RESUMO
Because of its potential as a low cost first-line monotherapy for the most common vulvovaginal infections, we evaluated fenticonazole nitrate in a prospective, open-label, multicenter pilot study with 101 sexually active women (per-protocol; 16 to 61 years of age) with vulvovaginitis involving single or mixed infections with Candida albicans, Trichomonas vaginalis, and/or Gardnerella vaginalis. Fenticonazole nitrate (1 g) was administered as vaginal ovules, once daily on days 1 and 3. Eradication (direct phase-contrast microscopy of vaginal swabs and/or microbiological culture) on day 8 was 90% (C. albicans, 26/29, p < 0.001), 70% (T. vaginalis, 7/10, p = 0.161), 67% (G. vaginalis, 22/33, p < 0.009), and 45% (mixed infection, 13/29, p = 0.001). After 28 days, relapse was 0% for candidiasis and trichomoniasis, 27% (6/22) for G. vaginalis, and 23% (3/13) for mixed infection. Overall, eradication of all offending pathogens was achieved in 67% of the total per-protocol population, with a relapse rate of only 16%. Score sums for symptoms improved from 7.0 (baseline) to 1.7 (day 8), and 0.71 (day 28), (p < 0.001). Treatment was safe and well tolerated. The results of our pilot study suggest that application of fenticonazole nitrate 1 g intravaginal ovules on 2 alternate days is a suitable first-line treatment of vulvovaginitis with acceptable broad-spectrum efficacy against the most commonly involved pathogens and with a low rate of early relapse, reserving antibiotics for patients with treatment failure or relapse of infection. Our results should encourage further examination of this approach in larger and well controlled clinical trials.
Assuntos
Antifúngicos/uso terapêutico , Imidazóis/uso terapêutico , Vulvovaginite/tratamento farmacológico , Administração Intravaginal , Adolescente , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Candidíase/patologia , Esquema de Medicação , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Vulvovaginite/microbiologia , Vulvovaginite/patologiaAssuntos
Fertilização in vitro , Gravidez Ectópica , Transferência Embrionária , Feminino , Humanos , GravidezRESUMO
We constructed models of umbilical cord blood lead (PbB), with and without the addition of maternal PbB at delivery and earlier in pregnancy, to determine which factors explaining cord PbB depended upon maternal PbB and which did not. We prospectively studied women of low-to-middle socioeconomic status who lived in the Valley of Mexico from 12 weeks of pregnancy to delivery. We measured maternal venous PbB during pregnancy and at delivery, and umbilical cord PbB (1-38 micrograms/dl, 0.05-1.83 mumol/l). We used multiple regression analyses to model cord PbB and a logit analysis to model the maternal-cord PbB relationship. Older mothers using lead-glazed pottery and canned foods delivered babies with increased cord PbB, while those with occasional alcohol use during pregnancy, high milk intake, and more spontaneous abortions delivered babies with lower cord PbB. Maternal PbB at 36 weeks of pregnancy and at delivery independently explained additional variance in cord PbB, but maternal PbB earlier in pregnancy did not. Some of the effects of lead-glazed pottery, maternal abortions, alcohol use, and canned food use on cord PbB were mediated through maternal PbB. The effects of maternal age and milk intake on cord PbB were independent of their influence on maternal PbB near delivery. Cord PbBs were higher than maternal PbBs at delivery in 33% of the cases, and were predominant in mothers over 30 and those drinking milk less than once per day. Measurable influence of maternal PbB on delivery cord PbB is limited to the four to eight weeks prior to delivery. Many factors suspected of influencing bone lead also control cord PbB, some of them independently of their effect on maternal delivery PbB. Minimizing fetal exposure near the end of pregnancy may require long-term control of maternal lead exposure and good management of pregnancy and diet.
Assuntos
Chumbo/sangue , Exposição Materna , Cordão Umbilical/irrigação sanguínea , Adolescente , Adulto , Cerâmica/efeitos adversos , Intervalos de Confiança , Exposição Ambiental , Comportamento Alimentar , Feminino , Humanos , Recém-Nascido , Chumbo/efeitos adversos , Modelos Logísticos , Análise por Pareamento , Idade Materna , Exposição Materna/estatística & dados numéricos , Troca Materno-Fetal , México/epidemiologia , Razão de Chances , Gravidez , Estudos ProspectivosRESUMO
The first step in modeling lead kinetics during pregnancy includes a description of sequential maternal blood lead (PbB) during pregnancy and the factors controlling it. We analyzed PbB of 105 women living in the Valley of Mexico from week 12 to week 36 of pregnancy and again at parturition. We also used data from all women contributing blood at any stage of pregnancy to determine antecedents of PbB. Pregnancies were uneventful, and offspring were normal. Although geometric mean PbB level averaged around 7.0 micrograms/dl (0.34 mumol/l), with a range of 1.0-35.5 micrograms/dl throughout pregnancy, analysis of variance revealed a significant decrease in mean PbB from week 12 to week 20 (1.1 micrograms/dl) and various significant increases in mean PbB from week 20 to parturition (1.6 micrograms/dl). Regression analyses confirmed the positive linear PbB trend from 20 weeks to parturition and additional contributions of dietary calcium, reproductive history, lifetime residence of Mexico City, coffee drinking, and use of indigenous lead-glazed pottery. Although decreasing hematocrit has been suggested to explain first-half pregnancy PbB decrease, the time course of hematocrit decrease in the present study did not match the sequential changes in PbB. While hemodilution and organ growth in the first half of pregnancy may account for much of the PbB decrease seen between 12 and 20 weeks, the remaining hemodilution and accelerated organ growth of the last half of pregnancy do not predict the trend toward increasing maternal PbB concentration from 20 weeks to delivery. Mobilization of bone lead, increased gut absorption, and increased retention of lead may explain part of the upward PbB trend in the second half of pregnancy. Reduction of lifetime lead exposure may be required to decrease risk of fetal exposure.
Assuntos
Chumbo/sangue , Gravidez/sangue , Adulto , Peso Corporal , Feminino , Hematócrito , Humanos , México , Trimestres da Gravidez , Análise de RegressãoRESUMO
PIP: Lead exposure even at low levels has adverse effects for the central nervous system (CNS), but pregnant women, neonates, lactating infants, and preschool and school age children are most susceptible to it. In rats anatomical alterations included swelling in the mitochondria of renal duct cells (at 26 mcg/dl); biochemical effects involved marked reduction of cytochrome content in the cerebral cortex (36 mcg/dl); and physiological effects were induced at the level of 30-50 mcg/dl. Central nervous system effects entailed persistent decrease of visual acuity (65 mcg/dl at birth and 7 mcg/dl 90 days later), the increase of the latency of primary and secondary components of evoked visual responses during the prenatal and adult period (65 mcg/dl and 7 mcg/dl on days 21 and 90 after birth, respectively). 30 and even 20 mcg/dl of lead in the blood produced nerve conductivity deficits. A study of 425 children with lead poisoning showed a 39% rate of mental retardation and convulsions impervious to treatment. Lead levels within a range of 10-25 mcg/dl reduced the score on the mental development inventory by 4-8 points. The population of the Valley of Mexico numbers 15-20 million with 50% of Mexico's industry. A who investigation indicated blood levels of an average of 22.5 mcg/dl in a group of school teachers, the highest in 10 major population centers in the world. Blood levels in 405 pregnant women in Mexico City averaged 20.3 mcg/dl, and the sample from the umbilical cord of fetuses showed 13.6 mcg/dl. Another study disclosed blood levels of 16 mcg/dl in mothers and 13 mcg/dl in their offspring. The most probable sources of lead are: leaded gasoline, secondary recapture of lead for making batteries, use of paints, ceramics used for storing and cooking food, lead seal of milk containers, and consumption of food contaminated with lead.^ieng