0 eight days after the second dose of vaccine. In vaccinated animals, elevated liver function tests in the serum, and titer of virus and histopathologic abnormalities in the liver were significantly reduced for each strain tested compared with infected, unvaccinated controls. Cultures of the heart, skeletal muscle, pancreas, blood, and spleen were all negative. Thus, clinical strains of coxsackie group B viruses produced isolated hepatitis in baby rabbits. Prophylaxis with a polyvalent, inactivated-virus vaccine significantly reduced the severity of liver involvement for all 12 clinical strains tested.
Asunto(s)
Infecciones por Coxsackievirus/prevención & control , Enterovirus Humano B/inmunología , Hepatitis Viral Animal/prevención & control , Vacunas Virales/inmunología , Enfermedad Aguda , Animales , Anticuerpos Antivirales/sangre , Femenino , Formaldehído , Embarazo , Conejos , Vacunación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Natural killer (NK) cells are important effectors for the lysis of both neoplastic and virus-infected cells. Lectin-like receptors on human NK cells, such as NKR-PIA and CD94, bind to target cell carbohydrate ligands and initiate the lytic process. In addition, P58 and P70 bind to major histocompatibility class I antigens on targets and mediate negative signals. Models using NK cell-deficient mice have proven useful in elaborating the role of NK cells in the immune defence against multiple viral agents. In addition, studies in humans have suggested a vital role of NK cells in the host defence against human immunodeficiency virus, herpesviruses, hepatitis B and C and other viruses. Several genetic disorders, chronic illnesses and infections have been associated with decreased NK function.
Asunto(s)
Células Asesinas Naturales/fisiología , Lectinas Tipo C , Virosis/fisiopatología , Animales , Antígenos CD/metabolismo , Antígenos de Superficie/metabolismo , Muerte Celular , Humanos , Lectinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Ratones , Subfamilia B de Receptores Similares a Lectina de Células NK , Subfamília D de Receptores Similares a Lectina de las Células NK , Receptores Mitogénicos/metabolismoRESUMEN
A rule-based expert system, Customized Treatment Strategies for HIV (CTSHIV), which encodes information from the literature on known drug-resistant mutations was developed. Additional rules include ranking and weighting based on antiviral activities, redundant mechanisms of action, overlapping toxicities, relative levels of drug-resistance, and proportion of drug-resistant clones in the HIV quasispecies. Plasma was obtained from HIV-infected patients and the RNA was extracted. Segments of the HIV pol gene encoding the entire protease, reverse transcriptase, and integrase proteins were amplified by reverse transcriptase-polymerase chain reaction (using a total of three primer pairs) and cloned. Sequencing was performed on five clones from each of two patients. When the patient's RNA sequencing data were entered into the expert program, and the information was downloaded directly into the CTSHIV program, the five most effective two, three, and four drug regimens coupled with an explanation for their choice were displayed for each patient. Thus, the CTSHIV system couples efficient genetic sequencing with an expert program that recommends regimens based on information in the current medical literature. It may serve as a useful tool in the design of clinical trials and in the management of HIV-infected patients.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Quimioterapia Asistida por Computador , Sistemas Especialistas , Infecciones por VIH/tratamiento farmacológico , VIH/efectos de los fármacos , Fármacos Anti-VIH/farmacología , Clonación Molecular , Resistencia a Medicamentos/genética , Genes pol , VIH/genética , Humanos , Mutación , Reacción en Cadena de la PolimerasaRESUMEN
Extracts of Echinacea purpurea and Panax ginseng were evaluated for their capacity to stimulate cellular immune function by peripheral blood mononuclear cells (PBMC) from normal individuals and patients with either the chronic fatigue syndrome or the acquired immunodeficiency syndrome. PBMC isolated on a Ficoll-hypaque density gradient were tested in the presence or absence of varying concentrations of each extract for natural killer (NK) cell activity versus K562 cells and antibody-dependent cellular cytotoxicity (ADCC) against human herpesvirus 6 infected H9 cells. Both echinacea and ginseng, at concentrations > or = 0.1 or 10 micrograms/kg, respectively, significantly enhanced NK-function of all groups. Similarly, the addition of either herb significantly increased ADCC of PBMC from all subject groups. Thus, extracts of Echinacea purpurea and Panax ginseng enhance cellular immune function of PBMC both from normal individuals and patients with depressed cellular immunity.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/inmunología , Citotoxicidad Celular Dependiente de Anticuerpos/efectos de los fármacos , Síndrome de Fatiga Crónica/inmunología , Células Asesinas Naturales/efectos de los fármacos , Panax/química , Extractos Vegetales/farmacología , Plantas Medicinales/química , Síndrome de Inmunodeficiencia Adquirida/sangre , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Adulto , Citotoxicidad Celular Dependiente de Anticuerpos/inmunología , Síndrome de Fatiga Crónica/sangre , Síndrome de Fatiga Crónica/tratamiento farmacológico , Femenino , Humanos , Células Asesinas Naturales/inmunología , Cinética , Masculino , Extractos Vegetales/efectos adversos , Valores de ReferenciaRESUMEN
Thirty patients who fulfilled clinical criteria defined by the CDC for Chronic Fatigue Syndrome were treated with alfa 2a interferon or placebo in a double-blind crossover study. Outcome was evaluated by Natural Killer (NK) cell function, lymphocyte proliferation to mitogens and soluble antigens, CD4/CD8 counts and a 10 item Quality of Life (QOL) survey. Although mean NK function rose from 87.8 +/- 19.6 to 129.3 +/- 20.7 lytic untis (LU; p < .05) with 12 weeks of interferon therapy, there was no significant change in the other immunologic parameters or QOL scores. When the 26 patients who completed the study were stratified according to their baseline NK function and lymphocyte proliferation, 4 groups were identified: 3 patients had normal NK cell function and lymphocyte proliferation when compared to normal, healthy controls, 9 had isolated deficiency in lymphocyte proliferation, 7 had diminished NK function only, and 7 had abnormalities for both parameters. QOL scores were not significantly different for the four groups at baseline. After 12 weeks of interferon therapy, QOL score significantly improved in each of the seven patients with isolated NK cell dysfunction (mean score, 16.3 +/- 7.9) compared to baseline (39.7 +/- 12.1; p < .05). In these patients the mean NK function increased from 35.1 +/- 11.7 to 91.5 +/- 22.7 LU (p < .01). Significant improvement was not recorded for QOL in the other three groups. Thus, therapy with alpha interferon has a significant effect on the QOL of that subgroup of patients with CFS manifesting an isolated decrease in NK function.
Asunto(s)
Antivirales/uso terapéutico , Síndrome de Fatiga Crónica/terapia , Factores Inmunológicos/uso terapéutico , Interferón-alfa/uso terapéutico , Adulto , Estudios Cruzados , Citotoxicidad Inmunológica/efectos de los fármacos , Método Doble Ciego , Síndrome de Fatiga Crónica/inmunología , Síndrome de Fatiga Crónica/psicología , Femenino , Humanos , Interferón alfa-2 , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Recuento de Linfocitos/efectos de los fármacos , Subgrupos Linfocitarios/efectos de los fármacos , Masculino , Persona de Mediana Edad , Calidad de Vida , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
To determine whether functional antibody responses correlate with factors associated with severe measles, measles-specific antibody-dependent cellular cytotoxicity (ADCC) and neutralizing antibodies were measured in 114 Filipino children with measles. Children > 24 months old were more likely to have ADCC antibody in acute sera than were those < or = 24 months (odds ratio = 3.6, 95% confidence interval = 1.7-7.8). This age-related difference in ADCC prevalence was most apparent between younger and older girls. Among children < or = 24 months, a higher prevalence of ADCC antibody was associated with male sex, absence of lymphopenia, and household exposure to measles. The presence of ADCC antibody was not associated with malnutrition or diarrhea. Neutralizing antibody titers were lower in children with lymphopenia but showed no relationship with the other variables. Thus, the ADCC antibody response is associated with some risk factors related to measles severity. Attenuation of this response may contribute to the severity of infection.
Asunto(s)
Anticuerpos Antivirales/sangre , Citotoxicidad Celular Dependiente de Anticuerpos , Sarampión/inmunología , Enfermedad Aguda , Factores de Edad , Preescolar , Femenino , Humanos , Lactante , Masculino , Sarampión/transmisión , Factores SexualesRESUMEN
Male CD-1 mice were challenged with a diabetogenic strain (E2) of coxsackievirus B4 (CVB4). At 7 weeks, 6 months, and 1 year after inoculation, mean histopathologic scores, postprandial blood glucose levels, and serum levels of antibody to islet cells were significantly elevated and mean fasting serum insulin levels significantly reduced in infected mice versus uninfected controls (P < .001 for each). At 7 weeks after infection, viral RNA, but not protein or infectious virus, was demonstrated in the pancreases of most infected mice. The pancreases of 4 of 12 and 0 of 10 infected animals were positive for viral RNA at 6 months and at 1 year after infection, respectively. Interferon-gamma-stimulated peritoneal macrophages were cytotoxic to islet cells with and without sera with high titers of islet cell autoantibody (ICA). Thus, islet cell destruction in mice infected with CVB4 strain E2 is associated with chronic islet cell inflammation, elevation of islet cell antibody, and prolonged presence of viral RNA in the pancreas. Stimulated peritoneal macrophages lyse islet cells directly and by an antibody-dependent mechanism.
Asunto(s)
Infecciones por Coxsackievirus/virología , Diabetes Mellitus/virología , Enterovirus Humano B/patogenicidad , Islotes Pancreáticos/patología , Páncreas/patología , Animales , Autoanticuerpos/sangre , Secuencia de Bases , Glucemia/análisis , Infecciones por Coxsackievirus/inmunología , Infecciones por Coxsackievirus/patología , Pruebas Inmunológicas de Citotoxicidad , Diabetes Mellitus/inmunología , Diabetes Mellitus/patología , Insulina/sangre , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/virología , Masculino , Ratones , Datos de Secuencia Molecular , Especificidad de Órganos , Páncreas/química , Páncreas/virología , ARN Viral/análisisRESUMEN
PURPOSE: Trimethoprim-sulfamethoxazole (TMP/SMX) is the preferred agent for prophylaxis of Pneumocystis carinii pneumonia (PCP) in patients with HIV infection, but frequent adverse events limit its usefulness. Intermittent dosing and supplementation with leucovorin have been tried in attempts to improve tolerance. We evaluated these strategies in persons with advanced HIV disease. METHOD: One hundred seven patients were enrolled. All had HIV infection, < 200 CD4+ lymphocytes per mm3, and no history of PCP. Fifty-two were randomized to TMP/SMX twice daily (BID); of these, 26 were randomized to leucovorin with each dose. Fifty-five patients were randomized to TMP/SMX (BID) 3 times per week; of these, 27 were randomized to leucovorin with each dose. All patients took zidovudine concurrently. RESULTS: The 24-week risk of discontinuation due to protocol-defined limiting toxicity was 24% with thrice-weekly TMP/SMX versus 42% with daily TMP/SMX (risk ratio 0.4; 95% CI 0.2 to 1.0). The risks of discontinuation for any reason were 41% and 59% (risk ratio 0.4; 95% CI 0.2 to 0.8). Clinical toxicity, such as headache and gastrointestinal distress, accounted for the observed difference in tolerance between dosing regimens. The 24-week risk of discontinuation due to protocol-defined toxicity was 33% in both the leucovorin and non-leucovorin groups (risk ratio 1.1; 95% CI 0.5 to 2.5). The risks of discontinuation for any reason were 53% and 47% (risk ratio 0.8; 95% CI 0.3 to 1.7). CONCLUSION: Intermittent therapy with TMP/SMX BID thrice weekly is better tolerated than daily BID therapy. Leucovorin use does not improve tolerance for chronic TMP/SMX dosing in AIDS, even among patients taking tablets daily.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Enfermedades de la Médula Ósea/prevención & control , Leucovorina/uso terapéutico , Neumonía por Pneumocystis/prevención & control , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Zidovudina/efectos adversos , Infecciones Oportunistas Relacionadas con el SIDA/virología , Adolescente , Adulto , Enfermedades de la Médula Ósea/inducido químicamente , Esquema de Medicación , Quimioterapia Combinada , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Neumonía por Pneumocystis/virología , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Zidovudina/uso terapéuticoRESUMEN
Treatment of cryptococcal meningitis with amphotericin B or fluconazole is often unsuccessful; in only 35%-40% of cases do CSF cultures become negative by 10 weeks after initiation of such therapy. We conducted a prospective, open-label clinical trial involving persons with AIDS to determine whether the rate of clinical success would improve when fluconazole (400 mg daily) was combined with flucytosine (150 mg/kg daily). At the conclusion of 10 weeks of therapy, 75% (95% confidence interval, 58%-87%) of 32 subjects' CSF cultures were negative. The Kaplan-Meier estimate of clinical success at 10 weeks was 63% (95% confidence interval, 48%-82%). The median time to negativity of the CSF culture was 23 days. Toxic side effects that were sufficiently severe to lead to the withdrawal of flucytosine were observed in nine subjects (28%). In this pilot study of fluconazole combined with flucytosine, the rate of clinical success at 10 weeks was greater than that previously reported with regard to the use of fluconazole alone or amphotericin B alone.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Fluconazol/uso terapéutico , Flucitosina/uso terapéutico , Meningitis Criptocócica/tratamiento farmacológico , Adulto , Líquido Cefalorraquídeo/microbiología , Cryptococcus neoformans/aislamiento & purificación , Quimioterapia Combinada , Femenino , Fluconazol/administración & dosificación , Flucitosina/administración & dosificación , Flucitosina/efectos adversos , Humanos , Masculino , Meningitis Criptocócica/líquido cefalorraquídeo , Proyectos Piloto , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
The individual antibacterial activities of clofazimine, ethambutol, and rifampin in the treatment of Mycobacterium avium complex bacteremia in patients with AIDS were determined. Sixty human immunodeficiency virus 1-infected patients who had at least one blood culture positive for M. avium complex were randomized to receive either clofazimine (200 mg), ethambutol (15 mg/kg), or rifampin (600 mg) once daily for 4 weeks. Only ethambutol resulted in a statistically significant reduction in the level of mycobacteremia. The median change in individual baseline colony counts was -0.60 log10 cfu/mL after 4 weeks of ethambutol (P = .046). In contrast, median changes in individual baseline colony counts were -0.2 log10 cfu/mL and +0.2 log10 cfu/mL for clofazimine and rifampin, respectively (both, P > .4). Ethambutol had greater antibacterial activity, as determined by changes in the level of mycobacteremia, than either rifampin or clofazimine, supporting its continued use in combination with other agents in the treatment of M. avium infection.