RESUMO
BACKGROUND: Human papillomavirus (HPV) infection is associated with precancerous cervical squamous intraepithelial lesions commonly seen among women infected with human immunodeficiency virus-1 (HIV). We characterized HPV infection in a large cohort of HIV-positive and HIV-negative women participating in the Women's Interagency HIV Study to determine the prevalence of and risk factors for cervicovaginal HPV infection in HIV-positive women. METHODS: HIV-positive (n = 1778) and HIV-negative (n = 500) women were tested at enrollment for the presence of HPV DNA in a cervicovaginal lavage specimen. Blood samples were tested for HIV antibody status, level of CD4-positive T cells, and HIV RNA load (copies/mL). An interview detailing risk factors was conducted. Univariate and multivariate analyses were performed. RESULTS: Compared with HIV-negative women, HIV-positive women with a CD4+ cell count of less than 200/mm3 were at the highest risk of HPV infection, regardless of HIV RNA load (odds ratio [OR] = 10.13; 95% confidence interval [CI] = 7.32-14.04), followed by women with a CD4+ count greater than 200/mm3 and an HIV RNA load greater than 20,000 copies/mL (OR = 5.78; 95% CI = 4.17-8.08) and women with a CD4+ count greater than 200/mm3 and an HIV RNA load less than 20,000 copies/mL (OR = 3.12; 95% CI = 2.36-4.12), after adjustment for other factors. Other risk factors among HIV-positive women included racial/ethnic background (African-American versus Caucasian, OR = 1.64; 95% CI = 1.19-2.28), current smoking (yes versus no; OR = 1.55; 95% CI = 1.20-1.99), and younger age (age < 30 years versus > or = 40 years; OR = 1.75; 95% CI = 1.23-2.49). CONCLUSIONS: Although the strongest risk factors of HPV infection among HIV-positive women were indicators of more advanced HIV-related disease, other factors commonly found in studies of HIV-negative women, including racial/ethnic background, current smoking, and age, were important in HIV-positive women as well.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/virologia , HIV/isolamento & purificação , Papillomaviridae , Infecções por Papillomavirus/virologia , Lesões Pré-Cancerosas/virologia , Infecções Tumorais por Vírus/virologia , Cervicite Uterina/virologia , Vaginite/virologia , Infecções Oportunistas Relacionadas com a AIDS/complicações , Adulto , Contagem de Linfócito CD4 , Feminino , HIV/genética , HIV/imunologia , Soronegatividade para HIV , Humanos , Modelos Logísticos , Prevalência , RNA Viral/análise , Fatores de Risco , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/virologiaRESUMO
Three measures of body size (weight, height, and obesity) were compared with other patient characteristics in 852 operable node-positive breast cancer patients (age, 25-74 years) newly diagnosed in the United States. Weight and obesity were significantly associated with number of positive nodes. In postmenopausal women, weight and obesity were weakly associated with estrogen receptors. Observed weight and height distributions were compared with national averages and found to be highly aberrant in older women. There was an excess of tall woman (greater than or equal to 66 inches) among the study group in all age groups. An excess of heavy women (greater than or equal to 140 pounds) among the study group was observed only in the 55-74 years age group.
Assuntos
Estatura , Peso Corporal , Neoplasias da Mama/fisiopatologia , Adulto , Fatores Etários , Idoso , Axila , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Menstruação , Pessoa de Meia-Idade , Prognóstico , Receptores de Estrogênio/análise , RiscoRESUMO
Many protocols for treatment of superficial bladder cancer include periodic cystoscopic examinations with resection of visible lesions. This allows pathological restaging of the disease at each examination. For example, this type of follow-up is common in clinical trials evaluating intravesical therapies. In such trials, clinical outcome is typically summarized using end-points that measure failure to control superficial disease. Alternative endpoints measuring failure to prevent progression to invasive disease are often ignored. In this report, the rationale for ignoring the invasive disease endpoints is given and flaws in the rationale are described. Evidence from actual data sets support the view that superficial disease endpoints may not be appropriate surrogates for invasive disease endpoints. It is recommended that time to invasive disease should be considered a major endpoint when designing and analyzing trials in superficial bladder cancer.
Assuntos
Ensaios Clínicos como Assunto , Neoplasias da Bexiga Urinária/terapia , Ensaios Clínicos como Assunto/métodos , Humanos , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/patologiaRESUMO
In a retrospective study of 153 testis cancer survivors, we examined the sociodemographic and clinical determinants of attitudes and behaviors toward illness-induced infertility. Five fertility adjustment responses were identified: sperm-banking awareness (SBA); adoption awareness (AA); fertility testing (FT); trying to father children (TFC); and fertility distress (FD). Although responses to infertility are multidetermined, these data demonstrate there is a distinct sociodemographic and clinical profile for the subgroups of men who engage in different fertility-related behaviors. Multivariate analysis results show that men most likely to be concerned with banking sperm are those who at diagnosis are younger (less than 35 years), childless, college educated, and whose relationships have become strained. Men who sought fertility tests were childless, college graduates, and able to ejaculate. The only factor predicting adoption was childlessness. Those married men attempting to father children were also less than 35 years of age at diagnosis and without ejaculatory dysfunction. The men at greatest risk for continued distress about infertility were those who remained childless and had posttreatment ejaculatory dysfunction. Residual infertility distress also was significantly associated with treatments that included extensive retroperitoneal lymph node dissection (RPLND) surgery, indicating that the latter is a "risk factor" in survivors' long-term distress. These data, while not definitive, show that the prerogative to have children is very important to men and that losing it sets into motion a range of both adverse emotions and adaptive responses. Adjustment to infertility is a complex process that begins at diagnosis and extends long after treatment is completed.
Assuntos
Infertilidade Masculina/psicologia , Ajustamento Social , Neoplasias Testiculares/complicações , Adolescente , Adoção/psicologia , Adulto , Atitude , Fatores de Confusão Epidemiológicos , Pai/psicologia , Humanos , Infertilidade Masculina/etiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Bancos de Esperma , Estresse Psicológico , Neoplasias Testiculares/psicologiaRESUMO
A study of 60 patients with clinical stage I nonseminomatous germ cell testicular tumor (NSGCT) was conducted to identify prognostic factors that may predict the likelihood of metastasis. Clinical features and histopathologic features of the primary testicular tumor were examined and analyzed for correlations with the presence of retroperitoneal nodal metastasis documented by surgery (N+) and with development of relapse (R+). Pathologic tumor stage greater than or equal to 2, with tumor extension into the tunica albuginea, rete testis, epididymis, or spermatic cord, was correlated with an increased rate of N+ compared with pathologic tumor stage I (P = .001). Vascular invasion was correlated with a higher rate of N+ (P = .05) and had a similar association with R+ (P = .08). Tumors containing less than 50% teratoma were found to have a higher rate of N+ than tumors with greater than or equal to 50% teratoma (P = .02). Based on the identified prognostic factors, a model for predicting the probability of retroperitoneal nodal metastasis in clinical stage I patients is proposed. The risk factors for nodal metastasis are: pathologic tumor stage greater than or equal to 2, vascular invasion, and less than 50% teratoma. Patients with none of the risk factors are considered at low risk and may be offered orchiectomy alone with surveillance for initial treatment. Patients with all three risk factors are at high risk and should be treated with a retroperitoneal lymph node dissection (RPLND) or possibly chemotherapy. Patients with one or two risk factors are at intermediate risk; it is recommended that they undergo RPLND. This risk model facilitates a rational approach to the management of clinical stage I NSGCT.
Assuntos
Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/patologia , Testículo/patologia , Adulto , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Modelos Biológicos , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/secundário , Prognóstico , Espaço Retroperitoneal , Fatores de RiscoRESUMO
PURPOSE: To compare the efficacy and safety of ciprofloxacin (CIP) and trimethoprim/sulfamethoxazole (TMS) for the prevention of bacterial infections in patients who received bone marrow transplantation (BMT) for the treatment of solid and hematopoietic neoplasms. PATIENTS AND METHODS: Adult inpatients about to undergo BMT for lymphoma, leukemia, or solid tumors were enrolled onto a prospective, randomized, double-blinded, controlled trial that compared CIP (750 mg orally twice per day) with TMS (160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day). Subjects were stratified before randomization according to tumor and BMT type. Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever, signs or symptoms of infection, serious adverse effects, or recovery of the absolute granulocyte count (AGC) to > or = to 400/microL. RESULTS: Seventy-five CIP recipients and 71 TMS recipients were assessable for efficacy. No difference was noted between the two groups in occurrence of fever during neutropenia, time to onset of first fever, or overall infection rates. Ten bacteremias occurred in CIP recipients versus six in TMS recipients (P = .43). Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients (P = .001). Four infections caused by gram-negative bacilli, including one bacteremia, occurred in TMS recipients versus none in CIP recipients (P = .06). No differences were noted in the incidence of rash or organ toxicity. TMS recipients had longer durations of granulocytopenia at AGC levels < or = to 500/microL and < or = to 100/microL than did CIP recipients (P = .08 for both comparisons). Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis. CONCLUSION: CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point. TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli, as well as a trend toward prolongation of granulocytopenia.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Transplante de Medula Óssea , Ciprofloxacina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Administração Oral , Adulto , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Causas de Morte , Ciprofloxacina/farmacocinética , Método Duplo-Cego , Esquema de Medicação , Resistência Microbiana a Medicamentos , Feminino , Febre de Causa Desconhecida/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Irradiação Corporal TotalRESUMO
After mastectomy, 265 postmenopausal patients with node-positive breast cancer were stratified according to pathologic nodal status and estrogen-receptor (ER) status and randomized to receive either 12 cycles of cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP), or CMFP plus tamoxifen (CMFPT), or observation alone. Patients entered the study between March 1978 and July 1981. Cox regression analysis indicated that, compared to observation alone, chemotherapy (CMFP and CMFPT groups combined) led to a significant reduction in relapses by the end of the first year of study in every examined prognostic subgroup. However, after the first year the relapse-free survival curves of all treatment groups tended to merge, so that by three years 52% of the observation group and 51% of the chemotherapy groups remained disease free. Chemotherapy continued to show a significantly superior relapse-free survival rate for three years only in the subgroup of patients with ER-negative tumors (the subgroup with the largest relapse-free survival advantage at one year). The addition of tamoxifen produced no benefit or harm in any prognostic subcategory examined. ER status was prognostically important for predicting early relapse only in those patients not receiving chemotherapy, due to the greater effectiveness of this chemotherapy to prevent early relapse in the ER-negative subgroup. Treatment has had no early effect on survival. As breast cancer continues to recur even after ten or more years, later relapse patterns may alter these results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Terapia Combinada , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Doenças Hematológicas/induzido quimicamente , Humanos , Metástase Linfática , Mastectomia , Menopausa , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas/tratamento farmacológico , Obesidade/complicações , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prognóstico , Distribuição Aleatória , Receptores de Estrogênio/análise , Risco , Tamoxifeno/efeitos adversosRESUMO
PURPOSE: The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. MATERIALS AND METHODS: Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. RESULTS: Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. CONCLUSION: This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Terapia Combinada/efeitos adversos , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Análise de Regressão , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Patients with laparotomy-staged (PS) III 1A Hodgkin's disease confined to the upper abdomen are believed to have a favorable prognosis and require less aggressive treatment than patients with more-extensive stage III disease. We evaluated prognostic factors and outcome in 93 patients with PS III 1A Hodgkin's disease treated either with radiation therapy (RT) alone or combined RT and chemotherapy (combined modality treatment [CMT]) to determine the extent of treatment needed in this subgroup of stage IIIA patients. MATERIALS AND METHODS: We retrospectively reviewed the freedom from relapse (FFR) rate, sites of recurrence, and survival rate of PS III 1A patients selected to receive extended-field irradiation (MPA, n = 27), total-nodal irradiation (TNI, n = 34), and CMT (n = 32) between 1969 and 1987. CMT consisted of six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and MPA. Patients treated with MPA were part of a prospective trial designed to reduce treatment to patients with minimal stage III disease with very favorable characteristics. RESULTS: Histologic subclass and treatment were the only prognostic factors for FFR and survival rates. Patients with nodular sclerosis or lymphocyte predominance histology had significantly higher FFR and survival rates compared to patients with mixed-cellularity (MC) histology. The 10-year actuarial FFR of PSIII 1A patients treated with MPA was only 39%, versus 55% for TNI (P = .02) and 94% for CMT (v MPA, P < .0001; v TNI, P = .006). The patterns of recurrence in patients who received MPA and TNI were significantly different, with MPA patients relapsing more often in untreated pelvic or inguinal nodes, and TNI patients relapsing more often in extranodal sites with or without nodal sites. The 10-year actuarial overall survival rate for patients treated with CMT was 89% versus 78% for MPA (v CMT, P = .09) and 70% for TNI (v CMT, P = .05). CONCLUSION: Patients with PSIII 1A Hodgkin's disease treated with RT have a significantly higher risk of relapse and potentially a poorer survival compared with patients treated with CMT. These findings suggest that CMT should play a greater role in the treatment of this favorable substage of patients. Management with modified chemotherapy and RT in an attempt to reduce long-term treatment-induced complications may be a preferred approach for future trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Terapia Combinada , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Humanos , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Estudos Prospectivos , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
OBJECTIVE: To model the relationships among HIV-1 replication, immune activation and CD4+ T-cell losses in HIV-1 infection. METHODS: Cross-sectional analysis of baseline data from the Viral Activation by Transfusion Study. Comparisons of unadjusted and adjusted correlative analyses to establish models for mechanisms of cell loss in AIDS. RESULTS: Using these analyses, significant correlations were found among plasma levels of tumor necrosis factor alpha (TNFalpha) and its type two receptor (TNFrII), interleukin-6 (IL-6), beta2-microglobulin, expression of CD38 and HLA-DR on CD8+ T lymphocytes and plasma levels of HIV-1 RNA. When correlations among these indices were adjusted for possible intermediary correlations, the relationship between HIV-1 RNA levels and all plasma markers of immune activation could be accounted for by the correlation between plasma HIV-1 RNA and plasma TNFrII levels. In addition, the negative correlations that both HIV-1 RNA levels and TNFrII levels had with CD4+ T-cell counts were partially accounted for by the correlations of HIV-1 RNA and TNFrII with CD38 expression on CD8+ T cells. In persons with advanced disease (CD4+ T cells < 50 x 10(6)/l) IL-6 levels were inversely correlated with CD4+ T-cell counts. CONCLUSIONS: This analysis is consistent with a model wherein HIV-1 replication induces TNFalpha expression that induces multiple other indices of immune activation. In this model, HIV-1 replication and TNFalpha expression induce CD4+ T-cell losses at least in part through mechanisms reflected in heightened CD38 expression.
Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/imunologia , HIV-1/imunologia , HIV-1/fisiologia , ADP-Ribosil Ciclase , ADP-Ribosil Ciclase 1 , Adulto , Antígenos CD/sangue , Antígenos de Diferenciação/metabolismo , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Glicoproteínas de Membrana , Modelos Biológicos , NAD+ Nucleosidase/metabolismo , RNA Viral/sangue , Receptores do Fator de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa/metabolismo , Replicação ViralRESUMO
OBJECTIVES: To determine factors associated with survival and to assess the relative strength of CD4 cell count and HIV-1 RNA in predicting survival in a cohort of HIV-1-infected women. DESIGN: Prospective cohort, enrolled during 1994-1995, with median follow-up of 29 months RESULTS: Of 1769 HIV-infected women 252 died. In multivariate analyses, lower CD4 cell count, higher quantitative plasma HIV-1 RNA, and the presence of a self-reported AIDS-defining (Class C) condition were significantly associated with shorter survival: the relative hazard (RH) of dying was 1.17, 3.27, and 8.46, respectively for women with baseline CD4 cell count of 200-349, 50-199, and < 50 x 10(6) cells/l, compared with women with CD4 cell count of > or = 350 x 10(6) cells/l. Compared with women with HIV-1 RNA levels of < 4000 copies/ml plasma, the RH of dying for women with baseline quantitative HIV-1 RNA measurements of 4000-20,000, 20,000-100,000, 100,000-500,000 and > 500,000 copies/ml, was 2.19, 2.17, 3.16, and 7.25, respectively. CD4 cell count had as strong a prognostic value as HIV-1 RNA level, particularly among participants with more advanced immunodeficiency. When the analysis was adjusted to eliminate the distortion created by having disproportionately sized strata of the categorized variables, the relative hazard of death associated with CD4 cell count became even larger in comparison with that for HIV-1 RNA. Eliminating from the analysis all follow-up time during which participants could have received highly active antiretroviral therapy did not change these findings. Age was not a predictor of survival after adjustment for covariates. CONCLUSIONS: CD4 cell count and HIV-1 RNA had similar prognostic value in this cohort of HIV-1-infected women. Even in the presence of a low viral burden, a substantially decreased CD4 cell count remained a strong predictor of mortality.
Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/mortalidade , HIV-1/isolamento & purificação , RNA Viral/sangue , Estudos de Coortes , Feminino , Seguimentos , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: To determine whether mode of delivery or the use of maternal or neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be detected in infected infants, particularly the probability of detection at birth. METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1 infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14 days of age were analysed. Weibull mixture models were used to estimate the cumulative proportion of infants with detectable levels of HIV-1 according to use of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were first tested, at a median age of 2 days. At birth, it was estimated that 36% [95% confidence interval (CI), 31-41%] of infants have levels of virus that can be detected by DNA PCR or cell culture. This percentage was not associated with either mode of delivery (35% for vaginal delivery versus 40% for cesarean section delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis. Among infants with undetectable levels of HIV-1 at birth, the median time to viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were exposed to antiretroviral therapy postnatally compared with infants who were not exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of an early virological test for HIV-1 is thought to be related directly to the timing of transmission and cesarean section delivery primarily reduces the risk of intrapartum transmission. The absence of an association between mode of delivery and viral detectability at birth was therefore unexpected. There was no evidence that foetal or neonatal exposure to prophylactic zidovudine delays substantially the diagnosis of infection, although this cannot be inferred for combination antiretroviral therapy.
Assuntos
Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez , Fatores Etários , Fármacos Anti-HIV/uso terapêutico , Cesárea , Feminino , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Humanos , Recém-Nascido , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Estudos Prospectivos , Zidovudina/uso terapêuticoRESUMO
PURPOSE: A study was undertaken adding the alkylating agent sensitizer etanidazole to intravenous melphalan and oral prednisone for patients with multiple myeloma. This study explored the toxicity profile of these agents when given together and assessed the ability to attain adequate serum levels of etanidazole to permit sensitization to occur. METHODS AND MATERIALS: Etanidazole was administered intravenously in two doses of 3 g/m2 and 5 g/m2 90 min apart immediately prior to the administration of intravenous melphalan and oral prednisone for three consecutive cycles (total dose 24 g/m2). Patients received three additional cycles without etanidazole, allowing a comparison of hematologic toxicity from melphalan with and without etanidazole. RESULTS: Hematologic toxicity was moderate (Grade 3 or 4), but severity was similar during cycles with and without etanidazole. Only one patient developed a Grade 1 peripheral neuropathy questionably related to etanidazole. Most patients had etanidazole levels of > or = 70 ug/ml for 7 h, a level felt to be necessary for sensitization to occur. CONCLUSION: Etanidazole, administered as described, results in adequate serum levels for potential alkylating agent sensitization, without significant toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etanidazol/farmacocinética , Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Etanidazol/administração & dosagem , Humanos , Infusões Intravenosas , Melfalan/administração & dosagem , Mieloma Múltiplo/metabolismo , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Prednisona/administração & dosagemRESUMO
PURPOSE: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. METHODS AND MATERIALS: Patients received 2 g/m2 of intravenous etanidazole followed by a second dose of 4 g/m2 90 min later, followed by intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. RESULTS: Two patients who received a total of 24 g/m2 of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole. CONCLUSION: Etanidazole, 2 g/m2 followed by 4 g/m2 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etanidazol/farmacocinética , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Ciclofosfamida/administração & dosagem , Etanidazol/administração & dosagem , Feminino , HumanosRESUMO
OBJECTIVE: To determine the sensitivity and specificity of anti-human immunodeficiency virus (HIV) IgA in identifying infected infants at or before 6 months of age among the offspring of HIV-infected mothers. DESIGN: Prospective comparison of anti-HIV IgA measurement performed in 2 different laboratories by 2 different methods with the criterion standard of blood culture. SETTING: Five centers in the United States and Puerto Rico. PATIENTS: Population-based sample of 156 infants of HIV-infected mothers in the Women and Infants Transmission Study. MAIN OUTCOME MEASURES: Results of anti-HIV IgA test in relation to the infection status of the infants as measured by blood culture. RESULTS: Six-month plasma or serum samples were first tested in the 2 laboratories. The sensitivity and specificity of anti-HIV IgA in detecting infected infants at this age by laboratories 1 and 2 were 69% and 63% and 100% and 99%, respectively. A look-back study of samples obtained at birth, 1, 2, and 4 months was then performed on all infected children and a matched set of uninfected children. The performance of the test at birth was unsatisfactory in both laboratories (sensitivity 44% and 33%, specificity 43% and 60%), whether peripheral or cord blood was examined. At 1, 2, and 4 months, the sensitivity of the test was lower than at 6 months, but specificity was high. A modest correlation of absent anti-HIV IgA antibody and low percentage of CD4 cells in peripheral blood was seen at 6 months of age. CONCLUSIONS: The anti-HIV IgA test has moderate sensitivity and high specificity for the diagnosis of HIV infection at 6 months of age in the offspring of infected mothers.
Assuntos
Anticorpos Anti-HIV/sangue , Infecções por HIV/diagnóstico , Infecções por HIV/transmissão , HIV-1/imunologia , Imunoglobulina A/sangue , Transmissão Vertical de Doenças Infecciosas , Feminino , Infecções por HIV/imunologia , Humanos , Lactente , Valor Preditivo dos Testes , Estudos Prospectivos , Porto Rico , Sensibilidade e Especificidade , Estados UnidosRESUMO
OBJECTIVE: To assess changes in lymphocyte subsets during pregnancy and 1 year postpartum in human immunodeficiency virus (HIV)-infected women. METHODS: Changes in CD4+ and CD8+ cell counts, CD4 and CD8 percent, CD4/CD8 ratio, and total lymphocyte count and percent were assessed in each of 226 HIV-infected women followed during pregnancy and 1 year postpartum, and for each of 100 nonpregnant HIV-infected woman during 1 year. Trends over time were compared between pregnant women with and without several covariates. Postpartum changes over a 1-year period were compared to a 1-year period in the nonpregnant cohort. RESULTS: There was a mean increase of 2.76 per week in the CD4+ cell count during pregnancy (P = .04). No other characteristics changed significantly during pregnancy. The mean CD4+ and CD8+ cell counts, the CD8 percent, and the total lymphocyte count and percent increased immediately postdelivery. During the first postpartum year, there were statistically significant declines in the absolute CD4+ and CD8+ cell counts, the relative CD4 and CD8 percentages, and the total lymphocyte count and percentage. The rate of change for CD4+ and CD8+ counts, but not for CD4 percent, was less during 1 year in the nonpregnant cohort than in the first postpartum year, and the CD8 percent increased in the nonpregnant women. A wide variability in trends of all measurements during pregnancy was seen. CONCLUSION: During pregnancy, CD4 and CD8 percentages remain stable. There are no clinically significant changes during pregnancy or postpartum in any lymphocyte parameter we assessed. Postpartum changes in lymphocytes and lymphocyte subsets most likely represent a return to baseline from the physiologic changes of pregnancy and the immediate postpartum period.
Assuntos
Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Infecções por HIV/imunologia , Complicações Infecciosas na Gravidez/imunologia , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Gravidez , Fatores de TempoRESUMO
Eighty patients with clinical stage I or II nonseminomatous germ cell tumors of the testis were managed with modified protocols, including modified nerve-sparing retroperitoneal lymph node dissection for patients with stage I cancer, retroperitoneal lymph node dissection for patients with low-volume stage II cancer, and initial chemotherapy with or without subsequent retroperitoneal lymphadenectomy for patients with high-volume stage II cancer. Patients with low-stage disease (clinical stage I) were treated successfully with modified retroperitoneal lymph node dissection (relapse rate, three of 40 patients). Clinical understaging was evidenced in 14 of 48 patients with clinical stage I disease who were found to have pathologic involvement of the retroperitoneal lymph nodes, including six patients with extensive retroperitoneal nodal involvement (pathologic stage B2). Of nine patients with retroperitoneal tumors less than 3 cm in diameter, four patients were satisfactorily treated with retroperitoneal lymph node dissection alone while five patients required chemotherapy after retroperitoneal lymph node dissection. Of 26 patients with retroperitoneal tumors 3 to 5 cm in diameter, 17 patients were treated with chemotherapy alone. All patients remain free of disease after the completion of definitive therapy. We conclude that therapeutic options should be modified based on histologic factors in the primary tumor, extent of retroperitoneal disease as indicated on a computed tomographic scan, and presence or absence of elevated tumor markers. By consideration these factors, optimum therapy can be selected to achieve the highest long-term survival rate with the least morbidity.
Assuntos
Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Seguimentos , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/mortalidade , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/secundário , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/mortalidade , Neoplasias Testiculares/patologia , Vimblastina/administração & dosagemRESUMO
PURPOSE: This clinical trial was designed to compare the effectiveness of vincristine, doxorubicin (Adriamycin), and dexamethasone (VAD) with VAD plus interferon alfa-2 in patients with refractory or relapsed multiple myeloma. PATIENTS AND METHODS: Between January 1990 and May 1992, 47 eligible patients with multiple myeloma who had failed one prior chemotherapeutic regimen were accrued to a multiinstitutional prospective randomized clinical trial. The trial was halted early because of poor accrual. RESULTS: After a minimum follow-up of 13 months, the objective overall response rate was 28% (25% in the VAD group, 30% in the VAD plus interferon group). The response duration and overall survival were similar for the two treatment groups, with medians of 3.6 and 8.3 months, respectively. Life-threatening or lethal nonhematologic toxicity was seen in 27%. Interferon did not appear to increase the frequency of toxic responses. CONCLUSION: This study shows no advantage to the use of interferon combined with VAD in refractory or relapsing myeloma. However, the small sample size decreased the statistical power to recognize small differences if present. Moreover, the survival data do not suggest a clear advantage to the administration of vincristine or doxorubicin as a 96-hour infusion compared with results of studies using bolus administration combined with high-dose corticosteroids.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon Tipo I/uso terapêutico , Mieloma Múltiplo/terapia , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Terapia Combinada , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Estudos Prospectivos , Proteínas Recombinantes , Recidiva , Indução de Remissão , Taxa de Sobrevida , Estados Unidos , Vincristina/administração & dosagemAssuntos
Perna (Membro)/inervação , Traumatismos da Medula Espinal/complicações , Traumatismos da Coluna Vertebral/complicações , Adolescente , Adulto , Calcinose/etiologia , Feminino , Fraturas Ósseas/complicações , Humanos , Artropatias/etiologia , Articulação do Joelho , Úlcera da Perna/etiologia , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Osteoporose/etiologiaRESUMO
We describe recent epidemiological changes in salmonellosis. Linking 1968-2000 National Salmonella Surveillance System to census data, we calculated population-based age- and sex-stratified rates of non-urinary salmonellosis for the top 30 non-typhoidal serotypes. Using 1996-1997, 1998-1999, and 2000-2001 population-based FoodNet surveys, we compared reported diarrhoea, medical visits, and stool cultures. Despite an overall female-to-male incidence rate ratio (FMRR) of 0.99, the sex-specific burden of salmonellosis varied by age (<5 years FMRR 0.92; 5-19 years 0.85; 20-39 years 1.09; 40-59 years 1.23, and 60 years 1.08) and serotype (FMRR range 0.87 for Mississippi to 1.25 for Senftenberg). Serotype-specific FMRRs and median age (range 2 years for Derby to 29 years for Senftenberg) were related (correlation 0.76, P<0.0001). Recently, the relative burden of salmonellosis in women has increased. FoodNet data suggest that this change is real rather than due to differential reporting. Excess salmonellosis in women may reflect differences in exposure or biological susceptibility.