To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postop... more To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postoperative endometrial carcinoma and to correlate vaginal toxicity with vaginal-surface-EQD2Gy3 dose (VS-EQD2Gy3). 319 patients (p) I-IIIC-Figo-stage were treated with 2 BT schedules. One schedule included 166p (Group-1) to whom 3 fractions (Fr) of 4-6Gy per week (w) of BT were administered after external beam radiotherapy (EBI) (125p) and 6Fr/2w of 4-6Gy in exclusive-BT (41p). The second schedule included 153p (Group-2) with BT administered daily with 2Fr/w of 5-6Gy after EBI (94p) and 5-6Gy/4Fr/w in exclusive-BT (59p). Doses were prescribed at 5mm from the vaginal surface. Toxicity was evaluated using RTOG scores for the rectum and bladder and objective LENT-SOMA scores for the vagina. Chi-square, Fisher and Student's-t tests. Mean follow-up (months): Group-1: 66.55 (7.73-115.40), Group-2: 41.49 (3.13-87.90). VCR: Group-1: 3p (1.88%); Group-2: 2p (1.3%). No differences were found between the two schedules comparing rectal (p=0.170), bladder (p=0.125) and vagina (p=0.680) late toxicities and comparing vagina EBI+BTp vs. exclusive-BTp (p=0.667). Significant differences in VS-EQD23Gy were observed considering EBI+BT (Groups 1+2) vs. exclusive-BT (Groups 1+2) (p<0.0001); nevertheless, no association was found between VS-EQD23Gy and vaginal complications. No differences were found between the two schedules. No association was found between vaginal toxicity and VS-EQD23Gy. Consequently, treatment with the least number of fractions is preferable.
Bioko is the only island known in the world with endemic onchocerciasis. The island&a... more Bioko is the only island known in the world with endemic onchocerciasis. The island's rural communities consist of villages and cocoa plantations inhabited by Bubi and Fang ethnic groups. The aim of this study was to evaluate the impact of 8 years of vertical ivermectin distribution on the prevalence and intensity of Onchocerca volvulus infection in the rural population by means of pre- (1989) and post-long term treatment (1998) epidemiological surveys. In both surveys, the entire population of 12 randomly selected communities (1723 and 1082 individuals) was examined. The mean ivermectin therapeutic coverage for the 8 years was 53.2%. Iliac crest skin snips were used for differential diagnosis between O. volvulus and Mansonella streptocerca. The crude O. volvulus infection prevalence before ivermectin intervention was 74.5% (1284/1723); after the intervention it was 38.4% (415/1082). The Community Microfilarial Load (CMFL) before and after ivermectin intervention was 28.29 microfilariae/snip vs. 2.32 microfilariae/snip. The reduction in prevalence and CMFL after eight annual rounds of ivermectin treatment corroborates the drug microfilaricidal activity and good tolerability. In the pre-treatment survey, the prevalence was higher in the Bubi group (77.1%, 1126/1461); post-treatment it was higher among the Fang (51.1%, 92/180). The reduction in prevalence and intensity of O. volvulus infection differed between ethnic groups and communities.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1995
The influence of haemoglobin genotype on the response to iron supplementation was studied in a ra... more The influence of haemoglobin genotype on the response to iron supplementation was studied in a randomized, double blind, placebo-controlled trial involving 497 multigravid pregnant women from a rural area of The Gambia. Women were randomly allocated to receive either oral iron (60mg elemental iron per day) or placebo. At 36 weeks of pregnancy, women who had received oral iron during pregnancy had higher mean haemoglobin, packed cell volume, plasma iron and ferritin levels than did women who received placebo. Iron supplementation of pregnant women with the AA haemoglobin genotype also resulted in increases in the packed cell volume (PCV) and haemoglobin level measured after delivery, and in the birth weight of the infant. However, in AS women PCV and haemoglobin level at delivery were lower in the supplemented group and supplementation was also associated with reduced birth weights. In malaria endemic areas, pregnant women with the haemoglobin genotype AS may not benefit from iron supplementation during pregnancy.
The administration of hormonal replacement treatment to women with an intact uterus needs to be s... more The administration of hormonal replacement treatment to women with an intact uterus needs to be supplemented with progestogenic compounds to avoid endometrial hyperplasia. However, progestins may cancel the beneficial effects of estrogens on the cardiovascular system. The goal of this study was to examine the effects of adding cyproterone acetate to estradiol (E(2))on aorta atherogenesis. Thirty-two cholesterol-fed New Zealand white rabbits were studied for 4 months. The animals underwent laparotomy and were randomly allocated to four groups. Twenty-four rabbits underwent bilateral ovariectomy, and the other eight were sham-operated (group S). The ovariectomized rabbits were allocated to three groups of eight animals each receiving E(2) valerate (group E), E(2) valerate plus cyproterone acetate (group EC), or placebo after sterilization (group C). After 4 months, the cholesterol-rich diet caused atherosclerotic aortic lesions in both treated groups that affected 17.91% +/- 10.19% and 28.16% +/- 7.97% of the aortic surface of groups E and EC, respectively, with a markedly lower aortic plaque size in group E than in groups C and S. Rabbits from group E (but not from group EC) had aortic cholesterol content significantly lower than rabbits from the sham-operated and control groups. E(2) valerate reduces aortic atheromatosis in cholesterol-fed, ovariectomized rabbits, and the addition of cyproterone acetate may neutralize this effect.
Radiotherapy for early vocal cord carcinoma affects quality of voice. Nevertheless, most patients... more Radiotherapy for early vocal cord carcinoma affects quality of voice. Nevertheless, most patients refer to having a high satisfaction level with their voice. The few acoustic studies on quality of voice have been performed only in prolonged vowel production, which is not a usual speech situation. The present study has been done with the aim of establishing which phonetic situations reflect a greater alteration in voice production related to irradiation. Eighteen male patients irradiated for Tis-T1 vocal cord carcinoma and a control group of 31 non-irradiated subjects were included in a study of acoustic voice analysis. This analysis was performed one year after radiotherapy. Patients and control group voices were tape recorded in extended vowel production, oral reading of a standard paragraph, spontaneous speech and in a song. Acoustic analysis was performed by a Kay Elemetric's Computerized Speech Lab (model CSL #4300). Fundamental frequency, jitter, shimmer and harmonics-to-noise ratio were obtained in both groups. Statistical test: Lin concordance coefficient and Pearson's correlation coefficient, Student's t-test and ROC curves. Concordance and correlation studies did not allow selection of any subgroup in acoustic parameters and different acoustic situations. Acoustic parameters had higher median values in irradiated patients. Student's t-test showed significant differences for fundamental frequency in sustained vowel production and spontaneous speech; for jitter there was statistical significance in all the acoustic situations and for shimmer in oral reading and song. Jitter showed a cut-off of 2.02% with a sensitivity of 89% and specificity of 97% in classifying irradiated and non-irradiated groups. The ROC curve for jitter correctly classified 94% of subjects into irradiated or non-irradiated groups. The present study showed that jitter obtained from spontaneous speech was the most relevant parameter in discriminating voice in irradiated patients by acoustic analysis. Jitter in spontaneous speech is in need of more analysis in bigger series and in more advanced stages of larynx cancer as its relevance has been demonstrated.
To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicit... more To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicity in the postoperative treatment of endometrial carcinoma (EC). From January 2007 to September 2010, 112 patients were treated with HDRBT after surgery for EC. FIGO staging: 24-IA, 48-IB, 14-II, 12-IIIA, 2-IIIB, 8-IIIC1 and 4-IIIC2. Pathology 99/112 endometrioid and 23/112 other types. Radiotherapy patients were divided into two groups-Group 1 (70/112) consists of external beam irradiation (EBI) plus HDRBT (2 fractions of 5-6 Gy) and Group 2 (42/112) consists of HDRBT alone (4 fractions of 5-6 Gy). Toxicity evaluation RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. Statistics bivariate analysis of Chi-square and Fisher exact tests. With a mean follow-up of 29.52 months (range 9.60-53.57) no patient developed vaginal-cuff relapse. In Group 1 early toxicity appeared in 9 % in rectum, 8.5 % in bladder (G1-G2) and 1.4 % in vagina (G1); late toxicity was present in 8.5 % in rectum (all G1-G2 but 1 G3) and in 25 % in vagina (all G1-G2 but one G4). In Group 2, 9.4 % developed G1-G2 bladder and 6.9 % acute vagina (G1-G2) toxicity. Only 2.3 % had a G1 rectal score and 6.9 % had G1-G2 as vaginal scores for late problems. (1) Daily HDRBT using two fractions of 5-6 Gy after EBI and four fractions of 5-6 Gy as exclusive treatment was a safe regime. (2) Group 1 showed a higher incidence of late vaginal toxicity.
To analyse the impact of prognostic factors on specific overall survival (SOS) after postoperativ... more To analyse the impact of prognostic factors on specific overall survival (SOS) after postoperative radiotherapy (P-RT) in carcinosarcomas. We retrospectively analysed 81 patients who received P-RT from 1977 to 2010 after the diagnosis of carcinosarcomas. 2009 FIGO stage: 25-IA, 20-IB, 6-II, 9-IIIA, 11-IIIC. Age, stage, vascular and lymphatic space invasion (VLSI), myometrial invasion, grade, mitotic index, sarcomatous/epithelial components, tumour size and necrosis were considered for the analysis. we used the Kaplan-Meier method for survival analysis and the Cox model for risk factor evaluation. The mean follow-up of the series was 78.86 months (range 7-381). The median age was 72 years (range 51-89). 30 out 81 (37 %) patients relapsed and died (22.2 % pelvic and abdominal, 13.5 % exclusive distant metastasis). On univariate and multivariate analysis only stage had a significant impact on SOS. At 5 years, stage I-II had a SOS of 66 % in comparison with stage III with 30 %. Two groups of patients showing different outcome were found after P-RT in uterine carcinosarcomas: stage I-II patients had a life expectancy 2.5-fold longer compared to stage III patients. New therapeutic strategies are warranted in carcinosarcomas considering the high incidence of distant metastasis.
American Journal of Obstetrics and Gynecology, 1996
Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone... more Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone (defined before treatment) and the woman's age both as single and combined predictors of ovarian response in an in vitro fertilization program where pituitary desensitization was routinely used. The study was a retrospective analytic investigation of 120 women undergoing the first cycle of in vitro fertilization. Forty consecutive cycles canceled because of poor follicular response were initially selected. As a control group, the nearest completed in vitro fertilization cycles before and after each canceled cycle (i.e., the closest cycles in temporal relationship to the index cycle) were used. The mean age and basal follicle-stimulating hormone level were significantly higher in the canceled than in the control group, whereas the basal inhibin level was significantly higher in the latter. Follicle-stimulating hormone and inhibin alone, with an accuracy (predictive value of ovarian response) of 70%, were better predictors of cancellation than age was. Any two or all three of these variables studied did not improve the predictive value of follicle-stimulating hormone or inhibin alone. Age is a poorer predictor than pretreatment basal follicle-stimulating hormone and inhibin levels for ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Basal follicle-stimulating hormone and inhibin have similar predictive properties and could therefore be used interchangeably.
To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postop... more To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postoperative endometrial carcinoma and to correlate vaginal toxicity with vaginal-surface-EQD2Gy3 dose (VS-EQD2Gy3). 319 patients (p) I-IIIC-Figo-stage were treated with 2 BT schedules. One schedule included 166p (Group-1) to whom 3 fractions (Fr) of 4-6Gy per week (w) of BT were administered after external beam radiotherapy (EBI) (125p) and 6Fr/2w of 4-6Gy in exclusive-BT (41p). The second schedule included 153p (Group-2) with BT administered daily with 2Fr/w of 5-6Gy after EBI (94p) and 5-6Gy/4Fr/w in exclusive-BT (59p). Doses were prescribed at 5mm from the vaginal surface. Toxicity was evaluated using RTOG scores for the rectum and bladder and objective LENT-SOMA scores for the vagina. Chi-square, Fisher and Student's-t tests. Mean follow-up (months): Group-1: 66.55 (7.73-115.40), Group-2: 41.49 (3.13-87.90). VCR: Group-1: 3p (1.88%); Group-2: 2p (1.3%). No differences were found between the two schedules comparing rectal (p=0.170), bladder (p=0.125) and vagina (p=0.680) late toxicities and comparing vagina EBI+BTp vs. exclusive-BTp (p=0.667). Significant differences in VS-EQD23Gy were observed considering EBI+BT (Groups 1+2) vs. exclusive-BT (Groups 1+2) (p<0.0001); nevertheless, no association was found between VS-EQD23Gy and vaginal complications. No differences were found between the two schedules. No association was found between vaginal toxicity and VS-EQD23Gy. Consequently, treatment with the least number of fractions is preferable.
Bioko is the only island known in the world with endemic onchocerciasis. The island&a... more Bioko is the only island known in the world with endemic onchocerciasis. The island's rural communities consist of villages and cocoa plantations inhabited by Bubi and Fang ethnic groups. The aim of this study was to evaluate the impact of 8 years of vertical ivermectin distribution on the prevalence and intensity of Onchocerca volvulus infection in the rural population by means of pre- (1989) and post-long term treatment (1998) epidemiological surveys. In both surveys, the entire population of 12 randomly selected communities (1723 and 1082 individuals) was examined. The mean ivermectin therapeutic coverage for the 8 years was 53.2%. Iliac crest skin snips were used for differential diagnosis between O. volvulus and Mansonella streptocerca. The crude O. volvulus infection prevalence before ivermectin intervention was 74.5% (1284/1723); after the intervention it was 38.4% (415/1082). The Community Microfilarial Load (CMFL) before and after ivermectin intervention was 28.29 microfilariae/snip vs. 2.32 microfilariae/snip. The reduction in prevalence and CMFL after eight annual rounds of ivermectin treatment corroborates the drug microfilaricidal activity and good tolerability. In the pre-treatment survey, the prevalence was higher in the Bubi group (77.1%, 1126/1461); post-treatment it was higher among the Fang (51.1%, 92/180). The reduction in prevalence and intensity of O. volvulus infection differed between ethnic groups and communities.
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1995
The influence of haemoglobin genotype on the response to iron supplementation was studied in a ra... more The influence of haemoglobin genotype on the response to iron supplementation was studied in a randomized, double blind, placebo-controlled trial involving 497 multigravid pregnant women from a rural area of The Gambia. Women were randomly allocated to receive either oral iron (60mg elemental iron per day) or placebo. At 36 weeks of pregnancy, women who had received oral iron during pregnancy had higher mean haemoglobin, packed cell volume, plasma iron and ferritin levels than did women who received placebo. Iron supplementation of pregnant women with the AA haemoglobin genotype also resulted in increases in the packed cell volume (PCV) and haemoglobin level measured after delivery, and in the birth weight of the infant. However, in AS women PCV and haemoglobin level at delivery were lower in the supplemented group and supplementation was also associated with reduced birth weights. In malaria endemic areas, pregnant women with the haemoglobin genotype AS may not benefit from iron supplementation during pregnancy.
The administration of hormonal replacement treatment to women with an intact uterus needs to be s... more The administration of hormonal replacement treatment to women with an intact uterus needs to be supplemented with progestogenic compounds to avoid endometrial hyperplasia. However, progestins may cancel the beneficial effects of estrogens on the cardiovascular system. The goal of this study was to examine the effects of adding cyproterone acetate to estradiol (E(2))on aorta atherogenesis. Thirty-two cholesterol-fed New Zealand white rabbits were studied for 4 months. The animals underwent laparotomy and were randomly allocated to four groups. Twenty-four rabbits underwent bilateral ovariectomy, and the other eight were sham-operated (group S). The ovariectomized rabbits were allocated to three groups of eight animals each receiving E(2) valerate (group E), E(2) valerate plus cyproterone acetate (group EC), or placebo after sterilization (group C). After 4 months, the cholesterol-rich diet caused atherosclerotic aortic lesions in both treated groups that affected 17.91% +/- 10.19% and 28.16% +/- 7.97% of the aortic surface of groups E and EC, respectively, with a markedly lower aortic plaque size in group E than in groups C and S. Rabbits from group E (but not from group EC) had aortic cholesterol content significantly lower than rabbits from the sham-operated and control groups. E(2) valerate reduces aortic atheromatosis in cholesterol-fed, ovariectomized rabbits, and the addition of cyproterone acetate may neutralize this effect.
Radiotherapy for early vocal cord carcinoma affects quality of voice. Nevertheless, most patients... more Radiotherapy for early vocal cord carcinoma affects quality of voice. Nevertheless, most patients refer to having a high satisfaction level with their voice. The few acoustic studies on quality of voice have been performed only in prolonged vowel production, which is not a usual speech situation. The present study has been done with the aim of establishing which phonetic situations reflect a greater alteration in voice production related to irradiation. Eighteen male patients irradiated for Tis-T1 vocal cord carcinoma and a control group of 31 non-irradiated subjects were included in a study of acoustic voice analysis. This analysis was performed one year after radiotherapy. Patients and control group voices were tape recorded in extended vowel production, oral reading of a standard paragraph, spontaneous speech and in a song. Acoustic analysis was performed by a Kay Elemetric's Computerized Speech Lab (model CSL #4300). Fundamental frequency, jitter, shimmer and harmonics-to-noise ratio were obtained in both groups. Statistical test: Lin concordance coefficient and Pearson's correlation coefficient, Student's t-test and ROC curves. Concordance and correlation studies did not allow selection of any subgroup in acoustic parameters and different acoustic situations. Acoustic parameters had higher median values in irradiated patients. Student's t-test showed significant differences for fundamental frequency in sustained vowel production and spontaneous speech; for jitter there was statistical significance in all the acoustic situations and for shimmer in oral reading and song. Jitter showed a cut-off of 2.02% with a sensitivity of 89% and specificity of 97% in classifying irradiated and non-irradiated groups. The ROC curve for jitter correctly classified 94% of subjects into irradiated or non-irradiated groups. The present study showed that jitter obtained from spontaneous speech was the most relevant parameter in discriminating voice in irradiated patients by acoustic analysis. Jitter in spontaneous speech is in need of more analysis in bigger series and in more advanced stages of larynx cancer as its relevance has been demonstrated.
To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicit... more To analyze the results of daily high-dose-rate brachytherapy (HDRBT) on local control and toxicity in the postoperative treatment of endometrial carcinoma (EC). From January 2007 to September 2010, 112 patients were treated with HDRBT after surgery for EC. FIGO staging: 24-IA, 48-IB, 14-II, 12-IIIA, 2-IIIB, 8-IIIC1 and 4-IIIC2. Pathology 99/112 endometrioid and 23/112 other types. Radiotherapy patients were divided into two groups-Group 1 (70/112) consists of external beam irradiation (EBI) plus HDRBT (2 fractions of 5-6 Gy) and Group 2 (42/112) consists of HDRBT alone (4 fractions of 5-6 Gy). Toxicity evaluation RTOG scores for bladder and rectum, and the objective criteria of LENT-SOMA for vagina. Statistics bivariate analysis of Chi-square and Fisher exact tests. With a mean follow-up of 29.52 months (range 9.60-53.57) no patient developed vaginal-cuff relapse. In Group 1 early toxicity appeared in 9 % in rectum, 8.5 % in bladder (G1-G2) and 1.4 % in vagina (G1); late toxicity was present in 8.5 % in rectum (all G1-G2 but 1 G3) and in 25 % in vagina (all G1-G2 but one G4). In Group 2, 9.4 % developed G1-G2 bladder and 6.9 % acute vagina (G1-G2) toxicity. Only 2.3 % had a G1 rectal score and 6.9 % had G1-G2 as vaginal scores for late problems. (1) Daily HDRBT using two fractions of 5-6 Gy after EBI and four fractions of 5-6 Gy as exclusive treatment was a safe regime. (2) Group 1 showed a higher incidence of late vaginal toxicity.
To analyse the impact of prognostic factors on specific overall survival (SOS) after postoperativ... more To analyse the impact of prognostic factors on specific overall survival (SOS) after postoperative radiotherapy (P-RT) in carcinosarcomas. We retrospectively analysed 81 patients who received P-RT from 1977 to 2010 after the diagnosis of carcinosarcomas. 2009 FIGO stage: 25-IA, 20-IB, 6-II, 9-IIIA, 11-IIIC. Age, stage, vascular and lymphatic space invasion (VLSI), myometrial invasion, grade, mitotic index, sarcomatous/epithelial components, tumour size and necrosis were considered for the analysis. we used the Kaplan-Meier method for survival analysis and the Cox model for risk factor evaluation. The mean follow-up of the series was 78.86 months (range 7-381). The median age was 72 years (range 51-89). 30 out 81 (37 %) patients relapsed and died (22.2 % pelvic and abdominal, 13.5 % exclusive distant metastasis). On univariate and multivariate analysis only stage had a significant impact on SOS. At 5 years, stage I-II had a SOS of 66 % in comparison with stage III with 30 %. Two groups of patients showing different outcome were found after P-RT in uterine carcinosarcomas: stage I-II patients had a life expectancy 2.5-fold longer compared to stage III patients. New therapeutic strategies are warranted in carcinosarcomas considering the high incidence of distant metastasis.
American Journal of Obstetrics and Gynecology, 1996
Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone... more Our purpose was to determine the relative power of basal inhibin and follicle-stimulating hormone (defined before treatment) and the woman's age both as single and combined predictors of ovarian response in an in vitro fertilization program where pituitary desensitization was routinely used. The study was a retrospective analytic investigation of 120 women undergoing the first cycle of in vitro fertilization. Forty consecutive cycles canceled because of poor follicular response were initially selected. As a control group, the nearest completed in vitro fertilization cycles before and after each canceled cycle (i.e., the closest cycles in temporal relationship to the index cycle) were used. The mean age and basal follicle-stimulating hormone level were significantly higher in the canceled than in the control group, whereas the basal inhibin level was significantly higher in the latter. Follicle-stimulating hormone and inhibin alone, with an accuracy (predictive value of ovarian response) of 70%, were better predictors of cancellation than age was. Any two or all three of these variables studied did not improve the predictive value of follicle-stimulating hormone or inhibin alone. Age is a poorer predictor than pretreatment basal follicle-stimulating hormone and inhibin levels for ovarian response in in vitro fertilization cycles stimulated with gonadotropin-releasing hormone agonist-gonadotropin treatment. Basal follicle-stimulating hormone and inhibin have similar predictive properties and could therefore be used interchangeably.
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