Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection

Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations including two cases of 47,XXY, four cases involving a 45,X cell line and three autosomal trisomies. Molecular analysis of the parental origin of the deleted or supernumerary chromosome was performed by using polymorphic microsatellite markers. Six cases involving a sex chromosome abnormality were found to be of paternal origin while the two trisomic cases that could be analysed were of maternal origin. Two cases involved the same infertile couple who had two consecutive ICSI pregnancies terminated because of a chromosome abnormality. The replaced embryos in both cases originated from a single batch of ICSI fertilized oocytes of which part was used to initiate the first pregnancy and part was cryopreserved and used to initiate the second pregnancy.      

Further investigation of the association between gastroesophageal reflux and bronchoconstriction

A double-blind modification of the intraesophageal acid perfusion challenge (Bernstein procedure) was performed in asthmatic subjects with and without gastroesophageal reflux, nonasthmatic subjects with reflux, and normal subjects. Conventional spirometric functions and total respiratory resistance (Rrs) were measured prior to and after the infusion. There were no changes in pulmonary functions except in the asthmatic subjects who had had a positive add challenge. The greatest changes occurred in Rrs, which increased significantly with reflux symptoms (p < 0.01) and decreased toward baseline (p < 0.05) when these symptoms were relieved with antacids. The response was even greater in asthmatic subjects who associated reflux symptoms with attacks of asthma. These results support previous findings that acid reflux symptoms could cause a bronchoconstrictive response in certain asthmatic patients.     

Suprabasal p53 immunoexpression is strongly associated with high grade dysplasia and risk for malignant transformation in potentially malignant oral lesions from Northern Ireland

AIMS: No good predictive marker for the malignant transformation of potentially malignant oral lesions (PMOLs) is currently available. This study re-evaluated the value of p53 immunoexpression to predict malignant transformation of PMOLs after discounting possible confounding factors. METHODS: PMOLs from 18 patients who showed progression to carcinoma, 16 of the respective carcinomas, and PMOLs from 18 matched controls were evaluated by immunohistochemistry (IHC) for p53 expression. A mouse monoclonal antibody that detects wild-type and mutant forms of human p53 was used. The p53 immunostaining pattern was also correlated with the degree of dysplasia. RESULTS: Suprabasal p53 staining was significantly associated with high grades of dysplasia (p < 0.01). The specificity and positive predictive value (PPV) for malignant transformation of suprabasal p53 staining were superior to the assessment of dysplasia, but sensitivity was inferior. All carcinomas derived from PMOLs with suprabasal p53 showed strong p53 immunostaining. However, the absence of suprabasal p53 staining and/or dysplastic changes did not preclude malignant transformation in a considerable proportion of PMOLs. CONCLUSIONS: This study confirms and extends previous findings that suprabasal p53 immunoexpression has a high PPV for malignant transformation of PMOLs and can be used as a specific marker for lesions that are at high risk for malignant transformation. The absence of suprabasal p53 staining (that is, absence of, or basal, p53 staining) is non-informative for prognostic purposes. Because of its limited sensitivity, p53 IHC is not a substitute for the assessment of dysplasia in the evaluation of PMOLs. Instead, p53 IHC emerges as a clinically useful supplement of histopathological assessment in the prognosis of PMOLs.     

Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association

BACKGROUND. Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS. We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS. The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS. In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.     

Secular trend in age at menarche for women born between 1920 and 1979 in Rio de Janeiro, Brazil

PRIMARY OBJECTIVE: This article presents data on the secular trend in age at menarche for 1955 women from 16 to 76 years of age born between 1920 and 1979 and studied under the Nutrition and Health Survey conducted in the municipality of Rio de Janeiro, Brazil, in 1996. METHODS AND PROCEDURES: Age at menarche was defined by the retrospective method. Women were grouped according to decade of birth, and the trend was estimated using simple linear regression between age at menarche and year of birth for the following specific periods: 1920-1940, 1920-1960, 1960-1979 and 1920-1979. MAIN OUTCOMES AND RESULTS: Mean age at menarche decreased from 13.07 to 12.40 years when comparing the group of women born in the 1920s with the 1970s birth cohort, corresponding to a mean rate of -0.0123 years per year (p < 0.001). The downward trend was -0.0120 years per year (p > 0.05) for the 1920s, 30s and 40s, -0.0093 years per year (p < 0.05) for the period from 1920 to 1960, and -0.0224 years per year (p < 0.01) for the 1960s/70s. CONCLUSIONS: The results suggest a secular trend in age at menarche. The literature points to such environmental variables as improved living conditions and expanded access to health services. Within this context, age at menarche could be used as a marker for social development.     

Is the outcome of in-vitro fertilization and embryo transfer treatment improved by spontaneous or surgical drainage of a hydrosalpinx?

A pilot study was designed to examine whether the outcome of embryo transfer in women with a hydrosalpinx might be improved by surgical drainage of the hydrosalpinx at the time of oocyte collection for in- vitro fertilization treatment. A comparative, controlled but retrospective analysis of the results was performed of all women with infective tubal damage aged <40 years old, who had ovulatory cycles, a normal uterus and a partner with normal spermatozoa. A standardized treatment regimen was used. A maximum of three embryos were transferred. Hydrosalpinx was defined by prior hysterosalpingography and/or laparoscopy with transcervical dye injection. A total of 237 embryo transfer cycles in women with hydrosalpinges (tubal distension not visible in 151, visible but not drained in 30 and drained in 56) were compared with 705 embryo transfer cycles in women with tubal disease but no hydrosalpinx. Results were analysed in the first three cycles but also separately in the first cycle to check for bias. Success rates were higher in the first cycle, but did not significantly influence overall differences. Implantation rates were significantly reduced overall in the hydrosalpinx group (8.0 versus 13.2% for controls; P < 0.001), being 8.3% (P < 0.01) in the subgroup without evident tubal distension and 7.5% (not significant) in the drained hydrosalpinx group. This study shows that tubal damage with distal occlusion is associated with a marked reduction in embryo implantation, even in the absence of obvious fluid distension. Surgical drainage of distended hydrosalpinges appears to offer no benefit.      

HL-A Antigens in Leprosy

HL—A phenotype frequencies were studied in 30 patients with leprosy and in 149 healthy controls. Leprosy patients had a significantly higher frequency of HL—A14. In addition, a majority of the HL—A14 patients gave a negative response to leproma antigen using the Mitsuda test.