Homozygous Hb Stanleyville-II [alpha2 78(EF7) Asn>Lys; HBA2:c.237C>A, not C>G] associated with genotype -α 3.7/-α 3.7 in two Brazilian families.

INTRODUCTION: Several hemoglobin variants have electrophoretic behavior similar to hemoglobin S, which may lead to false diagnosis for sickle-cell disorders in newborn screening programs. A homozygous hemoglobin with S mobility was detected in two unrelated babies in Brazil. METHODS: Isoelectric focusing and high-performance liquid chromatography assays, gene sequencing, and restriction fragment length polymorphism with AfeI were used to characterize the hemoglobin. RESULTS: Hb Stanleyville-II and -α(3.7) /-α(3.7) type I deletion in the α-globin gene was diagnosed. Parents were heterozygous for both Hb Stanleyville-II and α-thalassemia. Hypochromia and microcytosis were probably due to the homozygous α-thalassemia. CONCLUSION: Stanleyville-II gene mutation is HBA2:c.237C>A, or C>G, and this information on the Globin Gene Server should be updated; AfeI test is a fast and accurate method to detect it; NBS programs should consider the possibility of Hb Stanleyville-II whenever IEF shows one band in the HbS position, and another one between S and C.

Frequency of 8 CFTR gene mutations in cystic fibrosis patients in Minas Gerais, Brazil, diagnosed by neonatal screening

The nature and frequency of cystic fibrosis mutations in Brazil is not uniform due to the highly varied ethnic composition of the population. The average frequency of the F508del mutation has been reported to be 48.6 percent. Other common mutations in Brazil are G542X, R1162X, and N1303K. The aim of this study was to analyze the frequency of 8 mutations (F508del, G542X, R1162X, N1303K, W1282X, G85E, 3120+1G>A, and 711+1G>T) in a sample of 111 newborn patients with cystic fibrosis diagnosed by the Cystic Fibrosis Neonatal Screening Program of Minas Gerais State. The mutations were tested by allele-specific oligonucleotide PCR with specially designed primers. An allele frequency of 48.2 percent was observed for the F508del mutation, and allele frequencies of 5.41, 4.50, 4.05, and 3.60 percent were found for the R1162X, G542X, 3120+1G>A, and G85E mutations, respectively. The genotypes obtained were in Hardy-Weinberg equilibrium. These data demonstrate that the 8-mutation panel studied here has extensive coverage (68 percent) for the cystic fibrosis mutations in Minas Gerais. These data improve our knowledge of cystic fibrosis in Brazil, particularly in this region. In addition, this investigation contributed to the establishment of a sensitive and population-specific mutation panel, which can be helpful for molecular diagnosis of cystic fibrosis.

Frequency of 8 CFTR gene mutations in cystic fibrosis patients in Minas Gerais, Brazil, diagnosed by neonatal screening.

The nature and frequency of cystic fibrosis mutations in Brazil is not uniform due to the highly varied ethnic composition of the population. The average frequency of the F508del mutation has been reported to be 48.6%. Other common mutations in Brazil are G542X, R1162X, and N1303K. The aim of this study was to analyze the frequency of 8 mutations (F508del, G542X, R1162X, N1303K, W1282X, G85E, 3120+1G>A, and 711+1G>T) in a sample of 111 newborn patients with cystic fibrosis diagnosed by the Cystic Fibrosis Neonatal Screening Program of Minas Gerais State. The mutations were tested by allele-specific oligonucleotide PCR with specially designed primers. An allele frequency of 48.2% was observed for the F508del mutation, and allele frequencies of 5.41, 4.50, 4.05, and 3.60% were found for the R1162X, G542X, 3120+1G>A, and G85E mutations, respectively. The genotypes obtained were in Hardy-Weinberg equilibrium. These data demonstrate that the 8-mutation panel studied here has extensive coverage (68%) for the cystic fibrosis mutations in Minas Gerais. These data improve our knowledge of cystic fibrosis in Brazil, particularly in this region. In addition, this investigation contributed to the establishment of a sensitive and population-specific mutation panel, which can be helpful for molecular diagnosis of cystic fibrosis.

Diagnóstico da hepatite C em pacientes com doença renal crônica em hemodiálise: qual a melhor estratégia? / Diagnosis of hepatitis C in hemodialysis patients with end-stage renal disease (ESRD): what is the best strategy?

hepatite (HCV), comparados à população em geral, face à exposição frequente ao sangue e à contaminação nosocomial. Entretanto, o diagnóstico da hepatite C nesses pacientes é dificultado por sintomas inespecíficos, valores normais de alanina aminotransferase (ALT), na maioria dos casos, sorologia falso-negativa e baixa viremia. Objetivo: definir e avaliar a acurácia dos métodos diagnósticos da hepatite C em pacientes em HD. Métodos: foram avaliados 500 pacientes com DRC em HD, com anti HCV negativo, histórico e prospectivo de três meses, e avaliação de uma amostra de HCV RNA qualitativo e ALT mensal durante o seguimento. Foram excluídos pacientes com diagnóstico prévio de hepatite B e C, HIV, transplantados, em diálise peritoneal e com acesso venoso por cateter duplo-lúmen. Resultados: o tempo médio de HD foi de 48,8 ± 41,2 meses; ALT revelou-se normal em 92%; anti-HCV e HCV RNA negativos em 99,8% dos pacientes; apenas um paciente (0,2%) apresentou viremia positiva, ALT normal e anti HCV falso-negativo durante o período de seguimento. Conclusões: o teste anti-HCV e a ALT não detectaram precocemente a hepatite C em paciente renal crônico com viremia positiva, o que pode ser explicado pelo comprometimento da resposta imune associada à uremia, ou devido ao período prolongado de janela imunológica antes da soroconversão. Entretanto, o valor preditivo negativo do anti-HCV foi alto, sugerindo que uma redução no intervalo de seis meses da dosagem do anti-HCV pode ser uma estratégia para o monitoramento e a detecção precoce da hepatite C nesses pacientes

Introduction: Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are at a higher risk of infection with hepatitis C virus (HCV), when compared to the general population, due to frequent blood exposure and nosocomial infections. However, the diagnosis of hepatitis C in those patients is very difficult due to non-specific symptoms, normal alanine aminotransferase (ALT) levels, in most cases, false-negative serology, and low viral load. Objective: To define and evaluate the accuracy of hepatitis C diagnostic methods on HD patients. Methods: Five hundred HD patients with ESRD, negative anti-HCV in the past, and, for the next three months, underwent monthly qualitative HCV RNA and ALT testing during follow-up. Patients with a diagnosis of hepatitis B and C, HIV, with kidney grafts, in peritoneal dialysis, and with venous access with double-lumen catheter were excluded. Results: Mean time of HD was 48.8 ± 41.2 months; it was detected normal ALT in 92% of patients; negative anti-HCV and HCV RNA in 99.8% of patients; only one patient (0.2%) showed positive viremia, normal ALT, and false-negative anti-HCV during the follow-up period. Conclusions: Anti-HCV and ALT did not allow early detection of hepatitis C in a patient with ESRD and positive viremia, which can be explained by the disruption of the immune response associated with uremia or due to the prolonged immunologic window before seroconversion. However, anti-HCV showed a high negative predictive value, suggesting that a reduction in the six-month interval of the anti-HCV test could be a strategy for monitoring and early detection of hepatitis C in those patients

Total laparoscopic radical hysterectomy (type III) and pelvic lymphadenectomy.

A case of Stage IIA, G2 carcinoma of the cervix treated by total laparoscopic radical hysterectomy and pelvic lymphadenectomy is reported. To our knowledge, a total laparoscopic radical hysterectomy with laparoscopic lymphadenectomy has not been previously described in Italy.

Fertility after laparoscopic myomectomy of large uterine myomas: operative technique and preliminary results.

OBJECTIVE: The purpose of this study was to evaluate indications and complications of laparoscopic myomectomy with regard to the reproductive outcome of infertile women with a large leiomyomatous uterus. METHODS: From January 1997 to July 1999, 144 patients underwent laparoscopic myomectomy for a myoma measuring > or = 5 cm in diameter. Indications for surgery were increase in size of myoma in infertile patients (70.8%), pain (44.4%) or abnormal bleeding (68%). Average size of myomas were 7.8 cm with a range of 5 cm to 18 cm. The myomas were intramural/submucosal (n = 108), subserosal (n = 15), intraligamentous (n = 14) and peduncolated (n = 7). The laparotomy conversion rate was 1.39% (n = 2); one case required a blood transfusion. Operating time ranged from 58 to 180 minutes with an average of 95 minutes. Average hospital stay was 2.6 days and the overall complication rate was 2.08%. Eighteen patients (12.5%) underwent second-look laparoscopy. The rate of postoperative adhesion was 33.3%; there were no adnexal adhesions. In all cases ultrasonography was done one day after the operation and five weeks postoperatively to compare wound healing, the last control showed an irregular hypodense area in only 14 patients (9.7%). RESULTS: Twenty-six patients operated on in 1997 went on to conceive: nine vaginal deliveries, 12 Caesarean sections, four miscarriages and one ectopic pregnancy. No uterine rupture was observed. The pregnancy rate for patients submitted to laparoscopic myomectomy in 1997 (n = 38) was 34.21% at six months (n = 13) and 55.26% (n = 21) at 12 months after the procedures. CONCLUSIONS: Our preliminary results confirm that conception occurs in the majority of infertile women with a large leiomyomatous uterus who undergo myomectomy and second-look laparoscopy leads to a low complication rate.

Breast cancer incidence rates in Slovenia 1971-1993.

BACKGROUND: Analyses of time trends in breast cancer incidence and mortality have generally revealed cohort-based changes in the rates. These have been linked to cohort-based changes in lifestyle factors. The effect of the changes in the reproductive risk factors on the changes in the rates, and the relative importance of the reproductive characteristics in Slovenia, a country which has not had much breast cancer screening, are investigated. METHODS: Data on breast cancer incidence for 1971-1993 were obtained from the Cancer Registry of Slovenia (Registry). The Registry covers the whole population of the Republic of Slovenia (1.99 million on 30 June 1993). The statistical analysis uses parametric age-period-cohort models. RESULTS: Breast cancer incidence has increased by 70% in Slovenia from 1971 to 1993, These changes are dominated by cohort effects and the cohorts born in 1907-1922 have the greatest increase in incidence. Period effects on changes in incidence were modest. The percentage of nulliparous women in the cohort and the average family size in the cohort explained 38% of the variation in the cohort effects. CONCLUSIONS: The percentage of nulliparous women in the cohort is the most important reproductive variable associated with the trends in the rates, with breast cancer risk predicted to be higher in cohorts with a larger percentage of nulliparous women. As the cohorts born 1932-1946 have a more favourable reproductive pattern as regards breast cancer risk, compared to the 1907-1922 cohorts, age-specific incidence rates in Slovenia would be predicted to decline in the future in the absence of changes in the other risk factors.

Induced abortion and contraception: survey of 576 young women in Naples.

The aim of the study was to investigate the link between induced abortion and contraceptive methods. Five hundred and seventy-six women who underwent induced abortions at the Obstetrics and Gynecology Institute of the Second University of Naples were interviewed. They were asked about their knowledge of contraception methods; age, school attendance rate and marital status were also considered. The women were 27.8 (mean age) years old, high school educated (58.5%), married (41%), nulliparous (63%). Twenty-four percent of the women admitted a previous induced abortion. Withdrawal (176 women), condoms (104) and oral contraceptives (74 women) were the most widely used contraceptive methods. Withdrawal (37%) resulted in being the most utilized method during the cycle in which conception occurred; no method had been employed by 31% of the women. We found that 35% of the women had used their contraceptive method in a regular way but become pregnant nevertheless. Another group of 40% had forgotten to use their contraceptives for a few days and became pregnant by accident. In the last group of 25% of the women had not used any contraceptive methods. The diffusion of modern methods of fertility regulation influences the number of induced abortions as shown by its reduction since 1982. Our data confirm that induced abortion is the consequence of an insufficient use of modern contraceptives. Therefore more information is necessary to get women and men to use contraceptive methods regularly.

[Acute pancreatitis. Our experience during 20 years]. / Pancreatite acuta. La nostra esperienza nell'arco di venti anni.

BACKGROUND: On the basis of personal experience and studies, the importance to diagnose quickly the seriousness of an acute pancreatitis with the help of simple and credible criteria of evaluation is underlined. It's also underlined the help of endoscopic papillosphincterotomy in the initial phase of a biliary pancreatitis; in fact this exam permits to perform a laparoscopic cholecystectomy in a second time and reduce surgical trauma. METHODS: Personal experience with 288 cases of acute pancreatitis (AP), during a twenty-year period (1975-1996) is described. In 61% of cases the AP was associated with biliary illness, and in 13% with alcohol abuse. Real important for therapeutic implication and prognostic significance is the classification of severity of acute attack, by using clinical evaluation (pain, fever, jaundice, abdominal tenderness), multiparametric score (i.e. Imrie's score, Ranson's criteria, SAPS or APACHE II score system) and morphological evaluation of the pancreas (echo and CT scan). 151 patients have been admitted at different times to surgery, the cholecystectomy being the more common surgical procedure, with a surgical rate of 52%. RESULTS: The overall mortality has been 7.2%, ranging from 45.4% in 17 severe necrotic haemorrhagic AP to 2.1% for the mild one. CONCLUSIONS: The widespread use of endoscopic retrograde colangiopancreatography (associated to endoscopic sphincterotomy if necessary) and the recent but universally accepted diffusion of laparoscopic cholecystectomy have changed the modern approach to surgical treatment of biliary associated AP, ensuring mininvasive less traumatic surgical procedures.

Inhibitory effect of exogenous oxytocin on ACTH and cortisol secretion during labour.

Complex mechanisms which are still not completely defined, are responsible for the spontaneous onset of labour: an essential role is attributed to endocrine factors. A massive increase, even three times higher than normal physiological values of ACTH and cortisol, has been reported during labour. Similar behaviour has also been recorded for oxytocin at the end of pregnancy as well as during labour. The relationship between oxytocin and the adrenal axis are still debated thus the goal of our study was to attempt to clarify this rapport. Sixty-two women at the end of a term-pregnancy agreed to participate in this study: 46 were innoculated with oxytocin (syntocinon) every 20 minutes for 1 hour; 16 were administered a natural placebo every 20 minutes for 1 hour (control group). ACTH and cortisol values from plasma samples were taken every 20 minutes and analyzed. Our results demonstrated an inhibitory effect of exogenous oxytocin on ACTH and cortisol release. This inhibitory effect, as shown by our results, is time and dose-related. High oxytocin levels, as during exogenous infusion, could induce an effect opposite a normal physiologic one.

Effect of gap length and position on results of treatment of cancer of the larynx in Scotland by radiotherapy: a linear quadratic analysis.

PURPOSE: This paper reports on the analysis of the effect of the length and position of unplanned gaps in radiotherapy treatment schedules. MATERIALS AND METHODS: Data from an audit of the treatment of carcinoma of the larynx are used. They represent all newly diagnosed cases of glottic node-negative carcinoma of the larynx between 1986 and 1990, inclusive, in Scotland that were referred to one of the five Scottish Oncology Centres for primary radical radiotherapy treatment. The end-points are local control of cancer of the larynx in 5 years and the length of the disease-free period. The local control rates at > or =5 years, Pc were analyzed by log linear models and Cox proportional hazard models were used to model the disease-free period. RESULTS: Unplanned gaps in treatment are associated with poorer local control rates and an increased hazard of a local recurrence through their effect on extending the treatment time. A gap of 1 day is potentially damaging but the greatest effect is at treatment extensions of 3 or more days, where the hazard of a failure of local control is increased by a factor of 1.75 (95% confidence interval 1.20-2.55) compared to no gap. The time factor for the actual time was imprecisely estimated at 2.7 Gy/day with a standard error of 13.2 Gy/day. Among those cases who had exactly one gap resulting in a treatment extension of 1 day, there is no evidence that gap position influences local control (P = 0.17). The treatment extension as a result of the gap is more important than the position of the gap in the schedule. CONCLUSIONS: Gaps in the treatment schedule have a detrimental effect on the disease-free period. A gap has a slightly greater effect than an increase in the prescribed treatment time. Any gap in treatment is potentially damaging. The position of the gap in the schedule was shown to be not important.

Efeito do líquido folicular bovino tratado com carväo ativado na secreçäo de FSH em novilhas pré-púberes intatas e ovariectomizadas / Effect of charcoal-treated bovine follicular fluid on the secretion of FSH in ovariectomized and intact prepubertal heifers

O presente trabalho objetivou determinar o efeito do líquido folicular bovino tratado com carväo ativado (LFb) na secreçäo do hormônio folículo estimulante (FSH) de novilhas pré-púberes ovariectomizadas ou intatas. A aplicaçäo de LFb (quatro injeçöes de 10 ml com intervalo de 8 horas) provocou uma queda de aproximadamente 44 por cento na concentraçäo plasmática de FSH nas novilhas ovariectomizadas, mas näo teve efeito nas novilhas intatas. Näo foi observada hipersecreçäo de FSH após o término da aplicaçäo do LFb. Esses resultados sugerem que proteínas presentes no LFb atuam ao nível hipofisiário para inibir a secreçäo de FSH e, diferentemente das intatas, as novilhas ovariectomizadas constituem um modelo adequado para evidenciar esse efeito, particularmente quando o LFb possui reduzida atividade supressora do FSH

Perfis endócrinos e taxa de ovulaçäo de vacas superovuladas com FSH após imunizaçäo passiva contra líquido folicular bovino livre de esteróides / Endocrine profiles and ovulation rate of cow superovulated with FSH following passive immunization against steroid free-bovine follicular fluid

Dez vacas multíparas, secas, foram distribuídas aleatoriamente em dois grupos de cinco animais cada. Nos dias 8 a 12 do diestro, o primeiro grupo recebeu 100 ml de anti-soro contra líquido folicular livre de esteróides (anti-LFb) produzido em ovelhas ovariectomizadas. O segundo grupo (controle) recebeu 100 ml de soro de ovelhas näo-imunizadas. Seis horas após a aplicaçäo, os dois grupos foram superovulados com FSH (18 NIH-FSH-S1 unidades) e LH (0,29 NIH-LH-S1 unidades) administrados em quantidades decrescentes durante quatro dias. Na manhä do terceiro dia, foi administrada uma dose luteolítica de cloprostenol. Duas inseminaçöes foram realizadas 48 e 60 horas após. Os embriöes foram recuperados pelo método cervical 7 dias após a primeira inseminaçäo. Amostras de sangue foram coletadas durante todo o período experimental para determinar, por radioimunoensaio, as concentraçöes plasmáticas de FSH, LH e progesterona. Todas as vacas do grupo imunizado e 3 do grupo controle apresentaram mais de 2 CL. Näo existiu diferença significativa (p>0,05) na taxa de ovulaçäo entre os grupos imunizado e controle (14,4 e 9,9, respectivamente). O número de embriöes recuperado näo foi significativamente diferente (p>0,05) entre os grupos, embora o grupo imunizado tenha apresentado maior número de embriöes transferíveis (3,4 ñ 1,0 versus 0,8 ñ 0,4, p<0,05). As concentraçöes de gonadotrofinas plasmáticas näo foram correlacionadas com a taxa de ovulaçäo ou com o número de embriöes recuperados. As concentraçöes de progesterona plasmática foram positivamente correlacionadas (r = 0,88, p<0,01) com a taxa de ovulaçäo. Os resultados sugerem que o anti-LFb, aplicado antes da superovulaçäo, näo reduz a variabilidade da resposta ovariana

Breast cancer prevalence measured by the Lombardy Cancer Registry.

AIMS AND BACKGROUND: Breast cancer is the most important malignant neoplasm affecting women in Western countries. An increasing number of women undergo regular medical checkups, especially during the first years following the diagnosis. Therefore, from the health planning point of view, it is essential to have prevalence measures to furnish estimates for the demands that the health care system could possibly undergo. METHODS: By means of PREVAL, a computerized program, breast cancer prevalence has been measured in the Varese province using incidence and follow-up data from the Lombardy Cancer Registry (LCR). RESULTS: During the 1986-1988 period, breast cancer prevalence for patients alive within 10 years from diagnosis was about 625 per 100,000 resident women. Of these, 54% were over 60 years and 9% were under 45 years of age. Patients alive within 2 years from diagnosis were about 200 per 100,000 residents; considering the 1978-1980 period, patients alive within 2 years from diagnosis were just 140 per 100,000 residents. This dramatic increase in breast cancer prevalence is present also for long-term survivors (i.e. patients alive at 10-13 years from the diagnosis). Extrapolating breast cancer prevalence measured in the Varese province to the whole Lombardy region, the expected number of prevalent cases alive within 10 years of the diagnosis, presently living in Lombardy, would be 27,500. LCR's breast cancer prevalence figures were compatible with available data provided by the Finnish Cancer Registry. CONCLUSION: Owing to aging of the population, the improvement in survival and the increasing incidence, the number of prevalent cases will increase. This phenomenon has and will have great importance for the health planning.

Stimulus generalization of lifted weights in older and younger women.

Older (62 to 86 years) and younger (17 to 30 years) women were essentially similar in acquisition of weight discriminations and in generalized responding to a range of weights during postdiscrimination tests. In both age groups, acquisition was facilitated by increases in the difference between the positive and negative stimuli, and postdiscrimination gradients were displaced away from the value of the negative stimulus, particularly when it was the heavier of the training pair. The finding from personality test scores that the older women were more introverted than the younger ones, together with the absence of age differences in acquisition and generalization, does not support the Eysenck-Gray hypothesis that introversion influences conditioning processes. The results do suggest that basic conditioning processes are maintained with increasing age in healthy older adults.