Você pesquisou por y - Revista Brasileira de Ginecologia e Obstetrícia
Summary
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):537-543
DOI 10.1590/S0100-72032008001100002
PURPOSE: to evaluate the effect of tibolone use on dopplervelocimetric parameters of ophthalmic and retinal arteries. METHODS: clinical, prospective, longitudinal, randomized, placebo-controlled, triple-blind study, in which among 100 menopausal women, 50 have used 2.5 mg of the active principle tibolone (Tib Group) and 50, placebo as a means to form the control-group (Plac Group). In the Tib Group, 44 of the 50 women returned after 84 days to finish the exams, and in the Plac Group, 47. The ophthalmic and retinal arteries were studied to determine the resistance index (RI), the pulsatility index (PI) and the systole/diastole ratio (S/D). Assessments have been done before and 84 days after medication. The t-Student test has been used for the comparison of means between the groups in independent samples, as well as for within-group comparisons in dependent samples. RESULTS: in both groups, the women's characteristics were similar in age, menopause duration, body mass index, arterial blood pressure, deliveries and cardiac rate. The Tib Group presented the following values in the ophthalmic artery: RI(pre)=0.71±0.05, RI(post)0.72±0.08 (p=0.43); PI(pre)=1.29±0.22, PI(post)=1.30±0.25 (p=0.4) and S/D(pre)=3.49±0.77, SD(post)=3.65±0.94 (p=0.32). In the retinal artery, the following values have been found: RI(pre)=0.67±0.09, RI(post)=0.69±0.10 (p=0.7); PI(pre)=1.20±0.29, PI(post)=1.22±0.3 (p=0.2) and SD(pre)=3.29±0.95, SD(post)=3.30±1.07 (p=0.3). Also, the tibolone and control groups did not show any significant difference in regard to the above indexes in the end of the study. CONCLUSIONS: the 2.5 mg dose of tibolone had no effect on the Doppler velocimetry indexes of the ophthalmic and retinal arteries.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):537-543
DOI 10.1590/S0100-72032008001100002
PURPOSE: to evaluate the effect of tibolone use on dopplervelocimetric parameters of ophthalmic and retinal arteries. METHODS: clinical, prospective, longitudinal, randomized, placebo-controlled, triple-blind study, in which among 100 menopausal women, 50 have used 2.5 mg of the active principle tibolone (Tib Group) and 50, placebo as a means to form the control-group (Plac Group). In the Tib Group, 44 of the 50 women returned after 84 days to finish the exams, and in the Plac Group, 47. The ophthalmic and retinal arteries were studied to determine the resistance index (RI), the pulsatility index (PI) and the systole/diastole ratio (S/D). Assessments have been done before and 84 days after medication. The t-Student test has been used for the comparison of means between the groups in independent samples, as well as for within-group comparisons in dependent samples. RESULTS: in both groups, the women's characteristics were similar in age, menopause duration, body mass index, arterial blood pressure, deliveries and cardiac rate. The Tib Group presented the following values in the ophthalmic artery: RI(pre)=0.71±0.05, RI(post)0.72±0.08 (p=0.43); PI(pre)=1.29±0.22, PI(post)=1.30±0.25 (p=0.4) and S/D(pre)=3.49±0.77, SD(post)=3.65±0.94 (p=0.32). In the retinal artery, the following values have been found: RI(pre)=0.67±0.09, RI(post)=0.69±0.10 (p=0.7); PI(pre)=1.20±0.29, PI(post)=1.22±0.3 (p=0.2) and SD(pre)=3.29±0.95, SD(post)=3.30±1.07 (p=0.3). Also, the tibolone and control groups did not show any significant difference in regard to the above indexes in the end of the study. CONCLUSIONS: the 2.5 mg dose of tibolone had no effect on the Doppler velocimetry indexes of the ophthalmic and retinal arteries.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):544-549
DOI 10.1590/S0100-72032008001100003
PURPOSE: to compare the efficacy of tinidazole and cephazolin on the febrile and infectious morbidity of post vaginal and abdominal hysterectomy antibiotic prophylaxis. METHODS: randomized clinical study, where women admitted to hospital for hysterectomy were randomly allocated in one of the following antibiotic prophylaxis groups: Group C (2 g of IV cephazolin in the anesthetic induction); Group T (2 g of tinidazole orally, 12 hours before the surgery); or Group C+T (2 g of tinidazole orally 12 hours before the surgery and 2g of IV cephazolin in the anesthetic induction). Cervicovaginal smears were collected for specific cultures and the diagnosis of bacterial vaginosis (BV) was based in Amsel and Nugent's criteria. The patients were reevaluated 7 and 30 days after the surgery for signs of febrile and/or infectious morbidity. The χ2 or the Fisher's exact test was used to assess differences among the three groups, with a significance level of 5%. The sample power (1-β) was calculated through the SAS program. RESULTS: seven days after the hysterectomy, infectious morbidity was diagnosed in 6.6% of the women, but with no significant difference among the three groups studied (p=0.12). There was no febrile or infectious morbidity at the immediate post-surgical period or after 30 days from the surgery. BV ratio at the pre-surgical period was significantly higher among the women submitted to vaginal hysterectomy, rather than among the ones submitted to abdominal hysterectomy (27 versus 7%, p=0.02). BV ratio was also higher after 30 days, among the women submitted to vaginal hysterectomy (20 versus 8%), though without statistical significance (p=0.19). CONCLUSIONS: the use of tinidazole, isolated or associated with cephazolin has not presented higher efficacy, than the use of cephazolin, alone to prevent febrile or infectious morbidity post hysterectomy. The high ratio of BV at the immediate pre-surgery period among the women submitted to vaginal hysterectomy suggests that this infection must be better investigated and properly treated before the surgery.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):544-549
DOI 10.1590/S0100-72032008001100003
PURPOSE: to compare the efficacy of tinidazole and cephazolin on the febrile and infectious morbidity of post vaginal and abdominal hysterectomy antibiotic prophylaxis. METHODS: randomized clinical study, where women admitted to hospital for hysterectomy were randomly allocated in one of the following antibiotic prophylaxis groups: Group C (2 g of IV cephazolin in the anesthetic induction); Group T (2 g of tinidazole orally, 12 hours before the surgery); or Group C+T (2 g of tinidazole orally 12 hours before the surgery and 2g of IV cephazolin in the anesthetic induction). Cervicovaginal smears were collected for specific cultures and the diagnosis of bacterial vaginosis (BV) was based in Amsel and Nugent's criteria. The patients were reevaluated 7 and 30 days after the surgery for signs of febrile and/or infectious morbidity. The χ2 or the Fisher's exact test was used to assess differences among the three groups, with a significance level of 5%. The sample power (1-β) was calculated through the SAS program. RESULTS: seven days after the hysterectomy, infectious morbidity was diagnosed in 6.6% of the women, but with no significant difference among the three groups studied (p=0.12). There was no febrile or infectious morbidity at the immediate post-surgical period or after 30 days from the surgery. BV ratio at the pre-surgical period was significantly higher among the women submitted to vaginal hysterectomy, rather than among the ones submitted to abdominal hysterectomy (27 versus 7%, p=0.02). BV ratio was also higher after 30 days, among the women submitted to vaginal hysterectomy (20 versus 8%), though without statistical significance (p=0.19). CONCLUSIONS: the use of tinidazole, isolated or associated with cephazolin has not presented higher efficacy, than the use of cephazolin, alone to prevent febrile or infectious morbidity post hysterectomy. The high ratio of BV at the immediate pre-surgery period among the women submitted to vaginal hysterectomy suggests that this infection must be better investigated and properly treated before the surgery.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):550-555
DOI 10.1590/S0100-72032008001100004
PURPOSE: to analyze interobserver variability in the histopathological diagnosis of premalignant breast lesions before and after training with diagnostic standardized criteria. METHODS: Slides containing histological sections representative of three kinds of breast lesions (atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion), revised by an international specialist in breast pathology whose diagnoses were considered as golden standard, have been used. The same slides have been evaluated at two different times by five pathologists from the community according to a specific protocol for classifying the lesions. In the first evaluation, the cases were analyzed and classified according to the specific criteria adopted in each service. At the second time, the pathologists were given a tutorial containing diagnostic criteria and representative images, and the lesions were classified again, employing the standardized criteria. Interobserver analysis using percent agreement and weighted Kappa index has been performed. RESULTS: There has been a large diagnostic variation among the pathologists in the initial analysis without the use of standardized diagnostic criteria concerning the diagnostic, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis varied from 0.15 to 0.40). In the second evaluation using standardized criteria, there has been a significant improvement in the diagnostic concordance among the five pathologists concerning the diagnosis, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis have varied from 0.42 to 0.80). CONCLUSIONS: interobserver concordance related to diagnosis and classification of breast premalignant lesions may be improved with specific training and the use of standardized histopathological criteria.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):550-555
DOI 10.1590/S0100-72032008001100004
PURPOSE: to analyze interobserver variability in the histopathological diagnosis of premalignant breast lesions before and after training with diagnostic standardized criteria. METHODS: Slides containing histological sections representative of three kinds of breast lesions (atypical ductal hyperplasia, ductal carcinoma in situ and ductal carcinoma in situ with microinvasion), revised by an international specialist in breast pathology whose diagnoses were considered as golden standard, have been used. The same slides have been evaluated at two different times by five pathologists from the community according to a specific protocol for classifying the lesions. In the first evaluation, the cases were analyzed and classified according to the specific criteria adopted in each service. At the second time, the pathologists were given a tutorial containing diagnostic criteria and representative images, and the lesions were classified again, employing the standardized criteria. Interobserver analysis using percent agreement and weighted Kappa index has been performed. RESULTS: There has been a large diagnostic variation among the pathologists in the initial analysis without the use of standardized diagnostic criteria concerning the diagnostic, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis varied from 0.15 to 0.40). In the second evaluation using standardized criteria, there has been a significant improvement in the diagnostic concordance among the five pathologists concerning the diagnosis, nuclear grade and histological grade (weighted Kappa indexes related to diagnosis have varied from 0.42 to 0.80). CONCLUSIONS: interobserver concordance related to diagnosis and classification of breast premalignant lesions may be improved with specific training and the use of standardized histopathological criteria.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):556-560
DOI 10.1590/S0100-72032008001100005
PURPOSE: to evaluate whether the sample adequacy influences the detection of precursor cervical cancer lesions. METHODS: a transversal study from January 2004 to December 2005. A number of 10,951 results of cervical cytotopathological exams from users of the National Health System (Sistema Único de Saúde, SUS) in Goiânia, Goiás , Brazil, was studied. These women had spontaneously looked for the services from the Family Health Program or from the Basic Units of Health. Samples were collected by medical doctors and nurses, through the conventional technique to detect cervical cancer. The analyzed smears were classified by the Bethesda System, the sample adequacy being defined along the routine screening and categorized as: satisfactory, satisfactory but presenting factors that might partially jeopardize the analysis, and unsatisfactory. Results were stored in the Epi-Info 3.3.2 program. The χ2 test was used to compare altered results with the adequacy of the samples from cytopathological smears. Differences with probability of rejection of the null hypothesis lower than 5% (p<0.05) were considered as significant. RESULTS: From 10,951 smears, 51.1% were classified as having satisfactory adequacy for analysis, 46.6% as satisfactory, but presenting some limiting factors, and 2.3%, as unsatisfactory. The main factors which have partially jeopardized the analysis were: lack of endocervical cells (52.2%), dried smears (22.8%), purulence (14.9%), or smears with some thick areas (9.5%). There was a higher rate of altered smears when the sample had been classified as satisfactory for analysis and with representation of endocervical cells ASC-US (2.3%), ASC-H (0.6%), LSIL (3.2%), HSIL (1.7%) and 0.3% of AGC. Differences were significant when p=0.001. The rate of low and high grade lesions was higher when the smears were satisfactory for analysis. CONCLUSIONS: the rate of precursor uterine cervix cancer lesions varies according to the sample adequacy, and the main adequacy limitations of the sample are mainly related to the collection condition.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):556-560
DOI 10.1590/S0100-72032008001100005
PURPOSE: to evaluate whether the sample adequacy influences the detection of precursor cervical cancer lesions. METHODS: a transversal study from January 2004 to December 2005. A number of 10,951 results of cervical cytotopathological exams from users of the National Health System (Sistema Único de Saúde, SUS) in Goiânia, Goiás , Brazil, was studied. These women had spontaneously looked for the services from the Family Health Program or from the Basic Units of Health. Samples were collected by medical doctors and nurses, through the conventional technique to detect cervical cancer. The analyzed smears were classified by the Bethesda System, the sample adequacy being defined along the routine screening and categorized as: satisfactory, satisfactory but presenting factors that might partially jeopardize the analysis, and unsatisfactory. Results were stored in the Epi-Info 3.3.2 program. The χ2 test was used to compare altered results with the adequacy of the samples from cytopathological smears. Differences with probability of rejection of the null hypothesis lower than 5% (p<0.05) were considered as significant. RESULTS: From 10,951 smears, 51.1% were classified as having satisfactory adequacy for analysis, 46.6% as satisfactory, but presenting some limiting factors, and 2.3%, as unsatisfactory. The main factors which have partially jeopardized the analysis were: lack of endocervical cells (52.2%), dried smears (22.8%), purulence (14.9%), or smears with some thick areas (9.5%). There was a higher rate of altered smears when the sample had been classified as satisfactory for analysis and with representation of endocervical cells ASC-US (2.3%), ASC-H (0.6%), LSIL (3.2%), HSIL (1.7%) and 0.3% of AGC. Differences were significant when p=0.001. The rate of low and high grade lesions was higher when the smears were satisfactory for analysis. CONCLUSIONS: the rate of precursor uterine cervix cancer lesions varies according to the sample adequacy, and the main adequacy limitations of the sample are mainly related to the collection condition.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):561-565
DOI 10.1590/S0100-72032008001100006
PURPOSE: to evaluate the influence of age on the quality of semen in men submitted to spermatic analysis in a human reproduction service, in cases of conjugal infertility. METHODS: a retrospective study in which the spermiograms of all men in process of investigation for conjugal infertility in a service of assisted reproduction in the Northeast of Brazil were evaluated from September 2002 to December 2004. A number of 531 individuals submitted to 531 spermatic evaluations were included in the study. The following parameters have been analyzed: spermatic volume, concentration, motility and morphology. The men under investigation have been divided in groups, according to the results obtained in each of the variables studied. Seminal volume groups were divided in: hypospermia, normospermia and hyperspermia. Spermatic concentration groups were divided in: azoospermia, oligospermia, normospermia and polyspermia. Motility groups were divided in: normal motility and asthenospermia. Morphology groups were divided in: normal morphology and teratospermia. The t test has been used to compare the average age of patients in groups with normal and in groups with altered parameters. The program XLSTAT (p<0.05) has been used for the statistical analysis. RESULTS: the individuals studied presented an average of 37±7.9 years old, with an average of seminal volume of 3±1.4 mL, a spermatic concentration of 61.4±66.4 spermatozoids by mL of semen, a progressive motility of 44.7±19.4% of the total of spermatozoids and normal morphology of 11.2±6.6% of the spermatozoids. Average age among groups were similar, except for that of individuals with hypospermia, which was significantly higher than the one from men with normospermia (39.6±10.3 versus 36.5±7.3, p=0.001). CONCLUSIONS: age interferes in an inversely proportional way on the ejaculated volume, but does not influence spermatic concentration, motility and morphology.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):561-565
DOI 10.1590/S0100-72032008001100006
PURPOSE: to evaluate the influence of age on the quality of semen in men submitted to spermatic analysis in a human reproduction service, in cases of conjugal infertility. METHODS: a retrospective study in which the spermiograms of all men in process of investigation for conjugal infertility in a service of assisted reproduction in the Northeast of Brazil were evaluated from September 2002 to December 2004. A number of 531 individuals submitted to 531 spermatic evaluations were included in the study. The following parameters have been analyzed: spermatic volume, concentration, motility and morphology. The men under investigation have been divided in groups, according to the results obtained in each of the variables studied. Seminal volume groups were divided in: hypospermia, normospermia and hyperspermia. Spermatic concentration groups were divided in: azoospermia, oligospermia, normospermia and polyspermia. Motility groups were divided in: normal motility and asthenospermia. Morphology groups were divided in: normal morphology and teratospermia. The t test has been used to compare the average age of patients in groups with normal and in groups with altered parameters. The program XLSTAT (p<0.05) has been used for the statistical analysis. RESULTS: the individuals studied presented an average of 37±7.9 years old, with an average of seminal volume of 3±1.4 mL, a spermatic concentration of 61.4±66.4 spermatozoids by mL of semen, a progressive motility of 44.7±19.4% of the total of spermatozoids and normal morphology of 11.2±6.6% of the spermatozoids. Average age among groups were similar, except for that of individuals with hypospermia, which was significantly higher than the one from men with normospermia (39.6±10.3 versus 36.5±7.3, p=0.001). CONCLUSIONS: age interferes in an inversely proportional way on the ejaculated volume, but does not influence spermatic concentration, motility and morphology.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):566-572
DOI 10.1590/S0100-72032008001100007
PURPOSE: to verify the prevalence and clinical characteristics of patients with primary amenorrhea and XY caryotype, evaluated in our Service, aiming at identifying findings which could help their recognition. METHODS: from January 1975 to November 2007, 104 patients with amenorrhea were evaluated. All the cases were analyzed by the caryotype by GTG bands. Among them, 21 (20.2%) presented a XY 46 constitution. Nevertheless, two of them were excluded from the study, because of incomplete data in their patient's chart. Most of the 19 patients who formed the sample had been referred to us by the gynecology clinics (63.2%). Their ages varied from 16 to 41 years old (an average of 22.1). Data were collected about their family and previous history, physical examination and results of complementary exams and the information was taken into consideration to determine the diagnosis. RESULTS: the predominant diagnosis was resistance to androgens syndrome (n=12; 63.2%); five patients (25.3%) presented XY pure gonadal dysgenesis (XY PGD), one (5.3%) 17 alpha-hydroxylase deficiency, and one (5.3%), 5 alpha-reductase deficiency. Clinical findings frequently found in these patients included abnormal development of secondary sexual characters (n=19), uterine agenesia with a blind vagina (n=14), family history of amenorrhea (n=8), and palpable gonads in the inguinal canal (n=5). Two of them presented a history of inguinal hernia. Systemic arterial hypertension was only diagnosed in the patient with 17 alpha-hydroxylase deficiency, and gonadal malignization, in the one with XY PGD. CONCLUSIONS: the rate of patients with XY caryotype (20%) was higher than the one described in the literature (3 to 11%). It is believed that this fact is related to the way patients are usually referred to our service. Some findings from the clinical history and from the physical examination should be evaluated as a routine in individuals with primary amenorrhea. This way, there would be a more precocious detection of XY 46 patients, and a better clinical management of them, as a consequence.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):566-572
DOI 10.1590/S0100-72032008001100007
PURPOSE: to verify the prevalence and clinical characteristics of patients with primary amenorrhea and XY caryotype, evaluated in our Service, aiming at identifying findings which could help their recognition. METHODS: from January 1975 to November 2007, 104 patients with amenorrhea were evaluated. All the cases were analyzed by the caryotype by GTG bands. Among them, 21 (20.2%) presented a XY 46 constitution. Nevertheless, two of them were excluded from the study, because of incomplete data in their patient's chart. Most of the 19 patients who formed the sample had been referred to us by the gynecology clinics (63.2%). Their ages varied from 16 to 41 years old (an average of 22.1). Data were collected about their family and previous history, physical examination and results of complementary exams and the information was taken into consideration to determine the diagnosis. RESULTS: the predominant diagnosis was resistance to androgens syndrome (n=12; 63.2%); five patients (25.3%) presented XY pure gonadal dysgenesis (XY PGD), one (5.3%) 17 alpha-hydroxylase deficiency, and one (5.3%), 5 alpha-reductase deficiency. Clinical findings frequently found in these patients included abnormal development of secondary sexual characters (n=19), uterine agenesia with a blind vagina (n=14), family history of amenorrhea (n=8), and palpable gonads in the inguinal canal (n=5). Two of them presented a history of inguinal hernia. Systemic arterial hypertension was only diagnosed in the patient with 17 alpha-hydroxylase deficiency, and gonadal malignization, in the one with XY PGD. CONCLUSIONS: the rate of patients with XY caryotype (20%) was higher than the one described in the literature (3 to 11%). It is believed that this fact is related to the way patients are usually referred to our service. Some findings from the clinical history and from the physical examination should be evaluated as a routine in individuals with primary amenorrhea. This way, there would be a more precocious detection of XY 46 patients, and a better clinical management of them, as a consequence.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):573-582
DOI 10.1590/S0100-72032008001100008
PURPOSE: to identify valid guidelines for the approach of women with cytopathological diagnosis of undetermined significance atypias in squamous cells (ASC), discussing its applicability to the Brazilian scenario. METHODS: an electronic search of publications at PubMed, National Guidelines Clearinghouse and Scholar Google was carried out, as well as a manual search of references from the texts found. The guidelines identified, and specifically related to the theme, were evaluated according to its validity and the recommendations were criticized and summarized. RESULTS: guidelines for the United Kingdom, France, Australia, the USA and New Zealand have been considered as valid. These documents recommend repeating the cytology in six or twelve months, in ASCs of undetermined significance (ASC-US) before referring to colposcopy, and immediate referral to colposcopy in ASCs, when it is not possible to disregard high degree lesions (ASC-H). We have also found valid colposcopy recommendations for women with ASC-US in special situations (immune deficient women requiring specialist assistance) and the use of oncogenic HPV test, which, when present in women over 20, should motivate referral to colposcopy. CONCLUSIONS: the clinical guidelines recommended for the Programa Nacional de Controle do Cancer do Colo do Útero in Brazil can be improved with the referral to colposcopy in special situations (immune deficient women requiring specialist assistance), the use of test for the detection of oncogenic HPV in women over 20 (when present, refer to colposcopy), the investigation of vaginal lesions, the use of estrogens before the colposcopy in post-menopausal women, and disregard biopsia in case of slighter alterations.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2008;30(11):573-582
DOI 10.1590/S0100-72032008001100008
PURPOSE: to identify valid guidelines for the approach of women with cytopathological diagnosis of undetermined significance atypias in squamous cells (ASC), discussing its applicability to the Brazilian scenario. METHODS: an electronic search of publications at PubMed, National Guidelines Clearinghouse and Scholar Google was carried out, as well as a manual search of references from the texts found. The guidelines identified, and specifically related to the theme, were evaluated according to its validity and the recommendations were criticized and summarized. RESULTS: guidelines for the United Kingdom, France, Australia, the USA and New Zealand have been considered as valid. These documents recommend repeating the cytology in six or twelve months, in ASCs of undetermined significance (ASC-US) before referring to colposcopy, and immediate referral to colposcopy in ASCs, when it is not possible to disregard high degree lesions (ASC-H). We have also found valid colposcopy recommendations for women with ASC-US in special situations (immune deficient women requiring specialist assistance) and the use of oncogenic HPV test, which, when present in women over 20, should motivate referral to colposcopy. CONCLUSIONS: the clinical guidelines recommended for the Programa Nacional de Controle do Cancer do Colo do Útero in Brazil can be improved with the referral to colposcopy in special situations (immune deficient women requiring specialist assistance), the use of test for the detection of oncogenic HPV in women over 20 (when present, refer to colposcopy), the investigation of vaginal lesions, the use of estrogens before the colposcopy in post-menopausal women, and disregard biopsia in case of slighter alterations.
