RESUMO
Cytomegalovirus (CMV) transmission via stem cells or marrow in CMV donor seropositive/recipient seronegative (D+/R-) hematopoietic cell transplantation (HCT) is surprisingly inefficient, and factors associated with transmission in these high-risk HCT recipients are unknown. In a retrospective cohort of D+/R- HCT recipients, cumulative incidence curve estimates were used to determine posttransplantation rates of CMV and multivariable Cox proportional models to assess risk factors associated with transmission. A total of 447 patients from 1995 to 2007 were eligible for enrollment. Overall, 85 of 447 (19.0%) acquired CMV at a median of 49 days (IQR 41-60) posttransplantation. CMV disease before day 100 occurred in 6 of 447 (1.3%) patients and in 7 of 447 (1.6%) after day 100. The donor graft, specifically the total nucleated cell count (adjusted hazard ratio [HR] 2.7; 95% confidence interval [CI], 1.4-4.7, P = .0002), was the only factor associated with CMV transmission in multivariable analyses. Notably, the source stem cells (marrow versus peripheral blood stem cell [PBSC]), screening method, and graft-versus-host disease (GVHD) were not associated with transmission. Thus, a highly cellular graft was the only identifiable risk factor associated with CMV transmission, suggesting that viral genomic content of the donor graft determines transmission efficiency in D+/R- HCT recipients.
Assuntos
Anticorpos Antivirais/imunologia , Transplante de Medula Óssea/efeitos adversos , Infecções por Citomegalovirus/transmissão , Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Anticorpos Antivirais/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/imunologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Transplante Homólogo , Estados Unidos/epidemiologiaRESUMO
Herpes virus (cytometalovirus [CMV], herpes simplex virus, varicella zoster virus) and invasive fungal infections continue to cause significant morbidity and mortality in allogeneic hematopoietic cell transplant (HCT) recipients despite the availability of effective therapies. In this study, we developed an Internet-based survey, which was distributed to all hematopoietic cell transplant centers participating in the Center for International Blood and Marrow Transplant Research (CIBMTR) program, to gather information on strategies utilized for the prevention of disease caused by herpes viruses and fungal infections between 1999 and 2003. The survey response rate was 72%, representing 175 programs from 32 countries. Generally, reported center strategies were in accord with the Center for Disease Control and Prevention guidelines published in 2000, with 81% of programs using low-dose acyclovir prophylaxis for herpes simplex virus seropositive patients, 99% of programs reporting use of a CMV prevention strategy during the first 100 days posttransplant for all patients at risk of CMV disease, and 90% of programs using antifungal prophylaxis. Seventy percent of programs reported routine use of a CMV prevention strategy in high-risk patients after day 100. The greatest departure from published guidelines was the use of acyclovir prophylaxis for varicella zoster virus seropositive recipients in 75% of programs. There were very few reported changes within centers in practices over the study time period. Significant regional variations were found with regard to surveillance procedures and treatment durations. There were no significant differences in treatment practices by center size and very few differences found between those centers that reported treating primarily pediatric patients versus primarily adult patients. In summary, our survey demonstrates overall agreement with published guidelines for the prevention of disease because of herpesviruses and fungal infections with significant regional differences found in duration of antiviral prophylaxis, duration of preemptive therapy, and duration and dosing of antifungal prophylaxis. Center size and age of primary patient population were not associated with many reported differences in strategies.
Assuntos
Candidíase/prevenção & controle , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Simples/prevenção & controle , Herpes Zoster/prevenção & controle , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Ásia , Austrália , Candida , Candidíase/tratamento farmacológico , Candidíase/epidemiologia , Candidíase/microbiologia , Criança , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Saúde Global , Pesquisas sobre Atenção à Saúde , Herpes Simples/tratamento farmacológico , Herpes Simples/epidemiologia , Herpes Simples/virologia , Herpes Zoster/tratamento farmacológico , Herpes Zoster/epidemiologia , Herpes Zoster/virologia , Herpesvirus Humano 3 , Humanos , América Latina , Oriente Médio , América do Norte , Simplexvirus , África do Sul , Transplante HomólogoRESUMO
The dermatology service is frequently consulted to assess cutaneous eruptions after hematopoietic stem cell transplantation. We describe a case of cutaneous toxoplasmosis in a stem cell transplant patient where toxoplasmosis trophozoites elicited a reaction pattern mimicking an interface dermatitis. At first blush, these findings may be misinterpreted as either a reaction to a drug or graft-versus-host disease. We hope that this case will prove helpful for dermatopathologists in asserting the correct diagnosis of cutaneous toxoplasmosis-if left untreated or treated incorrectly, this disease has a dismal prognosis.
Assuntos
Doença Enxerto-Hospedeiro/diagnóstico , Dermatopatias Parasitárias/diagnóstico , Toxoplasmose/diagnóstico , Adolescente , Animais , Diagnóstico Diferencial , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pele/parasitologia , Pele/patologia , Dermatopatias Parasitárias/patologia , Toxoplasma/patogenicidade , Toxoplasmose/patologiaRESUMO
Insulin sensitivity and the activity of the hypothalamic-growth hormone (GH)- insulin-like growth factor-I (IGF-I) axis both decline with age. Treatment with IGF-I increases insulin sensitivity in healthy young subjects. We hypothesized that increasing plasma IGF-I in postmenopausal women to levels characteristic of young women would enhance insulin sensitivity. To test the hypothesis, fasting glucose kinetics and insulin sensitivity were measured in 24 healthy, normoglycemic, postmenopausal women before and after 5 weeks of treatment with either recombinant human (rh)IGF-I (15 microg/kg body weight/d twice daily) or placebo in a double-blind study. Diet energy content and composition were rigidly controlled to maintain energy balance. A hyperglycemic clamp (8 mmol/L) coupled with stable isotope infusion ([6,6(2)H]glucose) was performed before and after treatment to assess whole-body insulin sensitivity; defined as the glucose rate of disappearance (Rd) or rate of infusion (GRIF) scaled to the steady-state insulin concentration (I). There were no differences in fasting glucose or insulin concentrations, glucose kinetics, or glucose oxidation after either treatment. During the clamps, steady-state insulin concentrations with placebo (pre = 151 +/- 28 pmol/L, post = 173 +/- 31 pmol/L) were slightly different than with IGF-I (pre = 182 +/- 37 pmol/L, post = 163 +/- 33 pmol/L), but the variations were not significant. No significant changes in whole-body insulin sensitivity were observed after treatment with IGF-I, calculated as Rd/I (pre = 17.7 +/- 2.6 microg/kg/min/pmol/L, post = 19.3 +/- 2.0 microg/kg/min/pmol/L for IGF-I v pre = 24.2 +/- 2.5 microg/kg/min/pmol/L, post = 22.8 +/- 3.4 microg/kg/min/pmol/L for placebo) or as GRIF/I (pre = 18.0 +/- 3.9 microg/kg/min/pmol/L, post = 22.3 +/- 3.5 microg/kg/min/pmol/L for IGF-I v pre = 26.4 +/- 6.2 microg/kg/min/pmol/L, post = 26.9 +/- 4.8 microg/kg/min/pmol/L for placebo). Baseline insulin sensitivity in women using hormone replacement therapy (HRT, n = 15) was similar to nonusers (n = 9), but HRT users derived a greater portion of energy expenditure from carbohydrate oxidation compared with nonusers. HRT use had no impact on the response to IGF-I. Overall, we observed subtle, but physiologically insignificant, variations after IGF-I treatment in the direction of enhanced insulin sensitivity. The data suggest that 5 weeks of low-dose rhIGF-I treatment has no material influence on whole-body insulin sensitivity in normoglycemic postmenopausal women.
Assuntos
Envelhecimento , Glicemia/metabolismo , Técnica Clamp de Glucose , Fator de Crescimento Insulin-Like I/administração & dosagem , Insulina/farmacologia , Glicemia/análise , Composição Corporal , Peso Corporal , Método Duplo-Cego , Metabolismo Energético , Terapia de Reposição de Estrogênios , Jejum , Feminino , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Cinética , Pessoa de Meia-Idade , Oxirredução , Placebos , Pós-Menopausa , Proteínas Recombinantes/administração & dosagemRESUMO
The effect of increasing doses of sun-dried raisins (SDR) on intestinal transit time (TT), fecal weight (FW), and fecal bile acids (FBA) was investigated in 16 healthy adults (6 men and 10 women). In three cycles of 2 weeks each, subjects consumed 84, 126, or 168 g/day of SDR. Four-day fecal collections were performed during the second week of each cycle, and TT, FW, and FBA were measured. FW (mean +/- SEM), increased from 168 +/- 14 g/day without raisins (cycle 1), with a TT of 54 +/- 6 hours, to 200 +/- 24 g/day with 168 g/day raisins (cycle 4), with a TT of 42 +/- 6 hours. Intermediate increases in FW and decreases in TT were observed for cycles 2 and 3. A physiologically meaningful decrease in TT (less than 2 days), to 44 +/- 6 hours, was reached at cycle 2 (not statistically significant). FBA, a possible indicator of colon cancer risk, showed a significant decrease, from 1.00 +/- 0.18 mg/g wet feces at baseline to 0.38 +/- 0.07 mg/g in cycle 2 (P <.005), and remained low in cycles 3 and 4. Major decreases were observed in cycle 2 for fecal lithocholic (P <.02), deoxycholic (P <.002), chenodeoxycholic, and cholic acids, and their concentrations remained low in cycles 3 and 4. Two servings of raisins per day (84 g/day), a relatively small change in diet, can cause beneficial changes in colon function and may decrease the risk for colon cancer.
Assuntos
Ácidos e Sais Biliares/metabolismo , Colo/efeitos dos fármacos , Fezes/química , Trânsito Gastrointestinal/efeitos dos fármacos , Vitis , Adulto , Idoso , Idoso de 80 Anos ou mais , Ácidos e Sais Biliares/análise , Colo/fisiologia , Neoplasias do Colo/prevenção & controle , Fibras na Dieta/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tartaratos/farmacologiaRESUMO
PROBLEM: Female genital tract secretions inhibit herpes simplex virus (HSV) infection, however, the intra- and inter-subject variability, contribution of specific mediators, and impact of reproductive hormones have not been defined. METHOD: of study Cervicovaginal lavage (CVL) (n = 89) obtained from nine cyclers and seven women on hormonal contraception (HC), who completed between three and eight weekly visits, were examined for anti-herpes simplex virus activity and concentrations of mediators. RESULTS: The CVL inhibited HSV infection by a mean value of approximately 57% during the follicular or luteal phase, but only by 36% in hormonal contraceptive users. Human neutrophil peptides 1-3 (HNP1-3) (P = 0.03), IL-8 (P = 0.003), lactoferrin (P = 0.005), lysozyme (P = 0.003), IgA (P = 0.002), and IgG (P = 0.02) correlated with antiviral activity. Intra-subject and inter-subject variability was observed, suggesting that factors other than hormones contribute to innate defense. CONCLUSION: Endogenous antimicrobial activity may provide a biomarker of healthy mucosal immunity and may be reduced in the setting of HC. However, larger prospective studies are needed.
Assuntos
Genitália Feminina/imunologia , Genitália Feminina/virologia , Herpes Genital/imunologia , Herpes Genital/prevenção & controle , Herpesvirus Humano 2/imunologia , Imunidade nas Mucosas , Adolescente , Adulto , Colo do Útero/imunologia , Anticoncepcionais Orais Hormonais/farmacologia , Feminino , Humanos , Imunidade nas Mucosas/efeitos dos fármacos , Projetos Piloto , Estudos Prospectivos , Solubilidade , Vagina/imunologia , Adulto JovemRESUMO
The effects of prolonged caloric restriction (CR) on protein kinetics in lean subjects has not been investigated previously. The purpose of this study was to test the hypotheses that 21 days of CR in lean subjects would 1) result in significant losses of lean mass despite a suppression in leucine turnover and oxidation and 2) negatively impact exercise performance. Nine young, normal-weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2 +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and 2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1). Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool model in the postabsorptive state during rest and 50 min of exercise (EX) at 50% of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise performance were measured throughout the intervention. At rest, leucine flux (approximately 131 micromol.kg(-1).h(-1)) and oxidation (R(ox); approximately 19 micromol.kg(-1).h(-1)) did not differ pre- and post-CR. During EX, leucine flux (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR than they were pre-CR. Nitrogen balance was negative throughout the intervention ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/- 203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric restriction reduced leucine flux and R(ox) during exercise in normal-weight young men. However, despite negative nitrogen balance and loss of lean mass, whole body exercise performance was well maintained in response to CR.